Dysfunctional Bronchial Cilia Are a Feature of Chronic Obstructive Pulmonary Disease (COPD)

Abstract

Impaired mucociliary clearance may increase COPD exacerbation risk. We aimed to compare bronchial ciliary function and epithelial ultrastructure of COPD patients to healthy controls and explore its relationship to exacerbator phenotypes (frequent [FE] and infrequent [IFE] exacerbator). In this cross-sectional study, 16 COPD patients and 12 controls underwent bronchial brushings. Ciliary beat frequency (CBF) and dyskinesia index (DI; % of dyskinetic cilia) were assessed using digital high-speed video microscopy, and epithelial ultrastructure using transmission electron microscopy (TEM). Bronchial epithelium in COPD showed lower CBF and higher DI, compared to controls (median [IQR] CBF: 6.8 (6.1–7.2) Hz vs 8.5 (7.7–8.9) Hz, p<0.001 and DI: 73.8 (60.7–89.8) % vs 14.5 (11.2–16.9) %, p<0.001, respectively). This was true for FE and IFE phenotypes of COPD, which were similar in terms of bronchial CBF or DI. Subgroup analyses demonstrated lower CBF and higher DI in FE and IFE COPD phenotypes compared to controls, irrespective of smoking status. TEM showed more loss of cilia, extrusion of cells, cytoplasmic blebs and dead cells in COPD patients versus controls. Profound dysfunction of bronchial cilia is a feature of COPD irrespective of exacerbation phenotype and smoking status, which is likely to contribute to poor mucus clearance in COPD.

Supplemental data for this article is available online at https://doi.org/10.1080/15412555.2021.1963695 .

Keywords:

• Chronic obstructive pulmonary disease
• ciliary function
• exacerbation
• smoking
• epithelial ultrastructure

Acknowledgments

The authors thank the subjects for their participation in this study. They also thank the following Research nurses and coordinators for their assistance in conducting the study: Chwee Bee Yap, Nicole Yu Chia Shuang and Karen Tan (Dept. of Respiratory and Critical Care Medicine, Singapore General Hospital, Singapore); Michellore Aguilar and Robyn Yip Yeok (SingHealth Investigational Medicine Unit, Singapore). Finally, they thank Roy Sudipto (Institute of Cell and Molecular Biology, A*STAR) for helping with the TEM samples, and Wan Loo Tan and staff of the Molecular Laboratory (Department of Molecular Pathology) for their help in the molecular microbiology tests.

Declaration of interest

No potential conflict of interest was reported by the author(s).

Authors contributions

B. Thomas and T.S. Lapperre, both guarantor of the paper, were involved in the conception, design and conduct of the study and preparation of the manuscript. M.S. Koh, S.Y. Low, T.H. Ong, C.M. Loo and Teoh O.H were involved in the design, conduction of the study and critically reviewed and revised the manuscript. C. O’Callaghan, A. Rutman and R.A. Hirst were involved in the design of the study, conduction of TEM studies, and critically reviewed and revised the manuscript. J Connolly and J.C. Allen Jr were involved in the design and reviewed the manuscript. L.L.E. Oon was responsible for the microbiology investigations and reviewed the manuscript. W.T. Lim was involved in the design of the study, and the recruitment and measurements in healthy control subjects, and reviewed the manuscript. Q. He performed ciliary function studies.

Additional information

Funding

This research was supported by the Singapore National Medical Research Council (NMRC) [grant number NMRC/CNIG/1104/2013] and by the NIHR GOSH BRC. The views expressed are those of the authors and not necessarily those of the NMRC, NHS, the NIHR or the Department of Health.