Throat Bacteria May Predict Childhood Asthma

COPENHAGEN, Oct. 10 -- If bacteria colonize the throat of a one-month-old infant, the risk of later persistent wheezing and asthma is sharply increased, researchers here found.

The increase was associated with colonization of the hypopharynx by one or more of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis, according to Hans Bisgaard, M.D., D.M.Sc., of the Danish Pediatric Asthma Center at the Copenhagen University Hospital.

The finding offers a "predictive marker" that may help further research on the development and treatment of childhood asthma, Dr. Bisgaard and colleagues concluded in the Oct. 11 issue of the New England Journal of Medicine.

Dr. Bisgaard said it is not yet clear whether the presence of the bacteria cause the wheezing and asthma or are simply a result of some other process -- such as a weakened immune system -- that also causes later breathing disorders.

The finding emerged in the Copenhagen Prospective Study on Asthma in Childhood (COPSAC) -- a prospective, longitudinal birth-cohort study -- that enrolled 321 newborns whose mothers had current or previous asthma.

Researchers took samples from the children at one month and 12 months, and they were then followed for five years for the development of wheezing. Asthma was diagnosed at age five on the basis of Global Initiative for Asthma guidelines.

At one month, 66 of the infants (21%) were colonized with one or more of the three bacterial species, the researcher found.

The study found that bacterial colonization was associated with:

• Persistent wheeze. The hazard ratio was 2.40, with a 95% confidence interval from 1.45 to 3.99.
• Acute severe exacerbation of wheeze. The hazard ratio was 2.99, with a 95% confidence interval from 1.66 to 5.39.
• Hospitalization for wheeze. The hazard ratio was 3.85, with a 95% confidence interval from 1.90 to 7.79.
• Asthma at age five. The hazard ratio was 4.57 with a 95% confidence interval from 2.18 to 9.57.

The prevalence of asthma at age five was 14% overall, but was 33% in colonized children and 10% in those not colonized, the researchers found.

Interestingly, the cultures taken at 12 months showed no association between colonization and later breathing disorders, Dr. Bisgaard and colleagues said.

The researchers noted that the study included high-risk infants and should be repeated in other populations.

The study "suggests that events in the first weeks of life may be of particular importance in inducing asthma," commented Erika von Mutius, M.D., of the University Children's Hospital in Munich, Germany, writing in an accompanying editorial.

Dr. von Mutius said the most likely explanation is that early bacterial colonization reflects an innate immune defect that promotes the development of asthma.

The alternative idea -- that the bacteria cause asthma to develop -- is less likely, she said, because evidence from cohort studies shows that anti-bacterial therapy at the age has little effect on the development of asthma.

"Bisgaard and colleagues may have found an interesting and new sentinel rather than a causative signal," Dr. von Mutius said.

Dr. Bisgaard reports receiving lecture and pediatric advisory board fees from Aerocrine, Altana, AstraZeneca, GlaxoSmithKline, MedImmune, Merck, and Pfizer.

Dr. von Mutius reported that she has no potential conflicts.