Global strategy for the diagnosis, management, and prevention of chronic obstructive lung disease 2017 report

American Journal of Respiratory and Critical Care Medicine

Volumn 195, Issue 5, 2017, Pages 557-582

  Vogelmeier, Claus F ^a   Criner, Gerard J ^b   Martinez, Fernando J ^c   Anzueto, Antonio ^d,e   Barnes, Peter J ^f   Bourbeau, Jean ^g   Celli, Bartolome R ^h   Chen, Rongchang ⁱ   Decramer, Marc ^j   Fabbri, Leonardo M ^k   Frith, Peter ^l   Halpin, David M G ^m   Varela, M Victorina López ⁿ   Nishimura, Masaharu ^o   Roche, Nicolas ^p   Rodriguez Roisin, Roberto ^q   Sin, Don D ^r   Singh, Dave ^s   Stockley, Robert ^t   Vestbo, Jørgen ^s   Wedzicha, Jadwiga A ^f   Agustí, Alvar ^q   more..

^a PHILIPPS UNIVERSITY MARBURG   (Germany)

^b TEMPLE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c WEILL CORNELL MEDICAL CENTER   (United States)

^d UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT SAN ANTONIO   (United States)

^e SOUTH TEXAS VETERANS HEALTH CARE SYSTEM   (United States)

^f NATIONAL HEART AND LUNG INSTITUTE   (United Kingdom)

^g MCGILL UNIVERSITY HEALTH CENTRE   (Canada)

^h BRIGHAM AND WOMEN S HOSPITAL   (United States)

ⁱ GUANGZHOU MEDICAL UNIVERSITY   (China)

^j UNIVERSITY OF LEUVEN   (Belgium)

^k UNIVERSITY OF MODENA AND REGGIO EMILIA   (Italy)

^l FLINDERS UNIVERSITY   (Australia)

^m ROYAL DEVON AND EXETER HOSPITAL   (United Kingdom)

ⁿ UNIVERSIDAD DE LA REPÚBLICA   (Uruguay)

^o HOKKAIDO UNIVERSITY   (Japan)

^p ASSISTANCE PUBLIQUE HÔPITAUX DE PARIS   (France)

^q UNIVERSITY OF BARCELONA   (Spain)

^r UNIVERSITY OF BRITISH COLUMBIA   (Canada)

^s UNIVERSITY OF MANCHESTER   (United Kingdom)

^t UNIVERSITY HOSPITALS BIRMINGHAM NHS FOUNDATION TRUST   (United Kingdom)

more..

Author keywords

Chronic obstructive pulmonary disease; COPD diagnosis; COPD management; COPD prevention

Indexed keywords

ALPHA 1 ANTITRYPSIN; ANTIBIOTIC AGENT; ANTIINFLAMMATORY AGENT; BRONCHODILATING AGENT; GLUCOCORTICOID; INFLUENZA VACCINE; MUCOLYTIC AGENT; MUSCARINIC RECEPTOR BLOCKING AGENT; PHOSPHODIESTERASE IV INHIBITOR; PNEUMOCOCCUS VACCINE;

ALPHA 1 ANTITRYPSIN DEFICIENCY; ASSISTED VENTILATION; BRONCHOSCOPY; CARDIOVASCULAR DISEASE; CHRONIC OBSTRUCTIVE LUNG DISEASE; DEPRESSION; DIABETES MELLITUS; DISEASE COURSE; EMPHYSEMA; FOLLOW UP; GASTROESOPHAGEAL REFLUX; HOSPICE CARE; HUMAN; HYPERTENSION; LUNG CANCER; MEDICAL EDUCATION; MEDICAL HISTORY; METABOLIC SYNDROME X; NUTRITIONAL SUPPORT; OXYGEN THERAPY; PERIPHERAL VASCULAR DISEASE; PRIORITY JOURNAL; PULMONARY REHABILITATION; RESPIRATORY TRACT DISEASE ASSESSMENT; REVIEW; RISK FACTOR; SELF CARE; SMOKING CESSATION; SMOKING CESSATION PROGRAM; SPIROMETRY; TERMINAL CARE; VACCINATION; GLOBAL HEALTH; INTERNATIONAL COOPERATION; PRACTICE GUIDELINE; PULMONARY DISEASE, CHRONIC OBSTRUCTIVE;

