Childhood asthma after bacterial colonization of the airway in neonates

N Engl J Med. 2007 Oct 11;357(15):1487-95. doi: 10.1056/NEJMoa052632.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Asthma / drug therapy
  • Asthma / immunology
  • Asthma / microbiology*
  • Bacterial Infections / complications*
  • Bacterial Infections / immunology
  • 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


  • Bronchodilator Agents
  • Immunoglobulin E
  • Budesonide