ABSTRACT
BACKGROUND AND OBJECTIVES: The development of childhood asthma is associated with neonatal colonization with pathogenic bacteria in hypopharynx. Furthermore, established asthma is associated with systemic low-grade inflammation. We here report on the association between neonatal colonization with pathogenic bacteria in hypopharynx and the development of systemic low-grade inflammation. METHODS: Bacterial colonization of the hypopharynx with Moraxella catharralis, Haemophilus influenzae, and/or Streptococcus pneumoniae was assessed in asymptomatic children from the Copenhagen Prospective Studies on Asthma in Childhood2000 (COPSAC2000 ) cohort at age 1 month by culturing technique (N = 238) and by quantitative polymerase chain reaction (qPCR) technique (N = 249) and in the COPSAC2010 cohort by culturing at age 1 month (N = 622) and again at age 3 months (N = 613). Systemic low-grade inflammation was determined in both cohorts at age 6 months by measuring plasma levels of high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), and interleukin-6 (lL-6). RESULTS: In both cohorts, bacterial colonization was associated with increased levels of hs-CRP: COPSAC2000 , 1 month culturing (geometric mean ratio of colonized/noncolonized [95% CI]), 1.39 [0.97-2.01], P = .08; 1 month qPCR, 1.55 [1.14-2.10], P < .01; COPSAC2010 , 1 month, 1.52 [1.23-1.87], P < .01; and 3 month, 1.57 [1.30-1.90], P < .01. A multiparametric principal component analysis incorporating hs-CRP, TNF-α, and IL-6 confirmed a systemic inflammatory profile in children colonized with M. catharralis, H. influenzae. and/or S. pneumoniae in the hypopharynx compared to noncolonized children (P-values < .05). CONCLUSION: The composition of the upper airway microbiome in early life may cause systemic low-grade inflammation.
