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Predictive value of lung function below the normal
range and respiratory symptoms for progression of
chronic obstructive pulmonary disease
M Albers, T Schermer, Y Heijdra, J Molema, R Akkermans, C van Weel
Radboud University Nijmegen
Medical Centre, Nijmegen, The
Netherlands
Correspondence to:
M Albers, Radboud University
Nijmegen Medical Centre,
Department of Primary Care
[117-HAG], PO Box 9101, 6500
HB Nijmegen, The Netherlands;
m.albers@hag.umcn.nl
Received 30 June 2006
Accepted 12 August 2007
Published Online First
27 September 2007
ABSTRACT
Background: Chronic obstructive pulmonary disease
(COPD) is an insidiously starting disease. Early detection
has high priority because of the possibility of early
implementation of smoking cessation interventions. An
evidence based model for case finding of COPD is not yet
available.
Objective: To describe the early development of COPD,
and to assess the predictive value of early signs
(respiratory symptoms, lung function below the normal
range, reversibility).
Design and methods: In a prospective study, based in
general practice, formerly undiagnosed subjects
(n = 464) were assessed at baseline and at 5 years for
respiratory symptoms and pulmonary function. Odds
ratios for early signs were calculated (adjusted for age,
gender, pack-years at baseline and smoking behaviour
during follow-up), and defined as possible indicators of
disease progression.
Results: Over a 5 year period, the percentage of subjects
with obstruction increased from 7.5% (n = 35) at baseline
to 24.8% (n = 115) at 5 years. The presence of mild early
signs and lung function below the normal range at
baseline were related to an increased risk of developing
mild to moderate COPD (GOLD I: OR 1.87 (95% CI 1.22 to
2.87); GOLD II: OR 2.08 (95% CI 1.29 to 3.37) to 2.54
(95% CI 1.25 to 5.19)) at 5 years.
Conclusion: Lung function below the normal range and
early respiratory signs predict the development and
progression of COPD.
In the past decades, an increase in the prevalence of
chronic obstructive pulmonary disease (COPD)
and asthma has been observed.
12
As a result of
demographic changes, the global burden of COPD
is expected to shift from the sixth leading cause of
death in 1990 to third position by 2020.
3
This
evolution is a significant challenge for primary
care, as the prevalence of COPD is expected to
nearly double over the period 1994–2015.
45
Although it is generally recognised that patients
with COPD should be identified before the disease
becomes substantial, early stage COPD often
remains undiagnosed
6
or misdiagnosed.
7
To
decrease morbidity and mortality from this chronic
lung disorder, the Global Initiative for Chronic
Obstructive Lung Disease (GOLD) programme was
initiated.
8
In a number of cross sectional, popula-
tion based surveys,
9–11
the GOLD guidelines were
used to estimate the prevalence of COPD. One of
the first surveys, the confronting COPD
International Survey,
12
confirmed the huge burden
to society and, furthermore, identified a significant
disparity between subjects’ perception of disease
severity and the assessed degree of severity.
The hallmark of COPD is the presence of airway
obstruction. Recently, the prevalence of undiag-
nosed airflow obstruction was estimated by review-
ing data from 13 (mainly cross sectionally designed)
studies.
13
Prevalence ranged from 3% to 12%.
Furthermore, the GOLD guidelines define a very
early stage of COPD, in which subjects are
considered to be ‘‘at risk’’ for COPD.
14
This so-called
GOLD stage 0 is defined by chronic respiratory
symptoms without measurable obstruction.
Meanwhile, prospective long term and population
based studies, focusing on early stage COPD in
relation to respiratory disease years later, are
scarce.
10 15
In one study,
10
the Copenhagen City
Heart Study, the authors concluded that GOLD
stage 0 was not prognostic for the development of
COPD. In the Obstructive Lung Disease in Northern
Sweden study,
15
subjects with respiratory symptoms
at study entry showed an increased risk of develop-
ing COPD. As this ambiguity warrants further
research, the objective of the current study was to
investigate the value of early respiratory symptoms
and lung function below the normal range as
indicators for progression of COPD.
