Descriptive Epidemiological Features of Bronchiolitis in a Population-Based Cohort Mieke Koehoorn, Catherine J. Karr, Paul A.

Demers, Cornel Lencar, Lillian Tamburic and Michael Brauer Pediatrics 2008;122;1196-1203 DOI: 10.1542/peds.2007-2231

The online version of this article, along with updated information and services, is located on the World Wide Web at: http://www.pediatrics.org/cgi/content/full/122/6/1196

PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly publication, it has been published continuously since 1948. PEDIATRICS is owned, published, and trademarked by the American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk Grove Village, Illinois, 60007. Copyright 2008 by the American Academy of Pediatrics. All rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275.

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ARTICLE

Descriptive Epidemiological Features of Bronchiolitis in a Population-Based Cohort

Mieke Koehoorn, PhDa,b, Catherine J. Karr, MD, PhDc,d, Paul A. Demers, PhDa,b, Cornel Lencar, MFa, Lillian Tamburic, BSce, Michael Brauer, ScDa
a

School of Environmental Health, bSchool of Population and Public Health, and eCentre for Health Services and Policy Research, University of British Columbia, Vancouver, Canada; Departments of cPediatrics and dEnvironmental and Occupational Health Sciences, University of Washington, Seattle, Washington

The authors have indicated they have no nancial relationships relevant to this article to disclose.

Whats Known on This Subject

In clinical populations bronchiolitis is associated with socio-demographic, clinical and environmental factors.

What This Study Adds

To our knowledge, this is the rst population-based study of bronchiolitis risk in Canada and one of few in the world. Cases included outpatient visits and hospitalizations.

ABSTRACT
OBJECTIVE. The goal was to investigate the epidemiological features of incident bron-

chiolitis by using a population-based infant cohort.

METHODS. Outpatient and inpatient health records were used to identify incident
www.pediatrics.org/cgi/doi/10.1542/ peds.2007-2231 doi:10.1542/peds.2007-2231
Key Words bronchiolitis, epidemiological features, cohort studies, population-based studies, Cox proportional-hazards models Abbreviation RSVrespiratory syncytial virus
Accepted for publication Mar 3, 2008 Address correspondence to Mieke Koehoorn, PhD, Department of Health Care and Epidemiology, University of British Columbia, 5804 Fairview Ave, Vancouver, British Columbia, Canada V6T 1Z3. E-mail: mieke. koehoorn@ubc.ca PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275). Copyright 2008 by the American Academy of Pediatrics

bronchiolitis cases among 93 058 singleton infants born in the Georgia Air Basin between 1999 and 2002. Additional health-related databases were linked to provide data on sociodemographic variables, maternal characteristics, and birth outcome measures.
RESULTS. From 1999 to 2002, bronchiolitis accounted for 12 474 incident health care

encounters (inpatient or outpatient contacts) during the rst year of life (134.2 cases per 1000 person-years). A total of 1588 hospitalized bronchiolitis cases were identied (17.1 cases per 1000 person-years). Adjusted Cox proportional-hazard analyses for both case denitions indicated an increased risk of incident bronchiolitis in the rst year of life (follow-up period: 212 months) for boys, infants of First Nations status, infants with older siblings, and infants living in neighborhoods with smaller proportions of maternal postsecondary education. The risk also was elevated for infants born to young mothers (20 years of age) or mothers who did not initiate breastfeeding in the hospital. Infants with low (1500 2400 g) or very low (1500 g) birth weight and those with congenital anomalies also had increased risk. Maternal smoking during pregnancy increased the risk of hospitalized bronchiolitis.

CONCLUSIONS. This population-based study of the epidemiological features of bronchiolitis provides evidence for inter-

vening with high-risk infants and their families. Clinical and public health interventions are recommended for the modiable risk factors of maternal breastfeeding and smoking and for modication of vulnerable environments where possible (eg, limiting exposure to other young children), during high-risk periods such as the rst few months of life or the winter season. Pediatrics 2008;122:11961203

