Determinants of asthma after severe respiratory syncytial virus bronchiolitis

Abstract

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.

FIG 1

Enrollment and follow-up of participants through the RBEL study. Patients were enrolled during an episode of severe RSV bronchiolitis and followed prospectively through the first 6 years of life. GE, Gastroesophageal.

FIG 2

Survival curves for time to development of the first 3 wheezing illnesses and physician's diagnosis of asthma subsequent to the index RSV bronchiolitis episode. The vertical axis represents the probability of not wheezing (for times to first, second, and third wheezing episodes) or not having physician-diagnosed asthma (blue circles). Blue triangles represent the first subsequent parent-reported wheezing episode, brown triangles represent the second subsequent parent-reported wheezing episode, green triangles represent the third subsequent parent-reported wheezing episode, and blue circles represent a physician's diagnosis of asthma.

FIG 3

ROC curves for a post-RSV Asthma Predictive Index for physician-diagnosed asthma and active asthma. A, The model for physician-diagnosed asthma, incorporating the clinically derived predictors that were significant in the univariate analyses. B, The model for physician-diagnosed asthma (red) and active asthma (blue) incorporating nasal CCL5 levels alone at enrollment.