Otologic disease among patients with primary ciliary dyskinesia - an international observational study

Importance Otologic disease is common among people with primary ciliary dyskinesia, yet little is known about its spectrum and severity. Objective We characterized otologic disease among participants with primary ciliary dyskinesia using data from the Ear-Nose-Throat Prospective International Cohort of PCD patients (EPIC-PCD). Design Cross-sectional analysis of baseline cohort data. Setting Twelve specialized primary ciliary dyskinesia centers in 10 countries. Participants We prospectively included children and adults with primary ciliary dyskinesia diagnoses, routine ENT examinations, and completed symptom questionnaires at the same visit or within 2 weeks. Exposures Potential risk factors associated with increased risk of ear disease. Main outcomes and measures We describe the prevalence and characteristics of patient-reported otologic symptoms and findings from otologic examinations; we identify potential factors associated with increased risk of ear inflammation and hearing impairment. Results We included 397 (211 males) participants with median age 15 (range 0–73). A total of 204 (51%) reported ear pain, 110 (28%) ear discharge, and 183 (46%) hearing problems. Adults reported ear pain and hearing problems more frequently when compared with children. Otitis media with effusion—usually bilateral—from otoscopy was most common among 121 (32%) of 384 participants. Retracted tympanic membrane and tympanic sclerosis were more commonly seen among adults. Tympanometry was performed on 216 participants and showed pathologic type B results for 114 (53%). Audiometry was performed on 273 participants and showed hearing impairment in at least 1 ear, most commonly mild. Season of visit was the strongest risk factor for problems related to ear inflammation (autumn compared with spring odds ratio, 95% confidence interval: 2.4, 1.5–3.8) and age 30 and older of hearing impairment (age 41–50 compared with age 10 years and younger odds ratio, 95% confidence interval: 3.3, 1.1–9.9). Conclusion and relevance Many people with primary ciliary dyskinesia suffer from ear problems yet frequency varies, highlighting disease expression differences and possible clinical phenotypes. Understanding differences in otologic disease expression and progression during lifetime may inform clinical decisions about follow-up and medical care. We recommend multidisciplinary primary ciliary dyskinesia management includes regular otologic assessments for all ages even without specific complaints. Question What are the characteristics of otologic disease among patients with primary ciliary dyskinesia (PCD)? Findings Baseline data from a large multicenter cohort of patients with PCD showed frequent reports of ear pain and reduced hearing with age as the main factor associated with hearing impairment. Otitis media with effusion was the most common otoscopic finding; adults often presented with tympanic sclerosis following history of previous ear infections. Meaning Since otologic disease is an important yet underreported part of PCD’s clinical expression, we recommend otologic assessments for all age groups as part of regular clinical follow-up. ### Competing Interest Statement P Latzin received grants, honorary, for participation in data safety monitoring board or advisory board from Vertex, Vifor, OM Pharma, Polyphor, Santhera (DMC), Sanofi Aventis within the last 36 months, unrelated to the content of the manuscript. J Roehmel received grants, clinical study recompensations from Vertex, INSMED, Medical Research Council/UK, BMBF, Mukoviszidose Institut within the last 36 months,, unrelated to the content of the manuscript. ### Funding Statement Funding: The study was supported by a Swiss National Science Foundation Ambizione fellowship (PZ00P3_185923). The authors participate in the BEAT-PCD clinical research collaboration, supported by the European Respiratory Society, and most centers participate in the ERN-LUNG (PCD core). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study has been reviewed and approved by the local Human Research Ethics Committees at every participating centre, based on local legislation. We list below the names of the ethics committees which approved the study and the approval reference numbers, when applicable. A. The following centres have a pre-existing or new ethical approval, which allows the contribution of pseudonymised data to observational collaborative international studies (covers the EPIC-PCD study): 1.University Childrens Hospital Charité-Universitätsmedizin, Berlin, Germany: Ethical Committee Charité (EA2/003/21) 2. University Childrens hospital, Bern, Switzerland: Cantonal Ethics Committee of Bern (KEKBE: 060/2015) 3. University of Cyprus: Ethical Committee for biomedical research in Leukosia Cyprus (EEBK/EΠ/2013/21) 4. Marmara University Istanbul, Turkey: Ethical Committee of Marmara University (09.2018.395) 5. University Hospital of Southampton, United Kingdom: Southampton and South West Hampshire research ethics committee (06/Q1702/109) B. The following centres applied for ethical approval to participate specifically to the EPIC-PCD study: 1. VU University medical center (VUmc), Amsterdam, The Netherlands: The Medical Ethics Review Committee of VU University Medical Center reviewed the application and concluded on 24th of November 2020 that no approval is needed to participate to the EPIC-PCD cohort as the Medical Research Involving Human Subjects Act does not apply to the study. 2. Hacettepe University, Ankara, Turkey: Non-interventional clinical research EC of Hacettepe University (2020/11-47) 3. University Hospital of Leuven, Belgium: Ethical Committee for Research of University Hospitals Leuven (S64411) 4. Hospital Universitario La Fe in Valencia, Spain: Ethical Committee of medical investigations of Hospital Universitario La Fe (2020-498-1) 5. University Hospital Bicetre Paris-Sud, Paris, France: The AP-HP Direction de la Recherche Clinique et de l'Innovation reviewed the application and concluded on 4th of February 2021 that that no approval is needed to participate to the EPIC-PCD cohort as the Jardé law that regulates clinical research in France does not apply to the study. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors