Childhood asthma after bacterial colonization of the airway in neonates

Hans Bisgaard, Mette Northman Hermansen, Frederik Buchvald, Lotte Loland, Liselotte Brydensholt Halkjaer, Klaus Bønnelykke, Martin Brasholt, Andreas Heltberg, Nadja Hawwa Vissing, Sannie Vester Thorsen, Malene Stage, Christian Bressen Pipper

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

BACKGROUND: Pathological features of the airway in young children with severe recurrent wheeze suggest an association between bacterial colonization and the initiating events of early asthma. We conducted a study to investigate a possible association between bacterial colonization of the hypopharynx in asymptomatic neonates and later development of recurrent wheeze, asthma, and allergy during the first 5 years of life.

METHODS: The subjects were children from the Copenhagen Prospective Study on Asthma in Childhood birth cohort who were born to mothers with asthma. Aspirates from the hypopharyngeal region of asymptomatic 1-month-old infants were cultured for Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Staphylococcus aureus. Wheeze was monitored prospectively on diary cards during the first 5 years of life. Blood eosinophil count and total IgE and specific IgE were measured at 4 years of age. Lung function was measured and asthma was diagnosed at 5 years of age.

RESULTS: Hypopharyngeal samples were cultured from 321 neonates at 1 month of age. Twenty-one percent of the infants were colonized with S. pneumoniae, M. catarrhalis, H. influenzae, or a combination of these organisms; colonization with one or more of these organisms, but not colonization with S. aureus, was significantly associated with persistent wheeze (hazard ratio, 2.40; 95% confidence interval [CI], 1.45 to 3.99), acute severe exacerbation of wheeze (hazard ratio, 2.99; 95% CI, 1.66 to 5.39), and hospitalization for wheeze (hazard ratio, 3.85; 95% CI, 1.90 to 7.79). Blood eosinophil counts and total IgE at 4 years of age were significantly increased in children colonized neonatally with S. pneumoniae, M. catarrhalis, H. influenzae, or a combination of these organisms, but specific IgE was not significantly affected. The prevalence of asthma and the reversibility of airway resistance after beta2-agonist administration at 5 years of age were significantly increased in the children colonized neonatally with these organisms as compared with the children without such colonization (33% vs. 10% and 23% vs. 18%, respectively).

CONCLUSIONS: Neonates colonized in the hypopharyngeal region with S. pneumoniae, H. influenzae, or M. catarrhalis, or with a combination of these organisms, are at increased risk for recurrent wheeze and asthma early in life.

Original languageEnglish
JournalThe New England Journal of Medicine
Volume357
Issue number15
Pages (from-to)1487-95
Number of pages9
ISSN0028-4793
DOIs
Publication statusPublished - 11 Oct 2007

Bibliographical note

Copyright 2007 Massachusetts Medical Society.

Keywords

  • Asthma/drug therapy
  • Bacterial Infections/complications
  • Bronchodilator Agents/therapeutic use
  • Budesonide/therapeutic use
  • Child, Preschool
  • Cohort Studies
  • Female
  • Haemophilus influenzae/isolation & purification
  • Humans
  • Hypersensitivity/microbiology
  • Hypopharynx/microbiology
  • Immunoglobulin E/blood
  • Infant
  • Infant, Newborn
  • Kaplan-Meier Estimate
  • Male
  • Moraxella catarrhalis/isolation & purification
  • Neutrophils/physiology
  • Respiratory Sounds/etiology
  • Respiratory Tract Infections/complications
  • Risk Factors
  • Staphylococcus aureus/isolation & purification
  • Streptococcus pneumoniae/isolation & purification

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