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PedersenCJ, etal. BMJ Open 2020;10:e042380. doi:10.1136/bmjopen-2020-042380
Open access
Prevalence of atopic dermatitis, asthma
and rhinitis from infancy through
adulthood in rural Bangladesh: a
population- based, cross- sectional survey
Courtney J Pedersen,1 Mohammad J Uddin,2 Samir K Saha,2
Gary L Darmstadt 1
To cite: PedersenCJ, UddinMJ,
SahaSK, etal. Prevalence of
atopic dermatitis, asthma and
rhinitis from infancy through
adulthood in rural Bangladesh:
a population- based, cross-
sectional survey. BMJ Open
2020;10:e042380. doi:10.1136/
bmjopen-2020-042380
►Prepublication history for
this paper is available online.
To view these les, please visit
the journal online (http:// dx. doi.
org/ 10. 1136/ bmjopen- 2020-
042380).
Received 08 July 2020
Revised 23 September 2020
Accepted 29 September 2020
1Department of Pediatrics,
Stanford University School of
Medicine, Stanford, CA, USA
2Child Health Research
Foundation, Dhaka, Bangladesh
Correspondence to
Dr Gary L Darmstadt;
gdarmsta@ stanford. edu
Original research
© Author(s) (or their
employer(s)) 2020. Re- use
permitted under CC BY- NC. No
commercial re- use. See rights
and permissions. Published by
BMJ.
ABSTRACT
Objective Describe the pattern of atopic disease
prevalence from infancy to adulthood.
Design Cross- sectional household survey.
Setting Community- based demographic surveillance site,
Mirzapur, Bangladesh.
Participants 7275 individuals in randomly selected
clusters within 156 villages.
Primary and secondary outcome measures The
12- month prevalence of atopic dermatitis (by UK Working
Party Criteria (UK criteria) and International Study of
Asthma and Allergies in Childhood (ISAAC)), asthma and
rhinitis (by ISAAC); disease severity (by ISAAC); history of
ever receiving a medical diagnosis.
Results Children aged 2 years had the highest prevalence
of atopic dermatitis—18.8% (95% CI 15.2% to 22.4%) by
UK criteria and 14.9% (95% CI 11.6% to 18.1%) by ISAAC—
and asthma (20.1%, 95% CI 16.4% to 23.8%). Prevalence of
rhinitis was highest among 25–29 year olds (6.0%, (95% CI%
4.5 to 7.4%). History of a medical diagnosis was lowest for
atopic dermatitis (4.0%) and highest for rhinitis (27.3%) and
was signicantly associated with severe disease compared
with those without severe disease for all three conditions
(atopic dermatitis: 30.0% vs 11.7%, p=0.015; asthma; 85.0%
vs 60.4%, p<0.001; rhinitis: 34.2% vs 7.3%, p<0.001) and
having a higher asset- based wealth score for asthma (29.7%
(highest quintile) vs 7.5% (lowest quintile), p<0.001) and
rhinitis (39.8% vs 12.5%, p=0.003). Prevalence of having
>1 condition was highest (36.2%) at 2 years and decreased
with age. Having atopic dermatitis (ISAAC) was associated
with signicantly increased odds ratios (OR) for comorbid
asthma (OR 5.56 (95% CI 4.26 to 7.26)] and rhinitis (3.68
(95% CI 2.73 to 4.96)). Asthma and rhinitis were also strongly
associated with each other (OR 8.39 (95% CI 6.48 to 10.86)).
Conclusions Atopic disease burden was high in this
rural Bangladeshi population. Having one atopic condition
was signicantly associated with the presence of another.
Low incidence of ever obtaining a medical diagnosis
highlights an important opportunity to increase availability
of affordable diagnosis and treatment options for all age
groups.
INTRODUCTION
Atopic diseases are a set of conditions
including atopic dermatitis, asthma and
allergic rhinitis that are estimated to affect
approximately20 of the world’s popula-
tion.1Atopic dermatitis is the leading contrib-
utor to the global burden of skin disease,
affecting an estimated 230 million people,
while asthma is estimated to affect nearly
340 million people and is the most common
chronic disease among children.2 3 The
International Study of Asthma and Allergies
(ISAAC) was a global epidemiological effort
to standardise research on the prevalence
of these conditions. Their data revealed
an increasing prevalence of atopic derma-
titis, asthma and rhinitis globally, however,
with great variations within and between
countries.4–6 The most rapid increases in
prevalence were seen among countries with
previously documented low prevalence of
Strengths and limitations of this study
►Despite increasing prevalence of atopic disease in
low- income and middle- income countries, there are
limited data describing the pattern of atopic disease
prevalence across the life course; to our knowledge,
this is the rst description of the cross- sectional
period prevalence of atopic conditions from in-
fancy through adulthood reported from the Indian
subcontinent.
►We conducted population- based household surveil-
lance in rural Bangladesh using validated instru-
ments for detection of atopic diseases.
►We lacked longitudinal data that would allow us
to suggest a driving mechanism for comorbidity
among atopic conditions, such as the atopic march;
a prospective cohort study would more easily enable
conclusions to be drawn about risk factors and the
relationships among the three atopic diseases.
