Smoking is associated with shortened airway cilia.
BACKGROUND
Whereas cilia damage and reduced cilia beat frequency have been implicated as causative of reduced mucociliary clearance in smokers, theoretically mucociliary clearance could also be affected by cilia length. Based on models of mucociliary clearance predicting that cilia length must exceed the 6-7 microm airway surface fluid depth to generate force in the mucus layer, we hypothesized that cilia height may be decreased in airway epithelium of normal smokers compared to nonsmokers.


RESULTS
Cilia length in normal nonsmokers and smokers was evaluated in aldehyde-fixed, paraffin-embedded endobronchial biopsies, and air-dried and hydrated samples were brushed from human airway epithelium via fiberoptic bronchoscopy. In 28 endobronchial biopsies, healthy smoker cilia length was reduced by 15% compared to nonsmokers (p<0.05). In 39 air-dried samples of airway epithelial cells, smoker cilia length was reduced by 13% compared to nonsmokers (p<0.0001). Analysis of the length of individual, detached cilia in 27 samples showed that smoker cilia length was reduced by 9% compared to nonsmokers (p<0.05). Finally, in 16 fully hydrated, unfixed samples, smoker cilia length was reduced 7% compared to nonsmokers (p<0.05). Using genome-wide analysis of airway epithelial gene expression we identified 6 cilia-related genes whose expression levels were significantly reduced in healthy smokers compared to healthy nonsmokers.


CONCLUSIONS
Models predict that a reduction in cilia length would reduce mucociliary clearance, suggesting that smoking-associated shorter airway epithelial cilia play a significant role in the pathogenesis of smoking-induced lung disease.
Leopold
Philip L
PL
Department of Genetic Medicine, Weill Cornell Medical College, New York, New York, USA.
O'Mahony
Michael J
MJ
Lian
X Julie
XJ
Tilley
Ann E
AE
Harvey
Ben-Gary
BG
Crystal
Ronald G
RG
D000328:Adult; D001706:Biopsy; D002923:Cilia / Q000473:pathology*; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D008875:Middle Aged; D009079:Mucociliary Clearance; D016612:Paraffin Embedding; D020545:Respiratory Mucosa / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D012137:Respiratory System / Q000473:pathology* / Q000503:physiopathology; D012907:Smoking / Q000009:adverse effects*; D016707:Tissue Fixation