Content uploaded by Ulhas Pandurangi
Author content
All content in this area was uploaded by Ulhas Pandurangi
Content may be subject to copyright.
Editor-in-Chief
V.K. VIJAYAN
Former Editor-in-Chief
R. Viswanathan (1959-1982)
A.S. Paintal (1983-1998)
Editors
J.N. Pande
S.K. Jindal
Ashok Shah
S.K. Sharma
Associate Editors
S.K. Chhabra
V.K. Arora
Alladi Mohan
Dheeraj Gupta
Editorial Board
A.N. Aggarwal
G. Ahluwalia
R.S. Bedi
D. Behera
S.K. Bhargava
Arati Bhatia
Mridula Bose
S.N. Dwivedi
S.N. Gaur
R. Guleria
H.S. Hira
M.S. Jawahar
S. Kashyap
G.C. Khilnani
Raj Kumar
T. Mohan Kumar
A.A. Mahashur
B.N. Panda
C.N. Paramasivan
R. Prasad
G.K. Rath
P. Ravindran
J.C. Suri
Sudha Suri
Journal Coordinators
R.K. Gupta
D.K. Sahu
THE INDIAN JOURNAL OF
CHEST DISEASES AND
ALLIED SCIENCES
THE INDIAN JOURNAL OF CHEST DISEASES AND ALLIED SCIENCES (ISSN
0377-9343) is published quarterly, by the Vallabhbhai Patel Chest Institute,
University of Delhi, Delhi and the National College of Chest Physicians (India).
The Journal covers the Clinical and Experimental work dealing with all aspects
of Chest Diseases and Allied Sciences. It publishes Original Articles, Review
Articles, Radiology Forum, Case Reports, Short Communications, Book Reviews
and Letter to the Editor.
THE INDIAN JOURNAL OF CHEST DISEASES AND ALLIED SCIENCES.
Copyright © 2006, by Vallabhbhai Patel Chest Institute, University of Delhi, Delhi.
All rights reserved; no part of this publication may be reproduced, stored in a
retrieved system or transmitted in any form or by any means electronic, mechanical,
photocopying, recording or otherwise, without the prior permission of the Indian
Journal of Chest Diseases and Allied Sciences or in the USA by the Copyright Clearance
Center, 222, Rosewood Drive, Danvers, MA 01923.
The statements and opinions contained in the articles of this Journal are solely those
of the authors. The Editor-in-Chief, the Indian Journal of Chest Diseases and Allied
Sciences, its Editorial Board Members, and employees disclaim all responsibility
for any injury to persons or property resulting from any ideas or products referred
to in articles or advertisements contained in this Journal. The appearance of
advertisements or services advertised or of their effectiveness, quality or safety
are solely those of the advertisers.
The Journal is abstracted and indexed in Index Medicus, Excerpta Medica, Medline and
Chemical Abstracts.
Note
(i) Overseas subscription rates include airmail postal charges.
(ii) Subscription Agencies are eligible for a 10% discount on annual rates for
institutional subscription only. Subscription Agencies must provide
complete address of the Institution for which subscription is sent in their
subscription order.
(iii) Payments should be made only by Banker's Cheque/Demand Draft,
drawn in favour of the Director, V.P. Chest Institute, Delhi.
(iv) The above rates are not subject to any Tax Deduction at Source.
Subscription Rates
Individual Institutional
India Overseas India Overseas
(In Rs.) (In US $) (In Rs.) (In US $)
Single Issue 250.00 40.00 300.00 40.00
One Volume 800.00 100.00 1000.00 100.00
(4 Issues)
2006; Vol. 48 The Indian Journal of Chest Diseases & Allied Sciences 239
240 The Indian Journal of Chest Diseases & Allied Sciences 2006; Vol. 48
NATIONAL COLLEGE OF CHEST PHYSICIANS (INDIA)
GOVERNING COUNCIL
[w.e.f.: 1st April 2006]
President
(2006-2007)
Vice-President
(2005-2007)
Dr Rajendra Prasad Dr J.N. Banavaliker
Lucknow Delhi
President-Elect
(2007-2008)
Immediate Past President
(2005-2006)
Dr J.N. Banavaliker Dr N.K. Jain
Delhi Jaipur
Secretary
(2004-2007)
Joint Secretary
(2006-2008)
Dr S.N. Gaur Dr K.B. Gupta
Delhi Rohtak
Treasurer
(2006-2009)
Dr V.K. Singh
Delhi
Councillors
Dr S.K. Bhargawa Dr V.K. Dhingra Dr Jai Kishan
Delhi New Delhi Patiala
Dr Rajesh N. Solanki Dr R.S. Bedi Dr Raj Kumar
Ahmedabad Patiala Delhi
Zonal Chairmen
North South Central East West
Dr M.M. Singh Dr P. Ravindran Dr S.K. Katiyar Dr S.N. Tripathy Dr N.K. Jain
New Delhi Trivandrum Kanpur Cuttack Jaipur
Co-opted Member
Dr B.O. Tayade
Nagpur
THE INDIAN JOURNAL OF CHEST DISEASES AND ALLIED SCIENCES
Vol. 48 October–December 2006 No. 4
CONTENTS
2006; Vol. 48 The Indian Journal of Chest Diseases & Allied Sciences 241
Pages
Editorial
Managing lung cancer in developing countries: difficulties and solutions
D. Behera .. 243
Prof. Raman Viswanathan – VPCI Oration 2006
The challenges of tuberculosis
C.N. Deivanayagam .. 245
Original Articles
Is routine mediastinoscopy indicated for patients with T1 non-small cell lung cancer?
S.I. Dincer, A. Demir, H. Akin, M.Z. Gunluoglu, M. Metin, H. Melek and A. Gurses .. 249
A five-year review of tuberculosis mortality amongst hospitalised patients in Ile-Ife
G.E. Erhabor, O.O. Adewole and O. Ogunlade .. 253
Pleurocutaneous Flap: How useful it is in management of chronic empyema
A. Kohli, G. Singh, Anita Vig, K.R. Dubey and R. Singh .. 257
Aetiology and clinical profile of spontaneous pneumothorax in adults
D. Gupta, S. Mishra, S. Faruqi and A.N. Aggarwal .. 261
Review Article
Role of bronchoscopy in early diagnosis of lung cancer
A.V. Kamath and P.N. Chhajed .. 265
Case Reports
High intensity exercise training programme following cardiac transplant
A.J. Rajendran, U.M. Pandurangi, A.S. Mullasari, S. Gomathy, K.V. Kuppu Rao and
V.K. Vijayan .. 271
Superior vena cava syndrome caused by pulmonary amoebic abscess
K.B. Gupta, M. Manchanda, Uma Chaudhary and M. Verma .. 275
Uncommon parathyroid mediastinal cyst compressing the trachea
D. Agrawal, T.K. Lahiri, Anshu Agrawal and M.K. Singh .. 279
Pulmonary hyalinizing granuloma with ureteric fibrosis: a case report and review of
relevant literature
D. Agrawal, R. Deshpande, S. Maheshwari, A. Patel and Z.F. Udwadia .. 283
Life threatening exacerbation in idiopathic pulmonary hemosiderosis salvaged by
cyclophosphamide infusion
R. Naithani, J. Chandra, V. Singh, V. Kumar and N.K. Dubey .. 287
242
Editorial
[Indian J Chest Dis Allied Sci 2006; 48: 243-244]
Lung cancer has been the most common cancer in the
World since 1985, and by 2002, there were 1.35 million
new cases, representing 12.4% of all new cancers. It was
also the most common cause of death from cancer, with
1.18 million deaths, or 17.6% of the World total. Almost
half (49.9%) of the cases occur in the developing
countries of the World—a big change since 1980, when
it was estimated that 69% were in developed countries.
Worldwide, it is by far the most common cancer of men,
with the highest rates observed in North America and
Europe (especially Eastern Europe). Moderately high
rates are also seen in Australia/New Zealand and
Eastern Asia (China and Japan). In women, incidence
rates are lower with a global rate of 12.1 per 100,000
women compared to 35.5 per 100,000 in men
1
.
Population-based as well as hospital-based data from
the Cancer Registry of the Indian Council of Medical
Research (ICMR) and the Cancer Atlas Programme of
the ICMR revealed that lung cancer has increased in
India during the last few years
2-4
. Of the 10 centers from
which data was available, it was the most common form
of malignancy in males in six centers, and 2
nd
and 3
rd
in
order in two other centers. From many of the centers
including one from a rural centre, lung cancer ranks
among 10 cancer sites in women. The Cancer Atlas
Programme revealed very interesting data
2-4
. Lung
cancer is the commonest form of malignancy in the
north-east region of the country–a hither-to-unknown
fact. In fact, the region may be called as “hot-spot” for
lung cancer and particularly in women of this region,
which is akin to that seen in women in the Western
World. Published clinical data from all regions of India
also testifies the fact that cancer is increasing in our
country
5
. Further, the assessment of risk factors in
Indian patients revealed that bidi smoking is the major
risk factor for lung cancer in India in contrast to the
cigarette or cigar smoking in USA
6
. Further, in non-
smoking Indian women indoor air pollution due to
domestic cooking fuels particularly the biomass fuel is
a significant risk facstor
7
.
Lung cancer remains a highly lethal disease. Survival
at five years in the United States is 15%, the best
recorded at the population level. The average survival
in Europe is 10%, not much better than the 8.9%
observed in developing countries
1
. The situation is
similar in India. Published reports do not mention about
the five–year survival rates. One-year survival has been
reported as 9.8 percent
8
. Where should we go from
here? Should we treat these patients? What are the
problems in the management of lung cancer for Indian
scenario? Who are all to be associated with the
management of these cases? Unfortunately at the time
of presentation, lung cancer presents at an advanced
Managing Lung Cancer in Developing Countries:
Difficulties and Solutions
stage
9
. Even diagnosis at earlier stages (where surgery
could be offered) is possible only in about 80% of all
lung cancer cases in the Western World. Unfortunately,
only less than 5% of cases present in such stages in our
country. However because of associated smoking,
COPD and other cardio-vascular causes, some of them
cannot be taken up for surgical treatment. Further, it is
a fact that our country does not have sufficient number
of thoracic surgeons who will be interested in thoracic
oncology surgery as a matter of preference. This delay
in dignosis occurs because of the fact that most
symptoms of lung cancer and pulmonary tuberculosis
are similar and most patients receive anti-tubercular
therapy for varying period of time before a definite
diagnosis could be made. This is more so if the patient
is below the age of 40 years. Diagnostic facilities like
fiberoptic bronchoscopy and other invasive procedures
like fine needle aspiration cytology/biopsy are not
available uniformly throughout the country. Because of
the advanced stage of the disease the only option is
systemic chemotherapy. The radiotherapy can be used
as an adjuvant and is a localised form of treatment.
Moreover, radiotherapy facilities are not available at all
medical colleges in our country. As regards
chemotherapy there are a number of problems. It is well
established that chemotherapy is better than best
supportive care
10,11
. Prolongation of life even for few
weeks to months is important for many socio-economic
reasons. Then should we give chemotherapy to all?
These drugs are toxic, costly and we need expertise to
deliver such therapy. All drugs used in lung cancer
treatment are now available in India. The cost of drugs
and administration of therapy will vary according to the
set up where it is given. Whereas one of the best
combinations of chemotherapy
12
will cost around
Rs.15000 to Rs.20000 per cycle in a government hospital,
but in other corporal and private settings the cost will
be much more. Can we send all patients to medical
oncologists? Again there are not enough medical
oncologists in all the medical colleges in India. Thus,
there may be a point where the chest physician came
into the picture. He sees the patient, makes a diagnosis,
manages the complications like pleurodesis, treatment
of pneumonia and hemoptysis, etc. Then he should be
able to deliver chemotherapy. However, to deliver
chemotherapy also, the chest physician will need some
specialised training in handling anti neoplastic drugs
along with management of associated complications of
such therapy. The current approach of lung cancer
management has been directed towards molecular
based targeted therapies
13,14
. We should have more
studies on the molecular and genetic aberrations in lung
cancer in our population, although some information is
244
available from this country
15-17
. Such targeted therapy is
also possible now in this country with benefit
18, 19
.
While we are attempting to treat the disease, our
efforts should be concentrated on the prevention of the
lung cancer particularly with more aggressive and anti-
smoking campaign and propaganda. Secondly, we
should try to diagnose patients at an early stage, which
can come with awareness and use of various diagnostic
modalities.
D. Behera
Professor
Department of Pulmonary Medicine
PGI , Chandigarh-160012
Tele.: 91-172-2756822
E-mail: dbehera@glide.net.in
REFERENCES
1. Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics,
2002. CA Cancer J Clin 2005; 55: 74-108.
2. National Cancer Registry Programme. An epidomiological
study. Indian Council of Medical Research, Biennial Report, 1988-
1989. New Delhi: ICMR; pp 3-42.
3. National Cancer Registry Programme. Consolidated Report of
the Population-based Cancer Registries 1990-1996. New Delhi:
Indian Council of Medical Research. 2002.
4. Nandkumar A, Gupta PC, Gangadharan P, Visweswara RN.
Development of an Atlas of Cancer in India: First All India Report
2001-2002. National Cancer Registry Programme 2001-2004.
Bangalore: Indian Council of Medical Research. 2004.
5. Behera D, Balamugesh T. Lung cancer in India. Indian J Chest
Dis Allied Sci 2004; 46: 19-31.
6. Notani P, Sanghavi LD. A retrospective study of lung cancer
in Bombay. Br J Cancer 1974; 29: 477-82.
7. Behera D, Balamugesh T. Indoor air pollution as a risk factor
for lung cancer in women. J Assoc Physicians India 2005; 53:
190-2.
8. Behera D, Aggarwal AN, Sharma SC, Gupta D, Jindal SK.
Ifosfamide containing regimen for non-small cell lung cancer
(NSCLC). Indian J Chest Dis Allied 2004; 46: 9-15.
9. Jindal SK, Behera D. Clinical spectrum of primary lung
cancer: review of Chandigarh experience of 10 years. Lung
India 1990; 8: 94-8.
10. Non-small Cell Lung Cancer Collaborative Group.
Chemotherapy in non-small cell lung cancer: meta-analysis
using updated data on individual patients from 52
randomized clinical trials. Br Med J 1995; 311: 899-909.
11. Shajeem O, Behera D, Aggarwal AN. Chemotherapy versus
best supportive care in the management of lung cancer. J
Assoc Physicians India 2003; 51: 261-4.
12. Schiller JH, Harrington D, Belani CP, Langer C, Sandler A,
Krook J, et al and Eastern Cooperative Oncology Group.
Comparison of four chemotherapy regimens for advanced
non-small cell lung cancer. N Engl J Med 2002; 346: 92-8.
13. Ettinger DS. Clinical implications of EGFR expression in the
development and progression of solid tumors: focus on non-
small cell cancer. Oncologist 2006; 11: 358-73.
14. Tsao MS, Sakurada A, Cutz JC, Zhu CQ, Kamel-Reid S,
Squire J, et al. Erlotinib in lung cancer: molecular and clinical
predictors of outcome. N Engl J Med 2005; 353: 333-44.
15. Mir S, Radhika S, Wali A, Majumdar S, Joshi K, Behera D.
Expression of p53 protein and the apoptotic regulatory
molecules Bcl-2, Bcl-X
L
and Bax in locally advanced
squamous cell carcinoma of the lung. Lung Cancer 2004; 45:
181-8.
16. Wali A, Srinivasan R, Shabnam MS, Majumdar S, Joshi K,
Behera D. Loss of fragile histidine triad gene expression in
advanced lung cancer is consequent to allelic loss at 3p14
locus and promoter methylation. Mol Cancer Res 2006; 4: 93-
9.
17. Jain N, Singh V, Hedau S, Kumar S, Daga MK, Dewan R, et al.
Infection of human papillomavirus type 18 and p53 codon 72
polymorphism in lung cancer patients from India. Chest 2005;
128: 3999-4007.
18. Behera D, Aggarwal A, Gupta D, Jindal SK, Aggarwal R,
Sharma SC, et al. Gefitinib (Geftinat) in advanced non-small
cell lung cancer: a preliminary observation in Indian patients.
Lung Cancer 2005; 49 (Suppl 2): S365.
19. Thatcher N, Change A, Parikh P, Rodrigues Pereira J,
Ciuleanu T, von Pawel J, et al. Gefitinib plus best supportive
care in previously treated patients with refractory advanced
non-small cell lung cancer: results from a randomised,
placebo-controlled, multicentre study (Iressa Survival
Evaluation in Lung Cancer). Lancet 2005; 366: 1527-37.
Editorial D. Behera
Prof. Raman Viswanathan – VPCI Oration 2006
According to the World Health Organization, India has
more new tuberculosis cases annually than any other
country. For the World as a whole, the biggest challenge
of tuberculosis (TB) is its ability to survive in most
countries and to flourish in Southern Countries even in
the year 2006 of the Common Era (CE).
Challenges in Tuberculosis
There are other challenges as well. These are : (1)
diagnostic difficulties, especially in children and those
with sputum negative disease; (2) ability to team up
with Diabetes Mellitus, silicosis and most recently with
human immunodeficiency virus (HIV) infection and
disease; (3) ability to lie dormant for many years in
people, only to re-activate later, much later; and (4)
ability to bounce back within weeks or months of
apparent completion of treatment-relapses. These
challenges and the versatile nature of the tubercular
bacillus pose a great challenge in the successful control
of tuberculosis and its eradication. It is estimated that by
2010, the World will see a mortality of 20 million and a
case burden of 80 million!
History of Tuberculosis
How old is the life history of Mycobacterium tuberculosis
Hominis (MTB)? It is estimated to be about 12 to 20,000
years old. It entered humans at least 7000 years ago, the
spread was likely to have been from domesticated
cattle, birds or other animals. Tuberculosis resembles
cholera, small pox and HIV in spreading from animals
to man.
The Europeans dreaded the “White Plague”, that
was recognised as a major public health problem in the
14
th
to 18
th
centuries. The Captain amongst these men of
death (John Bunyan) caused nearly 20% of all deaths in
London around the year 1650 AD. Around 1820 AD, it
caused nearly seven million deaths and in modern era
in 2004, it caused 2.8 million deaths. This excludes
deaths in association with HIV that would amplify the
magnitude of the problem further.
Ethnic Differences
Are there Ethnic/Racial differences in ‘Catching TB’?
People with no ancestral experiences with TB catch and
suffer more easily. These include native American tribes
who acquired it form white immigrants, land locked
Nepalis who got it from British colonization, the AINU
of Hokkadio and Shakalin Isles of Japan and the natives
of Western Scottish Isles. These “virgin” populations
suffered haematogenous TB spread (miliary) and often
galloping disease. The Japanese considered TB as a
“Death Sentence” in the first half of 20
th
Century. In
The Challenges of Tuberculosis
India the word TB carries a big social stigma. There is
often ostracism and there is difficulty in arranging
marriage for daughters.
Trends in Epidemiology
Is TB such a big killer now? Fortunately, no. It began to
decline in the Western World from the mid to late 19
th
Century. However, the picture is turning dismal again.
In the US the downward trend stalled and reversed in
the 1980s. This is likely to have occurred because of
dismantled social support system, immigration and the
emerging epidemic of HIV. New York City alone had to
spend over $800 million to limp back from the mini
surge of TB epidemic.
What caused the decline of TB in the West? There are
several reasons for this: (1) rising standard of living
reflected in improved nutrition, housing, water supply,
sanitation and clean air; (2) segregation and eventual
recovery/death of the more extensively affected; and (3)
eradication of Bovine TB. It is noteworthy that drugs
and chemotherapy (the magic bullets) played no part in
this recorded decline. Waksman and streptomycin
appear on stage only in 1944!. It is, thus, clear that TB is
no ordinary infectious epidemic but a sensitive index of
socio-economic status. It may be called a “barometer of
social condition” and is “an archetypal disease of
poverty”.
Natural History
The natural history of TB starts with the droplet nuclei
reaching the lungs of an uninfected person. As many as
70% of these exposed persons do not get infected. Only
30% develop infection. Amongst these exposed and
infected 30%, about 5% develop early primary TB (early
progression). However, almost 40% develop early
primary TB, if they have concurrent HIV infection. Of
the original 30%, another 5% develop late TB (late
progression). Thus amongst those actually infected, 90%
successfully contain the infection for life! They are just
Tuberculin Positive-Period!. The estimated dose of
bacilli required to cause infection is 10
3
to 10
4
while the
estimated dose of bacilli required to cause disease is
about 10
7
to 10
8
. A prolonged and close contact increases
the chances of transmission. The estimated burden of
bacilli in patients may be upto 10
10
.
Are there natural variations in virulence? Yes. Group
C drug susceptible outbreaks in Manhattan Shelters and
the Group W or Beijing-HIV linked nosocomial
outbreaks in NYC-MDRTB are examples of this. Group
W grows 4-5 times faster inside macrophages than
others which cause no secondary outbreaks. The basis
of attenuation of BCG and H37Ra or the virulence of M.
Bovis and H37Rv remain unclear.
[Indian J Chest Dis Allied Sci 2006; 48: 245-247]
246
Introduction of DOTS
How are we responding to the challenges? The New
York resurgence of TB shook the Western World. WHO
declared TB as a Global Health Emergency (1993) and
offered ‘DOTS’ as the ‘mantra’ to contain and overcome
TB! A large chunk of Africa-Sub-Saharan Africa (SSA)-
suffered decimation on account of TB, and WHO
declared TB as Regional Medical Emergency! Many in
India play the same tune and sing “DOTS for all-all for
DOTS”!
DOTS: A Reality Check
A reality check on DOTS is revealing. In Ethiopia, DOTS
has performed below par. Reasons are the distance to
the Health Centre, cost of transportation and poor
awareness about the disease. In Pakistan, DOTS center
attendance is reported to be irregular because of time
and travel costs, ill health of the patients, need to pursue
own occupation and the DOTS provider attitudes that
are cynical and uncaring. DOTS centre timing and
schedules more suited to provider than to the patient.
There is more emphasis on “tablet watching” and no
effort towards “patient support”.
In India, in the city of New Delhi, patients in absolute
poverty, socially marginalised, itinerant labourers and
poorly integrated in the city are excluded from DOTS.
The programme, thus, excludes the most vulnerable
from the best available care (V. Singh, et al. Trop Med Int
Health 2002; 7: 693-700). In Kerala 26.5% of patients who
were recorded as having received DOTS did not
actually receive it. (V.N. Balasubramanian, et al. Int J
Tuberc Lung Dis 2002; 4: 409-13). In Tamil Nadu
Tiruvallur programme of the Tuberculosis Research
Centre, 74% patients were cured, 17% defaulted, 5%
died and 4% failed. Amongst multidrug-resistant
tuberculosis (MDR-TB), 33% patients failed. A higher
death rate was recorded for body weight <35 kg, and a
history of previous antituberculous therapy (T. Santha,
et al. Int J Tuberc Lung Dis 2002; 6: 780-8). In Mumbai, at
a Medical College in the year 2004, there were 673
smear positive, 71 HIV positive cases out of which only
72% were cured or declared “completed treatment”.
Counterpoint: DOTS vs SAT (Indian Experience)
What is the Indian experience in comparing DOTS with
SAT (self administered treatment)? In the Madurai
randomised controlled trial carried out by the
Tuberculosis Research Centre, Chennai, twice weekly
DOTS (2HRZ/4HR) and daily SAT (6HR) were
compared with a 36-month follow-up. Almost 87%
improved in both the groups. There were three relapses
in DOTS and two in SAT. There were 11% adverse
reactions in DOTS and one percent in SAT. (M.S.
Jawahar, et al. Trop Med Int Health 2005; 10: 1090-8.)
Counterpoint (World View)
There is a counter point in the world view too.
According of Medicines Sans Frontiers (MSF), DOTS
does not detect TB in paediatric age or in extra-
pulmonary or smear negative cases. Sputum
microscopy picks up only 45% of lung TB in non-HIV
and only 38% of lung TB in HIV-positive patients and
detects less than 5% of lung TB in children. DOTS
excludes many people with active TB.
According to Social Scientists, simplifying policy
approaches to “One-Size-fits-all” carries inherent risks
and can be perceived to harm locally appropriate
preferences. (J. Ogden, et al. Social Sci Med 2003; 57: 179-
88). “The Chinese have done well with DOTS” is a
common refrain. (Comment in Lancet 2004; 364: 391-2).
The heretical notion “Strong health systems in the
overall rich areas (of China) were responsible for
effective TB control, not the DOTS strategy” is
supported. Further, Shanghai has effectively controlled
TB through strong health systems and does not use
either free treatment or DOTS. (Editorial comment by C.C.
Whalen. Clin Infect Dis 2006; 42: 1048-50).
There has been a failure of DOTS in Africa, and there
has been a call for new approaches. In sub Saharan
Africa, the TB incidence rates have surpassed 1000
cases/100000 in some areas. Near Cape Town, TB rates
increased 2-5 fold amongst adolescents and 20-39 year
olds despite a levelling off of HIV. Thus, DOTS is not
optimally designed to interrupt the spread of TB and
only alters the duration of treatment. It does not
address the number and frequency of contacts or the
likelihood of disease after infection.
Controlling TB in India
What about TB control efforts in India? Clearly the
brand and mantra “DOTS” will not work in each and
every region of India. The basic premise of DOTS
“Persons with TB (read-mostly poor and disadvant-
aged) cannot be relied upon to take their medicines
regularly” smacks of paternalism and pro-fascist ideas.
All are born equal and the Government must treat them
equally. The Constitution makers of India have rightly
rejected votes only for those with property and/or
education. We have Universal Franchise.
There is a need to change the approach to epidemic
control: empower the people, make them strong. They
will resist TB infection and disease effectively.
Suggestions
Urgent inputs are required. These should include the
following:
1. Measures to reduce poverty and illiteracy. Extreme
poverty is still found in rural areas of Bihar,
Madhya Pradesh, Uttar Pradesh and West Bengal.
The Challenges of Tuberculosis C.N. Deivanayagam
2006; Vol. 48 The Indian Journal of Chest Diseases & Allied Sciences 247
Rural Employment Guarantee Scheme is a step in
the right direction. Once the socio-economic status
improves, TB declines.
2. Improve public sector clinics and hospitals—
improve access and drugs availability.
3. Individualise diagnosis and treatment approaches.
Give back choice to the patients. If they want
DOTS so be it! If they want SAT so be it!
4. Treat latent TB infection with INH for 9-12 months.
C.N. Deivanayagam
Member, National Council on AIDS
and
President, Health India Foundation
E-mail: cdeivanayagam@hotmail.com
242 The Indian Journal of Chest Diseases & Allied Sciences 2006; Vol. 48
Book Review
Practical Approach to Critical Respiratory Medicine: Sleep Disorders and Fiberoptic
Bronchoscopy .. 290
Some Forthcoming Scientific Events .. 291
Abstracts' Service .. 292
Authors' Index (Vol. 48, No. 1-4) .. 298
Guidelines to Authors .. 301
Announcements .. 248, 260, 270, 274
278, 282, 286
Pages
248 The Indian Journal of Chest Diseases & Allied Sciences 2006; Vol. 48
Full text articles published in IJCDAS from July-September
2003 onwards can be accessed online on Internet through the
following sites
V.P. Chest Institute’s site: http://www.vpci.org.in
Indmed’s site: http://medind.nic.in
Guidance for Authors appears in every issue.
Authors’ Index appears in the last issue of the year
Original Article
Is Routine Mediastinoscopy Indicated for Patients with T1
Non-small Cell Lung Cancer?
Seyyit Ibrahim Dincer, Adalet Demir, Hasan Akin, Mehmet Zeki Gunluoglu, Muzafer Metin,
Huseyin Melek and Atilla Gurses
Department of Thoracic Surgery, Yedikule Teaching Hospital for Chest Diseases and Thoracic Surgery,
Istanbul, Turkey
ABSTRACT
Objective. Mediastinoscopy is gold standard in the staging patients with non–small cell lung cancer (NSCLC) patients. Yet,
its necessity in every patient is being questioned as new data is being collected. In the present study, we compared pathology
reports of the cases with T1 NSCLC both after mediastinoscopy and thoracotomy, and discussed about the necessity of
mediastinoscopy.
Methods. We retrospectively reviewed the records of 74 patients (73 patients with pathologic T1 NSCLC patients who
underwent pulmonary resection and one patient clinically T1 who did not undergo pulmonary resection), between 1996 and
2002. Clinically 80% of the cases were at T1 stage, and the rest were at T2 stage. The distribution of clinical lymph node status
was N0 in 85%, 15% N2.
Results. Fifty-three (71.6%) cases underwent mediastinoscopy. Mediastinoscopy showed that one patient had contralateral
lymph node involvement and the remaining cases had no lymph node metastases. No mortality occurred and morbidity rate
was 1.9%. Lobectomy was performed in 60 cases, pneumonectomy in seven, wedge resection in five, and segmentectomy
in one. The histopathologic types were; squamous cancer in 40 (55%) cases, adenocarcinoma in 29 (40%), and large cell
carcinoma in four (5%). Only two cases (2.7%) who had no detectable lymph node metastases at mediastinoscopy were found
to have N2 disease after thoracotomy. In rest of the cases, N0 was observed in 48 (66%) and N1 in 23 (31.5%). Five-year sur-
vival of the cases was calculated to be 73%. The two cases with N2 disease are alive at seven and four years after the operation.
Conclusion. Routine mediastinoscopy does not appear to be necessary for patients with clinical T1 non-small cell carcinoma
having no enlarged lymph nodes on computerised tomography.
[Indian J Chest Dis Allied Sci 2006; 48: 249-252]
Key words: Mediastinoscopy, T1 non-small cell lung cancer.
[Received: June 13, 2005; accepted after revision: February 27, 2006]
Correspondence and reprint requests: Dr Adalet Demir, Yuzyil mah. Kisla Cad. Yesil zengibar sitesi, A-3 Block, D-9 Bagcilar,
Istanbul, Turkey; Tele.: 90 212 6641700; Telefax: 90 212 5472233; E-mail: dradalet@hotmail.com.
INTRODUCTION
Surgical resection is still at top of treatment modalities
of non-small cell lung cancer (NSCLC) to provide a
good survival. Unfortunately this is only possible in
patients with early stage tumours. The most important
prognostic indicator of local dissemination is the status
of the mediastinal lymph nodes which should be
clarified before surgical resection
1-3
. Many techniques
including thorax computed tomography (CT), positron
emission tomography (PET), ultrasonography-guided
transesophageal biopsy, selective or routine
mediastinoscopy, mediastinotomy, and video-assisted
thoracoscopic (VATS) biopsy have been used to achieve
this goal
1
. In the last two decades, CT and (PET)
received great interest because mediastinosocopy is an
invasive procedure despite of its effectiveness and high
accuracy. But, it is still be gold standard cited in the
literature
1-4
.
