Acute otitis media severity: Association with cytokine gene polymorphisms and other risk factors

Abstract

Background We have previously shown an association between polymorphisms of proinflammatory cytokine genes and susceptibility to upper respiratory tract infection and acute otitis media. It has not been known whether polymorphisms or risk factors are associated with the severity of acute otitis media. Objective To evaluate the influences of proinflammatory cytokine gene polymorphisms and other risk factors on severity of acute otitis media following upper respiratory infection. Methods In a prospective, longitudinal study, children aged 6-35 months were followed for one year for occurrences of upper respiratory tract infection and acute otitis media. Children were studied for TNFα-308, interleukin (IL)- 6-174 and IL-1 ß+3953 polymorphisms, taking into account age, gender, race, family history of otitis, tobacco smoke exposure, breast feeding, day of upper respiratory tract infection at the time of diagnosis and pneumococcal vaccine status. Symptoms and signs of acute otitis media were graded according to a validated scale. The association between acute otitis media clinical severity, polymorphic genotypes, and risk factors was analyzed using statistical models that account for multiple episodes of acute otitis media per child. Results A total of 295 episodes of acute otitis media in 128 subjects were included. More severe acute otitis media symptoms were associated with young age (P=0.01), family history of acute otitis media (P=0.002), tobacco smoke exposure (P=0.008), and early diagnosis of otitis after onset of upper respiratory tract infection (P=0.02). Among children with a bulging or perforated tympanic membrane (206 episodes, 104 subjects), those who had the IL- 1 ß+3953 polymorphism, experienced higher symptom scores (P<0.02). Conclusion This is the first report of the association between risk factors and acute otitis media severity. Risk factors such as tobacco smoke exposure and a positive family history appear to be more significantly associated with acute otitis media severity than proinflammatory gene polymorphisms. Clinical severity may be an important factor contributing to the incidence and costs of acute otitis media, because children with more severe symptoms might be more likely to be brought for a medical visit, receive a diagnosis of acute otitis media, and be prescribed an antibiotic.

Acute Otitis Media- An Update

“…AOM is considered the most common inflammatory disease [7,9,10], and the most common indication of prescribing antimicrobial in children [2,7,11,12]. US spends $2-3.5 billion per year for treatment of this condition [2,13].…”

“…AOM has multiple interactive host, environmental, microbiological and genetic factors that interplay with each other to make the patient more susceptible to have AOM [10,15,12].…”

“…Some investigators have linked this susceptibility to poor ET function [2]. Specific polymorphisms of cytokines have been correlated to the susceptibility of an individual to OM and to the severity of the disease as well [10,12]; IL-1s, IL-6 and TNFα have been found in nasopharyngeal secretions during URTI and increased levels of IL-1s is linked to the transition to AOM [12]. TNFα-308 polymorphisms are associated with AOM that follows URTI.…”

“…The importance of other environmental factors cannot be underestimated in the pathogenesis of AOM; Paternal smoking is one of OM risk factors [1,3,8,10,14]; it causes mucosal inflammation, goblet hyperplasia and an increase in the production of mucus, by this it impairs mucosal immunity and increases bacterial colonization by enhancing bacterial binding to respiratory epithelium [1,10]. Children of mothers who smoked during pregnancy and stopped after delivery still have higher incidence of AOM [10].…”

“…Children of mothers who smoked during pregnancy and stopped after delivery still have higher incidence of AOM [10]. Children with bottle feeding is another well known risk factor [1,3,8,10]; it is believed that passive immunity through the breast milk gives some protection [1], bottle-fed infants have higher nontypeable Haemophilus influenzae prevalence and lower immunoglobulin G antibodies [8]. Some studies found a role of Gastro esophageal reflux (GERD) disease [1,18]; GERD is found in 62.9% of patient with rOM.…”