Paediatrica Indonesiana

January 

VOLUME 53

NUMBER 1

Original Article

Risk factors of bronchiolitis

I Gde Doddy Kurnia Indrawan1, IB Subanada1, Rina Triasih2

Abstract
Background%URQFKLROLWLVSHDNLQFLGHQFHLVLQFKLOGUHQDJHG
months. History of atopy in parents, non-exclusive breastfeeding,
exposure to cigarette smoke, and infants living in crowded areas
may be risk factors for bronchiolitis. Gestational of age at birth is
also influences the mortality of lower respiratory tract infection.
Objective To evaluate the following conditions as possible
risk factors for bronchiolitis: history of atopy, non-exclusive
breastfeeding, preterm infants, exposure to cigarette smoke, and
SHUVRQVUHVLGLQJLQWKHKRPH
Methods $ VH[PDWFKHG FDVHFRQWURO VWXG\ ZDV FRQGXFWHG
by collecting data from medical records at Sanglah Hospital,
Denpasar. The case group subjects met the diagnostic criteria
IRUEURQFKLROLWLVDQGZHUHDJHGPRQWKV7KHFRQWUROJURXS
included patients with diagnoses unrelated to the respiratory
system. Data was analyzed using bivariate (Mc.Nemar) and
PXOWLYDULDWHPHWKRGVORJLVWLFUHJUHVVLRQZLWKFRQILGHQFH
LQWHUYDOVDQGVWDWLVWLFDOVLJQLILFDQFHYDOXHRI3
Results 7KHUH ZHUH  VXEMHFWV LQ RXU VWXG\ FRQVLVWHG RI 
VXEMHFWV LQ WKH FDVH JURXS DQG  LQ WKH FRQWURO JURXS 7KH
case and control groups were similar in baseline characteristics.
7KH SUHVHQFH RI KLVWRU\ RI DWRS\ 25  &,  WR 
3 QRQH[FOXVLYHEUHDVWIHHGLQJ25&,WR
3 H[SRVXUHWRFLJDUHWWHVPRNH25&,WR
3 DQGSHUVRQVOLYLQJLQWKHKRPH25
&,WR3ZHUHIRXQGWREHVLJQLILFDQWULVN
factors for bronchiolitis, while the preterm infants seem not
VLJQLILFDQWDVDULVNIDFWRURIEURQFKLROLWLV25&,WR
3 
Conclusion History of atopy, non-exclusive breastfeeding,
H[SRVXUHWRFLJDUHWWHVPRNHDQGSHUVRQVOLYLQJLQWKHKRPH
are found to be risk factors, while preterm infants seem not a risk
factor for bronchiolitis. [Paediatr Indones. 2013;53:21-5.]
Keywords: bronchiolitis, risk factors, children

ronchiolitis is a disease of the lower

respiratory tract characterized by bronchiole
obstruction. Bronchiolitis is a major public
health problem in the world,1 and often
RFFXUV LQ FKLOGUHQ XQGHU  \HDUV RI DJH ZLWK WKH
KLJKHVWLQFLGHQFHLQWKHFKLOGUHQDJHGPRQWKV
Some factors that have been associated with
an increased risk of bronchiolitis in children include
history of atopy, duration of breastfeeding, gestational
DJH H[SRVXUH WR FLJDUHWWH VPRNH DQG   SHUVRQV
living in the home. The influence of parental history
of asthma on the occurrence of bronchiolitis is still
controversial. Breast milk contains several elements
that may prevent disease by respiratory syncytial virus
569 DQG RWKHU PLFUREHVLQ WKH ILUVW  PRQWKV RI
life.3 Gestational age at birth also affects mortality
in children with lower respiratory tract infections.
Preterm infants have a higher risk for developing
bronchiolitis compared to full term infants. Exposure
to cigarette smoke in infants has been reported to be
a strong risk factor for acute bronchiolitis. Children
who live with relatives in a home with more than 6
children are more likely to have lower respiratory

