The severity-dependent relationship of infant bronchiolitis on the risk and morbidity of early childhood asthma

Article Outline

• Abstract
• Methods
  • Study design and population
  • Predictor variables
  • Outcome variables
  • Statistical analysis
• Results
• Discussion
• Acknowledgment
• Table E1. 
• References
• Copyright

Background

Infants hospitalized for bronchiolitis have a high rate of early childhood asthma. It is not known whether bronchiolitis severity correlates with the risk of early childhood asthma or with asthma-specific morbidity.

Objectives

We sought to determine whether a dose-response relationship exists between severity of infant bronchiolitis and both the odds of early childhood asthma and asthma-specific morbidity.

Methods

We conducted a population-based retrospective birth cohort study of term healthy infants born from 1995-2000 and enrolled in a statewide Medicaid program. We defined bronchiolitis severity by categorizing infants into mutually exclusive groups based on the most advanced level of health care for bronchiolitis. Health care visits, asthma-specific medications, and demographics were identified entirely from Medicaid and linked vital records files. Asthma was ascertained at between 4 and 5.5 years of age, and 1-year asthma morbidity (hospitalization, emergency department visit, or oral corticosteroid course) was determined between 4.5 and 5.5 years among children with prevalent asthma.

Results

Among 90,341 children, 18% had an infant bronchiolitis visit, and these infants contributed to 31% of early childhood asthma diagnoses. Relative to children with no infant bronchiolitis visit, the adjusted odds ratios for asthma were 1.86 (95% CI, 1.74-1.99), 2.41 (95% CI, 2.21-2.62), and 2.82 (95% CI, 2.61-3.03) in the outpatient, emergency department, and hospitalization groups, respectively. Children hospitalized with bronchiolitis during infancy had increased early childhood asthma morbidity compared with that seen in children with no bronchiolitis visit.

Conclusion

To our knowledge, this is the first study to demonstrate the dose-response relationship between the severity of infant bronchiolitis and the increased odds of both early childhood asthma and asthma-specific morbidity.

Key words: Bronchiolitis, asthma

Abbreviations used: ED, Emergency department, EGA, Estimated gestational age, ICD-9, International Classification of Diseases, Ninth Revision, OR, Odds ratio, RSV, Respiratory syncytial virus, TABS, Tennessee Asthma Bronchiolitis Study

Asthma is one of the most common chronic conditions of childhood and accounts for significant morbidity.¹ The cause and morbidity of asthma are thought to be due to a number of modifiable and nonmodifiable factors, including family history, genetic predisposition, and environmental exposures, such as viral infections.², ³, ⁴ Viral bronchiolitis results in significant morbidity, affecting 20% of infants annually.⁵, ⁶ Furthermore, up to 3% of healthy infants in the United States are hospitalized for bronchiolitis, resulting in an estimated 120,000 hospitalizations annually, and bronchiolitis rates are increasing.⁷ Not only is morbidity high related to the infant bronchiolitis episode, but also a high rate of asthma within the first decade of life has been observed after severe bronchiolitis during infancy.⁸, ⁹, ¹⁰ Although observational studies have reported that more than 30% of infants hospitalized with bronchiolitis subsequently have asthma, the relationship between the infant bronchiolitis episode and later asthma is not completely understood because the majority of infants with bronchiolitis do not have asthma.¹¹