most common cause of bronchiolitis is respiratory syncytial virus (RSV) (90% of cases in North America).2 However, a number of other respiratory viruses (such as inuenza, parainuenza, rhinovirus, human metapneumovirus, and bocavirus) also can cause bronchiolitis. Bronchiolitis is the leading cause of morbidity among infants 1 year of age in North America and Europe,1,36 and hospital admission rates have been increasing over the past 2 decades.1 Given the frequency and burden of illness, there are very few population-based, epidemiological studies of risk factors associated with bronchiolitis. A Medline search identied 1811 articles focused on bronchiolitis or bronchiolitis, viral, of which 468 were focused on infant or child. Of those, 72 were on risk factors or epidemiology of bronchiolitis. A review of the abstracts for those 72 articles identied 21 that provided epidemiological evidence of risk factors for the primary onset of bronchiolitis, as opposed to articles on clinical outcomes among children with bronchiolitis,7 diagnostic or clinical practice guidelines,8 bronchiolitis as a risk factor for other outcomes such as asthma,9 review articles,10 or editorials.11 Of the 21 articles on the epidemiological features of bronchiolitis, 11 were cross-sectional clinical studies (eg, hospitalized sample),1222 9 were case-control or case-crossover studies,2331 and only 1 was a population-based study.32 One additional clinical study was identied from study references.33 The majority of the studies investigated hospitalization or mortality outcomes for bronchiolitis, with 2 exceptions; 1 study included outpatient visits as part
1196 KOEHOORN et al

RONCHIOLITIS IS AN infection of the lower respiratory tract that usually affects infants in the rst year of life.1 The

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of a combined outcome,19 and the population-based study32 investigated RSV-positive test results via outpatient physician visits. The populations for the clinical studies ranged from 89 hospitalized infants20 to 8265 hospitalized infants16 with the exception of a national study of emergency department visits, with almost 2 million hospitalization outcomes over 10 years.22 The case-control studies ranged from 34 pairs30 to 18 595 case subjects with 10 matched control subjects.27 The population-based, 1-year, follow-up study of 1179 healthy infants identied male gender and 1 month of or no breastfeeding as risk factors for RSV infection in multivariate models adjusted for sociodemographic factors.32 It also found a protective interaction effect for breastfeeding among mothers with a lower education level. Studies of clinical populations indicate that native or aboriginal infants (eg, First Nations or Inuit)13,17 have higher rates of hospital admissions related to bronchiolitis, although this may be attributable to unmeasured socioeconomic factors rather than genetic factors. Bronchiolitis (and RSV) is also more common in male infants,13,32 infants of low birth weight or gestational age,14,15,17,18,23,25,30,33 and infants born to young mothers.18,19 It is associated with no breastfeeding or early weaning,23,25,29,32 living in crowded conditions or in the presence of older siblings14,18,30,32,33 or attending day care,14 exposure to secondhand smoke or tobacco during pregnancy,18,19,23,33 and social disadvantage.16,26,32 Casecontrol studies identied environmental exposures associated with the risk of bronchiolitis, including exposure to wood-burning in the home24 and air quality measures (2.5-m particulate matter levels).27 The purpose of this study was to conduct a large, population-based, epidemiological study of a comprehensive set of concurrent risk factors for bronchiolitis, including both hospitalizations and outpatient visits to physicians. Although bronchiolitis is common, there are limited population-based studies on the epidemiological features of this condition, and little is known about what causes infants to be susceptible to infection in the general population. METHODS Overview This was a retrospective cohort study of infants born between 1999 and 2002 in the geographic area dened as the Georgia Air Basin, British Columbia (N 119 345). The analysis excluded multiple births and births of 25 weeks of gestation (n 2606). A total of 14 488 births were excluded because of missing data on maternal age or First Nations status and 9193 births because of incomplete residential history (because this cohort was the basis for a study investigating residential air pollution exposures and risk of bronchiolitis), for a nal study population of 93 058 births. Data Sources Health data are available from the British Columbia Linked Health Database for research purposes, through an approved process34 governed by a data access agree-