From the Department of Child Health, Udayana University Medical

School, Sanglah Hospital, Denpasar1 and Gadjah Mada University
Medical School, Sardjito Hospital, Yogyakarta.
Reprint requests to: I Gde Doddy Kurnia Indrawan, Department of Child
Health, Udayana University Medical School, Sanglah Hospital, Jl. Pulau
1LDV'HQSDVDU%DOL7HO)D[(PDLOdoddy_kurnia90@
yahoo.com

Paediatr Indones, Vol. 53, No. 1, January 201321

I Gde Doddy Kurnia Indrawan et al: Risk factors of bronchiolitis

tract infections, including bronchiolitis, compared

to families with fewer than 6 siblings.5 In our study,
we aimed to evaluate the following conditions as risk
factors of bronchiolitis: history of atopy, non-exclusive
breastfeeding, preterm infants, exposure to cigarette
smoke, and > 6 people living in the home.

RI7KHQXPEHURIVXEMHFWVQHHGHGZDVSHU
group. Data was analyzed for each factor separately
by bivariate analysis (Mc.Nemar). Multivariate
analysis was performed using backward stepwise
logistic regression. Results are presented in the form
RI25ZLWKFRQILGHQFHLQWHUYDOVDQGDVWDWLVWLFDO
VLJQLILFDQFHYDOXHRI3

Methods
Results
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DJHG  PRQWKV ZKR ZHUH DGPLWWHG WR WKH
Department of Child Health, Udayana University
0HGLFDO 6FKRRO6DQJODK +RVSLWDO 'HQSDVDU IURP
0DUFKWR0D\'DWDZDVFROOHFWHGIURPPHGLFDO
records.
Subjects in the case group were children
diagnosed with bronchiolitis according to standard
diagnostic parameters of Sanglah Hospital, Denpasar.
Subjects in the control group were children without
primary and secondary diagnoses related to the
respiratory system, such as acute diarrhea, Dengue
fever, or febrile seizures. Patients with congenital
heart disease or Down syndrome were excluded.
We also excluded patients with incomplete data.
The first step was to identify the bronchiolitis and
non-bronchiolitis groups and match them by gender.
Next, we retrospectively obtained the history of
atopy, non-exclusive breastfeeding, gestational age,
exposure to cigarette smoke, and population density
of the home. This study was approved by the Ethics
&RPPLWWHHRI8GD\DQD8QLYHUVLW\0HGLFDO6FKRRO
Sanglah Hospital, Denpasar.
The required sample size was calculated using
matching case control, with an assumed odds ratio
(OR) of each variable (history of atopy, non-exclusive
breastfeeding, preterm infants, exposure to cigarette
smoke, and > 6 people living in the home). The
sample size was calculated with the largest OR of nonH[FOXVLYHEUHDVWIHHGLQJW\SH,HUURURIDQGSRZHU

One hundred patients fulfilled the inclusion criteria,

but four were excluded due to congenital heart
disease (3 patients) and clinical Down syndrome
 SDWLHQW 7KHUH ZHUH  VXEMHFWV LQ HDFK JURXS
the case group (bronchiolitis) and the control group
(non-bronchiolitis). None of our subjects had severe
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Baseline characteristics of subjects are shown in Table
1 and were similar between groups.
The possible risk factors of bronchiolitis using
Mc.Nemar are shown in Table 2. Univariate analysis
revealed that all variables tested were risk factors for
bronchiolitis, except gestational age (preterm infant).
Furthermore, based on multivariate analysis, the
presence of history of atopy, non-exclusive breastfeeding,
H[SRVXUHWRFLJDUHWWHVPRNHDQGSHUVRQVOLYLQJLQ
WKHKRPHZHUHULVNIDFWRUVIRUEURQFKLROLWLV25
&,  WR  3  25  &,
Table 1. Baseline characteristics of subjects
Case group
(n=48)

Characteristics

Median age (IQ), months

Nutritional status, n (%)
Undernourished
Well-nourished
Birth weight, n (%)
< 2500 g
2500-4000 g

Control group
(n=48)

(3-12)

10

(6-13)

15
33

(31)
(69)

