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A prospective study of respiratory symptoms
associated with chronic arsenic exposure in
Bangladesh: findings from the Health Effects of
Arsenic Longitudinal Study (HEALS)
Faruque Parvez,
1
Yu Chen,
2
Paul W Brandt-Rauf,
1
Vesna Slavkovich,
1
Tariqul Islam,
3
Alauddin Ahmed,
3
Maria Argos,
4
Rabiul Hassan,
3
Mahbub Yunus,
3
Syed E Haque,
3
Olgica Balac,
1
Joseph H Graziano,
1
Habibul Ahsan
4
ABSTRACT
Background and aims A prospective cohort study was
conducted to evaluate the effect of arsenic (As)
exposure from drinking water on respiratory symptoms
using data from the Health Effects of Arsenic Exposure
Longitudinal Study (HEALS), a large prospective cohort
study established in Ariahazar, Bangladesh in
2000e2002. A total of 7.31, 9.95 and 2.03% of the
11 746 participants completing 4 years of active follow-
up reported having a chronic cough, breathing problem or
blood in their sputum, respectively, as assessed by
trained physicians.
Methods Cox regression models were used to estimate
HRs for respiratory symptoms during the follow-up period
in relation to levels of chronic As exposure assessed at
baseline, adjusting for age, gender, smoking, body mass
index, education and arsenic-related skin lesion status.
Results Significant positive associations were found
between As exposure and respiratory symptoms. As
compared with those with the lowest quintile of water
As level (#7
m
g/l), the HRs for having respiratory
symptoms were 1.27 (95% CI 1.09 to 1.48), 1.39 (95%
CI 1.19 to 1.63), 1.43 (95% CI 1.23 to 1.68) and 1.43
(95% CI 1.22 to 1.68) for the second to fifth quintiles of
baseline water As concentrations (7e40, 40e90,
90e178 and >178
m
g/l), respectively. Similarly, the
corresponding HRs in relation to the second to fifth
quintiles of urinary arsenic were 1.10 (95% CI 0.94 to
1.27), 1.11 (95% CI 0.95 to 1.29), 1.29 (95% CI 1.11 to
1.49) and 1.35 (95% CI 1.16 to 1.56), respectively.
These associations did not differ appreciably by cigarette
smoking status.
Conclusions This prospective cohort study found
a doseeresponse relationship between As exposure and
clinical symptoms of respiratory diseases in Bangladesh.
In particular, these adverse respiratory effects of As
were clearly evident in the low to moderate dose range,
suggesting that a large proportion of the country’s
population may be at risk of developing serious lung
diseases in the future.
BACKGROUND
Nearly 150 million people from Bangladesh and
West Bengal continue to be exposed to arsenic (As)
from drinking water despite the fact that As was
identified as a carcinogen decades ago.
1
It is well
documented that As is related to an increased risk
of lung, bladder and kidney cancers as well as
adverse dermatological, reproductive and intellec-
tual outcomes among adults and children.
2e10
There is considerable evidence concerning non-
malignant respiratory effects of As although this is
mostly based on studies with methodological
limitations.
11e17
Most of the published studies used
retrospective designs, involved small sample sizes or
measured As exposure ecologically. Evidence for the
doseeresponse relationship between, in particular,
low-level exposure and non-malignant respiratory
diseases has not been well established.
To evaluate the effects of low to moderate levels
of As exposure on the risk for respiratory symp-
toms, we conducted analyses using data from the
Health Effects of Arsenic Longitudinal Study
(HEALS) in Araihazar, Bangladesh, a prospective
cohort established in 2000. Compared with most
earlier studies, this study population has been
exposed to a wide range of water As concentrations
(0.1e864
m
g/l) and includes a large number of study
participants exposed to low to moderate levels of
As, thus providing a unique opportunity to
examine relationships between As exposure and the
risk of symptoms of respiratory disease at low to
moderate levels of exposure.
METHODS
Study participants
Using population-based sampling, the HEALS
cohort recruited 11 746 participants during
2000e2002 in Araihazar, Bangladesh. The overall
goal of the HEALS study is to examine health
effects of As exposure from drinking water and
mitigation strategies in order to guide relevant
prevention strategies and policies. A detailed
description of the study has been published else-
where.