►We were able to identify subjects whose atopic
condition was diagnosed by a medical provider,
but lacked data on medical management of atopic
conditions.
2PedersenCJ, etal. BMJ Open 2020;10:e042380. doi:10.1136/bmjopen-2020-042380
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these conditions and were mostly low- income and middle-
income countries (LMICs).5 7
The natural history of atopic conditions classically
begins with atopic dermatitis and progresses in an addi-
tive manner to include asthma and allergic rhinitis—a
pattern known as the ‘atopic march.’8 However, limited
research in LMICs suggests that atopic sensitisation is
not as strongly correlated with the sequential develop-
ment of atopic dermatitis, asthma and rhinitis as it is in
high- income countries (HICs) where the atopic march
was first described.9–11 Additionally, despite associations
between allergic sensitisation and atopic conditions, the
atopic march was not observed among a birth cohort in
Uganda.12 The authors concluded that environmental
exposures in late childhood may dissociate atopic condi-
tions from each other.
The hygiene hypothesis is a widely accepted explana-
tion for both the higher prevalence of atopic diseases in
HICs and the trend of increasing prevalence in LMICs
as they industrialise, arguing that reduced exposure to
microbes early in life increases the risk of developing
immunoregulatory disorders including atopic disease.13
However, research is beginning to show that these condi-
tions are multifactorial and even within risk factors there
can be great variation.14 15 For example, until recently,
helminths have been thought to be universally protective
against the development of atopic conditions but recent
evidence shows that these associations are heterogeneous
and vary drastically even within helminth species.16 17
While much of the global effort to understand atopic
conditions has focused on the paediatric population, it
is essential to understand the prevalence of atopic condi-
tions in children and adults in order to inform policy
and the implementation of interventions that target the
appropriate populations. This is especially true as the
prevalence of these conditions increases in LMICs. Here,
we present the findings of a cross- sectional study of the
period prevalence of atopic conditions from infancy to
adulthood in rural Bangladesh.
METHODS
The methods and reporting of this study followed
Strengthening the Reporting of Observational Studies in
Epidemiology guidelines (https://www. strobe- statement.
org/ fileadmin/ Strobe/ uploads/ checklists/ STROBE_
checklist_ v4_ combined. pdf).
Study population
The study took place within the demographic surveillance
site (DSS) of the Child Health Research Foundation and
the International Centre for Diarrhoeal Disease Research,
Bangladesh in Mirzapur, Bangladesh. Mirzapur is a rural
subdistrict of Bangladesh located approximately 60 km
north of Dhaka, the capital city. Bangladesh is classified
by the World Bank as an LMIC, with a per capita gross
domestic product of Int$4372 in 2018, ranking 137th
among 182 countries. Mirzapur is representative among
Bangladesh subdistricts, falling towards the middle
in terms of educational, health and economic indica-
tors. The economy is mostly dependent on agriculture.
Mirzapur is also broadly representative of the Gangetic
plains region of the Indian subcontinent. There are
three main seasons in Mirzapur: summer (March–June),
monsoon (June–October) and winter (October–March).
The Mirzapur DSS was created in 2007 and has nearly
300 000 individuals enrolled in approximately 70 000
households. The DSS is served by Kumudini Hospital, a
private, non- profit 750- bed referral hospital.
Study design
We conducted a community- based cross- sectional survey
of households enrolled in the Mirzapur DSS from
November 2017 to April 2018. This study was nested
within the weekly household visits that community health
workers (CHW) perform while conducting active surveil-
lance of serious childhood illness within the Mirzapur
DSS. The target sample size of 2149 under-5 children was
calculated assuming a 6.5% prevalence of atopic derma-
titis and a 95% CI of ±1% precision in a population of
27 000. Each of the 156 villages in the DSS was subdi-
vided into 110 clusters and ten clusters among them were
chosen at random to be included in the study, achieving
the desired population- based sample. The CHWs were
bilingual, had an educational attainment of secondary
school or higher, and were well known to the community.
They attended 2 days of classroom instruction on the aims
of the study and on atopic disease identification, ISAAC
protocol, UK Working Party Criteria, and the research
study protocol after which they performed 1 day of field
practice with observation and feedback. One month
after the initial training session, they received a refresher
training. Supervisors, who also attended the training,
monitored the CHWs’ work weekly.
Surveillance for atopic diseases
CHWs visited DSS members in their homes to admin-
ister oral informed consent for enrolment. As this study
was nested within a severe childhood illness surveil-
lance programme, the female head of household typi-
cally responded for herself and for all of the children,
including adolescents. Other adults within the household
responded to questionnaires about their own health.
Questionnaires took between 5 and 20 min per person to
complete; more questions were asked if the participant
screened positive for any one condition. Households
with all adults missing during the first visit were visited a
second time and if missing on the second visit, that house-
hold was excluded from the study.
