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Clinical Investigations: ASTHMA |

Predictors of Methacholine Responsiveness in a General Population*

Joel Schwartz, PhD; Christian Schindler, PhD; Elisabeth Zemp, MD; André P. Perruchoud, MD, FCCP; Jean-Pierre Zellweger, MD; Brunello Wüthrich, MD; Philippe Leuenberger, MD; Ursula Ackermann-Liebrich, MD; SAPALDIA Team
Author and Funding Information

Affiliations: *From the Institute of Social and Preventive Medicine (Drs. Schindler, Zemp, and Ackermann-Liebrich), University of Basel, Basel, Switzerland; Harvard School of Public Health (Dr. Schwartz), Boston, MA; Department of Internal Medicine (Dr. Perruchoud), University Clinic Basel, Basel, Switzerland; Division of Pulmonology (Drs. Zellweger and Leuenberger), University of Lausanne, Lausanne, Switzerland; and Department of Dermatology (Dr. Wüthrich), University Hospital Zurich, Zurich, Switzerland.,  A complete list of participants is given in the Appendix.

Correspondence to: Ursula Ackermann-Liebrich, MD, Institute of Social and Preventive Medicine, Steinengraben 49, CH–4051, Basel, Switzerland


Affiliations: *From the Institute of Social and Preventive Medicine (Drs. Schindler, Zemp, and Ackermann-Liebrich), University of Basel, Basel, Switzerland; Harvard School of Public Health (Dr. Schwartz), Boston, MA; Department of Internal Medicine (Dr. Perruchoud), University Clinic Basel, Basel, Switzerland; Division of Pulmonology (Drs. Zellweger and Leuenberger), University of Lausanne, Lausanne, Switzerland; and Department of Dermatology (Dr. Wüthrich), University Hospital Zurich, Zurich, Switzerland.,  A complete list of participants is given in the Appendix.


Chest. 2002;122(3):812-820. doi:10.1378/chest.122.3.812
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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 FEV1 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 FEV1.

Results: We found a nonlinear relationship between methacholine slope and baseline FEV1 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, FEV1, 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.

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