ment between the researchers and the data stewards. Medical services and hospitalization data were provided and governed by the Ministry of Health, Government of British Columbia, and vital statistics data by the British Columbia Vital Statistics Agency. These data were merged, through an additional data access agreement, with records in the provincial perinatal database, governed by the British Columbia Reproductive Care Program. The research database was constructed by merging vital statistics birth records (for cohort enumeration according to residential postal codes) with outpatient medical services billing records and inpatient hospital discharge records, for identication of cases for the period of 1999 2003 (allowing a minimum of a 1-year follow-up period for all births). Birth and health records were merged with the provincial perinatal database for maternal characteristics (maternal age, infant age, breastfeeding initiation, smoking during pregnancy, and parity) and birth outcome measures (gestational age, preterm complications, and low birth weight complications). First Nations status was available from hospital discharge records for all births, with socioeconomic indicators for education and household income from Statistics Canada census data. The research database was provided to the research team with all personal identiers removed and replaced by anonymous study identiers. The identiers were unique to each infant and enabled identication of the same infants across data sources. The research protocol was approved by the University of British Columbia Behavioral Research Ethics Committee. Outcomes Infants were monitored from the second to 12th month after birth, and cases were identied from the rst health care encounter with an International Classication of Diseases, Ninth Revision, Clinical Modication diagnosis code35 of 466 (acute bronchitis and bronchiolitis) in the outpatient medical charts (general practitioner or specialist visit) or a principal diagnosis code of 466.1 (acute bronchiolitis) in the hospital discharge records. Only the rst encounter (either outpatient visit or hospitalization) for each infant was counted as the case. The outpatient medical services records allow for 1 diagnosis code, coded to the rst 3 digits only of the International Classication of Diseases, Ninth Revision, Clinical Modication coding system, which necessitated the broader inclusion criteria for this data set. A second case denition was limited to hospitalizations only, with the morespecic diagnosis code of 466.1. Only the rst hospitalization was counted as the case. These data do not include emergency department visits unless they resulted in a hospital admission. The databases are considered comprehensive for outpatient and inpatient encounters, given a universal, publicly funded, health care system. Risk Factors The analyses investigated the risk of a rst clinical encounter related to bronchiolitis associated with infant gender, maternal age (20 years, 20 29 years, or 29
PEDIATRICS Volume 122, Number 6, December 2008 1197

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2000 Hospitalizations 1500 Outpatient Visits

2000 Hospitalizations 1500 Outpatient Visits

1000
1000

500
500

0
th s 10 11
0 Jan Feb Mar Apr May June Jul Aug Sep Oct Nov Dec

M on

FIGURE 1 Frequency of bronchiolitis cases according to month of diagnosis.

FIGURE 2 Frequency of bronchiolitis cases according to age of diagnosis.

years), maternal education (in quartiles), household income (in quintiles), urban versus rural residence, maternal smoking during pregnancy, breastfeeding initiation in the hospital, First Nations status, parity (yes or no, as a proxy measure for older siblings), birth weight (normal: 2500 4000 g; low: 1500 2500 g; very low: 1500 g; high: 4000 g), gestational age (2528 weeks, 29 32 weeks, 3335 weeks, or 36 weeks), preterm complications (yes or no), and low birth weight complications (yes or no). Urban residence, based on census data, is dened as living in an area with 400 people per km2.36 Education and household income variables, also based on census data, represent the distribution of median household incomes (in quintiles) and the proportion of the population with postsecondary education (in quartiles) according to neighborhood (ie, census subdivisions). These census variables were assigned to infants on the basis of their mothers postal code of residence within a neighborhood. Analysis Follow-up monitoring was from the second to 12th month of life; the rst month of life was excluded because bronchiolitis infection is not common among infants in the rst month18 and exclusion reduces misclassication of other acute respiratory infections. The Cox proportional-hazard model37 was used to investigate the association between risk factors and an infants rst clinical encounter related to bronchiolitis. Factors associated with bronchiolitis at the bivariate level (95% condence interval for the hazard rate ratio) were entered into the nal multivariate model. Models were constructed for both case denitions of bronchiolitis, for comparison purposes. RESULTS The study cohort included 93 058 singleton births in the Georgia Air Basin between 1999 and 2002 with complete data. The cohort was 48.6% female, 1.2% of First Nations status, and 45.9% rstborn. Eighty-two percent of infants had a normal birth weight (2500 4000 g), and 89.0% were born at term (gestational age of 38 weeks). Less than 10% of infants had complications related to either preterm status (7.1%) or low birth
1198 KOEHOORN et al

