- Email: [email protected]
COPD management: need for more consensus
Correspondence
for Chronic Obstructive Lung Disease (GOLD) 2011 pharmacotherapy recommendations for stable COPD, which abandoned the usual stepwise approach to treatment. All subsequent GOLD updates, including the most recent one from 2015, are confusing, difficult to use, and do not give clear guidance on pharmacological management. Since most primary care doctors in practice rely only on the tables and figures of the GOLD At-A-Glance Desk Reference as opposed to the 117 pages of the full GOLD document they will miss the problem—that most patients in C and D stages are non-exacerbators2 yet the first-choice recommendation for exacerbation prophylaxis is inhaled corticosteroids. This issue might explain the widespread overuse of these drugs even without clear indication. Adding the algorithm from Cooper and Barjaktarevic to the multidimensional GOLD assessment would overcome the most important weakness of the current GOLD document and enable its use in routine practice, in both primary and secondary care. However, several features of the algorithm deserve further considerations. First, Clinical Stage 0 might not be necessary because smoking cessation and environmental or occupational hygiene strategies are needed for everyone affected, irrespective of the unpredictable subsequent development of COPD. Second, Clinical Stage 1 COPD with intermittent breathlessness or wheezing is a fairly unusual presentation because such patients usually cope even without treatment for their symptoms.3 If patients in Clinical Stage 1 COPD are seeking medical care at all they need further diagnostic procedures to exclude New York Heart Association stage 1 or 2 heart failure or asthma. Both disorders need treatment other than shortacting bronchodilators. Furthermore, patients with true www.thelancet.com/respiratory Vol 3 July 2015
Clinical Stage 1 COPD already reduce their physical activity 4 because they have exertional dyspnoea. If compared with shortacting bronchodilators, as recommended by Cooper and Barjaktarevic, these patients could benefit more from a longacting bronchodilator, which would be better for the prevention of dynamic hyperinflation, the most common cause of shortness of breath on exertion in patients with COPD.5 Currently available shortacting muscarinic antagonists are not rapid-acting and as a monotherapy would not be preferred treatment for shortness of breath on exertion in most patients. Third, the authors use of the term of uncontrolled COPD (in parallel with asthma) might be misleading— COPD patients never achieve asthmalike disease control, with respect to the persistent airflow limitation, which is an integral part of the COPD definition. Certainly, COPD is a treatable disease, but available treatments can only relieve, not abolish, symptoms. Fourth, although the role of inhaled corticosteroids in fixed combinations for the treatment of COPD is controversial,6 these drugs probably should not be restricted exclusively to use in patients diagnosed with the poorly defined asthma-COPD overlap syndrome, as Cooper and Barjaktarevic seem to suggest. Finally, I believe that the most important strength of Cooper and Barjaktarevic’s Comment 1 is its introduction of highly relevant and clinically readily available phenotyping for severe COPD, thus differentiating between general and phenotypic treatment for patients with very severe disease. This approach is similar to that used in the Global Initiative for Asthma 2014 asthma treatment algorithm. This phenotyping will also encourage a proactive search for comorbidities in patients with severely symptomatic COPD.
I declare no competing interests.
Peter Kardos [email protected] Group Practice and Centre for Allergy, Respiratory, and Sleep Medicine, Maingau Red Cross Hospital, 60318 Frankfurt, Germany 1
2
3
4
5
6
Cooper CB, Barjaktarevic I. A new algorithm for the management of COPD. Lancet Respir Med 2015; 3: 266–68. Agusti A, Hurd S, Jones P, et al. FAQs about the GOLD 2011 assessment proposal of COPD: a comparative analysis of four different cohorts. Eur Respir J 2013; 42: 1391–401. Buffels J, Degryse J, Heyrman J, Decramer M. Office spirometry significantly improves early detection of COPD in general practice: the DIDASCO Study. Chest 2004; 125: 1394–99. Watz H, Waschki B, Meyer T, Magnussen H. Physical activity in patients with COPD. Eur Respir J 2009; 33: 262–72. O’Donnell DE, Laveneziana P. Dyspnea and activity limitation in COPD: mechanical factors. COPD 2007; 4: 225–36. Celli BR, Decramer M, Wedzicha JA, Wilson KC, Agusti A, Criner GJ et al. An official American Thoracic Society/European Respiratory Society statement: research questions in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2015; 191: e4–e27.
