More than one million tympanostomy tube placement procedures take place per year in North America for children with recurrent or chronic otitis media, and about 7% of children in the United States undergo this procedure during early childhood.39
Similarly, in our study ~6% of children had undergone tympanostomy tube placement. Thus, given the significant number of children affected by atopic conditions in the United States, assessing atopic conditions as a risk factor for frequent and persistent ear infections is worthwhile.
In our study, children with asthma had a higher incidence rate of tympanostomy tube placement compared with those without asthma. This was also true for those with allergic rhinitis. This association could be caused by a detection bias because parents of children with asthma might be more likely to seek medical evaluations for upper respiratory infections than those without asthma. However, this association did not change before and after a physician diagnosis of asthma, suggesting a physician diagnosis did not seem to influence this association. In addition, we previously reported similar health care use between asthmatic and nonasthmatic patients and no differences in risk of outcome events between asthmatic patients with and without a physician diagnosis of asthma in our study setting.40–42
In support of our study findings, the literature suggests a potential association between atopic conditions and risk of otitis media. A cross-sectional study by Eldeirawi et al.
using data from >7000 children between 2 and 11 years of age found that the lifetime prevalence of asthma was significantly associated with increased risk of otitis media.14
Also, Bentdal et al.
reported a significant cross-sectional association between allergic diseases and atopic diseases, especially asthma, among 2,600 children aged 10 years in Oslo.22
Moreover, using data from the International Study of Asthma and Allergies in Childhood, Chen et al.
found a significantly higher prevalence of infectious diseases including otitis media in children with asthma, allergic rhinitis, or atopic dermatitis.24
The biological mechanisms underlying this association between atopic disease and otitis media are unknown. We can postulate a few plausible mechanisms at both the structural and the functional levels. At a structural level, perhaps children with asthma or allergic rhinitis might be more likely to have allergic inflammation on upper respiratory tract, which might result in Eustachian tube dysfunction leading to otitis media.43
At a functional level, recent studies suggest a potential role of bacterial infections in development of asthma or bronchial hyperresponsiveness44,45
and the benefit from antibiotic treatment for asthma symptoms or bronchial reactivity.45,46
Our study results might not exclude this possibility of reverse causality (i.e.
, microbial infections or colonization might provoke airway symptoms and development of asthma).
However, given the reported increased risk of serious pneumococcal disease in atopics8,9
and impaired innate47–50
and adaptive immune functions,51–54
we believe that patients with atopic conditions might be intrinsically susceptible to microbial infections or colonization due to impaired immune functions because microbial infections or colonization are unlikely to impair immune functions. Specific to pneumococcal immune functions in individuals with atopy, we recently reported a lower anti-pneumococcal polysaccharide antibody levels in asthmatic patients compared with nonasthmatic patients.55
Therefore, with the reported impairment in other innate and adaptive immune functions, the increased risk of otitis media, which is primarily caused by pneumococci, among children with asthma might be immunologically plausible.
One noteworthy finding of our study is the absence of a significant difference in the risk of recurrent or persistent otitis media (tympanostomy tube placement) before and after the index date of asthma. These results may potentially suggest that immunogenetic predisposition to asthma alone might be an important risk factor for recurrent or persistent otitis media. We reported similar findings on the increased risk of Streptococcus pyogenes
infection before the onset of clinically defined asthma or other atopic conditions among children with asthma or other atopic conditions.42,56
Therefore, we postulate that susceptibility to microbial infections in individuals with atopic conditions is likely to be associated with the immunologic underpinnings of atopic conditions, and susceptibility to microbial infections and atopic status might be different outcomes of the same underlying biological factor. One example of such a biological factor associated with risk of atopic dermatitis and increased risk of skin infections is filaggrin, a crucial antimicrobial peptide in skin barrier.57,58
Recent studies suggest that filaggrin mutations, indeed, affect risks of asthma and allergic rhinitis as well.57,59,60
Thus, atopic patients with increased risk of microbial infections could be a phenotypic characteristic of filaggrin mutations and our study findings potentially support this notion.
The strengths of our study include study design as a cohort study, epidemiological advantages of study setting (self-contained health care environment with a unified medical record system for research), and predetermined criteria for asthma and actual incidence of events (tympanostomy tube placement as a marker for frequent and persistent ear infections) instead of self-report. However, our study has inherent limitations as a retrospective study. There were a significant number of missing data points for certain variables limiting our ability to adjust our study results for, but missing data points are likely to be subject to nondifferential misclassification. Along these lines, some pertinent variables were not available (e.g.
, allergic sensitization status or crowdedness in household). Our study was based on a small sample size. In addition, given the higher proportion of white population and people working in health care industry in our study setting, whether our study findings are generalizable to other settings needs to be interpreted carefully. For example, whether referral processes for tympanostomy tube placement or ear, nose, and throat practices in Olmsted County, MN, might differ from other settings is unknown and was not addressed. In addition, asthma prevalence in our study was relatively high because of the inclusive nature of asthma criteria and overrepresentation of children with asthma in our study subjects who participated in a previous vaccine study. However, underdetection or diagnosis of asthma has been also suggested. For example, Bisgaard and Szefler reported that of the 9,490 children from the United States and Europe, 32% of children were reported to suffer from recurrent symptoms of cough, wheeze, or breathlessness but they were not properly diagnosed and treated for asthma.61
Our study results need to be interpreted in these contexts.
In conclusion, asthma or allergic rhinitis may be unrecognized risk factors for recurrent or persistent otitis media. Immunogenetic predisposition to asthma itself might be a risk factor for recurrent and persistent otitis media. However, given the small sample size of the study, a cohort study with a larger sample size is necessary.