ABSTRACT
The
timing of a child's first acute lower respiratory infection (ALRI) is
important, because the younger a child is when he or she experiences ALRI, the
greater the risk of death. Indoor exposure to particulate matter less than or
equal to 2.5 µm in diameter (PM2.5) has been associated with
increased frequency of ALRI, but little is known about how it may affect the
timing of a child's first ALRI. In this study, we aimed to estimate the
association between a child's age at first ALRI and indoor exposure to PM2.5
in a low-income community in Dhaka, Bangladesh. We followed 257 children from
birth through age 2 years to record their age at first ALRI. Between May 2009
and April 2010, we also measured indoor concentrations of PM2.5 in
children's homes. We used generalized gamma distribution models to estimate the
relative age at first ALRI associated with the mean number of hours in which PM2.5
concentrations exceeded 100 µg/m3. Each hour in which PM2.5
levels exceeded 100 µg/m3 was independently associated with a 12%
decrease (95% confidence interval: 2, 21; P = 0.021) in age at first ALRI.
Interventions to reduce indoor exposure to PM2.5 could increase the
ages at which children experience their first ALRI in this urban community.
EPIDEMIOLOGY DESCRIPTIONS
A.
Definition
Epidemiology
is the study of the frequency, distribution and determinants
of diseases and other
health
related
conditions
in human populations, and the application of this study to the promotion
of health, and to the prevention and control of health problems.
B. Major components of the definition
1. Population.
The main focus of epidemiology
is on the effect of disease on the population rather than individuals.
2. Frequency.
This shows that epidemiology
is mainly a quantitative science. Epidemiology
is concerned with the frequency (occurrence) of diseases and other health related conditions.
Frequency of diseases is measured
by morbidity and mortality rates.
3.
Health related conditions.
Epidemiology is concerned not only with
disease but also with other health related conditions
because every thing around us
and what we do also affects
our health. Health related conditions
are conditions which directly or indirectly affect or
influence health. These may be injuries,
births, health related behaviors like smoking, unemployment, poverty etc.
4.
Distribution.
Distribution refers to the geographical
distribution of diseases, the distribution
in time, and distribution by type of persons
affected.
5.
Determinants.
Determinants are factors which determine whether
or not a person will get a disease.
6.
Application of the studies to the promotion of health and to
the prevention and control of health problems.
This means the
whole aim in studying the frequency, distribution, and determinants of disease is to identify
effective disease prevention
and control strategies.
CHAPTER
I
INTRODUCTION
A.
Background
Acute
lower respiratory infection (ALRI) is the leading cause of death in Bangladeshi
children, and 30%–50% of all children under 2 years of age suffer from ALRI
each year. The greatest burden of child death in Bangladesh is among infants,
who are at increased risk of death from ALRI compared with older children. From
2002 to 2006, the estimated mortality rate among children under age 5 years in
Bangladesh was 65 per 1,000 livebirths, but 90% of the burden (61 per 1,000) occurred
among children under 12 months of age and 37% (37 per 1,000) occurred in neonates.
Forty-eight percent of all deaths among children aged more than 29 days but
less than 1 year were caused by acute respiratory infection in 2004, but only
17% of deaths were precipitated by acute respiratory infection among children
aged 1-4 years.
The
age at which a child develops ALRI has been shown to be an important
determinant of severity of ALRI and death from ALRI. In a California study,
Izurieta et al. reported that rates of hospitalization for pneumonia, which is
a marker of severity, were 2-10 times higher for infants than for children aged
1- 4 years, depending on the season. Another study from rural Indonesia
suggested that children under 4 months of age with severe pneumonia were 5.6
times more likely to die from their illness than older children. One review of
pneumonia mortality rates showed that the case fatality ratio among infants was
15-19 times higher than that among 1 to 4-year-olds. Most epidemiologic studies
on ALRI have investigated exposures associated with increased frequency of ALRI
but not the timing of the first ALRI. Efforts to identify modifiable risk
factors associated with younger age at first ALRI could lead to interventions
to reduce severity of and risk of death from ALRI.
