Ciliary dysfunction and ultrastructural abnormalities are features of severe asthma

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Abstract

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. © 2010 American Academy of Allergy, Asthma & Immunology.

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APA

Thomas, B., Rutman, A., Hirst, R. A., Haldar, P., Wardlaw, A. J., Bankart, J., … O’Callaghan, C. (2010). Ciliary dysfunction and ultrastructural abnormalities are features of severe asthma. Journal of Allergy and Clinical Immunology, 126(4). https://doi.org/10.1016/j.jaci.2010.05.046

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