For links to GOLD recommendations see http:// www.goldcopd.org/Guidelines/ guidelines-resources.html For more on the Global Initiative for Asthma 2014 see http://www.ginasthma.org/ local/uploads/files/GINA_ Report_2015.pdf
We question the potential effect of the new algorithm proposed by Christopher Cooper and Igor Barjaktarevic1 for the management of patients with chronic obstructive pulmonary disease (COPD). In the algorithm, clinical phenotyping is only suggested in patients with “uncontrolled disease”.1 However, patients with mild airflow limitation and bronchial hyperresponsiveness might respond well to inhaled corticosteroids. Eosinophil count has been shown to be a promising biomarker for response to inhaled corticosteroids.2 Additionally, patients with low-severity airflow limitation, but substantial static hyperinflation and exercise-induced dyspnoea, might benefit from optimum bronchodilator therapy.3 Therefore, early clinical phenotyping seems necessary to provide appropriate pharmacological therapy, even in patients with intermittent symptoms of dyspnoea. The choice of longacting beta agonist or longacting muscarinic antagonist seems interchangeable in Cooper and Barjaktarevic’s algorithm.1 Initiation of monotherapy e21
Correspondence
Scott Camazine/Science Photo Library
before step up to dual longacting bronchodilation is based on costs, simplicity, and physician preference.1 Because these drugs are combined in the same inhaler, simplicity can now be regarded as equal. Importantly, the expiratory airflow limitation seems more accelerated, and therefore more relevant, in the initial phases of COPD than in the later phases.4 To have an effect on the natural history of COPD, optimisation of treatment in the earlier stages is logical, particularly in patients with a rapid decline in lung function (which again points to the importance of early phenotyping).4 Shortacting drugs disappear after the clinical stage defined by persistent symptoms.1 Nevertheless, these patients in particular request as-needed rescue treatment in addition to optimum longacting bronchodilator therapy. Respiratory failure is recognised in the description of the clinical phenotypes of severe COPD. However, the potential of non-invasive ventilation in such patients is completely ignored.5 The proposed algorithm is also too simple to cover the complex, non-pulmonary features and common comorbidities of COPD. Cooper and Barjaktarevic do state that “reconditioning exercise is recommended for patients with moderate to severe COPD and evidence of impaired exercise performance or involuntary weight loss—ie, the debilitated phenotype”. According to the authors, a “debilitated” patient with COPD has a 6-min walk distance below 140 m, which needs to be treated with rehabilitative exercise and anabolics. Nevertheless, the 2013 statement on pulmonary rehabilitation from the American Thoracic Society and the European Respiratory Society clearly states that pulmonary rehabilitation should be considered in patients with chronic lung disease and daily symptoms, activity limitations, or poor adjustment to the disease, despite otherwise optimum medical treatment. 6 As such, the group of patients eligible e22
for pulmonary rehabilitation is clearly broader than only the so-called debilitated phenotype. Moreover, safety and efficacy of anabolic hormonal supplementation in combination with exercise training has been little studied in patients with COPD.6 As such, it is too early to recommend its use in all patients with COPD who have a 6-min walk distance below 140 m. Occupational therapy, nutritional counselling, and psychological counselling should be considered, on the basis of a pre-rehabilitation assessment. Finally, evidence also exists to show that (collaborative) self-management interventions have a positive effect on daily symptoms, disease-specific health status, and health-care use in patients with COPD.7 This approach is also missing from the proposed algorithm. We strongly believe that Cooper and Barjaktarevic’s proposed algorithm is too restricted to improve future management of individual patients with COPD. Because the degree of airflow limitation is moderately associated with daily symptoms, comorbidities, exercise intolerance, and impaired health status in patients with COPD, and non-pharmacological therapy based on early clinical phenotyping, need to be emphasised in the management of COPD. EFMW has received payment for board membership from Nycomed, research grants from AstraZeneca and GlaxoSmithKline, and payment for service on speakers bureaus from AstraZeneca, GlaxoSmithKline, and Novartis. All other authors declare no competing interests.
*Lowie E G W Vanfleteren, Frits ME Franssen, Emiel F M Wouters, Martijn A Spruit lowievanfl[email protected] Department of Respiratory Medicine, Maastricht University Medical Center, Maastricht, 6200 MD, Netherlands (LEGWV, FMEF, EFMW); and Rehabilitation Research Center (REVAL), Biomedical Research Institute (BIOMED), Faculty of Medicine and Life Sciences, Hasselt University, Diepenbeek, Belgium (MAS) 1
Cooper CB, Barjaktarevic I. A new algorithm for the management of COPD. Lancet Respir Med 2015; 3: 266–68.