weight (6.7%). Less than 1% of the study cohort had congenital anomalies. Maternal smoking during pregnancy was recorded for 9% of the birth cohort, and lack of breastfeeding initiation at the hospital was recorded for 7.5% of the cohort. The majority (57.3%) of infants were born to mothers 29 years of age. The excluded population had similar proportions of female infants (48.5%) and mothers in the lowest education quartile (25.9% vs 24.0%) and household income quintile (21.9% vs 21.6%) but a larger proportion of infants of First Nations status (2.9%). A total of 12 474 incident bronchiolitis cases (134.1 cases per 1000 person-years) were identied from outpatient and inpatient encounters among cohort infants during the rst year of life (second to 12th month). A total of 1588 bronchiolitis cases were identied from hospitalizations only (17.1 cases per 1000 person-years). The rates of bronchiolitis were higher in the excluded population (146.1 and 23.1 cases per 1000 person-years, respectively). An analysis of bronchiolitis cases according to calendar month of diagnosis (Fig 1) and age of diagnosis (Fig 2) indicated that incident cases occurred more frequently during the winter months (December through March) and in the rst months of life. The same trends were observed for bronchiolitis dened on the basis of outpatient visits as noted for hospitalizations. The distributions of risk factors between infants with and without bronchiolitis, by outpatient and inpatient case denitions, are shown in Table 1. Because of quantitative correlations or conceptual overlap between the measures of maternal education and household income (Spearmans 0.43), gestational age and birth weight (Spearmans 0.30), congenital anomalies and preterm complications (Spearmans 0.32), and low birth weight complications and preterm complications (Spearmans 0.97), only maternal education, birth weight, and congenital anomalies were entered in the nal multivariate models. In the nal regression models adjusted for covariates (Table 2), the risk of incident bronchiolitis in the rst year of life remained elevated for male infants, infants of First Nations status, infants with older siblings, and infants living in neighborhoods with smaller proportions of maternal postsecondary education (lowest quartile,