Several seminal observational studies have tracked childhood asthma outcomes among children with a history of a bronchiolitis hospitalization during infancy and a nonhospitalized comparison group.⁸, ⁹, ¹¹, ¹², ¹³, ¹⁴, ¹⁵, ¹⁶, ¹⁷ However, asthma outcomes for outpatient infant bronchiolitis-related events in the nonhospitalized groups were not reported, and thus the relationship between infant bronchiolitis severity and subsequent risk or morbidity of asthma is not known from these investigations. A limited number of prospective birth cohorts, including 2 with children at high risk for asthma, have also contributed to our understanding of asthma risk among children with a history of bronchiolitis or wheezing lower respiratory tract illness in the first years of life.⁶, ¹⁰, ¹⁸, ¹⁹, ²⁰, ²¹ However, the wheezing illnesses identified within these cohorts were primarily outpatient events, and the risk and morbidity of asthma associated with infant bronchiolitis requiring emergency department (ED) visits or hospitalizations were both infrequent and not reported. Therefore despite several longitudinal investigations focused on the role of viral infections in asthma inception, it is not known whether there is a severity-dependent relationship between the severity of infant bronchiolitis and both the risk and morbidity of early childhood asthma. Nor is it known, at a population-based level, what proportion of children with asthma had clinically significant bronchiolitis as infants or whether a familial predisposition to asthma modifies the risk of asthma after infant bronchiolitis.

To answer these questions, we used our population-based retrospective birth cohort of more than 90,000 term, non–low birth weight, otherwise healthy children in the Tennessee Asthma Bronchiolitis Study (TABS) constructed from health care visits, asthma-specific medications, and demographics identified from Medicaid claims, pharmacy data, and linked vital records files. We hypothesized that the severity of clinically significant bronchiolitis, including both outpatient and inpatient health care, would be positively correlated with both an increased odds of early childhood asthma and increased asthma-specific morbidity among children with prevalent disease. Lastly, in a subset of mother-infant dyads in whom maternal history could be determined, we investigated how maternal asthma modified the association between bronchiolitis and early childhood asthma inception.

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Methods 

Study design and population 

To estimate the association of bronchiolitis during infancy with the development of early childhood asthma, we conducted a population-based retrospective birth cohort study of more than 90,000 term, non–low birth weight infants enrolled in TennCare within the first month of life (1995-2000, the TABS). Only children born between 1995 and 2000 were included because all children were followed to 5.5 years by using the years for which data were available. In 1994, TennCare replaced the federal Medicaid program as a state-based managed health care program that covered Medicaid-eligible individuals and the uninsured.²² TennCare provides health insurance for approximately 50% of infants born in Tennessee. Data were obtained from linked TennCare administrative data files and Tennessee State vital records files using previously described methods at our study institution.²³, ²⁴ Analysis files contained no personal identifiers, and study results are reported in aggregate and cannot be linked to individuals. The protocol was approved by the Institutional Review Board of Vanderbilt University and reviewed and approved by representatives of the Tennessee Department of Health and the Bureau of TennCare.

Eligible children were continuously enrolled in TennCare during the first year of life, during which health care visits for bronchiolitis were captured, and between 3.5 and 5.5 years of age, during which early childhood asthma was defined. Continuous enrollment was considered no more than 21 days of nonenrollment during the first 12 months of life and no more than 60 days of nonenrollment between 3.5 and 5.5 years of life. This investigation included only term (estimated gestational age [EGA], >37 weeks), non–low birth weight (>2500 g), and otherwise healthy infants to investigate the association of bronchiolitis during infancy and subsequent asthma without the potential confounding of low birth weight or chronic disease. We determined EGA in weeks by date of last menstrual period on the birth certificate (87%) or imputed it based on median gestational period in weeks for the infant's race, birth weight, and birth year (13%).²⁵ We excluded infants with any of the following before 3.5 years of age (4.6%): Current Procedural Terminology code indicating surgery for congenital heart disease, receipt of respiratory syncytial virus (RSV) immunoprophylaxis, or International Classification of Diseases, Ninth Revision (ICD-9), code indicating congenital heart disease, chronic lung disease (bronchopulmonary dysplasia), congenital anomaly of the upper airway, upper alimentary tract atresia or stenosis, neurologic disorder, immunodeficiency, cystic fibrosis, diabetes mellitus, renal disease, or cancer.

