Early Bronchiolitis, With and Without RSV, Linked to Risk for Pediatric Asthma

Bronchiolitis during the first 2 years of life, regardless of etiology and severity, was associated with at least 3 times the risk for recurrent wheezing (RW) and/or asthma in children up to 5 years old and an increased prevalence of asthma in those aged 5 and above, according to study findings published in the Journal of Infectious Diseases.

Bronchiolitis, a common cause of hospitalization in children under 2 years of age —especially in young children with respiratory syncytial virus (RSV) — is believed to be associated with pediatric asthma, although that association is not fully understood. Investigators in Spain therefore conducted a population-based, retrospective cohort study, using the Valencia Health System Integrated Database, to assess the association between RW/asthma and previous bronchiolitis (PB) in the first 2 years of life. The study also explored the effect of PB etiology (ie, nonspecific, laboratory-confirmed RSV positive, and RSV negative), severity (attended primary care [PC] or hospital admission), and age on subsequent risk of RW/asthma in children aged older than 2 years of age.  

The database included 287,497 children (mean age at bronchiolitis, 7.0 [SD 5.2] years; 52% male; 5% preterm) residing in Valencia, Spain, born from 2009 to 2015 and followed up until 2019 or prior exit from the public health system. Of those children, 79,007 had a PB episode in the first 2 years of life; 9682 of these children were hospitalized and 60% of those hospitalized had severe RSV-PB. Infants in the first 6 months of life accounted for 85.5% of hospitalized PB cases and 43% of PB cases treated in primary care.

Children with PB were divided based on PB etiology and severity into 5 cohorts: (1) severe RSV-PB (n=5813); (2) severe non-RSV-PB (n=2475); (3) severe miscellaneous-PB (n=1394); (4) primary care (PC)-PB (n=69,325); and (5) no-PB (n= 208,490).

Overall, 16% of the children (44,655) had RW/asthma between ages 2 and 4 years, with a higher percentage in the cohorts with PB (28% to 36%) vs the no-PB cohort (11%). Children with PC-PB were 3 times more likely to develop RW/asthma, compared with the no-PB cohort (odds ratio [OR], 3.02; 95% CI, 2.95-3.09). Severe RSV-PB participants had a 3.25 times greater risk of RW/asthma vs the no-PB cohort (OR, 3.25; 95% CI, 3.06-3.45). The severe miscellaneous-PB and non-RSV-PB cohorts had a greater risk (OR, 3.87; 95% CI, 3.46-4.34 and OR, 4.17; 95% CI, 3.83-4.54, respectively).

Among the 249,081 children in the database at least 5 years of age, 15,831 (6.4%) had an asthma episode after their fifth birthday: 8821 (55.7%) asthma cases were from the no-PB cohort, and 7010 (44.3%) were in the PB cohorts. Among the children with PB, the percentage of those with asthma was greater in the severe non-RSV-PB group (13%) and severe miscellaneous-PB group (15%) compared with the severe RSV-PB and PC-PB cohorts (9% and 10%, respectively). The percentage of children with asthma was 5% in the no-PB cohort.

In the preterm subgroup of 14,465 children, 23% (3264) had RW/asthma between ages 2 and 4 years. The association between PB and risk of RW/asthma and asthma after age 5 years in the preterm group had the same patterns as in the general population. For the 12,292 preterm children at least 5 years of age, 998 (8.1%) had an asthma episode after their fifth birthday

Among the limitations, most RSV tests were requested during hospitalization, which prevented specifying the etiology of bronchiolitis in PC, and some variability occurred in the tests used for detecting RSV. Also, nonhospitalized infants and those without complications other than shortened gestation and low birth may not have been recorded as preterm, and residual confounding cannot be excluded.

“Our results seem to support the hypothesis of a shared predisposition to bronchiolitis (irrespective of etiology) and RW/asthma,” stated the investigators. “However, it is the severity and high disease burden of RSV-bronchiolitis (86% of hospitalizations for bronchiolitis occur in children younger than 6 months, and 60% of hospitalized bronchiolitis in our setting are due to RSV) that should be paramount in decision-making about imminent RSV prevention strategies.”

Disclosure: This research was supported in part by a research grant from the Investigator-Initiated Studies Program of Merck Sharp & Dohme LLC. Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.