Children
in both urban and rural Bangladeshi households are exposed to concentrations of
particulate matter inside their homes many times higher than the World Health
Organization recommended guideline of <25 μg/m3. Indoor exposure
to particulate matter has been consistently associated with increased risk of
lower respiratory infection in children. One study from urban Bangladesh showed
that infants, in particular, were at increased risk of ALRI from indoor
exposure to particulate matter less than or equal to 2.5 µm in diameter (PM2.5),
but there are no data available on how exposure to PM2.5 may affect
the timing of a child's first ALRI. Our objective in this analysis was to
estimate the association between indoor PM2.5 concentration and age
at first ALRI among children under 2 years of age in a low-income, urban cohort
in Dhaka, Bangladesh.
B.
Problem Formulation
Based on the background discussed can be
formulated as follows :
1. What
are the First Acute Lower Respiratory Infection in Low-Income?
2. What
are the greatest burden of child deaths in Bangladesh from 2002 to 2006?
3. How
to measure indoor concentrations of PM2.5 at home?
C.
Purpose
1. We
aimed to estimate the association between a child's age at first ALRI and
indoor exposure to PM2.5 in a low-income community in Dhaka,
Bangladesh.
2. To
Fulfill task of epidemiology subject.
3. Increase knowledge of Age at First Acute Lower Respiratory Infection in a Low-
Income Urban Community
CHAPTER
II
DISCUSSION
A.
Methods
Enrollment in the birth cohort
Between January 2008 and March 2009,
investigators at the International Centre for Diarrhoeal Disease Research,
Bangladesh (ICDDR,B) enrolled a cohort of newborns in Mirpur, a densely
populated, low-income community in Dhaka, to study the etiology of childhood
infections and cognitive development. The study area comprised approximately 3
km2 with a population of approximately 19,000 persons. All pregnant
women in the study area were identified through house-to-house visits, and all
women who were planning to reside there for the next 2 years were invited to
participate in the study. In exchange for participation, mothers were offered
free primary medical care for their children from the study clinic. Mothers of
all children enrolled in this birth cohort who were still participating in the
study during April 2009 were invited to participate in our study examining the
relationship between indoor air pollution and acute respiratory infection.
B.
Child Follow-Up and Surveillance for ALRI
A detailed description of the methods used for
children's enrollment and follow-up has been published elsewhere. Trained
research assistants used standard protocols to measure children's weight and
length within 72 hours of birth and at approximately 3 and 6 months of age. All
enrolled children were visited every 3–4 days by trained community health
workers for the duration of the study to identify signs and symptoms of
illness. Children were referred to the study clinic if they experienced 1 major
sign of illness (subjective fever; rapid, labored, or noisy breathing;
inability to eat or drink; convulsion; cyanosis) or 2 minor signs (cough;
rhinorrhea; sore throat; muscle or joint pain; chills; headache; irritability;
repeated vomiting) on the day of the visit. Study children lived within
approximately 2 km of the study clinic. Pediatricians at the study clinic
recorded the symptoms reported by the mother or caretaker and physically
examined the children.
An incident of ALRI was defined as an acute
respiratory illness observed by the study physician that included either cough
or difficult breathing and either age-specific tachypnea or physician-observed
chest in-drawing, per criteria proposed by the World Health Organization .
Tachypnea was defined as a measurement of ≥60 breaths/minute for children aged
<2 months, ≥50 breaths/minute for children aged 2–11 months, and ≥40
breaths/minute for children aged 12–23 months.
C.
Measurement
of Household Risk Factors and Indoor Particulate Matter Levels
All
children still participating in the birth cohort during April 2009 were
eligible to participate in our study of particulate matter exposure and
incidence of ALRI. One child was enrolled per household. Every child was
visited during May 2009, and characteristics of the household were recorded on
a structured questionnaire, as previously described. We recorded the type of
stove and fuel used in the home, indoor cigarette smoking, the number of people
residing in the house, and measures of education and household wealth.
The
yearly average concentrations of fine particulate matter in the child's
sleeping space were measured. Typically, the place where the child slept and
spent the vast majority of his or her time was also the primary living space
for the family. Details on the methods used for measurement of indoor
particulate matter concentrations in these households have been published
elsewhere. In brief, once per month from May 2009 through April 2010, a
particulate matter air monitor manufactured by the Berkeley Air Monitoring
Group (University of California, Berkeley, California) was placed on the wall
approximately 2 feet (0.6 m) above the child's sleeping space. The monitor
logged the average PM2.5 concentration in the preceding 60 seconds
once per minute for a 24-hour period, following the manufacturer's
instructions. Children who had at least 11 monthly measurements, with at least
1,300 minute readings each, were included in the analysis.
