title: Avoiding deep inspirations increases the maximal response to methacholine without altering sensitivity in non-asthmatics.
abstract: Airway hyperresponsiveness is characterised by a leftward shift of the dose-response curve (DRC) and an increase in the maximal response. Deep inspiration (DI) avoidance increases responsiveness in non-asthmatic, but not asthmatic, subjects. The aim was to determine the effect of DI avoidance on the sensitivity and maximal response of the FEV(1) DRC to methacholine. Thirteen non-asthmatic and ten asthmatic subjects underwent a standard cumulative high-dose methacholine challenge (0.1-200μmol). Subsequently, on separate days, increasing single doses of methacholine were administered after 10min of DI avoidance. A sigmoidal equation was fitted to the data to obtain values for α, the position constant, as a measure of sensitivity. The fall in FEV(1) at the highest common dose was used as a measure of the maximal response. The change in flow at 40% control vital capacity on the maximal (V˙40m) and partial (V˙40p) curves were calculated from the first manoeuvre after methacholine and the ratio of the values for V˙40m and V˙40p was calculated as a measure of the bronchodilator effect of DI (BD(DI)). In non-asthmatic subjects, avoiding DI increased the maximum fall in FEV(1) at the highest common dose (p=0.0001) but did not alter α (p=0.75). Avoiding DI before challenge did not alter BD(DI) (p=0.13). DI avoidance had no effect on airway responsiveness in asthmatic subjects. In non-asthmatic subjects, DI avoidance increases airway responsiveness by increasing the maximal response, but does not alter the sensitivity, suggesting that the loss of the effect of DI in asthma contributes to excessive bronchoconstriction.
authors.affiliation: Woolcock Institute of Medical Research, PO Box M77 Missenden Road, Sydney, NSW 2050, Australia. dcha7069@woolcock.org.au
authors.forename: David G
authors.initials: DG
authors.lastname: Chapman
authors.forename: Gregory G
authors.initials: GG
authors.lastname: King
authors.forename: Norbert
authors.initials: N
authors.lastname: Berend
authors.forename: Chantale
authors.initials: C
authors.lastname: Diba
authors.forename: Cheryl M
authors.initials: CM
authors.lastname: Salome
mesh_terms: D001249:Asthma / Q000473:pathology / Q000503:physiopathology*; D001985:Bronchial Provocation Tests / Q000379:methods; D016084:Bronchoconstriction / Q000187:drug effects; D016085:Bronchoconstrictor Agents / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000503:physiopathology*; D008297:Male; D016210:Methacholine Chloride / Q000008:administration & dosage*; D012129:Respiratory Function Tests / Q000379:methods; D015656:Respiratory Mechanics / Q000187:drug effects / Q000502:physiology; D014797:Vital Capacity / Q000187:drug effects / Q000502:physiology
chemical_list: D016085:Bronchoconstrictor Agents; D016210:Methacholine Chloride