Asthma and lower airway disease
Determinants of asthma after severe respiratory syncytial virus bronchiolitis

https://doi.org/10.1016/j.jaci.2012.02.010Get rights and content

Background

The development of asthma after respiratory syncytial virus (RSV) bronchiolitis has been demonstrated in case-control studies, although the determinants of post-RSV asthma remain undefined.

Objectives

We sought to evaluate the potential determinants of physician-diagnosed asthma after severe RSV bronchiolitis during infancy.

Methods

We enrolled 206 children during an initial episode of severe RSV bronchiolitis at 12 months of age or less in a prospective cohort study and followed these children for up to 6 years. In a subset of 81 children, we analyzed CCL5 (RANTES) mRNA expression in upper airway epithelial cells.

Results

Forty-eight percent of children had physician-diagnosed asthma before the seventh birthday. Independent determinants significantly associated with increased risk for physician-diagnosed asthma by the seventh birthday included maternal asthma (odds ratio [OR], 5.2; 95% CI, 1.7-15.9; P = .004), exposure to high levels of dog allergen (OR, 3.2; 95% CI, 1.3-7.7; P = .012), aeroallergen sensitivity at age 3 years (OR, 10.7; 95% CI, 2.1-55.0; P = .005), recurrent wheezing during the first 3 years of life (OR, 7.3; 95% CI, 1.2-43.3; P = .028), and CCL5 expression in nasal epithelia during acute RSV infection (OR, 3.8; 95% CI, 1.2-2.4; P < .001). White children (OR, 0.19; 95% CI, 0.04-0.93; P = .041) and children attending day care (OR, 0.18; 95% CI, 0.04-0.84; P = .029) had a decreased risk of physician-diagnosed asthma.

Conclusions

Approximately 50% of children who experience severe RSV bronchiolitis have a subsequent asthma diagnosis. The presence of increased CCL5 levels in nasal epithelia at the time of bronchiolitis or the development of allergic sensitization by age 3 years are associated with increased likelihood of subsequent asthma.

Section snippets

Study population

From 1998 to 2001, we enrolled 206 infants 12 months of age or less in the RSV Bronchiolitis in Early Life (RBEL) prospective cohort study. Selection of the study population and characteristics of the cohort at study entry are described in detail elsewhere.17 Included infants were required to have bronchiolitis severe enough to require emergency department care or hospitalization, a positive nasopharyngeal swab result confirming infection with RSV, and physician-documented wheezing during the

Results

Of 206 children enrolled in the RBEL cohort, 201 (98%) had at least 1 follow-up contact during the study period. Fig 1 and the Results section in this article’s Online Repository at www.jacionline.org show recruitment and retention over the course of the study. One hundred fifty-nine (77%) subjects provided data between ages 3 and 6 years. Children who did not provide data between ages 3 and 6 years did not differ from those with data in terms of age, sex, race, bronchiolitis severity, smoke

Discussion

We have demonstrated that severe RSV bronchiolitis in the first year of life is followed by a diagnosis of childhood asthma by the seventh birthday in nearly half of children. Factors assessed around the time of bronchiolitis that were associated with increased risk of physician-diagnosed asthma in our cohort included maternal asthma, exposure to high levels of dog allergen, and increased upper airway expression of CCL5, whereas white race and longer birth length decreased the risk. The

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    Supported by National Institutes of Health grant HL 61895.

    Disclosure of potential conflict of interest: L. B. Bacharier is on the advisory board for AstraZeneca, has received honoraria from GlaxoSmithKline, and is on the advisory board and has received honoraria from Merck. M. Castro is a consultant and speaker for Asthmatx; is on the advisory board and is a speaker for Genentech; is a speaker for AstraZeneca, Merck, and GlaxoSmithKline; has received research support from Asthmatx, Amgen, Ception/Cephalon, Genentech, MedImmune, Merck, the National Institutes of Health, Novartis, and GlaxoSmithKline; and has received royalties from Elsevier. The rest of the authors declare that they have no relevant conflicts of interest.

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