The chance of mediastinal lymph node metastasis of
T1 NSCLC has been reported in a wide spectrum in
different series. It is especially quite low if chest CT is
negative for mediastinal lymphadenopathy. For this
reason it has been questioned more frequently whether
to perform routine mediastinoscopy in this group of
patients
3, 4
.
In this study we compared pathology reports
of the cases with T1 NSCLC both after mediastinoscopy
and thoracotomy, and discussed about the necessity of
mediastinoscopy.
MATERIAL AND METHODS
Between 1996 and 2002, 758 patients with NSCLC were
admitted to our clinic. Our current practice is to perform
mediastinoscopy in all cases except in patients with T1
squamous carcinoma and no evidence of lymph nodes
more than 1 cm size in diameter on CT scan of the chest.
But before the year 2000 mediastinoscopy was routinely
250
performed in all cases with NSCLC. Patients with no
mediastinal nodal disease directly underwent
thoracotomy and appropriate resection. When N2 or N3
disease was detected, the patients were referred to
oncological therapy (n=104); but, after year 2000
patients with N2 disease of single station or without
capsule involvement referred to oncology clinic for
neoadjuvant therapy (n=72).
The remaining 582 cases underwent thoracotomy.
When the tumour is localised to a single lobe with no
sump involvement, lobectomy with systematic lymph
node sampling was done. Should the tumour involves
adjacent lobe or sump lymph nodes, bilobectomy or
pneumonectomy and systematic lymph node sampling
was performed.
Mediastinoscopy, as described by Carlens in 1959,
was performed by either a consultant or a trainee under
general anesthesia with a single lumen tracheal
intubation in supine position with neck extension. All
the lymph node stations that can be accessible by
standard mediastinoscopy were sampled. The patients
were extubated in the operating room at the end of the
procedure.
The study population consisted of 74 patients who
had T1 lung carcinoma at the final pathology report.
One patient had N3 disease after mediastinoscopy and
referred to oncology. We analysed the clinical data of 73
out of these 582 patients who had T1 tumour according
to histopathology report.
All cases underwent chest CT, fiberoptic
bronchoscopy, complete blood count, and routine
biochemistry, electrocardiogram, and arterial blood gas
analysis. Some had also undergone transthoracic needle
aspiration biopsy. Cranial CT, abdominal ultrasound or
radionuclide bone scanning were not performed unless
the patient was symptomatic. No patient was evaluated
with PET scanning.
In 46 patients (62%) the tumour was located on the
right side. Clinically, 59 cases (80%) had T1 tumours and
63 of the cases had no detectable lymph node on thorax
CT (cN0). Mediastinoscopy was performed in 53
patients (71.6%) and the remaining 21 cases (28.3%)
underwent thoracotomy without mediastinoscopy. One
patient who had been discovered to have N3 was refe-
rred to oncology. Resected specimens were examined
histopathologically. Staging was performed according
to the new international staging system for lung cancer
5
.
Data are presented as mean and percentages.
Survival was estimated by the Kaplan-Meier method
and differences in survival were determined by long-
rank analysis.
RESULTS
Out of the 74 patients, there were 65 males and nine
females. Their mean age was 59±9 years (range 32–76
years). Fifty-three (71.6%) cases underwent mediast-
inoscopy, but only one patient was found to have
contralateral mediastinal lymph node involvement (N3)
and was referred to oncology. No other mediastinal
lymph node involvement was detected at mediast-
inoscopy. The clinical characteristics of these patients
are shown in table 1. No mortality occurred. Only one
patient had hoarseness of voice (1.9%).
Table 1. Clinical characteristics of 74 patients with non-small cell
lung cancer
Characteristics No. (%)
Age (years)* 59±9 (32-76)
Sex Male 65 (88%)
Female 9 (12%)
Location of tumour
Right 46 (62%)
Left 28 (38%)
Clinical T status
T1 59 (80%)
T2 15 (20%)
Clinical N status
N0 63 (85%)
N2 11 (15%)
Mediastinoscopy
Yes 53 (71.6%)
No 21 (28.3%)
*=Mean ± SD (range).
Table 2. Characteristics of 73 patients with non-small cell lung
cancer who underwent pulmonary resection
Variable No. (%)
Surgical procedure
Lobectomy 60 (82%)
Pneumonectomy 7 (9%)
Segmentectomy 1 (2%)
Wedge resection 5 (7%)
Mediastinal dissection
Systematic 41 (56%)
Random sampling 32 (44%)
Average tumour size 2.2 cm
Histologic type
Squamous cell carcinoma 40 (55%)
Adenocarcinoma 29 (40%)
Large cell 4 (5%)
Nodal status (postoperative)
N0 48 (66%)
N1 23 (31.5%)
N2 2 (2.7%)
The preferred type of resection (Table 2) was
lobectomy which was performed in 60 cases (80.8%).
Five cases underwent wedge resection and one
underwent segmentectomy due to insufficient
pulmonary capacity. Seven patients underwent
pneumonectomy. This included four cases with upper
lobe tumour invading lymphatic sump detected
intraoperatively with frozen section, and three cases
with severe hilar adhesions (which caused pulmonary
hemorrhage in two of them). For mediastinal lymph
nodes either systematic sampling (n=41) or random
sampling (n=32) was performed at the discretion of the
Mediastinoscopy in Non-small Cell Lung Cancer S.I. Dincer et al
2006; Vol. 48 The Indian Journal of Chest Diseases & Allied Sciences 251
surgeon. The mean diameter of the tumour was 2.2 cm.
The most common histologic type was squamous cell
carcinoma (55%). Postoperative pathology report
revealed that 48 of the cases had N0, 23 had N1, and
only two had N2 disease.
Two patients had mediastinal lymph node
metastases after thoracotomy. Both of these cases had
undergone mediastinoscopy before thoracotomy, but no
metastasis was found at that time. One of them with
squamous cell carcinoma in the right upper lobe was
found to have right lower paratracheal lymph node
metastases. The patient was staged clinically T1N2 and
underwent right upper lobectomy. Thus, the rate of
mediastinal lymph node metastases in cN2 group was
one in 11 cases (9%). Another patient with squamous
cell carcinoma in the left lower lobe had subcarinal
lymph node metastases. He was staged T1N0 clinically
and underwent left lower lobectomy. In contrast to high
rate lymph node metastases in cN2 group, the rate of
lymph node metastases in cN0 group was 1.6%. Both of
them were referred to oncology for adjuvant therapy.
Five-year survival was found in 73% of cases (Figure
1). The case with positive right lower paratracheal and
the other with subcarinal lymph nodes are both alive
and disease free at 7
th
and 4
th
year respectively.
Comparison of the N status in the present study with
observations from other published studies is shown in
table 3.
DISCUSSION
In lung cancer many procedures have been used to
explore mediastinum for staging but mediastinoscopy
remains to be the gold standard. Recently, it has been
used routinely in patients with NSCLC. We had
performed preoperative mediastinoscopy in almost all
patients who were eligible for surgical operation, to
assess N factors before the operation. But after the year
2000 we did not perform mediastinoscopy if the patient
had T1, epidermoid type NSCLC and with no
detectable lymph nodes on CT scan of the chest.
Though mediastinoscopy is considered a minimally
invasive technique, it is not totally safe because it carries
a certain morbidity and mortality. In published
literature the morbidity and mortality of mediast-
inoscopy has been reported to be 0.03% to 2.3%
3,4,6
. We
recently reported our experience with mediast-
inoscopy
6
. Our mortality and morbidity rates were 0.3%
and 1.7% respectively. For this reason it becomes a
dilemma whether to perform mediastinoscopy
routinely, especially in clinical T1 cases in whom the
incidence of mediastinal metastases is very low.
Many reports have presented the results of
mediastinoscopy in patients with lung cancer
4-8, 14-16
,
whereas detailed analysis of the results of medias-
tinoscopy by N factors, in particular those of T1 cases,
has been limited
1,7,8,10
. It has been reported that the rate
of mediastinal lymph node metastases in pathological
T1 cases can increase up to 18%, whereas when
published series with more than 100 cases are consid-
ered the rate decreases to as low as 2.5%
1, 5, 7-13
(Table 3).
The source of different rates in the literature originates
from the variations of the patients’ characteristics. Some
studies included clinical or radiological N2 cases and
some included only certain histopathologic types. In
Sakao et al
11
series all cases had adenocarcinoma, while
Funatsu et al
1
had observed adenocarcinoma in most of
the cases.
In the present series N2 rate is quite low when
compared to some series in the literature
1,5,7-13
. A possible
explanation of this low rate could be relatively high rate
of squamous cell carcinoma in our series (Table 3).
Interestingly this series had relatively higher rate of N1
disease compared to literature
1, 5, 7-13
.
Figure 1. Cumulative survival of all resected pathological T1
non-small cell lung cancer patients.
Table 3. N status of previous studies with pathological T1 tumours
Study (year) No. of N0 N1 N2 N3
Cases No. No. (%) No. (%) No. (%)
Coughlin et al (1985)
7
202 - - 30 (14.9) -
Jolly et al (1991)
8
145 - - 15 (10) -
Funatsu et al (1994)
1
164 125 16 20 (12) 3 (2)
Mountain et al (1997)
5
640 511 76 (11.8) 53 (8.3) -
van Rens et al (2000)
9
513 416 84 (16.3) 13 (2.5) -
Tahara et al (2000)
12
17 13 1 3 (8) -
Sakao et al (2003)
11
54 43 2 9 (17) -
Lardinois et al (2003)
13
23 - - 2 (9) 5 (22)
Current series 74 48 23 (31.5) 2 (2.7) 1 (1.3)
Time (months)
Cumulative Survival
0
0
0
0
0
0
0
0
0
252
Only one patient was found to have contralateral
mediastinal lymph node involvement (N3 disease)
(1.7%) at mediastinoscopy. After thoracotomy two cases
had N2 disease; one at right paratracheal station
(number 4R) and the other subcarinal area (number 7).
Resection was possible in both cases and they were
referred to oncology for adjuvant therapy. The patient
with right upper lobe tumour was clinically T1N2 and
underwent mediastinoscopy. Right lower paratracheal
station was sampled and no disease was detected in
four lymph nodes. After thoracotomoy only one out of
six lymph nodes contained metastasis (minimal N2).
The other patient with positive subcarinal lymph node
was clinically T1N0 and also underwent medias-
tinoscopy. At thoracotomy two out of seven lymph
nodes contain metastasis and the lymph node was
located at posterior subcarinal area.
A striking finding is that mediastinal lymph node
metastases in clinical N2 group was found to be 9%,
whereas in clinical N0 group the rate of metastases was
only 1.6%. A recent study from our center
4
reported that
the chance of detecting mediastinal lymph node
metastases among all clinically N0 patients was 7.6%
after mediastinoscopy and 5% after thoracotomy in
patients found having no N2 disease with
mediastinoscopy.
In the literature, 5-year survival of T1 stage ranged
between 54% and 82%
14-19
. Five-year survival of T1N2
patients was reported to be between 20% and 41%
14-19
.
Recent reviews reported 5-year survival of T1N2, T2N2
and T3N2 cases to 41%, 22% and 13% respectively
20, 21
.
Overall, 5-year survival in this series was 73%. The case
with positive right lower paratracheal and the other
with subcarinal lymph nodes are both alive and disease
free at 7
th
and 4
th
year.
In our hospital, mediastinoscopy costs the patients
approximately 800ε. Mediastinoscopy revealed only one
patient with contralateral lymph node involvement,
and two patients had minimal N2 disease which could
not be detected at mediastinoscopy. No unnecessary
thoracotomy was performed in this series.
As a result, in patients with clinical T1 disease
especially with negative chest CT for mediastinal
lymphadenopathy, routine mediastinoscopy should be
used cautiously in order to prevent unnecessary
complications, to save time, and to decrease the cost of
treatment because the rate-mediastinal involvement is
extremely low in these patients.
REFERENCES
1. Funatsu T, Matsubara Y, Ikeda S, Hatakenaka R, Hanawa T,
Ishida H. Preoperative mediastinoscopic assessment of N
factors and the need for mediastinal lymph node dissection
in T1 lung cancer. J Thorac Cardiovasc Surg 1994; 108: 321-8.
2. Bury T, Dowlati A, Paulus P, Corhay JL, Hustinx R, Ghaye B,
et al. Whole-body 18FDG positron emission tomography in
the staging of non-small cell lung cancer. Eur Respir J 1997; 10:
2529-34.
3. Hammoud ZT, Anderson RC, Meyers BF, Guthrie TJ, Roper
CL, Cooper JD, et al. The current role of mediastinoscopy in
the evaluation of thoracic disease. J Thorac Cardiovasc Surg
1999; 118: 894-9.
4. Gurses A, Turna A, Bedirhan MA, Ozalp T, Kocaturk C,
Demir A, et al. The value of mediastinoscopy in preoperative
evaluation of mediastinal involvement in non-small cell lung
cancer patients with clinical NO disease. Thorac Cardiovasc
Surg 2002; 50: 174-7.
5. Mountain CF. Revisions in the new international staging
system for lung cancer. Chest 1997; 111: 1710-7.
6. Metin M, Solak O, Sayar A, Kutlu CA, Cuhadaroglu S,
Kocaturk C, et al. The results of staging and diagnostic
mediastinoscopy. Solumn 2002; 4: 402-5.
7. Coughlin M, Deslauriers J, Beaulieu M, Fournier B, Piraux M,
Rouleau J, et al. Role of mediastinoscopy in pretreatment
staging of patients with primary lung cancer. Ann Thorac Surg
1985; 40: 556-60.
8. Jolly PC, Hutchinson CH, Detterbeck F, Guyton SW, Hofer B,
Anderson RP. Routine computed tomographic scans,
selective mediastinoscopy, and other factors in evaluation of
lung cancer. J Thorac Cardiovasc Surg 1991; 102: 266-70.
9. van Rens MT, de la Riviere AB, Elbers HR, van Den Bosch
JM. Prognostic assessment of 2,361 patients who underwent
pulmonary resection for non-small cell lung cancer, stage I, II,
and IIIA. Chest 2000; 117: 374-9.
10. Gunluoglu Z, Solak O, Metin M, Gurses A. The prognostic
significance of skip mediastinal lymphatic metastasis in
resected non-small cell lung cancer. Eur J Cardiothorac Surg
2002; 21: 295.
11. Sakao Y, Sakuragi T, Natsuaki M, Itoh T. Clinicopathological
analysis of prognostic factors in clinical 1A peripheral adeno-
carcinoma of the lung. Ann Thorac Surg 2003; 75: 1113-7.
12. Tahara RW, Lackner RP, Graver LM. Is there a role for routine
mediastinoscopy with peripheral T1 lung cancers? Am J Surg
2000; 180: 488-92.
13. Lardinois D, Schallberger A, Betticher D, Ris HB.
Postinduction video-mediastionscopy is as accurate and safe
as video-mediastinoscopy in patients without pretreatment
for potentially operable non-small cell lung cancer. Ann
Thorac Surg 2003; 75: 1102-6.
14. Goldstraw P. The practice of cardiothoracic surgeons in the
preoperative staging of non-small cell cancer. Thorax 1992; 47:
1-2.
15. Miller JD, Gorenstein LA, Paterson GA. Staging; the key to
rational management of lung cancer. Ann Thorac Surg 1992;
53: 170-8.
16. Van Schil PE, Van Hee RH, Schoofs EL. The value of
mediastinoscopy in preoperative staging of bronchogenic
carcinoma. J Thorac Cardiovasc Surg 1989; 97: 240-4.
17. Jones DR, Detterbeck FC. Surgery for stage I non-small cell
lung cancer. In: Detterback FC, Rivera MP, Socinski MA,
Rosenman JG, editors. Diagnosis and Treatment of Lung Cancer:
An Evidence-Based Guide for the Practicing Clinician.
Philadelphia : W.B. Saunders Company; 2001: pp 177-90.
18. Mountain CF. A new international staging system for lung
cancer. Chest 1986; 89 (4 suppl): 225S-233S.
19. Naruke T, Goya T, Tsuchiya R, Suemasu K. Prognosis and
survival in resected lung carcinoma based on the new
international staging system. J Thorac Cardiovasc Surg 1988; 96:
440-7.
20. Vansteenkiste JF, De Leyn PR, Deneffe GJ, Lerut TE, Demedts
MG. Clinical prognostic factors in surgically treated stage
IIIA-N2 non-small cell lung cancer: analysis of the literature.
Lung Cancer 1998; 19: 3-13.
21. Detterbeck FC, Jones DR. Surgical treatment of stage IIIA
(N2) non-small cell lung cancer. In: Detterbeck FC, Rivera
MP, Socinski MA, Rosenman JG, editors. Diagnosis and
Treatment of Lung Cancer: An Evidence-based Guide for the
Practicing Clinician. Philadelphia: W.B. Saunders Company;
2001: pp 244-56.
Mediastinoscopy in Non-small Cell Lung Cancer S.I. Dincer et al
Original Article
A Five-Year Review of Tuberculosis Mortality Amongst
Hospitalised Patients in Ile-Ife
G.E. Erhabor, O.O. Adewole and O. Ogunlade
Department of Medicine, Obafemi Awolowo University Teaching Hospital Complex, Ile-Ife, Osun State,
Nigeria
ABSTRACT
Background. Death from tuberculosis (TB) is the longest recorded indicator of the TB epidemic in industrialised countries.
This study aims at investigating into various factors associated with death in hospitalised patients with tuberculosis in Ile-
Ife, Nigeria.
Methods. A retrospective study of all admissions into the medical wards, total number of deaths and number of cases of
deaths due to TB during the period 1998-2000 was done.
Results. Tuberculosis represented 8% (268) of all admissions (n=3464). The overall hospital mortality during the period under
review was 1030 (30%). Tuberculosis was responsible for 5% of all deaths while TB specific mortality was 18.3 percent. The
highest mortality was observed among patients between the 3
rd
and 4
th
decade of life with a male to female ratio 1.3 : 1. About
70% of the patients died within a week of admission. Pulmonary TB was responsible for 69% of deaths followed by
tuberculous meningitis (14%), retroviral illness (24%), anaemia (60%). Delayed presentation and diagnosis were identified
as factors commonly associated with death rate.
Conclusions. Delayed presentation and diagnosis were commonly associated with death. There is a need for more awareness
among patients and health care providers about tuberculosis. [Indian J Chest Dis Allied Sci 2006; 48: 253-256]
Key words: Tuberculosis, Human immunodeficiency virus, Anaemia, Hypertension.
[[Received: November 10, 2004; accepted after revision: November 23, 2005]
Correspondence and reprint requests: Dr G.E. Erhabor, Department of Medicine, Obafemi Awolowo University Teaching
Hospital Complex, PMB 5538, Ile-Ife, Osun State, Nigeria; E-mail: gregerhabor@yahoo.com.
INTRODUCTION
Morbidity and mortality from tuberculosis (TB) have
been on the increase in spite of increased understanding
of its natural history and advances in therapy. Indeed
Mycobacterium tuberculosis remains a leading cause of
death from a single infectious disease world over.
Every year about eight million people develop this
disease and some three million die of it, over 95% of
these from developing countries
1-4
. Projections suggest
that by the year 2050, annual death rate will exceed five
million a year. Majority of the deaths due to TB in Africa
occur between the age group of 15 and 59 years, making
TB a leading cause of a treatable disease within the
economically productive age group in the world
5,6
.
Tuberculosis is responsible for 26% of avoidable adult
deaths in the developing world
7
. Although the TB case
rate has declined during the past few years, there
remains a huge reservoir of individual infected with M.
tuberculosis
8
.
We undertook this study as a follow-up evaluation,
basing on our experience with previous studies, to
identify the risk factors associated with death in patients
with TB.
MATERIAL AND METHODS
This study covers a period of five years (1998-2002) and
the following inclusion criteria were applied: presence
of constitutional symptoms (fever, weight loss and
fatigue); chronic cough; and or pulmonary infiltrates on
chest radiograph which were consistent with the
diagnosis of TB; proven cases of TB by positive Ziehl-
Neelsen (ZN) stain of a diagnostic specimen such
sputum smears or smear of tissue [e.g., lymph node
biopsy, ascitic fluid, cerebrospinal fluid (CSF) and
histological or cytological diagnosis of TB in tissue
biopsy and ZN staining of aspirates]. Tuberculosis
patients who were seen only at out-patient clinics and
who were never admitted during the period under
review were not included in this study.
Each patient was assessed to determine the form of
TB, degree of delay due to patient, general practitioner
(GP) or a specialist hospital. They were also assessed to
determine if they were new or re-treatment cases by
questioning and by review of case-notes. Intervals from
admission to death were obtained by case-notes review
and admission records. Post-mortem reports were
obtained and reviewed in TB cases wherever possible.
254
Tuberculosis Mortality in Ile-Ife G.E. Erhabor et al
Additionally, patients were assessed to determine
whether the diagnosis of TB had been established, what
part TB played in the death of the patients and whether
there were any potential error in the management of
these cases.
Patients’ delay was defined as the presence of
symptoms for more than four weeks before presentation
at a formal health center. Delay due to GP or specialist
hospital was defined as the delay in referring patients to
chest clinic after three visits or commencing treatment
after more than one week of admission. Diagnosis of TB
was said to be never established when TB was
considered as a diagnosis but patients were not started
on treatment and diagnosis was confirmed at autopsy.
The diagnosis of TB meningitis, abdominal TB, TB
spine, renal TB and others were made on clinical
grounds supported by appropriate laboratory
investigations, such as CSF stain for acid-fast bacilli
(AFB), cytology, and biochemistry, ascitic fluid for
cytology and AFB. Abdominal scan was done in
patients with TB abdomen and renal TB.
Thoracolumbar x-rays were done in suspected cases of
TB spine. The abdominal scans and radiographs were
reviewed with radiologists. Cytology reports showing
lymphocytes, giant cells were taken as suggestive of TB,
even if ZN stain was negative for AFB.
RESULTS
There were 3464 admission in the medical wards over
the five-year period, of which 268 admissions were TB.
Overall 1030 patients (30%) died; 49 of the 268 patients
(18.3%) admitted with TB died. Forty-nine patients died
from TB giving a mortality rate of 18.3 percent.
Tuberculosis deaths represented 5% of all mortality.
The age of patients ranged from 9-79 years (mean
age 42 years). The highest mortality was recorded
between the 3
rd
and 4
th
decades of life. Socio-
demographic characteristics of TB patients who died are
shown in table 1. Mortality was also high among the
married patients and unskilled workers (Table 1).
Table 2 shows the interval between admission and
death, 51% of the deaths occurred within the first week
of admission while only 4.1% died after four weeks. The
average number of months the patients had TB was 5.5
months. Majority of deaths occurred in patients already
or supposed to be on continuation phase of treatment.
Seven patients were on re-treatment while the
remaining 42 were new patients.
As shown in table 3, majority of the mortality was
due to TB with active disease contributing 59.2% of the
mortality. Also shown is that TB was a contributing
factor in 20.4%, while the diagnosis of TB was not
established in nine patients.
Majority of patients (69.4%) died due to pulmonary
TB while miliary TB and tuberculosis meningitis
contributed to 14.3% and 10.2% deaths, respectively.
There was no recorded death due to renal TB.
Table 4 shows associated co-morbid factors. Human
immunodeficiency virus (HIV) topped the list with
16.3%, coming close to it were anaemia and
hypertension accounting for 14.3% and 12.2%,
respectively. In 22.4%, there were no identifiable co-
morbid condition.
Table 5 shows that diagnosis delay by patients was
responsible for about two-thirds of deaths, while delay
caused by general practitioners and specialist hospital
contributed 6.1% and 14.5%, respectively. Poor drug
compliance was identified as the main management
shortcoming in 12.2% of deaths.
Table 1. Socio-demographic characteristics of 49 patients who
died due to tuberculosis
Variable No. (%)
Sex
Male 28 (57.1)
Female 21 (42.9)
Age (years)
0-9 2 (4.1)
10-19 5 (10.5)
20-29 7 (14.2)
30-39 10 (20.4)
40-49 9 (18.4)
50-59 4 (8.2)
60-69 9 (18.4)
70-79 3 (6.1)
Marital Status
Married 37 (75.5)
Single 12 (24.5)
Occupation
Skilled 5 (10.2)
Unskilled 31 (63.3)
Unemployed 13 (26.5)
Religion
Christianity 39 (79.6)
Islam 10 (20.4)
Table 2. Time interval between admission and death
Time interval (weeks) No. (%)
<1 25 (51.0)
2-4 22 (44.9)
>4 02 (4.1)
Total 49 (100)
Table 3. Classification of patients certified as having died due to
tuberculosis
Assessor’s Classification No. (%)
Died due to tuberculosis
Active disease 29 (59.2)
Late effects of inactive disease 1 (2.0)
Died with tuberculosis as a contributing factor
Active disease 6 (12.2)
Late effects of inactive disease 4 (8.2)
Tuberculosis present but irrelevant –
Diagnosis of TB never established 9 (18.4)
Total 49 (100.0)
2006; Vol. 48 The Indian Journal of Chest Diseases & Allied Sciences 255
DISCUSSION
Our study corroborates previous studies on TB in
developing countries, in which mortality was mainly in
the second and third decades of life
11
. Published data
suggests that 80% of those infected in industrialised
nations are aged 50 years and above, while 75% of those
in developing countries are less than 50 years
1
. This
finding contrasted with earlier study by Bandele et al
12
on TB mortality in Nigeria. In that study
12
conducted
about two decades ago, 240 deaths were recorded due
to TB. Active immunization with Bacille Calmette-Gurin
(BCG) vaccine and improve nutrition and emphasis on
child health may have tilted the balance towards the
adult age group as seen in our study. Moreover, HIV
would have lead to reactivation of TB in patients who
were previously infected and have gone into dormant
phase. In our study, 16.3% deaths were associated with
HIV. Of all the risk factors for the development of TB,
HIV is by far the most potent with a relative risk of 6 to
100 when compared with HIV-negative individuals
13
.
Another major cause of increasing mortality from
TB-HIV co-infection is the problem of drug resistance.
Drug resistance (either mono or multidrug-resistance) is
increasing rapidly in under privileged, non-compliant,
and minority groups in developed countries in whom it
is fatal
14, 15
. Africa in particular is experiencing a major
resurgence in TB mainly as a consequence of the overlap
between increasing levels of latent TB and increasing
levels of HIV infections
16
, with the prevalence of HIV-TB
co-infection ranging from 20 percent to 65 percent.
However, mortality rate is higher in patients with HIV/
AIDS and TB
17, 19
.
Mortality is highest among those who presented
within one week of admission. This high figure of
patients dying within one week could be attributed to
delay in presentation. Delay in presentation is a major
problem in most parts of the world, especially in our
environment. The frequency of patient delay is lower
than the 29% found in India and 44% found in
Ghana
20, 21
. In the earlier study referred to done in
Lagos
12
, 45.6% of delay in diagnosis were due to
patients delay. In this study, about 56% of deaths were
associated with delay in diagnosis due to patient
factors. In another 22%, compliance with clinic
attendance and medication were sub-optimal. This is
reflected by the fact that majority of the patients had a
mean delay of 5.5 months.
Delays are often multi-factorial; they may occur as a
result of patient’s perceptions of the disease, fear of
stigma or difficult access to health facilities. In certain
cases some patients may prefer seeking treatment in the
traditional or private sector. Delay in diagnosis of TB is
unacceptable as it may compromise the chance of a
successful outcome, and lead to increase transmission of
TB both in the household and in the community. Delay
is also costly both to the patients and to health facilities.
It strains already weak health system especially in
developing countries as more resources will have to be
allocated to take care of the complications that could
develop from delay. As shown in this study,
considerable delay occurred due to general practitioner
or specialist hospitals. This is a reflection of poor
awareness of diagnostic practices about TB in our
environment.
Pulmonary TB, especially smear negative TB, was
the most common form of lesion in this study associated
with the highest death rate. It was responsible for death
in 69.4% followed by miliary TB (14.3%). The
pulmonary TB is of great importance, as sputum smear-
positive TB has a much higher fatality than sputum
smear-negative TB
23
. This is exemplified in a long-term
follow-up study of TB patients to Swiss Sanatorium
between 1912 and1927 where case fatality approached
60% in open TB compared to 10% to 15% in smear-
negative TB
22
. Though there have been no recent follow
up studies, mortality from pulmonary TB is still highest
in Nigeria irrespective of the sputum AFB status. This
might not be unconnected with the fact that pulmonary
TB is the most common lesion generally in Nigeria,
accounting more than 80% of cases
23
.
Anaemia was associated with death in 14.3% of the
cases. In a recent review of clinico-radiological
presentation of 340 adults with TB in the Gambia over a
third of the patients, were found to be anaemic
24
. This
was corroborated by other studies from India
25
and
Hungary
26
where the prevalence of anaemia was 84% to
86% and 32%, respectively. The presence of anaemia
could be considered a bad prognostic index. The causes
of anaemia in these patients could be multi-factorial and
could be due to causes, such as chronic malnutrition
and haemoptysis. Co-morbid medical conditions, like
chronic renal disease and chronic liver disease as seen in
this study, could also be contributory. Also, bone
Table 5. Factors associated with death in 49 patients who died
due to tuberculosis
Factor No. (%)
Diagnostic delay caused by patient 32 (65.3)
Diagnostic delay in specialist hospital 7 (14.3)
Patient management shortcomings 6(12.2)
Diagnostic delay caused by general practitioners 3 (6.1)
Management shortcomings in specialist hospital 1 (2.0)
Table 4. Associated medical conditions in patients who died due
to tuberculosis
Medical Condition No. (%)
Nil 11 (22.4)
HIV 8 (16.3)
Anaemia 7 (14.3)
Hypertension 6 (12.2)
Heart failure 4 (8.2)
Malnutrition 2 (4.1)
Chronic renal failure 2 (4.1)
Chronic liver disease 1 (2.0)
HIV = human immunodeficiency virus
256
marrows findings in patients with TB in a study done in
Ibadan
27
revealed that there were depressed erythroid
activity in 69% of the patients, micronormoblastic
changes in 18% and megaloblastic changes in 16.6%,
while stainable iron in the marrow was found to be low
or negative in 88.8% of the patients
28
.
Tuberculosis may be missed as a primary diagnosis
in most groups of patients who are not producing
sputum and especially in patients with extra-
pulmonary TB. There is, therefore, increased index of
suspicion is required in an environment where TB is
endemic and improved diagnostic methods are not
routinely available. This underscores the importance of
detecting patients with latent TB infection.
Within the limit of retrospective analysis one would
say that a typical patient likely to die of TB will be a
young male, presenting late and poorly compliant to
therapy. The presence of HIV infection and anaemia
would lead to further deterioration of the patient’s
condition. The challenge is to diagnose patients early
and to ensure prompt treatment. Directly observed
treatment, short-course (DOTS) has helped to improve
compliance in our environment, however, it is still to be
universally applied in Nigeria. Our study is limited by
the fact that we do not study the role of drug resistance.
