Persistent recurring wheezing in the fifth year of life after laboratory-confirmed, medically attended respiratory syncytial virus infection in infancy

Abstract

BackgroundRespiratory syncytial virus (RSV) infection in infancy is associated with subsequent recurrent wheezing.MethodsA retrospective cohort study examined children born at ≥32 weeks gestation between 1996–2004. All children were enrolled in an integrated health care delivery system in Northern California and were followed through the fifth year of life. The primary endpoint was recurrent wheezing in the fifth year of life and its association with laboratory-confirmed, medically-attended RSV infection during the first year, prematurity, and supplemental oxygen during birth hospitalization. Other outcomes measured were recurrent wheezing quantified through outpatient visits, inpatient hospital stays, and asthma prescriptions.ResultsThe study sample included 72,602 children. The rate of recurrent wheezing in the second year was 5.6% and fell to 4.7% by the fifth year. Recurrent wheezing rates varied by risk status: the rate was 12.5% among infants with RSV hospitalization, 8% among infants 32–33 weeks gestation, and 18% in infants with bronchopulmonary dysplasia. In multivariate analyses, increasing severity of respiratory syncytial virus infection was significantly associated with recurrent wheezing in year 5; compared with children without RSV infection in infancy, children who only had an outpatient RSV encounter had an adjusted odds ratio of 1.38 (95% CI,1.03–1.85), while children with a prolonged RSV hospitalization had an adjusted odds ratio of 2.59 (95% CI, 1.49–4.50).ConclusionsLaboratory-confirmed, medically attended RSV infection, prematurity, and neonatal exposure to supplemental oxygen have independent associations with development of recurrent wheezing in the fifth year of life.

The Burden and Long-term Respiratory Morbidity Associated with Respiratory Syncytial Virus Infection in Early Childhood

“…Recurrent wheezing: ≥3 episodes of bronchial obstruction not verified by a physician1 and 3At 1 year:Asthma (mean: 11% vs. 0% ( P = 0.004)Recurrent wheezing (mean: 4% vs. 8% (NS))At 3 years:Asthma (mean: 23% vs. 1% ( P < 0.001)Recurrent wheezing (mean: 21% vs. 12% (NS))Karaman 2011 [44]TurkeyProspective study of 70 children, 40 with RSV and 30 with non-RSV bronchiolitis0–36 months oldWheezing not defined1–3Recurrent wheezing: 35% vs. 53.3% ( P = 0.064; NS)Escobar 2010 [39]USRetrospective cohort study of 71,102 children born ≥32 wGA1.7% with medically attended RSV <12 months oldRecurrent wheezing: combination of encounter events, patient diagnoses using ICD codes, and prescription patterns3Recurrent wheezing: 16.2% vs. 6.2% a Bont 2004 [35]NetherlandsProspective cohort study of 140 infants with RSV (29% born 25–36 wGA; 3% cardiac disease, 2% CLD)≤12 months oldRespiratory symptoms and wheezing episodes: parent-reported (daily log). Disease episode: presence of respiratory symptoms for ≥2 consecutive days3Wheezing: >50% decrease in first year of follow-up ( P < 0.001)Escobar 2013 [38]USRetrospective cohort study of 72,602 children born ≥32 wGA1.74% with medically attended RSV < 12 months old [0.69% hospitalized and 1.05% treated as outpatient)Recurrent wheezing: as in Escobar 2010 [39], using a combination of encounter events, patient diagnoses, and prescription patterns5Recurrent wheezing year 5: 12.5% vs. 4.6% a Recurrent wheezing year 3-5: 40.0% vs. 12.3% a Carbonell-Estrany 2015 [14]SpainMulticenter, observational, nested, case-control study of preterm (32-35 wGA) infants with RSV ( n  = 125) and controls ( n  = 362)<12 months oldRecurrent wheezing: ≥3 wheezing episodes within 12 months. Severe recurrent wheezing: recurrent wheezing associated with at least one episode of hospitalization, or ≥3 medical attendances or ≥1 courses of systemic steroids, or asthma medication for ≥3 consecutive months or 5 cumulative months in a year6At 6 years of age:Recurrent wheezing: 46.7% vs. 27.4% ( P = 0.001)Severe wheezing: 37.7% vs. 23.7% ( P = 0.010)Total wheezing: 71.4% vs. 54.4% ( P = 0.006)Zomer-Kooijer 2014...…”

Early-life respiratory infections and asthma development

“…There is direct relationship between the risk of future asthma and the severity of the initial RSV lower respiratory tract infection (LRTI), with the greatest risk of asthma following episodes that required hospitalization 7, 8 . This severity-outcome association may explain the observation that increased asthma risk persisted into early adulthood in a cohort of children hospitalized in infancy for RSV LRTI 9 ; while among children who had less severe RSV bronchiolitis, with predominantly outpatient episodes, this association diminished with age and became non-significant by the age of 13 years 10 .…”

Infection-induced wheezing in young children

“…RSV bronchiolitis is the leading cause for hospitalization during the winter months among young children in the US, and has a major role in the inception of wheezing and asthma as up to 50% of the children hospitalized for RSV bronchiolitis are diagnosed with asthma during the first 6 years of life 4 . The likelihood of recurrent wheezing or asthma following bronchiolitis is directly associated with the severity of the initial illness, as children who require hospitalization are more likely to have these long-term outcomes compared to children who experience milder cases of bronchiolitis 5, 6 . Moreover, RSV bronchiolitis requiring hospitalization remains a risk factor for asthma at least until the age of 18 years, while the risk following non-hospitalized RSV bronchiolitis may abate by the age of 13 years 2 .…”