title: Increased airway closure is a determinant of airway hyperresponsiveness.
abstract: In order to investigate whether increased airway closure is a component of airway hyperresponsiveness (AHR), airway closure was compared during induced bronchoconstriction in 62 asthmatic, 41 nonasthmatic nonobese (control) and 20 nonasthmatic obese (obese) subjects. Airway closure and airway narrowing were measured by spirometry as percentage change in forced vital capacity (%DeltaFVC) and change in forced expiratory ratio (DeltaFER), respectively. Multiple regression analyses were used to assess the determinants of AHR, assessed by the dose response slope (DRS). The DRS was significantly increased in asthmatics compared with controls but did not differ between obese and controls. The spirometric predictors of logDRS were baseline FER, DeltaFER, body mass index (BMI) and %DeltaFVC. There was a negative relationship between BMI and logDRS in the regression, suggesting a protective effect. The present findings suggest that the extent of airway closure during induced bronchoconstriction is a determinant of airway hyperresponsiveness, independent of the level of airway narrowing. However, after adjusting for airway closure, obesity appears to protect against airway hyperresponsiveness.
authors.affiliation: Woolcock Institute of Medical Research, Box M77 Missenden Rd PO, Camperdown NSW 2050 Australia. dcha7069@woolcock.org.au
authors.forename: D G
authors.initials: DG
authors.lastname: Chapman
authors.forename: N
authors.initials: N
authors.lastname: Berend
authors.forename: G G
authors.initials: GG
authors.lastname: King
authors.forename: C M
authors.initials: CM
authors.lastname: Salome
mesh_terms: D000328:Adult; D001249:Asthma / Q000503:physiopathology* / Q000628:therapy; D015992:Body Mass Index; D001980:Bronchi / Q000473:pathology*; D016084:Bronchoconstriction / Q000187:drug effects* / Q000502:physiology; D016085:Bronchoconstrictor Agents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism; D009765:Obesity / Q000503:physiopathology; D013147:Spirometry / Q000379:methods
chemical_list: D016085:Bronchoconstrictor Agents; D016210:Methacholine Chloride; D009569:Nitric Oxide