This could not be done as drug susceptibility is not
routinely done in our environment.
ACKNOWLEDGEMENTS
We want to express our gratitude to the Staff of the Chest Clinic for
their assistance, the Damien Foundation for providing free drugs
for our tuberculosis patients and Miss Jumoke and Folake for their
secretarial assistance.
REFERENCES
1. Kochi A. The global tuberculosis situation and the new
control strategy of the World Health Organization. Tubercle
1999; 72: 1-6.
2. Martin P. Tuberculosis at the end of the Century. Med Digest
1996; 22: 10-4.
3. Benatar R. Prospects for global health: lesson from
tuberculosis. Thorax 1995; 50: 487-9.
4. Brown P. A disease that is alive and kicking. World Health
1993; 4: 4-5.
5. Porter J, Adam K, Feachem R. The challenge in international.
World Health 1993; 4: 10-12.
6. Murrary CJ, Styblo K, Rouillon A. Tuberculosis in developing
countries: burden, intervention and cost. Bull Int Union Tubere
Lung Dis 1990; 65: 6-24.
7. Bloom BR, Murray CJ. Tuberculosis: commentary on a re-
emergent killer. Science 1992; 257: 1055-64.
8. Centers for Disease Control and Prevention. Guidelines for
preventing the transmission of Mycobactcrium tuberculosis in
health cane facilities, 1994. MMWR 1994; 43: 1-132.
9. Erhabor GE, Aghanwa HS, Yusuph M, Adebayo RA,
Arogundade FA, Omidiora A. Factors influencing in patients
with tuberculosis on directly observed therapy at Ile-Ife,
Nigeria. East Afri Med J 2000; 75: 325-9.
10. Erhabor GE, Adewole O, Adisa AO, Olajolo OA. Directly
observed short course therapy for tuberculosis: a preliminary
report of a three-year experience in a Teaching Hospital. J
Natl Med Assoc 2003; 95: 1082-8.
11. Kolawole TM, Onadeko EO, Sofowora EO, Esan GF.
Radiographical pattern of pulmonary tuberculosis in Nigeria.
Trop Geogr Med 1975; 27: 339-50.
12. Bandele EO, Olude IO. An analysis of deaths due to
tuberculosis at the Lagos University Teaching Hospital. J Natl
Med Assoc 1985; 7: 643-6.
13. Nunn PP, Elliot AM, Mc Adam KP. Tropical respiratory
medicine. 2. Impact of human immunodeficiency virus on
tuberculosis in developing countries. Thorax 1994; 49: 511-8.
14. Valway SE, Richards SB, Kovacovich J, Greinfinger RB,
Crawford JT, Dooley SW. Outbreak of multidrug-resistant
tuberculosis in a New York State prison 1991. Am J Epidemiol
1994; 140: 113-22.
15. Espinal MA, Laserson K, Camacho M, Fusheng Z, Kim SJ,
Tlali RE, et al. Determinants of drug-resistant tuberculosis:
analysis of 11 countries. Int J Tuberc Lung Dis 2001; 5: 887-93.
16. Lucas SB, Hounnou A, Peacock C, Beaumel A, Djmand G,
N’Gbichi JM, et al. The mortality and pathology of HIV
infection in a West African City. AIDS 1993; 7: 1569-79.
17. World Health Organization. Global tuberculosis control:
surveillance, planning, financing. WHO Report 2002. Available
at URL: http//www.who.int/gtb/publications/globrep02/
contents.html. Accessed on May 8, 2005.
18. Harries AD, Hargreaves NJ, Chimzizi R, Salanoponi FM.
Highly active antiretroviral therapy and tuberculosis control
in Africa: synergies and potentials. Bull World Health Organ
2002; 80: 464-9.
19. Salami AK, Oluboyo PO. Hospital prevalence of pulmonary
tuberculosis and co-infection with human immunodeficiency
virus in Ilorin: a review of nine years (1991-1999). West Afr J
Med 2002; 21: 24-7.
20. Rajeswari R, Chandrasekaran V, Suhadev M,
Sivasubramaniam S, Sudha G, Renu G. Factors associated
with patient and health system delays in the diagnosis of
tuberculosis in south India. Int J Tuberc Lung Dis 2002; 6: 789-
95.
21. Lawn SD, Afful B, Acheampong JW. Pulmonary tuberculosis:
diagnostic delay in Ghanaian adults. Int J Tuberc Lung Dis
1998; 2: 635-40.
22. Krebs W, Die Falle Von. Lungentuberkulose in den aqrgauischer
Heilstatte Barmelweid aus den Jahnen 1912-1927. Beitrklin Tuberk
1930; 74: 345-79.
23. National Tuberculosis and Leprosy Control Programme.
Workers Manual, 3
rd
edn. Nigeria: Federal Ministry of Health,
2003; pp 1-43.
24. Rathman G, Sillah J, Hill PC, Murry JF, Adegbola R, Corrah
T, et al. Clinical and radiological presentation of 340 adults
with smear-positive tuberculosis in the Gambia. 2003; 7: 942-
7.
25. Singh KJ, Ahluwalia G, Sharma SK, Saxena R, Chaudhary
VP, Anant M. Significance of haeamatological manifestation
in patients with tuberculosis. J Assoc Physicians India 2001; 49:
788, 790-4.
26. Bozoky G, Ruby E, Gother I, Toth J, Mohos A. Haemato-
logical abnormalities in pulmonary tuberculosis. Orv Hetil
1997; 138: 1053-6.
27. Olaniyi JA, Aken’ Ova YA. Bone marrow findings in patients
with pulmonary tuberculosis. Afr J Med Sci 2003; 32: 155-7.
Tuberculosis Mortality in Ile-Ife G.E. Erhabor et al
Original Article
Pleurocutaneous Flap: How Useful It is in Management of
Chronic Empyema
Arvind Kohli, Gurjit Singh, Anita Vig, Kavi Raj Dubey and Rajinder Singh
Cardiothoracic and Vascular Surgery Unit, Government Medical College, Jammu, India
ABSTRACT
Background. Definitive surgical treatment of chronic empyema is associated with considerable morbidity and mortality.
Methods. Retrospective study of 50 patients with chronic empyema who underwent pleurocutaneous flap procedure during
the period 1994 to 2003.
Results. Their age ranged from 14 to 70 years; there were 32 males. Thirty-seven (74%) patients were on intercostal tube
drainage; nine (18%) presented with bronchopleural fistula; and four (8%) had past-pneumonectomy empyema. Following
pleurocutaneous flap procedure, 28 (56%) responded with re-expansion of the lung; 15 (30%) had persistence of pus discharge
and air-leak suggestive of bronchopleural fistula. Definitive surgery could be undertaken in nine of the 15 patients.
Conclusions. Pleurocutaneous flap procedure renders the patient ambulatory, facilitates re-expansion of the lung and helps
as a tide-over procedure before definitive surgery in patients with chronic empyema.
[Indian J Chest Dis Allied Sci 2006; 48:
257-259]
Key words: Chronic empyema, Pleurocutaneous flap procedure.
[Received: August 2, 2005; accepted after revision: December 9, 2005]
Correspondence and reprint requests: Dr Arvind Kohli, 39B/D, Gandhi Nagar, Jammu Tawi - 180004 (J & K), India;
E-mail: Drarvind7@sancharnet.in.
INTRODUCTION
The diagnosis and treatment of empyema was first
described by Hippocrates over 2000 years ago. Virtually
nothing else pertaining to this disease was recorded
until the early 18
th
Century. Since that time, numerous
treatments have been described including open and
closed tube drainage, thoracentesis and thoracoplasty
1
.
Open drainage was often successful and did not
result in pneumothorax, because most cases of
empyema were associated with adhesions and
thickened visceral pleura that prevented the lung from
collapsing. The epidemic of group A streptococcal
pneumonia in military camps in 1917-1918 was
associated with the rapid and early accumulation of
empyema fluid and was the catalyst renewed study of
empyema. Use of open drainage to manage this illness
resulted in a high immediate mortality rate, probably
because patients developed pneumothorax. The work
of Graham
2
and the Empyema Commission married the
physiological understanding of pleural mechanics with
rational clinical treatment and paved the way for
further advances in thoracic surgery.
Eloesser
3
observed that the cure of empyema is made
difficult by the tenacity with which the underlying lung
resists expansion. Furthermore, it is made difficult by
the unfavourable effect of an in-dwelling drainage tube
of any kind leading to sepsis. The desire to obviate the
drainage lead to this operation in which a
pleurocutaneous flap is created leading to open
drainage of pleural space. We report our experience
with this procedure.
MATERIAL AND METHODS
Fifty patients presenting with chronic empyema who
underwent pleurocutaneous flap formation at our unit
from 1994 to 2003 were studied. The diagnosis of
chronic empyema was clinical and patients were not fit
for undergoing definitive surgery at the outset.
The patients included in the study were not having
desired response to conservative management. In
addition to this, most of the patients were unable to
undergo decortication because of the poor general
condition. Posteriorly placed empyema which was
unsuitable for tube placement and patients having
mental illness not cooperating with prolonged tube
drainage were also given the benefit of this procedure.
A detailed history was obtained and a thorough
clinical examination was done. Chest radiograph in
postero-anterior and lateral views were done in all the
patients. The procedure was conducted under local
anesthesia.
A U-shaped flap of skin and subcutaneous tissue was
outlined anterior to posterior axillary line and inferior
scapular angle. However, the exact placement of
258
formation of flap was thought of after assessing the site
of loculation or the site of an already introduced
intercostal tube. The flap had a base of two inches width
and was about two-and-a-half inch long to reach the
pleural cavity without tension. The rib underlying the
flap was resected, amount resected equaling the width
of the flap. The tip of the flap was turned into the chest
and tacked to parietal pleura with one or two sutures
and this kept the window open allowing the lung to re-
expand after which it closes spontaneously and
automatically (Figure 1). Adequate drainage of pus was
the criterion for a good pleurocutaneuos window.
Patient himself or his attendant could change the
dressing.
Although we did not refuse this procedure to any
patient, the contraindications kept in mind were in
patients in whom the lung was so badly affected that
expansion to any degree did not seem possible, patients
who had persistence of bacilli bearing sputum with
large cavities and extensive parenchymal damage in
whom definitive procedure in the form of thoracoplasty
was thought to be safer.
Post-operative follow-up carried at one, three and six
months and at one year intervals. Clinical examination,
daily pus discharge and airleak, culture sensitivity of
pus, chest radiograph indicating the re-expansion of the
lung were assessed during follow-up visits.
RESULTS
Their age ranged from 14 to 70 years, there were 32
males. Majority of the patients (n=21) were in their third
decade of life. Thirty-seven patients (74%) presented
had already undergone tube thoracostomy and were on
intercostal tube drainage; nine (18%) with
bronchopleural fistula; and four 8% had post-
pneumonectomy empyema. Thirty-eight (76%) patients
were already receiving antituberculosis treatment.
The response was in the form of re-expansion of lung
in 28 (56%) patients which occurred 3 to 24 months after
the formation of the flap (Figures 1, 2 and 3). The
majority of these patients had presented with complete
collapse of the lung against the mediastinum despite a
functional pleural drainage tube, and a few of them had
minimal re-expansion of the lung with persisting pus
discharge. Along with the re-expansion there was
cessation of pus discharge, as well as spontaneous
closure of the flap in these patients. Fifteen (30%)
patients had persistence of pus discharge and
prolonged air-leak, suggestive of bronchopleural fistula
and re-expansion could not be achieved in them. Nine
of them were taken up for definitive surgery. The
procedures conducted were decortication in six cases,
pneumonectomy in one and lobectomy in two cases.
One patient died following definitive surgery. Pus
culture was positive in 22 (44%) patients. This included
S. aureus (n=13), S. pneumoniae (n=7) and P. aeruginosa
Pleurocutaneous Flap in Chronic Empyema A. Kohli et al
Figure 1. Pleurocutaneous flap in a male patient with chronic
empyema formed on the right side.
Figure 2. Chest radiograph (postero-anterior view) of the same
patient at the time of formation of the flap.
2006; Vol. 48 The Indian Journal of Chest Diseases & Allied Sciences 259
(n=2). They were treated with appropriate antibiotics as
per culture sensitivity. Seven (14%) patients were lost to
follow-up.
DISCUSSION
This study highlights the usefulness of pleuro-
cutaneous flap in three ways; the patient become free
from the intercostal tube, become ambulatory and can
undergo domiciliary treatment. It also helps in
achieving re-expansion of the lung obviating any major
definitive surgical procedure and finally in sick patients,
it can act as tide-over procedure, which subsequently
can be complemented with a definitive procedure.
Wilcox
4
described a modification of the original tech-
nique by Eloesser in which a rectangular flap of skin
and subcutaneous tissue is elevated along the line of the
rib to be removed with its base lateral or medial. After
excision of the long segment of the rib, the skin flap is
tacked lightly to the parietal pleura and periosteum
creating a tract lined on one aspect with epidermis.
Galvin et al
5
described the procedure of triangular
window thoracostomy for management of empyema
with bronchopleural fistula. They recommended its use
either as a permanent stoma or as an interim measure
before definitive surgical treatment.
Ali et al
6
presented a series of 47 patients managed
for primary mixed tuberculosis empyema with near or
Figure 3. Chest radiograph (postero-anterior view) of the same
patient after six months showing progressive expansion of the
lung.
total lung collapse over a period of seven years. In this
study
6
, 28 patients achieved complete re-expansion the
lung after 4 to 30 months of drainage and were
completely cured, 11 were in the stage of re-expansion
and in eight patients there was no-expansion. In their
study
6
, irrigation of the cavity was performed after
creating a pleurocutaneous window. Re-expansion was
gradual, progressive and dependent upon improved
compliance, clearing of bronchial inflammation and
obstruction and pleural cleansing, as was observed in
our study. In cases with bronchopleural fistula, the
closure is accomplished by sealing the granulation
tissue against the chest wall.
Katsuragi et al
7
presented a retrospective analysis of
33 cases who underwent open window thoracostomy
for chronic tuberculosis empyema with bronchopleural
fistula. They concluded that in elderly with severe
impairment of the pulmonary function, open window
thoracostomy does not control the empyema well and
has a high rate of mortality.
Graham
3
described the mechanism of lung re-
expansion in patients with open drainage for bacterial
empyema and attributed this re-expansion to the
gradual pull of adhesions between the lungs and the
chest wall. Such has not been the experience with
tuberculosis empyema (which was frequently
encountered in our series), where lack of expansion
necessitated decortication, lung resection and thora-
coplasty in the past. However with the advent of
modern-day antituberculosis treatment, the pulmonary
and bronchial components are controlled and lung
becomes capable of re-expansion. Only nine (18%)
patients had to undergo decortication/lung resection in
our series.
REFERENCES
1. Somers J, Faber LP. Historical developments in the manage-
ment of empyema. Chest Surg Clin North Am 1996; 6: 403-18.
2. Aboud FC, Verghese AC. Evarts Ambrose Graham,
empyema, and the dawn of clinical understanding of
negative intrapleural pressure. Clin Infect Dis 2002; 34: 198-
203. (Epub. 2001 Dec. 7).
3. Eloesser L. An operation for tuberculous empyema. Surg
Gynecol Obstet 1935; 60: 1096.
4. Wilcox BR. Chronic empyema. In: Glenn’s Thoracic and Cardio-
vascular Surgery; 4
th
ed. Philadelphia: W.B. Saunders & Co.;
1983: pp 155.
5. Galvin IF, Gibbons JR, Maghout MH. Bronchopleural fistula:
a novel type of window thoracostomy. J Thorac Cardiovasc
Surg 1988; 96: 433-5.
6. Ali SM, Siddiqui A, Mclaughlin JS. Open drainage of massive
tuberculous empyema with progressive re-expansion of lung:
an old concept revisited. Ann Thorac Surg 1996; 62: 218-23;
discussion 223-4.
7. Kasturagi N, Shiraishi Y, Nakajima Y, Kurai M, Takahashi N.
Evaluation of open window thoracostomy for chronic
tuberculous empyema with bronchopleural fistula: a
retrospective analysis of 33 cases. Kyobu Geka 2005; 58: 175-80;
discussion 181-3.
8. Graham E, Singer J, Ballon H. Surgical Diseases of Chest.
Philadelphia: Lea & Febiger; 1935: pp 118-81.
260 The Indian Journal of Chest Diseases & Allied Sciences 2006; Vol. 48
ICMR-NIC Centre for Biomedical Information, designated as 17th International MEDLARS
Centre or Indian MEDLARS Centre (IMC), offers medical professionals/researchers/medical library
professionals with:
• IndMED database: Free access to bibliographic information from over 70 Indian peer
reviewed Indian biomedical journals.
• medIND database: Unlimited free access to full-text of select peer reviewed Indian
biomedical journals. This database includes IndMED journals as well as prominent Indian
journals covered in Medline.
• Union Catalogue of Biomedical Periodicals: Free access to journals' holdings data from over
188 libraries across India. Helps in locating journals in libraries and is searchable by journals'
name or library names.
• OpenMED@NIC: Free access to open access archive for Medical and Allied Sciences. Free
registration for authors/owners to self-archive their scientific and technical documents.
• Training Programme: Training offered to medical professionals in “Biomedical Information
Retrieval”. Covers information retrieval techniques to search Web resources in an effective
and efficient manner.
Visit our website at http://indmed.nic.in
Aetiology and Clinical Profile of Spontaneous Pneumothorax in
Adults
Dheeraj Gupta, Sanjay Mishra, Shoaib Faruqi and Ashutosh N. Aggarwal
Department of Pulmonary Medicine, Postgraduate Institute of Medical Education and Research,
Chandigarh, India
ABSTRACT
Background. Limited information is available on epidemiology of spontaneous pneumothorax (SP) from India. The present
study was aimed at studying aetiology and clinical profile of patients with SP.
Methods. All patients admitted at a tertiary care hospital with the diagnosis of SP between January 2001 and March 2002
were prospectively studied. Detailed demographic and clinical data were recorded. Patients were divided into two groups-
primary spontaneous pneumothorax (PSP), if no underlying aetiology for pneumothorax was found, and secondary
spontaneous pneumothorax (SSP), when an underlying respiratory disorder could be identified. The clinical features were
compared between the two groups.
Results. Sixty patients (12 with PSP and 48 with SSP) were included in the study. Annual incidence of SP was calculated as
99.9 per 100,000 hospital admissions. Annual incidence figures for PSP and SSP were 20.0 and 80.0 per 100,000 hospital
admissions respectively. Age distribution showed a biphasic pattern and the overall male to female ratio was 5 : 1. The most
common cause of SSP was found to be pulmonary tuberculosis (41.7%).
Conclusions. Pneumothorax is more common among men. In India, SSP is far more common than PSP, and the predominant
underlying cause is pulmonary tuberculosis.
[Indian J Chest Dis Allied Sci 2006; 48: 261-264]
Key words: Spontaneous pneumothorax, Epidemiology.
[Received: July 7, 2005; accepted after revision: November 29, 2005]
Correspondence and reprint requests: Dr Dheeraj Gupta, Additional Professor, Department of Pulmonary Medicine,
Postgraduate Institute of Medical Education and Research, Chandigarh-160012, India; Tele.: 91-172-2756823; Telefax: 91-172-
2745959; E-mail: dheeraj@indiachest.org.
Original Article
INTRODUCTION
Pneumothorax is defined as the presence of air in the
pleural cavity. It is usually classified into spontaneous,
occurring without a preceding cause, and traumatic
which follows penetrating, blunt or barometric trauma
to the chest. Spontaneous pneumothorax (SP) is
subdivided into primary spontaneous penumothorax
(PSP), occurring in otherwise healthy individuals and
secondary spontaneous pneumothorax (SSP), which
occurs in patients with an underlying lung disease
1
.
The aetiology and clinical spectrum of
pneumothorax have undergone a marked change in the
recent years. For example, pulmonary manifestations of
acquired immunodeficiency syndrome (AIDS) have
emerged as important cause of SSP
2
. Data regarding
epidemiology and clinical profile of SP are limited,
especially so from the Indian subcontinent. Besides
several case reports focusing on pneumothorax, there
are few studies dealing with diagnosis and treatment of
SP in India
3-5
. Occasional studies have also dealt with
aetiology and clinical profile of SP in Indian adults and
children
6-8
. The present paper describes the aetiology
and clinical profile of adult patients admitted with SP to
a large tertiary care hospital.
MATERIAL AND METHODS
This was a prospective descriptive study conducted at a
tertiary care institute in North India between January
2001 and March 2002. All the patients admitted to the
hospital with a diagnosis of SP were included. A pre-
designed structured performa that had sections on
demographic details (age, gender, residence, smoking
habit), anthropometry [height, weight, body mass index
(BMI), upper segment to lower segment ratio], clinical
presentation (pre-existing known cardiopulmonary
disease or other comorbid conditions, respiratory and
other symptoms at presentation, findings on general,
respiratory and systemic examination), chest
radiography, and details of other relevant
investigations, was used to collect information.
Depending on results of initial clinical evaluation and
chest radiography, all patients underwent additional
262
detailed investigations to ascertain the underlying cause
for SP. The tests carried out for individual patients
included a variable combination of radiologic (e.g.,
thoracic CT scan), microbiological (e.g., sputum culture
and examination for acid-fast bacilli), serological (e.g.,
antibodies to bacteria, fungi, human immunodeficiency
virus), physiological (e.g., spirometry, static lung
volumes, diffusion capacity), and other investigations.
The patients were classified as having PSP if routine
clinical and radiologic evaluation, as well as results of
relevant additional investigations, failed to reveal a
disease process that could potentially explain the
occurrence of pneumothorax. All patients, in whom an
underlying pulmonary disorder that could be linked to
pneumothorax was detected, were categorized as
having SSP. Patients were treated with simple needle
aspiration or intercostal chest tube drainage as per the
standard practice at our institute
4
.
Group comparisons were made between patients
with PSP and SSP. Risk factor analysis for PSP was done
for variables like age, sex, smoking, BMI, height, upper
to lower segment ratio, and presence of exertion at the
onset, using patients with SSP as controls.
Results are described in a descriptive fashion using
percentage, mean and median. Statistical significance
was determined using Chi-square test, unpaired t-test
and Mann-Whitney test, and p value <0.05 was
considered significant. The study did not require any
intervention and was cleared by the ethics committee of
the hospital. Written informed consent was obtained
from all the patients before enrolment in the study.
RESULTS
Of the 60 patients included in the study, 12 (20%) had
PSP while 48 (80%) had SSP. Based on the total number
of admissions to our hospital during the study period,
the annual incidence of SP was calculated as 99.9 per
100,000 hospital admissions. Annual incidence figures
for PSP and SSP were similarly calculated as 20.0 and
80.0 per 100,000 hospital admissions respectively.
The patients studied had a mean age of 34.5 years
(range 13-74). Patients with PSP were significantly
younger as compared to patients with SSP (mean age
26.0 years vs 36.8 years, p<0.05). Majority of patients
included in the study were men, with an overall male to
female ratio of 5 : 1. The male preponderance was even
more dominant in PSP as compared to SSP (male to
female ratio 11:1 and 4.3 : 1 respectively). The age
distribution of patients showed a biphasic pattern. The
first peak occurred between 20 and 30 years of age, and
was mainly contributed by PSP, while the second
occurred between 40 and 50 years, and was mainly
contributed by SSP. Nearly half the patients (29 out of
60) had smoked tobacco, of whom four had PSP and 25
had SSP. Patients with PSP were significantly taller than
those with SSP. However, weight and BMI were lower
in patients with SSP. There were no significant
differences in the upper/lower segment ratio between
patients in the two groups (Table 1).
Table 1. Anthropometric data in patients presenting with
spontaneous pneumothorax
SP PSP SSP p
value
Height (cm)
Range 130-185 157-185 130-183
Mean 164.2 171.0 162.5 <0.01
Weight (kg)
Range 25-80 45-80 25-75
Mean 51.3 58.5 49.5 <0.05
Body mass index (kg/m
2
)
Range 11-29.5 14-29 11-27
Mean 18.9 20.2 18.6 >0.10
Upper/Lower segment
ratio
Mean 0.93 0.94 0.93 >0.10
SP=Spontaneous pneumothorax; PSP=Primary spontaneous
pneumothorax; SSP=Secondary spontaneous pneumothorax.
Table 2. Etiologic distribution of secondary spontaneous
pneumothorax
Diagnosis Number (%)
Pulmonary tuberculosis 20 (41.7)
Chronic obstructive pulmonary disease 12 (25.0)
Pneumonia 7 (14.6)
Human immunodeficiency virus (HIV) associated
Pulmonary tuberculosis 3 (6.2)
P. Jiroveci pneumonia 1 (2.1)
Miscellaneous 5 (10.1)
Lung malignancy 1 (2.1)
Esophageal tear 1(2.1)
Bullous lung disease 1 (2.1)
Pulmonary thromboembolism 1 (2.1)
Systemic lupus erythematosus 1 (2.1)
The clinical presentation was largely similar
irrespective of the category of SP. Dyspnoea was the
commonest symptom at presentation in 56 (93%)
patients, and was associated with pleuritic chest pain in
50 (83%) patients. In addition, 41 (68.3%) patients
reported cough. No patient had a family history of
pneumothorax. More patients (60%) had a right sided
pneumothorax, and three (5%) patients presented with
simultaneous bilateral pneumothoraces. A definite
history of exertion at the onset of pneumothorax was
elicited in only four patients.
The commonest aetiology for SSP was identified as
pulmonary tuberculosis (in 41% patients with SSP)
followed by chronic obstructive pulmonary disease
(COPD) and pyogenic infections. AIDS associated
pulmonary infections were seen in four (8.3%) patients
with SSP (Table 2).
All patients with SSP were managed with intercostal
chest tube drainage. All patients with PSP were initially
managed with simple needle aspiration. The outcome of
Spontaneous Pneumothorax in Adults D. Gupta et al
2006; Vol. 48 The Indian Journal of Chest Diseases & Allied Sciences 263
this procedure was universally good, except in one
patient with PSP who required placement of intercostal
chest tube following failed needle aspiration. No
treatment related complications were recorded in
patients with PSP. However, one patient with SSP had
developed empyema after intercostal tube placement.
DISCUSSION
Although the entity of pneumothorax has been well
recognized since the beginning of 19
th
century, very few
studies are available regarding its epidemiology,
particularly from India. The most widely quoted study
on the incidence of SP was conducted in Olmested
County, Minnesota
9
. In this study, the incidence of PSP
was 7.2 per 100,000 per year among men and 1.2 per
100,000 per year among women, while the incidence of
SSP was 6.3 per 100,000 per year and 2.0 per 100,000 per
year for men and women respectively. Recently, large
quantitative data from national databases in UK have
been presented
10
. The overall person consulting rate for
pneumothorax (primary and secondary combined) in
the general practice was 24.0 per 100,000 each year for
males and 9.8 per 100,000 each year for females.
Hospital admissions for pneumothorax as a primary
diagnosis occurred at an overall incidence of 16.7 per
100,000 per year and 5.8 per 100,000 per year for males
and females respectively. In the present study, the
incidence of SP was calculated to be 99.9 per year per
100,000 hospital admissions (~0.1%). This figure does
not reflect the true incidence of SP in the general
population and is not strictly comparable to the figures
quoted in Western studies, since our study is from a
tertiary care institute wherein the denominator
comprises of patients predominantly referred hospital
admissions.
The reported incidence of PSP among all patients
presenting with SP have been widely variable in the few
studies available from India, and has ranged from 12.5%
in a study from Jaipur
7
to 25% from Rohtak
3
and 64%
from Srinagar
6
. In the present study, the underlying
aetiology could be found in 48 patients (80%), leaving
only 12 (20%) in the PSP group. This high relative
incidence of SSP could partly be related to the fact that
most patients of PSP are managed at the primary and
secondary health care hospitals, while several patients
of SSP, who have associated co-morbidities, are referred
to tertiary care hospitals.
Similar to other reports from the Western world, age
distribution in our study also showed a biphasic
distribution. Classically, these two age peaks correspond
to PSP and SSP respectively, where PSP is
predominantly a disease of younger men. In our study,
the second age peak occurred a little earlier (40-50 years)
as compared to the 60-65 years range reported in the
other Western studies
9, 10
. The likely explanation for an
earlier occurrence of the second peak is that a large
number of the cases of SSP in this study were secondary
to tuberculosis and not COPD, which is the leading
cause of SSP in the West and occurs relatively later. The
sex ratio showed male predominance with male to
female ratio of 5 : 1. This is in keeping with previously
published studies. The higher incidence in men has
been attributed to higher rates of smoking, body habitus
and different mechanical properties of the lungs
11
.
Patients with PSP were relatively taller (mean height
171 cm), which is a well-known observation
11
. The
higher incidence in tall people is possible due to greater
pleural pressure gradient at the lung apex than at the
base
12
. Weight and BMI however, were lower in patients
with SSP, which may be explained by the nature of
chronic illnesses they suffered from.
Smoking is known to be an important risk factor for
development of PSP. In fact, a study from Sweden even
established that incidence of PSP was significantly
affected by the sale of cigarettes
13
. History of smoking
was obtained in only four out of 12 patients with PSP.
This could be related to the small number of patients
with PSP. Another commonly held belief is that exertion
could promote the onset of SP. This hypothesis, though
seemingly attractive, has never been proven in any
study
14
. We also could not demonstrate any such
significant association.
Until the description of PSP by Kjaegard
15
more than
70 years ago, tuberculosis was thought to be the leading
cause of SP. The scenario has changed over the years,
and COPD has now emerged as the leading cause of
SSP in the literature from the West
1,16
. We found
tuberculosis to be still the commonest aetiology for SSP,
while COPD accounted for only 25% cases of SSP.
Pulmonary infections other than tuberculosis, such as
pneumonia or lung abscess, were responsible for SP in
14.6% instances. Thus, pulmonary infections seem to
account for most SSPs in India. Similar results were
earlier reported in children, in whom pyogenic
infections and tuberculosis accounted for 75% and 21%
cases of spontaneous pneumothorax respectively
8
.
Tuberculosis has remained the dominant cause for SSP
in all studies in adults from India
6,7,17,18
. AIDS was
responsible for 12.5% of cases of SSP in this study. Much
higher figures are reported from the Western countries,
with some studies reporting AIDS related pulmonary
disorders in as high as 26% of patients with SSP
2
.
Majority of patients with AIDS in this study had either
P. Jiroveci pneumonia or mycobacterial infection.
In summary, spontaneous pneumothorax in India is
more often secondary to an underlying lung disease.
Pulmonary tuberculosis remains the commonest cause
of SSP, followed by COPD and other lung infections.
PSP occurs more commonly in tall young men.
Spontaneous pneumothorax has a good clinical
outcome.
264
REFERENCES
1. Shramel FM, Postmus PE, Vandershueren RG. Current
aspects of spontaneous pneumothorax. Eur Respir J 1997; 10:
1372-9.
2. Wait MA, Estrera A. Changing spectrum of spontaneous
pneumothorax. Am J Surg 1992; 164: 528-31.
3. Gupta KB, Mishra DS, Tandon S, Sindhwani G, Tanwar T.
Role of chest CT scan in determining etiology of primary
spontaneous pneumothorax. Indian J Chest Dis Allied Sci 2003;
45: 173-7.
4. Faruqi S, Gupta D, Aggarwal AN, Jindal SK. Role of simple
needle aspiration in the management of pneumothorax.
Indian J Chest Dis Allied Sci 2004; 46: 183-90.
5. Janmeja A, Raj B, Saini V, Gupta KB. Analysis of 100 cases of
spontaneous pneumothorax. Lung India 1995; 13: 12-6.
6. Ahangar AG, Hussain SS, Mir IA, Dar AM, Bhat MK, Lone
GN, et al. Spontaneous pneumothroax. Indian J Surg 2003; 65:
423-6.
7. Agnihotri S, Sharma, TN, Jain NK, Madan A, Mandhana RG,
Saxena A. Spontaneous pneumothorax : a clinical study of
eighty cases in Jaipur. Lung India 1987; 5: 189-92.
8. Beg MH, Reyazudin, Faridi MM, Ahmad SH, Shahab T.
Spontaneous pneumothorax in children: a review of 95 cases.
Ann Trop Paediatr 1988; 8: 18-21.
9. Melton LJ 3
rd
, Hepper NG, Offord KP. Incidence of
spontaneous pneumothorax in Olmsted County, Minnesota:
1950 to 1974. Am Rev Respir Dis 1979; 120: 1379-82.
10. Gupta D, Hansel A, Nichols T, Duong T, Ayres JG, Strachan
D. Epidemiology of pneumothorax in England. Thorax 2000;
55: 666-71.
11. Taussig LM, Cota K, Kaltenborn W. Different mechanical
properties of lung in boys and girls. Am Rev Respir Dis 1981;
123: 640-3.
12. Abolnik IZ, Lossos IS, Gillis D, Breuer R. Primary
spontaneous pneumothorax in men. Am J Med Sci 1993; 305:
297-303.
13. Bense L, Eklund G, Wiman LG. Smoking and increased risk
of contracting spontaneous pneumothorax. Chest 1987; 92:
1009-12.
14. De Vries WC, Wolfe WG. The management of spontaneous
pneumothorax and bullous emphysema. Surg Clin North Am
1980; 60: 851-6.
15. Kjaegard H. Spontaneous pneumothorax in apparently
healthy. Acta Med Scand 1932; 43 (Suppl): 1-159.
16. Ferraro P, Beauchamp G, Lord F, Emond C, Bastien E.
Spontaneous primary and secondary pneumothorax: a 10–
year study of management alternatives. Can J Surg 1994; 37:
197-202.
17. Beg MH, Reyazuddin. Bilateral simultaneous pneumothorax:
a study of 25 cases. Indian J Chest Dis Allied Sci 1990; 32: 25-7.
18. Boghani AB, Patel RB. Spontaneous pneumothorax : a clinical
study. Lung India 1985; 3: 37-40.
Spontaneous Pneumothorax in Adults D. Gupta et al
Review Article
Role of Bronchoscopy in Early Diagnosis of Lung Cancer
Ajay V. Kamath and Prashant N. Chhajed
1
Respiratory Medicine, Norfolk and Norwich University Hospital, Norwich, UK and Pulmonary Medicine
1
,
University Hospital Basel, Switzerland
ABSTRACT
Lung cancer is a leading cause of cancer deaths and the incidence is rising. Most patients with lung cancer present to the
clinician in a fairly advanced stage and at best only 25-30% of patients can be offered curative resection. Screening tests using
sputum cytology and chest radiograph have been used with limited success. Value of low dose spiral CT scan as screening
tool for lung cancer is being evaluated and its limitations include high costs, need for repeated scanning and necessity to
obtain histological confirmation with additional procedures. There have been significant advances in the early diagnosis of
lung cancer in high risk patient groups using bronchoscopic methods such as white light bronchoscopy, autofluorescence
bronchoscopy, high magnification bronchoscopy, narrow band imaging and endobronchial ultrasound. These techniques
appear to be promising tools as they might allow to visualise changes of early lung cancer and also permit sampling for
histological confirmation. [Indian J Chest Dis Allied Sci 2006; 48: 265-269]
Key words: Bronchoscopy, Lung cancer, Autofluorescence bronchoscopy, Endobronchial ultrasound, High magnification broncho-
videoscopy.
[Received: January 8, 2006; accepted after revision: March 29, 2006]
Correspondence and reprint requests: Dr Prashant N. Chhajed, Pulmonary Medicine, University Hospital Basel,
Petersgraben 4, CH-4031, Basel, Switzerland; Tele.: 41-61-3286339 (office direct); 41-76-3419917; Telefax: 41-61-2654587; E-mail:
PChhajed@uhbs.ch.
INTRODUCTION
Lung cancer is a leading cause of cancer deaths and the
incidence is rising
1
. By the time patients present to
clinicians the condition is fairly advanced and at best
only 25-30% of patients can be offered curative
resection
2-4
. There has been a lot of interest in screening
tests for detection of early lung cancer. Screening tests
using sputum cytology and chest radiograph have been
used with limited success and a recent meta-analysis
5
has shown that these strategies are not very useful and
newer strategies need to be evaluated. Low dose spiral
computerised tomographic scan (CT Scan) has also been
explored as screening tool for lung cancer. A study by
Henschke et al
6
detected 27 lung cancers using spiral CT
whereas only seven of these were visible on chest
radiographs which were obtained at the same time.
Another study
7
looked at chest radiograph
retrospectively in 44 cases of lung cancer diagnosed by
using low-dose spiral CT as a screening tool and found
that chest radiograph failed to detect 79% of lesions
which were less than or equal to 2 cm. This highlights
the importance of spiral CT in detecting small lesions in
asymptomatic patients. However spiral CT is not yet
the perfect tool for lung cancer screening due to the high
cost of scanning and need for follow-up scans, small
risk of cancer associated with multiple follow-up scans
and the inability to do biopsies at the same sitting.
Bronchoscopic techniques for early detection of lung
cancer are a promising tool as they might allow to
visualise changes of early lung cancer and also permit
sampling for histological confirmation. It is important to
detect bronchial carcinoma in situ (CIS) since over 40%
of these can develop into invasive cancer
8
. There is
strong evidence from the treatment of cervical dysplasia
or CIS, resulting in reduction in the incidence and
mortality of invasive cervical cancer
9
, suggesting that a
similar strategy may be useful in lung cancer. The role
of conventional fibreoptic bronchoscopy in the
diagnosis and management of lung cancer has been
well established over the past few decades. There have
been exciting innovations in the last decade in this field
which can help with the goal of early detection of lung
cancer by bronchoscopic techniques and coupled with
new modalities of treatment such as chemoprevention
and endobronchial therapies, the prognosis and
outcome of these patients can potentially be altered in
the near future.
Autofluorescence Bronchoscopy
The need to look for superficial bronchial mucosa
malignancy was first addressed by Kato and Cortese
10
using porphyrin injection, followed by bronchoscopic
observation using a laser monochromatic light source.
Tumour drug fluorescence was detected at 630 nm
wavelength which was quite distinct from normal
266
fluorescence at 500-580 nm. Though this technology
improved sensitivity, the prohibitive cost and
photosensitivity reaction meant that it could not be
applied in routine screening. Subsequent research by a
group in Canada
11,12
lead to the development of the LIFE
(light imaging fluorescence endoscope). This
technology uses blue light at 442 nm from a laser light
source. Autofluorescence distinctions between normal
and malignant mucosa can be made using image
intensified cameras in real time. Bronchial epithelial
fluorescence is measured in red (>630 nm) and green
(520 nm). For the diagnosis of early lung cancer, the
findings at white light bronchoscopy (WLB) are
classified as (1) normal (2) abnormal - areas with
increased redness and hypervascularity, swelling or
thickening of the bronchial mucosa, focal thickening of
subcarina (3) suspicious – nodular or polypoid lesions,
irregularity of bronchial mucosa. On autofluorescence,
normal bronchial mucosa appears green, abnormal
lesions appear slight brown with ill defined margins
and areas suspicious for high grade dysplasia or cancer
appear brown or brownish-red
13-15
.
In a multicentre study Lam et al
13
used LIFE as an
adjunct to WLB to detect and perform biopsies from
areas suspicious of intraepithelial neoplasia as
compared to WLB alone. This study involved 173
patients and 700 biopsies were examined. This study
showed that LIFE together with WLB had a relative
sensitivity of 6.3 for detecting intraepithelial neoplastic
lesions and 2.7 when invasive carcinomas were
included, as compared to WLB alone. This set the stage
for the use of LIFE for detecting early stage lung cancer.
However, another smaller study by Kurie et al
16
involving 53 patients did not show any additional
benefit of using LIFE. One of the reasons for the
difference between the two studies might have been
that the study by Lam et al
13
included patients with
known or suspected lung cancer whereas the study by
Kurie et al
16
included patients with heavy smoking
history (>20 pack years) but free of active cancer.
A D-Light fluorescence-reflectance system has been
developed. This uses noncoherent ultraviolet to blue
300W xenon filtered lamp (380-460 nm) to excite broad
emission spectra of the different chromophores in tissue.
Using this system the normal tissues appear bluish and
the areas with high grade dysplasia and CIS give darker
images. The LIFE system is somewhat bulky and does
not allow direct and immediate comparison of white
light and autofluorescence images. The D-Light system
allows direct comparison of images between the two
modalities. A study by Herth et al
17
compared the D-
Light system with the LIFE system in 332 patients and
included 1,117 biopsies. Differences between the two
systems were observed only in five biopsies which was
not statistically significant (p=0.3). This study
demonstrates that the D-Light and LIFE are
comparable. The examination time by the D-Light
sysem was much less (7.4 vs 11.4 mins, p<0.001)
probably due to direct switch between white light and
autofluorescence imaging.
Other systems being used are the system of
autofluorescence endoscopy (SAFE) 1000 auto-
Bronchoscopy and Lung Cancer A.V. Kamath and P.N. Chhajed
Figure. Comparison of white light bronchoscopy and light imaging fluorescence endoscopy (LIFE). White light
bronchoscopy is normal and autofluorescence bronchoscopy revealed a suspicious lesion.
White Light Bronchoscopy
Light Imaging Fluorescence Endoscopy
LtB1+2b/c biopsy revealed severe dysplasia
2006; Vol. 48 The Indian Journal of Chest Diseases & Allied Sciences 267
fluorescence system using a xenon-lamp (420–480 nm)
and a camera with a fluorescence filter and an image
intensifier
18
. Another new fluorescence–reflectance
imaging system is the ONCO-LIFE with a view to
reduce equipment costs and to make the
autofluorescence bronchoscopy much easier.
All the above studies have used fibreoptic
bronchoscopes for the WLB. However, fibreoptic
systems are now being replaced by flexible
videobronchoscopy (FVB) where the images are clearer
and sharper. A study comparing FVB and LIFE in
patients at high risk of lung cancer
19
showed that the
sensitivity was 72% and 96% and the specificity was
53% and 23% respectively. The relative sensitivity of
LIFE over FVB was 1.33. This is in striking contrast to
the study by Lam et al
13
which showed a relative
sensitivity of 6.3 of LIFE over WLB using fibreoptic
bronchoscopy and most likely attributable to better
quality of images obtained using FVB.
High Magnification Bronchovideoscopy and
Narrow Band Imaging
Conventional WLB is not as sensitive as
autofluorescence bronchoscopy at detecting the early
stages of dysplasia or CIS. The only findings of note
using WLB with a bronchovideoscope are swelling and
redness at bronchial bifurcations in contrast to the LIFE
system
20
. A high magnification bronchovideoscope
combining two systems — a video observation system
for high magnification observation and a fibre
observation system for orientation of the bronchoscope
tip, has been reported
21
. Using this system the
magnification obtained is four times that of a standard
bronchovideoscope. The scope is inserted like a normal
bronchovideoscope into the tracheobronchial system
using the fibre orientation system until the target area of
suspicious mucosa is reached and then the mucosa is
observed at high magnification on a television monitor.
Areas of bronchial dysplasia, detected by auto-
fluorescence bronchoscopy, are characterised by
increased thickening of bronchial epithelium and vessel
growth implying that neovascularisation might be have
a role in the development of bronchial dysplasia. High
magnification bronchovideoscopy helps in observing
the mucosa closely and pick up these lesions. Shibuya et
al
21
conducted a study in which they did
autofluorescence bronchoscopy in high risk patients for
lung cancer followed by high magnification
bronchovideoscopy and observed vascular patterns in
areas of normal and abnormal fluorescence and biopsies
were performed at normal and abnormal sites. The
areas with increased vessel growth and complex
network of tortuous vessels of various sizes on high
magnification bronchovideoscopy were assumed to be
positive for dysplasia and areas with vascular networks
with a regular pattern were assumed to be negative for
dysplasia. The sensitivity and specificity using this
criterion were 71.4% and 90.9% respectively as
confirmed by histology.
As a further improvisation high magnification
bronchovideoscopy was combined with narrow band
imaging (NBI)
22
. In this system the normal red, green,
blue (RGB) broadband filter was changed to the new
NBI filter. The NBI filter used wavelengths of B1 : 400-
430 nm, B2: 420-470 nm and G: 560-590 nm. This
contrasts with the conventional RGB filters using B: 400-
500 nm, G: 500-600 nm and R: 600-700 nm. Of particular
note is the fact that the NBI filter includes the NBI-B1
(400-430 nm) filter which includes the 410 nm
absorption wavelengths for haemoglobin with perhaps
more accurate detection of vessel structures. This would
allow focused and detailed observation of bronchial
vascular patterns. The optical absorption and scattering
properties for tissues are strongly wavelength
dependent
23
. Blue light, which has a shorter wavelength
than visible light, reaches into shallow surfaces
24
which
is helpful for detecting the submucosal vessels and
patterns of vascularisation. With conventional RGB light
delivered through an endoscope, some of the light is
reflected from the tissue, some is scattered or absorbed
within the tissue and little is detected to form an image
viewed on the monitor. However, with the NBI there is
less scattering of light and clearer images are viewed on
the television monitor.
It is important to note that areas with abnormal
appearance on autofluorescence bronchoscopy may
show inflammation on histology as opposed to
dysplasia. A new morphological entity named
angiogenic squamous dysplasia (ASD) was detected in
the large central airways on autofluorescence
bronchoscopy. This consisted of network of capillary
blood vessels closely juxtaposed to and projecting into
dysplastic bronchial epithelium
25,
26
. Bronchial squamous
dysplasia often has increased vessel density in the
submucosa
27, 28
implying that angiogenesis is a relatively
early event in lung cancer pathogenesis
29
. It is difficult
to distinguish conventional squamous dysplasia from
ASD using white light or fluorescence bronchoscopy.
Shibuya et al
22
have reported that high magnification
bronchovideoscopy combined with narrow band
imaging to be useful in the detection of capillary blood
vessels in angiogenic squamous dysplasia lesions at
sites of abnormal fluorescence. This might enable the
discrimination between angiogenic squamous dysplasia
and other pre-invasive bronchial lesions. A future
prospect for detecting angiogenic squamous dysplasia
may be quantitative fluorescence imaging combined
with fluorescence reflectance imaging and
spectrofluoremetry
30, 31
.
Endobronchial Ultrasound (EBUS)
Endobronchial application of ultrasound
32
using a
miniature probe introduced via a fibreoptic
bronchoscope channel was first described in 1992 and
268
over the last decade huge strides have been made in its
applications. EBUS has been widely used for sampling
mediastinal lymph nodes, endobronchial ultrasound -
transbronchial needle aspiration (EBUS-TBNA) using
both the radial probe as well as the convex probe
33, 34
and for peripheral lung lesions by transbronchial
biopsies (EBUS-TBB)
35
.
EBUS can be performed using a radial probe
introduced through the working channel of a flexible
bronchoscope. The working channel needs to be 2.8 mm
or more in diameter. A balloon sheath filled with saline
is inflated and the transducer is rotated through 360°
within this balloon window to form an image of the
airway and its surrounding structures. The 20 MHz
EBUS probe has a penetration depth of 2 cm, which
provides optimum resolution with sufficient airway-
wall image penetration
36
. A new technique utilising
flexible bronchoscope equipped with a 7.5 MHz convex
probe for endobronchial ultrasound (CP-EBUS) that
scans parallel to the insertion direction of the
bronchoscope has also been developed
37
.
On the basis of EBUS in vitro studies a seven layer
ultrasound structure of the cartilaginous portions of
trachea or extra/intrapulmonary airways has been
described
38,39
. The layers from the lumina outwards are:
1. Mucosa: hyperechoic – this appears as very bright
enhanced by the adjacent balloon (first),
2. Submucosa: hypoechoic – clearly distinguishable
from the other structures of the bronchial wall
(second),
3. Cartilage: appears as three layers;
(a) hyperechoic – endochondrium (third),
(b) hypoechoic – internal layer (fourth),
(c) hyperechoic – perichondrium (fifth),
4. Supporting connective tissue – hypoechoic (sixth),
5. Adventitia – hyperechoic (seventh).
The three-layer structure of the membranous portion
of the extra-pulmonary bronchi is:
First layer – hyperechoic – epithelium and initial part
of submucosa,
Second layer – hyoechoic – smooth muscle and
Third layer – hyperechoic – adventitia.
Kurimoto et al
40
performed EBUS in 45 specimens of
normal human trachea or bronchi that had previously
been excised for non-neoplastic indications and
corroborated them with microscopic findings on
histology. They found a good correlation between
microscopy and EBUS images and on this basis
proposed a five layer EBUS appearance for the
tracheobronchial wall. In a further 24 lung cancer
resected specimens, comparison of the determination of
the depth of tumour invasion on the basis of EBUS and
histopathologic findings showed that the findings were
the same in 23 lesions (95.8%) and different in only one
lesion (4.2%), in which lymphocytic infiltration
protruding between the cartilages was misinterpreted
by EBUS as tumour invasion. A number of other
studies
14,42
have shown that there is good correlation
between EBUS findings and histology.
Treatment of Early Stage Lung Cancer
One of the contentious issues in detecting early cancer is
whether or not they would ultimately progress to
invasive carcinoma and how to manage them. A follow-
up study using AFB-LIFE at regular intervals showed
that CIS ultimately progressed to squamous cell
carcinoma
43
, indicating that CIS is the point of no return.
Photodynamic therapy (PDT) is a modality which uses
photosensitisers, combined with laser illumination of
the tumour area to obtain selective necrosis. This is a
modality which is the treatment of choice for early stage
cancer
44-46
and a significant proportion may be spared
surgery after initial PDT. This may be a prudent
approach to preserve healthy lung tissue and quality of
life
45, 47, 48
. Chemoprevention strategies might be used in
treating patients with early lung cancer
49
.
To summarise, there have been significant advances
in the early diagnosis of lung cancer in high risk patient
groups using bronchoscopic methods. Success of a
screening or diagnostic program will rely on a
diagnostic tool that is routinely available and not
expensive. A more proactive role is needed to detect
lung cancer at CIS stage, so that best chance of cure can
be offered to the patients.
REFERENCES
1. Jemal A, Murray T, Ward E, Samuels A, Tiwari RC, Ghafoor
A, et al. Cancer statistics, 2005. CA Cancer J Clin 2005; 55: 10-
30.
2. Humphrey EW, Smart CR, Winchester DP, Steele GD (Jr),
Yarbro JW, Chu KC, et al. National survey of the pattern of
care for carcinoma of the lung. J Thorac Cardiovasc Surg 1990;
100: 837-43.
3. Laroche C, Wells F, Coulden R, Stewart S, Goddard M, Lowry
E, et al. Improving surgical resection rate in lung cancer.
Thorax 1998; 53: 445-9.
4. Chhajed PN, Athavale AU, Shah AC. Clinical and
pathological profile of 73 patients with lung carcinoma : is the
picture changing? J Assoc Physicians India 1999; 47: 483-7.
5. Manser RL, Irving LB, Byrne G, Abramson MJ, Stone CA,
Campbell DA. Screening for lung cancer: a systematic review
and meta-analysis of controlled trials. Thorax 2003; 58: 784-9.
6. Henschke CI, McCauley DI, Yankelevitz, Naidich DP,
McGuinness G, Miettinen OS, et al. Early Lung Cancer Action
Project : overall design and findings from baseline screening.
Lancet 1999; 354: 99-105.
7. Sone S, Li F, Yang ZG, Takashima S, Maruyama Y, Hasegawa
M, et al. Characteristics of small lung cancers invisible on
conventional chest radiography and detected by population
based screening using spiral CT. Br J Radiol 2000; 73: 137-45.
8. Lam S, Becker HD. Future diagnostic procedures. Chest Surg
Clin N Am 1996; 6: 363-80.
9. Anderson GH, Boyes DA, Benedet JL, Le Riche JC, Matisic JP,
Suen KC, et al. Organisation and results of the cervical
cytology screening programme in British Columbia, 1955-85.
Br Med J (Clin Res Ed) 1988; 296: 975-8.
10. Kato H, Cortese DA. Early detection of lung cancer by means
of hematoporphyrin derivative fluorescence and laser
photoradiation. Clin Chest Med 1985; 6: 237-53.
Bronchoscopy and Lung Cancer A.V. Kamath and P.N. Chhajed
2006; Vol. 48 The Indian Journal of Chest Diseases & Allied Sciences 269
11. Palcic B, Lam S, Hung J, MacAulay C. Detection and
localization of early lung cancer by imaging techniques. Chest
1991; 99: 742-3.
12. Hung J, Lam S, LeRiche JC, Palcic B. Autofluorescence of
normal and malignant bronchial tissue. Lasers Surg Med 1991;
11: 99-105.
13. Lam S, Kennedy T, Unger M, Miller YE, Gelmont D, Rusch V,
et al. Localization of bronchial intraepithelial neoplastic
lesions by fluorescence bronchoscopy. Chest 1998; 113: 696-
702.
14. Venmans BJ, van der Linden JC, van Boxem AJ, Postmus PE,
Smit EF, Sutedja G. Early detection of pre-invasive lesions in
high risk patients: a comparison of conventional fiberoptic
and fluorescence bronchoscopy. J Bronchol 1998; 5: 280-3.
15. Lam S, MacAulay C, Le Riche JC, Ikeda N, Palicic B. Early
localization of bronchogenic carcinoma. Diagn Therap
Endoscopy 1994; 1: 75-8.
16. Kurie JM, Lee JS, Morice RC, Walsh GL, Khuri FR, Broxson A,
et al. Autofluorescence bronchoscopy in the detection of
squamous metaplasia and dysplasia in current and former
smokers. J Natl Cancer Inst 1998; 90: 991-5.
17. Herth FJF, Ernst A, Becker HD. Autofluorescence
bronchoscopy: a comparison of two systems (LIFE and D-
Light). Respiration 2003; 70: 395-8.
18. Kakihana M, Kim Kl, Okunaka T. Early detection of bronchial
lesions using system of autofluorescence endoscopy (SAFE)
1000. Diagn Ther Endoscopy 1999; 5: 99-104.
19. Chhajed PN, Shibuya K, Hoshino H, Chiyo M, Yasufuku K,
Hiroshima K, et al. A comparison of video and auto-
fluorescence bronchoscopy in patients at high risk of lung
cancer. Eur Respir J 2005; 25: 951-5.
20. Shibuya K, Fujisawa T, Hoshino H, Baba M, Saitoh Y, Iizasa
T, et al. Fluorescence bronchoscopy in the detection of
preinvasive bronchial lesions in patients with sputum
cytology suspicious or positive for maligancy. Lung Cancer
2001; 32: 19-25.
21. Shibuya K, Hoshino H, Chiyo M, Yasufuku K, Iizasa T, Saitoh
Y, et al. Subepithelial vascular patterns in bronchial
dysplasias using a high magnification bronchovideoscope.
Thorax 2002; 57: 902-7.
22. Shibuya K, Hoshino H, Chiyo M, Iyoda A, Yoshida S, Sekine
Y, et al. High magnification bronchovideoscopy combined
with narrow band imaging could detect capillary loops of
angiogenic squamous dysplasia in heavy smokers at high
risk for lung cancer. Thorax 2003; 58: 989-95.
23. Cheong W, Prahl S, Welch A. A review of the optical
properties of biological tissues. IEEE J Quantum Electron
1990; 26: 2166-85.
24. DaCosta RS, Wilson BC, Marcon NE. Ligh-induced
fluorescence endoscopy of the gastrointestinal tract.
Gastrointest Endosc Clin N Am 2000; 10: 37-69.
25. Franklin WA. Diagnosis of lung cancer : pathology of
invasive and preinvasive neoplasia. Chest 2000; 117 (4 suppl
1) 80S-89S.
26. Keith RL, Miller YE, Gemmill RM, Drabkin HA, Dempsey
EC, Kennedy TC, et al. Angiogenic squamous dysplasia in
bronchi of individuals at high risk of lung cancer. Clin Cancer
Res 2000; 6: 1616-25.
27. Fisseler-Eckhoff A, Rothstein D, Muller KM.
Neovacularization in hyperplastic, metaplastic and
potentially preneoplastic lesions of the bronchial mucosa.
Virchows Arch 1996; 429: 95-100.
28. Fontanini G, Calcinai A, Boldrini L, Lucchi M, Mussi A,
Angeletti CA, et al. Modulation of neoangiogenesis in
bronchial preneoplastic lesions. Oncol Rep 1999; 6: 813-7.
29. Gazdar AF, Minna JD. Angiogenesis and the multistage
development of lung cancers. Clin Cancer Res 2000; 6: 1616-25.
30. Kennedy TC, Lam S, Hirsch FR. Review of recent advances in
fluorescence bronchoscopy in early localisation of central
airway lung cancer. Oncologist 2001; 6: 257-62.
31. Kusunoki Y, Imamaura F, Udo H, Mano M, Horai T. Early
detection of lung cancer with laser induced fluorescence
endoscopy and spectrofluoremetry. Chest 2000; 118: 1776-82.
32. Hurter T, Hanrath P. Endobronchial sonography: feasibility
and preliminary results. Thorax 1992; 47: 565-7.
33. Herth F, Becker HD, Ernst A. Conventional vs endobronchial
ultrasound-guided transbronchial needle aspiration: a
randomized trial. Chest 2004; 125: 322-5.
34. Yasufuku K, Chiyo M, Sekine Y, Chhajed PN, Shibuya K,
Iizasa T, et al. Real-time endobronchial ultrasound-guided
transbronchial needle aspiration of mediastinal and hilar
lymph nodes. Chest 2004; 126: 122-8.
35. Paone G, Nicastri E, Lucantoni G, Dello lacono R, Battistoni
P, D’Angeli AL, et al. Endobronchial ultrasound-driven
biopsy in the diagnosis of peripheral lung lesions. Chest 2005;
128: 3551-7.
36. Silverstein FE, Martin RW, Kimmey MB, Jiranek GC, Franklin
DW, Proctor A. Experimental evaluation of an endoscopic
ultrasound probe: in vitro and in vivo canine studies.
Gastroenterology 1989; 96: 1058-62.
37. Yasufuku K, Chhajed PN, Sekine Y, Nakajima T, Chiyo M,
Iyoda A, et al. Endobronchial ultrasound using a new convex
probe: a preliminary study on surgically resected specimens.
Oncol Rep 2004; 11: 293-6.
38. Lam S, Becker HD. Future diagnostic procedures. Chest Surg
Clin N Am 1996; 6: 363-80.
39. Herth F, Becker HD. Endobronchial ultrasound of the
airways and the mediastinum. Monaldi Arch Chest Dis 2000;
55: 36-44.
40. Kurimoto N, Murayama M, Yoshioka S, Nishisaka T, Inai K,
Dohi K. Assessment of usefulness of endobronchial
ultrasonography in determination of depth of
tracheobronchial tumour invasion. Chest 1999; 115: 1500-6.
41. Miyazu Y, Miyazawa T, Iwamoto Y, Kano K, Kurimoto N.
The role of endoscopic techniques, laser-induced fluorescent
endoscopy and endobronchial ultrasonography in choice of
appropriate therapy for bronchial cancer. J Bronchol 2000; 8:
10-6.
42. Baba M, Sekine Y, Suzuki M, Yoshida S, Shibuya K, Iizasa T,
et al. Correlation between endobronchial ultrasonography
(EBUS) images and histologic findings in normal and
tumour-invaded bronchial wall. Lung Cancer 2002; 35: 65-71.
43. Miyazu Y, Miyazawa T, Kurimoto N, Iwamoto Y, Kanoh K,
Kohno N. Endobronchial ultrasonography in the assessment
of centrally located early-stage lung cancer before
photodynamic therapy. Am Respir Crit Care Med 2002; 165:
832-7.
44. Hayata Y, Kato H, Furuse K, Kusunoki Y, Suzuki S, Mimura
S. Photodynamic therapy of 169 early stage cancers of the
lung and oesophagus: a Japenese multi-centre study. Laser
Med Sci 1996; 11: 255-9.
45. Cortese DA, Edell ES, Kinsey JH, Photodynamic therapy for
early stage squamous cell carcinoma of the lung. Mayo Clin
Proc 1997; 72: 595-602.
46. Sutedja G, Lam S, Le Riche JC, Postmus PE. Response and
pattern of failure after photodynamic therapy for
intraluminal stage I lung cancer. J Bronchol 1994; 1: 295-8.
47. Sutedja G, Codrington H, Risse EK, Breuer RH, van Mourik
JC, Golding RP, et al. Autofluorescence bronchoscopy
improves staging of radiographically occult lung cancer and
has an impact on therapeutic strategy. Chest 2001; 120: 1327-
32.
48. Venmans BJ, van Boxem TJ, Smit EF, Postums PE, Sutedja TG.
Outcome of bronchial carcinoma in situ. Chest 2000; 117: 1572-
6.
49. Saba NF, Khuri FR. Chemoprevention strategies for patients
with lung cancer in the context of screening. Clin Lung Cancer
2005; 7: 92-9.
270
RADIOLOGY FORUM
It is proposed to extend the scope of the Radiology Forum of
our Journal by inviting our readers as well as other workers in the
field or Respiratory Medicine to submit brief report of patients with
interesting clinical and radiological features for publication. These
will be published, provided that :
(
a
) the condition is of sufficient clinical and radiological
interest;
(
b
) photographs (10 cm × 8 cm) are of excellent quality for
printing (Maximum : 3 photographs);
(
c
) the diagnosis in each case has been confirmed;
(
d
) the chest radiograph is accompanied by brief clinical
account, not exceeding one page typescript.
