Treatment responsiveness of phenotypes of symptomatic airways obstruction in adults

doi:10.1016/j.jaci.2015.01.013

Journal of Allergy and Clinical Immunology

Volume 136, Issue 3, September 2015, Pages 601-609

https://doi.org/10.1016/j.jaci.2015.01.013 Get rights and content

Background

Asthma and chronic obstructive pulmonary disease (COPD) are heterogeneous disorders encompassing different phenotypes of airflow obstruction, which might differ in their response to treatment.

Objective

The aim of this study was to determine distinct phenotypes comprising the syndromes of asthma and COPD and the treatment responsiveness of these phenotypes to inhaled β-agonist, antimuscarinic, and corticosteroid therapy.

Methods

We undertook a cross-sectional study with 3 phases. In phase 1, 1,264 participants aged 18 to 75 years with self-reported current wheeze and breathlessness were identified from a random population sample of 16,459. In phase 2, 451 participants attended for detailed assessment, including responsiveness to inhaled salbutamol and ipratropium bromide. In phase 3, 168 steroid-naive participants were enrolled in a 12-week trial of inhaled budesonide. Cluster analysis was performed in 389 participants who completed phase 2 with full data. Treatment responsiveness was compared between phenotypes.

Results

Cluster analysis identified 5 phenotypes: moderate-to-severe childhood-onset atopic asthma, asthma-COPD overlap, obese-comorbid, mild childhood-onset atopic asthma, and mild intermittent. Bronchodilation after salbutamol was equal to or greater than that after ipratropium for all phenotypes. The moderate-to-severe childhood-onset atopic asthma, asthma-COPD overlap, and obese-comorbid phenotypes had greater efficacy with inhaled corticosteroid treatment than the mild intermittent group.

Conclusion

Cluster analysis of adults with symptomatic airflow obstruction identifies 5 disease phenotypes, including asthma-COPD overlap and obese-comorbid phenotypes, and provides evidence that patients with the asthma-COPD overlap syndrome might benefit from inhaled corticosteroid therapy.

Section snippets

Methods

This study was a 3-phase cross-sectional study. Study methods are summarized, with additional details provided in this article's Online Repository at www.jacionline.org. The study was approved by the New Zealand Central Ethics Committee, and all participants provided written informed consent. The trial was registered on the Australian New Zealand Clinical Trials Registry (ACTRN12610000666022).

Screening and enrollment

Participant flow through the study is shown in Fig 1. Of 16,459 subjects, 11,397 (69.2%) responded to the questionnaire, and 1,264 (14.8%) of 8,563 respondents with completed questionnaires had wheeze and breathlessness in the last 12 months and were invited to attend for detailed evaluation. Four hundred fifty-one participants were enrolled in phase 2, and 389 (86.3%) had complete data. A description of the 389 participants included in the cluster analysis is shown in Table I.

Cluster analysis

Discussion

This study identified 5 phenotypes in adults with symptoms of airflow obstruction. We confirmed the presence of an asthma-COPD overlap group and identified 2 groups of childhood-onset atopic asthma distinguished by severity; a symptomatic adult-onset group associated with obesity, comorbidities and systemic inflammation; and an adult-onset group with mild intermittent disease. The responses to inhaled β-agonist, antimuscarinic, and corticosteroid treatments differed between phenotypes and might

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Asthma-COPD Overlap and Chronic Airflow Obstruction: Definitions, Management, and Unanswered Questions
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Asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) is a common clinical presentation of chronic airways disease in which patients show some features usually associated with asthma, and some usually associated with COPD. There is ongoing debate over whether ACO is a discrete clinical entity, or if it is part of a continuum of airways disease. Furthermore, there is considerable variation among current definitions of ACO, which makes diagnosis potentially challenging for clinicians. Treating ACO may be equally challenging because ACO is an understudied population, and the evidence base for its management comes largely from asthma and COPD studies, the relevance of which deserves careful consideration. In this review, we synthesize the various approaches to ACO diagnosis and evaluate the role of currently available diagnostic tests. We describe the potential benefits of existing asthma and COPD therapies in treating patients with ACO, and the value of a “treatable traits” approach to ACO management. Throughout the review, we highlight some of the pressing, unanswered questions surrounding ACO that are relevant to the clinical community. Ultimately, addressing these questions is necessary if we are to improve clinical outcomes for this complex and heterogeneous patient population.
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Disease phenotyping is a key step towards an increasingly personalized approach to COPD, leading to more precise assessment, treatment and definition of disease outcomes. Indeed, a number of COPD phenotypes differing in natural history, degree of severity, exacerbation rates and response to specific treatments have been described [4,5]. Interestingly, a recent study applying clustering to different COPD cohorts indicated that rather than discrete phenotypes, the heterogeneity of COPD reflects continuous disease traits concomitantly expressed, in variable degrees, within each patient [6].
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: The primary funder of the study was the Health Research Council of New Zealand (grant no. 10/174). Additional research funding was provided by AstraZeneca AB, Sweden; AstraZeneca Limited, New Zealand; and Genentech.

: Disclosure of potential conflict of interest: D. Bowles is employed by the Medical Research Institute of New Zealand, which has received funding from the HRC of New Zealand, and has received travel support from Boehringer Ingelheim. R. Beasley has received personal fees from GlaxoSmithKline, Cytos Biotechnology, Pharmaxis, Novartis, AstraZeneca, Boehringer Ingelheim, Nycomed, and Otsuka Pharmaceuticals and he has received grants from Novartis, AstraZeneca, Cephalon, Chiesi, and Genentech. The rest of the authors declare that they have no relevant conflicts of interest.

: Australian New Zealand Clinical Trials Registry no. ACTRN12610000666022.

View full text

Asthma and lower airway diseaseTreatment responsiveness of phenotypes of symptomatic airways obstruction in adults

Background

Objective

Methods

Results

Conclusion

Section snippets

Methods

Screening and enrollment

Cluster analysis

Discussion

Lancet

Lancet

J Allergy Clin Immunol

Respir Med

Respir Med

Lancet

Lancet

Asthma phenotypes: the evolution from clinical to molecular approaches

Nat Med

Chronic obstructive pulmonary disease phenotypes: the future of COPD

Am J Respir Crit Care Med

Asthma Phenotypes and Interleukin-13—moving closer to personalized medicine

N Engl J Med

Moving from the Oslerian paradigm to the post-genomic era: are asthma and COPD outdated terms?

Thorax

Multi–dimensional phenotyping: towards a new taxonomy for airway disease

Clin Exp Allergy

Use of cluster analysis to define COPD phenotypes

Eur Respir J

Identification and prospective validation of clinically relevant chronic obstructive pulmonary disease (COPD) subtypes

Thorax

Cluster analysis and clinical asthma phenotypes

Am J Respir Crit Care Med

Towards individualised medicine for airways disease: identifying clinical phenotype groups

Eur Respir J

Standardisation of spirometry

Eur Respir J

Complete reference ranges for pulmonary function tests from a single New Zealand population

N Z Med J

ATS/ERS recommendations for standardized procedures for the online and offline measurement of exhaled lower respiratory nitric oxide and nasal nitric oxide, 2005

Am J Respir Crit Care Med

A self-complete measure of health status for chronic airflow limitation. The St. George's Respiratory Questionnaire

Am Rev Respir Dis

Asthma and lower airway disease
Treatment responsiveness of phenotypes of symptomatic airways obstruction in adults