Chest
Volume 139, Issue 6, June 2011, Pages 1395-1401
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Original Research
Asthma
Predictors of Airway Hyperresponsiveness Differ Between Old and Young Patients With Asthma

https://doi.org/10.1378/chest.10-1839Get rights and content

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.

Section snippets

Subjects

Subjects were recruited by advertising throughout The University of Sydney and from the volunteer database at the Woolcock Institute of Medical Research. Inclusion criteria were physician diagnosis of asthma plus current symptoms of asthma requiring regular treatment. Subjects were excluded if they had smoked within the last 6 months, had a smoking history ≥ 10 pack-years, had any major respiratory disease other than asthma, had a respiratory tract infection, or used oral prednisone in the

Subjects

One hundred four subjects with asthma participated in the study. Table 1 shows the characteristics of subjects in the young and old groups. The prevalence of AHR was lower in the old group (49%) than in the young group (70%, P = .03). Compared with young patients with asthma, the old patients with asthma had longer disease duration, more airflow obstruction, less severe AHR, and lower Feno. Diffusion-dependent ventilation heterogeneity (Sacin) was worse in the old group than in the young group,

Discussion

In this study of young (18-46 years) and old (≥ 50 years) adults with asthma, we found differences in the pathophysiologic determinants of AHR. The presence of significant interactions between age group and key predictor variables implied that there were significant qualitative differences between age groups in their relationship with AHR, which made it essential to analyze the two groups separately. In old patients with asthma, AHR was predicted by gas trapping (% predicted RV), Sacin, and

Acknowledgments

Author contributions: Ms Hardaker and Dr Salome had access to the data and take responsibility for the integrity of the data and the accuracy of the data analysis.

Ms Hardaker: contributed to the implementation, statistical analysis, interpretation, and writing.

Dr Downie: contributed to the design, implementation, interpretation, and writing.

Ms Kermode: contributed to the implementation, interpretation, and writing.

Dr Farah: contributed to the implementation, interpretation, and writing.

Dr Brown:

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    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).

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