All the material received for publication in the Radiology Forum
will be evaluated to judge the suitability for publication by our
experts panel.
Editor-in-Chief
The Indian Journal of Chest Diseases & Allied Sciences 2006; Vol. 48
High Intensity Exercise Training Programme Following
Cardiac Transplant
A.J. Rajendran, U.M. Pandurangi, A.S. Mullasari, S. Gomathy, K.V. Kuppu Rao
1
and
V.K. Vijayan
2
Institute of Cardio-vascular Diseases, Chennai, Cardio-pulmonary Medicine Unit
1
,
Tuberculosis Research Centre,
Indian Council of Medical Research, Chennai, and Vallabhbhai Patel Chest Institute
2
, University of Delhi, Delhi;
India
ABSTRACT
A 26-year-old male patient who presented with symptoms of end stage cardiac failure as a result of dilated cardiomyopathy,
had an orthotopic cardiac transplantation. A comprehensive cardiac rehabilitation programme was provided to him and he
was introduced to a sport (tennis). The exercise training programme progressed from low intensity training to high intensity
programme over a period of 15 months. A cardio-pulmonary exercise test done 22 months after surgery suggested that he
was able to achieve the aerobic capacity comparable to that of a normal South Indian subject. He participated successfully
in the World Transplant Games in Sydney and returned safely. This suggests that after a proper cardiac rehabilitation
programme, patients undergoing heart transplantation can achieve normal physiological responses to lead a normal active
life. [Indian J Chest Dis Allied Sci 2006; 48: 271-273]
Key words: Cardio-pulmonary exercise testing, Cardiac transplantation, Cardiac rehabilitation.
Case Report
INTRODUCTION
Orthotopic heart transplantation is an established
therapeutic procedure for end stage heart failure
patients
1
. The haemodynamic responses following
transplant during exercise in the supine and in the
upright posture have been well documented
2,3
. In
general, less than normal increase in cardiac output at
more than normal ventricular filling pressures is noted
during exercise in a transplant recipient. These
observations have been attributed among many
reasons, mainly to the effects of cardiac denervation, a
mismatch of donor and recipient cardiac size,
myocardial fibrosis resulting from rejection and graft
vascular disease
4,5
. The beneficial effects of exercise
training programme for transplant recipients are well
known
6,7
.
CASE REPORT
A 26-year-old male patient, who presented at our
Institute of Cardio-vascular Diseases, Chennai, with end
stage cardiac failure as a result of dilated
cardiomyopathy, underwent orthotopic cardiac
transplantation on 5
th
December 1995. The post-
operative course was uneventful, leading to a complete
recovery. Regular follow up including endomyocardial
biopsies, coronary angiograms, 2D echocardiograms
and clinical assessments were done periodically to
assess rejection episodes and improvement in his
physical endurance according to the protocol
8
. His
aptitude to learn tennis and his zeal to participate in
World Transplant Games (WTG), Sydney, Australia
were identified and encouraged. A comprehensive
rehabilitation programme
9
was offered to him to re-
develop his exercise tolerance. After six months of
transplantation, he was constantly motivated to ensure
compliance and was guided through the exercise
programme, which progressed from a low intensity
training to a high intensity training programme for a
period of 15 months. At the beginning of the exercise
programme, patient had dyspnea (class II), no evidence
of clinical congestive cardiac failure, normal chamber
dimensions and normal ejection fraction by 2D
echocardiogram. Towards the end of this training
programme, his rating of perceived exertion was in the
range of 16-17
10
. One week before his departure to
participate in WTG, a graded exercise test was done in
September 1997 in the Cardio-pulmonary Medicine
Unit of the Tuberculosis Research Centre (ICMR) using
a motorised treadmill and with a metabolic cart which
analysed respiratory gases (Morgan, Chatham, UK).
The Bruce protocol was used for the exercise testing
11, 12
.
Analyzers were calibrated with gases of known
concentrations before each session. The participants
[Received: February 23, 2005; accepted after revision: June 26, 2006]
Correspondence and reprint requests: Dr V.K. Vijayan, Director, V. P. Chest Institute, University of Delhi, Delhi – 110 007
E-mail: vijayanvk@hotmail.com.
272
breathed through a mouth piece and wore nose clips
throughout. Expired gas collection was performed with
a low resistance, small dead space Rudolph valve.
Ventilatory parameters were measured with an intake
turbine ventilometer. Expired O
2
content was
determined with a model QA 500 paramagnetic
analyzer and carbon dioxide content was measured by
a model 901 infrared CO
2
analyzer (PK Morgan
Instruments Inc.). Data were supplied to a Magna 88
computer, which provided 15-second averages of
oxygen consumption, minute ventilation, tidal volume,
respiratory rate, respiratory exchange ratio and
ventilatory equivalent for oxygen and carbon dioxide.
Heart rate and arterial oxygen saturation were
measured by a pulse oximeter (Ohmeda model IV A)
continuously during the exercise test. Data were
initially obtained for three minutes at rest. Maximal
exercise effort was defined by fatigue, facial flushing,
dyspnoea and unsteady gait in conjunction with
respiratory exchange ratio over 1.0 or achieving
maximal heart rate (% predicted
+ 5%). Maximal
oxygen consumption and ventilatory parameters were
taken as the highest achieved during exercise. Basic gas
and flow measurements were corrected for ambient
temperature, barometric pressure and water vapour.
Anaerobic threshold was defined as VO
2
at which
expired carbon dioxide increased non-linearly relative
to oxygen consumption (v-slope).
On treadmill, our subject could perform Bruce stage
IV attaining appropriate blood pressure response.
Patient could attain 70% of control VO
2
max and 93% of
maximal control heart rate. There were no arrhythmias
and ST-T changes. The cause of termination of test was
fatigue. Cardio-pulmonary exercise data compared with
age- and sex-matched control South Indian subjects are
given in table. The data suggest that, if a properly
structured Comprehensive Rehabilitation Programme is
offered to a cardiac transplant patient, he can achieve
the aerobic capacity of a normal person, and this has
helped our patient to participate in an enduring sport
competition like lawn tennis at WTG held at Sydney,
Australia in 1997. He successfully participated in the
WTG and returned safely. The last follow up in January
2004 revealed that his physical endurance is maintained
and he achieved 10 metabolic equivalents (METs) on
treadmill test by Bruce Protocol and one metabolic
equivalent is equal to 3.5 ml O
2
/kg/min.
DISCUSSION
The denervated donor heart has a higher resting heart
rate and smaller resting stoke volume
13
. The peak heart
rate achieved during exercise is lower. Inappropriate
response to circulating catecholamine leads to reduced
stroke volume during exercise and thereby, limiting the
exercise tolerance
14
. Another potential cause is altered
muscle metabolism secondary to immunosuppressive
therapy
15
. Cyclosporine A, the common immuno-
suppressive agent used to treat post transplant patients
has been shown to affect muscle metabolism.
Cyclosporine A significantly reduces muscle mito-
chondrial respiration and therefore result in sub
maximal exercise endurance
15
. Lean tissue loss
following major surgery is common and is exacerbated
by steroid administration. This is also the result of
prolonged, preoperative physical inactivity due to
cardiac illness. This reduction in muscle mass plays a
major role in limiting maximum exercise performance.
Because of low peak oxygen uptake, exercise is quickly
halted by fatigue. Anxiety and postoperative debility
can also significantly limit exercise tolerance. Several
studies have shown that a constructive rehabilitation
programme involving multidisciplinary efforts would
Exercise Testing in Cardiac Transplantation A.J. Rajendran et al
.
.
Table. Cardio-pulmonary exercise test parameters
Parameters Patient Control % of
Control
(a) Metabolic Parameters
1. VO
2
(ml/min)
Rest 335 380 88
Maximal Exercise 1600 2300 70
2. VO
2
/kg (ml/min/kg)
Rest 5.2 5.9 88
Maximal Exercise 24.6 35.9 69
3. VO
2
at AT (ml/min) 1320 1935 -
(% of VO
2
max) (82.5%) (84%) -
(b) Gas Exchange Parameters
1. VE/VO
2
(ml/min)
Rest 33.8 32.4 104
Maximal Exercise 41.3 38.7 107
2. VE/VCO
2
(ml/min)
Rest 31.5 32.4 97
Maximal Exercise 30.2 32.7 92
3. Respiratory Exchange Ratio
Rest 0.9 0.9 100
Maximal Exercise 1.4 1.2 117
(c) Ventilatory Parameters
1. Respiratory Rate (/min)
Rest 21 19 111
Maximal Exercise 44 44 100
2. Tidal Volume (ml)
Rest 546 634 86
Maximal Exercise 1457 2374 61
3. Ventilation (L/min)
Rest 11.4 12.3 93
Maximal Exercise 71.5 90.7 79
(d) Cardiovascular Parameters
1. Pulse (beats/min)
Rest 100 75 133
Maximal Exercise 172 184 93
2. O
2
–Pulse (ml/min)
Rest 3.4 5.1 67
Maximal Exercise 9.3 12.5 74
3. O
2
Saturation (%)
Rest 96 98 98
Maximal Exercise 97 97 100
VO
2
=Oxygen consumption; AT=Anaerobic threshold;
VE/VO
2
=Ventilatory equivalent for oxygen;
VE/VCO
2
=Ventilatory equivalent for carbon dioxide.
.
.
.
.
..
.
.
.
.
.
.
.
2006; Vol. 48 The Indian Journal of Chest Diseases & Allied Sciences 273
enable the heart transplant recipients to improve
exercise tolerance significantly
16-18
.
Our subject was able to achieve normal physiological
responses to exercise after the cardiac transplantation.
This was possible by the right motivation and the
excellent cardiac rehabilitation programme provided to
the patient. This emphasizes that individuals with end
stage cardiac failure who had undergone successful
cardiac transplant and had appropriate and sustained
cardiac rehabilitation can lead a normal active life. We
believe that our case is the first report of an Indian
Cardiac Transplant recipient undergoing supervised
high intensity exercise programme to achieve normal
physical endurance. The fact that he was able to achieve
10 METs on treadmill test by Bruce Protocol eight years
after the transplantation was an indication that he was
maintaining his physical endurance at least eight years
following the transplant.
ACKNOWLEDGEMENTS
Authors would like to thank Dr K.M. Cherian, Institute of Cardio-
Vascular Diseases, Chennai, and his surgical team who had
performed the cardiac transplantation.
REFERENCES
1. Kaye MP. The Registry of the International Society for Heart
and Lung Transplantation: Tenth official report–1993. J Heart
Lung Transplant 1993; 12: 541-8.
2. Hosenpud JD, Morton MJ, Wilson RA, Pantley GA, Norman
DJ, Cobanoglu MA, et al. Abnormal exercise haemodynamics
in cardiac allograft recipients one year after cardiac
transplantation: relation to preload reserve. Circulation 1989;
80: 525-32.
3. Rudas L, Pflugfelder PW, Kostuk WJ. Comparison of
haemodynamic responses during dynamic exercise in the
upright and supine posture after orthotopic cardiac
transplantation. J Am Coll Cardiol 1990; 16: 1367-73.
4. Degre SG, Niset GL, De Smet JM, Ibrahim T, Stoupel E, Le
Clerc JL, et al. Cardiorespiratory response to early exercise
testing after orthotopic cardiac transplantation. Am J Cardiol
1987; 60: 926-8.
5. Kappagoda CT, Haennel RG, Serrance–Fiz, Davis DH,
English TA. The haemodynamic responses to upright
exercise after orthotopic cardiac transplant. Arch Phys Med
Rehabil 1993; 74: 484-9.
6. Mandak JS, Aaronson KD, Mancini DM. Serial assessment of
exercise capacity after heart transplantation. J Heart Lung
Transplant 1995; 14: 468-78.
7. Osada N, Chaitman BR, Donohue TJ, Wolford TL, Stelken
AM, Miller LW. Long term cardiopulmonary exercise
performance after heart transplantation. Am J Cardiol 1997; 79:
451-6.
8. Baughman KL. Monitoring of allograft rejection. In:
Baumgartner WA, Reitz BA, Achuff SC, editors. Heart and
Heart-Lung Transplantation. Philadelphia: W.B. Saunders Co.;
1990: p. 86.
9. Brannor FJ, Foley MW, Starr JA, Saul LM. The exercise
prescription. In: Fithion M, Schnee M, editors.
Cardiopulmonary Rehabilitation: Basic Theory and Application; 3
rd
edn. Philadelphia: FA Davis Co.; 1998.
10. Borg G. Psychophysical bases of perceived exertion. Med Sci
Sports Exerc 1982; 14: 377-81.
11. Bruce RA, Mc Donough JR. Stress testing is screening for
cardiovascular disease. Bull N Y Acad Med 1969; 45: 1288-1305.
12. Strzelczyk TA, Cusick DA, Pfeifer PB, Boudmass MD, Quigg
RJ. Value of the Bruce protocol to determine peak exercise
oxygen consumption in patients evaluated for cardiac
transplantations. Am Heart J 2001; 142: 466-75.
13. de Marneffe M, Jacobs P, Haardt R, Englert M. Variations in
normal sinus node function in relation to age: role of
autonomic influence. Eur Heart J 1986; 7: 662-72.
14. Kavanagh T, Yacoub MH, Merten DJ, Kennedy J, Campbell
RB, Swayer P. Cardiorespiratory responses to exercise
training after orthotopic cardiac transplantation. Circulation
1988; 77: 162-71.
15. Hokanson JF, Mercier JG, Brooks GA. Cyclosporine A
decreases rat skeletal muscle mitochondrial respiration in
vitro. Am J Respir Crit Care Med 1995; 151: 1848-51.
16. Keteyian S, Shepard R, Ehrman J, Fedel F, Glick C, Rhoads K,
et al. Cardiovascular responses of heart transplant patients to
exercise training. J Appl Physiol 1991; 70: 2627-31.
17. Savin WM, Haskell WL, Schroeder JS, Stinson EB.
Cardiorespiratory responses of cardiac transplant patients to
graded symptom limited exercise. Circulation 1980; 62: 55-60.
18. Degre S, Niset G, De Smet JM, Abramowicz M, Ibrahim T,
Stoupel E, et al. Effect of physical training on the denervated
human heart after orthotopic cardiac transplantation. Ann
Cardiol Angeiol 1986; 35: 147-9.
274
FOR SUBSCRIBERS
Subscription payments will be accepted only through Banker’s Cheque/
Demand Draft and the same should be drawn in favour of the Director, V.P.
Chest Institute, Delhi.
Payments by any other mode are not acceptable.
Subscription Agencies are eligible for a 10% discount on annual rates for
institutional subscription only. Subscription Agencies must provide
complete address of the Institution for which subscription is sent in their
subscription order.
Editor-in-Chief
MISSING ISSUE CLAIMS
Claims for missing issues of the Journal will be allowed only if received
within six months of the month of Publication/issue of the Journal.
Editor-in-Chief
The Indian Journal of Chest Diseases & Allied Sciences 2006; Vol. 48
Superior Vena Cava Syndrome Caused by Pulmonary
Amoebic Abscess
K.B. Gupta, Manav Manchanda, Uma Chaudhary
1
and Manish Verma
Departments of Tuberculosis and Chest Diseases and Microbiology
1
, Pt. B.D. Sharma Postgraduate Institute
of Medical Sciences, Rohtak, India
ABSTRACT
Isolated pulmonary amoebiasis without involvement of liver and other systems is extremely rare. Its presentation with
superior vena cava (SVC) syndrome is not well documented. The case of 38-year-old male who developed SVC syndrome
due to a large pulmonary amoebic abscess, which initially mimicked a pulmonary neoplasm with distal lung abscess is
presented here. Subsequent bacteriological examination of the aspirated pus and the sputum along with suggestive serology
confirmed the diagnosis of pulmonary amoebic abscess. [Indian J Chest Dis Allied Sci 2006; 48: 275-277]
Key words: Superior vena cava syndrome, Abscess, Pulmonary, Amoebic.
[Received: June 30, 2005; accepted after revision: October 17, 2005]
Correspondence and reprint requests: Dr K.B. Gupta, 18/6J, Medical Enclave, Pt. B.D. Sharma PGIMS, Rohtak-124001
(Haryana), India; Tele.: 91-01262-213837.
Case Report
INTRODUCTION
Amoebiasis is a protozoan infection caused by
Entamoeba histolytica. Prevalence of amoebic colitis and
liver abscess is high in developing regions than the
industrialised world
1
.
Pleuropulmonary amoebiasis occurs in 2%-3% of
patients with invasive amoebiasis and is frequently
associated with liver abscess. Lung disease without liver
involvement is exceptional and it is believed that
infection of the lung is a result of haematogenous
spread from a primary site, usually colon
2
.
Superior vena cava (SVC) obstruction is oftenly
caused by malignant process, such as bronchogenic
carcinoma or lymphoma. However, in a small number
of patients the obstruction results from a benign, non-
malignant process which includes mediastinitis,
mediastinal tumours, cardiac and vascular causes,
trauma among others. Of these, tuberculosis,
retrosternal thyroid, aortic aneurysm and thymoma are
common. Among pulmonary causes, mediastinal
emphysema and pneumothorax have also been
reported
3
. Few cases of severe pulmonary infection by
Escherichia coli and Klebsiella
4
have been reported.
Lichtenstein et al
5
reported a case of pulmonary abscess
due to E. histolytica causing SVC obstruction along with
cerebral and intestinal involvement. We report an
unusual case of large pulmonary amoebic abscess that
presented as SVC syndrome without extra-pulmonary
involvement.
CASE REPORT
A 38-year-old male presented with progressive swelling
of his face and neck for 10 days. He also complained of
progressively increasing breathlessness on exertion,
cough with expectoration of brown thick sputum and
mild chest pain on right side. There was no history of
fever, gastrointestinal symptoms, abdominal pain,
hoarseness of voice or weight loss. He denied any past
illness of chronic bloody diarrhea. He had a history of
bidi smoking for 13 years. The patient was a truck-driver
by occupation, unmarried and a chronic alcoholic.
History of poor food hygiene was also present.
Physical examination showed the patient in mild
dyspnea. He was anemic. These was no evidence of
pedal edema. Blood pressure was 116/80 mmHg, pulse
was 84 per minute, respirations was 20 per minute and
temperature was 98.4
o
F. He had swelling of face and
neck along with marked periobital oedema and
collateral circulation on face, neck, anterior chest wall
and abdominal wall. Neck veins were distended and
non-pulsatile. Clubbing of digits was present. On chest
percussion, a dull note was found in the areas
corresponding to right upper lobe. Decreased breath
sounds and sucussion splash were found in right
axillary region on auscultation. There was no
organomegaly or peripheral lymphadenopathy.
Chest radiograph (Figure 1) showed a large abscess
with air fluid level in right upper lung field with rest of
lung field looking apparently normal. Laboratory
investigations revealed haemoglobin: 6.5 gm/dl, total
276
leukocyte count: 9500 per mm
3
, with a differential
leukocyte count of neutrophils: 75%, lymphocytes: 15%,
monocytes: 2% and eosinophills: 8%. Arterial blood gas
analysis showed pH: 7.414, PaCO
2
: 33.4 mmHg, PaO
2
:
56.9 mmHg, bicarbonate: 20.7 mEq/l, base excess: 2.1
mEq/l and oxygen saturation: 90.3%. Sputum was
negative for acid-fast bacilli (AFB) on direct and
concentrated smears. Serological testing for human
immunodeficiency virus (HIV) was nagative. Serum
aspartate aminotransferase (AST), alanine amino-
transferage (ALT) levels were within normal limits.
Stool examination for ova cysts of E. histolytica was
negative on three occasions. In view of short history,
rapidly progressive SVC obstruction syndrome and
absence of signs of infective pathology, an initial
presumptive diagnosis of a neoplasm causing distal
lung abscess with SVC syndrome was made.
Ultrasonography of thorax and abdomen was
performed which revealed a thick-walleld cystic area of
size 10.6 cm × 11 cm with internal echoes in the right
upper zone. Liver was normal. Contrast enhanced
computerised tomographic (CECT) scan of the chest
showed a peripherally enhancing cystic lesion with air-
fluid level in the right upper lobe which was
compressing superior vena cava leading to obliteration
of lumen of SVC (Figure 2).
Diagnostic tap was done and about 200 ml of brown
coloured turbid fluid was aspirated from the right
axillary region. Aspirated fluid was negative for AFB
and malignant cells and was sterile for pyogenic
culture. Biochemical examination showed protein level
greater than 6.0 g/dl. In view of young age and brown
coloured fluid, we also suspected pulmonary
amoebiasis and fluid was also examined for trophozites
of E. histolytica. Wet mount preparation and
hematoxylin and eosin staining of fluid revealed E.
histolytica trophozoites with RBCs. Subsequently, E.
histolytica trophozoites were also found in the sputum.
Later on, enzyme-linked immunosorbent assay (ELISA)
further supported the diagnosis of amoebiasis (value =
1.2 units in our patient, normal value < 0.4 units).
During initial stage, treatment with broad-spectrum
antibiotics for one week did not show any response and
chest radiograph showed increase in size of the lung
abscess. After confirmation of diagnosis of amoebic
pathology, patient was treated with metronidazole (800
mg thrice a day) and chloroquine (300 mg twice a day
for two days and 150 mg twice a day for 19 days).
Repeated therapeutic aspirations of fluid were also
done. After two weeks of treatment patient showed
marked clinical improvement with disappearance of
facial oedema and significant decrease in size of lung
abscess (Figure 3).
Figure 1. Chest radiograph (postero-anterior view) showing lung
abscess on the right side with air-fluid level (arrow).
Figure 2. Computed tomographic scan of the chest (mediastinal
window) showing lung abscess in right upper zone with
compression of superior vena cava (arrow).
Figure 3. Chest radiograph (postero-anterior view) showing
significant decrease in the size of the abscess.
Pulmonary Amoebic Abscess K.B. Gupta et al
2006; Vol. 48 The Indian Journal of Chest Diseases & Allied Sciences 277
DISCUSSION
The syndrome of SVC compression is not an
uncommon entity
6
. The SVC syndrome is usually
related to malignant process, but frequently benign
causes have also been described. Mediastinitis caused
by various granulomatous processes is probably the
most common cause of the benign SVC syndrome
3
.
There has been reports of SVC obstruction caused by
pulmonary and mediastinal infection caused by
tuberculosis
7
, histoplasmosis
8
, and nocardiosis
9
, E. coli
and Klebsiella
4
. A case of pulmonary abscess due to E.
histolytica causing SVC obstruction along with cerebral
and intestinal involvement has been reported
5
. In this
report
5
, liver enzymes of the patient were within normal
range and no abnormality of liver was found on
ultrasonography. Histological examination of the
excised tissue (after right pneumonectomy),
immunofluorescence using anti-entamoeba histolytica
antibodies and serology confirmed the diagnosis of
amoebiasis. The patient improved on treatment with
cytriaxone and metronidazole
5
. However, isolated
pulmonary involvement in amoebiasis without
evidence of involvement of extra-pulmonary site along
with SVC has not been documented previously.
The most frequent extra-intestinal site of
involvement in amoebiasis is the liver (3–9% of all
cases). The lung is invaded far less often, being affected
usually by the extension of liver abscess (6–40% of
patients with amoebic liver abscess)
10
. The lower and
middle lobes of the right lung are mostly affected in
form of empyema, abscess and hepatobronchial fistula.
Isolated upper lobe involvement without pleural and
hepatic involvement is extremely rare.
In our patient, poor hygiene of food can be related as
source of infection and lung involvement may be
secondary to haematogenous spread from the colon, but
we did not find evidence of intestinal involvement
either in history or during investigation. There have
been sporadic case reports showing appearance of
amoebic lung diseases without liver involvement
11
. In
our patient, large pulmonary amoebic abscess was
causing SVC syndrome. Adequate treatment with
metronidazole and chloroquine along with aspiration of
pus caused improvement in symptoms and decrease in
size of abscess.
In the present case, SVC obstruction might have been
caused by an inflammatory exudate and oedema.
Benign type of SVC is usually compatible with long life
without complications. Treatment in such cases is
variable. Several surgical procedures have been used to
relieve the obstruction, but majority of experts did not
advocate surgical intervention when clinical history is
suggestive of benign SVC obstruction, especially of
infective and inflammatory in origin. In fact, during sur-
gery to control bleeding, sometimes important venous
collaterals may be ligated leading to much hemorrhage
3
.
Most cases of SVC syndrome have a malignant
aetiology and work up to rule it out should be
aggressive. We recommend that E. histolytica should be
included as a possible cause in differential diagnosis of
lung lesions in young patients, especially in countries
where amoebiasis is endemic because lung amoebiasis
is a life threatening but treatable condition.
REFERENCES
1. Anonymous. Amebiasis. Wkly Epidemiol Rec 1997; 72: 97-9.
2. Shamsuzzaman SM, Hashiguchi Y. Thoracic amebiasis. Clin
Chest Med 2002; 23: 479-92.
3. Mahajan V, Strimlan V, Ordstrand HS, Loop FD. Benign
superior vena cava syndrome. Chest 1975; 68: 32-5.
4. Kim JY, Lim CM, Koh Y, Choe KH, Kim WS, Kim WD. A case
of superior vena cava syndrome caused by Klebsiella
pneumoniae. Eur Respir J 1997; 10: 2902-3.
5. Lichtenstein A, Kondo AT, Visvesvara GS, Fernandez A,
Paiva EF, Mauad T, et al. Pulmonary amoebiasis presenting as
superior vena cava syndrome. Thorax 2005; 60: 350-2.
6. McIntire FT, Sykes EM. Obstruction of the superior vena
cava: a review of the literature and report of two personal
cases. Ann Intern Med 1949; 30: 925-60.
7. Steinberg I. Superior vena cava syndrome due to
tuberculosis: report of three cases. Am J Roentgenol Radium
Ther Nucl Med 1966; 98: 440-6.
8. Urschel HC, Razzuk MA, Netto GJ, Disiere J, Chung SY.
Sclerosing mediastinitis: improved management with
histoplasmosis titer and ketoconazole. Ann Thorac Surg 1990;
50: 215-21.
9. Abdelkafi S, Dubail D, Bosschaerts T, Brunet A, Van Camp G,
Marneffe M, et al. Superior vena cava syndrome associated
with Nocardia farcinica infection. Thorax 1997; 52: 492-3.
10. Petri WA Jr, Singh U. Diagnosis and management of
amebiasis. Clin Infect Dis 1999; 29: 1117-25.
11. Afsar S, Choudhri AN, Ali J, Muneer A. Primary pulmonary
amoebiasis: an unusual case of pulmonary consolidation. J
Pak Med Assoc 1992; 42: 245-6.
278
ATTENTION SUBSCRIBERS
Due to substantial increase in the cost of printing, paper, postal charges and other
overhead expenses, it has been decided to revise the Subscription Rates w.e.f. 1st
January, 2005. New rates are given below:
Subscription Rates
(w.e.f. 1st January, 2005)
Individual Institutional
India Overseas India Overseas
(In Rs.) (In US $) (In Rs.) (In US $)
Single Issue 250.00 40.00 300.00 40.00
One Volume 800.00 100.00 1000.00 100.00
(4 Issues)
Note
(i) Overseas subscription rates include airmail postal charges.
(ii) Subscription Agencies are eligible for a 10% discount on annual rates for
institutional subscription only. Subscription Agencies must provide complete
address of the Institution for which subscription is sent in their subscription
order.
(iii) Payments should be made only by Banker's Cheque/Demand Draft, drawn
in favour of the Director, V.P. Chest Institute, Delhi.
(iv) The above rates are not subject to any Tax Deduction at Source.
Sd/-
Publishers/Editor-in-Chief
The Indian Journal of Chest Diseases & Allied Sciences 2006; Vol. 48
Uncommon Parathyroid Mediastinal Cyst Compressing
the Trachea
D. Agrawal, T.K. Lahiri, Anshu Agrawal
1
and Manish Kumar Singh
1
Department of Cardiothoracic Surgery and General Surgery
1
, Institute of Medical Sciences, Banaras Hindu
University, Varanasi, Uttar Pradesh, India
ABSTRACT
Mediastinal parathyroid cyst is a rare cause of space occupying lesion in the mediastinum. No specific symptomatology may
be attributed to the non-functioning parathyroid cyst. The diagnosis is rarely made before exploration. The cysts are thin
walled, smooth, of varying sizes and contained clear, opalescent or haemorrhagic fluid. Histopathological examination reveals
clusters of parathyroid cells dispersed in the wall of the cyst. Surgical removal is the treatment of choice and can be performed
with minimal morbidity. [Indian J Chest Dis Allied Sci 2006; 48: 279-281]
Key words: Mediastinal cyst, Parathyroid cyst, Sub-total resection.
[Received: May 12, 2005; accepted after revision: October 27, 2005]
Correspondence and reprint requests: Dr D. Agrawal, Reader and Head, Department of Cardiothoracic Surgery, Institute
of Medical Sciences, Banaras Hindu University, Varanasi-221005, (U.P.), India; Tele.: 91-0542-2307530, 2309484.
INTRODUCTION
Mediastinal parathyroid cysts are embryologic
aberration. They may be incidental, accidental,
functional or non-functional
1
. Due to asymptomatic
presentation of the non-functional cyst, diagnosis is
seldom made before the operation. Compression of the
trachea by the non-functional parathyroid cyst is a rare
presentation. Paucity of cases in the literature promoted
us to report this case.
CASE REPORT
A 62-year-old female presented with a four months
history of swelling of left lower neck along with dull
aching pain. Fine needle aspiration from the swelling on
the left supraclavicular area, which was nonpulsatile,
compressible, globular, nontender, partially mobile and
approximately 5 cm in diameter, revealed clear fluid
only. There were no symptoms referable to the chest.
Coughing with small quantities of sputum in the
morning was admitted by the patient. She had no
dyspnoea, dysphagia or weight loss. There were no
signs or symptoms of hyperthyroidism. On physical
examination fullness was present at left root of the neck.
General physical and systemic examinations were
unremarkable. Laboratory tests were in indexed range
including serum T
3
, T
4
thyroid stimulating hormone
(TSH) levels. Routine chest radiograph showed a large
mass on the left upper mediastinum along with
encroachment to the left upper lung field. This also
revealed shifting of the trachea towards the right along
with indentation (Figure 1). Contrast enhanced
computed tomographic (CT) scan confirmed a mass
(10.3 cm × 8.1 cm) in the superior mediastinum to the
Case Report
Figure 1. Chest radiograph (postero-anterior view) showing a
large left superior mediastinal mass with displacement, and
indentation on the left side of the trachea.
