title: Ciliary dysfunction and ultrastructural abnormalities are features of severe asthma.
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, r(s) = -0.68; dyskinesia index, r(s) = 0.86; immotility index, r(s) = 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute for Lung Health, Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, United Kingdom.
authors.forename: Biju
authors.initials: B
authors.lastname: Thomas
authors.forename: Andrew
authors.initials: A
authors.lastname: Rutman
authors.forename: Robert A
authors.initials: RA
authors.lastname: Hirst
authors.forename: Pranab
authors.initials: P
authors.lastname: Haldar
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Wardlaw
authors.forename: John
authors.initials: J
authors.lastname: Bankart
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Brightling
authors.forename: Christopher
authors.initials: C
authors.lastname: O'Callaghan
mesh_terms: D000328:Adult; D001249:Asthma / Q000473:pathology / Q000503:physiopathology*; D001980:Bronchi / Q000473:pathology / Q000503:physiopathology / Q000648:ultrastructure*; D002923:Cilia / Q000473:pathology* / Q000648:ultrastructure; D002925:Ciliary Motility Disorders / Q000473:pathology / Q000503:physiopathology; D004848:Epithelium / Q000473:pathology / Q000503:physiopathology / Q000648:ultrastructure*; D005260:Female; D006801:Humans; D008297:Male; D046529:Microscopy, Electron, Transmission; D018715:Microscopy, Video / Q000379:methods; D008875:Middle Aged; D012720:Severity of Illness Index; D055815:Young Adult