Smoking Is Associated with Shortened Airway Cilia 英文参考文献.docVIP

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Smoking Is Associated with Shortened Airway Cilia 英文参考文献.doc

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Smoking Is Associated with Shortened Airway Cilia 英文参考文献

SmokingIsAssociatedwithShortenedAirwayCilia PhilipL.Leopold1,2.,MichaelJ.O’Mahony1,2.,X.JulieLian1.,AnnE.Tilley1,2,Ben-GaryHarvey1,2 , RonaldG.Crystal1,2 * 1DepartmentofGeneticMedicine,WeillCornellMedicalCollege,NewYork,NewYork,UnitedStatesofAmerica,2DivisionofPulmonaryandCriticalCareMedicine,Weill CornellMedicalCollege,NewYork,NewYork,UnitedStatesofAmerica Abstract Background: Whereas cilia damage and reduced cilia beat frequency have been implicated as causative of reduced mucociliaryclearanceinsmokers,theoreticallymucociliaryclearancecouldalsobeaffectedbycilialength.Basedonmodels ofmucociliaryclearancepredictingthatcilialengthmustexceedthe6–7mmairwaysurfacefluiddepthtogenerateforcein themucuslayer,wehypothesizedthatciliaheightmaybedecreasedinairwayepitheliumofnormalsmokerscomparedto nonsmokers. Methodology/Principal Findings: 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% comparedtononsmokers(p,0.05).In39air-driedsamplesofairwayepithelialcells,smokercilialengthwasreducedby 13%comparedtononsmokers(p,0.0001).Analysisofthelengthofindividual,detachedciliain27samplesshowedthat smokercilialengthwasreducedby9%comparedtononsmokers(p,0.05).Finally,in16fullyhydrated,unfixedsamples, smokercilialengthwasreduced7%comparedtononsmokers(p,0.05).Usinggenome-wideanalysisofairwayepithelial geneexpressionweidentified6cilia-relatedgeneswhoseexpressionlevelsweresignificantlyreducedinhealthysmokers comparedtohealthynonsmokers. Conclusions/Significance:Modelspredictthatareductionincilialengthwouldreducemucociliaryclearance,suggesting thatsmoking-associatedshorterairwayepithelialciliaplayasignificantroleinthepathogenesisofsmoking-inducedlung disease. Citation: Leopold PL, O’Mahony MJ, Lian XJ, Tilley AE, Harvey B-G, et al. (2009) Smo