Predictor variables 

We identified health care visits for bronchiolitis during the first 12 months of life using ICD-9 codes for bronchiolitis (466.1), RSV-induced pneumonia (480.1), or both. ICD-9 diagnoses of bronchiolitis in infants have been validated by using models to correlate with RSV circulation.²⁶ Clinically significant bronchiolitis was defined as a health care visit for bronchiolitis. Bronchiolitis severity was defined by categorizing children into mutually exclusive groups based on their most advanced level of health care (hospitalization, 23-hour observation, ED visit, or clinic visit with ICD-9 codes for bronchiolitis). Hospitalizations and 23-hour observations were combined into the hospitalization group. Infants without any bronchiolitis visits were categorized into the no-visit group.

Other demographic and baseline characteristics were determined from birth certificate data and TennCare files. Infant race/ethnicity (mutually exclusive categories of white, black, Hispanic, or other/unknown) and region of residence (urban, suburban, or rural) were identified from TennCare enrollment files. Demographic variables determined from birth certificate data included birth weight, sex, siblings (none, 1, or ≥2 based on report of number of prior live births), maternal age at delivery, maternal education level, quantified maternal smoking during pregnancy, and marital status.

We used maternal asthma, one measure of familial predisposition to asthma, to evaluate whether maternal asthma modified the association between bronchiolitis during infancy and subsequent asthma development. Maternal asthma was ascertained in the nested subgroup of mother-infant dyads who met the following criteria: infants were term and otherwise healthy, and mothers were continuously enrolled in TennCare from 180 days before pregnancy through delivery. Maternal continuous enrollment included no more than 45 days of nonenrollment from 180 days before pregnancy through delivery. Maternal asthma was similarly determined by using health care encounter file claims, pharmacy file claims, or both using a previously validated method of identifying individuals with asthma.²⁵

Outcome variables 

The main outcome was diagnosis of early childhood asthma between 4 and 5.5 years of age among the population-based cohort of 90,341 children. We used a 1.5-year ascertainment period to capture children with milder disease who might seek treatment only as needed or during well-child visits. We studied asthma diagnoses after 4 years to exclude “transient early wheezers” who wheeze with viral infections during the first years of life.⁴ Early childhood asthma was determined by using health care encounter file claims, pharmacy file claims, or both with similar algorithms used for both epidemiology and outcomes research.²⁷, ²⁸ Children with an ICD-9 diagnosis code of 493 (asthma) in any of the discharge diagnosis fields for inpatient, other hospital care (23-hour observation), or ED visit or 2 outpatient physician visit claims were considered to have asthma. In addition, children with 2 prescriptions for any short-acting β-agonist within a 12-month period or a prescription for other asthma medications (including inhaled corticosteroids and long-acting β-agonists) were considered to have early childhood asthma.

We also assessed the relationship between bronchiolitis severity during infancy and 1-year asthma morbidity among children with prevalent disease by 4.5 years of age. For this analysis, we required children to meet the definition of asthma between 3.5 and 4.5 years of age and have a full year of follow-up from 4.5 to 5.5 years of age during which the morbidity of their asthma was determined. One-year asthma morbidity was defined between ages 4.5 and 5.5 years as an asthma hospitalization, ED visit, and/or course of systemic corticosteroids among children with prevalent asthma diagnosed between 3.5 and 4.5 years of age.

