ORIGINAL ARTICLE Effect of obesity on breathlessness and airway responsiveness to methacholine in non-asthmatic subjects CM Salome 1,2,3 , PA Munoz 1,2 , N Berend 1,2,3,4 , CW Thorpe 1,2,5 , LM Schachter 1,3 and GG King 1,2,3,4 1 Woolcock Institute of Medical Research, Camperdown, New South Wales, Australia; 2 Cooperative Research Centre for Asthma, Camperdown, New South Wales, Australia; 3 Department of Medicine, University of Sydney, Sydney, New South Wales, Australia; 4 Department of Respiratory Medicine, Royal North Shore Hospital, St Leonards, New South Wales, Australia and 5 Bioengineering Institute, University of Auckland, Auckland, New Zealand Background: Obesity is associated with increased prevalence and incidence of asthma, but the mechanism is unknown. Obesity reduces lung volumes, which can increase airway responsiveness, and increases resistive and elastic work of breathing, which can increase dyspnea. Objective: To determine if the intensity of dyspnea due to airway narrowing or if airway responsiveness is increased in obese, non-asthmatic subjects. Subjects: Twenty-three obese (BMI (body mass index) X30 kg m 2 ) and 26 non-obese (BMI o30 kg m 2 ) non-asthmatic subjects, aged between 18 and 70 years. Methods: High-dose methacholine challenge was used to determine the sensitivity and the maximal response to methacholine. Respiratory system resistance (Rrs) and reactance were measured, using the forced oscillation technique, as indicators of resistive and elastic loads during challenge. Perception of dyspnea was measured by the Borg score during challenge. Static lung volumes were measured by body plethysmography. Results: Static lung volumes were reduced in the obese subjects. There were no significant differences in the sensitivity or maximal response to methacholine between obese and non-obese subjects. The magnitude of change in Rrs was similar in both groups, but obese subjects had more negative reactance after challenge (P ¼ 0.002) indicating a greater elastic load. The intensity of dyspnea was greater in obese subjects (P ¼ 0.03). Conclusions: Obesity reduces lung volumes, but does not alter the sensitivity or maximal response to methacholine. However, obese subjects have enhanced perception of dyspnea, associated with greater apparent stiffness of the respiratory system, and may therefore be at greater risk of symptoms. International Journal of Obesity (2008) 32, 502–509; doi:10.1038/sj.ijo.0803752; published online 23 October 2007 Keywords: airway responsiveness; static lung volumes; elastance Introduction Obesity has been linked with an increased risk of asthma in at least 30 cross-sectional or case–control studies 1 and longitudinal studies have demonstrated that both obesity and weight gain precede the development of asthma. 2 In the majority of these studies, the presence of asthma was detected by questionnaire, using self-reported symptoms or self-reported asthma to define the condition. However, there is little evidence from population studies that obesity is associated with objective markers of asthma such as airway hyperresponsiveness (AHR), 3–7 airway obstruction 8 or airway inflammation. 9 Asthma is defined by both episodic symptoms and variable airway obstruction. AHR, defined as excessive airway narrowing in response to provoking stimuli, is a marker of the tendency to variable airway obstruction and is a fundamental characteristic of asthma. To understand the association between obesity and asthma, we need to know if obesity can affect symptoms in the absence of any effect on AHR. Airway hyperresponsiveness is characterized both by increased sensitivity to provoking stimuli, defined by a leftward shift in the dose–response curve, and by increased maximal narrowing, defined by an increase in the maximal response plateau on the dose–response curve. 10,11 Previous Received 12 April 2007; revised 3 September 2007; accepted 9 September 2007; published online 23 October 2007 Correspondence: Dr C Salome, Woolcock Institute of Medical Research, PO Box M77, Missenden Road, Camperdown, NSW 2050, Australia. E-mail: cms@woolcock.org.au International Journal of Obesity (2008) 32, 502–509 & 2008 Nature Publishing Group All rights reserved 0307-0565/08 $30.00 www.nature.com/ijo