18 19
In brief, between October 2000 and
May 2002, 11 746 adults who consumed ground-
water with a wide range of As concentrations for at
least 3 years were recruited. Since recruitment, the
cohort has been actively followed-up by trained
study physicians every 2 years with in-person home
visits. Demographic and lifestyle data, water and
urine samples were collected at baseline and at each
follow-up visit. Assessment of respiratory symp-
toms (see below) was also conducted during the
visit. This study was approved by the Institutional
Review Boards of Columbia University, University
1
Department of Environmental
Health Sciences, Mailman
School of Public Health,
Columbia University, New York,
USA
2
Department of Environmental
Medicine, New York University
School of Medicine, New York,
USA
3
Columbia University/University
of Chicago Arsenic Research
Office in Bangladesh, Dhaka,
Bangladesh
4
Department of Health Studies
and Cancer Research Center,
University of Chicago, Chicago,
USA
Correspondence to
Habibul Ahsan, Department of
Health Studies and
Comprehensive Cancer Center,
University of Chicago, Chicago,
USA; habib@uchicago.edu
Received 7 May 2009
Accepted 28 March 2010
528 Thorax 2010;65:528e533. doi:10.1136/thx.2009.119347
Environmental exposure
of Chicago and the Bangladesh Medical Research Council. The
current study included the original 11 746 cohort members who
underwent the first two follow-up visits that took place in
September 2002eMay 2004 and April 2004eAugust 2006.
Assessment of respiratory symptoms
At baseline, information on respiratory symptoms was collected
through the following question: ‘Do you have any problems in
breathing with normal daily activities or due to any illness?’All
participants answering ‘yes’to this question at baseline were
excluded from the current analyses. During the follow-up visits,
trained study physicians, who were blind to As exposure history
and baseline disease status, assessed each participant for
respiratory illness (and other illnesses) using a structured clinical
protocol. Respiratory symptoms identified at follow-up were
based on the following three separate questions: (1) ‘Do you
have a frequent cough that has lasted for over 3 months in the
past year?’; (2) ‘Do you have difficulty in breathing?’; and (3)
‘Do you have a cough that is accompanied by blood?’. The
presence of respiratory symptoms was defined as having
answered ‘yes’to any of these questions.
Sample collection, storage and processing:
Water sample collection and As assay
Water samples from the wells from which the study participants
drank regularly were collected in 50 ml acid-washed tubes
following pumping of the well for 5 min. These samples were
analysed for As concentration by graphite furnace atomic-
absorption (GFAA) with a Hitachi Z-8200 system in the
Geochemistry Laboratory at Lamont Doherty Earth Observa-
tory of Columbia University. A detailed description of the water
collection procedure is presented elsewhere.
20
Those water
samples that had an As concentration less than the detection
limit (5
m
g/l) were subsequently analysed by an Axiom Single
Collection high-resolution inductively coupled mass spectrom-
eter (ICP-MS) which has a detection limit of 0.1
m
g/l. Analyses
for time-series samples collected from 20 tube wells in the study
area showed that the As concentration in well water is relatively
stable over time.
21
Urine sample collection and As assay
At each visit, spot urine samples were collected in 50 ml acid-
washed tubes and kept in portable coolers with ice-packs
(carried by the research team) until storage in 208C freezers
within 3e5 h. All samples were frozen until shipment to
Columbia University on dry ice. Urinary As analyses were
performed with GFAA using a Perkin-Elmer Analyst 600 graphite
furnace system in the trace metal core laboratory at Columbia
University, as described.
22
Levels of As in urine were expressed as
micrograms of As per gram of creatinine. Creatinine was
analysed by a colorimetric method based on the Jaffe reaction
and it was used to correct for differences in urine concentration.
In a random sample of 10% of the cohort (n¼1123), urine
samples were further analysed to distinguish individual urinary
As metabolites.
23
The correlation of arsenobetaine and arsen-
ocholine with total urinary As was weak (<0.10).
23
On the
other hand, the correlation between total urinary As and As
from the wells was 0.76.
824
Therefore, analyses were not
adjusted for seafood consumption.
Statistical analysis
We considered the primary outcome as a positive response to
any of the three respiratory symptom questions at any of the
two follow-up visits in cohort analyses. Participants with
breathing problems with normal daily activities or due to any
illness were excluded. The analysis included a total of 10 833
participants with absence of problems with breathing and
coughing at baseline.