Statistical analysis 

The main predictor variable for each analysis was severity of bronchiolitis during infancy defined by the type of bronchiolitis health care visit. The main outcome variables were as follows: (1) early childhood asthma ascertained between 4 and 5.5 years of age for analysis of the relationship between infant bronchiolitis severity and asthma diagnosis and (2) 1-year asthma morbidity ascertained between 4.5 and 5.5 years of age in children with prevalent disease between 3.5 and 4.5 years of age for analysis of the relationship of infant bronchiolitis severity with early childhood asthma morbidity. We compared the proportion of children with asthma by using the predictor variables with χ² statistics. Multivariable logistic regression models were used to measure the relative adjusted odds of asthma during early childhood associated with infant bronchiolitis severity.²⁹ The statistical models were adjusted for birth weight, sex, infant race/ethnicity, maternal smoking during pregnancy, maternal education level, region of residence, and other living siblings. We also determined the risk of early childhood asthma in children with a history of no infant bronchiolitis visits or 1 or 2 or more bronchiolitis episodes. Distinct bronchiolitis episodes were new ICD-9 diagnoses separated by at least 4 weeks. A multivariable logistic regression model was also applied to assess the joint effect of maternal asthma and bronchiolitis severity on the odds of early childhood asthma by including a cross-product in the model. In stratified analyses we determined whether a history of maternal asthma or other baseline and demographic characteristics modified the relationship between bronchiolitis and early childhood asthma. Lastly, we assessed the adjusted relative odds of 1-year asthma morbidity between 4.5 and 5.5 years of age in the subset of children given diagnoses of asthma between 3.5 and 4.5 years of age. Analyses were conducted with SAS version 9.1 (SAS Institute, Inc, Cary, NC) and R version 2.6.1 software.

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Results 

A total of 90,341 term healthy children were included in the cohort. Forty-nine percent of the children were girls; the children were white (56%), black (39%), and Hispanic (2%; Table I). The median EGA was 40 weeks, and the median birth weight was 3289 g. Overall, 26% of children had mothers who smoked during pregnancy. Eighteen percent of children had at least 1 health care visit for bronchiolitis during infancy, and children were classified into the following groups: no visit (82%), outpatient (9%), ED (4%), or hospitalization (5%). In total, 11% were given diagnoses of asthma between 4 and 5.5 years of age. The 18% of children with clinically significant bronchiolitis during infancy accounted for 31% of children with early childhood asthma.

Table I. Infant and maternal characteristics by infant bronchiolitis severity among children enrolled in Tennessee Medicaid, 1995-2000

Characteristic	All (n = 90,341)		No visit for bronchiolitis (n = 73,940)		Bronchiolitis clinic visit (n = 7,858)		Bronchiolitis ED visit (n = 3,825)		Bronchiolitis hospitalization (n = 4,718)
Birth weight (g), median (IQR)	3,289 (3,005-3,600)		3,289 (3,005-3,600)		3,289 (3,005-3,629)		3,260 (2,977-3,572)		3,260 (2,977-3,572)
EGA (wk), median (IQR)	40 (39-40)		40 (39-40]		39 (39-40)		39 (39-40)		39 (39-40)
Maternal age∗ (y), median (IQR) (n = 90,170)	22 (19-26)		22 (19-26)		22 (19-25)		21 (19-25)		21 (19-25)
	n	Percent	n	Percent	n	Percent	n	Percent	n	Percent
Infant sex
Male	46,329	51	36,845	50	4,519	58	2,241	59	2,724	58
Female	44,012	49	37,098	50	3,339	42	1,584	41	1,994	42
Infant race
White	50,269	56	39,938	54	5,270	67	1,790	47	3,271	69
Black	34,919	39	29,696	40	2,214	28	1,839	48	1,170	25
Hispanic	2,041	2	1,779	2	121	2	60	2	81	2
Other/unknown	3,112	3	2,527	3	253	3	136	4	196	4
Maternal education (n = 90,174)
<12 y	39,597	44	31,939	43	3,357	43	1,882	49	2,329	49
12 y	39,832	44	32,752	44	3,537	45	1,595	42	1,948	41
>12 y	10,835	12	9,100	12	953	12	345	9	437	9
Maternal asthma† (n = 51,669)
No	47,842	93	38,879	93	4,095	91	2,275	90	2,593	89
Yes	3,827	7	2,860	7	386	9	253	10	328	11
Maternal age (y) (n = 90,170)
15-19	26,782	30	21,993	30	2,213	28	1,184	31	1,392	30
20-29	51,773	57	41,905	57	4,712	60	2,269	59	2,887	61
30-44	10,929	12	9,323	13	869	11	335	9	402	9
Maternal smoking‡ (n = 90,106)
Nonsmoker	66,492	74	55,308	75	5,433	69	2,741	72	3,010	64
Smoker	23,614	26	18,436	25	2,403	31	1,078	28	1,697	36
No. of siblings (n = 90,268)
0	37,028	41	30,839	42	3,113	40	1,420	37	1,656	35
1	27,969	31	22,448	30	2,663	34	1,211	32	1,647	35
≥2	25,271	28	20,592	28	2,072	26	1,193	31	1,414	30
Region of residence (n = 90,267)
Urban	39,204	43	33,013	45	2,601	33	2,249	59	1,341	28
Suburban	20,720	23	16,838	23	2,136	27	713	19	1,033	22
Rural	30,343	34	24,025	33	3,115	40	863	23	2,340	50