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12

M on

th s

TABLE 1 Bivariate Results for Bronchiolitis Among Infants in the Georgia Air Basin Region in 1999 2002
Variable Outpatient or Inpatient Bronchiolitis Case Denition n (%) Bronchiolitis Gender Female Male Maternal age 2029 y 29 y 20 y Maternal educationa High Medium high Medium low Low Maternal smoking during pregnancy No Yes Breastfeeding initiation at hospital Yes No First Nations status No Yes Parity (siblings) No Yes Birth weight 25004000 g 4000 g 15002500 g 1500 g Congenital anomalies No Yes Household incomeb High Medium high Medium Medium low Low Residencec Urban Small town Rural fringe Rural Gestational aged 35 wk 3335 wk 2932 wk 2528 wk Preterm complications No Yes Low birth weight complications No Yes 5150 (41.3) 7324 (58.7) 4580 (36.7) 7524 (60.3) 370 (3.0) 2531 (20.3) 3056 (24.5) 3286 (26.3) 3601 (28.9) 11 217 (89.9) 1257 (10.1) 11 267 (90.3) 1207 (9.7) 12 210 (97.9) 264 (2.1) 4560 (36.6) 7914 (63.4) 10 222 (81.9) 1666 (13.4) 489 (3.9) 97 (0.8) 12 355 (99.0) 119 (1.0) 1635 (13.1) 2246 (18.0) 2643 (21.2) 2930 (23.5) 3020 (24.2) 11 148 (89.3) 120 (1.0) 955 (7.7) 261 (2.1) 11 949 (95.8) 346 (2.8) 121 (1.0) 58 (0.5) 11 457 (91.8) 1017 (8.2) 11 504 (92.2) 970 (7.8) No Bronchiolitis 40 028 (49.7) 40 524 (50.3) 26 343 (32.7) 52 335 (65.0) 1874 (2.3) 21 051 (26.1) 20 716 (25.7) 20 092 (24.9) 18 693 (23.2) 73 432 (91.2) 7120 (8.8) 74 788 (92.8) 5764 (7.2) 79 738 (99.0) 814 (1.0) 38 162 (47.4) 42 390 (52.6) 66 380 (82.4) 11 371 (14.1) 2492 (3.1) 309 (0.4) 79 932 (99.2) 620 (0.8) 13 272 (16.5) 15 485 (19.2) 16 945 (21.0) 17 490 (21.7) 17 360 (21.6) 71 061 (88.2) 841 (1.0) 7040 (8.7) 1632 (2.0) 78 369 (97.3) 1603 (2.0) 436 (0.5) 144 (0.2) 74 995 (93.1) 5557 (6.9) 75 273 (93.4) 5279 (6.6) Unadjusted Hazard Rate Ratio (95% Condence Interval) 1.00 1.37 (1.321.42) 1.00 0.84 (0.810.87) 1.12 (1.011.25) 1.00 1.21 (1.151.28) 1.34 (1.271.41) 1.56 (1.481.64) 1.00 1.14 (1.081.21) 1.00 1.36 (1.281.44) 1.00 1.98 (1.762.24) 1.00 1.52 (1.471.58) 1.00 0.95 (0.901.01) 1.25 (1.141.37) 1.88 (1.542.29) 1.00 1.22 (1.021.46) 1.00 1.17 (1.091.24) 1.25 (1.171.33) 1.33 (1.261.42) 1.38 (1.301.47) 1.00 0.91 (0.761.09) 0.87 (0.820.93) 1.02 (0.901.15) 1.00 1.37 (1.231.53) 1.70 (1.422.04) 2.33 (1.803.01) 1.00 1.18 (1.111.26) 1.00 1.19 (1.121.27) Inpatient Bronchiolitis Case Denition n (%) Bronchiolitis 628 (39.5) 960 (60.5) 586 (36.9) 935 (58.9) 67 (4.2) 300 (18.9) 377 (23.7) 415 (26.1) 496 (31.2) 1351 (85.1) 237 (14.9) 1383 (87.1) 205 (12.9) 1516 (95.5) 72 (4.5) 474 (29.9) 1114 (70.1) 1239 (78.0) 185 (11.7) 122 (7.7) 42 (2.6) 1560 (98.2) 28 (1.8) 207 (13.0) 295 (18.6) 320 (20.2) 378 (23.8) 388 (24.4) 1374 (86.5) 21 (1.3) 155 (9.8) 38 (2.4) 1432 (90.2) 87 (5.5) 44 (2.8) 25 (1.6) 1378 (86.8) 210 (13.2) 1386 (87.3) 202 (12.7) No Bronchiolitis 44 550 (48.7) 46 888 (51.3) 30 337 (33.2) 58 924 (64.4) 2177 (2.4) 23 282 (25.5) 23 395 (25.6) 22 963 (25.1) 21 798 (23.8) 83 298 (91.1) 8140 (8.9) 84 672 (92.6) 6766 (7.4) 90 432 (98.9) 1006 (1.1) 42 248 (46.2) 49 190 (53.8) 75 363 (82.4) 12 852 (14.1) 2859 (3.1) 364 (0.4) 90 727 (99.2) 711 (0.8) 14 700 (16.1) 17 436 (19.1) 19 268 (21.1) 20 042 (21.8) 19 992 (21.9) 80 805 (88.4) 940 (1.0) 7839 (8.6) 1854 (2.0) 88 886 (97.2) 1862 (2.0) 513 (0.6) 177 (0.2) 85 074 (93.0) 6364 (7.0) 85 391 (93.4) 6047 (6.6) Unadjusted Hazard Rate Ratio (95% Condence Interval) 1.00 1.46 (1.321.62) 1.00 0.82 (0.740.91) 1.58 (1.232.04) 1.00 1.25 (1.081.46) 1.41 (1.221.64) 1.78 (1.552.06) 1.00 1.78 (1.552.04) 1.00 1.86 (1.612.16) 1.00 4.23 (3.345.35) 1.00 2.04 (1.832.04) 1.00 0.88 (0.751.02) 2.56 (2.123.08) 6.56 (4.828.92) 1.00 2.26 (1.563.29) 1.00 1.20 (1.011.44) 1.19 (1.001.41) 1.35 (1.141.60) 1.39 (1.171.64) 1.00 1.30 (0.841.99) 1.15 (0.981.36) 1.20 (0.871.66) 1.00 2.85 (2.303.54) 5.08 (3.776.86) 8.04 (5.4211.9) 1.00 2.02 (1.752.34) 1.00 2.04 (1.762.37)

Analyses were performed with Coxs proportional-hazards model. a High was dened as 44% of neighborhood residents with postsecondary education, medium high as 36% to 44%, medium low as 28% to 36%, and low as 28%; infants were assigned to categories on the basis of mothers postal codes of residence. b The distribution of median household incomes within a neighborhood according to quintile was determined; infants were assigned to categories on the basis of mothers postal codes of residence. c Categories were based on Census population density data, with urban dened as an area with 400 people per km2. d Categories were based on American Academy of Pediatrics guidelines.52

