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      Weighing the evidence for pharmacological treatment interventions in mild COPD; a narrative perspective

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          Abstract

          There is increasing focus on understanding the nature of chronic obstructive pulmonary disease (COPD) during the earlier stages. Mild COPD (Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage 1 or the now-withdrawn GOLD stage 0) represents an early stage of COPD that may progress to more severe disease. This review summarises the disease burden of patients with mild COPD and discusses the evidence for treatment intervention in this subgroup.

          Overall, patients with mild COPD suffer a substantial disease burden that includes persistent or potentially debilitating symptoms, increased risk of exacerbations, increased healthcare utilisation, reduced exercise tolerance and physical activity, and a higher rate of lung function decline versus controls. However, the evidence for treatment efficacy in these patients is limited due to their frequent exclusion from clinical trials. Careful assessment of disease burden and the rate of disease progression in individual patients, rather than a reliance on spirometry data, may identify patients who could benefit from earlier treatment intervention.

          Electronic supplementary material

          The online version of this article (10.1186/s12931-019-1108-9) contains supplementary material, which is available to authorized users.

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          Susceptibility to exacerbation in chronic obstructive pulmonary disease.

          John R. Hurst, Jørgen Vestbo, Antonio Anzueto … (2010)
          Although we know that exacerbations are key events in chronic obstructive pulmonary disease (COPD), our understanding of their frequency, determinants, and effects is incomplete. In a large observational cohort, we tested the hypothesis that there is a frequent-exacerbation phenotype of COPD that is independent of disease severity. We analyzed the frequency and associations of exacerbation in 2138 patients enrolled in the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study. Exacerbations were defined as events that led a care provider to prescribe antibiotics or corticosteroids (or both) or that led to hospitalization (severe exacerbations). Exacerbation frequency was observed over a period of 3 years. Exacerbations became more frequent (and more severe) as the severity of COPD increased; exacerbation rates in the first year of follow-up were 0.85 per person for patients with stage 2 COPD (with stage defined in accordance with Global Initiative for Chronic Obstructive Lung Disease [GOLD] stages), 1.34 for patients with stage 3, and 2.00 for patients with stage 4. Overall, 22% of patients with stage 2 disease, 33% with stage 3, and 47% with stage 4 had frequent exacerbations (two or more in the first year of follow-up). The single best predictor of exacerbations, across all GOLD stages, was a history of exacerbations. The frequent-exacerbation phenotype appeared to be relatively stable over a period of 3 years and could be predicted on the basis of the patient's recall of previous treated events. In addition to its association with more severe disease and prior exacerbations, the phenotype was independently associated with a history of gastroesophageal reflux or heartburn, poorer quality of life, and elevated white-cell count. Although exacerbations become more frequent and more severe as COPD progresses, the rate at which they occur appears to reflect an independent susceptibility phenotype. This has implications for the targeting of exacerbation-prevention strategies across the spectrum of disease severity. (Funded by GlaxoSmithKline; ClinicalTrials.gov number, NCT00292552.)
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            The natural history of chronic airflow obstruction.

            C. Fletcher, R. Peto (1977)
            A prospective epidemiological study of the early stages of the development of chronic obstructive pulmonary disease was performed on London working men. The findings showed that forced expiratory volume in one second (FEV1) falls gradually over a lifetime, but in most non-smokers and many smokers clinically significant airflow obstruction never develops. In susceptible people, however, smoking causes irreversible obstructive changes. If a susceptible smoker stops smoking he will not recover his lung function, but the average further rates of loss of FEV1 will revert to normal. Therefore, severe or fatal obstructive lung disease could be prevented by screening smokers' lung function in early middle age if those with reduced function could be induced to stop smoking. Infective processes and chronic mucus hypersecretion do not cause chronic airflow obstruction to progress more rapidly. There are thus two largely unrelated disease processes, chronic airflow obstruction and the hypersecretory disorder (including infective processes).
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              Regular physical activity reduces hospital admission and mortality in chronic obstructive pulmonary disease: a population based cohort study.