BRONCHODILATOR AGENTS; GLOBAL HEALTH; HUMANS; INTERNATIONALITY; PULMONARY DISEASE, CHRONIC OBSTRUCTIVE; RISK FACTORS; SPIROMETRY;

EID: 85014789444     PISSN: 1073449X     EISSN: 15354970     Source Type: Journal    
DOI: 10.1164/rccm.201701-0218PP     Document Type: Review

References (339)

1. Woodruff PG, Barr RG, Bleecker E, Christenson SA, Couper D, Curtis JL, Gouskova NA, Hansel NN, Hoffman EA, Kanner RE, et al.; SPIROMICS Research Group. Clinical significance of symptoms in smokers with preserved pulmonary function. N Engl J Med 2016; 374:1811-1821.
2. Regan EA, Lynch DA, Curran-Everett D, Curtis JL, Austin JH, Grenier PA, Kauczor HU, Bailey WC, DeMeo DL, Casaburi RH, et al.; Genetic Epidemiology of COPD (COPDGene) Investigators. Clinical and radiologic disease in smokers with normal spirometry. JAMA Intern Med 2015;175:1539-1549.
3. Lamprecht B, McBurnie MA, Vollmer WM, Gudmundsson G, Welte T, Nizankowska-Mogilnicka E, Studnicka M, Bateman E, Anto JM, Burney P, et al.; BOLD Collaborative Research Group. COPD in never smokers: results from the population-based burden of obstructive lung disease study. Chest 2011;139: 752-763.
4. Thomsen M, Nordestgaard BG, Vestbo J, Lange P. Characteristics and outcomes of chronic obstructive pulmonary disease in never smokers in Denmark: a prospective population study. Lancet Respir Med 2013; 1:543-550.
5. Barker DJ, Godfrey KM, Fall C, Osmond C, Winter PD, Shaheen SO. Relation of birth weight and childhood respiratory infection to adult lung function and death from chronic obstructive airways disease. BMJ 1991;303:671-675.
6. Todisco T, de Benedictis FM, Iannacci L, Baglioni S, Eslami A, Todisco E, Dottorini M. Mild prematurity and respiratory functions. Eur J Pediatr 1993;152:55-58.
7. Stern DA, Morgan WJ, Wright AL, Guerra S, Martinez FD. Poor airway function in early infancy and lung function by age 22 years: a non-selective longitudinal cohort study. Lancet 2007; 370:758-764.
8. Lawlor DA, Ebrahim S, Davey Smith G. Association of birth weight with adult lung function: findings from the British Women's Heart and Health Study and a meta-analysis. Thorax 2005;60: 851-858.
9. Kohansal R, Martinez-Camblor P, Agustí A, Buist AS, Mannino DM, Soriano JB. The natural history of chronic airflow obstruction revisited: an analysis of the Framingham offspring cohort. Am J Respir Crit Care Med 2009;180:3-10.
10. Raad D, Gaddam S, Schunemann HJ, Irani J, Abou Jaoude P, Honeine R, Akl EA. Effects of water-pipe smoking on lung function: a systematic review and meta-analysis. Chest 2011;139:764-774.
11. She J, Yang P, Wang Y, Qin X, Fan J, Wang Y, Gao G, Luo G, Ma K, Li B, et al. Chinese water-pipe smoking and the risk of COPD. Chest 2014;146:924-931.
12. Günen H, Tarraf H, Nemati A, Al Ghobain M, Al Mutairi S, Aoun Bacha Z. Waterpipe tobacco smoking. Tuberk Toraks 2016;64: 94-96.
13. Tan WC, Lo C, Jong A, Xing L, Fitzgerald MJ, Vollmer WM, Buist SA, Sin DD; Vancouver Burden of Obstructive Lung Disease (BOLD) Research Group. Marijuana and chronic obstructive lung disease: a population-based study. CMAJ 2009;180:814-820.
14. Yin P, Jiang CQ, Cheng KK, Lam TH, Lam KH, Miller MR, Zhang WS, Thomas GN, Adab P. Passive smoking exposure and risk of COPD among adults in China: the Guangzhou Biobank Cohort Study. Lancet 2007;370:751-757.
15. Tager IB, Ngo L, Hanrahan JP. Maternal smoking during pregnancy: effects on lung function during the first 18 months of life. Am J Respir Crit Care Med 1995;152:977-983.
16. Paulin LM, Diette GB, Blanc PD, Putcha N, Eisner MD, Kanner RE, Belli AJ, Christenson S, Tashkin DP, Han M, et al.; SPIROMICS Research Group. Occupational exposures are associated with worse morbidity in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2015;191:557-565.