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TABLE 2 Multivariate Results for Bronchiolitis Among Infants in the Georgia Air Basin in 1999 2002
Variable Adjusted Hazard Rate Ratio (95% Condence Interval) Outpatient or Inpatient Case Denition Gender Female Male Maternal age 2029 y 29 y 20 y Maternal educationa High Medium high Medium low Low Maternal smoking during pregnancy No Yes Breastfeeding initiation at hospital Yes No First Nations status No Yes Parity (older siblings) No Yes Birth weight 25004000 g (normal) 4000 g (high) 15002500 g (low) 1500 g (very low) Congenital anomalies No Yes 1.00 1.38 (1.331.43) 1.00 0.81 (0.780.84) 1.23 (1.101.37) 1.00 1.16 (1.101.22) 1.24 (1.181.31) 1.39 (1.321.46) 1.00 1.03 (0.971.09) 1.00 1.19 (1.121.26) 1.00 1.65 (1.461.86) 1.00 1.58 (1.531.65) 1.00 0.89 (0.840.93) 1.29 (1.181.42) 1.84 (1.502.25) 1.00 1.18 (0.981.41) Inpatient Case Denition

(hazard rate ratio: 1.49; 95% condence interval: 1.27 1.72). DISCUSSION This is the rst study to evaluate the epidemiological features of bronchiolitis in Canada by using a population-based cohort, a comprehensive set of risk factors through linkage of several longitudinal and retrospective databases, and the inclusion of outpatient visits in the case denition. Our data suggested that 13.4% of singleton infants born in the Georgia Air Basin had incident bronchiolitis requiring a clinical encounter within the rst year of life and 1.7% of cases were serious enough to warrant hospitalization. This rate is lower than previously reported rates of acute hospitalized bronchiolitis for Canadian infants5,38 and for infants in other countries,16,22 although the lowest rates were reported in the province of British Columbia (2.5%).38 The previous studies were not limited to rst encounters for calculation of hospitalization rates, and others studies tended to use a broader denition of hospitalized bronchiolitis.22 The prevalence of hospitalized bronchiolitis in this study is closer to bronchiolitis rates in other studies that used a conrmed RSV lower respiratory tract infection outcome.32,38 However, 2.3% of our excluded population met the hospitalized case denition, an estimate closer to previous reports for British Columbia,38 which may indicate a conservative bias in the current ndings. Comparable population-based studies are limited, but one using physician visits as the rst point of contact32 indicated a comparable overall bronchiolitis rate of 10.4% in a study of 1179 infants. Our study used administrative health records to capture outpatient visits and hospitalizations for bronchiolitis, as well as administrative databases for infant and maternal characteristics. An assessment of the validity and reliability39 of key variables captured in the perinatal database (relative to patient charts) indicated good sensitivity and specicity for maternal smoking status (79% and 98%, respectively) and breastfeeding initiation (95% and 73%, respectively). In addition, the breastfeeding initiation rate of 92.5% in the current study parallels the population estimates for breastfeeding (of any duration) reported by women in the Canadian Community Health Survey for the province of British Columbia (93.1%) and the city of Vancouver (90.4%),40 the most densely populated area of the study region. The survey data also indicated that the majority (81.8%) of women in Vancouver who breastfeed do so for 6 months. The validity and reliability of coding for bronchiolitis have not been established for these data sources, but the consistency of ndings between the more-specic hospitalized bronchiolitis denition and the bronchiolitis denition that included outpatient visits supports the validity of using outpatient records to capture cases. In addition, bronchiolitis cases followed recognized seasonal6 and temporal41 patterns for infection for both outpatient and inpatient case denitions. Higher risk estimates for all signicant variables for hospitalized bronchiolitis may indicate greater specicity for more-severe inpa-

1.00 1.49 (1.341.64) 1.00 0.78 (0.700.87) 1.65 (1.272.15) 1.00 1.20 (1.031.40) 1.23 (1.051.42) 1.44 (1.241.66) 1.00 1.47 (1.271.69) 1.00 1.33 (1.141.54) 1.00 2.94 (2.313.75) 1.00 2.24 (2.012.51) 1.00 0.80 (0.680.93) 2.64 (2.193.18) 6.19 (4.538.48) 1.00 2.16 (1.493.14)

Analyses were performed with Coxs proportional-hazards model. a High was dened as 44% of neighborhood residents with postsecondary education, medium high as 36% to 44%, medium low as 28% to 36%, and low as 28%; infants were assigned to categories on the basis of mothers postal codes of residence.