              J Garcia-Aymerich, P Lange, M Benet … (2006)
              Information about the influence of regular physical activity on the course of chronic obstructive pulmonary disease (COPD) is scarce. A study was undertaken to examine the association between regular physical activity and both hospital admissions for COPD and all-cause and specific mortality in COPD subjects. From a population-based sample recruited in Copenhagen in 1981-3 and 1991-4, 2386 individuals with COPD (according to lung function tests) were identified and followed until 2000. Self-reported regular physical activity at baseline was classified into four categories (very low, low, moderate, and high). Dates and causes of hospital admissions and mortality were obtained from Danish registers. Adjusted associations between physical activity and hospital admissions for COPD and mortality were obtained using negative binomial and Cox regression models, respectively. After adjustment for relevant confounders, subjects reporting low, moderate or high physical activity had a lower risk of hospital admission for COPD during the follow up period than those who reported very low physical activity (incidence rate ratio 0.72, 95% confidence interval (CI) 0.53 to 0.97). Low, moderate and high levels of regular physical activity were associated with an adjusted lower risk of all-cause mortality (hazard ratio (HR) 0.76, 95% CI 0.65 to 0.90) and respiratory mortality (HR 0.70, 95% CI 0.48 to 1.02). No effect modification was found for sex, age group, COPD severity, or a background of ischaemic heart disease. Subjects with COPD who perform some level of regular physical activity have a lower risk of both COPD admissions and mortality. The recommendation that COPD patients be encouraged to maintain or increase their levels of regular physical activity should be considered in future COPD guidelines, since it is likely to result in a relevant public health benefit.
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                Author and article information

                Contributors
                Dave Singh: +44 (0)161 946 4073 , dsingh@meu.org.uk
                Anthony D. D’Urzo: tonydurzo@sympatico.ca
                James F. Donohue: james_donohue@med.unc.edu
                Edward M. Kerwin: ekerwin@allergyasthmaso.com
                Journal
                Journal ID (nlm-ta): Respir Res
                Journal ID (iso-abbrev): Respir. Res
                Title: Respiratory Research
                Publisher: BioMed Central (London )
                ISSN (Print): 1465-9921
                ISSN (Electronic): 1465-993X
                Publication date (Electronic): 8 July 2019
                Publication date PMC-release: 8 July 2019
                Publication date (Print): 2019
                Volume: 20
                Electronic Location Identifier: 141
                Affiliations
                [1 ]GRID grid.498924.a, University of Manchester, Medicines Evaluation Unit, , Manchester University NHS Foundation Trust, ; Manchester, M23 9QZ UK
                [2 ]ISNI 0000 0001 2157 2938, GRID grid.17063.33, Department of Family and Community Medicine, , University of Toronto, ; Toronto, Ontario Canada
                [3 ]ISNI 0000 0001 1034 1720, GRID grid.410711.2, Division of Pulmonary Diseases & Critical Care Medicine, , University of North Carolina Pulmonary Critical Medicine, ; Chapel Hill, North Carolina, USA
                [4 ]GRID grid.477143.2, Clinical Research Institute, ; Medford, Oregon, USA
                Article
                Publisher ID: 1108
                DOI: 10.1186/s12931-019-1108-9
                PMC ID: 6615221
                PubMed ID: 31286970
                SO-VID: 2802d5b2-36e8-47b6-9f52-d559da44ab54
                Copyright © © The Author(s). 2019
                License:

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                Date received : 5 March 2019
                Date accepted : 24 June 2019
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100004325, AstraZeneca;
                Award ID: N/A
                Categories
                Subject: Review
                Custom metadata
                issue-copyright-statement © The Author(s) 2019

                ScienceOpen disciplines: Respiratory medicine
                Keywords: chronic obstructive pulmonary disease,corticosteroid,early intervention
                Data availability:
                ScienceOpen disciplines: Respiratory medicine
                Keywords: chronic obstructive pulmonary disease, corticosteroid, early intervention

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