METHODS
Design
The Detection, Intervention and Monitoring of
COPD and Asthma in general practice (DIMCA
study) is a prospective cohort study, designed to
assess the feasibility of active detection of early
stage chronic respiratory disease (COPD, asthma)
in the Dutch general population
16
(fig 1). The
initial cohort can be regarded as a random sample
from the Dutch general population. Adult subjects
(20–70 years) without a medical history of COPD,
asthma or other chronic respiratory disease were
included. All subjects took part in a screening
programme for COPD or asthma at the earliest
possible stage of disease. The assessment consisted
of a respiratory symptoms questionnaire and lung
function measurement. The criteria in the original
screening programme, further referred to as early
signs of respiratory morbidity,
i
were used to define
the baseline respiratory status of screened subjects.
Subjects with either respiratory symptoms, lung
function below the normal range
17
or a response on
salbutamol (reversibility) at baseline were consid-
ered to have an increased risk of developing
respiratory morbidity. Otherwise, subjects were
labelled as having no abnormalities. Subsequently,
at risk subjects were invited to participate in a
Chronic obstructive pulmonary disease
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2 year monitoring programme. After monitoring, those showing
persistent signs and symptoms (of varying severity) were
invited for an intervention study with inhaled corticosteroids
in a series of three randomised controlled trials. The results of
the trials are described elsewhere.
18–20
For the present study, subjects were reassessed after 5 years
with regard to their respiratory symptoms and lung function.
Invited were the following: all subjects with an increased risk of
developing respiratory morbidity who participated in monitor-
ing (n = 384) and a random sample of subjects with no baseline
abnormalities (n = 199) (fig 1).
The course of respiratory morbidity was operationalised by
the change in lung function, reversibility, respiratory symptoms
and self-reported smoking behaviour over the 5 year period.
Subjects were classified by COPD stages, as the recently
developed GOLD guidelines
21
facilitate such classification. To
study whether early signs and symptoms of respiratory
morbidity precede development of actual disease, an algorithm
based on the GOLD criteria (table 1) was used to allocate
subjects to one of the following categories: asthmatic, at risk for
COPD (GOLD 0), mild COPD (GOLD I), moderate COPD
(GOLD II), severe COPD (GOLD III) or no COPD or asthma.
The medical ethics review board of the University Medical
Centre Nijmegen approved the study. Subjects gave their
written informed consent.
Measurements
Lung function and reversibility
Lung function was assessed by two trained lung function
technicians at two different points in time (at baseline and at
5 years). Measurements were performed according to the
American Thoracic Society standards.
22
ECCS reference values
were used.
23
Variation in spirometer performance was assessed
and accounted for. Reversibility
24
was assessed 15 min after
inhalation of 800 mg of salbutamol by spacer. At the moment of
screening, lung function below the normal range
17
was defined
as bronchodilator forced expiratory volume in 1 s/vital capacity
(FEV
1
/VC) less than or equal to the lower limit of normal
(predicted minus 1.64 SD). Reversibility was defined as positive
if after bronchodilatation the change in FEV
1
(relative to the
predicted value) was at least 15%.
24
In the GOLD based disease
classification,
21
definitions were for obstruction, a post-bronch-
odilator FEV
1
/VC ,70%, and for reversibility, a 12% change in
predicted FEV
1
after bronchodilatation with a change of at least
200 ml.
Respiratory symptoms and smoking behaviour
The occurrence of respiratory symptoms was measured at
baseline and at 5 years with the Dutch modified version of the
Medical Research Council questionnaire.
25
Chronicity of respira-
tory symptoms was defined by occurrence of symptoms for
more than 3 months per year. Mucus hypersecretion was
defined as continuous production of sputum in the winter
season. Furthermore, subjects were asked whether they were
current smokers, ex-smokers or never smokers.