2
3
4
5
6
7
Pascoe S, Locantore N, Dransfield MT, Barnes NC, Pavord ID. Blood eosinophil counts, exacerbations, and response to the addition of inhaled fluticasone furoate to vilanterol in patients with chronic obstructive pulmonary disease: a secondary analysis of data from two parallel randomised controlled trials. Lancet Respir Med 2015; 3: 435–42. O’Donnell DE, Fluge T, Gerken F, et al. Effects of tiotropium on lung hyperinflation, dyspnoea and exercise tolerance in COPD. Eur Respir J 2004; 23: 832–40. Tantucci C, Modina D. Lung function decline in COPD. Int J Chron Obstruct Pulm Dis 2012; 7: 95–99. Kohnlein T, Windisch W, Kohler D, et al. Non-invasive positive pressure ventilation for the treatment of severe stable chronic obstructive pulmonary disease: a prospective, multicentre, randomised, controlled clinical trial. Lancet Respir Med 2014; 2: 698–705. Spruit MA, Singh SJ, Garvey C, et al. An official American Thoracic Society/European Respiratory Society statement: key concepts and advances in pulmonary rehabilitation. Am J Resp Crit Care Med 2013; 188: e13–64. Zwerink M, Brusse-Keizer M, van der Valk PD, et al. Self management for patients with chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2014; 3: CD002990.
Authors’ reply We appreciate the supportive comments from Peter Kardos about our proposed new algorithm for the management of chronic obstructive pulmonary disease (COPD).1 Clearly, we share similar concerns about the absence of guidance provided by the current Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommendations and the need for a clear and accessible set of recommendations for disease management. At the same time, we acknowledge the criticisms of Lowie Vanfleteren and colleagues, who point out that COPD is complex because of its unpredictable time course and its diverse clinical manifestations and comorbidities. Our algorithm is intentionally simple and certainly not perfect, but we hope it might offer new insights into the management of COPD that could be readily embraced by primary care physicians and pulmonary specialists alike. The most important concepts in the algorithm are symptomatic staging, with earlier recognition of persistent symptoms leading www.thelancet.com/respiratory Vol 3 July 2015
for Chronic Obstructive Lung Disease (GOLD) 2011 pharmacotherapy recommendations for stable COPD, which abandoned the usual stepwise approach to treatment. All subsequent GOLD updates, including the most recent one from 2015, are confusing, difficult to use, and do not give clear guidance on pharmacological management. Since most primary care doctors in practice rely only on the tables and figures of the GOLD At-A-Glance Desk Reference as opposed to the 117 pages of the full GOLD document they will miss the problem—that most patients in C and D stages are non-exacerbators2 yet the first-choice recommendation for exacerbation prophylaxis is inhaled corticosteroids. This issue might explain the widespread overuse of these drugs even without clear indication. Adding the algorithm from Cooper and Barjaktarevic to the multidimensional GOLD assessment would overcome the most important weakness of the current GOLD document and enable its use in routine practice, in both primary and secondary care. However, several features of the algorithm deserve further considerations. First, Clinical Stage 0 might not be necessary because smoking cessation and environmental or occupational hygiene strategies are needed for everyone affected, irrespective of the unpredictable subsequent development of COPD. Second, Clinical Stage 1 COPD with intermittent breathlessness or wheezing is a fairly unusual presentation because such patients usually cope even without treatment for their symptoms.3 If patients in Clinical Stage 1 COPD are seeking medical care at all they need further diagnostic procedures to exclude New York Heart Association stage 1 or 2 heart failure or asthma. Both disorders need treatment other than shortacting bronchodilators. Furthermore, patients with true www.thelancet.com/respiratory Vol 3 July 2015
Clinical Stage 1 COPD already reduce their physical activity 4 because they have exertional dyspnoea. If compared with shortacting bronchodilators, as recommended by Cooper and Barjaktarevic, these patients could benefit more from a longacting bronchodilator, which would be better for the prevention of dynamic hyperinflation, the most common cause of shortness of breath on exertion in patients with COPD.5 Currently available shortacting muscarinic antagonists are not rapid-acting and as a monotherapy would not be preferred treatment for shortness of breath on exertion in most patients. Third, the authors use of the term of uncontrolled COPD (in parallel with asthma) might be misleading— COPD patients never achieve asthmalike disease control, with respect to the persistent airflow limitation, which is an integral part of the COPD definition. Certainly, COPD is a treatable disease, but available treatments can only relieve, not abolish, symptoms. Fourth, although the role of inhaled corticosteroids in fixed combinations for the treatment of COPD is controversial,6 these drugs probably should not be restricted exclusively to use in patients diagnosed with the poorly defined asthma-COPD overlap syndrome, as Cooper and Barjaktarevic seem to suggest. Finally, I believe that the most important strength of Cooper and Barjaktarevic’s Comment 1 is its introduction of highly relevant and clinically readily available phenotyping for severe COPD, thus differentiating between general and phenotypic treatment for patients with very severe disease. This approach is similar to that used in the Global Initiative for Asthma 2014 asthma treatment algorithm. This phenotyping will also encourage a proactive search for comorbidities in patients with severely symptomatic COPD.
