Ciliary beating is depressed in nasal cilia from chronic obstructive pulmonary disease subjects

Abstract

COPD is characterized by increased cough, mucus production, and airway inflammation. Beating epithelial cell cilia contribute to mucociliary clearance with ciliary beat frequency (CBF) an important measure of cilia function. However, whether CBF varies with COPD severity is unknown.

Aims: 1) to compare nasal cilia samples and their CBF from healthy non-smokers (Control), COPD and At Risk (cough and sputum production) subjects. 2) to determine the effect of pharmacologic agents that modulate mediators implicated in the pathogenesis of COPD on nasal CBF. Nasal brushings of ciliated cells were obtained from Control, At Risk and COPD subjects. Using high speed digital imaging, we measured baseline CBF ex vivo. Then, CBF was re-measured after 30 min perfusion with pharmacologic agents that modulate mediators implicated in COPD (salmeterol xinafoate, tiotropium bromide, licofelone, luteolin, YM976, Defensin HNP-1) and again after 30 min washout. CBF was significantly depressed in moderate and severe COPD compared to At Risk and Control subjects. There was an evident and persistent rise in CBF with all agents tested in COPD cilia except that YM976 effects persisted only in severe COPD. Only YM976 and tiotropium caused a persistent increase in CBF in At Risk cilia. The reduction of nasal CBF in moderate and severe COPD implies that impaired ciliary function may impact mucociliary clearance in COPD, potentially contributing to retention of secretions and infection. Pharmacologic agents with different mechanisms of action can increase CBF of COPD cilia. Further investigation of the signalling pathways influencing CBF of COPD cilia is needed.