Statistical analysis
To describe the course of respiratory morbidity, the mean
individual change over the 5 year follow-up period in lung
function was compared for the group of subjects with no
Figure 1 Flow chart of the initial general
population cohort in the Detection,
Intervention and Monitoring of COPD and
Asthma in general practice (DIMCA
study) program, and the follow-up group
reassessed at 5 years. *12% (n = 239)
were excluded because respiratory
disease had already been diagnosed by
their general practitioner. {At 5 years, the
follow-up cohort was reduced, leaving
400 subjects in the at-risk group and 200
subjects in the group without respiratory
abnormalities. {Total number of 145 at
risk subjects participated in one of the
randomised controlled trials.
18 20 39
Chronic obstructive pulmonary disease
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abnormalities versus the group of at risk subjects. The
appropriate univariate statistical tests were used.
Progression of COPD was studied using multinomial logistic
modelling. The dependent variable was respiratory morbidity at
5 years. This outcome was defined by the three categories of
absence of COPD or asthma, mild COPD or moderate to severe
COPD. Initially obstructed subjects were excluded from the
analysis. Odds ratios (OR) of early signs of respiratory
morbidity were calculated and defined as possible indicators of
disease progression. Because of gained insight, mucus hyperse-
cretion was added to the signs initially defined at the screening.
ORs were based on adjustment for age, gender, number of pack-
years at baseline and smoking behaviour during the 5 year
follow-up period. Following disease classification at 5 years
(table 1), categories were compared on lung function and
obstruction over the 5 years using confidence limits. The SAS
statistical package (V8.2 for Windows) was used for all analyses.
Two sided p values of ,0.05 were considered to be statistically
significant.
RESULTS
The flow of the DIMCA cohort (fig 1; n = 1749) showed
different rates of non-participation. Over the 5 year period, 10
subjects were lost to follow-up because of death (none was
COPD related). Between the initial (screened) sample and the
(on GOLD stage) classified sample at 5 years there were no signs
of selection (dropout
ii
, trial participants
iii
). A total of 583
subjects were invited for reassessment at 5 years. In the group
without respiratory abnormalities (n = 199), the response was
76%; in the at risk group (n = 384), the response was 82%.
Symptoms and lung function in screened subjects
The characteristics of the study population, and their evolution
over the 5 year period, are given in table 2. At baseline, there was
no difference in age, gender, height or smoking history between
subjects without respiratory abnormalities and at risk subjects.
Both at baseline and at the reassessment after 5 years, at risk
subjects had more symptoms (p = 0.001), lower post-bronchodi-
lator FEV
1
(p = 0.0001) and lower post-bronchodilator FEV
1
/VC
Table 1 Algorithm for the classification of chronic respiratory disease (based on the GOLD criteria
21
)
Lung function Respiratory symptoms* Reversibility{Disease classification
No obstruction{Yes Asthmatic
No chronic symptoms No No COPD or asthma
Chronic symptoms No At risk for COPD (GOLD 0)
Obstruction{Yes Inadequately managed asthma
and FEV
1
1>80% No Mild COPD (GOLD I)
or 50%(FEV
1
,80% No Moderate COPD (GOLD II)
or 30%(FEV
1
,50% No Severe COPD (GOLD III)
*Chronic symptoms: cough and sputum production for at least 3 months in each of two consecutive years.
{Reversibility: a 12% change in predicted FEV
1
after bronchodilatation with a change of at least 200 ml.
{Obstructive if FEV
1
/vital capacity ,70%.
1Post-bronchodilator forced expiratory volume.
COPD, chronic obstructive pulmonary disease; FEV
1
, forced expiratory volume in 1 s; GOLD, Global Initiative for Chronic Obstructive
Lung Disease.