D.
Statistical
analyses
We
used descriptive statistics to characterize study children and their
households. The particulate matter monitors we used had a minimum limit of
detection of 50 μg/m3. Therefore, we used threshold metrics to
summarize PM2.5 concentration measurements from each child's
sleeping space. Specifically, we calculated the mean number of hours for which
the PM2.5 concentration exceeded 100 μg/m3 (daily hours
>100 μg/m3) over the year in which PM2.5
concentrations were measured. Although daily hours of a PM2.5 level
greater than 100 μg/m3 is not a threshold known to be associated
with illness, we chose this threshold because it represented twice the limit of
detection of the monitors and 4 times the World Health Organization guidelines
for mean daily indoor-air particulate matter concentrations (25 μg/m3).
We also calculated the mean number of hours in which PM2.5 exceeded
thresholds of 50 μg/m3 and 250 μg/m3 (5 times the limit
of detection) and the time-weighted mean of PM2.5 for sensitivity
analyses.
The
time origin for the survival analysis was birth, the time axis was the age (in
months) of the child, and events were defined as the first ALRI. Children were
censored from the analysis after their first ALRI or when they reached their
second birthday. First, we fitted Kaplan-Meier curves to graph the proportion of children who had
not yet experienced their first ALRI over time. To explore whether children's
ages at first development of ALRI differed by particulate matter exposure, we classified
children as being exposed either above the median PM2.5
concentration (>100 µg/m3 for ≥5.3 hours/day) or below the median PM2.5
concentration (>100 µg/m3 for <5.3 hours/day) and fitted
Kaplan-Meier curves for each group. We recorded the signs and symptoms children
experienced during their first ALRI.
Our
primary interest was to quantify the relative time to first ALRI associated
with PM2.5 exposure rather than the relative hazard. We therefore
used the generalized gamma distribution, which is a parametric approach that
yields relative times as the measure of association. The time axis represented
the age of the child, so the relative time measure of association in this model
was equivalent to the relative age of children at the first ALRI. An added
benefit of using the generalized gamma distribution is that the method does not
assume that the ratio of hazards remains constant over time. This model was
implemented using the streg command in Stata 10 (StataCorp LP, College Station,
Texas).
We
first estimated the association between exposures and children's ages at first
ALRI in bivariate analyses. We primarily investigated the relationship between
the number of hours in which PM2.5 levels exceeded 100 μg/m3
and first ALRI. Then, we constructed a multivariate model using hours of PM2.5
>100 μg/m3 as the exposure variable and adjusted for potential
confounders between the risk of ALRI and particulate matter exposure as
described in the meta-analysis by Dherani et al. The potential confounders we
considered included socioeconomic status, mother's education, household
crowding, malnutrition, and duration of breastfeeding. Ownership of both a
television and a cell phone was used as an indicator of household wealth. We
created a dichotomous variable for mother's education to indicate whether or
not the mother had more than an elementary school education. We used the
indicator of household wealth and mother's education as proxies for
socioeconomic status. Crowding was represented in the model by the number of persons
per square meter of household floor space. Children's mean weight-for-age z
scores observed at birth, 3 months of age, and 6 months of age and the duration
of breastfeeding (in months) were included in the model as linear variables.
Children who weighed less than 2,500 g when they were enrolled in the study
within 72 hours of birth were classified as being low birth weight.
Exposure
to indoor tobacco smoke and vaccination status were also proposed as possible
confounders of the relationship between indoor particulate matter exposure and
ALRI. Exposure to indoor cigarette smoking was not included in our multivariate
model because we considered indoor tobacco smoke to be a contributor to our
measurement of PM2.5, not a confounder. We did not include vaccination
status in the model because coverage for measles, diphtheria, and pertussis
vaccines was greater than or equal to 95% among cohort children (Rashidul
Haque, ICDDR,B, personal communication, 2011). At the time this study was
conducted, neither influenza virus nor pneumococcal vaccine was included in the
immunization schedule or available commercially in the local market.