International Study of Asthma and Allergies in Childhood
The questionnaire was translated from English to Bangla
(by author MJU) and back- translated from Bangla to
English to verify accuracy by Zabed bin Ahmed, Senior
Research Officer at the Child Health Research Founda-
tion. The questionnaire was pilot tested in the community,
3
PedersenCJ, etal. BMJ Open 2020;10:e042380. doi:10.1136/bmjopen-2020-042380
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discussed with CHWs and adjusted following the recom-
mendations of the ISAAC phase 3 Manual.18 Demo-
graphic data were obtained from the Mirzapur DSS data
repository linked to the individual and household identi-
fication numbers of participants in this study.
The 12- month prevalence of atopic dermatitis, asthma
and rhinitis were ascertained using the ISAAC Phase
3 core symptom questionnaires. Atopic dermatitis was
defined as an itchy rash at any time coming and going for
at least 6 months that had at any time affected the folds
of the elbows, behind the knees, in front of the ankles,
under the buttocks or around the neck, ears or eyes in
the past 12 months. Severe atopic dermatitis was defined
as being kept awake one or more nights per week on
average by this itchy rash in the past 12 months. While
previous surveys with ISSAC have not included infants, if
the child was under the age of 6 months we considered
any presence of rash as affirmative and determined a
positive screen by an affirmative response to the question
regarding anatomical location of the rash as described
above. Asthma was defined as the presence of whistling or
wheezing in the previous 12 months. Severe asthma was
defined as any of the following in the previous 12 months:
more than three attacks of wheezing, sleep disturbed by
wheezing on average one or more nights per week, or at
least one episode where wheezing limited speech to only
two words or cries at a time between breaths. Rhinitis was
defined as sneezing, rhinorrhoea or nasal obstruction
in the previous 12 months not associated with the cold
or influenza. Severe rhinitis was defined as having this
nose problem interfere with daily activities ‘a lot’ in the
previous 12 months.
UK criteria
We also administered the UK criteria,19–21 a modification
of the Hanifin and Rajka criteria,22 to screen for atopic
dermatitis since the ISAAC questionnaires have been
primarily used in children over the age of 5 years. The
ISAAC and UK criteria have been administered together
in previous studies among non- Caucasian populations
and have yielded heterogeneous results.23–25 However,
the UK criteria have been validated in infants25 26 and
young children.21 The ‘questions- only’ format was used
as recommended for population- based surveys.27–29 Using
this criteria, atopic dermatitis was defined as having a
history of itchy skin within the past 12 months and at
least two of the following: (1) history of flexural derma-
titis (fronts of elbows, behind the knees, fronts of ankles,
around the neck, on the cheeks or around the eyes), (2)
onset <age of 2 years (not applied if a child was <4 years of
age), (3) personal history of asthma or allergic rhinitis or
maternal/paternal history of either if a child was <4 years
of age and (4) affected by dry skin in general.
Data analysis
Study data were collected and managed using Research
Electronic Data Capture tools hosted at the Stanford
University School of Medicine.30
For each of the four conditions (ISAAC atopic derma-
titis, asthma and rhinitis and UK criteria atopic dermatitis),
we calculated the prevalence using the total number of
individuals in each age group as the denominator for that
age group. In one instance where age was missing, that
individual was deleted from analysis. The corresponding
95% CIs were calculated separately for each age group.
In order to have a sufficient sample size for comparison
of atopic conditions between groups while still main-
taining age groups at various developmental stages, we
ran χ2 tests on the following age groups: under 5 years,
6–14 years, 15–24 years and ≥25 years. We used bivariate
logistic regression analysis to calculate ORs. Asset- based
wealth index quintiles were calculated based on source
of drinking water, toilet facility, household building mate-
rials, livestock, land use and number of rooms in the
home.31 Wealth indices were calculated using the entire
Mirzapur DSS, of which our sample is a subset as previ-
ously described. We used SAS Studio 3.8 (SAS Institute)
to perform all data analysis.
Patient and public involvement
Patients or the public were not involved in the design,
conduct, reporting, or dissemination plans of our
research.
Verbal informed consent was obtained from heads of
households after informing them of the study’s proce-
dures and the purpose of the study.
RESULTS
During the study period, 2068 households were
approached for enrolment; no households that were
approached refused participation. We surveyed 7275 indi-
viduals with a mean age of 18.8 years (SD 14.4 years) of
whom 2242 (30.8%) were under 5 years of age (table 1).
The sample included 3425 (47.1%) men and 3850
(52.9%) women. The majority of households (86.6%)
were Muslim. Approximately half of adult women (50.7%)
and men (48.9%, not shown) had not completed primary
school. The highest wealth index quintile comprised
32.9% of the sample and the lowest comprised 5.6%.
Atopic dermatitis
The UK criteria identified 550 participants as having
atopic dermatitis for an overall 12- month prevalence of
7.6% (95% CI 7.0% to 8.1%). Atopic dermatitis preva-
lence showed a bimodal pattern increasing from 9.3%
in children <1 year (95% CI 6.7% to 12.0%) and peaking
at 18.8% (95% CI 15.2% to 22.4%) at 2 years (figure 1).