IQR, Interquartile range.

The proportions of children with early childhood asthma by severity of infant bronchiolitis were as follows: no visit (9%), outpatient (16%), ED (19%), and hospitalization (22%; P < .001; Table II). Relative to children without a bronchiolitis visit during infancy (the no-visit group), the odds ratios (ORs) for asthma between 4 and 5.5 years of age were 1.86 (95% CI, 1.74-1.99), 2.41 (95% CI, 2.21-2.62), and 2.82 (95% CI, 2.61-3.03) in the outpatient, ED, and hospitalization groups, respectively, adjusted for birth weight, sex, race, maternal smoking during pregnancy, maternal age at delivery, maternal education level, region of residence, and other living siblings at birth. Overall, 15% of children had a single bronchiolitis episode during infancy, and 3% had 2 or more episodes. Compared with children with no ICD-9 diagnosis of bronchiolitis during infancy, the adjusted ORs for early childhood asthma were 2.01 (95% CI, 1.91-2.12) and 3.33 (95% CI, 3.09-3.66) for those with 1 and 2 or more bronchiolitis episodes, respectively.

Table II. Relative odds of asthma-specific morbidity event∗ by infant bronchiolitis severity among children enrolled in Tennessee Medicaid, 1995-2005, and diagnosed with asthma between 3.5 and 4.5 years (n = 7,607)

From the cohort of 90,341 children, a nested subset of 51,669 who had mothers with available history and who met the continuous enrollment criteria were studied to investigate the odds of early childhood asthma with bronchiolitis during infancy in models stratified by maternal asthma. Seven percent (3,827/51,669) of mothers met the definition for asthma. When adjusted for having a mother with asthma, the relationship between bronchiolitis severity during infancy and early childhood asthma was similar when comparing the entire cohort to the children with maternal asthma identified from the nested subset (Fig 1). There was no statistically significant interaction by maternal asthma on the relationship between bronchiolitis severity during infancy and early childhood asthma (P = .29).

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• Fig 1. 

  ORs and proportions of early childhood asthma by bronchiolitis severity during infancy among children enrolled in Tennessee Medicaid, 1995-2000, and among children with maternal asthma identified from the subset with mothers continuously enrolled in Tennessee Medicaid.

Although the risk of early childhood asthma was higher in children with a history of maternal asthma, the patterns of early childhood asthma risk associated with the severity of bronchiolitis during infancy were similar in the children with and without maternal asthma. Among children whose mothers had asthma, the adjusted ORs for asthma between 4 and 5.5 years of age were 1.85 (95% CI, 1.43-2.38), 2.46 (95% CI, 1.84-3.29), and 2.25 (95% CI, 1.73-2.94) in the outpatient, ED, and hospitalization groups, respectively. Similarly, among children whose mothers did not have asthma, the analogous ORs were 1.84 (95% CI, 1.68-2.02), 2.53 (95% CI, 2.26-2.83), and 2.86 (95% CI, 2.58-3.16) in the outpatient, ED, and hospitalization groups, respectively. Because of the combined effects of the independent variables of maternal asthma and bronchiolitis during infancy, the relative odds of early childhood asthma increased with severity of infant bronchiolitis and were greatest in those with a history of maternal asthma. Among children with both a maternal history of asthma and an infant hospitalization for bronchiolitis, the odds of early childhood asthma were 4.18 times those of children without either risk factor (data not shown).