17. Eisner MD, Anthonisen N, Coultas D, Kuenzli N, Perez-Padilla R, Postma D, Romieu I, Silverman EK, Balmes JR; Committee on Nonsmoking COPD, Environmental and Occupational Health Assembly. An official American Thoracic Society public policy statement: novel risk factors and the global burden of chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2010; 182:693-718.
18. Orozco-Levi M, Garcia-Aymerich J, Villar J, Ramírez-Sarmiento A, Antó JM, Gea J. Wood smoke exposure and risk of chronic obstructive pulmonary disease. Eur Respir J 2006;27:542-546.
19. Gan WQ, FitzGerald JM, Carlsten C, Sadatsafavi M, Brauer M. Associations of ambient air pollution with chronic obstructive pulmonary disease hospitalization and mortality. Am J Respir Crit Care Med 2013;187:721-727.
20. Ezzati M. Indoor air pollution and health in developing countries. Lancet 2005;366:104-106.
21. Zhou Y, Zou Y, Li X, Chen S, Zhao Z, He F, Zou W, Luo Q, Li W, Pan Y, et al. Lung function and incidence of chronic obstructive pulmonary disease after improved cooking fuels and kitchen ventilation: a 9-year prospective cohort study. Plos Med 2014;11:e1001621.
22. Silva GE, Sherrill DL, Guerra S, Barbee RA. Asthma as a risk factor for COPD in a longitudinal study. Chest 2004;126:59-65.
23. Rijcken B, Schouten JP, Weiss ST, Speizer FE, van der Lende R. The relationship of nonspecific bronchial responsiveness to respiratory symptoms in a random population sample. Am Rev Respir Dis 1987; 136:62-68.
24. Hospers JJ, Postma DS, Rijcken B, Weiss ST, Schouten JP. Histamine airway hyper-responsiveness and mortality from chronic obstructive pulmonary disease: a cohort study. Lancet 2000;356: 1313-1317.
25. Tashkin DP, Altose MD, Connett JE, Kanner RE, Lee WW, Wise RA; The Lung Health Study Research Group. Methacholine reactivity predicts changes in lung function over time in smokers with early chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1996; 153:1802-1811.
26. de Marco R, Accordini S, Marcon A, Cerveri I, Antó JM, Gislason T, Heinrich J, Janson C, Jarvis D, Kuenzli N, et al.; European Community Respiratory Health Survey (ECRHS). Risk factors for chronic obstructive pulmonary disease in a European cohort of young adults. Am J Respir Crit Care Med 2011;183:891-897.
27. Drummond MB, Kirk GD. HIV-associated obstructive lung diseases: insights and implications for the clinician. Lancet Respir Med 2014;2:583-592.
28. Menezes AM, Hallal PC, Perez-Padilla R, Jardim JR, Muiño A, Lopez MV, Valdivia G, Montes de Oca M, Talamo C, Pertuze J, et al.; Latin American Project for the Investigation of Obstructive Lung Disease (PLATINO) Team. Tuberculosis and airflow obstruction: evidence from the PLATINO study in Latin America. Eur Respir J 2007;30: 1180-1185.
29. Jordan TS, Spencer EM, Davies P. Tuberculosis, bronchiectasis and chronic airflow obstruction. Respirology 2010;15:623-628.
30. Byrne AL, Marais BJ, Mitnick CD, Lecca L, Marks GB. Tuberculosis and chronic respiratory disease: a systematic review. Int J Infect Dis 2015;32:138-146.
31. Buist AS, McBurnie MA, Vollmer WM, Gillespie S, Burney P, Mannino DM, Menezes AM, Sullivan SD, Lee TA, Weiss KB, et al.; BOLD Collaborative Research Group. International variation in the prevalence of COPD (the BOLD Study): a population-based prevalence study. Lancet 2007;370:741-750.
32. Miravitlles M, Worth H, Soler Cataluña JJ, Price D, De Benedetto F, Roche N, Godtfredsen NS, van der Molen T, Löfdahl CG, Padullés L, et al. Observational study to characterise 24-hour COPD symptoms and their relationship with patient-reported outcomes: results from the ASSESS study. Respir Res 2014;15:122.
33. Elliott MW, Adams L, Cockcroft A, MacRae KD, Murphy K, Guz A. The language of breathlessness: use of verbal descriptors by patients with cardiopulmonary disease. Am Rev Respir Dis 1991;144: 826-832.