Cox proportional hazard models were used to estimate the
HRs for respiratory symptoms detected at follow-up visits in
relation to age, gender, demographic and lifestyle variables, and
levels of baseline well As and urinary As concentrations. We
computed HRs in relation to various As exposure levels
adjusting for potential confounding variables including age,
gender, educational attainment, smoking status, body mass
index (BMI), visit to visit changes in urinary As and well
switching status. The status of respiratory symptoms at the
follow-up visits was considered censored for those who died
(n¼201), moved (n¼463) or who were lost to follow-up
(n¼152). We calculated person-years of observation from the
date of the baseline visit to the date of the follow-up visit for
those who reported having respiratory symptoms, to the date of
death for those who had died, to the date of the move reported
by close relatives or neighbours for those who moved and to the
date of the last follow-up visit for those who reported not
having any respiratory symptoms. Urine samples were provided
by 95.6, 94.5 and 91.2% of the total cohort participants at
baseline, first follow-up and second follow-up, respectively.
Individuals with missing data on visit to visit changes in urinary
As were included in the analyses using an indicator variable.
Analyses were also conducted excluding these participants; the
results were similar and therefore are not shown.
In addition, to evaluate whether there was an interaction
between As exposure and cigarette smoking, we computed HRs in
relation to joint As exposure and smoking status. All analyses
were conducted using the SAS 9.1.3 statistical package for
Windows (SAS Institute, Cary, North Carolina, USA).
RESULTS
In total, 1874 (15.95%) participants had experienced at least one
respiratory symptom; 7.31, 9.95 and 2.03% of participants
reported having chronic cough, breathing problems or blood in
their sputum, respectively. The average age of the study
participants was 39 years at baseline.
Table 1 shows the HRs for the effect of As exposure at
baseline and respiratory symptoms during follow-up
adjusted for demographic and lifestyle factors including age,
gender,durationofeducation,smoking,presenceofskin
lesions and well switching status. Older participants were
more likely to have respiratory symptoms. Participants aged
30e40 years and older (>40 years) showed significantly
higher rates of respiratory symptoms (HR 1.16, 95% CI 1.02
to 1.32; and HR 1.51, 95% CI 1.32 to 1.72, respectively)
than those under 30 years. Overall the rate of respiratory
symptoms was greater among smokers (HR 1.93, 95% CI
1.67 to 2.22) as compared with never smokers. The HRs for
having a respiratory symptom(s) were 1.56 (95% CI 1.27 to
1.92), 2.03 (95% CI 1.73 to 2.37) and 2.15 (95% CI 1.80 to
2.58) for past smokers, current light smokers and current
heavy smokers, respectively, as compared with never
smokers, suggesting a doseeresponse effect of smoking.
After adjustment for smoking and other variables, women
had a higher risk of respiratory effects than men (HR 1.35,
95% CI 1.17 to 1.56). Individuals with a lower BMI (#18)
had a slightly higher risk of experiencing a respiratory
problem (HR 1.11, 95% CI 1.02 to 1.32). Interestingly, we
also observed a strong inverse association between duration
Thorax 2010;65:528e533. doi:10.1136/thx.2009.119347 529
Environmental exposure
of education and the risk of respiratory symptoms: the HR
for respiratory symptoms was markedly decreased for
those with 1e6years and >6 years of school attendance
compared with those with no formal education. The risk of
respiratory symptoms did not differ by skin lesion status
at baseline. About 40% of the study participants reported
that they had switched to drinking water from low
As-contaminated wells since baseline. Individuals who had
switched were less likely to report having any respiratory
symptoms compared with those who did not switch.