In stratified analyses, we also evaluated whether the severity of bronchiolitis during infancy and early childhood asthma varied by other demographic and baseline characteristics (see Table E1 in this article's Online Repository at www.jacionline.org). In general, the same dose-response relationship with bronchiolitis severity was seen for all characteristics assessed. In particular, increased odds of childhood asthma were observed for children who at birth had a mother who did not smoke during pregnancy, had 1 or more siblings, were black, or lived in an urban region of the state compared with their respective counterparts.

Next we investigated the association between the severity of bronchiolitis during infancy and early childhood asthma morbidity. Among the 7,607 cohort children meeting our definition of asthma between 3.5 and 4.5 years of age, 1,455 (19%) met the criteria for an asthma-specific morbidity event, as defined by at least 1 asthma hospitalization, ED visit, or prescription filled for oral corticosteroids during the follow-up year from 4.5 to 5.5 years of age. We characterized these 7,607 children according to their infant bronchiolitis histories and determined the odds of having an asthma-specific morbidity event between 4.5 and 5.5 years of age as 18%, 17%, 22%, and 24% in the no-visit, outpatient, ED, and hospitalization groups, respectively (P < .001, Table II). Compared with the no-visit group, the adjusted ORs of having an asthma-specific event were 0.95 (95% CI, 0.80-1.14) in the outpatient, 1.12 (95% CI, 0.91-1.38) in the ED, and 1.51 (95% CI, 1.26-1.80) in the hospitalization groups.

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Discussion 

Although the association of viral lower respiratory tract infection during infancy and subsequent childhood wheezing is well established, this study addresses important gaps in our knowledge regarding the relationship of bronchiolitis severity on early childhood asthma risk and asthma morbidity. To our knowledge, this is the first study to demonstrate the dose-response relationship between the severity of infant bronchiolitis and the increased odds of both early childhood asthma and increased asthma-specific morbidity, as well as establishing that the phenotype of asthma after infant bronchiolitis in a population-based sample of low-risk infants accounts for nearly one third of early childhood asthma.

We also investigated whether a familial predisposition to asthma, as measured by having a mother with asthma, modified the association between infant bronchiolitis and early childhood asthma. As expected, a greater proportion of children with a mother who had asthma had early childhood asthma compared with children whose mothers did not have asthma. There was no interaction between familial predisposition to asthma and the severity of infant bronchiolitis on the odds of early childhood asthma. The odds of asthma increased with increasing severity of infant bronchiolitis in children with and without a maternal history. However, because of the joint effects, the absolute odds of asthma in patients with infant bronchiolitis were appreciably greater in children with a maternal history of asthma.