280
left of midline having fluid component, and right
shifting of the mediastinal structure (Figure 2).
Bronchoscopy revealed distortion of the trachea on the
right along with compression effect over the carina.
number of cells had light eosinophilic stained
cytoplasm. The thyroid glandular follicles presented
normal appearance with a few of them contained
colloid in the lumen (Figure 3).
Figure 2. CECT chest showing a large cystic mass in the
mediastinum with attenuation and enhancement and shifting of
the mediastinal structures to the right.
Fine needle aspiration cytology (FNAC) from the left
supraclavicular mass showed degenerated red blood
cells in pale eosinophilic back ground with no signs of
malignant cells. A provisional diagnosis of left
paratracheal cyst was made.
The patient underwent left posterolateral
thoracotomy which revealed a cystic mass of 10 cm × 9
cm anterior to the left subclavian artery extending upto
the clavicle. The mass compressed the left subclavian
artery, arch of the aorta and the trachea. About 30 to 40
ml of colourless fluid aspirated from the cystic mass
which was excised subtotally. Examination of the
aspirated fluid revealed total cholesterol 150 mg/dl
(normal 150–220 mg/dl), total protein 7.3 g/dl (normal
6.6–8.7 g/dl), triglycerides 108 mg/dl (normal value not
established in fluid, but in serum < 200 mg/dl).
Examination of the excised mass revealed a thin-
walled cyst (10 cm × 8 cm in size) along with small
nodules. Microscopic examination showed wall of cyst
formed by thick zone of densely arranged
fibrocollageneous tissue. The inner surface was covered
by loosely arranged laminated layers of organized
blood clots and at a few places by flattened cells. The
outer portion of the cyst showed lobules of proliferated
parathyroid glandular tissue, and at a few places by
groups of thyroid follicles. The lobules of parathyroid
glands mainly consisted of round or cuboidal cells
arranged in small acinar pattern having deeply stained
round nuclei, and vacuolated or clear cytoplasm. Small
Figure 3. Photomicrograph of the resected cyst showing lobules
of proliferated parathyroid gland consisting of cuboidal or
rounded cells having deeply stained round nuclei and
vacuolated clear cytoplasm (H&E × 150).
Immunocytochemistry disclosed pancytokeratin
weakly
1
positive in thyroid follicles, and in flattened
lining cells of the cyst wall, Factor VIII positive in the
inner surface of the wall of the cyst, thyroglobulin
positive in thyroid follicles only, and negative calcitonin,
smooth muscles actin (SMA), and leucocyte common
antigen (LCA, CD 45). The above findings were
compatible with parathyroid cyst of the mediastinum.
Post-operative examination of the serum revealed
calcium 9.9 mg/dl (normal 8–10 mg/dl), phosphorus 5.6
mg/dl (normal in serum 2.7–4.7 mg/dl), alkaline
phosphatase 175 IU/L (normal 108–306 IU/L), and
parathormone level 8.1 pg/ml (normal 8–72 pg/ml).
The post-operative course of the patient was
uneventful and the post-operative follow up after three
months, patient became asymptomatic but chest
Mediastinal Parathyroid Cyst D. Agrawal et al
2006; Vol. 48 The Indian Journal of Chest Diseases & Allied Sciences 281
radiograph still showed indentation over the trachea.
DISCUSSION
Tumours and cysts occur in the mediastinum.
Uncommon causes are thyroid cysts, parathyroid cysts
and thoracic duct cysts. De Quervain first operated a
case of mediastinal parathyroid cyst in 1925
2
. Enlarged
superior parathyroid cyst tends to locate in the
tracheoesophageal groove, in the middle mediastinum,
or else can be in retropharyngeal space. The inferior
parathyroid cysts are found under the thyroid capsule,
frankly intrathyroidal, within the thymus in the anterior
mediastinum, or when undescended at the carotid
bulb
2
. The missing parathyroid cysts are located in the
neck in approximately 50% of the cases. The places are
medial to the upper pole of the thyroid, superior
mediastinum in the thymic capsule, retroesophageal, in
the carotid sheath and when undescended upto the
hyoid bone (para-pharyngeous). Mediastinal locations
are anterior superior, posterior mediastinum and aorto
pulmonary window
3
. Mediastinal parathyroid cysts are
rare and 94 cases have been collected until 1999
4
. The
location of the cysts are anterosuperior (the pretracheal
portion of the visceral compartment of the
mediastinum) in 56 patients, in the middle region
(retrotracheal upto thoracic spine) of the mediastinum
in 26, and in the anterior, prevascular region in 12
patients. In our case the parathyroid cyst was
compressing the trachea, left subclavian artery and arch
of the aorta.
Parathyroid cysts present as functional or non-
functional. Functional cysts present as symptoms of
hyperparathyroidism with hypercalcaemia (99%), renal
impairment (nephrolithiasis, nephrocalcinosis, impaired
glomerular filtration rate) in 32%–84%, and skeletal
manifestation (osteitis fibrosa cystica, absent lamina
dura, diffuse spinal osteopenia, subperiosteal bone
reabsorption, salt-and-pepper skull) in 41%–91%. Non-
functional cyst is usually asymptomatic, or may present
as a neck mass with symptoms of hoarseness,
dysphagia, tracheal compression, recurrent laryngeal
nerve palsy or innominate vein compression,
predominantly in the females and attains a large
size
1,5,10
.
Parathyroid cysts are thought to arise from cystic
degeneration in a parathyroid adenoma or hyperplastic
gland. Other possibilities are remnants of vestigeal
pharyngobranchial ducts and Kursteiner canals,
coalescence of the clefts, retention of secretion in the
microcysts, and presence of foetal remnants of the third
and fourth branchial clefts
3,8
.
The diagnosis of mediastinal parathyroid cyst is
seldom made before operation. Functional cysts are
diagnosed with serum calcium level, PTH assay and
Sestamibi parathyroid imaging scan with single photon
emission CT imaging, and gamma camera during
operation
2,6
. Non-functional cyst usually diagnosed as
incidental. Clear, colourless watery fluid with high level
of PTH (600 to 600,0000 pg/ml) strongly suggestive of
parathyroid cyst
7
. Definite diagnosis is made only by
histopathologic examination. Grossly transparent cyst
wall with clear low specific gravity fluid is detected.
Microscopically cyst is lined by solitary layer of
compressed cuboidal low columnar epithelium and
contains eosinophilic colloid material, and stain positive
for glycogen
2
. Immunocytochemistry positivity for
pancytokeratin, (thyroid epithelium), and weakly
positive Factor VIII (for endothelial cells) can be
detected.
Surgical removal of the cyst is indicated in
symptomatic patients. The approaches are cervical
approach, through posterolateral thoracotomy,
occasionally median sternotomy, and now minimally
invasive surgery
1,2
. Recently pure closed endoscopic
parathyroidectomy or video-assisted gasless parathy-
roidectomy through the axillary, anterior chest, lateral
neck, and anterior neck approach have been advocated
9
.
In the indexed case left posterolateral thoractomy and
subtotal excision of the mass has been performed.
In conclusion, non-functional mediastinal
parathyroid cysts are rare causes of space occupying
lesions to be dealt with by the clinician. The cysts
produce symptoms due to compression on adjacent
structures. They should be considered in the differential
diagnosis of space occupying cystic lesion of the
mediastinum. The presence of parathyroid cells in the
lining of the cyst wall proves the diagnosis.
REFERENCES
1. Downey RJ, Cerfolio RJ, Deschamps C, Grant CS, Pairolero
PC. Mediastinal parathyroid cysts. Mayo Clin Proc 1995; 70:
946-50.
2. Carty SE. Prevention and management of complications in
parathyroid surgery. Otolaryngol Clin North Am 2004; 37: 897-
907.
3. Shaha AR. Parathyroid re-exploration. Otolaryngol Clin North
Am 2004; 37: 833-43.
4. Shields TW, Immerman SC. Mediastinal parathyroid cysts
revisited. Ann Thorac Surg 1999; 67: 581-90.
5. Margolis IB, Wayne R, Organ CH(Jr). Parathyroid cysts:
functional and mediastinal. Surgery 1975; 77: 462-6.
6. Hauet EJ, Paul MA, Salu MK. Compression of the trachea by
a mediastinal parathyroid cyst. Ann Thorac Surg 1997; 64:
851-2.
7. Pacini F, Antonelli A, Lari R, Gasperini L, Baschieri L,
Pinchera A. Unsuspected parathyroid cysts diagnosed by
measurement of thyroglobulin and parathyroid hormone
concentrations in fluid aspirates. Ann Intern Med 1985; 102:
793-4.
8. Clark OH. Parathyroid cysts. Am J Surg 1978; 135: 395-402.
9. Ng WT. Continuing evolution of the truly minimally invasive
parathyroidectomy. Arch Surg 2003; 138: 1024.
10. Umemori Y, Makihara S, Kotani K, Washio K. Mediastinal
parathyroid cyst with tracheal construction. Japanese J Thorac
Cardiovasc Surg 2002; 50: 85-7.
282
NATIONAL COLLEGE OF CHEST PHYSICIANS (INDIA)
Fellowship/Membership Fee
Membership (Annual) : Rs.300.00
Membership (Life) : Rs.3000.00
Fellowship : Rs.5000.00
Enrolement (new members only) : Rs.500.00
Payments should be made by Cheque/Demand Draft, drawn in favour of the
Secretary, National College of Chest Physicians (I). Please add Rs.75/- to all out-
station cheques.
Annual membership is valid for one financial year (April-March) only.
Sd/-
Secretary
NATIONAL COLLEGE OF CHEST PHYSICIANS (INDIA)
Fellows and Members of the College are requested to mention their old
address also while informing for change of address alongwith their Fellowship/
Membership number to the Secretary, NCCP (I) and/or to Publication
Department, IJCDAS to avoid any mistake/delay in mailing the Journal's
copy as well as College's information.
Sd/-
Secretary
The Indian Journal of Chest Diseases & Allied Sciences 2006; Vol. 48
Case Report
Pulmonary Hyalinizing Granuloma with Ureteric Fibrosis:
A Case Report and Review of Relevant Literature
D. Agrawal, R. Deshpande, S. Maheshwari, A. Patel and Z.F. Udwadia
Departments of Pulmonology, Pathology and Radiology, P.D. Hinduja Hospital and Medical Research Centre,
Mumbai, India
ABSTRACT
A 52-year-old, asymptomatic patient presented with bilateral lung nodules on chest radiograph. She was diagnosed to have
“pulmonary hyalinizing granuloma” on an open lung biopsy. We review the clinical features of this rare disease. [Indian J
Chest Dis Allied Sci 2006; 48: 283-285]
Key words: Bilateral pulmonary nodules, Pulmonary hyalinizing granuloma, Ureteric fibrosis.
[Received: November 1, 2004; accepted after revision: October 27, 2005]
Correspondence and reprint requests: Dr Z.F. Udwadia, Consultant Pulmonologist, P.D. Hinduja Hospital, Veer Savarkar
Marg, Mahim, Mumbai-400016, India; Tele.: 91-22-24451515.
INTRODUCTION
Pulmonary hyalinizing granuloma is a rare, non-
infectious disease of the lung, of unknown aetiology. It
is usually diagnosed on open lung biopsy or after
resection of nodules noted on chest radiography
1,2
. We
report one such case of this rare entity, as there is a
paucity of Indian data on this condition.
CASE REPORT
A 52-year-old housewife from Surat came to our
Hospital in Mumbai in June 2004 for evaluation of
bilateral lung nodules on chest radiograph. In 1996 she
was admitted at a private hospital in Surat with
complaints of dry cough and low grade fever. She was
then diagnosed to have right lung opacity on the chest
radiograph for which she was treated with a 10-day
course of antibiotics. Her routine haematological and
biochemical tests were normal. Antinuclear antibody
(ANA) test, antineutrophilic cytoplasmic antibody
(ANCA) and rheumatoid factor (RF) were negative.
Two months later she was empirically started on
antituberculosis treatment in addition to 30 mg of
prednisolone daily.
In view of persistent radiological features,
computerised tomographic (CT) scan of chest and
bronchoscopy were done. Transbronchial lung biopsy
and CT-guided percutaneous transthoracic fine needle
aspiration cytology (FNAC) were non-diagnostic.
Antituberculosis treatment was discontinued as myco-
bacterial and fungal cultures of bronchoalveolar lavage
fluid were negative. She was then lost to follow-up.
In 2004, she was re-admitted at Surat for abdominal
pain. Routine chest radiograph and CT-scan during this
admission showed bilateral lung nodules (Figures 1 &
2) and she was referred to our centre for further
evaluation.
Figure 1. Chest radiograph (postero-anterior view) of 2004
showing a large irregular opacity in the right mid zone and
opacities in the left upper zone.
She was asymptomatic at presentation to us. No
crackles or wheeze were auscultated. Pulmonary
function testing revealed forced expiratory volume in
the first second (FEV
1
) – 68% of predicted and the ratio
of FEV
1
and forced vital capacity (%) [FEV
1
/FVC – 80
percent. All routine haematological and biochemical
tests were normal. Erythrocyte sedimentation rate (ESR)
rate was 8 mm at the end of first hour. Repeat (ANA)
and ANCA tests were negative. An open lung biopsy
was done as it was considered mandatory to rule out
malignancy. Histopathology showed well-defined
284
nodules of dense collagen arranged in a storiform
pattern and in whorls (Figure 3), which confirmed
pulmonary hyalinizing granuloma. CT scan of the
abdomen was reviewed at our hospital and the cause of
her abdominal pain was believed to be secondary to
ureteric and retroperitoneal fibrosis as shown in figure
4 with soft tissue encasing the right proximal ureter.
DISCUSSION
The term “Pulmonary hyalinizing granuloma” was
introduced by Engleman et al
3
in 1977 to describe
multiple bilateral pulmonary nodules. It is a rare
fibrosing nodular disease of the lung which is usually
discovered incidentally on chest radiograph and poses
diagnostic difficulties but has excellent prognosis
1
. A
detailed medline search revealed only one other case
report from India
2
.
Age range of patients reported in two large series by
Engleman et al
3
and Yousem et al
4
of 20 and 2 patients
respectively was 24 to 77 years with a mean age of 42.3
years. The sex distribution reported by them was equal
with no racial predominance. Our patient was slightly
older than the average age mentioned. However, her
radiographic abnormality had been there for eight years
prior to the diagnosis.
Size of the tumours in above series varied from
several millimeters to 15 cm in greatest dimension; 73%
of their patients had multiple lesions
3,4
. Multiple
symptoms have been reported in different series and
case reports
3,4
. These include cough, dyspnea, weight
loss and pleuritic chest pain. Many patients are
asymptomatic with lesions being seen on routine health
screening examinations
3,4
. Cases complicated with
sclerosing mediastinitis, retroperitoneal fibrosis and
amyloidosis have also been reported
3
. Our patient had
abdominal complaints and on further evaluation of this
complaint was noted to have right ureteric fibrosis.
Pulmonary hyalinising granuloma can also present
as dysphagia due to either direct involvement of the
esophagus or due to tight stricture from associated
mediastinal fibrosis
2,5
. Neoplastic diseases have rarely
been reported with pulmonary hyalinizing granuloma.
These include abdominal lymphoma, multiple
myeloma, Paget’s disease of the breast and astrocytoma
of the brain
6,7
.
The aetiology of pulmonary hyalinizing granuloma
is uncertain; however it has been proposed that it
represents an abnormal immune reaction to tuberculous
bacilli, histoplasma organisms or other infectious
agents
8
. Autoimmune mechanism has also been
suggested supported by the association of many
immune-mediated diseases like rheumatoid arthritis,
uveitis and retroperitoneal fibrosis
2
. Microscopically the
disease is characterised by a dense network of
concentric hyalinized collagen in the center surrounded
by perivascular lymphoplasmacytic infiltrate that
rarifies in the center of the nodule
3
. Although
pulmonary hyalinizing granuloma is a benign entity,
30% of patients may have progressive disease
manifested by enlarging nodules and increasing
dyspnea
4
.
Isolated lesions are often resected with resultant cure.
No definite treatment is available for multiple lesions
but the prognosis is good with no significant impact on
Figure 2. CT scan of chest of 2004 showing multiple subpleural
nodules.
Figure 3. Photomicrograph of the open lung biopsy specimen's,
microscopy showing dense collagenous bands arranged in
storiform pattern and in whorls. Lung periphery showing
interstitial fibrosis and nodular aggregates of lymphocytes (H &
E × 400).
Figure 4. Contrast enhanced CT-scan of abdomen showing
enhancing soft tissue encasing right proximal ureter.
Pulmonary Hyalinizing Granuloma D. Agrawal et al
2006; Vol. 48 The Indian Journal of Chest Diseases & Allied Sciences 285
longevity
8
. In selected patients with pulmonary
hyalinizing granuloma who experience disabling
symptoms and worsening pulmonary function, a trial of
corticosteroids is warranted
7
.
In summary, pulmonary hyalinizing granuloma
should be considered in the differential diagnosis of
pulmonary nodules. A high index of suspicion with use
of lung biopsy would achieve the diagnosis.
REFERENCES
1. Russell AF, Suggit RI, Kazzi JC. Pulmonary hyalinizing
granuloma: a case report and literature review. Pathology
2000; 32(4): 290-3.
2. Khilnani GC, Kumar A, Gupta SD, Surendranath A, Sharma
S. Pulmonary hyalinizing granuloma presenting with
dysphagia. J Assoc Physicians India 2003; 51: 519-21.
3. Engleman P, Liebow AA, Gmelich J, Friedman PJ. Pulmonary
hyalinizing granuloma. Am Rev Respir Dis 1977; 115: 997-1008.
4. Yousem SA, Hochholzer L. Pulmonary hyalinizing
granuloma. Am J Clin Pathol 1987; 87: 1-6.
5. Gossot D, Fromont G, Galetta D, Debrosse D, Grunenwald D.
Pulmonary hyalinizing granuloma with mediastinal fibrosis:
a cause of dysphagia. Ann Chir 2003; 128: 622-5.
6. Ren Y, Raitz EN, Lee KR, Pingleton SK, Tawfik O. Pulmonary
small lymphocytic lymphoma (mucosa-associated lymphoid
tissue type) associated with pulmonary hyalinizing
granuloma). Chest 2001; 120: 1027-30.
7. O' Reilly KM, Boscia JA, Kaplan KL, Sime PJ. A case of steroid
responsive pulmonary hyalinising granuloma: complicated
by deep venous thrombosis. Eur Respir J 2004; 23(6): 954-6.
8. Drasin H, Blume MR, Rosenbaum EH, Klein HZ. Pulmonary
hyalinizing granulomas in a patient with malignant
lymphoma with development nine years later of multiple
myeloma and systemic amyloidosis. Cancer 1979; 44: 215-20.
286
ATTENTION SUBSCRIBERS
Due to substantial increase in the cost of printing, paper, postal charges and other
overhead expenses, it has been decided to revise the Subscription Rates w.e.f. 1st
January, 2005. New rates are given below:
Subscription Rates
(w.e.f. 1st January, 2005)
Individual Institutional
India Overseas India Overseas
(In Rs.) (In US $) (In Rs.) (In US $)
Single Issue 250.00 40.00 300.00 40.00
One Volume 800.00 100.00 1000.00 100.00
(4 Issues)
Note
(i) Overseas subscription rates include airmail postal charges.
(ii) Subscription Agencies are eligible for a 10% discount on annual rates for
institutional subscription only. Subscription Agencies must provide complete
address of the Institution for which subscription is sent in their subscription
order.
(iii) Payments should be made only by Banker's Cheque/Demand Draft, drawn
in favour of the Director, V.P. Chest Institute, Delhi.
(iv) The above rates are not subject to any Tax Deduction at Source.
Sd/-
Publishers/Editor-in-Chief
The Indian Journal of Chest Diseases & Allied Sciences 2006; Vol. 48
Case Report
Life Threatening Exacerbation in Idiopathic Pulmonary
Hemosiderosis Salvaged by Cyclophosphamide Infusion
Rahul Naithani, Jagdish Chandra, Varinder Singh, Veerendra Kumar and N.K. Dubey
Pulmonary and Critical Care Division, Kalawati Saran Children’s Hospital and Lady Hardinge Medical
College, New Delhi, India
ABSTRACT
A seven-year-old girl presented with frequent fever, cough and shortness of breath of three months duration. On the basis
of her clinical features, peripheral blood and sputum findings, she was diagnosed as a case of idiopathic pulmonary
hemosiderosis. After initial stabilisation with steroids and chloroquine, she presented four years later with massive
pulmonary hemorrhage and respiratory failure, which responded dramatically to cyclophosphamide infusion. The rare
occurrence of pulmonary hemosiderosis and different treatment regimens is discussed. [Indian J Chest Dis Allied Sci 2006; 48:
287-289]
Key words: Hemosiderosis, Exacerbation, Cyclophosphamide, Immunosuppression.
[Received: April 4, 2005; accepted after revision: November 23, 2005]
Correspondence and reprint requests: Dr Rahul Naithani, Department of Hematology, First Floor, IRCH Building, All India
Institute of Medical Sciences, New Delhi-110029, India; Tele.: 91-11-261915694; Telefax: 91-11-23365792; E-mail:
dr_rahul6@hotmail.com.
INTRODUCTION
The term pulmonary hemosiderosis describes a number
of rare conditions characterised by abnormal
accumulation of hemosiderin in lungs. Hemosiderin
deposits follow diffuse alveolar hemorrhage and may
occur either as primary disease of lung or secondary to
cardiac or systemic vascular diseases
1,2
. Mortality rate
for this disease can be as high as 50 percent. Exact
etiology is unknown, although it may be associated
with immune-mediated mechanisms
1-3
.
Although high-dose corticosteroids had been the
treatment of choice during the acute stage of idiopathic
pulmonary hemosiderosis (IPH) to decrease the
frequency of pulmonary hemorrhage; the long-term
benefit of this treatment is still in doubt
3, 4
. Long-term
treatment with steroids, azathioprine, chloroquine and
cyclophosphamide, have been instituted in a small
number of cases, which have resulted in subsequent
remissions
3-11
.
We report a case of IPH with acute severe
exacerbation, which was salvaged by cyclophos-
phamide infusion on two occasions.
CASE REPORT
A seven-year-old girl, who had experienced frequent
fever, cough and shortness of breath for three months,
was admitted to our hospital in November 1997. She
had earlier received three blood transfusions. On
examination, she had pallor, tachypnoea, tachycardia
and bilateral diffuse coarse crepitations. Rest of general
physical or systemic examination was normal.
Laboratory investigations revealed a haemoglobin of 5.6
g/dl; reticulocyte count of 7%, total leukocyte count of
11500/mm
3
and a platelet count of 189 × 10
3
/mm
3
,
normal liver and renal function tests, serum iron 53 µg/
dl, total iron binding capacity 310 µg/dl, serum ferritin
108 ng/ml. Peripheral smear showed a dimorphic
anemia. Coagulation profile was normal. Stool was
negative for occult blood. Mantoux test was negative.
Chest radiograph showed bilateral diffuse alveolar
infiltrates with consolidations in the right middle lobe.
Electrocardiogram (ECG) showed sinus tachycardia but
echocardiography was normal. Computed tomographic
(CT) scan of the thorax revealed bilateral diffuse ground
glass attenuation, diffuse hazy nodular pattern and
patches of consolidation associated with early fibrotic
changes (Figure). Microscopic examination of gastric
aspirate showed hemosiderin-laden macrophages and
was negative for acid-fast bacilli by Ziehl-Neelsen stain.
She was started empirically on antibiotics,
hematinics and supportive therapy. After one week of
treatment marked improvement was observed and her
chest radiograph improved too, but she continued to
have mild cough and pigment-laden macrophages
persisted in gastric aspirates even after three months.
Antinuclear antibody (ANA) was negative and C
3
and
C
4
were normal. She was diagnosed as a case of
idiopathic pulmonary hemosiderosis. She was started
on oral prednisolone (2 mg/kg) and discharged.
288
Her hemoglobin dropped from 13.1g/dl at discharge
to 7.5 g/dl in four months. Prednisolone was then
stopped and chloroquine, as an immunosuppressant in
the dose of 50 mg/day was started. She continued on
chloroquine for four years and her average
haemoglobin during this period was 9.1 g/dl (7.1–11.9
g/dl). The drug was discontinued for about eight weeks
due to deranged liver function tests, which improved to
baseline in the said period. During these four years the
patient was admitted on three occasions for similar
symptoms of cough, shortness of breath, and
respiratory distress.
In January 2002 she developed fever and progressive
dyspnea. Chest radiograph revealed diffuse bilateral
alveolar infiltrates. She was put on oxygen, steroids,
intravenous fluids and antibiotics and transfused
packed red blood cells but her condition continued to
deteriorate. Seventeen hours later she was shifted to
intensive care unit and mechanical ventilation was
started. Her ventilatory requirements kept on increasing
for the next 24 hours and she experienced a bout of
pulmonary haemorrhage when it was decided to
institute cyclophosphamide infusion in a dose of
2 mg/kg body-weight over one hour. Her condition
stabilised in next 28 hours when we started reducing
ventilatory settings. She continued to show gradual
improvement and could be weaned off the ventilator in
next 88 hours and started on supplemental oxygen and
saline nebulisation. Pulmonary haemorrhage resolved
by third day of cyclophosphamide infusion. She
developed spiking fevers after extubation. Tracheal
aspirate grew Klebsiella spp that was sensitive to
ceftazidime; she recovered after institution of appro-
priate antibiotics. Cyclophosphamide infusion was
continued for three days after ventilatory support and
later switched to oral cyclophosphamide with
prednisolone (2 mg/kg/day). She was discharged on
oral antibiotics and alternate day cyclophosphamide (2
mg/kg/day).
She had regular follow-up visits at our hospital.
Three weeks later she presented with a low platelet
count of 25000/mm
3
. However, no evidence of
petechiae or spontaneous bleeding was found. Platelet
counts showed prompt recovery to stoppage
of
cyclophosphamide for 14 days after which it was
reinstituted in the same dosage. She was eventually
weaned off from both cyclophosphamide and steriod
therapy in next nine months.
After 18 months of event-free period, she developed
hemoptysis and shortness of breath for which she was
re-admitted. At this time the chest radiograph showed
diffuse pulmonary infiltrates. During this acute episode
cyclophosphamide intravenous infusion (2 mg/kg/
day) along with prednisolone was administrated from
the beginning and her condition was immediately
controlled. This time ventilatory support was not
required. Cyclophosphamide infusion was continued
for eight days. She was discharged on oral cyclophos-
phamide (2 mg/kg/day) but continued to have mild
cough. Three months later chloroquine 150 mg per day
was re-started.
During the subsequent year, the disease has
stabilised without evidence of progression (e.g.,
hemoptysis or pulmonary infiltrates). Because of the
patient’s good response to cyclophosphamide and the
chronic course of pulmonary hemosiderosis, we
continued with cyclophosphamide (2 mg/kg given
every other day) and chloroquine; and closely monitor
the disease progression as well as the possible adverse
effects of the treatment.
DISCUSSION
In children, the estimated incidence of idiopathic
pulmonary hemosiderosis (IPH) is 0.24–1.23 cases per
million
2
. It is characterised by accumulation of
hemosiderin in lungs following diffuse alveolar
hemorrhage. An absolute requirement for the diagnosis
is identification of hemosiderin-laden macrophages in
sputum or confirmed by flexible fiberoptic broncho-
scopy with a bronchoalveolar lavage (BAL) study
2
.
Most therapeutic efforts institute immuno-
suppressive agents in an attempt to impede the immune
responses, however, long-term benefits of such
treatments are still debatable. Initial use of high-dose
corticosteroids in acute episodes of IPH has proven to
decrease the frequency of pulmonary haemorrhage, and
is considered the treatment of choice
1,2
. One series of 23
patients with IPH on long-term, low-dose steroid
treatment showed that half of the patients had no
relapse after discontinuation of steroids and the
remaining cases continued normal life on a low-dose
steroid regimen
9
.
Other forms of immunosuppression, such as
azathioprine, chloroquine, or cyclophosphamide has
been used in patients who fail to respond to steroids or
develop unacceptable adverse effects
3,9
. A 22-year-old
Cyclophosphamide in Pulmonary Hemosiderosis Exacerbation R. Naithani et al
Figure. CT thorax showing bilateral diffuse ground glass
attenuation and patches of consolidation with early fibrotic
changes.
2006; Vol. 48 The Indian Journal of Chest Diseases & Allied Sciences 289
man with a life-threatening IPH experienced prompt
and lasting remission of his disease with institution of
azathioprine
3
. After discontinuation of this drug, the
patient remained well. Another 8-year-old girl with IPH
was sucessfully treated with prednisolone 1.5 mg/kg/
day for 14 years, although her symptoms re-appeared
when the dosage of both drugs were tapered
4
.
Chloroquine has been shown to have some benefit in
two earlier reports
5, 6
. Our patient also remained in
remission for four years with chloroquine after failing to
respond to prednisolone before the exacerbation when
cyclophosphamide infusion was required.
Cyclophosphamide possesses potent anti-
inflammatory and immunosuppressive action. It
inhibits both humoral and cell-mediated reactions
through unknown mechanisms
7
. Notable advantages of
this drug are the availability of oral route of
administration and the possibility of giving fractioned
doses over a period of time. Cyclophosphamide in IPH
has been used in three cases and had been efficacious in
controlling the disease with a decreased number of
crises
7
. Another series reported beneficial effect in three
patients
8
with cyclophosphamide and prednisone
7,9
.
Rarity of the disease makes the appropriate dosing
regimen difficult. Clinical status and deteriorating
ventilatory requirements that improved with cyclophos-
phamide infusion in our case suggest a beneficial
response to drug. Second episode that occurred nine
months after stopping the drug suggests prolonged
continuation and gradual tapering over a period of
time. Although the efficacy of these immuno-
suppressive agents is important but adverse effects may
develop on long-term usage. Various side-effects of
cyclophosphamide reported include thrombo-
cytopenia
9
, alopecia, mucosal ulceration, second
malignancy, haemorrhagic cystitis, interstitial pulmo-
nary fibrosis, cumulative hepatotoxicity and ovarian
and testicular dysfunction
7,10
. Fortunately for the patient
thrombocytopenia was noticed when it was asympto-
matic and improved after temporary discontinuation of
drug. A long-term follow-up is required to fully
understand the natural history of this disease.
REFERENCES
1. Dua T, Chandra J, Jain M, Passah SM, Dutta AK. Idiopathic
pulmonary hemosiderosis. Indian J Pediatr 2000; 67(9): 693-4.
2. Ohga S, Takahashi K, Miyazaki S, Kato H, Ueda K. Idiopathic
pulmonary haemosiderosis in Japan: 39 possible cases from a
survey questionnaire. Eur J Pediatr 1995; 154: 994-8.
3. Byrd RB, Gracey DR. Immunosuppressive treatment of
idiopathic pulmonary hemosiderosis. JAMA 1973; 226: 458-9.
4. Rossi GA, Balzano E, Battistini E, Oddera S, Marchese P,
Acquila M, et al. Long-term prednisone and azathioprine
treatment of a patient with idiopathic pulmonary
hemosiderosis. Pediatr Pulmonol 1992; 13: 176-80.
5. Bush A, Sheppard MN, Warner JO. Chloroquine in idiopathic
pulmonary hemosiderosis. Arch Dis Child 1992; 67: 625-7.
6. Zaki M, Al Saleh Q, Al Mutari J. Effectiveness of chloroquine
therapy in idiopathic pulmonary hemosiderosis. Pediatr
Pulmonol 1995; 20: 125-6.
7. Colombo JL, Stoltz SM. Treatment of life-threatening primary
pulmonary hemosiderosis with cyclophosphamide. Chest
1992; 102: 959-60.
8. Saeed MM, Woo MS, MacLaughlin EF, Margetis MF, Keens
TG. Prognosis in pediatric idiopathic pulmonary hemosi-
derosis. Chest 1999; 116: 721-5.
9. Huang SH, Lee PY, Niu CK. Treatment of pediatric idiopathic
pulmonary hemosiderosis with low dose cyclophosphamide.
Ann Pharmacother 2003; 37: 1618-21.
10. Yeager H Jr, Powell D, Weinberg RM, Bauer H, Bellanti JA,
Katz S. Idiopathic pulmonary hemosiderosis: ultrastructural
studies and responses to azathioprine. Arch Intern Med 1976;
136: 1145-9.
11. Chabner BA, Ryan DP, Ares LP, Carbonero RG, Calabresi P.
Antineoplastic agents. In: Hardman JG, Limberd LE, editors.
The Pharmacological Basis of Therapeutics. New York: Mc Graw
Hill and Co.; 2001: pp 1395-6.
Book Review
Practical Approach to Critical Respiratory Medicine: Sleep
Disorders and Fiberoptic Bronchoscopy
Editor: V.K. Arora; Associate Editor: Raksha Arora; Published by: Jaypee Brothers Medical Publishers Pvt
Ltd, New Delhi; Edition: 2006; Paperback; Pages: xx+750+27 colour photograph pages; Price: Rs.995-00;
ISBN 81–8061–731–9
The book is aimed mainly at the post-graduate students of pulmonary and critical care medicine and also at busy
clinicians. Critical care has evolved into an inseparable part of pulmonary medicine today and there is always a need
for compilations that are practically oriented rather than being too theoretical and full of technical jargon. This is the
biggest plus point of this book. Further, the addition of sections on sleep disorders and fibreoptic bronchoscopy may
be looked upon as a bonus. Inclusion of BTS guidelines on fibreoptic bronchoscopy and ACCP guidelines on
interventional pulmonary procedures further strengthens the book.
The book is divided in three sections, covering Critical Respiratory Medicine, Sleep Disorders and Fibreoptic
Bronchoscopy. The chapters on critical care medicine cover clinical presentations, diagnostic procedures in ICU,
noninvasive and mechanical ventilation and management of specific problems including infection, shock, arrhythmias,
ARDS and respiratory failure in asthma and COPD. Several chapters have described the practical aspects of patient
monitoring. Problems specific to pediatric population have also been well discussed. The sections on sleep disorders
discuss the technical aspects of polysomnography and management of these conditions. The section on bronchoscopy
is very informative covering diagnostic as well as interventional aspects. While not forgetting rigid bronchoscopy,
newer approaches including virtual bronchoscopy as well as pediatric bronchoscopy have also been presented.
The book draws on the clinical experience of several well-known workers in the field of pulmonary medicine in
India. Illustrating the theoretical aspects with clinical case studies is an excellent approach to put across the point. The
quality of printing is very good and the illustrations have come out very nicely. Radiographs have been excellently
reproduced. The chapters have been well edited to ensure a uniform format that highlights key points through bullets,
numbered lists and tables. The book is accompanied by a CD comprising video shots of fibreoptic bronchoscopy,
procedures and pictures of various pathological conditions diagnosed on bronchoscopy. This interactive CD will no
doubt be appreciated by the computer savvy physicians.
The book aims to familiarize the post-graduate students with the complexities of critical care medicine through an
easily readable and informative text. Given that it is a multi-author book, some overlap between chapters was perhaps
unavoidable, and also, the depth to which individual topics are covered was bound to be variable. One missed
discussion of nutrition, and common medical problems in the ICU such as renal failure, hepatic failure and
gastrointestinal hemorrhage. It is hoped that future editions will widen the scope of the book and include all the major
problems a pulmonary “intensivist” is likely to come across. The post-graduate students should find the book a very
useful introduction to the difficult and challenging area of critical care medicine.
S.K. Chhabra
Associate Editor
[Indian J Chest Dis Allied Sci 2006; 48: 290]
2006; Vol. 48 The Indian Journal of Chest Diseases & Allied Sciences 291
Some Forthcoming Scientific Events
Name of the Event Secretariat
[Venue and Date]
National Conference on Pulmonary Diseases Dr B.O. Tayade
NAPCON 2006 Organising Secretary
8th Joint Conference of National College of Chest Physicians (I) Professor and Head, Department of Chest Medicine
and Indian Chest Society Government Medical College
[Shri Vasantrao Deshpande Hall, Nagpur: Nagpur-440 003 (Maharashtra)
November 1–5, 2006] Phone: 11-0712-2706189
E-mail: botayade123@yahoo.com
Website: www.napcon2006ngp.org
40th National Conference on Allergy, Asthma and Dr H.J. Singh
Applied Immunology [ICAAICON–2006] Organising Secretary
[Desh Bhagat Yaadgar Hall, Jalandhar; Ranjit Hospital, Patel Chowk, Jalandhar
December 7–10, 2006] Phone: 0181-2620 600; Cell: 098142 17738;
Fax: 2620700
E-mail: drhj@sify.com
Website: www.ICAAICON2006.com
Abstracts' Service
[Indian J Chest Dis Allied Sci 2006; 48: 292-297]
Scoring System and Clinical Application of COPD Diagnostic Questionnaires
David B. Price, David G. Tinkelman, Robert J. Nordyke, Sharon Isonaka, and R.J. Halbert for the
COPD Questionnaire Study Group
Chest 2006; 129: 1531-1539
Objectives. In most primary care settings, spirometric
screening of all patients at risk is not practical. In prior
work, we developed questionnaires to help identify
COPD in two risk groups: (1) persons with a positive
smoking history but no history of obstructive lung
disease (case finding), and (2) patients with prior
evidence of obstructive lung disease (differential
diagnosis). For these questionnaires, we now present a
scoring system for use in primary care.
Methods. Scores for individual questions were based on
the regression coefficients from logistic regression
models using a spirometry-based diagnosis of
obstruction as the reference outcome. Receiver operator
characteristic analysis was used to determine
performance characteristics for each questionnaire.
Several simplified scoring systems were developed and
tested.
Results. For both scenarios, we created a scoring system
with two cut points intended to place subjects within
one of three zones: persons with a high likelihood of
having obstruction (high predictive value of a positive
test result); persons with a low likelihood of obstruction
(high predictive value of a negative test result); and an
intermediate zone. Using these scoring systems, we
achieved sensitivities of 54 to 82%, specificities of 58 to
88%, positive predictive values of 30 to 78%, and
negative predictive values of 71 to 93%.
Conclusions. These questionnaires can be used to help
identify persons likely to have COPD among specific
risk groups. The use of a simplified scoring system
makes these tools beneficial in the primary care setting.
Used in conjunction with spirometry, these tools can
help improve the efficiency and accuracy of COPD
diagnosis in primary care.
Rationale. International guidelines promote the use of
post-bronchodilator spirometry values in the definition
and severity classification of chronic obstructive
pulmonary disease. However, post-bronchodilator
reference values have not yet been developed.
Objectives. To derive reference values for post-broncho-
dilator forced expiratory volume in one second (FEV
1
),
forced vital capacity (FVC), and FEV
1
/FVC, and to
compare these reference values with locally derived and
existing pre-bronchodilator reference values.
Methods. Based on a random sample of a general adult
population, 2,235 subjects (70% of invited subjects)
performed spirometry with reversibility testing. A
reference population of healthy never-smokers constitu-
ted 23% of the study population (n=515). Reference
values for median and lower-limit-of-normal pre- and
post-bronchodilator lung function and bronchodilator
response were modeled using quantile regression
analyses.
Post-Bronchodilator Spirometry Reference Values in Adults and Implications
for Disease Management
Ane Johannessen, Severre Lehmann, Ernst R. Omenaas, Geir Egil Eide, Per S. Bakke, and
Amund Gulsvik
The American Journal of Respiratory and Critical Care Medicine 2006; 173: 1316-1325
Main Results. The reference population had equal
proportions of men and women in the age range 26–82
yr. Both FEV
1
and FVC decreased with age and
increased with height. FEV
1
/FVC decreased with age,
although this trend was not statistically significant for
men after bronchodilatation. Linear models gave the
best overall fit. Lower-limit-of-normal post-broncho-
dilator FEV
1
/FVC exceeded 0.7 for both sexes. Post-
bronchodilator prediction equations gave higher
predicted FEV
1
and FEV
1
/FVC than both locally
derived and existing pre-bronchodilator equations. The
bronchodilator response decreased with age.
Conclusions. The present study is the first to develop
reference values for post-bronchodilator lung function.
Post-bronchodilator prediction equations can facilitate
better management of patients with chronic obstructive
pulmonary disease by avoiding falsely high FEV
1
%
predicted with a subsequent underestimation of disease
severity.
2006; Vol. 48 The Indian Journal of Chest Diseases & Allied Sciences 293
Study Objectives. Asthmatic patients lose lung
function faster than normal subjects. The effectiveness
of early intervention with inhaled corticosteroids on this
decline in lung function is not established in recent-
onset disease.
Design. The Inhaled Steroid Treatment as Regular
Therapy in Early Asthma study was a randomized,
double-blind study in 7,165 patients (5 to 66 years old),
with persistent asthma for < 2 years to determine
whether early intervention with low-dose inhaled
budesonide prevents severe asthma-related events and
the decline in lung function. Patients received
budesonide (200 µg qd for children < 11 years old and
400 µg qd for others) or placebo for 3 years in addition
to usual asthma medications.
Effects of Early Intervention with Inhaled Budesonide on Lung Function in
Newly Diagnosed Asthma
Paul M. O'Byrne, Soren Pedersen, William W. Busse, Wan C. Tan, Yu-Zhi Chen, Stefan V. Ohlsson,
Anders Ullman, Carl Johan Lamm, and Romain A. Pauwels
Chest 2006; 129: 1478-1485
Results. Treatment with budesonide significantly
improved prebronchodilator and postbronchodilator
FEV
1
percentage of predicted and reduced the mean
declines from baseline for postbronchodilator FEV
1
at 1
year and 3 years: – 0.62% and –1.79% for budesonide
and –2.11% and –2.68% for placebo, respectively
(p<0.001). The decline was more marked for male
patients, active smokers, and patients > 18 years old,
and the smallest treatment effects were in adolescents.
Conclusions. Long-term, once-daily treatment with
low-dose budesonide improved both prebronchodilator
and postbronchodilator FEV
1
in patients with recent-
onset, persistent asthma, and reduced the loss of lung
function over time.
Background. Epidemiologic studies indirectly suggest
that the inhalation of carbonaceous particulate matter
impairs lung function in children. Using the carbon
content of airway macrophages as a marker of
individual exposure to particulate matter derived from
fossil fuel, we sought direct evidence of this association.
Methods. Airway macrophages were obtained from
healthy children through sputum induction, and the
area of airway macrophages occupied by carbon was
measured. Lung function was measured with the use of
spirometry. We modeled the exposure to primary
particulate matter (PM) that is less than 10 µm in
aerodynamic diameter (PM
10
) at or near each child's
home address. Linear regression was used to evaluate
associations between carbon content of alveolar
macrophages and variables that may affect individual
exposure. To determine whether lung function that is
reduced for other reasons is associated with an increase
in the carbon content of airway macrophages, we also
studied children with severe asthma.
Carbon in Airway Macrophages and Lung Function in Children
Neeta Kulkarni, Nevil Pierse, Lesley Rushton and Jonathan Grigg
The New England Journal of Medicine 2006; 355: 21-30
Results. We were able to assess the carbon content of
airway macrophages in 64 of 114 healthy children (56
percent). Each increase in primary PM
10
of 1.0 µg per
cubic meter was associated with an increase of 0.10 µm
2
(95 percent confidence interval, 0.01 to 0.18) in the
carbon content of airway macrophages, and each
increase of 1.0 µm
2
in carbon content was associated
with a reduction of 17 percent (95 percent confidence
interval, 5.6 to 28.4 percent) in forced expiratory volume
in one second, of 12.9 percent (95 percent confidence
interval, 0.9 to 24.8 percent) in forced vital capacity, and
of 34.7 percent (95 percent confidence interval, 11.3 to
58.1 percent) in the forced expiratory flow between 25
and 75 percent of the forced vital capacity. The carbon
content of airway macrophages was lower in children
with asthma than in healthy children.
Conclusions. There is a dose-dependent inverse
association between the carbon content of airway
macrophages and lung function in children. We found
no evidence that reduced lung function itself causes an
increase in carbon content.
294
Up-Regulated Membrane and Nuclear Leukotriene B4 Receptors in COPD
Emanuela Marian, Simonetta Baraldo, Annalisa Visentin, Alberto Papi, Marina Saetta,
Leonardo M. Fabbri and Piero Maestrelli
Chest 2006; 129: 1523–1530
Study Objectives. We investigated the role of two
leukotriene B4 (LTB4) receptors, BLT1 and peroxisome
proliferator-activated receptor (PPAR)-α, in conferring
the susceptibility to develop COPD in smokers.
Proinflammatory LTB4 activities are mediated by BLT1,
while the inactivation of LTB4 is promoted by PPARα.
Patients and Methods. BLT1 and PPARα proteins were
quantified by immunohistochemistry in specimens
obtained during lung surgery from 19 smokers with or
without COPD and from 7 nonsmoking subjects.
Results. We have shown that the percentages of
PPARα-positive alveolar macrophages and PPARα-
positive cells in the alveolar wall were increased in
COPD patients compared with control subjects.
Moreover, the patients with COPD exhibited a
significant increase of BLT1-positive alveolar
macrophages compared with nonsmokers and an
increased number of BLT1-positive cells in the alveolar
walls compared with non-COPD smokers. In contrast,
BLT1 and PPARα immunoreactivity did not differ
significantly between nonsmokers and non-COPD
smokers. Most of BLT1-positive cells in the alveolar
walls were neutrophils and CD8 cells. While the
number of neutrophils infiltrating the lung parenchyma
was similar among the three groups, the number of CD8
T cells was increased in COPD patients, but there was
no evidence that BLT1 was up-regulated specifically on
these cells in COPD patients.
Conclusions. The results demonstrated that BLT1 and
PPARα are detectable in alveolar macrophages and CD8
T cells in human lung tissue, and suggest that the dual
LTB4 receptor system is up-regulated in the peripheral
lungs of smokers who are susceptible to the
development of COPD. This system might represent a
novel target for therapeutic intervention in COPD
patients.
The Role of Abrams Percutaneous Pleural Biopsy in the Investigation of
Exudative Pleural Effusions
Biswajit Chakrabarti, Ida Ryland, John Sheard, Christopher J. Warburton and John E. Earis
Chest 2006; 129: 1549–1555
Introduction. Blind percutaneous pleural biopsy has
traditionally been performed to investigate the etiology
of exudative pleural effusion in which the initial
thoracentesis has been nondiagnostic. In view of the
increasing use of image-guided and thoracoscopic
pleural biopsies, this study examines the role of blind
Abrams pleural biopsy in the investigation of pleural
effusion in a large urban hospital.
Methods. Patients undergoing blind Abrams needle
biopsy between January 1997 and 2003 were identified
from the hospital pathology database. The case notes
and pathology records of these patients were analyzed
retrospectively. All patients had presented to respiratory
teams with an exudative pleural effusion and had initial
nondiagnostic thoracentesis.
Results. Seventy-five patients undergoing blind biopsy
were identified. Pleural tissue was obtained in 59
biopsies (79%), with no statistically significant
difference in pleural yield between respiratory specialist
registrars (equivalent to pulmonary fellows in training)
and senior house officers/preregistration house officers
(equivalent to junior residents and interns, respectively)
performing the biopsy (χ
2
test, p=0.43). When up to
three samples were obtained per episode, sufficient
pleural tissue was obtained in 18 of 25 patients (72%)
compared to 80% (32 of 40 patients) in whom four to six
samples were taken (χ
2
test, p=0.55 [not significant]).
For all diagnoses, blind biopsy had a sensitivity of 38%,
which rose to 43% when reviewing patients in whom
sufficient pleural tissue was obtained (for malignant
diagnosis alone, sensitivity values were 43% and 51%,
respectively; specificity, 100% negative and positive
predictive values, 51%). No fatalities were reported, and
pneumothorax was seen in eight patients (11%), with
only two patients requiring specific intervention.
Conclusions. Blind Abrams needle biopsy obtaining
pleural tissue was diagnostic in approximately 50% of
patients presenting with malignant effusion in the
sample, and can be performed safely by all grades of
medical staff with due attention to technique and
supervision. The data support the continued use of the
Abrams needle in the investigation of malignant pleural
disease.
Abstracts' Service 2006; Vol. 48
2006; Vol. 48 The Indian Journal of Chest Diseases & Allied Sciences 295
Cyclophosphamide versus Placebo in Scleroderma Lung Disease
Donald P. Tashkin, Robert Elashoff, Philip J. Clements, Jonathan Goldin, Michael D. Roth,
Daniel E. Furst, Edgar Arriola, Richard Silver, Charlie Strange, Marcy Bolster, James R. Seibold,
David J. Riley, Vivien M. Hsu, John Varga, Dean E. Schraufnagel, Arthur Theodore, Robert Simms,
Robert Wise, Fredrick Wigley, Barbara White, Virginia Steen, Charles Read, Maureen Mayes,
Kamal Mubarak, M. Kari Connolly, Jeffrey Golden, Mitchell Olman, Barri Fessler,
Naomi Rothfield, and Mark Metersky, for the Scleroderma Lung Study Research Group
The New England Journal of Medicine 2006; 354: 2655–66
Background. We conducted a double-blind, rando-
mized, placebo-controlled trial to determine the effects
of oral cyclophosphamide on lung function and health-
related symptoms in patients with evidence of active
alveolitis and scleroderma-related interstitial lung
disease.
Methods. At 13 clinical centers throughout the United
States, we enrolled 158 patients with scleroderma,
restrictive lung physiology, dyspnea, and evidence of
inflammatory interstitial disease on examination of
bronchoalveolar-lavage fluid, thoracic high-resolution
computed tomography, or both. Patients received oral
cyclophosphamide (≤ 2 mg per kilogram of body
weight per day) or matching placebo for one year and
were followed for an additional year. Pulmonary
function was assessed every three months during the
first year, and the primary end point was the forced
vital capacity (FVC, expressed as a percentage of the
predicted value) at 12 months, after adjustment for the
baseline FVC.
Results. Of 158 patients, 145 completed at least six
months of treatment and were included in the analysis.
The mean absolute difference in adjusted 12-month
FVC percent predicted between the cyclophosphamide
and placebo groups was 2.53 percent (95 percent
confidence interval, 0.28 to 4.79 percent), favoring
cyclophosphamide (P<0.03). There were also treatment-
related differences in physiological and symptom
outcomes, and the difference in FVC was maintained at
24 months. There was a greater frequency of adverse
events in the cyclophosphamide group, but the
difference between the two groups in the number of
serious adverse events was not significant.
Conclusions. One year of oral cyclophosphamide in
patients with symptomatic scleroderma-related
interstitial lung disease had a significant but modest
beneficial effect on lung function, dyspnea, thickening
of the skin, and the health-related quality of life. The
effects on lung function were maintained through the 24
months of the study.
Prospective Study of the Diagnostic Accuracy of the Simplify D-dimer Assay
for Pulmonary Embolism in Emergency Department Patients
Jeffrey A. Kline, Michael S. Runyon, William B. Webb, Alan E. Jones, and Alice M. Mitchell
Chest 2006; 129: 1417-1423
Objective. To determine if a d-dimer assay (Simplify D-
dimer; Agen Biomedical; Brisbane, Australia) can
reliably exclude pulmonary embolism (PE) by
producing a posttest probability of PE < 1% in low-risk,
symptomatic emergency department (ED) patients.
Methods. Hemodynamically stable patients were
evaluated for PE using a structured d-dimer centered
protocol; d-dimer testing was performed prior to
imaging. Prior to testing, physicians completed an
electronic data form that included their unstructured
clinical estimate for the pretest probability of PE (<15%,
15 to 40%, or > 40%) and the elements of the Charlotte
rule and Canadian score for PE. Criterion standard was
selective use of pulmonary vascular imaging and 90-
day follow-up.
Results. We enrolled 2,302 patients (mean age, 45± 16
years [±SD]; 31% male); 108 patients received a
diagnosis of PE (4.7%; 95% confidence interval [CI], 3.6
to 5.6%). The overall sensitivity and specificity of the d-
dimer assay were 80.6% (95% CI, 71.8 to 87.5%) and
72.5% (95% CI, 70.6 to 74.4%), respectively. The negative
likelihood ratio and negative predictive value were 0.27
(95% CI, 0.18 to 0.39) and 98.7% (95% CI, 98.0 to 99.1%),
respectively. The posttest prevalence of PE among low-
296
risk patients with negative d-dimer results was 0.7%
(95% CI, 0.3 to 1.4%) for the unstructured estimate, 1.2%
(95% CI, 0.7 to 2.0%) for the Canadian score, and 1.1%
(95% CI, 0.6 to 1.7%) for the Charlotte rule.
Conclusions. The simplify d-dimer assay had moderate
sensitivity and relatively high specificity for PE in low-
risk ED patients. The combination of a physician's
unstructured estimate of pretest probability of PE of
< 15% and a negative d-dimer result produced a
posttest probability of PE of 0.7% (95% CI, 0.3 to 1.4%).
Multidetector Computed Tomography for Acute Pulmonary Embolism
Paul D. Stein, Sarah E. Fowler, Lawrence R. Goodman, Alexander Gottschalk, Charles A. Hales,
Russell D. Hull, Kenneth V. Leeper Jr, John Popovich Jr, Deborah A. Quinn, Thomas A. Sos,
Dirk Sostman, Victor F. Tapson, Thomas W. Wakefield, John G. Weg, and Pamela K. Woodard, for
the PIOPED II Investigators
The New England Journal of Medicine 2006; 354: 2317-27
Background. The accuracy of multidetector computed
tomographic angiography (CTA) for the diagnosis of
acute pulmonary embolism has not been determined
conclusively.
Methods. The Prospective Investigation of Pulmonary
Embolism Diagnosis II trial was a prospective,
multicenter investigation of the accuracy of
multidetector CTA alone and combined with venous-
phase imaging (CTA-CTV) for the diagnosis of acute
pulmonary embolism. We used a composite reference
test to confirm or rule out the diagnosis of pulmonary
embolism.
Results. Among 824 patients with a reference diagnosis
and a completed CT study, CTA was inconclusive in 51
because of poor image quality. Excluding such
inconclusive studies, the sensitivity of CTA was 83
percent and the specificity was 96 percent. Positive
predictive values were 96 percent with a concordantly
high or low probability on clinical assessment, 92
percent with an intermediate probability on clinical
assessment, and nondiagnostic if clinical probability
was discordant. CTA–CTV was inconclusive in 87 of 824
patients because the image quality of either CTA or CTV
was poor. The sensitivity of CTA–CTV for pulmonary
embolism was 90 percent, and specificity was 95
percent. CTA–CTV was also nondiagnostic with a
discordant clinical probability.
Conclusions. In patients with suspected pulmonary
embolism, multidetector CTA–CTV has a higher
diagnostic sensitivity than does CTA alone, with similar
specificity. The predictive value of either CTA or CTA–
CTV is high with a concordant clinical assessment, but
additional testing is necessary when the clinical
probability is inconsistent with the imaging results.
Major Congenital Malformations after First-Trimester Exposure to ACE
Inhibitors
William O. Cooper, Sonia Hernandez-Diaz, Patrick G. Arbogast, Judith A. Dudley, Shannon Dyer,
Patricia S. Gideon, Kathi Hall, and Wayne A. Ray
The New England Journal of Medicine 2006; 354: 2443-51
Background. Use of angiotensin-converting-enzyme
(ACE) inhibitors during the second and third trimesters
of pregnancy is contraindicated because of their
association with an increased risk of fetopathy. In
contrast, first-trimester use of ACE inhibitors has not
been linked to adverse fetal outcomes. We conducted a
study to assess the association between exposure to
ACE inhibitors during the first trimester of pregnancy
only and the risk of congenital malformations.
Methods. We studied a cohort of 29,507 infants enrolled
in Tennessee Medicaid and born between 1985 and 2000
for whom there was no evidence of maternal diabetes.
We identified 209 infants with exposure to ACE
inhibitors in the first trimester alone, 202 infants with
exposure to other antihypertensive medications in the
first trimester alone, and 29,096 infants with no
exposure to antihypertensive drugs at any time during
gestation. Major congenital malformations were
Abstracts' Service 2006; Vol. 48
2006; Vol. 48 The Indian Journal of Chest Diseases & Allied Sciences 297
identified from linked vital records and hospitalization
claims during the first year of life and confirmed by
review of medical records.
Results. Infants with only first-trimester exposure to
ACE inhibitors had an increased risk of major
congenital malformations (risk ratio, 2.71; 95 percent
confidence interval, 1.72 to 4.27) as compared with
infants who had no exposure to antihypertensive
medications. In contrast, fetal exposure to other
antihypertensive medications during only the first
trimester did not confer an increased risk (risk ratio,
0.66; 95 percent confidence interval, 0.25 to 1.75). Infants
exposed to ACE inhibitors were at increased risk for
malformations of the cardiovascular system (risk ratio,
3.72; 95 percent confidence interval, 1.89 to 7.30) and the
central nervous system (risk ratio, 4.39; 95 percent
confidence interval, 1.37 to 14.02).
Conclusions. Exposure to ACE inhibitors during the
first trimester cannot be considered safe and should be
avoided.
248 The Indian Journal of Chest Diseases & Allied Sciences 2006; Vol. 48
Full text articles published in IJCDAS from July-September
2003 onwards can be accessed online on Internet through the
following sites
V.P. Chest Institute’s site: http://www.vpci.org.in
Indmed’s site: http://medind.nic.in
Guidance for Authors appears in every issue.
Authors’ Index appears in the last issue of the year
Authors' Index [Vol. 48, Nos 1-4]
Acharya VK. See under Sahoo, R (63)
Adewole OO. See under Erhabor, GE (253)
Afroz F. See under Khan, NA (187)
Agarwal R, Gulati M, Mittal BR and Jindal SK.
Clinical profile, diagnosis and management
of patients presenting with symptomatic
pulmonary embolism .. 111
Aggarwal AN, Chaudhry K, Chhabra SK,
D'souza GA, Gupta D, Jindal SK, Katiyar SK,
Kumar R, Shah B and Vijayan VK. Prevalence
and risk factors for bronchial asthma in Indian
adults: a multicentre study .. 13
Aggarwal AN. See under Jindal, SK (23, 37);
Gupta, D (31, 261)
Agrawal Anshu. See under Agrawal, D (279)
Agrawal D, Lahiri TK, Agrawal Anshu and
Singh MK. Uncommon parathyroid mediastinal
cyst compressing the trachea .. 279
Agrawal D, Deshpande R, Maheshwari S, Patel A
and Udwadia ZF. Pulmonary hyalinzing
granuloma with ureteric fibrosis: a case report
and review of relevant literature .. 283
Agrawal Dipika. See under Jain, S (217)
Agrawal GG. See under Prasad, R (103)
Akin H. See under Dincer, SI (249)
Ahmad Z, Pandey R, Sharma Sadhna and
Khuller GK. Alignate nanoparticles as anti-
tuberculosis drug carriers: formulation
development, pharmacokinetics and
therapeutic potential .. 171
Al-Qudah A. Treatment options of spontaneous
pneumothorax .. 191
Anuradha B, Vijayalakshmi V, Latha G. Suman,
Priya V. Hari Sai and Murthy KJR. Profile of
pollen allergies in patients with asthma,
allergic rhinitis and urticaria in Hyderabad .. 221
Arora Ruchi. See under Menon, B (207)
Balamugesh T, Behera D, Bhatnagar Archana and
Majumdar S. Inflammatory cytokine levels
in induced sputum and bronchoalveolar
lavage fluid in pulmonary sarcoidosis .. 177
Bambery P. See under Sharma, A (143)
Behera D, Sukhpal Kaur, Gupta D and Verma SK.
Evaluation of self-care manual in bronchial
asthma .. 43
Behera D. Managing lung cancer in developing
countries: difficulties and solutions .. 243
Behera D. See under Balamugesh, T (177)
Bhatnagar Archana. See under Balamugesh, T (177)
Bhutani Manisha, Pathak AK, Mohan A,
Guleria R and Kochupillai V. Small cell lung
cancer: an update on therapeutic aspects .. 49
Biyani V. See under Vigg, A (67)
Bose Mridula. The archetype of laboratory
diagnosis in tuberculosis: the shape of
things to come .. 167
Buch Archana and Kini Usha. A case report of
pulmonary transmogrification with review of
literature .. 147
Castillo J. See under Hamer, L (59)
Chandra J. See under Naithani, R (287)
Chaudhary Uma. See under Gupta, KB (275)
Chaudhry K. See under Aggarwal, AN (13);
Jindal, SK (23, 37) and Gupta, D (31)
Chhabra SK. Chronic obstructive pulmonary
disease and cardiovascular disease .. 95
Chhabra SK, Vijayan VK and Vasu T. Inhaled
formoterol versus ipratropium bromide in
chronic obstructive pulmonary disease .. 97
Chhabra SK. See under Aggarwal, AN (13);
Jindal, SK (23, 37) and Gupta, D (31)
Chhajed PN. See under Kamath, AV (265)
Das C. See under Guleria, R (133)
Deivanayagam CN. The challenges of
tuberculosis .. 245
Demir A. See under Dincer, SI (249)
Deshpande R. See under Agrawal, D (283)
Dhasmana JP. See under Saini, S (129)
Dincer SI, Demir A, Akin H, Gunluoglu MZ,
Metin M, Melek H and Gurses A. Is routine
mediasti-noscopy indicated for patients with
T1 non-small cell lung cancer? .. 249
D'souza GA. See underAggarwal, AN (13);
Jindal, SK (23, 37) and Gupta, D (31)
Dubey KR. See under Kohli, A (257)
Dubey NK. See under Naithani, R (287)
Dwivedi G. See under Dwivedi, S (213)
Dwivedi S, Srivastava S and Dwivedi G. Smoking
associated with malignancy, hypertension,
chronic obstructive pulmonary disease and
coronary artery disease: report of nine cases .. 213
Erhabor GE, Adewole OO and Ogunlade O. A
five-year review of tuberculosis mortality
amongst hospitalised patients in Ile-Ife .. 253
Faruqi S. See under Gupta, D (261)
Fink JN. See under Kurup, VP (115)
Gomathy S. See under Rajendran, AJ (271)
Gowrinath K, Sheshadri Shubha and Sean TG.
