title: Predictors of methacholine responsiveness in a general population.
abstract: OBJECTIVE
  Methacholine responsiveness is an end point widely used in epidemiologic studies of asthma. This study aims to quantify the relative importance of different predictors of responsiveness such as age, sex, airway caliber, smoking and atopic status, and potential interactions deserving further investigation.
  
  
  METHODS
  Methacholine challenge was performed in 7,126 participants (aged 18 to 60 years) of the Swiss Study on Air Pollution and Lung Diseases in Adults according to the European Respiratory Health Survey protocol. Responsiveness was quantified by the slope between percentage decrements in FEV(1) and cumulative methacholine dose. Variation of slopes according to sex, smoking, and atopy was then examined separately by multivariate regression models that controlled for baseline FEV(1).
  
  
  RESULTS
  We found a nonlinear relationship between methacholine slope and baseline FEV(1) for both sexes, which could be well described by a quadratic function. The corresponding curves were almost identical in the region of overlap for male and female neversmokers. Methacholine responsiveness declined with age. The slope of this decline was less steep among nonatopic persons and nonsmokers compared with atopic neversmokers. Methacholine responsiveness increased with the number of cigarettes smoked per day and with the number of positive skin-prick test results (except among heavy smokers).
  
  
  CONCLUSIONS
  Our multiple regression results show that bronchial responsiveness (BR) varies with age, FEV(1), and smoking and atopic status. They suggest that there is a physiologic basis for the univariate sex difference in BR. Secondly, they show that while smaller airways are more responsive than larger ones, the reduction of responsiveness diminishes with each increase of lung size. The quantification of the relative influence of the different factors examined should help in the interpretation of BR.
authors.affiliation: Harvard School of Public Health, USA.
authors.forename: Joel
authors.initials: J
authors.lastname: Schwartz
authors.forename: Christian
authors.initials: C
authors.lastname: Schindler
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Zemp
authors.forename: André P
authors.initials: AP
authors.lastname: Perruchoud
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Zellweger
authors.forename: Brunello
authors.initials: B
authors.lastname: Wüthrich
authors.forename: Philippe
authors.initials: P
authors.lastname: Leuenberger
authors.forename: Ursula
authors.initials: U
authors.lastname: Ackermann-Liebrich
mesh_terms: D000293:Adolescent; D000328:Adult; D000397:Air Pollution / Q000009:adverse effects; D000403:Airway Resistance / Q000187:drug effects*; D001249:Asthma / Q000175:diagnosis; D016535:Bronchial Hyperreactivity / Q000175:diagnosis; D001985:Bronchial Provocation Tests; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D008297:Male; D016210:Methacholine Chloride; D008875:Middle Aged; D012016:Reference Values; D012130:Respiratory Hypersensitivity / Q000175:diagnosis; D012907:Smoking / Q000009:adverse effects; D013557:Switzerland; D014505:Urban Population
chemical_list: D016210:Methacholine Chloride