There was a doseeresponse relationship between baseline As
exposure levels, measured using either water As or urinary As, and
risk of respiratory symptoms. For instance, the HRs of respiratory
symptoms were 1.00 (reference), 1.27 (95% CI 1.09 to 1.48), 1.39
(95% CI 1.19 to 1.63), 1.43 (95% CI 1.23 to 1.68) and 1.43 (95% CI
1.22 to 1.68) for increasing quintiles of water As concentration
(#7, 7e40, 40e90, 90e178 and >178
m
g/l). The HRs for respi-
ratory symptoms were 1.00 (reference) 1.10 (95% CI 0.94 to 1.27),
1.11 (95% CI 0.95 to 1.29), 1.29 (95% CI 1.11 to 1.49) and 1.35
(95% CI 1.16 to 1.56) for increasing quintiles of baseline urinary
As concentration (#90, 90e160, 160e246, 246e406 and >406
m
g/
g creatinine), after adjustment for visit to visit urinary As changes
and other variables. The HRs among participants without skin
lesions remained similar to those without lesions, and
Table 1 HRs* for respiratory symptoms in relation to baseline demographic, lifestyle, and arsenic
exposure variablesy
Baseline variables
Total no. (with and
without respiratory
symptoms) n[10 833
No. with respiratory
symptoms n[1874 HR (95% CI)z
Age (in years)
#30 3614 426 1.00
30e40 3777 633 1.16 (1.02 to 1.32)
>40 3430 814 1.51 (1.32 to 1.72)
Gender
Male 4648 977 1.00
Female 6185 897 1.35 (1.17 to 1.56)
Body mass index
#18 3709 612 1.11 (0.99 to 1.24)
18e20.5 3291 672 1.00
>20.5 3562 548 1.07 (0.95 to 1.21)
Unknown 271 42
Educational attainment (in years)
No formal 4754 977 1.00
1e6 3556 565 0.79 (0.71 to 0.88)
$6 years 2517 331 0.67 (0.59 to 0.77)
Baseline water arsenic concentration (
m
g/l)
#7 2300 333 1.0
7e40 2175 373 1.27 (1.09 to 1.48)
40e90 2034 372 1.39 (1.19 to 1.63)
90e178 2170 393 1.43 (1.23 to 1.68)
>178 2154 403 1.43 (1.22 to 1.68)
Baseline urinary arsenic concentration (
m
g/g creatinine)
#90 2110 306 1.0
90e160 2102 345 1.10 (0.94 to 1.27)
160e246 2037 342 1.11 (0.95 to 1.29)
246e406 2034 378 1.29 (1.11 to 1.49)
>406 2039 420 1.35 (1.16 to 1.56)
Unknown 511 83
Smoking status
Never 7048 927 1.0
Past smoker 679 144 1.56 (1.27 to 1.92)
Current light smokerx1841 462 2.03 (1.73 to 2.37)
Current heavy smoker 1257 339 2.15 (1.80 to 2.58)
Prevalent skin lesions
No 9933 1654 1.0
Yes 691 182 1.09 (0.92 to 1.28)
Unknown 209 38
Well switching status
No 6201 1121 1.0
Yes 4099 726 0.90 (0.81 to0.99)
Unknown 533 27
*Estimated from Cox proportional hazard models.
yCut-off points were determined on the quintiles of the overall study population.
zHRs for each of the variables were adjusted for all the other variables in the table except that HRs for well arsenic were not adjusted
for urinary arsenic, and vice versa.
xLight and heavy smokers were defined using the median value of daily cigarette consumption among current smokers.
530 Thorax 2010;65:528e533. doi:10.1136/thx.2009.119347
Environmental exposure
adoseeresponse effect was still seen. Among participants without
skin lesions at baseline, the HRs associated with well As were 1.00
(reference), 1.24 (95% CI 1.06 to 1.44), 1.35 (95% CI 1.15 to 1.59),
1.38 (95% CI 1.17 to 1.62) and 1.40 (95% CI 1.18 to 1.65) with
increasing quintiles of well As.
The relationships between As exposure variables and each of the
three recorded respiratory problems are summarised in table 2. In
general, the associations between well As and individual symp-
toms were stronger than those between urinary As and symp-
toms. The HRs for having both chronic cough and breathing
problems were 1.00 (reference), 1.56 (95% CI 1.02 to 2.39), 1.81
(95% CI 1.18 to 2.79), 1.93 (95% CI 1.25 to 2.98) and 1.82 (95% CI
1.16 to 2.84) in relation to increasing quintiles of well As, and were
1.00 (reference), 1.15 (95% CI 0.74 to 1.76), 1.36 (95% CI 0.90 to
2.07), 1.75 (95% CI 1.16 to 2.62) and 1.61 (95% CI 1.06 to 2.44) in
relation to increasing quintiles of urinary As.