It is not known whether children who have bronchiolitis during infancy also have an intrinsic predisposition to early childhood asthma or whether respiratory viruses that infect the infant host play a role in the development of subsequent recurrent wheezing or asthma.², ³⁰, ³¹, ³² The dose-response relationship of bronchiolitis severity on the odds of early childhood asthma demonstrated in this current study, which is not modified by a familial predisposition to asthma, could reflect either the magnitude of lung injury and impairment in lung development after infection or an alteration in host immune development. Although findings from animal models lend some credence to these hypotheses, evidence from human studies is limited and conflicting.², ³⁰, ³¹, ³², ³³, ³⁴, ³⁵ Recent experimental investigations provide possible mechanistic insight into the role of viral respiratory tract infections in the development of chronic lung inflammation and the augmentation of allergic airway inflammation.³¹, ³⁶ These effects are likely to be more pronounced in individuals who have a genetic susceptibility to asthma.³⁷ Because RSV IgE responses have been shown to positively correlate with increased frequency of subsequent recurrent wheeze, this might partly explain why bronchiolitis severity is positively associated with increased early childhood diagnosis, although this has not been replicated.³⁸ Evidence from a nonrandomized investigation of RSV immunoprophylaxis supports the hypothesis that modification of RSV severity in premature infants decreases the risk of subsequent recurrent wheezing.³⁹ Randomized longitudinal investigations aimed at modifying or preventing viral infection will ultimately clarify the association between viruses and the development of early childhood asthma, with potential implications for asthma prevention.

There are several limitations of this work. In this retrospective cohort study using existing data to categorize study variables, misclassification of the predictor variables is possible. For example, there might be infants in the no-visit group who had bronchiolitis but did not have a health care visit. This misclassification would bias results toward the null. Hospitalization for bronchiolitis has been used as a measure of severity for decades; however, it is possible that social factors and infant age influenced providers' decisions to hospitalize. Maternal asthma was the only marker of a genetic predisposition to asthma used. Therefore in the group of infants without maternal asthma, there are likely infants with an unmeasured familial predisposition to asthma.

Although bronchiolitis diagnoses were not confirmed, we used ICD-9 diagnoses, a method that captures objective physician-characterized outcomes at the time of illness, which would not be influenced by recall bias. In addition, the overall bronchiolitis incidence of 18% is consistent with that seen in previously published reports.⁵, ⁶ We defined asthma outcomes using ICD-9 diagnoses and medication use, and this might not detect asymptomatic individuals or those without diagnoses or individuals who have not sought treatment.⁴⁰ Historical and emerging data demonstrate the increased risk of recurrent wheezing or asthma after both RSV-induced bronchiolitis and non–RSV-induced bronchiolitis caused by viruses such as rhinovirus.⁸, ⁹, ¹⁰, ¹¹, ¹⁵, ¹⁷, ¹⁸, ²¹, ⁴¹ We did not capture the cause of bronchiolitis; however, in our previous studies we demonstrated that 80% of visits for bronchiolitis during infancy in the TABS cohort occurred during the winter virus season between November and April.⁴² Therefore findings from the current investigation likely reflect early childhood asthma outcomes predominately, but not exclusively, associated with RSV-induced bronchiolitis during infancy.

Although it is established that RSV-induced lower respiratory tract infection in the first years of life is associated with increased risk of recurrent wheeze or asthma at age 6 years, there are conflicting data about whether this association persists into adolescence.⁹, ¹⁰, ¹¹ However, the burden of early childhood asthma, even in the fifth and sixth years of life, is associated with substantial patient morbidity and health care use. Therefore delineating the relationship of environmental factors, such as viral bronchiolitis during infancy, with the subsequent development and morbidity of early childhood asthma is important in disease and morbidity prevention efforts.

Whether our results are generalizable to other populations is not known. We conducted our study in the Medicaid population in which approximately half of infants born in Tennessee are enrolled. It is likely that the relationship between bronchiolitis and early childhood asthma would be similar in non-Medicaid populations.

In conclusion, increased severity of infant bronchiolitis is associated with both an increased odds of early childhood asthma in a severity-dependent manner and increased asthma-specific morbidity during early childhood. The phenotype of early childhood asthma after infant bronchiolitis accounts for nearly one third of early childhood asthma.

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We thank the Tennessee Bureau of TennCare of the Department of Finance and Administration, and the Tennessee Department of Health, Office of Policy, Planning and Assessment for providing the data.

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Table E1. 

The effect of individual demographic and baseline characteristics on the relationship between infant bronchiolitis severity and early childhood asthma among children enrolled in Tennessee Medicaid, 1995-2005

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