Haemophilus influenzae type b vaccines were not included in the immunization
schedule but were commercially available in the study community for
approximately US$7 per dose (Nadira Sultana Kakoly, ICDDR,B, personal
communication, 2011). However, we did not collect information about H.
influenzae type b vaccination status from study children.
E.
Sensitivity
analyses
To explore the sensitivity of our results to
the threshold used in the analysis (mean hours of PM2.5 levels
>100 μg/m3), we conducted the same multivariate analyses using
alternative thresholds (50 μg/m3 and 250 μg/m3). In
addition, the same analysis was performed using the time-weighted average of PM2.5
concentrations.
F.
Human
subject considerations
Prior
to enrollment and data collection, mothers provided separate informed consent
for their children's participation in the birth cohort and in the substudy on
indoor exposure to particulate matter. The study protocol was reviewed and
approved by institutional review boards at the ICDDR,B (Dhaka, Bangladesh); the
University of Virginia (Charlottesville, Virginia); Johns Hopkins University
(Baltimore, Maryland); and the US Centers for Disease Control and Prevention
(Atlanta, Georgia).
CHAPTER
III
RESULT AND DISCUSSION
A.
Result
A
total of 265 children were enrolled in the birth cohort through April 2009.
Three children had left the study by April, so 262 children were eligible for
the air-quality monitoring study and were enrolled. Complete baseline
information and PM2.5 measurements were available for 257 (98%) of
the 262 children enrolled in the air monitoring study, and these children were
included in the analysis (Table 1). Cohort children were between the ages
of 1 week and 16 months (median, 9 months) when the air-quality monitoring
began. Children were breastfed for a median of 30 months, and 36% had low birth
weight (i.e., <2,500 g). The study children lived in crowded conditions,
with a median of 1.8 m2 of floor space per person. Six percent of the
children's families burned only biomass (including wood, bamboo, and paper) for
cooking, but 52% occasionally burned biomass when their natural gas or
electricity supply was interrupted. The median time-weighted average PM2.5
concentration in the children's sleeping spaces was 127 μg/m3
(interquartile range, 88–194). PM2.5 concentrations were over 100
μg/m3 for a median of 5.3 hours per day (interquartile range,
4.0–6.9) (Table 1). Results of additional analyses showing the seasonal
distribution and primary determinants of PM2.5 concentrations in
these children's homes are reported elsewhere.
a.
Table 1.
Baseline
Characteristics of Children Enrolled in the Mirpur Birth Cohort (n = 257) and
Their Households, Dhaka, Bangladesh, 2008–2011
|
Characteristic
|
No
|
%
|
Median
|
Interquartile
Range
|
|
|
Child
or Mother
|
|||||
|
Male Sex
|
137
|
53
|
|
|
|
|
Weighed
<2,500 g within 72 hours of birth
|
93
|
36
|
|
|
|
|
Mean weight-for-age z score from birth to age 6 months b,c
|
|
|
-1,4
|
-1,9 - 0,8
|
|
|
Duration
of breastfeeding, months
|
|
|
30
|
23-35
|
|
|
Experienced
ALRI during the first 2 years of life
|
169
|
66
|
|
|
|
|
Age
at first ALRI, months
|
|
|
8
|
3
to >24
|
|
|
Highest
level of formal education completed by mother
|
|
|
|
|
|
|
No formal education
|
92
|
36
|
|
|
|
|
Elementary school
|
92
|
36
|
|
|
|
|
Middle school
|
69
|
27
|
|
|
|
|
High school
|
4
|
2
|
|
|
|
|
Household
|
|||||
|
No.
of household members
|
|
|
5
|
4-6
|
|
|
Living
space floor area, m2
|
|
|
9.6
|
7.8 – 11.3
|
|
|
No.
of people per m2 of floor space
|
|
|
1.8
|
1.4 – 2.4
|
|
|
No.
of external windows and doors in the home
|
|
|
2
|
1 - 3
|
|
|
Ownership
of a cell phone
|
173
|
67
|
|
|
|
|
Ownership
of a television
|
160
|
62
|
|
|
|
|
Cookstove
located inside the home
|
84
|
33
|
|
|
|
|
Type of cooking
fuel used in the home
|
|||||
|
Only clean-burning fuels
|
107
|
42
|
|
|
|
|
Only biomass fuels
|
16
|
6
|
|
|
|
|
Primarily clean fuels but sometimes
biomass
|
134
|
52
|
|
|
|
|
Usually
burning kerosene in the home for any purpose
|
119
|
46
|
|
|
|
|
Tobacco
smoking inside the home
|
72
|
28
|
|
|
|
|
No.