Table 2 Characteristics of the study population
Screened subjects
Without baseline abnormalities
(n = 151)
With baseline abnormalities
(n = 313)
Year 0 Year 5 Year 0 Year 5
Age 42.9 (11.2) 48.0 (11.2) 44.0 (11.5) 49.2 (11.5)
Gender (% female) 50.3 50.3 59.4 59.4
FEV
1
* (ml) 3532 (833) 3335 (806) 3195 (795) 2938 (802)
FEV
1
/VC (%) 84.5 (8.3) 79.3 (7.9) 81.3 (9.8) 73.0 (8.8)
Screening criteria{
Respiratory symptoms{– 37.1 88.8 80.5
Lung function ,normal range1– 4.6 16.6 20.8
Reversibility"– 0.7 2.9 2.9
Mild early signs** – 9.3 31.6 32.6
Mucus hypersecretion{{ 0.7 4.6 14.4 13.7
Pack-years 8.9 (12.0) 8.7 (10.8)
Ever smokers (%) 43.1 43.7 32.6 34.2
Current smokers (%) 31.8 27.2 40.6 36.7
Values are mean (SD).
*Post-bronchodilator FEV
1
(at 5 years: n = 150 and n = 299, respectively).
{Screening criteria, used to determine the respiratory status of subjects (see table A1 in appendix 1).
{Dutch modified version of the Medical Research Council questionnaire.
1FEV
1
/VC (lower limit of normal.
">15% predicted.
**Combination of at least two out of three mild early signs (mild obstruction or reversibility, or a weather dependent cough or
shortness of breath, or a recurrent productive cough).
{{Continuous production of sputum in the winter season.
COPD, chronic obstructive pulmonary disease; FEV
1
, forced expiratory volume in 1 s; VC, vital capacity.
Chronic obstructive pulmonary disease
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(p = 0.0003 and p,0.0001, respectively), and were more often
current smokers (p = 0.07 and p = 0.04, respectively) than
subjects without baseline abnormalities. Over the 5 year period,
the overall individual change (n = 464) showed a decrease in post-
bronchodilator FEV
1
(2241 (SD 303) ml; on average, 248 ml/
year) and in post-bronchodilator FEV
1
/VC (7.1% (SD 9.9%)). At
risk subjects demonstrated more reduction in lung function
(post-bronchodilator FEV
1
2262 ml vs 2199 ml; p = 0.02) a nd a
lower average post-bronchodilator FEV
1
/VC (28.0 vs 25.2;
p=0.04).
Respiratory morbidity
The distribution of respiratory morbidity at 5 years is presented
in table 3. Over the 5 year period, the percentage of subjects
Table 3 Obstruction and respiratory morbidity
Obstructed subjects Respiratory morbidity Subject to
analysis (n)Baseline (n) 5 years (n) 5 years n (%)
No COPD or asthma 9 296 (63.8) 287
Mild COPD 12 60 60 (12.9) 48
Moderate COPD 10 49 49 (10.6) 39
At risk for COPD 1 7 (1.5)
Asthmatic 3 6 21 (4.5)
Missing 31 (6.7)
Total 35 115 464 (100) 374
COPD, chronic obstructive pulmonary disease.
Figure 2 The course of forced
expiratory volume in 1 s (FEV
1
) and FEV
1
/
vital capacity (FEV
1
/VC) in early
respiratory morbidity. Values are mean
(95% CI). *Statistically significant
difference between year 0 and year 5.
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with obstruction increased from 7.5% (n = 35) at baseline to
24.8% (n = 115) at 5 years. The change in lung function (post-
bronchodilator FEV
1
) and obstruction over the 5 year period is
presented in fig 2. The group of subjects labelled at 5 years as
not having COPD or asthma (n =296) did not show a decline in
lung function. There was a slight but significant decrease in
post-bronchodilator FEV
1
/VC, but subjects did not become
obstructive. Asthmatic subjects at 5 years (n= 21) showed no
decrease in lung function or post-bronchodilator FEV
1
/VC. Over
the 5 year period, subjects with mild COPD (n = 60) or
moderate to severe COPD (n = 49) had significantly decreased
lung function and also became obstructive.
Respiratory morbidity odds ratios
Assessment of respiratory morbidity at 5 years included 464
subjects (table 3). The multinomial logistic regression analysis
focused on subjects without COPD or asthma (n = 287), mild
COPD subjects (n = 48) and moderate to severe COPD subjects
(n = 39). Subjects with obstruction at baseline (n = 35) were
excluded from the analysis. ORs for early signs of respiratory
morbidity were adjusted for age, gender, number of pack-years
at baseline and smoking behaviour (table 4). Results showed
that subjects with a baseline presence of mild obstruction or
reversibility, or a weather dependent cough or shortness of
breath, or a recurrent productive cough
i
had an increased risk of
developing mild COPD (OR 1.87) or moderate COPD (OR 2.08).
