Mucociliary and cough clearance in primary ciliary dyskinesia as affected by mutations in RSPH1 or DNAH5
Year: 2025
Type: article
Study design: Observational Study
Abstract: Background Primary ciliary dyskinesia (PCD) is a rare disease caused by mutations in >50 genes that impair the function of motile cilia. The clinical phenotype is heterogeneous and recent studies have begun to investigate genotype–phenotype relationships to better understand disease pathogenesis and develop improved treatments. The major cause of morbidity and mortality among individuals with PCD is the lack of mucociliary clearance (MCC) that results in chronic respiratory infections and leads to bronchiectasis. Here we examine the relationship between MCC and genotype in two groups of PCD individuals; one with mutations in a gene ( DNAH5 ) that causes PCD with mostly immotile cilia and one with mutations in a gene ( RSPH1 ) that cause PCD with cilia that beat with a near-normal frequency, but an abnormal, sometimes circular waveform. Methods Patients with known pathogenic variants in DNAH5 (n=8) or RSPH1 (n=7), along with healthy controls (n=8), were assessed for clearance of an inhaled radioactive tracer by mucociliary and cough clearance as measured by gamma scintigraphy. Results Neither DNAH5 nor RSPH1 subjects showed clear evidence of MCC under either baseline or albuterol stimulated conditions. Unexpectedly, subjects with RSPH1 mutations demonstrated cough clearance (median 9.7%, IQR 6.2–17%) that was significantly higher than subjects with DNAH5 mutations (4.2% (0.94–5.1%); p=0.015) and was not significantly different from healthy control subjects (8.3% (4.2–16%); p=0.88). Conclusions The results confirm impaired MCC in people with PCD of both genotypes. However, in this small cohort, the results suggest cough clearance may differ between these two genotypes.
Source: ERJ Open Research
Authors: Lawrence E. Ostrowski, Sara Abu-Nasser, Kirby L. Zeman, Margaret W. Leigh, Maimoona A. Zariwala, Kenneth N. Olivier, Thomas W. Ferkol, Corinne N. Taylor, Agathe S. Ceppe, Michael R. Knowles, William D. Bennett
Institution: University of North Carolina at Chapel Hill
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $808
Funders: Remondi Family Foundation, Brain and Behavior Research Foundation, Alzheimer's Association, Alzheimer's Drug Discovery Foundation, University of Southern California, George Washington University, North Carolina State University, University of Victoria, Eastern Health Foundation, Northern California Institute for Research and Education, Veloxis Pharmaceuticals, Australian Government, International Coral Reef Society, Alzheimer's Society, ResMed, San Antonio Medical Foundation, National Institute for Health and Care Research, Leverhulme Trust, Japan Society for the Promotion of Science London, Natural History Museum, Deutsche Forschungsgemeinschaft, Japan Science and Technology Corporation, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, Fundação de Amparo à Pesquisa do Estado de São Paulo, National Natural Science Foundation of China, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Bundesministerium für Bildung und Forschung, Inje University, Cooperative Research Centres, Australian Government Department of Industry, Shanxi Scholarship Council of China, Conselho Nacional de Desenvolvimento Científico e Tecnológico, Korea Health Industry Development Institute, National Research Foundation of Korea, Khon Kaen University, Natural Science Foundation of Shanxi Province, Lietuvos Mokslo Taryba, Fundação de Amparo à Pesquisa do Estado de Minas Gerais, Fundação de Amparo à Pesquisa do Estado de Goiás, Medizinische Universität Wien, Shanxi Medical University, Universität Leipzig, Bayerisches Staatsministerium für Umwelt und Verbraucherschutz, Deutsches Zentrum für Lungenforschung, Lungenliga Schweiz, Gemeinsame Bundesausschuss, Lietuvos Sveikatos Mokslų Universitetas, International Science and Technology Cooperation Program of Shanxi Province, National Institutes of Health, University of Texas Health Science Center at San Antonio, Horizon 2020 Framework Programme, Canadian Institutes of Health Research, Center on Aging, University of Utah, Economic and Social Research Council, National Health and Medical Research Council, Science and Engineering Research Board, European Regional Development Fund, National Key Research and Development Program of China, Key Laboratory of Agricultural Information Service Technology, Conselleria de Innovación, Universidades, Ciencia y Sociedad Digital, Generalitat Valenciana, Zürcher Hochschule für Angewandte Wissenschaften, National Institute on Aging, National Heart, Lung, and Blood Institute, National Institute of Mental Health, National Institute on Drug Abuse, NIH Office of the Director, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institute of Biomedical Imaging and Bioengineering, National Center for Advancing Translational Sciences, National Institute on Minority Health and Health Disparities, Moonshot Research and Development Program, HORIZON EUROPE European Research Council
Awards: G1246947958, G3218375949
OpenAlex ID: W4413984084