Prevalence then decreased to 3.8% (95% CI 2.1% to
5.4%) in children 6–9 years old and increased again
during adolescence to 6.4% (95% CI 3.9% to 9.0%) in
the 15–19 years age group. In adulthood, the prevalence
decreased to a low of 2.8% (95% CI 1.4% to 4.3%) in
the ≥40 years age group. Females ≥25 years had a higher
prevalence of atopic dermatitis than males (5.9% vs 3.0%,
4PedersenCJ, etal. BMJ Open 2020;10:e042380. doi:10.1136/bmjopen-2020-042380
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p=0.001); there was no difference in childhood preva-
lence between the sexes.
ISAAC identified 498 participants with atopic derma-
titis for an overall 12- month prevalence of 8.1% (95% CI
4.6% to 11.6%) ranging from a high of 14.9% (95% CI
11.6% to 18.1%) at 2 years to lows of 3.2% (95% CI 1.8%
to 4.7%) and 3.4% (95% CI 1.8% to 5.0%) in the 35–39
years and ≥40 year age groups, respectively (figure 1).
Similar to the UK criteria, the ISAAC results displayed a
bimodal trend with peak prevalence in early childhood
and in adolescence (9.0% (95% CI 6.0% to 11.9%) in the
15–19 years age group). Prevalence of atopic dermatitis
was also higher in females than males in adulthood (5.3%
vs 3.1%, p=0.003) by this measure. Severe disease was
found among 12.4% of those affected overall. Males also
had more severe disease in early adulthood than females
(33.3% vs 4.4%, p=0.015). There were no differences in
severity among the other age groups.
Asthma
Five hundred and eight participants met the ISAAC
criteria for asthma for an overall 12- month prevalence
of 7.0% (95% CI 6.4% to 7.6%). The highest prevalence
was 20.1% (95% CI 16.4% to 23.8%) in children 2 years
old (figure 2). The prevalence then down- trended and
reached its nadir at 2.2% in the 15–19 (95% CI 0.7%
to 3.8%) and 20–24 (95% CI 1.1% to 3.3%) years age
groups before increasing again slightly to 3.9% (95%
CI 2.7% to 5.1%) and 4.1% (95% CI 2.5% to 5.7%) in
the 25–29 years and 35–39 age groups, respectively.
The prevalence of asthma was higher in males under 5
years of age compared with females (16.2% vs 13.3%,
Figure 2 The 12- month prevalence of asthma and
proportion of severe cases by age group of subjects in
Mirzapur, Bangladesh.
Table 1 Demographic characteristics of the study sample
(N=7275)
% (n)*
Age in years, mean (SD) 18.8 (14.4)
<1 year 6.2 (450)
1 year 6.5 (473)
2 years 6.3 (458)
3 years 6.1 (446)
4 years 5.7 (415)
5 years 1.5 (106)
6–9 years 6.9 (504)
10–14 years 6.0 (435)
15–19 years 4.9 (357)
20–24 years 9.5 (690)
25–29 years 13.6 (992)
30–34 years 11.9 (866)
35–39 years 8.1 (586)
≥40 years 6.8 (497)
Sex
Male 47.1 (3424)
Female 52.9 (3851)
Religion
Muslim 86.6 (6291)
Hindu 13.3 (963)
Highest female education (N=2053)
No primary 9.9 (205)
Less than primary 40.5 (837)
Primary 25.7 (530)
Some secondary 10.4 (210)
Secondary or higher 13.2 (271)
Wealth quintile
Poor 5.6 (111)
Lower middle 14.6 (288)
Middle 22.0 (432)
Upper middle 24.9 (490)
Wealthy 32.9 (647)
*Percentages may not sum to 100% due to rounding
Figure 1 The 12- month prevalence of atopic dermatitis
and proportion of severe cases by age group of subjects in
Mirzapur, Bangladesh. ISAAC, International Study of Asthma
and Allergies in Childhood.
5
PedersenCJ, etal. BMJ Open 2020;10:e042380. doi:10.1136/bmjopen-2020-042380
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p=0.049). Overall, 65.6% of those identified with asthma
met criteria for severe disease. Those >5 years were more
likely to have severe disease than those ≤5 years (73.2% vs
61.2%, p=0.010). There was no difference in prevalence
of severe asthma between the sexes (66.7% male vs 64.4%
female, p=0.620).
Rhinitis
For rhinitis, 303 participants met ISAAC criteria for an
overall 12- month prevalence of 4.2% (95% CI 3.7% to
4.6%). Prevalence was highest among participants from
the highest wealth quintile (5.1%, p=0.003). Among
under-5 children, the prevalence was highest in the 2- year
age group (4.8%, 95% CI 2.9% to 6.8%) and 4- year age
groups (4.8%, 95% CI 2.8% to 6.9%) (figure 3). Starting
from a low of 0.9% (95% CI 0.0% to 2.8%) at 5 years, prev-
alence increased until the 25–29 years age group where it
peaked at 6.0% (95% CI 4.5% to 7.4%) and decreased
again to 3.0% (95% CI 1.5% to 4.5%) in the ≥40 years age
group. Males had a higher prevalence in early childhood
(4.3% vs 2.7%, p=0.017) and lower prevalence in adult-
hood (3.7% vs 6.5%, p<0.001) compared with females in
the same age groups. Overall, 14.5% of those identified
with rhinitis had severe disease and those >5 years had a
higher proportion of severe rhinitis than those ≤5 years
(17.3% vs 7.2%, p=0.027).