The presence of lung function below the normal range and
mucus hypersecretion at baseline appeared to be predictive of
the development of moderate COPD (OR 2.54 and OR 1.88,
respectively). Female gender was significantly underrepresented
in mild COPD (OR 0.54) whereas older age (OR 1.06) and an
increased smoking history contributed to the risk of develop-
ment of moderate COPD (OR 1.06 and OR 1.05, respectively).
DISCUSSION
The main objective of the current study was to investigate the
value of early respiratory symptoms and lung function below
the normal range as indicators of progression of COPD. During
the study period, we observed a substantial increase in
morbidity in subjects who at baseline were considered to have
an increased risk for development of chronic obstructive airway
disease. The most prominent predictors for developing COPD
were lung function below the normal range and mild early signs
of reversibility, weather dependent cough or shortness of breath
or recurrent productive cough.
i
COPD appears to be an insidious disease at the start. Because
of subjects’ lack of perception of disease severity,
12
there is
enormous under-presentation of early signs of respiratory
morbidity
26
causing underdiagnosis of COPD in general practice.
As smoking cessation can reduce symptoms and prevent
progression of disease,
27
early detection is important.
Additional reasons to promote early detection is that treatment
of COPD can improve lung function and quality of life in many
patients, can reduce admissions to hospital and may even
improve survival.
27
Spirometry is considered the ‘‘gold standard’’
for detecting obstruction, and also provides prognostic informa-
tion.
11 28
. As yet, mass screening for obstruction is not
considered feasible in general practice
13
and until now there
has been no long term evidence on its effectiveness. Several
studies focused on screening of high risk groups,
29 30
but this will
only detect part of the population with obstruction.
31
For
Table 4 Odds ratios from multinomial regression analysis of early signs as predictors of respiratory
morbidity 5 years later
Respiratory morbidity{at 5 years (n = 374)
Mild COPD (12.8%) Moderate COPD (10.4%)
OR Adjusted OR OR Adjusted OR
Screening criteria*
Respiratory symptoms{1.30 [0.92 to 1.83] 1.41 [0.98 to 2.01] 0.96 [0.66 to 1.42] 0.94 [0.61 to 1.43]
Lung function below normal range11.45 [0.74 to 2.86] 1.46 [0.72 to 2.96] 2.02 [1.07 to 3.83] 2.54 [1.25 to 5.19]
Reversibility"1.04 [0.38 to 2.88] 1.02 [0.00 to 0.03] 0.56 [0.16 to 1.93] 0.94 [0.25 to 3.49]
Mild early signs** 1.69 [1.13 to 2.54] 1.87 [1.22 to 2.87] 1.97 [1.28 to 3.02] 2.08 [1.29 to 3.37]
Mucus hypersecretion{{ 1.35 [0.77 to 2.36] 1.17 [0.64 to 2.14] 2.53 [1.52 to 4.19] 1.88 [1.07 to 3.33]
Smoking behaviour
Pack-years (baseline) 0.99 [0.95 to 1.02] 1.05 [1.01 to 1.08]
Not smoking at 5 years 1.23 [0.79 to 1.92] 1.04 [0.56 to 1.90]
Smoking at 5 years 1.53 [0.96 to 2.46] 1.81 [0.99 to 3.30]
Smoking during follow-up 1.31 [0.54 to 3.17] 0.79 [0.21 to 2.96]
Age 1.00 [0.97 to 1.04] 1.06 [1.01 to 1.10]
Gender (female = 1) 0.54 [0.38 to 0.76] 1.13 [0.73 to 1.73]
Values are OR [95% confidence intervals].
*Screening criteria, used to determine the respiratory status of subjects (see table A1 in appendix 1).
{Mild COPD (n = 48), moderate COPD (n = 39).
