Abstract
Background Bronchiectasis can result from infectious, genetic, immunological and allergic causes. 60–80% of cases are idiopathic, but a well-recognised genetic cause is the motile ciliopathy, primary ciliary dyskinesia (PCD). Diagnosis of PCD has management implications including addressing comorbidities, implementing genetic and fertility counselling and future access to PCD-specific treatments. Diagnostic testing can be complex; however, PCD genetic testing is moving rapidly from research into clinical diagnostics and would confirm the cause of bronchiectasis.
Methods This observational study used genetic data from severe bronchiectasis patients recruited to the UK 100,000 Genomes Project and patients referred for gene panel testing within a tertiary respiratory hospital. Patients referred for genetic testing due to clinical suspicion of PCD were excluded from both analyses. Data were accessed from the British Thoracic Society audit, to investigate whether motile ciliopathies are underdiagnosed in people with bronchiectasis in the UK.
Results Pathogenic or likely pathogenic variants were identified in motile ciliopathy genes in 17 (12%) out of 142 individuals by whole-genome sequencing. Similarly, in a single centre with access to pathological diagnostic facilities, 5–10% of patients received a PCD diagnosis by gene panel, often linked to normal/inconclusive nasal nitric oxide and cilia functional test results. In 4898 audited patients with bronchiectasis, <2% were tested for PCD and <1% received genetic testing.
Conclusions PCD is underdiagnosed as a cause of bronchiectasis. Increased uptake of genetic testing may help to identify bronchiectasis due to motile ciliopathies and ensure appropriate management.
Abstract
Primary ciliary dyskinesia is underdiagnosed as a cause of idiopathic bronchiectasis. Whole-genome sequencing reveals variants in motile ciliopathy genes. https://bit.ly/3yKoBko
Footnotes
The Genomics England Research Consortium: D. Brown, J.C. Ambrose, P. Arumugam, R. Bevers, M. Bleda, F. Boardman-Pretty, C.R. Boustred, H. Brittain, M.J. Caulfield, G.C. Chan, T. Fowler, A. Giess, A. Hamblin, S. Henderson, T.J.P. Hubbard, R. Jackson, L.J. Jones, D. Kasperaviciute, M. Kayikci, A. Kousathanas, L. Lahnstein, S.E.A. Leigh, I.U.S. Leong, F.J. Lopez, F. Maleady-Crowe, M. McEntagart, F. Minneci, L. Moutsianas, M. Mueller, N. Murugaesu, A.C. Need, P. O'Donovan, C.A. Odhams, C. Patch, D. Perez-Gil, M.B. Pereira, J. Pullinger, T. Rahim, A. Rendon, T. Rogers, K. Savage, K. Sawant, R.H. Scott, A. Siddiq, A. Sieghart, S.C. Smith, A. Sosinsky, A. Stuckey, M. Tanguy, A.L. Taylor Tavares, E.R.A. Thomas, S.R. Thompson, A. Tucci, M.J. Welland, E. Williams, K. Witkowska, S.M. Wood.
Author contributions: Study conception and design: A. Shoemark, H. Griffin, G. Wheway, C. Hogg, J.S. Lucas, J.D. Chalmers, D. Morris-Rosendahl, H.M. Mitchison and A. De Soyza. Data collection: A. Shoemark, C. Hogg, J.S. Lucas, M. Carroll, M.R. Loebinger, D. Morris-Rosendahl and A. De Soyza. Data analysis: A. Shoemark, H. Griffin, G. Wheway, C. Camps, J.D. Chalmers, D. Morris-Rosendahl and H.M. Mitchison. Writing of the manuscript: A. Shoemark, H. Griffin, G. Wheway, C. Hogg, J.S. Lucas, J.D. Chalmers, D. Morris-Rosendahl, H.M. Mitchison and A. De Soyza. Revising critically for important intellectual content and final approval: all authors.
Conflict of interest: A. Shoemark has received grants from AstraZeneca. G. Wheway is currently employed by Illumina Inc. M.R. Loebinger has received consultancy or speaker fees from Insmed, AstraZeneca, Parion, Grifols and Armata. J.D. Chalmers has received grants or contracts from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Gilead Sciences, Novartis and Insmed; and received consultancy or speaker fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Insmed, Janssen, Novartis and Zambon. J.S. Lucas reports grants from NHS England, NIHR and AIR Charity. H.M. Mitchison is a Trustee of Ciliopathy Alliance. A. De Soyza reports grants from AstraZeneca, GlaxoSmithKline and Pfizer; consulting fees and lecture honoraria from Gilead, GlaxoSmithKline, AstraZeneca, LifeArc and 30T; participation on advisory board at Bayer; receipt of equipment from GlaxoSmithKline. All other authors have nothing to disclose.
Support statement: H.M. Mitchison acknowledges funding from the NIHR Biomedical Research Centre at Great Ormond Street Hospital and the Ministry of Higher Education in Egypt. The National PCD Service is commissioned and funded by NHS England; PCD research in Southampton is supported by NIHR Southampton Biomedical Research Centre, NIHR Clinical Research Facility, National Institute for Health Research (RfPB PB-PG-1215-20014; and 200470) and The AAIR Charity (registration number 1129698).
- Received January 25, 2022.
- Accepted May 12, 2022.
- Copyright ©The authors 2022. For reproduction rights and permissions contact permissions{at}ersnet.org
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