Successful outcome of medical therapy in a
case of acute massive pulmonary thrombo-
embolism presenting with saddle thrombo-
embolus .. 71
Gulati M. See under Agarwal, R (111)
Guleria R, Sharma R, Mohan A and Das C.
Cardiac sarcoidosis: an uncommon present-
ation of sarcoidosis in India .. 133
Guleria R. See under Bhutani, Manisha (49)
Gunluoglu MZ. See under Dincer, SI (249)
[Indian J Chest Dis Allied Sci 2006; 48: 298-300]
2006; Vol. 48 The Indian Journal of Chest Diseases & Allied Sciences 299
Gupta D, Aggarwal AN, Chaudhry K, Chhabra SK,
D'Souza GA, Jindal SK, Katiyar SK, Kumar R,
Shah B and Vijayan VK. Household environ-
mental tobacco smoke exposure, respiratory
symptoms and asthma in non-smoker adults:
a multicentric population study from India .. 31
Gupta D, Mishra S, Faruqi S and Aggarwal AN.
Aetiology and clinical profile of spontaneous
pneumothorax in adults .. 261
Gupta D. See under Aggarwal, AN (13);
Jindal, SK (23, 37) and Behera, D (43)
Gupta KB, Manchanda M, Parveen Kaur.
Bilateral spontaneous pneumothorax in
silicosis .. 201
Gupta KB, Manchanda M, Chaudhary Uma and
Verma M. Superior vena cava syndrome
caused by pulmonary amoebic abscess .. 275
Gurses A. See under Dincer, SI (249)
Hamer L and Castillo J. Coccidioidomycosis
presenting as a massive pleural effusion in a
postpartum women .. 59
Jain A. See under Prasad, R (183)
Jan N. See under Khan, NA (187)
Jain S, Agrawal Dipika, Shah T and Udwadia ZF.
Resection of a endobronchial hamartoma by
electrocautery and argon plasma ablation via
fiberoptic bronchoscopy .. 217
Jindal SK, Aggarwal AN, Chaudhry K, Chhabra
SK, D'souza GA, Gupta D, Katiyar SK,
Kumar R, Shah B and Vijayan VK. A multi-
centric study on epidemiology of chronic
obstructive pulmonary disease and its
relationship with tobacco smoking and
environmental tobacco smoke exposure .. 23
Jindal SK, Aggarwal AN, Chaudhry K, Chhabra
SK, D'Souza GA, Gupta D, Katiyar SK,
Kumar R, Shah B and Vijayan VK. Tobacco
smoking in India: prevalence, quit-rates and
respiratory morbidity .. 37
Jindal SK. See under Aggarwal, AN (13);
Agarwal, R (111) and Gupta, D (31)
Kamath AV and Chhajed PN. Role of broncho-
scopy in early diagnosis of lung cancer .. 265
Kasturi DP. See under Sahoo, R (63)
Katiyar SK. See under Aggarwal, AN (13);
Jindal, SK(23, 37) and Gupta, D (31)
Khan NA, Afroz F, Lone MM, Teli MA,
Muzaffar M and Jan N. Profile of lung cancer
in Kashmir, India: a five-year study .. 187
Khuller GK. See under Ahmad, Z (171)
Khyriem Annie B. See under Sivasankari, P (107)
Kini Hema. See under Sahoo, R (63)
Kini Usha. See under Buch, Archana (147)
Kochupillai V. See under Bhutani, Manisha (49)
Kohli A, Singh G, Vig Anita, Dubey KR and
Singh R. Pleurocutaneous flap: how useful it
is in management of chronic empyema .. 257
Kumar R. See under Aggarwal, AN (13);
Jindal, SK (23, 37) and Gupta, D (31)
Kumar S. See under Prasad, R (183)
Kumar V. See under Naithani, R (287)
Kuppu Rao KV. See under Rajendran, AJ (271)
Kurup VP, Zacharisen MC and Fink JN. Hyper-
sensitivity pneumonitis .. 115
Lahiri TK. See under Agrawal, D (279)
Latha G. Suman. See under Anuradha, B (221)
Lobo Flora D. See under Sahoo, R (63)
Lone MM. See under Khan, NA (187)
Maheshwari S. See under Agrawal, D (283)
Majumdar S. See under Balamugesh, T ( 177)
Manchanda M. See under Gupta, KB (201, 275)
Mantri S. See under Vigg, A (67)
Mathur N. See under Prasad, R (103)
Melek H. See under Dincer, SI (249)
Menon B, Singh P and Arora Ruchi. Interlobar
hydropneumothorax .. 201
Metin M. See under Dincer, SI (249)
Mishra S. See under Gupta, D (261)
Mittal BR. See under Agarwal, R (111)
Mohan A and Sharma SK. In search of a diagnostic
test for tuberculosis infection: where do we
stand? .. 5
Mohan A. See under Bhutani, Manisha (49);
Guleria, R (133)
Mullasari AS. See under Rajendran, AJ (271)
Muzaffar M. See under Khan, NA (187)
Mukhopadhyay S. See under Vinodh, BN (75)
Murty KJR. See under Anuradha, B (221)
Naithani R, Chandra J, Singh V, Kumar V and
Dubey NK. Life threatening exacerbation in
idiopathic pulmonary hemosiderosis salvaged
by cyclophosamide infusion .. 287
Ogunlade O. See under Erhabor, GE (253)
Ohri S. See under Sharma, A (143)
Pai RR, Raghuveer CV, Philipose RT and
Shetty AB. Primary pulmonary Hodgkin's
disease: a distinct entity .. 139
Pandey R. See under Ahmad, Z (171)
Pandurangi UM. See under Rajendran, AJ (271)
Parija SC. See under Sivasankari, P (107)
Parveen Kaur. See under Gupta, KB (201)
Patel A. See under Agrawal, D (283)
Pathak AK. See under Bhutani, Manisha (49)
Philipose RT. See under Pai, RR (139)
Prasad R, Verma SK, Agrawal GG and Mathur N.
Prediction model for peak expiratory flow in
north Indian population .. 103
300
Prasad R, Verma SK, Sahai S, Kumar S and Jain A.
Efficacy and safety of kanamycin, ethionamide,
PAS and cycloserine in multidrug-resistant
pulmonary tuberculosis patients .. 183
Priya V. Hari Sai. See under Anuradha, B (221)
Raghuveer CV. See under Pai, RR (139)
Rajendran AJ, Pandurangi UM, Mullasari AS,
Gomathy S, Kuppu Rao KV and Vijayan VK.
High intensity exercise training programme
following cardiac transplant .. 271
Ray Ruma. See under Vinodh, BN (75)
Reddy VAP. See under Vigg, A (67)
Sahai S. See under Prasad, R (183)
Sahoo R, Acharya VK, Kasturi DP, Lobo Flora D
and Kini Hema. Second primary lung cancer
with tuberculosis .. 63
Saini S and Dhasmana JP. Apical mass present-
ation of brachial plexus schwannoma .. 129
Saluja Jasjeet. See under Vasu, T (205)
Sean TG. See under Gowrinath, K (71)
Seith A. See under Vinodh, BN (209)
Shah B. See under Aggarwal, AN (13);
Jindal, SK (21, 37) and Gupta, D (31)
Shah T. See under Jain, S (217)
Sharma A, Ohri S, Bambery P and Singh S.
Idiopathic endogenous lipoid pneumonia .. 143
Sharma R. See under Guleria, R (133)
Sharma Sadhna. See under Ahmad, Z (171)
Sharma SK. See under Mohan, A (5) and
Vinodh, BN (75, 209)
Sheshadri Shubha. See under Gowrinath, K (71)
Shetty AB. See under Pai, RR (139)
Singh G. See under Kohli, A (257)
Singh MK. See under Agrawal, D (279)
Singh P. See under Menon, B (207)
Singh R. See under Kohli, A (257)
Singh S. See under Sharma, A (147)
Singh V. See under Naithani, R (287)
Sivasankari P, Khyriem Annie B, Venkatesh K
and Parija SC. Atypical mycobacterial
infection among HIV seronegative patients in
Pondicherry .. 107
Smith Rohrberg Duncan. See under Vinodh,
BN (209)
Srivastava S. See under Dwivedi, S (213)
Sukhpal Kaur. See under Behera, D (43)
Teli MA. See under Khan, NA (187)
Udwadia ZF. See under Jain, S (217) and
Agrawal, D (283)
Valiathan MS. Ethical issues in the practice of
medicine .. 7
Vasu T and Saluja Jasjeet. INH induced status
epilepticus: response to pyridoxine .. 205
Vasu T. See under Chhabra, SK (97)
Venkatesh K. See under Sivasankari, P (107)
Verma M. See under Gupta, KB (275)
Verma SK. See under Behera, D (43) and
Prasad, R (103, 183)
Vigg A, Mantri S, Reddy VAP and Biyani V. Acute
respiratory distress syndrome due to
Strongyloides stercoralis in non-Hodgkin's
lymphoma .. 67
Vigg Anita. See under Kohli, A (257)
Vijayalakshmi V. See under Anuradha, B (221)
Vijayan VK. See under Aggarwal, AN (13);
Chhabra, SK (97); Gupta, D (31);
Jindal, SK (23, 37); Rajendran, AN (271)
Vinodh BN, Shrama SK, Mukhopadhyay S and
Ray Ruma. Idiopathic pulmonary haemosider-
osis: two case reports .. 75
Vinodh BN, Sharma SK, Smith-Rohrberg Duncan
and Seith A. Tubercular oesophago-cutaneous
fistula .. 209
Zacharisen MC. See under Kurup, VP (115)
Authors' Index
The Indian Journal of Chest Diseases and Allied Sciences
considers for publication original articles dealing with
respiratory and cardiovascular diseases and in the fields
of anatomy, biochemistry, microbiology, mycology,
pathology, pharmacology, physiology, ultra-structure
and virology of respiratory, and cardiovascular systems.
However, only papers that make a significant contribu-
tion to the existing state of knowledge in a particular field
will be published. The journal publishes original articles,
case reports, radiology forum, short communications and
book reviews.
Submission of Manuscripts. Manuscripts should be
submitted in a floppy diskette in MS word (in addition
to hard copies). Typescript including figures (in triplicate)
should be sent to The Editor–in–Chief, The Indian
Journal of Chest Diseases and Allied Sciences, C/o
Publication Division, V.P. Chest Institute, University of
Delhi, Delhi-110007, Post Box No. 2101.
Manuscripts should be submitted with the
undertaking that they are not under consideration
elsewhere and have not been reported earlier partly/
totally. Submission of a manuscript indicates tacit
acknowledgement that all authors have made significant
contributions to the study and have read and approved
the contents. Any change in authorship following the
original submission must be justified and agreed to in
writing by the affected author(s). Manuscripts are
acknowledged upon receipt. When inquiring about a
manuscript, please refer to the number assigned to the
manuscript by the Publication Office of the IJCDAS.
Manuscripts are evaluated critically by the Editorial
Board with the help of Experts. Acceptance of
manuscripts for publication is based on: (a) originality of
contribution; (b) proper analysis of scientific data; (c)
clarity of presentation; and (d) ethically acceptable design
of the study. All accepted manuscripts are subject to
manuscript editing. Only one copy of rejected manuscripts
will be returned.
Preparation of Manuscript
Presentation of manuscripts should conform with the
uniform requirements for manuscripts submitted to
biomedical journals.
Authors are advised to see a recent issue of the Journal
to get familiar with the format adopted on various
elements of a paper. All the manuscripts should be
submitted in the order set forth below. Failure to follow
these instructions may result in the manuscript being returned
to the author(s) for revision before it will be reviewed.
General. Manuscripts must be typewritten, double-
spaced with wide margin on A-4 size good quality bond
paper. Each of these segments of the manuscript should
Guidelines to Authors
begin on a new page: title page; abstract; introduction;
references; legends; tables.
I. Title Page. This should be as concise and as
informative as possible. List (i) title; (ii) the initials
followed by the last name of each author; (iii) the name
of the department(s) and institution(s) to which the work
should be attributed; (iv) the name and address of the
author to whom queries, proofs and requests for reprints
should be sent; and (v) a short running title (not
exceeding 5-6 words).
II. Abstract and Key Words. The second page should
carry a structured abstract of not more than 200 words
with subheadings of Background and objectives,
Methods, Results and Conclusions (unstructured abstract
for case reports). It should be written for the readership
of both clinicians and basic investigators and should state
the hypothesis or central question of the study or
investigation, the study subjects or experimental animals,
observational and analytical methods, the main findings,
and a final statement of the principal conclusions. Three
to six key words using, where possible terms of medical
subjects headings list from Index Medicus.
III. Introduction. It should commence on separate page
and should briefly review the current state of knowledge
strictly concerning the topic of the paper. It should also
make a clear statement on the reasons for undertaking
the study being reported and what it hoped to achieve.
No mention should be made of the results obtained or
conclusions drawn.
IV. Material and Methods. The material (patients,
experimental animals, etc.) used for making observations
must be described along with all other relevant
information. The methods used in the study should be
described, giving sufficient information to permit the
work to be repeated. If a generally accepted technique has
been used, only a reference to that is enough. If, however,
such a technique has been modified by the workers, the
manner in which this has been done should be clearly
stated. If statistical analysis of the data has been done, the
methods used for analysis should be specified.
V. Results. This section should not include materials
suitable for inclusion in “Material and Methods’ or
“Discussion”. The results should be presented in logical
sequence in the text, tables and illustrations. The data
presented in the tables or figures should not be repeated
in the text. Only important and significant observations
should be included.
VI. Discussion. This should be limited to significance
of results obtained and what can and what cannot be
concluded and why. It should not be a repetition of the
findings already given under ‘Results’. Results should be
[Indian J Chest Dis Allied Sci 2006; 48: 301-306]
302
discussed in the light of others’ work in the field.
Speculative and purely theoretical discussion to which
results presented are not related will not be accepted.
VII. Acknowledgements. Acknowledgement should be
brief and made specific for scientific/technical assistance
and financial supports in the form of grants/drugs/
equipment only and for not providing routine
departmental facilities and for help in the preparation of
manuscript (including typing/secretarial assistance).
VIII. References. References should be typed on a
separate page after the text and these should be
numbered consecutively in the order in which they are
first mentioned in the text. Identify references in text,
tables, and legends by Arabic numerals in parentheses.
References cited only in tables or figure legends should
be numbered in accordance with the sequence established
by the first identification in the text of the particular table
or figure. The titles of journals should be abbreviated
according to the style used in Index Medicus. Consult the
List of Journals Indexed in Index Medicus, published
annually as a separate publication by the library and as
a list in the January issue of Index Medicus. The list can
also be obtained through the library’s web site
(http://www.nlm.nih.gov). Unpublished work should not
be cited in references, but may be cited fully
parenthetically within the text. List all the authors when
there are six or fewer; but when there are seven or more,
list the first six, then ‘et al’. Examples of correct form of
references are given here :
Articles in Journals
1. Standard journal article
Halpern SD, Ubel PA, Caplan AL. Solid-organ transplan-
tation in HIV-infected patients. N Engl J Med 2002; 347:
284-7.
More than six authors:
Rose ME, Huerbin MB, Melick J, Marion DW, Palmer
AM, Schiding JK, et al. Regulation of interstitial excita-
tory amino acid concentrations after cortical contusion
injury. Brain Res 2002; 935 (1-2): 40-6.
2. Article published electronically ahead of the print version
Yu WM, Hawley TS, Hawley RG, Qu CK. Immortaliza-
tion of yolk sac-derived precursor cells. Blood 2002 Nov
15; 100(10): 3828-31. Epub 2002 July 5.
3. Volume with supplement
Geraud G, Spierings EL, Keywood C. Tolerability and
safety of frovatriptan with short-and long-term use for
treatment of migraine and in comparison with
sumatriptan. Headache 2002; 42 Suppl 2: S93-9.
4. Issue with supplement
Glauser TA. Integrating clinical trial data into clinical
practice. Neurology 2002; 58 (12 Suppl 7): S6-12.
5. Type of article indicated as needed
Tor M, Turker H. International approaches to the pre-
scription of long-term oxygen therapy [letter]. Eur Respir
J 2002; 20(1): 242.
Lofwall MR, Strain EC, Brooner RK, Kindbom KA,
Bigelow GE. Characteristics of older methadone main-
tenance (MM) patients [abstract]. Drug Alcohol Depend
2002; 66 Suppl 1: S105.
6. Volume with part
Abend SM, Kulish N. The psychoanalytic method from
an epistemological viewpoint. Int J Psychoanal 2002; 83
(Pt 2): 491-5.
7. Issue with part
Ahrar K, Madoff DC, Gupta S, Wallace MJ, Price RE,
Wright KC. Development of a large animal model for
lung tumours. J Vasc Interv Radiol. 2002; 13(9 Pt 1):
923-8.
8. Issue with no volume
Banit DM, Kaufer H, Hartford JM. Intraoperative fro-
zen section analysis in revision total joint arthroplasty.
Clin Orthop 2002; (401): 230-8.
9. No volume or issue
Outreach: bringing HIV-positive individuals into care.
HRSA Careaction 2002 Jun: 1-6.
10. Pagination in roman numerals
Chadwick R, Schuklenk U. The politics of ethical con-
sensus finding. Bioethics 2002; 16(2): iii-v.
11. Organization as author
Diabetes Prevention Program Research Group. Hyper-
tension, insulin, and proinsulin in participants with
impaired glucose tolerance. Hypertension 2002; 40(5): 679-
86.
12. Both personal authors and an organization as author (This
example does not conform to NISO standards).
Vallancien G, Emberton M, Harving N, van Moorselaar
RJ; Alf-One Study Group. Sexual dysfunction in 1,274
European men suffering from lower urinary tract symp-
toms. J Urol 2003; 169(6): 2257-61.
13. No author given
21st century heart solution may have a sting in the tail.
BMJ 2002; 325(7357): 184.
14. Article containing retraction
Feifel D, Moutier CY, Perry W. Safety and tolerability of
a rapidly escalating dose-loading regimen for
risperidone. J Clin Psychiatry 2002; 63(2): 169. Retraction
of: Feifel D, Moutier CY, Perry W. J Clin Psychiatry 2000;
61(12): 909-11.
Guidelines to Authors 2006; Vol. 48
2006; Vol. 48 The Indian Journal of Chest Diseases & Allied Sciences 303
15. Article retracted
Feifel D, Moutier CY, Perry W. Safety and tolerability of
a rapidly escalating dose-loading regimen for
risperidone. J Clin Psychiatry 2000; 61(12): 909-11. Re-
traction in: Feifel D, Moutier CY, Perry W. J Clin Psychia-
try 2002; 63(2): 169.
16. Article republished with corrections
Mansharamani M, Chilton BS. The reproductive impor-
tance of P-type ATPases. Mol Cell Endocrinol 2002; 188(1-
2): 22-5. Corrected and republished from: Mol Cell
Endocrinol 2001; 183(1-2): 123-6.
17. Article with published erratum
Malinowski JM, Bolesta S. Rosiglitazone in the treatment
of type 2 diabetes mellitus: a critical review. Clin Ther
2000; 22(10): 1151-68; discussion 1149-50. Erratum in :
Clin Ther 2001; 23(2): 309.
18. Article not in English
(Note: NLM translates the title into English, encloses the
translation in square brackets, and adds an abbreviated
language designator.)
Ellingsen AE, Wilhelmsen I. Sykdomsangst blant medisin-
og jusstudenter. Tidsskr Nor Laegeforen 2002; 122(8): 785-7.
Personal Communication
Name of the person and date of communication should
be cited in parentheses in the text. For scientific articles,
authors should obtain written permission and confir-
mation of accuracy from the source of a personal com-
munication.
Unpublished Material
19. In press
(Note: NLM prefers “forthcoming” because not all items
will be printed.)
Tian D, Araki H, Stahl E, Bergelson J, Kreitman M. Sig-
nature of balancing selection in Arabidopsis. Proc Natl
Acad Sci USA. In press 2002.
Books and Other Monographs
20. Chapter in a book
Meltzer PS, Kallioniemi A, Trent JM. Chromosome al-
terations in human solid tumours. In: Vogelstein B,
Kinzler KW, editors. The Genetic Basis of Human Cancer.
New York: McGraw-Hill. 2002; pp 93-113.
21. Conference paper
Christensen S, Oppacher F. An analysis of Koza’s com-
putational effort statistic for genetic programming. In :
Foster JA, Lutton E, Miller J, Ryan C, Tettamanzi AG,
editors. Genetic programming. EuroGP 2002: Proceed-
ings of the 5th European Conference on Genetic Program-
ming; 2002 Apr 3-5; Kinsdale Ireland. Berlin: Springer.
2002; pp 182-91.
22. Personal author(s)
Murray PR, Rosenthal KS, Kobayashi GS, Pfaller MA.
Medical Microbiology; 4th ed. St. Louis: Mosby. 2002.
23. Editor(s), compiler(s) as author
Gilstrap LC (3rd), Cunningham FG, VanDorsten JP, edi-
tors. Operative Obstetrics. 2nd ed. New York: McGraw-
Hill. 2002.
24. Author(s) and editor(s)
Breedlove GK, Schorfheide AM. Adolescent Pregnancy.
2nd ed. Wieczorek RR, editor. White Plains (NY): March
of Dimes Education Services; 2001.
25. Organization(s) as author
Royal Adelaide Hospital; University of Adelaide, De-
partment of Clinical Nursing. Compendium of Nursing
Research and Practice Development, 1999-2000. Adelaide
(Australia): Adelaide University; 2001.
26. Conference proceedings
Harnden P, Joffe JK, Jones WG, editors. Germ cell
tumours V. Proceedings of the 5th Germ Cell Tumour
Conference; 2001 Sep 13-15; Leeds, UK. New York:
Springer; 2002.
27. Scientific or technical report
Issued by funding/sponsoring agency:
Yen GG (Oklahoma State University, School of Electri-
cal and Computer Engineering, Stillwater, OK). Health
monitoring on vibration signatures. Final report. Arling-
ton (VA): Air Force Office of Scientific Research (US),
Air Force Research Laboratory; 2002 Feb. Report No.:
AFRLSRBLTR020123. Contract No.: F496209810049.
Issued by performing agency:
Russelll ML, Goth-Goldstein R, Apte MG, Fisk WJ.
Method for measuring the size distribution of airborne
Rhinovirus. Berkeley (CA): Lawrence Berkeley National
Laboratory, Environmental Energy Technologies Divi-
sion; 2002 Jan. Report No.: LBNL49574. Contract No.:
DEAC0376SF00098. Sponsored by the Department of
Energy.
28. Dissertation
Borkowski MM. Infant sleep and feeding: a telephone
survey of Hispanic Americans [dissertation]. Mount
Pleasant (MI): Central Michigan University; 2002.
29. Patent
Pegedas AC, inventor; Ancel Surgical R& D Inc., as-
signee. Flexible endoscopic grasping and cutting device
and positioning tool assembly. United States patent US
20020103498. 2002 Aug 1.
304
Other Published Material
30. Newspaper article
Tynan T. Medical improvements lower homicide rate:
study sees drop in assault rate. The Washington Post. 2002
Aug 12; Sect. A:2 (col. 4).
31. Audiovisual material
Chason KW, Sallustio S. Hospital preparedness for
bioterrorism [videocassette]. Secaucus (NJ): Network for
Continuing Medical Education; 2002.
32. Legal Material
Public law:
Veterans Hearing Loss Compensation Act of 2002,
Pub.L.No. 107-9, 115 Stat. 11 (May 24, 2001).
Unenacted bill:
Healthy Children Learn Act, S. 1012, 107th Cong., 1st
Sess. (2001).
Code of Federal Regulations:
Cardiopulmonary Bypass Intracardiac Suction Control,
21 C.F.R. Sect. 870.4430 (2002).
Hearing:
Arsenic in Drinking Water: An Update on the Science,
Benefits and Cost: Hearing Before the Subcomm. on
Environment, Technology and Standards of the House
Comm. on Science, 107th Cong., 1st Sess. (Oct. 4, 2001).
33. Map
Pratt B, Flick, P, Vynne C, cartographers. Biodiversity
hotspots [map]. Washington: Conservation
International; 2000.
34. Dictionary and similar references
Dorland’s Illustrated Medical Dictionary. 29th ed. Phila-
delphia: W.B. Saunders; 2000. Filamin; p. 675.
Electronic Material
35. CD-ROM
Anderson SC, Poulsen KB. Anderson’s Electronic Atlas of
Hematology [CD-ROM]. Philadelphia: Lippincott Will-
iams & Wilkins; 2002.
36. Journal article on the Internet
Abood S. Quality improvement initiative in nursing
homes: the ANA acts in an advisory role. Am J Nurs [se-
rial on the Internet]. 2002 Jun [cited 2002 Aug 12]; 102(6)
: [about 3 p.]. Available from: http://www.nursingworld.
org/AJN/2002/june/Wawatch.htm
37. Monograph on the Internet
Foley KM, Gelband H, editors. Improving palliative care
for cancer [monograph on the Internet]. Washington:
National Academy Press; 2001 [cited 2002 Jul 9].
Available from: http://www.nap.edu/books/
0309074029/html/.
38. Homepage/Web site
Cancer-Pain.org [homepage on the Internet]. New York:
Association of Cancer Online Resources, Inc.; c2000-01
[updated 2002 May 16; cited 2002 Jul 9]. Available from:
http://www.cancer-pain.org/.
39. Part of a homepage/Web site
American Medical Association [homepage on the
Internet]. Chicago: The Association; c1995-2002 [updated
2001 Aug 23; cited 2002 Aug 12]. AMA Office of Group
Practice Liaison; [about 2 screens]. Available from: http/
/www.ama-assn.org/ama/pub/category1736.html.
40. Database on the Internet
Open database:
Who’s Certified [database on the Internet]. Evanston
(IL): The American Board of Medical Specialists. c2000-
[cited 2001 Mar 8]. Available from: http://
www.abms.org/newsearch.asp
Closed database:
Jablonski S. Online Multiple Congential Anomaly/Men-
tal Retardation (MCA/MR) Syndromes [database on the
Internet]. Bethesda (MD): National Library of Medicine
(US). c1999 [updated 2001 Nov 20; cited 2002 Aug 12].
Available from: http://www.nlm.nih.gov/mesh/
jablonski/syndrome_title.html
41. Part of a database on the Internet
MeSH Browser [database on the Internet]. Bethesda
(MD): National Library of Medicine (US); 2002 - [cited
2003 Jun 10]. Meta-analysis; unique ID: D015201; [about
3 p.]. Available from: http://www.nlm.nih.gov/mesh/
MBrowser.html Files updated weekly.
MeSH Browser [database on the Internet]. Bethesda
(MD): National Library of Medicine (US); 2002 - [cited
2003 Jun 10]. Meta-analysis; unique ID: D015201; [about
3 p.]. Available from: http://www.nlm.nih.gov/mesh/
MBrowser.html Files updated weekly.
Correctness of the reference list is the entire
responsibility of the author (s).
Figures and Tables
Figures. Glossy print photographs (in triplicate) are
required (usually 10 cm × 8 cm); good black and white
contrast is essential for good reproduction. All
illustrations must be numbered and cited in the text.
Legends should be provided for each illustration, listed
on a separate page. All lettering must be done
professionally. Freehand or typed lettering is not
acceptable. All figures should bear author’s name, short
title and an arrow indicating top of the figure in pencil
on the back of the photographs. Colour illustrations
must be paid by the authors. Please ask rates/charges
from the Publication Office of the IJCDAS.
Guidelines to Authors 2006; Vol. 48
2006; Vol. 48 The Indian Journal of Chest Diseases & Allied Sciences 305
Tables. Each table should be typed double-spaced on
a separate sheet. They should have an underlined title
followed by a legend, if any. Explanatory matter should
be in a footnote, not in the title. The approximate position
of each table in the text should be indicated in the margin
of the manuscript.
Page Proofs and Reprints. A galley proof will be sent to
the corresponding author which should be returned
within four days. Corrections should be limited to
printers errors only and no substantial additions/
deletions should be made. No change in the names of
authors (by way of additions and/or deletions) is
permissible at the proof stage. Twenty-five reprints of the
article will be sent free of cost to the corresponding author.
Papers which have been accepted/published become the
property of the Indian Journal of Chest Diseases and Allied
Sciences and permission to re-publish them must be obtained
from the Editor.
CHECKLIST FOR SUBMISSION OF MANUSCRIPT
— Covering letter including copy-right release
— Three copies of typescript of the article on A-4 size paper
— Name and address of author responsible for correspondence about the manuscript, including
highest degree and affiliations of each author.
— Abstract (upto 150 words) along with 3-6 key words
— Running title (5-6 words)
— Three glossy prints for each illustration (10 cm × 8 cm), appropriately labelled and each illustration
is cited in the text. Submit the legends on a separate sheet in the manuscript.
— Check all references for accuracy and completeness. Put references in proper format in numerical
order, making sure each is cited in the text.
306
The Indian Journal of Chest Diseases and Allied Sciences
Publication Division
V.P. Chest Institute
University of Delhi
Delhi - 110 007
UNDER TAKING BY AUTHORS
We, the undersigned, give an undertaking to the following effect with regard to our articleentitled
submitted for publication in the Indian Journal of Chest Diseases and Allied Sciences :-
1. The article mentioned above has not been published or submitted to or accepted for publication in any form,
in any other journal.
2. We also vouchsafe that the authorship of this article will not be contested by anyone whose name(s) is/are
not listed by use here.
3. We also agree to the authorship of the article in following sequence :-
Authors’ Names (in sequence) Signature of Authors
1.
2.
3.
4.
5.
6.
7.
8.
IMPORTANT
1. All the authors are required to sign this form independently in the sequence given above.
2. Each author should have generated at least a part of the intellectual content of the paper.
3. Each author should be able to defend publicly in the scientific community, that intellectual content of the
paper for which he/she can take responsibility.
4. No addition/deletion/or any change in the sequence of the authorship will be permissible at a later stage,
without valid reasons and permission of the Editor.
The Indian Journal of Chest Diseases and Allied Sciences 2006; Vol. 48