compared with highest quartile). The risk was also elevated for infants born to young mothers (20 years versus 20 29 years of age) and mothers who did not initiate breastfeeding in the hospital. Infants with a low (1500 2400 g) or very low (1500 g) birth weight and those born with a congenital anomaly also had an increased risk of bronchiolitis. The hazard rate ratios for all of the preceding risk factors were higher in the model of hospitalized bronchiolitis cases, compared with the combined inpatient and hospitalized denition, with an approximately twofold increased risk observed for infants with older siblings and a congenital anomaly, a threefold increased risk associated with First Nations status, and a sixfold increased risk associated with very low birth weight (1500 g, compared with 2500 4000 g). An elevated risk of bronchiolitis associated with maternal smoking during pregnancy remained signicantly elevated in the model for hospitalized bronchiolitis only
1200 KOEHOORN et al

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tient cases and some misclassication of respiratory illness by using the outpatient administrative data records. However, we conclude from our results that outpatient visits provide a reasonable measure of bronchiolitis in the general population and that estimates based on only clinical populations and hospitalized cases may underestimate the incidence and burden of disease in the general population (13.4%, compared with 1.7%, in the current study), even with a degree of misclassication with the 3-digit diagnostic code of 466 in the present study. We did not have conrmation of RSV infection among bronchiolitis cases. Therefore, our case denition represents the multitude of viral causes. We were interested in the outcome of bronchiolitis in general, as a public health burden, and not risk factors for a specic etiologic agent. Our data conrm previous ndings, based on smaller clinical populations, that the risk of bronchiolitis is seasonal and is associated with male gender, younger maternal age, lower maternal socioeconomic status, low birth weight, parity (as a surrogate measure for older siblings in the home), no breastfeeding initiation at the hospital, and First Nations status. Maternal smoking during pregnancy and congenital anomalies also were associated with increased risk of bronchiolitis, but only for cases severe enough to result in hospitalization. An increased risk of bronchiolitis for First Nations infants is consistent with previous ndings of higher hospitalization rates for bronchiolitis among Native American and Alaskan infants13,16 and among Inuit infants.17 It is not clear, on the basis of previous studies, whether this increased risk is attributable to cultural differences (ie, differences in breastfeeding patterns), reduced access to health care in remote areas,42 or environmental exposures such as indoor air pollution (wood smoke).24 However, an independent effect for First Nations status was found in the current study after adjustment for breastfeeding and socioeconomic factors, in an area with a universal health care system. The observed increased risk may still be attributable to residual confounding or unmeasured covariates, including respiratory system or immune system susceptibility. Infants with compromised physiological features,43 as indicated by the presence of congenital anomalies, had an increased risk of hospitalized bronchiolitis in the current study. It is important to note that our study variable identied only individuals with First Nations status (registered with the Canadian government for services and benets) and underrepresented individuals who identied themselves as native or aboriginal persons. According to 2001 statistics, 1.9% of the population in the greater Vancouver region is aboriginal (including North American Indian, Me tis, and Inuit persons), compared with 1.2% with First Nations status for those 1 year of age in the study cohort, and the proportion of aboriginal persons 4 years of age is probably greater, given a younger age distribution than in the overall population.44 Indeed, we observed a larger proportion of infants of First Nations status (and a higher rate of bronchiolitis) in the excluded

