Ciliary dysfunction and ultrastructural abnormalities are features of severe asthma

• Published in: Journal of allergy and clinical immunology Vol. 126; no. 4; pp. 722 - 729.e2
• Main Authors: Thomas, Biju, MD, Rutman, Andrew, CBiol, Hirst, Robert A., PhD, Haldar, Pranab, MD, Wardlaw, Andrew J., PhD, Bankart, John, PhD, Brightling, Christopher E., PhD, O'Callaghan, Christopher, PhD
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 01.10.2010; Elsevier; Elsevier Limited
• Subjects: Adult; Allergy and Immunology; Asthma; Asthma - pathology; Asthma - physiopathology; Biological and medical sciences; Bronchi - pathology; Bronchi - physiopathology; Bronchi - ultrastructure; Cilia - pathology; Cilia - ultrastructure; ciliary beat frequency; ciliary beat pattern; ciliary disorientation; ciliary dyskinesia; Ciliary Motility Disorders - pathology; Ciliary Motility Disorders - physiopathology; Ciliated epithelium; Epithelium - pathology; Epithelium - physiopathology; Epithelium - ultrastructure; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Humans; Immunopathology; Male; Medical sciences; Microscopy; Microscopy, Electron, Transmission; Microscopy, Video - methods; Middle Aged; Mortality; Nervous system (semeiology, syndromes); Nervous system as a whole; Neurology; Nitric oxide; refractory asthma; Rodents; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; severe asthma; Severity of Illness Index; Young Adult; refractory asthma; Forced vital capacity; IQR; ciliary beat pattern; ciliary dyskinesia; FVC; GINA; Global Initiative for Asthma; Interquartile range; severe asthma; ciliary disorientation; Ciliated epithelium; ciliary beat frequency; Immunopathology; Nervous system diseases; Treatment resistance; Beat frequency; Beat; Epithelium; Involuntary movement; Cerebral disorder; Immunology; Dysfunction; Ultrastructure; Central nervous system disease; Anomaly; Severe asthma; Neurological disorder; Extrapyramidal syndrome; Dyskinesia
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2010.05.046

Background Epithelial dysfunction has been implicated in asthma pathophysiology, but no studies have directly assessed ciliary function in asthma. Objective To study the ciliary function and epithelial ultrastructure of patients with asthma and healthy controls. Methods We studied ciliary beat frequency and beat pattern by using digital high-speed video imaging and ultrastructure by transmission electron microscopy of bronchial epithelial strips from 7 subjects with mild, 7 with moderate, and 19 with severe asthma and 9 healthy controls. Results The median (interquartile range) ciliary beat frequency was decreased in moderate (6.5 [4.4-8.5] Hz) and severe asthma (6.7 [6.1-7.6] Hz) compared with controls (10.5 [9.7-11.8] Hz; P  < .01). Dyskinesia and immotility indices were higher in severe asthma (65% [43%-75%]; 6.3% [1%-9.5%], respectively) compared with controls (4% [0%-6.7%; 0%, respectively; P  < .01). These abnormalities were related to disease severity (ciliary beat frequency, rs  = –0.68; dyskinesia index, rs  = 0.86; immotility index, rs  = 0.65; P  < .0001). The ultrastructure of the epithelium was abnormal in severe asthma with a reduction in ciliated cells, an increase in dead cells, and ciliary disorientation compared with all other groups ( P  < .05). Compared with patients with mild asthma and healthy controls, patients with severe asthma showed increased ciliary depletion, microtubular defects, mitochondrial damage, and cytoplasmic blebbing ( P  < .01). All of these changes were related to disease severity. Conclusion Ciliary dysfunction and ultrastructural abnormalities are closely related to asthma severity. Ciliary dysfunction is a feature of moderate to severe asthma, and profound ultrastructural abnormalities are restricted to severe disease. Whether these changes contribute to the development of severe asthma phenotype remains to be determined.