Examination of the risk of respiratory symptoms in relation to
joint status of smoking and As exposure suggests an additive
effect of the two factors, such that at any given level of As
exposure, the risk of having respiratory symptoms was greater
among ever smokers compared with never smokers (table 3).
The patterns of HRs associated with water and urinary As
exposure were consistent. Compared with never smokers with
the lowest level of water As, the risk associated with the highest
level of As exposure alone (HR¼1.37) was comparable with the
risk associated with smoking alone (HR¼1.50) (table 3).
DISCUSSION
To our knowledge, this is the first large prospective cohort study
that systematically evaluated As-induced respiratory effects
with detailed data on low to moderate levels of As exposure
measured at the individual level. We found a strong
doseeresponse relationship between both baseline water and
urinary As concentrations and clinical symptoms of respiratory
disease. More importantly, the findings suggest adverse effects
on respiratory symptoms at lower concentrations of water As
than reported earlier by others.
11e14
We also found that the
effects of smoking and As on respiratory symptoms were no
more than additive (no synergistic interaction).
Some studies from South America and Asia have also
reported that high levels of As exposure are associated with
non-malignant respiratory effects in populations living in As-
endemic areas.
11e17
For instance, reports from As-endemic areas
in Chile showed a high mortality and incidence of chronic
obstructive pulmonary disease (COPD) and bronchiectasis
among adults and children.
716
Studies conducted in India and
Bangladesh have found an increased risk of respiratory illnesses
and a reduced level of lung function among individuals with
high levels of As in their water (>500
m
g/l) or arsenical skin
lesions.
11e15
A study from Inner Mongolia reported a 13-fold
increased risk for cough and a high prevalence of bronchitis
among people living in As-exposed villages.
17
However, these
studies used retrospective designs, included small sample sizes or
measured As exposure ecologically. In addition, compared with
these studies, we observed respiratory effects at a much lower
level of As exposure. These findings warrant future studies of the
effects of low-level As exposure on clinically diagnosed respira-
tory disease.
Previous studies have shown a positive association between As
exposure and respiratory symptoms primarily among individuals
with skin lesions and exposed to high levels of As in drinking
water.
12 13
For instance, four studies from India and Bangladesh
found individuals with skin lesions or drinking water contami-
nated with high As concentrations (>500
m
g/l) had a risk of
cough and breathing problems
11e14 25
of between two and 15
times greater than individuals without skin lesions. An earlier
study in Chile reported excessive cough (38%) among school
children with skin lesions and living in an As-endemic area.
16
A
higher prevalence of respiratory symptoms among people with
skin lesions could also be partly due to recall bias.
11 25 26
This
could also explain why previous cross-sectional and caseecontrol
studies reported a much stronger association between skin lesion
status and respiratory symptoms than our study.
11 12
Although
we could not eliminate the potential recall bias in our study due
to the fact that the assessment of respiratory symptoms was
based on self-reported data, in our analyses the association
between As exposure and respiratory symptoms was also
clearly evident in participants with no skin lesionsdafinding
that cannot be explained by the potential recall bias. In addi-
tion, skin lesion status was not associated with risk of respi-
ratory symptoms after controlling for As exposure in the
analyses.
One previous study has observed As exposure-induced
breathing problems (OR 2.8, 95% CI 1.1 to 7.6) and cough (OR
2.8, 95% CI 1.2 to 6.6) and a 60% decreased lung function among
smokers.
15
Our analyses reveal that smoking increases respira-
tory symptoms significantly among past and present smokers as
compared with never smokers (table 1). However, cigarette
smoking did not significantly modify the relationship between
As exposure and respiratory symptoms. Nevertheless, it is
Table 2 HRs* for respiratory symptoms by levels of baseline water and urinary arsenic concentrationsy
Chronic cough HR
(95% CI) n[859
Breathing problem HR
(95% CI) n[1169
Blood in sputum HR
(95% CI) n[238
Water arsenic (
m
g/l)
#7 1.0 1.0 1.0
7e40 1.19 (0.95 to 1.50) 1.44 (1.20 to 1.74) 1.15 (0.75 to 1.76)
40e90 1.40 (1.11 to 1.75) 1.52 (1.25 to 1.84) 1.09 (1.69 to 1.70)
90e178 1.57 (1.25 to 1.97) 1.42 (1.16 to 1.73) 1.66 (1.10 to 2.51)
>178 1.60 (1.27 to 2.01) 1.41 (1.56 to 1.72) 1.51 (0.98 to 2.32)
Urinary arsenic (
m
g/g creatinine)
#90 1.0 1.0 1.0
90e160 0.98 (0.78 to 1.23) 1.14 (0.95 to 1.38) 1.16 (0.77 to 1.74)
160e246 1.14 (0.91 to 1.42) 1.16 (0.96 to 1.40) 1.05 (0.69 to 1.60)
246e406 1.52 (1.23 to 1.88) 1.28 (1.06 to 1.54) 1.03 (0.67 to 1.58)
>406 1.51 (1.21 to 1.87) 1.27 (1.05 to 1.53) 1.33 (0.89 to 1.99)
Adjusted for age, gender, body mass index, smoking, education, skin lesion and well switching status.
