Bisgaard H, Hermansen MN, Buchvald F, et al. N Engl J Med. 2007;357(15):1487–1495 PURPOSE OF THE 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. STUDY POPULATION. The subjects were children from the Copenhagen Prospective Study on Asthma in Childhood who were born to mothers with asthma. Samples were obtained from 321 subjects at the age of 1 month when the infants were asymptomatic. METHODS. Aspirates from the hypopharyngeal region 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. Peripheral eosinophil count, total immunoglobulin E (IgE) levels, and specific IgE levels were measured at 4 years of age. Lung function was measured and asthma was diagnosed at the age of 5. RESULTS. Overall, 21% of the infants were colonized with S pneumoniae, M catarrhalis, H influenzae, or a combination of these organisms. Colonization with ≥1 of these organisms, but not S aureus, was significantly associated with persistent wheeze, acute severe exacerbation of wheeze, and hospitalization for wheeze. Eosinophil counts and total IgE levels at age 4 were significantly increased in children colonized at age 1 month with S pneumoniae, M catarrhalis, or H influenzae, but the specific IgE level was not significantly affected. Children who had been colonized neonatally with S pneumoniae, M catarrhalis, or H influenzae also had, at age 5, increased prevalence of asthma, increased risk for hospitalization for wheeze, and increased reversibility of airway resistance after the administration of a bronchodilator. CONCLUSIONS. Neonates colonized in the hypopharyngeal region with S pneumoniae, M catarrhalis, H influenzae, or a combination of these organisms are at increased risk for recurrent wheeze and asthma early in life. REVIEWER COMMENTS. This is a fascinating study. Although it must be pointed out that this was a high-risk population (the mothers had asthma) and the “photograph” of these patients at ages 4 and 5 may not represent their final end point, this study gives new insight into the interaction between infectious disease, atopy, and asthma. I hope the investigators will extend this trial to older ages and that other groups will try to replicate these findings in both low- and high-risk populations of children.