Physician diagnosis
The proportion of participants who had received a
doctor’s diagnosis was 25/549 (4.6%) for the UK criteria,
20/495 (4.0%) for ISAAC atopic dermatitis, 95/507
(18.7%) for asthma and 82/300 (27.3%) for rhinitis.
Those with severe disease were significantly more likely
to have received a doctor’s diagnosis compared with
those without severe disease for atopic dermatitis (30.0%
vs 11.7%, p=0.015), asthma (85.0% vs 60.4%, p<0.001)
and rhinitis (34.2% vs 7.3%, p<0.001). For asthma, the
proportion of participants who had received a physician’s
diagnosis increased from 7.5% for the lowest wealth quin-
tile to 29.7% (p<0.001) for the highest quintile. A similar
trend was found with rhinitis ranging from 12.5% in the
lowest wealth quintile to 39.8% (p=0.003) in the highest
quintile. No association was found between atopic derma-
titis diagnosis and wealth quintile.
Concurrent atopic disease
The prevalence of having any one atopic condition
peaked early in life, affecting over one- third (36.2%)
of children 2 years of age (figure 4). The prevalence of
having two atopic conditions also peaked at 2 years of
age (10%), was lowest (1.4%) in children 6–9 years old
and rose again slightly in adulthood to between 3.3% and
3.4% in the 25–29 and 35–39 age groups, respectively.
The percentage of those with all three conditions ranged
from 0.0% to 1.2%. Participants with atopic dermatitis
as defined by the UK criteria had a higher prevalence
of asthma (24.2% vs 5.6%, p<0.001; OR 5.41 (95% 4.34–
6.75)) and rhinitis (15.6% vs 3.2%, p<0.001; OR 4.49
(95% CI 3.55 to 5.68)) compared with those without
atopic dermatitis. The same pattern was found for those
with atopic dermatitis as defined by the ISAAC criteria
for asthma (21.9% vs 5.9%, p<0.001; OR 5.56 (95% CI
4.26 to 7.26)) and rhinitis (12.1% vs 3.6%, p<0.001; OR
3.68 (95% CI 2.73 to 4.96)). Similarly, those with asthma
had a higher prevalence of rhinitis compared with those
without asthma (20.3% vs 2.9%, p<0.001; OR 8.39 (95%
CI 6.48 to 10.86)).
DISCUSSION
To our knowledge, this is the first description of the
period prevalence of atopic conditions over the life
course from infancy through adulthood reported from
the Indian subcontinent. Atopic dermatitis and asthma
followed a similar pattern, peaking in the second year
of life and decreasing in prevalence with age, although
with an upturn in prevalence of atopic dermatitis during
adolescence. Longitudinal studies from HICs similarly
have documented that children aged 2 years and under
3 years have the highest prevalences of atopic dermatitis
and wheezing, respectively.32–34 In contrast, rhinitis was
Figure 3 The 12- month prevalence of rhinitis and
proportion of severe cases by age group of subjects in
Mirzapur, Bangladesh.
Figure 4 Proportions of comorbid atopic conditions by age
group of subjects in Mirzapur, Bangladesh.
6PedersenCJ, etal. BMJ Open 2020;10:e042380. doi:10.1136/bmjopen-2020-042380
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relatively stable until increasing from adolescence to
adulthood. Global estimates of rhinitis are heterogeneous
and difficult to compare.35
As found in multiple previous studies,12 36–38 having
atopic dermatitis was associated with increased odds of
concurrently having asthma or rhinitis, and asthma was
associated with rhinitis. Thus, comorbid development
of these atopic diseases clearly occurs in this popula-
tion. However, the proportion of those affected with any
one condition decreased with age and those with two or
more conditions did not substantially increase. Research
among a Ugandan birth cohort found that atopic sensi-
tisation increased to the level of HICs with age, but the
prevalence of atopic disease did not increase as expected
based on data from HICs leading the authors to conclude
that the atopic march did not occur in this population.12
While our data support the comorbid nature of these
conditions, we lack the longitudinal data that would allow
us to suggest a driving mechanism, such as the atopic
march.
The most recent estimate of atopic dermatitis in Bangla-
desh was reported in 2005 among 6–7 and 13–14 years
age groups to be 6.0% and 7.1%, respectively, and 6.5%
overall.39 This falls within both the UK criteria and ISAAC
measures for our 10–14 years age group but is higher than
our estimates for the 6–9 years age group. The overall
estimate is also within our sample’s estimated prevalence
when the two groups are combined. More recently asthma
prevalence has been reported as high as 20.2% and 6.8%
in 4.5 and 10 years old, respectively.40 These are higher
than the estimates reported here; however, an asthma
prevalence of 8.7% in 5 years from the same surveillance
site was also reported, similar to the prevalence we report
here.41 These differences in prevalence could be due to
environmental variation between the research sites within
the country. Wide variations were seen between Indian
centres from the ISAAC Phase 3 study which reported
prevalence ranging from 4.6% to 45.7% for rhinitis and
0.9% to 9.2% for eczema among 13–14 years.42 While
we followed the ISAAC Phase 3 Manual instructions for
translation closely, there is also the possibility that differ-
ences in translation resulted in different understandings
of the questions for our study sample compared with
other samples within the country or region.
