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Original Research: ASTHMA |

Predictors of Airway Hyperresponsiveness Differ Between Old and Young Patients With Asthma

Kate M. Hardaker, BSc; Sue R. Downie, PhD; Jessica A. Kermode, BSc (Hons1); Claude S. Farah, MBBS; Nathan J. Brown, PhD; Norbert Berend, MD, FCCP; Gregory G. King, PhD; Cheryl M. Salome, PhD
Author and Funding Information

From the Woolcock Institute of Medical Research (Mss Hardaker and Kermode and Drs Downie, Farah, Brown, Berend, King, and Salome), Glebe; The University of Sydney, Sydney (Mss Hardaker and Kermode and Drs Downie, Farah, Brown, Berend, King, and Salome); the Cooperative Research Centre for Asthma and Airways (Mss Hardaker and Kermode and Drs Downie, Farah, Brown, Berend, King, and Salome), Glebe; and the Department of Respiratory Medicine (Dr King), Royal North Shore Hospital, St Leonards, NSW, Australia.

Correspondence to: Kate Hardaker, BSc, Woolcock Institute of Medical Research, PO Box M77, Missenden Rd, Glebe, NSW, 2050, Australia; e-mail: kateh@woolcock.org.au


Funding/Support: This study was funded by the National Health and Medical Research Council of Australia and the Asthma Foundation of New South Wales.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/site/misc/reprints.xhtml).


© 2011 American College of Chest Physicians


Chest. 2011;139(6):1395-1401. doi:10.1378/chest.10-1839
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Background:  Age-related increases in morbidity and mortality due to asthma may be due to changes in pathophysiology as patients with asthma get older. There is limited knowledge about the effects of age on the predictors of airway hyperresponsiveness (AHR), a key feature of asthma. The aim of this study was to determine if the pathophysiologic predictors of AHR, including inflammation, ventilation heterogeneity, and airway closure, differed between young and old patients with asthma.

Methods:  Sixty-one young (18-46 years) and 43 old (50-80 years) patients with asthma had lung function, lung volumes, fraction of exhaled nitric oxide, ventilation heterogeneity, and airway responsiveness to methacholine measured. Airway response to methacholine was measured by the dose-response slope, as the percent fall in FEV1 per micromole of methacholine. Indices of ventilation heterogeneity were calculated for convection-dependent and diffusion-dependent airways.

Results:  In young patients with asthma, the independent predictors of AHR were convection-dependent ventilation heterogeneity, exhaled nitric oxide, and % predicted FEV1/FVC (model r2 = 0.51, P < .0001). In old patients with asthma, the independent predictors of airway responsiveness were % predicted residual volume, diffusion-dependent ventilation heterogeneity, and % predicted FEV1 (model r2 = 0.57, P < .0001).

Conclusions:  In old patients with asthma, AHR is predicted by gas trapping and ventilation heterogeneity in peripheral, diffusion-dependent airways. In the young, it is predicted by ventilation heterogeneity in less peripheral conducting airways and by inflammation. These findings suggest that there are differences in the pathophysiologic determinants of AHR between young and old patients with asthma.

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