{Dutch modified version of the Medical Research Council questionnaire.
1FEV
1
/VC (lower limit of normal.
">15% predicted.
**Combination of at least two out of three mild early signs (mild obstruction, reversibility, weather dependent or recurrent
productive cough).
{{Continue production of sputum in winter.
Analysis was restricted to those 374/464 subjects who were free of ‘‘obstruction’’ at baseline. (ORs were adjusted for age, gender,
pack-years at baseline and smoking behaviour during follow-up.)
COPD, chronic obstructive pulmonary disease; FEV
1
, forced expiratory volume in 1 s; VC, vital capacity.
i
Screening criteria, used to determine the respiratory status of subjects (see table A1
in appendix 1).
ii
Baseline values of the several follow-up groups (see table A2 in appendix 1).
iii
Trial participants.
Chronic obstructive pulmonary disease
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reasons of feasibility and cost effectiveness, it is generally agreed
that case finding is the most appropriate tool in reducing
underdiagnosis of COPD in general practice. As a first step in
the development of an evidence based model for case finding,
risk factors for the detection of early COPD need to be
identified. Development of COPD was investigated in several
studies,
32–36
in which a great variety of risk factors (such as
middle age, current or past smoking status, a self reported
history or a general physician’s diagnosis of chronic obstructive
airway disease, laryngeal height, bronchial hyperresponsiveness,
respiratory symptoms, body mass index, accelerated decline in
lung function, exercise capacity, occupational exposure, air
pollution, asthma, genetic variation and functional status) were
used.
In the present study, in a population based sample with
initially undiagnosed subjects from general practice, we used
prospective data to describe early development of COPD, and to
identify risk factors. We used an algorithm, based on the
recently developed GOLD guidelines, to relate disease severity at
5 years to the baseline presence of early signs. However, there
are several points to raise. Firstly, in the study design, the early
signs were fixed by the screening criteria defined at baseline.
Because of gained insight, mucus hypersecretion (prominent in
former GOLD stage 0) was added to this selection of early signs.
Secondly, subjects were classified on the basis of a cross
sectional measurement at 5 years. Although a well defined
algorithm was used, classification was only based on post-
bronchodilator FEV
1
, VC, reversibility and respiratory symp-
toms. In daily practice, however, often additional clinical
assessment will be needed to arrive at an undisputed diagnosis,
with a reliable disease staging. On the other hand, in the present
study, reversibility data were used to distinguish between
COPD and asthma. Development of COPD was further
confirmed by progressive lung function decline and develop-
ment of obstruction (fig 2). In their study of the population
impact of different definitions of airway obstruction, Celli and
colleagues
11
stated that the rates according to the GOLD
guidelines were found to produce lower estimates than other
spirometry based definitions. This may be explained by the fact
that in that study, spirometry was performed only pre-
bronchodilator.
37
Celli et al did not have disposition of
reversibility testing, making it impossible to distinguish
reversible from irreversible obstruction.
11
In a recent editorial,
38
Vestbo indicated that GOLD has not attempted to separate 0
COPD from symptomatic asthma. With the algorithm used,
including an effort to minimise mislabelling of asthmatic
subjects, we used a prudent estimate of prevailing disease at
5 years. Thirdly, as in regression analysis, adjustment was
restricted to a limited set of risk factors (age, gender, pack-years
at baseline and smoking behaviour during follow-up) and not all
confounding factors may have been excluded. A further finding
concerned the steady (or slightly decreased) percentage of
subjects with respiratory signs and symptoms in the at risk
group. The most obvious explanation might be that after
assessment of symptoms, the problem is identified and subjects
will deal with it.