34. Medical Research Council Committee on the Aetiology of Chronic Bronchitis. Definition and classification of chronic bronchitis for clinical and epidemiological purposes: a report to the Medical Research Council by their Committee on the Aetiology of Chronic Bronchitis. Lancet 1965;1:775-779.
35. von Haehling S, Anker SD. Cachexia as a major underestimated and unmet medical need: facts and numbers. J Cachexia Sarcopenia Muscle 2010;1:1-5.
36. Schols AM, Soeters PB, Dingemans AM, Mostert R, Frantzen PJ, Wouters EF. Prevalence and characteristics of nutritional depletion in patients with stable COPD eligible for pulmonary rehabilitation. Am Rev Respir Dis 1993;147:1151-1156.
37. Holleman DR Jr, Simel DL. Does the clinical examination predict airflow limitation? JAMA 1995;273:313-319.
38. Kesten S, Chapman KR. Physician perceptions and management of COPD. Chest 1993;104:254-258.
39. van Dijk W, Tan W, Li P, Guo B, Li S, Benedetti A, Bourbeau J; CanCOLD Study Group. Clinical relevance of fixed ratio vs lower limit of normal of FEV1/FVC in COPD: patient-reported outcomes from the CanCOLD cohort. Ann Fam Med 2015;13:41-48.
40. Güder G, Brenner S, Angermann CE, Ertl G, Held M, Sachs AP, Lammers JW, Zanen P, Hoes AW, Störk S, et al. GOLD or lower limit of normal definition? A comparison with expert-based diagnosis of chronic obstructive pulmonary disease in a prospective cohortstudy. Respir Res 2012;13:13.
41. Vaz Fragoso CA, McAvay G, Van Ness PH, Casaburi R, Jensen RL, MacIntyre N, Gill TM, Yaggi HK, Concato J. Phenotype of normal spirometry in an aging population. Am J Respir Crit Care Med 2015; 192:817-825.
42. Vaz Fragoso CA, McAvay G, Van Ness PH, Casaburi R, Jensen RL, MacIntyre N, Yaggi HK, Gill TM, Concato J. Phenotype of spirometric impairment in an aging population. Am J Respir Crit Care Med 2016; 193:727-735.
43. Albert P, Agusti A, Edwards L, Tal-Singer R, Yates J, Bakke P, Celli BR, Coxson HO, Crim C, Lomas DA, et al. Bronchodilator responsiveness as a phenotypic characteristic of established chronic obstructive pulmonary disease. Thorax 2012;67:701-708.
44. Hansen JE, Porszasz J. Counterpoint: is an increase in FEV1 and/or FVC > 12% of control and > 200 mL the best way to assess positive bronchodilator response? No. Chest 2014;146:538-541.
45. Hill K, Goldstein RS, Guyatt GH, Blouin M, Tan WC, Davis LL, Heels-Ansdell DM, Erak M, Bragaglia PJ, Tamari IE, et al. Prevalence and underdiagnosis of chronic obstructive pulmonary disease among patients at risk in primary care. CMAJ 2010;182:673-678.
46. Ló pez Varela MV, Montes de Oca M, Rey A, Casas A, Stirbulov R, Di Boscio V; PUMA Team. Development of a simple screening tool for opportunistic COPD case finding in primary care in Latin America: the PUMA study. Respirology 2016;21:1227-1234.
47. Dirven JA, Tange HJ, Muris JW, van Haaren KM, Vink G, van Schayck OC. Early detection of COPD in general practice: implementation, workload and socioeconomic status. A mixed methods observational study. Prim Care Respir J 2013;22:338-343.
48. Fletcher CM. Standardised questionnaire on respiratory symptoms: a statement prepared and approved by the MRC Committee on the Aetiology of Chronic Bronchitis (MRC breathlessness score). BMJ 1960;2:1662.
49. Bestall JC, Paul EA, Garrod R, Garnham R, Jones PW, Wedzicha JA. Usefulness of the Medical Research Council (MRC) dyspnoea scale as a measure of disability in patients with chronic obstructive pulmonary disease. Thorax 1999;54:581-586.
50. Sundh J, Janson C, Lisspers K, Stä llberg B, Montgomery S. The Dyspnoea, Obstruction, Smoking, Exacerbation (DOSE) index is predictive of mortality in COPD. Prim Care Respir J 2012;21: 295-301.