I declare no competing interests.
Peter Kardos [email protected] Group Practice and Centre for Allergy, Respiratory, and Sleep Medicine, Maingau Red Cross Hospital, 60318 Frankfurt, Germany 1
2
3
4
5
6
Cooper CB, Barjaktarevic I. A new algorithm for the management of COPD. Lancet Respir Med 2015; 3: 266–68. Agusti A, Hurd S, Jones P, et al. FAQs about the GOLD 2011 assessment proposal of COPD: a comparative analysis of four different cohorts. Eur Respir J 2013; 42: 1391–401. Buffels J, Degryse J, Heyrman J, Decramer M. Office spirometry significantly improves early detection of COPD in general practice: the DIDASCO Study. Chest 2004; 125: 1394–99. Watz H, Waschki B, Meyer T, Magnussen H. Physical activity in patients with COPD. Eur Respir J 2009; 33: 262–72. O’Donnell DE, Laveneziana P. Dyspnea and activity limitation in COPD: mechanical factors. COPD 2007; 4: 225–36. Celli BR, Decramer M, Wedzicha JA, Wilson KC, Agusti A, Criner GJ et al. An official American Thoracic Society/European Respiratory Society statement: research questions in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2015; 191: e4–e27.
For links to GOLD recommendations see http:// www.goldcopd.org/Guidelines/ guidelines-resources.html For more on the Global Initiative for Asthma 2014 see http://www.ginasthma.org/ local/uploads/files/GINA_ Report_2015.pdf
We question the potential effect of the new algorithm proposed by Christopher Cooper and Igor Barjaktarevic1 for the management of patients with chronic obstructive pulmonary disease (COPD). In the algorithm, clinical phenotyping is only suggested in patients with “uncontrolled disease”.1 However, patients with mild airflow limitation and bronchial hyperresponsiveness might respond well to inhaled corticosteroids. Eosinophil count has been shown to be a promising biomarker for response to inhaled corticosteroids.2 Additionally, patients with low-severity airflow limitation, but substantial static hyperinflation and exercise-induced dyspnoea, might benefit from optimum bronchodilator therapy.3 Therefore, early clinical phenotyping seems necessary to provide appropriate pharmacological therapy, even in patients with intermittent symptoms of dyspnoea. The choice of longacting beta agonist or longacting muscarinic antagonist seems interchangeable in Cooper and Barjaktarevic’s algorithm.1 Initiation of monotherapy e21
Correspondence
Scott Camazine/Science Photo Library
before step up to dual longacting bronchodilation is based on costs, simplicity, and physician preference.1 Because these drugs are combined in the same inhaler, simplicity can now be regarded as equal. Importantly, the expiratory airflow limitation seems more accelerated, and therefore more relevant, in the initial phases of COPD than in the later phases.4 To have an effect on the natural history of COPD, optimisation of treatment in the earlier stages is logical, particularly in patients with a rapid decline in lung function (which again points to the importance of early phenotyping).4 Shortacting drugs disappear after the clinical stage defined by persistent symptoms.1 Nevertheless, these patients in particular request as-needed rescue treatment in addition to optimum longacting bronchodilator therapy. Respiratory failure is recognised in the description of the clinical phenotypes of severe COPD. However, the potential of non-invasive ventilation in such patients is completely ignored.5 The proposed algorithm is also too simple to cover the complex, non-pulmonary features and common comorbidities of COPD. Cooper and Barjaktarevic do state that “reconditioning exercise is recommended for patients with moderate to severe COPD and evidence of impaired exercise performance or involuntary weight loss—ie, the debilitated phenotype”. According to the authors, a “debilitated” patient with COPD has a 6-min walk distance below 140 m, which needs to be treated with rehabilitative exercise and anabolics. Nevertheless, the 2013 statement on pulmonary rehabilitation from the American Thoracic Society and the European Respiratory Society clearly states that pulmonary rehabilitation should be considered in patients with chronic lung disease and daily symptoms, activity limitations, or poor adjustment to the disease, despite otherwise optimum medical treatment. 6 As such, the group of patients eligible e22
