Infants whose airways are colonized by one or more of three bacterial species are significantly more likely to develop asthma by 5 years of age than are other children.
Dr. Hans Bisgaard and his colleagues from the Copenhagen University Hospital found colonization with Streptococcus pneumoniae, Haemophilus influenzae, and/or Moraxella catarrhalis in 1-month-old infants also was associated with significant increases in the risk of the later development of certain asthma precursors, including persistent wheeze (hazard ratio 2.01), acute severe exacerbation of wheeze (HR 3.14), and hospitalization for wheeze (HR 3.57). Colonization by Staphylococcus aureus at 1 month of age, on the other hand, was not associated with an increased risk of asthma or its precursors, nor was colonization with any of the organisms at 12 months of age (N. Engl. J. Med. 2007;357:1487–95).
It's unlikely that this association is causal, Dr. Erika von Mutius wrote in an accompanying editorial (N. Engl. J. Med. 2007;357:1545). Instead, early colonization with those three organisms may signal a defective innate immune response, and it is that defective immune response that promotes the development of asthma.
The investigators followed 321 infants as part of the Copenhagen Prospective Study on Asthma in Childhood (COPSAC). All infants were born to mothers with current or previous asthma. Physicians aspirated samples from the asymptomatic infants' hypopharyngeal region at 1 and 12 months of age, and these samples were cultured for the presence of the four bacterial species. At 1 month, 21% of the infants were found to be colonized with S. pneumoniae, H. influenzae, and/or M. catarrhalis, and 61% were colonized with S. aureus. At 12 months, 71% were colonized with the first three organisms and only 13% were colonized with S. aureus.
Children colonized at 1 month of age who were available for testing at 5 years had a 33% (17 of 52) prevalence of asthma at that age, compared with 10% (20 of 208) in those not colonized. Total IgE was increased by 47% in colonized children; there was no significant increase in specific IgE.
Investigators adjusted the results for a number of possible confounders.
While Dr. Bisgaard and his colleagues proposed that bacterial colonization may induce neutrophilic inflammation of the airways and thereby cause asthma, Dr. von Mutius, professor of pediatrics at Munich University Children's Hospital and head of the outpatient clinic for asthma and allergy, disagreed. Colonization may indicate a defective clearance of those flora. The impaired innate immune response also might be expected to decrease a child's resistance to viruses, and studies have recognized that people with asthma are unable to limit viral infections to the upper respiratory tract.
It's possible, Dr. von Mutius wrote, that exposure to certain bacterial strains may contribute to the development of asthma by inducing inflammatory responses in a child's airway. But, if that were the case, treatment with antibiotics during the first weeks of life should protect children from developing asthma. While no clinical trial has examined this question, several population-based cohort studies have failed to find an association between early antibiotic therapies and the risk of asthma.
The study was supported by unrestricted educational grants from Pharmacia/Pfizer Inc. and AstraZeneca. Dr. Bisgaard has received lecture and advisory board fees from Aerocrine Inc., Altana Inc., AstraZeneca, GlaxoSmithKline, MedImmune Inc., Merck & Co., and Pfizer.
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