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      COPD, stage and treatment in a large outpatient clinic

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          ABSTRACT

          Some COPD patients suffer from frequent exacerbations despite triple inhalation treatment. These frequent exacerbators should be identified, as exacerbations often lead to decreasing lung function and increasing mortality. Roflumilast reduces exacerbations in patients with a previous history of exacerbations. Our aim was to describe COPD patient characteristics and compare roflumilast treatment eligible to non-eligible patients. An observational cross-section study was conducted. Patients were included from a large COPD outpatient clinic. Information regarding COPD patient characteristics was registered on a standardized form and lung function was measured. Patients were categorized according to the GOLD classification. Eligibility for roflumilast treatment was assessed and patient characteristics compared between groups. 547 patients were included. Most patients (54%) were in GOLD group D. 62 patients (11.3%) met the criteria for treatment with roflumilast. Among the patients eligible for roflumilast treatment, only 14 patients (22.6%) were receiving treatment. There were no significant differences in FEV 1, number of exacerbations, hospitalization due to exacerbation, MRC grade, age, smoking status and medication use between patients receiving roflumilast and not treated eligible patients. Our study documents low use of roflumilast treatment. In view of the established effect of roflumilast we think that this treatment should be considered more consistently as an option among COPD patients fulfilling the criteria for this therapy.

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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 chronic bronchitic phenotype of COPD: an analysis of the COPDGene Study.

            Victor Kim, MeiLan K Han, Gwendolyn Vance … (2011)
            Chronic bronchitis (CB) in patients with COPD is associated with an accelerated lung function decline and an increased risk of respiratory infections. Despite its clinical significance, the chronic bronchitic phenotype in COPD remains poorly defined. We analyzed data from subjects enrolled in the Genetic Epidemiology of COPD (COPDGene) Study. A total of 1,061 subjects with GOLD (Global Initiative for Chronic Obstructive Lung Disease) stage II to IV were divided into two groups: CB (CB+) if subjects noted chronic cough and phlegm production for ≥ 3 mo/y for 2 consecutive years, and no CB (CB-) if they did not. There were 290 and 771 subjects in the CB+ and CB- groups, respectively. Despite similar lung function, the CB+ group was younger (62.8 ± 8.4 vs 64.6 ± 8.4 years, P = .002), smoked more (57 ± 30 vs 52 ± 25 pack-years, P = .006), and had more current smokers (48% vs 27%, P < .0001). A greater percentage of the CB+ group reported nasal and ocular symptoms, wheezing, and nocturnal awakenings secondary to cough and dyspnea. History of exacerbations was higher in the CB+ group (1.21 ± 1.62 vs 0.63 ± 1.12 per patient, P < .027), and more patients in the CB+ group reported a history of severe exacerbations (26.6% vs 20.0%, P = .024). There was no difference in percent emphysema or percent gas trapping, but the CB+ group had a higher mean percent segmental airway wall area (63.2% ± 2.9% vs 62.6% ± 3.1%, P = .013). CB in patients with COPD is associated with worse respiratory symptoms and higher risk of exacerbations. This group may need more directed therapy targeting chronic mucus production and smoking cessation not only to improve symptoms but also to reduce risk, improve quality of life, and improve outcomes. ClinicalTrials.gov; No.: NCT00608764; URL: www.clinicaltrials.gov.
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              Phosphodiesterase-4 inhibitor therapy for lung diseases.

              L. Fabbri, K. F. Rabe, Bianca Beghè (2013)
              Phosphodiesterases (PDEs) are a superfamily of enzymes that catalyze the breakdown of cAMP and/or cyclic guanosine monophosphate (GMP) to their inactive form. PDE4 is the main selective cAMP-metabolizing enzyme in inflammatory and immune cells. Because PDE4 is highly expressed in leukocytes and other inflammatory cells involved in the pathogenesis of inflammatory lung diseases, such as asthma and chronic obstructive pulmonary disease (COPD), inhibition of PDE4 has been predicted to have an antiinflammatory effect and thus therapeutic efficacy. The limited and inconsistent efficacy and side effects of the early compounds made their further development less desirable in asthma, given the excellent efficacy/tolerability ratio of inhaled steroids. The lack of effective antiinflammatory drug treatment for COPD has thus shifted the interest in development toward COPD. Roflumilast, the only PDE4 inhibitor that has reached the market because of the good efficacy/tolerability ratio, is recommended for patients with COPD with severe airflow limitation, symptoms of chronic bronchitis, and a history of exacerbations, whose disease is not adequately controlled by long-acting bronchodilators. Albeit safe, it maintains significant side effects (diarrhea, nausea, weight loss) that make it intolerable in some patients. Future developments of PDE4 inhibitors include extended indications of roflumilast (1) in patients with COPD, and (2) in other respiratory (e.g., asthma) and nonrespiratory chronic inflammatory/metabolic conditions (e.g., diabetes), as well as (3) the development of new molecules with PDE4 inhibitory properties with an improved efficacy/tolerability profile.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Eur Clin Respir J
                Journal ID (iso-abbrev): Eur Clin Respir J
                Journal ID (archive): ZECR
                Journal ID (publisher-id): zecr20
                Title: European Clinical Respiratory Journal
                Publisher: Taylor & Francis
                ISSN (Electronic): 2001-8525
                Publication date Collection: 2017
                Publication date (Electronic): 4 January 2017
                Volume: 4
                Issue: 1
                Electronic Location Identifier: 1267470
                Affiliations
                [ a ]Department of Respiratory Medicine, Copenhagen University Hospital , Hvidovre, Denmark
                [ b ]Department of Endocrinology, Copenhagen University Hospital , Hvidovre, Denmark
                [ c ]Lunge- og allergiklinikken , Hellerup, Denmark
                Author notes
                CONTACT Claire Præst Holm claire.p.holm@ 123456dadlnet.dk
                Article
                Publisher ID: 1267470
                DOI: 10.1080/20018525.2017.1267470
                PMC ID: 5328358
                SO-VID: e5e5d5d8-9da4-44e4-9798-a95be20a1033
                Copyright © © 2017 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 23 March 2016
                Date accepted : 29 November 2016
                Date revision received : 3 November 2016
                Page count
                Figures: 2, Tables: 1, References: 11, Pages: 6
                Categories
                Subject: Other
                Subject: Short Communication

                Keywords: copd,exacerbations,roflumilast,phosphodiesterase-4 inhibitor,gold groups,outpatients,frequent exacerbator
                Data availability:
                Keywords: copd, exacerbations, roflumilast, phosphodiesterase-4 inhibitor, gold groups, outpatients, frequent exacerbator

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