*Estimated from Cox proportional hazard models.
yCut-off points were determined on the quintiles of the overall study population.
Thorax 2010;65:528e533. doi:10.1136/thx.2009.119347 531
Environmental exposure
interesting to note that the risk associated with the highest level
of As exposure alone is comparable with the risk associated with
smoking alone (table 3), indicating that As exposure may be as
strong a risk factor for respiratory illness as smoking in
Bangladesh. Given that the effect is evident even at a low dose
range, and that As exposure is equally prevalent in men and in
women (unlike smoking), the future burden of respiratory illness
due to As exposure in Bangladesh could be substantial.
The role of gender on respiratory effects remains somewhat
unclear.
9
For instance, two studies from India reported a higher
risk for respiratory symptoms in males, while one from
Bangladesh found a higher risk in females.
11e13
Interestingly, one
study reported a higher risk for respiratory symptoms among
males, but observed statistically significant effects only among
females exposed to high levels of As.
11
We found that there was
a higher risk in females compared with males (HR 1.35, 95% CI
1.17 to 1.56) after adjusting for smoking status. The
doseeresponse relationship between As exposure levels and
respiratory symptoms however does not differ appreciably by
gender (data not shown). Other factors such as nutritional factors
and indoor air pollution from cooking might explain some of the
differences in risks across gender
11 25 28
; however, more research is
needed to uncover the underlying mechanisms.
In our analyses, we controlled for changes in urinary As over
time since baseline, and we found that the baseline As exposure
levels were predictive of respiratory symptoms. Changes in As
exposure, measured using visit to visit urinary As, however, were
not related to the risk of respiratory symptoms (data not
shown). We estimated that the pair-wise correlation between
urinary As measured at each visit was high (all $0.60). On
average, in the overall cohort, the urinary As level decreased by
52
m
g/g creatinine from baseline to the first follow-up visit
and then stayed at the same level at the second follow-up,
with a high correlation (0.74) between urinary As at the two
follow-up visits. A study among 398 school children in Anto-
fagasta, Chile has reported a reduction of cough from 38% to 7%
after an As removal plant was installed in the area.
16
However,
the sample size of the study was small and the reliability of self-
reported symptoms in children is questionable. With longer
follow-up times in our cohort, future analyses will include the
evaluation of the effects of long-term changes in As exposure on
the risk of respiratory diseases.
A limitation of this study is that information on respiratory
symptoms was collected at baseline and follow-up using ques-
tions which were not exactly the same. Therefore, although we
conducted prospective analyses, some of the study participants
with chronic cough but no breathing problems at baseline may
have been included in the analyses, and thus our effect estimates
may not reflect true incidence cases. However, the association
between As exposure and having both breathing problems and
chronic cough remained strong and significant, providing
evidence of the adverse effect of As exposure on subsequent risk
of multiple respiratory symptoms. Although the reliability and
validity of the questions for respiratory symptoms were not
assessed before the study, the relationships between conven-
tional risk factors for respiratory diseases and respiratory
symptoms were consistent with the literature, suggesting
content validity of the outcomes. In a subsample of 112 subjects
with lung function test results available, lung function level
decreased with increasing number of symptoms (data not
shown), suggesting the validity of the questions. Further studies
are needed to evaluate the relationship between As exposure and
respiratory end points based on more extensive diagnostic tests.