21
27

(44)
(56)

6
42

(13)
(87)

2
46

(4)
(96)

IQ: interquartile range (25th -75th percentile)

Table 2. Univariate analysis of risk factors for bronchiolitis

Variables
History of atopy, n (%)
Non-exclusive breastfeeding, n (%)
Preterm infants, n (%)
Exposure to cigarette smoke, n (%)
RGQRNGNKXKPIKPVJGJQOGP


Case
17 (35)
32 (67)
3 (6)
32 (67)
34 (71)

22Paediatr Indones, Vol. 53, No. 1, January 2013

Control
1 (2)
16 (33)
1 (2)
17 (35)
11 (23)

OR
17.00
4.20
3.00
2.67
12.5

95% CI
3.08 to 359.90
1.66 to 12.50
0.31 to 78.99
1.26 to 6.04
3.46 to 78.30

P value
0.001
0.002
0.625
0.014
0.001

I Gde Doddy Kurnia Indrawan et al: Risk factors of bronchiolitis

Table 3. Multivariate analysis of risk factors for bronchiolitis
Variables

OR

History of atopy
Non-exclusive breastfeeding
Exposure to cigarette smoke
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34.74
4.30
3.05
7.92

 WR  3  25  &,  WR

3 DQG25&,WR
3UHVSHFWLYHO\Table 3).

Discussion
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causes of hospitalization during infancy. Respiratory
syncytial virus causes bronchiolitis and by the age
of two years most children have been infected, with
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More boys than girls are reportedly admitted with
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to 1.1, However, a cross-sectional study in Jakarta
showed a greater proportion of males than females,
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3 6 In our study, more males than females
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male incidence may be due to a relatively narrower
respiratory tract caliber in males than females.6
Breast milk has antibodies against RSV, including
LPPXQRJOREXOLQ,J*DQG,J$DVZHOODVLQWHUIHURQ
gamma (IFN-J), all of which may serve to neutralize
RSV activity.In addition, the immunoregulators and
immunomodulators contained in breast milk may
enhance maturation of the infant immune system.
Studies in children who were not breastfed have been
shown to be at a higher risk of RSV infection (OR
&,WR9 and suffer from bronchiolitis
25&,WR3  In our study,
non-exclusive breastfeeding was a risk factor of
EURQFKLROLWLV25&,WR
Prenatal exposure to cigarette smoke may affect
morphogenesis or postnatal development of the lungs
and immune system of the child. The mechanism by
which passive smoking increases respiratory symptoms
and decreases lung function in children is not known.
Parental smoking has been shown to enhance allergic
sensitization in infants and school children with a close

95% CI
3.28 to 366.93
1.42 to 13.01
1.01 to 9.20
2.61 to 24.03

P value
0.003
0.010
0.047
<0.0001

family history of atopic disease.11$Q$PHULFDQVWXG\

found that cigarette smoke extract (CSE) inhibited
RSV-induced IFN-D in plasmacytoid dendritic
cells (pDCs), as well as the release of interleukins
(IL-1E DQG ,/ DQG LQWHUIHURQJDPPDLQGXFHG
SURWHLQ  &;&/ +RZHYHU WKH SURGXFWLRQ RI
additional cytokines and chemokines such as IL-6,
TNF-D &&/ &&/ &&/ DQG &;&/ ZDV QRW
altered. Quantitative RT-PCR analysis indicated that
CSE decreased the expression of toll-like receptor
7/5DQGLQWHUIHURQUHJXODWRU\IDFWRU,5)LQ
RSV-infected pDCs. Furthermore, determination of
,5)SKRVSKRU\ODWLRQE\IORZF\WRPHWU\VKRZHGWKDW
&6(SUHYHQWHG,5)DFWLYDWLRQ7KHVHGDWDSURYLGH
evidence that cigarette smoke suppresses key pDC
functions upon viral infection by a mechanism that
LQYROYHV GRZQUHJXODWLRQ RI 7/5 H[SUHVVLRQ DQG
GHFUHDVHGDFWLYDWLRQRI,5) History of exposure
to cigarette smoke (> 1 smoker) in children increased
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13 Children with smoking mothers have been
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&,  WR   $QRWKHU VWXG\ UHSRUWHG WKH
prevalence of acute respiratory tract infections to
KDYHLQFUHDVHGIURPWRLQLQIDQWVZLWK
exposure to cigarette smoke.6 Exposure to cigarette
smoke was reported to be a risk factor for bronchiolitis
>25315DQG25&,WR
@16 In our study, exposure to cigarette smoke was
DOVRDULVNIDFWRUIRUEURQFKLROLWLV25&,
WR3 
Household sanitation is also closely related
to morbidity from infectious diseases, especially
respiratory infections. The housing environment
plays a large role in the emergence and spread of
these infections and population density in the home
has an influence on respiratory events in children
under five years of age. In a home with a very high
population density and inadequate ventilation,
there is increased moisture in the home. Children