Over the 5 year period, the number of subjects with
obstruction increased considerably. In other terms, screened
subjects, considered to have an increased risk for development of
COPD, appeared to have a more than threefold risk of actually
developing mild or moderate COPD. The most prominent
predictor for development of moderate COPD was a baseline
presence of lung function below the normal range (OR 2.54). In
this cohort of initially undiagnosed subjects, a baseline presence
of mild obstruction or reversibility, or a weather dependent
cough or shortness of breath, or a recurrent productive cough
were predictive for the development of mild COPD (OR 1.87) or
moderate COPD (OR 2.08) 5 years later. Furthermore, baseline
mucus hypersecretion (in the absence of airflow obstruction
without full reversibility) appeared to be predictive (OR 1.88)
for subsequent development of moderate COPD. A prolonged
follow-up from early stage COPD onwards, followed by an
undisputed clinical diagnosis, may further clarify these rela-
tions. In terms of healthcare, identification of risk factors for
early detection of COPD may contribute to the development of
an evidence based model for case finding. This is specifically of
interest for the studied cohort, as these undiagnosed subjects
did not present themselves in primary care.
In conclusion, lung function below the normal range and
early respiratory signs are possible predictors of progression of
COPD. As a result, implementation of GOLD guidelines in
general practice may reduce underdiagnosis and under treat-
ment.
Acknowledgements: The authors thank Guido van den Boom. His former support
and contribution were critical to the present article. The authors also wish to thank Lea
Peters and Joke Grootens for their support in data collection, logistics and generating
graphs.
Competing interests: None.
Ethics approval: Yes.
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APPENDIX
Appendix 1
Table A1 shows the screening criteria used to determine respiratory status of subjects
and table A2 shows the baseline values of the respective follow-up groups
Appendix 2
A total number of 145 at risk subjects participated in one of the randomised controlled
trials (for a period varying between 12 and 30 months), in which inhaled
corticosteroids (n = 68) were compared with placebo treatment (n = 77). The mean
individual change in post-bronchodilator FEV
1
over the 5 year period was 2352 ml
(SD 287) in the corticosteroid treated group versus 2280 ml (SD 307) in the placebo
treated group. Based on the individual change over the 5 year period, corticosteroid
treatment did not show a different course in respiratory symptoms, post-
bronchodilator FEV
1
(p = 0.09) or post-bronchodilator FEV
1
/VC (p = 0.96) from
placebo treatment. As a consequence, participants in the intervention study were
included in the sample.
Table A1 Screening criteria used to determine the respiratory status of subjects
Criteria
Respiratory symptoms Wheezing, dyspnoea, cough (>3 months/year) or an asthma attack or
shortness of breath due to an allergic reaction (in the previous 12 months)
Lung function below the normal range FEV
1
/VC (lower limit of normal (predicted 21.64 SD)
Reversibility FEV
1
reversibility >15% predicted
(at least two out of three) mild early signs FEV
1
/VC (predicted value minus 1 SD and/or
FEV
1
reversibility >10% predicted and/or
weather dependent (productive) cough or shortness of breath or the occurrence
of more than one period of (productive) cough in the previous two years
FEV
1
, forced expiratory volume in 1 s; VC, vital capacity.
Table A2 Baseline values of the respective follow-up groups
n Age (y)
Gender (%
female)
Pre-FEV
1
*
(ml)
Pack-year
(No)
Smoking status
(% ever smokers)
At risk subjects
Baseline group 604 43.4 59.9 3058 9.1 32.0
Monitoring group 384 42.9 57.6 3109 8.9
Reassessed group (year 5) 313 43.9 59.4 3065 8.7 32.6
Subjects without abnormalities
Baseline group 551 42.9 50.3 3440 7.0 37.4
Reassessed group (year 5) 151 42.9 50.3 3477 8.9 43.1
*Pre-bronchodilator forced expiratory volume.
FEV
1
, forced expiratory volume in 1 s.
Chronic obstructive pulmonary disease
Thorax 2008;63:201–207. doi:10.1136/thx.2006.068007 207
group.bmj.com on December 26, 2015 - Published by http://thorax.bmj.com/Downloaded from
pulmonary disease
progression of chronic obstructive
normal range and respiratory symptoms for
Predictive value of lung function below the
Weel
M Albers, T Schermer, Y Heijdra, J Molema, R Akkermans and C van
doi: 10.1136/thx.2006.068007
2008 63: 201-207 originally published online September 28, 2007Thorax
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