of particulate matter measurements per household
|
|
|
12
|
11 - 12
|
|
|
Daily
duration of PM2.5 concentrations >100 µg/m3, hours
|
|
|
5.3
|
4.0 – 6.9
|
|
|
Time-weighted
mean PM2.5 concentration, µg/m3 b
|
|
|
127
|
88 - 194
|
|
Abbreviations: ALRI, acute lower
respiratory infection; PM2.5, particulate matter less than or equal
to 2.5 µm in diameter.
a . 25th–75th percentiles.
b . The mean value was calculated for
each individual; the median value for the entire cohort
is presented.
c.
Normal range for z scores.
Of
the 257 children, 169 (66%) experienced their first ALRI before 2 years of age.
Ten percent of the children experienced an ALRI by 1.7 months of age, 25% by
3.3 months of age, and 50% by 8.5 months of age (Figure 1). Ninety-three
percent (157/169) of the children had physician-observed tachypnea during their
first ALRI, and 52% (88/169) had chest in-drawing (Table 2). No
hospitalizations or deaths from ALRI were observed among cohort study children.
a.
Table 2.
Signs and Symptoms
Experienced by Children in the Mirpur Birth Cohort During Their First Acute
Lower Respiratory Infection (n = 169), Dhaka, Bangladesh, 2008–2011
|
Sign
or Symptom
|
No
|
%
|
|
Total
|
169
|
100
|
|
Mother-reported
:
|
||
|
Cough
|
168
|
99
|
|
Fever
|
157
|
93
|
|
Difficulty breathing
|
97
|
57
|
|
Reluctance/inability to eat
|
50
|
30
|
|
Physician-observed
:
|
||
|
Tachypneaa
|
157
|
93
|
|
Crepitations
|
124
|
73
|
|
Chest in-drawing
|
88
|
52
|
a Defined by age: ≥60
breaths/minute for children aged <2 months, ≥50 breaths/minute for children
aged 2–11 months, and ≥40 breaths/minute for children aged 12–23 months.
b.
Figure
1
Proportion of children who
had not yet experienced an acute lower respiratory infection (ALRI) through 2
years of age in the Mirpur Birth Cohort (n = 257), Dhaka, Bangladesh,
2008–2011.
Children
exposed to PM2.5 concentrations above 100 µg/m3 for 5.3
or more hours per day (the median value) experienced their first ALRI at a
median of 3.8 months of age. For children exposed to concentrations above 100
µg/m3 for less than 5.3 hours per day, the median age at first ALRI was 8.5
months (Figure 2). In bivariate analyses, each 1-hour increase in the
number of hours for which mean PM2.5 concentrations exceeded 100
µg/m3 was associated with a 13% decrease in children's age at first ALRI (95%
confidence interval (95% CI): 4, 21; P = 0.005) (Table 3). Children who
lived in households with both a television and a cell phone were 60% older (95%
CI: 5, 142; P = 0.028) when they first experienced ALRI than children whose
families did not have these assets. In multivariate analysis, each hour that PM2.5
concentrations exceeded 100 µg/m3 was associated with a 12% decrease
(95% CI: 2, 21; P = 0.021) in children's age at first ALRI, after adjustment
for potential confounders. Indoor PM2.5 concentration was the only
exposure that was independently associated with children's age at first ALRI
(Table 3). Sensitivity analyses showed similar estimates of relative age
at first ALRI, regardless of the PM2.5 exposure metric used
(Tables 1–3).
A.
Discussion
of Result
Half
of all children in this study experienced their first ALRI by 8 months of age,
and each hour that PM2.5 concentrations exceeded 100 µg/m3
was associated with a 12% decrease in a child's age at first ALRI. These
results suggest that reducing indoor exposure to PM2.5 in this
low-income urban setting could increase the average age at which children
experienced their first ALRI and therefore could decrease the severity of these
infections.
