title: Bronchodilator responsiveness of peripheral airways in smokers with normal spirometry.
abstract: Cigarette smoke exposure increases airway smooth muscle (ASM) contractility. Abnormalities in peripheral airway function in smokers with normal spirometry could be due to the effects of ASM tone. We aimed to determine the contribution of ASM tone to peripheral airway function in smokers with normal spirometry from the response to bronchodilator (BD).
  
  
  
  Ventilation heterogeneity in peripheral conductive (Scond) and acinar (Sacin) airways were measured in 50 asymptomatic smokers and 20 never-smokers using multiple breath nitrogen washout, before and 20 min after inhalation of 200 µg salbutamol and 80 µg ipratropium bromide. Z-scores were calculated to define abnormality in Sacin and Scond.
  
  
  
  Nineteen smokers had abnormal Sacin, and 12 had abnormal Scond; 7 had abnormalities in both. After BD, Sacin improved in smokers with normal Sacin (6.5 ± 15.9%, P = 0.02), smokers with abnormal Sacin (9.2 ± 16.9%, P = 0.03) and in control subjects (11.7 ± 18.2%, P = 0.01), with no differences in improvements between groups. Sacin remained abnormal in 15/19 smokers and their post-BD values correlated with smoking exposure (r = 0.53, P = 0.02). After BD, Scond improved in smokers with abnormal Scond (28.3 ± 15.9%, P = 0.002) and normalized in 9/12 subjects, but not in those with normal Scond (0.25 ± 32.7%, P = 0.44) or control subjects (-1.7 ± 21.2%, P = 0.64).
  
  
  
  In smokers with normal spirometry, abnormal conductive airway function could be attributed to increased bronchomotor tone. In contrast, bronchomotor tone in acinar airways is unaffected by smoking and functional abnormality. There may be different causal mechanisms underlying acinar and conductive airway abnormalities in smokers with normal spirometry.
authors.affiliation: Woolcock Institute of Medical Research, Glebe, New South Wales, Australia. Kanika.jetmalani@sydney.edu.au.|Sydney Medical School, The University of Sydney. Kanika.jetmalani@sydney.edu.au.
authors.forename: Kanika
authors.initials: K
authors.lastname: Jetmalani
authors.affiliation: Woolcock Institute of Medical Research, Glebe, New South Wales, Australia.|Sydney Medical School, The University of Sydney.|Vermont Lung Centre, University of Vermont College of Medicine, Burlington, Vermont, United States.
authors.forename: David G
authors.initials: DG
authors.lastname: Chapman
authors.affiliation: Woolcock Institute of Medical Research, Glebe, New South Wales, Australia.|Sydney Medical School, The University of Sydney.
authors.forename: Cindy
authors.initials: C
authors.lastname: Thamrin
authors.affiliation: Woolcock Institute of Medical Research, Glebe, New South Wales, Australia.|Sydney Medical School, The University of Sydney.|Department of Respiratory Medicine, Concord Hospital, Concord.
authors.forename: Claude S
authors.initials: CS
authors.lastname: Farah
authors.affiliation: Woolcock Institute of Medical Research, Glebe, New South Wales, Australia.|Sydney Medical School, The University of Sydney.|Department of Respiratory Research, George Institute of Global Health.
authors.forename: Norbert
authors.initials: N
authors.lastname: Berend
authors.affiliation: Woolcock Institute of Medical Research, Glebe, New South Wales, Australia.|Sydney Medical School, The University of Sydney.
authors.forename: Cheryl M
authors.initials: CM
authors.lastname: Salome
authors.affiliation: Woolcock Institute of Medical Research, Glebe, New South Wales, Australia.|Sydney Medical School, The University of Sydney.|Department of Respiratory Medicine, Royal North Shore Hospital, Sydney, New South Wales, Australia.
authors.forename: Gregory G
authors.initials: GG
authors.lastname: King
mesh_terms: D000328:Adult; D000420:Albuterol / Q000494:pharmacology*; D001993:Bronchodilator Agents / Q000494:pharmacology*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D009241:Ipratropium / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009130:Muscle, Smooth / Q000187:drug effects*; D012119:Respiration / Q000187:drug effects*; D012907:Smoking; D013147:Spirometry; D055815:Young Adult
chemical_list: D001993:Bronchodilator Agents; D009241:Ipratropium; D000420:Albuterol
keywords: chronic obstructive pulmonary disease; inflammation; respiratory structure and function; tobacco; ventilation