Neonatal bronchial hyperresponsiveness precedes acute severe viral bronchiolitis in infants

J Allergy Clin Immunol. 2012 Aug;130(2):354-61.e3. doi: 10.1016/j.jaci.2012.04.045. Epub 2012 Jun 17.

Abstract

Background: Respiratory syncytial virus and other respiratory tract viruses lead to common colds in most infants, whereas a minority develop acute severe bronchiolitis often requiring hospitalization. We hypothesized that such an excessive response to respiratory tract viral infection is caused by host factors reflected in pre-existing increased bronchial responsiveness.

Objective: We sought to compare bronchial responsiveness and lung function in 1-month-old neonates who later develop acute severe bronchiolitis with those who do not.

Methods: We measured infant lung function (n=402) and bronchial responsiveness to methacholine (n=363) using the raised-volume rapid thoracoabdominal compression technique before any respiratory symptoms in 1-month-old neonates from the Copenhagen Prospective Study of Asthma in Childhood birth cohort born to mothers with asthma. The children were prospectively monitored for respiratory symptoms and given a diagnosis of acute severe bronchiolitis according to a fixed algorithm.

Results: Thirty-four (8.5%) infants had acute severe bronchiolitis before 2 years of age, 21 (62%) were hospitalized, and 23 (67%) of the cases were associated with respiratory syncytial virus. Children who later had acute severe bronchiolitis irrespective of viral species had a 2.5-fold increased responsiveness to methacholine (provocative dose of methacholine producing a 15% decrease in transcutaneous oxygen pressure [PD(15)]) at age 1 month compared with control subjects (median PD(15) in cases vs control subjects, 0.13 vs 0.33 μmol; P=.01), whereas differences in baseline airflow were not significant for forced expiratory volume at 0.5 seconds (mean z score for cases vs control subjects, -0.18 vs -0.01; P=.36) and forced expiratory flow at 50% of forced vital capacity (mean z score for cases vs control subjects, -0.37 vs -0.09; P=.13).

Conclusion: Bronchial hyperresponsiveness in at-risk neonates precedes acute severe bronchiolitis in response to infections with respiratory tract virus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Bronchial Hyperreactivity / complications
  • Bronchial Hyperreactivity / immunology*
  • Bronchial Hyperreactivity / virology
  • Bronchial Provocation Tests
  • Bronchiolitis, Viral / complications
  • Bronchiolitis, Viral / immunology*
  • Bronchiolitis, Viral / virology
  • Child, Preschool
  • Female
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Methacholine Chloride / immunology
  • Prospective Studies
  • Respiratory Function Tests
  • Respiratory Syncytial Virus Infections / complications
  • Respiratory Syncytial Virus Infections / immunology*
  • Respiratory Syncytial Virus Infections / virology
  • Respiratory Syncytial Viruses / immunology
  • Severity of Illness Index
  • Time Factors

Substances

  • Methacholine Chloride