The mechanism of As-induced non-malignant respiratory
effects is not known. However, tissue inflammation by deposition
of As on the epithelium and damage has been suggested.
26
This
may increase pulmonary fibrosis and ultimately impair lung
function.
29e32
De and colleagues suggest that As may induce lung
Table 3 HRs* for respiratory symptoms in relation to joint baseline smoking status and baseline arsenic exposure levelsy
Effect modifier
Numbers (cases/total within
exposure level)
HR for respiratory symptoms
(stratified analyses)
HR for respiratory symptoms
(joint effect)
Water arsenic (
m
g/l) Smoking status n¼927/7048
#7 Never 177/1498 1.0 (ref) 1.0 (ref)
7e40 Never 183/1426 1.13 (0.92e1.39) 1.13 (0.91e1.39)
40e90 Never 169/1311 1.11 (0.89e1.38) 1.11 (0.89e1.38)
90e178 Never 183/1413 1.15 (0.92e1.43) 1.14 (0.92e1.42)
>178 Never 215/1400 1.39 (1.12e1.73) 1.37 (1.11e1.69)
n¼946/3780
#7 Ever 156/800 1.0 1.50 (1.17e1.92)
7e40 Ever 190/749 1.43 (1.14e1.78) 2.18 (1.72e2.76)
40e90 Ever 202/722 1.72 (1.38e2.14) 2.63 (2.08e3.32)
90e178 Ever 210/757 1.75 (1.40e2.18) 2.70 (2.14e3.42)
>178 Ever 188/752 1.45 (1.15e1.83) 2.25 (1.77e2.87)
Urinary arsenic (
m
g/g creatinine) Smoking status n¼882/6692
#90 Never 154/1328 1.0 (ref) 1.0 (ref)
90e160 Never 180/1372 1.11 (0.90e1.37) 1.13 (0.91e1.40)
160e246 Never 147/1253 0.99 (0.79-1.23) 0.99 (0.79e1.25)
246e406 Never 180/1340 1.12 (0.91e1.38) 1.12 (0.90e1.40)
>406 Never 221/1399 1.24 (1.01e1.52) 1.26 (1.02e1.55)
n¼908/3625
#90 Ever 152/781 1.0 1.63 (1.27e2.10)
90e160 Ever 165/728 1.10 (0.88e1.36) 1.86 (1.45e2.38)
160e246 Ever 195/784 1.25 (1.01e1.54) 2.15 (1.69e2.74)
246e406 Ever 197/693 1.47 (1.19e1.82) 2.56 (2.01e3.26)
>406 Ever 199/639 1.47 (1.18e1.82) 2.53 (1.99e3.22)
Adjusted for age, gender, body mass index, smoking, education, skin lesion and well switching status.
*Estimated from Cox proportional hazard models.
yCut-off points were determined on the quintiles of water and urinary arsenic.
532 Thorax 2010;65:528e533. doi:10.1136/thx.2009.119347
Environmental exposure
toxicity by inflammation mediated through the immune
response.
13
One study in 125 individuals with arsenical lesions in
Bangladesh observed a reduced level of immune response induced
by As, suggesting that As induces toxicity by changing the
humoral and mucosal responses.
33
Previous findings from our
group on the association between As and the serum level of Clara
cell protein CC16 also provided a biological basis for the adverse
effects of As exposure on respiratory function.
26
In summary, compared with previous reports, we observed
respiratory effects at a much lower level of As exposure in this
Bangladeshi population. This finding indicates that w80% of the
HEALS participants and their families and a vast majority of the
country’s population are at an increased risk of developing
serious respiratory diseases (including COPD, bronchitis and
interstitial lung disease) in future.
12 13 34
Future As mitigation
and research activities should focus not only on high As-endemic
areas but also on areas with relatively low exposures to evaluate
the mortality and morbidity due to As-related respiratory
diseases.
Acknowledgements We would like to thank our staff, field workers and study
participants in Bangladesh without whom this work would have been impossible.
Funding This research was supported by US National Institutes of Health Grants P42
ES10349, P30 ES09089, R01 CA107431 and R01 CA102484.
Competing interests None.
Ethics approval This study was conducted with the approval of the Institutional
Review Boards of Columbia University, University of Chicago and the Bangladesh
Medical Research Council.
Provenance and peer review Not commissioned; externally peer reviewed.
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