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

• Published in: Respiratory medicine Vol. 106; no. 8; pp. 1139 - 1147
• Main Authors: Yaghi, Asma, Zaman, Aisha, Cox, Gerard, Dolovich, Myrna B.
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 01.08.2012; Elsevier; Elsevier Limited
• Subjects: Adult; Aged; Bacteriology; Biological and medical sciences; Bronchodilator Agents - pharmacology; Case-Control Studies; Chronic obstructive; Chronic obstructive pulmonary disease, asthma; Cilia - drug effects; Cilia - physiology; Cilia function; Ciliary Motility Disorders - etiology; Ciliary Motility Disorders - physiopathology; Disease; Epithelium; Female; Gene expression; Humans; In vitro drug effects; Lung disease; Male; Medical sciences; Middle Aged; Mucociliary Clearance - physiology; Nasal Mucosa - drug effects; Nasal Mucosa - physiopathology; Pneumology; Proteins; Pulmonary Disease, Chronic Obstructive - complications; Pulmonary Disease, Chronic Obstructive - physiopathology; Pulmonary/Respiratory; Respiratory Mechanics - physiology; Severity of Illness Index; Smoking; Specimen Handling - methods; Sputum - cytology; Studies; Canada; Lung disease; Cilia function; In vitro drug effects; Chronic obstructive; Epithelium; Human; Drug; Respiratory disease; In vitro; Chronic; Nose; Bronchus disease; Chronic obstructive pulmonary disease; In vitro drug effects; Cilia; Pneumology
• ISSN: 0954-6111; 1532-3064; 1532-3064
• DOI: 10.1016/j.rmed.2012.04.001

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.