51. Nishimura K, Izumi T, Tsukino M, Oga T. Dyspnea is a better predictor of 5-year survival than airway obstruction in patients with COPD. Chest 2002;121:1434-1440.
52. Jones PW. Health status measurement in chronic obstructive pulmonary disease. Thorax 2001;56:880-887.
53. Guyatt GH, Berman LB, Townsend M, Pugsley SO, Chambers LW. A measure of quality of life for clinical trials in chronic lung disease. Thorax 1987;42:773-778.
54. Jones PW, Quirk FH, Baveystock CM, Littlejohns P. A self-complete measure of health status for chronic airflow limitation: the St. George's Respiratory Questionnaire. Am Rev Respir Dis 1992;145: 1321-1327.
55. Agusti A, Calverley PM, Celli B, Coxson HO, Edwards LD, Lomas DA, MacNee W, Miller BE, Rennard S, Silverman EK, et al.; Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) investigators. Characterisation of COPD heterogeneity in the ECLIPSE cohort. Respir Res 2010;11:122.
56. Nishimura K, Mitsuma S, Kobayashi A, Yanagida M, Nakayasu K, Hasegawa Y, Jones PW. COPD and disease-specific health status in a working population. Respir Res 2013;14:61.
57. Miravitlles M, Soriano JB, García-Río F, Muñoz L, Duran-Tauleria E, Sanchez G, Sobradillo V, Ancochea J. Prevalence of COPD in Spain: impact of undiagnosed COPD on quality of life and daily life activities. Thorax 2009;64:863-868.
58. Jones PW, Tabberer M, Chen WH. Creating scenarios of the impact of COPD and their relationship to COPD Assessment Test (CAT™) scores. BMC Pulm Med 2011;11:42.
59. Hurst JR, Vestbo J, Anzueto A, Locantore N, Müllerova H, Tal-Singer R, Miller B, Lomas DA, Agusti A, Macnee W, et al.; Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) Investigators. Susceptibility to exacerbation in chronic obstructive pulmonary disease. N Engl J Med 2010;363:1128-1138.
60. Soler-Cataluña JJ, Martínez-García MA, Román Sánchez P, Salcedo E, Navarro M, Ochando R. Severe acute exacerbations and mortality in patients with chronic obstructive pulmonary disease. Thorax 2005; 60:925-931.
61. 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;3:435-442.
62. Siddiqui SH, Guasconi A, Vestbo J, Jones P, Agusti A, Paggiaro P, Wedzicha JA, Singh D. Blood eosinophils: a biomarker of response to extrafine beclomethasone/formoterol in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2015;192:523-525.
63. Soriano JB, Visick GT, Muellerova H, Payvandi N, Hansell AL. Patterns of comorbidities in newly diagnosed COPD and asthma in primary care. Chest 2005;128:2099-2107.
64. National Institute for Health and Care Excellence. Multimorbidity: clinical assessment and management, in press. 2016 [accessed 2016 Aug 1]. Available from: https://www.nice.org.uk/guidance/indevelopment/gid-cgwave0704/documents
65. Vanfleteren LE, Spruit MA, Groenen M, Gaffron S, van Empel VP, Bruijnzeel PL, Rutten EP, Op 't Roodt J, Wouters EF, Franssen FM. Clusters of comorbidities based on validated objective measurements and systemic inflammation in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2013; 187:728-735.
66. Soriano JB, Lamprecht B, Ramírez AS, Martinez-Camblor P, Kaiser B, Alfageme I, Almagro P, Casanova C, Esteban C, Soler-Cataluña JJ, et al. Mortality prediction in chronic obstructive pulmonary disease comparing the GOLD 2007 and 2011 staging systems: a pooled analysis of individual patient data. Lancet Respir Med 2015;3:443-450.
67. Goossens LM, Leimer I, Metzdorf N, Becker K, Rutten-van Mölken MP. Does the 2013 GOLD classification improve the ability to predict lung function decline, exacerbations and mortality: a post-hoc analysis of the 4-year UPLIFT trial. BMC Pulm Med 2014;14:163.
68. Kim J, Yoon HI, Oh YM, Lim SY, Lee JH, Kim TH, Lee SY, Lee JH, Lee SD, Lee CH. Lung function decline rates according to GOLD group in patients with chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis 2015;10:1819-1827.
