Nasal microbiota profiles, vitamin D, and cytokines are associated with chronic otitis media with effusion in preschool children: a case-control study

Abstract

Chronic otitis media with effusion (COME) is a common childhood condition in which ongoing fluid in the middle ear causes hearing impairment that may lead to delayed learning and development. I aimed to improve our understanding of the pathogenesis of COME by determining risk factors that were independent of potential confounders. A case-control design compared children aged 3 and 4 years having tympanostomy tube placement for COME to healthy controls, using multivariable analyses. COME was strongly associated with upper respiratory infection and nasal obstruction. Higher serum 25-hydroxyvitamin D (25(OH)D) concentration was associated with a reduced risk of COME. Children with COME had a less diverse nasal microbiota, a higher abundance of pathogens, fewer commensals, and profiles dominated by one or two taxa, as measured by culture-independent methods. However, pathogens were as likely to be present in healthy children as in cases. COME was also associated with a higher serum concentration of the cytokines IL-10 and TNFa. I propose that viral respiratory infection triggers endogenous pathobionts dwelling in the nasal passages in a biofilm state to overgrow and release virulent dispersed bacteria, which ascend the Eustachian tube. The COME-prone child is more likely to suffer an excessive inflammatory response to the presence of these otopathogens in the middle ear, as reflected by raised serum IL-10 and TNFa concentration, resulting in goblet cell hyperplasia that produces chronic effusion. A more diverse nasal microbiota may help to protect against biofilm overgrowth, and higher 25(OH)D concentration may reduce the risk of an excessive inflammatory response. Co-morbid nasal obstruction may result from a combination of biofilm overgrowth and goblet cell hyperplasia in the nasal passages of the at-risk child. My findings establish new directions for the investigation, prevention, and treatment of COME.