Inhaled Corticosteroid Use and Self-Reported Voice Problems in a Nordic Population-Based Cohort

Sofia Ögefeldt,1,2 Greta Öhlund Wistbacka,1,3 Ellika Schalling,1,3 Henrik Johansson,2– 4 Andrei Malinovschi,5 Christer Janson,2 Helena Backman,6 Mathias Holm,7 Ane Johannessen,8 Caroline Ahlroth Pind,2,9 Elin Dahlén,10,11 Össur Ingi Emilsson2,121Department of Public Health and Caring Sciences; Speech-Language Pathology, Uppsala University, Uppsala, Sweden; 2Department of Medical Sciences, Respiratory, Allergy and Sleep Research, Uppsala University, Uppsala, Sweden; 3Department of Geriatrics, Rehabilitation, Pain Centre and Palliative Care, Uppsala University Hospital, Uppsala, Sweden; 4Department of Women’s and Children’s Health: Physiotherapy and Behavioral medicine, Uppsala University, Uppsala, Sweden; 5Department of Medical Sciences, Clinical Physiology, Uppsala University, Uppsala, Sweden; 6Department of Public Health and Clinical Medicine, the OLIN and Sunderby Research Unit, Umeå University, Umeå, Sweden; 7Occupational and Environmental Medicine, School of Public Health and Community Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; 8Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway; 9Centre for Clinical Research Västmanland, Uppsala University, Västerås, Sweden; 10Department of Pharmacy; Drug Epidemiology, Uppsala University, Uppsala, Sweden; 11The NEPI Foundation-Network for Pharmacoepidemiology, Stockholm, Sweden; 12Faculty of Medicine, University of Iceland, Reykjavik, IcelandCorrespondence: Sofia Ögefeldt, Email sofia.ogefeldt@uu.se Össur Ingi Emilsson, Email ossur.emilsson@medsci.uu.seBackground: Voice problems are frequently reported among users of inhaled corticosteroids (ICS), but it remains unclear whether these problems reflect pharmacological effects, asthma, or comorbid chronic cough.Aim: This study aimed to examine the association between ICS use and voice problems in a Nordic population-based cohort, accounting for asthma symptoms and chronic cough. Secondary aims included dose–response patterns and differences by inhaler device type.Methods: Cross-sectional data from adults in Sweden and Norway participating in the Respiratory Health in Northern Europe IV study (RHINE, n=5,986) were linked to national prescription registers. ICS exposure during 2021 was quantified using annual filled defined daily doses (FDDD), calculated from dispensed prescriptions based on the corticosteroid content per inhalation and number of dispensed doses. Associations between self-reported voice problems and ICS use, asthma symptoms, and chronic cough were analyzed using logistic regression, adjusted for multiple confounders. Dose–response, exposure overlap, and inhaler device type were examined in secondary analyses.Results: Voice problems increased with higher ICS exposure, from 15.5% among non-users to 59.7% in the highest dose category. The dose–response pattern showed a steep increase at lower doses with attenuation at higher exposure levels. In adjusted analyses including ICS use, asthma symptoms and chronic cough, ICS use remained associated with voice problems (aOR 1.54 [1.13– 2.10] for 1– 150 FDDD; 2.88 [1.98– 4.21] for 151– 300 FDDD; and 3.00 [2.03– 4.43] for > 300 FDDD); as did asthma symptoms (aOR 2.31 [1.90– 2.82] for one symptom; 3.14 [2.45– 4.03] for ≥ 2 symptoms); and chronic cough (aOR 2.03 [1.67– 2.46]). The highest prevalence was observed among participants with overlapping ICS use, asthma symptoms, and chronic cough. Inhaler device type did not affect voice problems, with reservation for low statistical power.Conclusion: ICS use, asthma symptoms, and chronic cough were independently associated with voice problems, with a clear dose–response for ICS, underscoring the need to consider both medication and respiratory symptoms in clinical assessment.Keywords: asthma, inhaled corticosteroids, chronic cough, voice problems, dysphonia, hoarseness, ICS, asthma symptoms