The prevalence provided by the UK criteria was higher
than the ISAAC prevalence for 1–5 years. The ISAAC
questionnaires are typically deployed in populations 6–7
and 13–14 years old but they have been used in children
as young as 2 years in modified versions.12 Here, we used a
modified ISAAC questionnaire for atopic dermatitis and
it showed good agreement with the UK criteria in chil-
dren <1 year. The deviation in the 1–4 years age groups,
with higher prevalence measured by the UK criteria than
ISAAC, was likely due to the use of the ‘questions only’
format of the UK criteria, which uses one major criterion
plus two or more minor criteria and eliminates the photo-
graphical protocol. This format showed increased sensi-
tivity and decreased specificity in a paediatric population
under 11 years of age.28 The original authors of the UK
critieria also suggested that in communities with lower
prevalence of atopic dermatitis, this modified version may
exhibit a reduced specificity due to increased prevalence
of pruritus of other aetiologies.28
Of concern, there was a paucity of official medical diag-
noses among participants who were positive by the study’s
various criteria. There are several potential reasons for
this, including limited care- seeking, and limitations in
reaching a medical diagnosis. Rhinitis was most likely to
be diagnosed, possibly due to it being a condition expe-
rienced later in life and frequently for more years than
asthma and atopic dermatitis. Asthma was more commonly
medically diagnosed than atopic dermatitis, likely due in
part to a higher proportion of severe disease. Rasul et al
found that within Bangladesh, higher educational attain-
ment and socioeconomic status, shorter distance from
the household to the health centre, and fewer household
members with a chronic disease were associated with
seeking care for a chronic non- communicable disease,
such as asthma, from a qualified provider.43 They also
found a high burden of out- of- pocket medical expendi-
tures, mostly related to pharmaceutical treatments. This
supports our findings that those from the highest wealth
quintiles were more likely to have received a diagnosis
of their condition. We also speculate that there may be
limitations in the capabilities of medical practitioner to
identify atopic diseases and distinguish them from other
common conditions, for example, differentiating scabies
from atopic dermatitis. Taken together, it is clear that
there is an important opportunity to increase affordable
medical interventions, both in identification and diag-
nosis of cases as well as in prevention and treatment.
Limitations
Cross- sectional studies have well- known limitations
inherent to their design. Recording the disease preva-
lence across age groups is not as informative as recording
the natural history of a disease especially in such a rapidly
LMIC such as Bangladesh where the living conditions
and health systems experienced by age groups through
their respective lifetimes are substantially different. While
cross- sectional data do provide insight into the burden
of disease of various age groups, a prospective cohort
study would more easily allow us to draw conclusions
about risk factors and the relationships among the three
atopic diseases. There is a lack, however, of longitudinal
data from LMICs on prevalence of atopic diseases. Addi-
tionally, while households were chosen at random from
a subset of zones within the DSS, there was an imbalance
of wealth quintiles among all participants, suggesting
that there was some imbalance in the study subset. We
are missing asset data from 50 households—33 migrated
out of the DSS area and 17 were not home during the
DSS assessment. Poorer households may have been more
likely to migrate out of the area for work or more likely
to have all adults engaged in the workforce such that they
would not be available during DSS activities.
7
PedersenCJ, etal. BMJ Open 2020;10:e042380. doi:10.1136/bmjopen-2020-042380
Open access
CONCLUSION
Research is beginning to suggest differences in the pattern
and etiologies of atopic diseases between HICs and LMICs.
As LMICs experience increasing prevalence of these
conditions, research should continue to re- evaluate the
associations among atopic diseases previously established
by data from HICs in both paediatric and adult popula-
tions. Additionally, given the high disease burden in early
childhood and substantial proportion that persists into
adulthood, there is great opportunity to increase educa-
tional outreach to both healthcare providers and patients
and their families about the medical importance of these
conditions and options for management. Lastly, it is
imperative that policies are formulated to allow increased
access to affordable medical interventions for diagnosis,
treatment and prevention for all age groups.
Twitter Gary L Darmstadt @gdarmsta
Contributors CP and GLD conceptualised and designed the study, interpreted
the data, drafted the initial manuscript and reviewed and revised the manuscript.
CP also designed the data collection instruments, participated in oversight of data
collection and conducted the analysis of the data. MJU and SKS participated in
designing the study and the data collection instruments, supervised data collection
and reviewed and revised the manuscript. All authors approved the nal manuscript
as submitted and agreed to be accountable for all aspects of the work.
Funding CP received a Medical Scholars award from the Stanford University
School of Medicine, and a Benjamin H Kean Travel Fellowship from the American
Society of Tropical Medicine and Hygiene. REDCap platform services are made
possible by the Stanford University School of Medicine Research Ofce. The
REDCap platform services at Stanford are subsidised by the National Center for
Research Resources and the National Center for Advancing Translational Sciences,
National Institutes of Health (NIH).
Disclaimer The data content is solely the responsibility of the authors and does
not necessarily represent the ofcial views of the NIH.
Competing interests None declared.
Patient and public involvement Patients and/or the public were not involved in
the design, or conduct, or reporting, or dissemination plans of this research.
Patient consent for publication Not required.
Ethics approval Ethical approval was obtained from the Institutional Review
Boards at both the Stanford University School of Medicine (protocol #41405) and
the Bangladesh Institute of Child Health in Dhaka.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement Data are available on reasonable request to the
senior author through a data sharing agreement.
Open access This is an open access article distributed in accordance with the
Creative Commons Attribution Non Commercial (CC BY- NC 4.0) license, which
permits others to distribute, remix, adapt, build upon this work non- commercially,
and license their derivative works on different terms, provided the original work is
properly cited, appropriate credit is given, any changes made indicated, and the use
is non- commercial. See:http:// creativecommons. org/ licenses/ by- nc/ 4. 0/.
ORCID iD
Gary LDarmstadt http:// orcid. org/ 0000- 0002- 7522- 5824
REFERENCES
1 Bantz SK, Zhu Z, Zheng T. The atopic March: progression from
atopic dermatitis to allergic rhinitis and asthma. J Clin Cell Immunol
2014;5:202.
2 Global Asthma Network. The global asthma report 2019. Auckland,
New Zealand, 2018.
3 Hay RJ, Johns NE, Williams HC, etal. The global burden of skin
disease in 2010: an analysis of the prevalence and impact of skin
conditions. J Invest Dermatol 2014;134:1527–34.
4 Odhiambo JA, Williams HC, Clayton TO, etal. Global variations in
prevalence of eczema symptoms in children from Isaac phase three.
J Allergy Clin Immunol 2009;124:e23:1251–8.
5 Asher MI, Montefort S, Björkstén B, etal. Worldwide time trends in
the prevalence of symptoms of asthma, allergic rhinoconjunctivitis,
and eczema in childhood: Isaac phases one and three repeat
multicountry cross- sectional surveys. Lancet 2006;368:733–43.
6 Aït- Khaled N, Pearce N, Anderson HR, etal. Global map of the
prevalence of symptoms of rhinoconjunctivitis in children: the
International study of asthma and allergies in childhood (Isaac) phase
three. Allergy 2009;64:123–48.
7 Williams H, Stewart A, von Mutius E, etal. Is eczema really on the
increase worldwide? J Allergy Clin Immunol 2008;121:e15:947–54.
8 Hill DA, Spergel JM. The atopic March: critical evidence and clinical
relevance. Ann Allergy Asthma Immunol 2018;120:131–7.
9 Weinmayr G, Weiland SK, Björkstén B, etal. Atopic sensitization and
the International variation of asthma symptom prevalence in children.
Am J Respir Crit Care Med 2007;176:565–74.
10 Solis Soto MT, Patiño A, Nowak D, etal. Prevalence of asthma,
rhinitis and eczema symptoms in rural and urban school- aged
children from Oropeza Province - Bolivia: a cross- sectional study.
BMC Pulm Med 2014;14:40.
11 Flohr C, Weiland SK, Weinmayr G, etal. The role of atopic
sensitization in exural eczema: ndings from the International
study of asthma and allergies in childhood phase two. J Allergy Clin
Immunol 2008;121:141–7.
12 Lule SA, Mpairwe H, Nampijja M, etal. Life- Course of atopy and
allergy- related disease events in tropical sub- Saharan Africa: a birth
cohort study. Pediatr Allergy Immunol 2017;28:377–83.
13 Wills- Karp M, Santeliz J, Karp CL. The germless theory of allergic
disease: revisiting the hygiene hypothesis. Nat Rev Immunol
2001;1:69–75.
14 Beasley R, Semprini A, Mitchell EA. Risk factors for asthma: is
prevention possible? Lancet 2015;386:1075–85.
15 Strachan DP, Aït- Khaled N, Foliaki S, etal. Siblings, asthma,
rhinoconjunctivitis and eczema: a worldwide perspective from the
International study of asthma and allergies in childhood. Clin Exp
Allergy 2015;45:126–36.
16 Flohr C, Quinnell RJ, Britton J. Do helminth parasites protect against
atopy and allergic disease? Clin Exp Allergy 2009;39:20–32.
17 Leonardi- Bee J, Pritchard D, Britton J. Asthma and current intestinal
parasite infection: systematic review and meta- analysis. Am J Respir
Crit Care Med 2006;174:514–23.
18 Ellwood P, Asher MI, Beasley R, etal. ISAAC phase three manual.
Auckland, 2000.
19 Williams HC, Burney PG, Hay RJ, etal. The U.K. Working
Party's diagnostic criteria for atopic dermatitis. I. derivation of a
minimum set of discriminators for atopic dermatitis. Br J Dermatol
1994;131:383–96.