population, which indicates that hazard rate ratios may be underestimated in the current study. We observed an elevated risk for younger gestational age in the bivariate regression analyses and for the correlated variable of birth weight in the multivariate analyses. Younger infants, including premature infants, are thought to be susceptible to viral infections as a result of missing the transplacental transfer of antibodies.4547 Our nding of a protective effect for mothers who reported breastfeeding initiation is consistent with the importance of the transfer of maternal antibodies to infants for reducing the risk of infection.45,48 Lower birth weight and young gestational age also may indicate a relatively immature immune or respiratory system, increasing susceptibility to infection.4,33 Maternal characteristics of younger age and lower socioeconomic status were identied previously but may be explained by reduced access to health care services,42 or lower rates of breastfeeding and smoking status49 among disadvantaged mothers. The current study identied an independent effect of younger maternal age after adjustment for breastfeeding initiation and an independent effect of socioeconomic status (education level) after adjustment for smoking status during pregnancy, among a cohort of mothers and infants with universal access to health care services. Although the independent effect of maternal age may be attributable to other, unmeasured, socioeconomic factors, it also may suggest a biological mechanism related to maternal nutrition, health status, or stress that alters the development of the respiratory system of the fetus. The independent effect of socioeconomic status may be a surrogate measure for important environmental exposures for infant respiratory outcomes27 worthy of further investigation, including both outdoor (eg, living near major highways, with increased exposure to poor air quality) and indoor (eg, wood smoke) air quality exposures. Measures of socioeconomic status (education level) were aggregate, neighborhood-level variables based on Census data and residence. This may result in some misclassication but is considered to be nondifferential in the current study and probably an issue of a 1-category difference, rather than misclassication from the lowest quartile to the highest quartile. The nding that exposure to maternal smoking was associated with the risk of hospitalized bronchiolitis is in agreement with previous studies33 and specically ndings for more-severe infections.18,50 Maternal and paternal environmental tobacco smoke has been linked to reduced lung function and increased airway responsiveness, which may predispose infants to more-severe infections.51 Although it is likely that a large proportion of mothers who smoke during pregnancy continue to do so after birth, we had only a measure of maternal smoking during pregnancy. Although this is a potential limitation, our nding is consistent with a previous study linking maternal smoking during pregnancy with severe bronchiolitis outcomes (death)18 and provides evidence that smoking during pregnancy is itself associated with bronchiolitis. We also found that a higher birth order (or parity) among infants was associated with bronchiolitis in the
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rst year of life. Higher birth order is likely associated with having older siblings and/or sharing a room with siblings, which increases the likelihood of viral infection transmission. These specic factors were identied previously as risks for bronchiolitis and other respiratory tract infections6,33 and have some public health relevance for reducing risks associated with crowding during peak periods, especially in public facilities such as day care centers. One of the main strengths of our study is the large sample that is representative of the population of British Columbia. Unlike most other studies, we investigated the epidemiological features of bronchiolitis by using a population-based sample and a wide range of variables concurrently. The comprehensive risk prole provides direction for recommendations to reduce the incidence and burden of bronchiolitis in the general population. From a public health perspective, interventions are warranted to increase breastfeeding initiation and to reduce maternal smoking (especially for reducing the numbers of more-severe, hospitalized cases). Clinicians can support parents to alter these modiable risk factors, especially for high-risk infants (such as those born with low birth weight or born to young mothers) and during periods of higher risk (such as the rst few months after birth and the winter season). In addition, public health practitioners and clinicians need to be aware of the entire environment of the infant and to advise families on making changes that might reduce the risk or severity (hospitalization) of bronchiolitis, such as limiting exposure to other young children or outdoor/indoor air pollution for at-risk infants during high-risk periods. ACKNOWLEDGMENTS Dr Koehoorn was supported in part by the Michael Smith Foundation for Health Research Scholar Award. The research was supported in part by Health Canada via an agreement with the British Columbia Centre for Disease Control to the Border Air Quality Study, and by the Center for Health and Environment Research (CHER) at the University of British Columbia. CHER is funded by the Michael Smith Foundation for Health Research. The linked research database was provided by the Centre for Health Services and Policy Research, University of British Columbia via the British Columbia Linked Health Database. Medical services and hospitalization data were provided by the Ministry of Health, Government of British Columbia; Vital Statistics data by the British Columbia Vital Statistics Agency; and perinatal data by the British Columbia Reproductive Care Program. REFERENCES
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PEDIATRICS Volume 122, Number 6, December 2008

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Descriptive Epidemiological Features of Bronchiolitis in a Population-Based Cohort Mieke Koehoorn, Catherine J. Karr, Paul A. Demers, Cornel Lencar, Lillian Tamburic and Michael Brauer Pediatrics 2008;122;1196-1203 DOI: 10.1542/peds.2007-2231
Updated Information & Services References including high-resolution figures, can be found at: http://www.pediatrics.org/cgi/content/full/122/6/1196 This article cites 45 articles, 14 of which you can access for free at: http://www.pediatrics.org/cgi/content/full/122/6/1196#BIBL This article has been cited by 1 HighWire-hosted articles: http://www.pediatrics.org/cgi/content/full/122/6/1196#otherartic les This article, along with others on similar topics, appears in the following collection(s): Infectious Disease & Immunity http://www.pediatrics.org/cgi/collection/infectious_disease Information about reproducing this article in parts (figures, tables) or in its entirety can be found online at: http://www.pediatrics.org/misc/Permissions.shtml Information about ordering reprints can be found online: http://www.pediatrics.org/misc/reprints.shtml

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