for pulmonary rehabilitation is clearly broader than only the so-called debilitated phenotype. Moreover, safety and efficacy of anabolic hormonal supplementation in combination with exercise training has been little studied in patients with COPD.6 As such, it is too early to recommend its use in all patients with COPD who have a 6-min walk distance below 140 m. Occupational therapy, nutritional counselling, and psychological counselling should be considered, on the basis of a pre-rehabilitation assessment. Finally, evidence also exists to show that (collaborative) self-management interventions have a positive effect on daily symptoms, disease-specific health status, and health-care use in patients with COPD.7 This approach is also missing from the proposed algorithm. We strongly believe that Cooper and Barjaktarevic’s proposed algorithm is too restricted to improve future management of individual patients with COPD. Because the degree of airflow limitation is moderately associated with daily symptoms, comorbidities, exercise intolerance, and impaired health status in patients with COPD, and non-pharmacological therapy based on early clinical phenotyping, need to be emphasised in the management of COPD. EFMW has received payment for board membership from Nycomed, research grants from AstraZeneca and GlaxoSmithKline, and payment for service on speakers bureaus from AstraZeneca, GlaxoSmithKline, and Novartis. All other authors declare no competing interests.
*Lowie E G W Vanfleteren, Frits ME Franssen, Emiel F M Wouters, Martijn A Spruit lowievanfl[email protected] Department of Respiratory Medicine, Maastricht University Medical Center, Maastricht, 6200 MD, Netherlands (LEGWV, FMEF, EFMW); and Rehabilitation Research Center (REVAL), Biomedical Research Institute (BIOMED), Faculty of Medicine and Life Sciences, Hasselt University, Diepenbeek, Belgium (MAS) 1
Cooper CB, Barjaktarevic I. A new algorithm for the management of COPD. Lancet Respir Med 2015; 3: 266–68.
2
3
4
5
6
7
Pascoe S, Locantore N, Dransfield MT, Barnes NC, Pavord ID. Blood eosinophil counts, exacerbations, and response to the addition of inhaled fluticasone furoate to vilanterol in patients with chronic obstructive pulmonary disease: a secondary analysis of data from two parallel randomised controlled trials. Lancet Respir Med 2015; 3: 435–42. O’Donnell DE, Fluge T, Gerken F, et al. Effects of tiotropium on lung hyperinflation, dyspnoea and exercise tolerance in COPD. Eur Respir J 2004; 23: 832–40. Tantucci C, Modina D. Lung function decline in COPD. Int J Chron Obstruct Pulm Dis 2012; 7: 95–99. Kohnlein T, Windisch W, Kohler D, et al. Non-invasive positive pressure ventilation for the treatment of severe stable chronic obstructive pulmonary disease: a prospective, multicentre, randomised, controlled clinical trial. Lancet Respir Med 2014; 2: 698–705. Spruit MA, Singh SJ, Garvey C, et al. An official American Thoracic Society/European Respiratory Society statement: key concepts and advances in pulmonary rehabilitation. Am J Resp Crit Care Med 2013; 188: e13–64. Zwerink M, Brusse-Keizer M, van der Valk PD, et al. Self management for patients with chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2014; 3: CD002990.
Authors’ reply We appreciate the supportive comments from Peter Kardos about our proposed new algorithm for the management of chronic obstructive pulmonary disease (COPD).1 Clearly, we share similar concerns about the absence of guidance provided by the current Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommendations and the need for a clear and accessible set of recommendations for disease management. At the same time, we acknowledge the criticisms of Lowie Vanfleteren and colleagues, who point out that COPD is complex because of its unpredictable time course and its diverse clinical manifestations and comorbidities. Our algorithm is intentionally simple and certainly not perfect, but we hope it might offer new insights into the management of COPD that could be readily embraced by primary care physicians and pulmonary specialists alike. The most important concepts in the algorithm are symptomatic staging, with earlier recognition of persistent symptoms leading www.thelancet.com/respiratory Vol 3 July 2015