20 Williams HC, Burney PG, Strachan D, etal. The U.K. Working Party's
diagnostic criteria for atopic dermatitis. II. Observer variation of
clinical diagnosis and signs of atopic dermatitis. Br J Dermatol
1994;131:397–405.
21 Williams HC, Burney PG, Pembroke AC, etal. The U.K. Working
Party's diagnostic criteria for atopic dermatitis. III. independent
Hospital validation. Br J Dermatol 1994;131:406–16.
22 Hanin JM, Rajka G. Diagnostic features of atopic dermatitis. Acta
Derm Venereol 1980;92:44–7.
23 Chalmers DA, Todd G, Saxe N, etal. Validation of the U.K. Working
Party diagnostic criteria for atopic eczema in a Xhosa- speaking
African population. Br J Dermatol 2007;156:111–6.
24 Haileamlak A, Lewis SA, Britton J, etal. Validation of the International
study of asthma and allergies in children (Isaac) and U.K. criteria for
atopic eczema in Ethiopian children. Br J Dermatol 2005;152:735–41.
25 De D, Kanwar AJ, Handa S. Comparative efcacy of Hanin and
Rajka's criteria and the UK Working Party's diagnostic criteria in
diagnosis of atopic dermatitis in a hospital setting in North India. J
Eur Acad Dermatol Venereol 2006;20:853–9.
26 Fleming S, Bodner C, Devereux G, etal. An application of the United
Kingdom Working Party diagnostic criteria for atopic dermatitis in
Scottish infants. J Invest Dermatol 2001;117:1526–30.
27 Popescu CM, Popescu R, Williams H, etal. Community validation
of the United Kingdom diagnostic criteria for atopic dermatitis in
Romanian schoolchildren. Br J Dermatol 1998;138:436–42.
28 Williams HC, Burney PG, Pembroke AC, etal. Validation of the U.K.
diagnostic criteria for atopic dermatitis in a population setting. U.K.
diagnostic criteria for atopic dermatitis Working Party. Br J Dermatol
1996;135:12–17.
29 Williams HC. So how do I dene atopic eczema? A pratical training
manual for research wishing to dene atopic eczema. UK: University
of Nottingham, 1996.
8PedersenCJ, etal. BMJ Open 2020;10:e042380. doi:10.1136/bmjopen-2020-042380
Open access
30 Harris PA, Taylor R, Thielke R, etal. Research electronic data capture
(REDCap)--a metadata- driven methodology and workow process
for providing translational research informatics support. J Biomed
Inform 2009;42:377–81.
31 Saif- Ur- Rahman KM, Anwar I, Hasan M, etal. Use of indices to
measure socio- economic status (Ses) in South- Asian urban health
studies: a scoping review. Syst Rev 2018;7:196.
32 Illi S, von Mutius E, Lau S, etal. The natural course of atopic
dermatitis from birth to age 7 years and the association with asthma.
J Allergy Clin Immunol 2004;113:925–31.
33 Halkjaer LB, Loland L, Buchvald FF, etal. Development of atopic
dermatitis during the rst 3 years of life: the Copenhagen prospective
study on asthma in childhood cohort study in high- risk children. Arch
Dermatol 2006;142:561–6.
34 Resiliac J, Grayson MH. Epidemiology of infections and development
of asthma. Immunol Allergy Clin North Am 2019;39:297–307.
35 Mims JW. Epidemiology of allergic rhinitis. Int Forum Allergy Rhinol
2014;4 Suppl 2:S18–20.
36 Pinart M, Benet M, Annesi- Maesano I, etal. Comorbidity of eczema,
rhinitis, and asthma in IgE- sensitised and non- IgE- sensitised children
in MeDALL: a population- based cohort study. Lancet Respir Med
2014;2:131–40.
37 Ballardini N, Kull I, Lind T, etal. Development and comorbidity of
eczema, asthma and rhinitis to age 12: data from the BAMSE birth
cohort. Allergy 2012;67:537–44.
38 Khan DA. Allergic rhinitis and asthma: epidemiology and common
pathophysiology. Allergy Asthma Proc 2014;35:357–61.
39 Kabir ML, Rahman F, Hassan MQ, etal. Asthma, atopic eczema and
allergic rhino- conjunctivitis in school children. Mymensingh Med J
2005;14:41–5.
40 Nozawa Y, Hawlader MDH, Ferdous F, etal. Effects of intrauterine
growth restriction and postnatal nutrition on pediatric asthma in
Bangladesh. J Dev Orig Health Dis 2019;10:627–35.
41 Takeuchi H, Khan AF, Hasan MI, etal. Comment on IgE responses to
Ascaris and mite tropomyosins are risk factors for asthma. Clin Exp
Allergy 2016;46:178–80.
42 Singh S, Sharma BB, Salvi S, etal. Allergic rhinitis,
rhinoconjunctivitis, and eczema: prevalence and associated factors
in children. Clin Respir J 2018;12:547–56.
43 Rasul FB, Kalmus O, Sarker M, etal. Determinants of health seeking
behavior for chronic non- communicable diseases and related out- of-
pocket expenditure: results from a cross- sectional survey in northern
Bangladesh. J Health Popul Nutr 2019;38:48.