Ciliary dysfunction and ultrastructural abnormalities are features of severe asthma - 07/08/11
, Christopher O’Callaghan, PhD ⁎ 
Reprint requests: Christopher O’Callaghan, PhD, Department of Infection, Immunity and Inflammation, University of Leicester, PO Box 65, Leicester Royal Infirmary, Leicester, LE2 7LX, United Kingdom.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.
El texto completo de este artículo está disponible en PDF.Key words : Ciliated epithelium, ciliary beat frequency, ciliary beat pattern, ciliary disorientation, ciliary dyskinesia, refractory asthma, severe asthma
Abbreviations used : FVC, GINA, IQR
Esquema
| C.E.B. obtained support from the Wellcome Trust, Asthma UK, and GlaxoSmithKline, which funded this study in part. Ciliary function analysis and electron microscopy analysis were performed in C.O.’s laboratory and were not supported by these sources. |
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| Disclosure of potential conflict of interest: A. J. Wardlaw serves on advisory boards for GlaxoSmithKline and receives research support from GlaxoSmithKline, Pfizer, and AstraZeneca. C. E. Brightling serves on advisory boards for GlaxoSmithKline, AstraZeneca, MedImmune, Roche, and Aerovance; receives honoraria from Novartis; and receives research support from GlaxoSmithKline, AstraZeneca, and MedImmune. The rest of the authors have declared that they have no conflict of interest. |
Vol 126 - N° 4
P. 722 - octobre 2010 Regresar al número
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