A
randomized controlled trial of the introduction of improved cookstoves to
reduce indoor exposure to particulate matter in Guatemala found that the
intervention was associated with a decrease in the incidence of severe
pneumonia episodes but not in the incidence of all pneumonia. Our study
findings provide one possible explanation for the results of the Guatemala
study: The reduction in PM2.5 exposure from the intervention may
have increased the age at which children first experienced ALRI, reducing the
severity but not the incidence of all episodes. Our study findings are limited
by our measurements of PM2.5 exposure. Children were enrolled as
they were born into the community from January 2008 through April 2009, but our
measurements of particulate matter did not begin until May 2009. Therefore, our
exposure measurements did not temporally overlap with the time at which most children
experienced their first ALRI. Rather than a time-varying measure of exposure to
PM2.5 in the home, our measurements were combined into a crude,
yearly average metric of PM2.5 concentrations in children's homes.
Nevertheless, we observed a strong association between PM2.5
exposure and age at first ALRI, and since we do not suspect that our
misclassification of children's exposure was related to our measurement of age
at first ALRI, the magnitude of the true effect may be higher than what we
report. In addition, the threshold cutoff we used (100 µg/m3) was
arbitrary; however, it was preferable to time-weighted average measurements
because of the lower limit of detection of our monitors. Despite these
limitations in our measurements, they are probably more useful than other proxy
measurements of PM2.5 exposure in this community, considering that
PM2.5 concentrations were high in these households, even for homes
that used electric or natural gas cookstoves. Previous analyses suggested that
sources external to the household, such as smoke from neighbors' homes or
ambient pollution could be contributing to exposure in these homes.
We
defined ALRI according to criteria suggested by the World Health Organization,
based on clinical assessments conducted by study physicians when children
appeared at the study clinic for care. This definition is useful because it
means that our results are comparable to those of other studies in low-income
settings where these clinical criteria are most frequently used. Children in our
cohort were visited frequently in their homes to identify the onset of
respiratory symptoms and were quickly referred to free, high-quality medical
care at the nearby study clinic. This study design is a strength for measuring
age at first ALRI, but since children received care so quickly, their clinical
illnesses were probably less severe than would have occurred without this
intervention. One important indicator of disease severity is hospitalization,
but children in our cohort with relatively more severe disease may not have
received care at hospitals because they had access to free care nearby. In
addition, physicians may have been more comfortable treating children on an
outpatient basis, rather than referring them to hospitals, since they knew that
the children would be followed up closely at home after the clinic visit. Thus,
one important limitation of this study is that we were unable to investigate
severity of ALRI, particularly hospitalization, as an outcome. Some children
who were referred to the clinic may not have actually visited the study clinic;
although study staff reported that this was rare, we did not routinely collect
data on how many children's mothers did not comply with our referrals. We
provided free health care to all study children and the study clinic was near
their homes, so this probably reduced the possibility that some mothers would
comply with referrals more than others.
CHAPTER IV
CONCLUSION AND
SUGGESTION
A.
Conclusion
Our study suggests that increased
exposure to PM2.5 in this community puts children at risk for
developing ALRI at a younger age. Therefore, interventions to reduce indoor air
pollution, particularly for neonates and young infants, could be effective in
increasing the age at which children experience their first ALRI in this and
similar communities. This could, in turn, reduce the severity of first ALRI in
the age group most likely to die from these infections Our study findings are
probably generalizable to other settings where exposure to PM2.5 has
been associated with increased risk of ALRI among young children. Efforts to
reduce reliance on biomass burning may improve indoor air quality in many
households, but interventions to reduce particulate matter exposure in
households that use cleaner-burning fuels also deserve further investigation.
B.
Suggestions
The results of this study can encourage disease
prevention treatment ALRI through efforts to:
1. Conducting outreach to motivate
people in the procurement and use of environmental
facilities that meet the health requirements.
2. Encourage and foster community to
maintain health surrounding environment.
3. Improving the environment with the
existing facilities sominimizes the risk of ALRI.
FOOTNES
Abbreviations: ALRI, acute lower respiratory
infection; CI, confidence interval; ICDDR,B, International Centre for
Diarrhoeal Disease Research, Bangladesh; PM2.5, particulate matter less than or
equal to 2.5 µm in diameter.
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