Predictors of asthma following severe respiratory syncytial virus (RSV) bronchiolitis in early childhood

Abstract

Background: We sought to identify predictors of asthma development following severe early childhood RSV bronchiolitis. Different definitions of asthma were also compared.

Methods: This longitudinal, observational study (N = 343) followed patients (<2 years old) from a placebo-controlled trial (N = 979) of montelukast after RSV bronchiolitis to identify clinical, demographic, or biochemical predictors of asthma, atopic disorders, and chronic asthma therapy use at 6 years of age (Clinical Trials Registry Number: NCT01140048). Asthma (primary definition) was based on parental identification of wheeze at 6 AND 12 months before 6 years of age; definitions based on physician diagnosis as well as parental identification of wheeze at 6 OR 12 months (to consider seasonal effect) were also assessed. Post-hoc analyses evaluated agreement among asthma diagnosis criteria.

Results: Prevalence of asthma (primary definition by parental identification), asthma (physician diagnosis), atopic disorders, and chronic asthma therapy use (parental identification) was 6.1%, 22.4%, 36.2%, and 14.5%, respectively. Predictors for asthma (primary definition) included male gender, a relative with asthma, and RAST positive for dog dander; for physician diagnosis of asthma, high severity score for RSV bronchiolitis, high respiratory rate, and asthma diagnosis before enrollment. Predictors of atopic disorders included allergic rhinitis before enrollment, a relative with asthma, and the plasma biomarkers IL-5, IL-16, and IL-18. Predictors of chronic asthma therapy use included asthma diagnosis before enrollment and geographic region (Europe and Africa). Only 42% of patients with asthma (primary definition) also met the asthma definition by physician diagnosis and chronic asthma therapy use.

Conclusion: Among children with early RSV bronchiolitis, hereditary factors (i.e., having a relative with asthma) and RSV bronchiolitis severity were predictors of asthma and atopic disorders at 6 years of age. Of interest, there was poor agreement among the asthma definitions evaluated. Pediatr Pulmonol. 2016;51:1382-1392. © 2016 Wiley Periodicals, Inc.

Keywords: RSV bronchiolitis; asthma; asthma diagnosis; respiratory syncytial virus.

Conflict of interest statement

Conflicts of Interests

SL, HG, LN, AM, HP, BK, and TR are or were employees of Merck & Co., Inc., Kenilworth, NJ.

TH and ME report no conflicts of interest.

© 2016 Wiley Periodicals, Inc.

Figures

Figure 1

Accounting of patients included in follow up study. Study sites with ≥3 children completing the 24-week clinical trial were invited to participate in the follow-up study.

Figure 2

Odds ratios (95% CI) for pairwise comparisons of demographic factors predictive of asthma (primary definition), atopic disorders (primary definition), and use of chronic asthma therapy. An odds ratio between 0 and 1 indicates a lower incidence in the first class listed compared to the second class listed. An odds ratio of 1 indicates no difference and an odds ratio between 1 and infinity indicates a higher incidence of the first class mentioned compared to the second one.

Figure 3

Odds ratios (95% CI) for pairwise comparisons of demographic factors predictive of Asthma (Physician’s Clinical Asthma Diagnosis). An odds ratio between 0 and 1 indicates a lower incidence in the first class listed compared to the second class listed. An odds ratio of 1 indicates no difference and an odds ratio between 1 and infinity indicates a higher incidence of the first class mentioned compared to the second one.

Figure 4

Venn diagrams demonstrating weak correlation of asthma diagnoses according to different definitions of asthma. (A) Number (%) of patients with asthma according to questionnaire (primary definition), Physician’s clinical asthma diagnosis, or Use of chronic asthma therapy; (B) Number (%) of patients with asthma according to questionnaire (wheezing in last 12 months), Physician’s clinical asthma diagnosis, or Use of chronic asthma therapy. Circles are drawn to approximate scale.