Paediatr Indones, Vol. 53, No. 1, January 201323

I Gde Doddy Kurnia Indrawan et al: Risk factors of bronchiolitis

ZKROLYHZLWKIDPLO\PHPEHUVKDGDQLQFUHDVHG
ULVNRIKRVSLWDOL]DWLRQIRU569LQIHFWLRQ25
3 15 The risk severity of RSV infection in
children increased when living with a large number
RIIDPLO\PHPEHUV25&,WR5
$ FDVHFRQWURO VWXG\ VKRZHG WKDW WKH SRSXODWLRQ
density in the home was a risk factor for bronchiolitis
25&,WR Similarly, we found
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ULVNIDFWRURIEURQFKLROLWLV25&,WR
3
In the early months of life, preterm infants have
increased risk of hospitalization with RSV infection.
The immaturity of the humoral and cell-mediated
immune systems and inhibited lung development
before the age of 36 weeks, reduces the capacity of the
remaining lung function. However, we did not see
a significant difference in the proportion of infants
gestational ages in the case and control groups since
the overall proportion of premature infants was only
 +HQFH ZH ZHUH XQDEOH WR EHWWHU DVVHVV WKH
incidence of bronchiolitis in preterm infants.
$WRS\LVDSUHGLVSRVLQJIDFWRURIEURQFKLROLWLV
Children with a history of atopy produce less IFN-J.
Respiratory syncytial virus infection would suppress
the function of IFN-J causing the level and function
of IFN-J to decrease. In addition, children with a
history of atopy in parents lead to the development
RI7KLPPXQLW\DQGLPSDLUHGGHYHORSPHQWRI7K
LPPXQLW\ 6WURQJ 7K FHOO UHVSRQVH LQ FKLOGUHQ
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,/ DQG ,/ WKDW VWLPXODWH % O\PSKRF\WHV WR
differentiate into plasma cells which then produce IgE
producing growing severity of infection.5,19 Children
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LQFUHDVHGULVNRIDFXWHEURQFKLROLWLV&,WR
 $ KLVWRU\ RI DWRS\ ZDV D VLJQLILFDQW IDFWRU
associated with the occurrence of bronchiolitis (OR
&,WR6 Similarly, we found
that a history of atopy was a risk factor for bronchiolitis
25&,WR3 
There were several limitations in this study.
Retrieving data retrospectively from medical records
and validation of the information was sometimes
difficult to do. In addition, we did not measure the
duration of cigarette exposure, the total number of
cigarettes smoked per day, nor the spatial areas of
subjects homes.

24Paediatr Indones, Vol. 53, No. 1, January 2013

In conclusion, we find that history of atopy,

non-exclusive breastfeeding, exposure to cigarette
VPRNHDQGDSRSXODWLRQGHQVLW\RISHUVRQVLQ
the home are significant risk factors for bronchiolitis.
However, preterm birth is not a risk factor for
bronchiolitis.

Acknowledgment
We would like to extend our highest gratitude to I Gde Raka
Widiana, for assistance in methodology construction and statistical
analysis.

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Paediatr Indones, Vol. 53, No. 1, January 201325