69. Han MK, Muellerova H, Curran-Everett D, Dransfield MT, Washko GR, Regan EA, Bowler RP, Beaty TH, Hokanson JE, Lynch DA, et al. GOLD 2011 disease severity classification in COPDGene: a prospective cohort study. Lancet Respir Med 2013;1:43-50.
70. Alpha 1-antitrypsin deficiency: memorandum from a WHO meeting. Bull World Health Organ 1997;75:397-415.
71. Celli BR, Cote CG, Marin JM, Casanova C, Montes de Oca M, Mendez RA, Pinto Plata V, Cabral HJ. The body-mass index, airflow obstruction, dyspnea, and exercise capacity index in chronic obstructive pulmonary disease. N Engl J Med 2004;350:1005-1012.
72. Jones RC, Donaldson GC, Chavannes NH, Kida K, Dickson-Spillmann M, Harding S, Wedzicha JA, Price D, Hyland ME. Derivation and validation of a composite index of severity in chronic obstructive pulmonary disease: the DOSE Index. Am J Respir Crit Care Med 2009;180:1189-1195.
73. Puhan MA, Garcia-Aymerich J, Frey M, ter Riet G, Antó JM, Agustí AG, Gomez FP, Rodríguez-Roisín R, Moons KG, Kessels AG, et al. Expansion of the prognostic assessment of patients with chronic obstructive pulmonary disease: the updated BODE index and the ADO index. Lancet 2009;374:704-711.
74. van Eerd EA, van der Meer RM, van Schayck OC, Kotz D. Smoking cessation for people with chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2016;8:CD010744.
75. A clinical practice guideline for treating tobacco use and dependence: a US Public Health Service report. The Tobacco Use and Dependence Clinical Practice Guideline Panel, Staff, and Consortium Representatives. JAMA 2000;283:3244-3254.
76. van der Meer RM, Wagena EJ, Ostelo RW, Jacobs JE, van Schayck CP. Smoking cessation for chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2003;2:CD002999.
77. Clinical Practice Guideline Treating Tobacco Use and Dependence 2008 Update Panel, Liaisons, and Staff. A clinical practice guideline for treating tobacco use and dependence: 2008 update. A U.S. Public Health Service report. Am J Prev Med 2008;35: 158-176.
78. McNeill A, Brose LS, Calder R, Hitchman SC. E-cigarettes: an evidence update. A report commissioned by Public Health England. London: Public Health England; 2015.
79. McRobbie H, Bullen C, Hartmann-Boyce J, Hajek P. Electronic cigarettes for smoking cessation and reduction. Cochrane Database Syst Rev 2014;12:CD010216.
80. Kalkhoran S, Glantz SA. E-cigarettes and smoking cessation: authors' reply. Lancet Respir Med 2016;4:e26-e27.
81. Malas M, van der Tempel J, Schwartz R, Minichiello A, Lightfoot C, Noormohamed A, Andrews J, Zawertailo L, Ferrence R. Electronic cigarettes for smoking cessation: a systematic review. Nicotine Tob Res 2016;18:1926-1936.
82. Beard E, West R, Michie S, Brown J. Association between electronic cigarette use and changes in quit attempts, success of quit attempts, use of smoking cessation pharmacotherapy, and use of stop smoking services in England: time series analysis of population trends. BMJ 2016;354:i4645.
83. Tashkin DP, Rennard S, Hays JT, Ma W, Lawrence D, Lee TC. Effects of varenicline on smoking cessation in patients with mild to moderate COPD: a randomized controlled trial. Chest 2011;139: 591-599.
84. Tashkin D, Kanner R, Bailey W, Buist S, Anderson P, Nides M, Gonzales D, Dozier G, Patel MK, Jamerson B. Smoking cessation in patients with chronic obstructive pulmonary disease: a doubleblind, placebo-controlled, randomised trial. Lancet 2001;357: 1571-1575.
85. Cahill K, Stevens S, Perera R, Lancaster T. Pharmacological interventions for smoking cessation: an overview and network meta-analysis. Cochrane Database Syst Rev 2013;5: CD009329.
86. Glynn T, Manley M. How to help your patients stop smoking: a National Cancer Institute manual for physicians. NIH Publication No. 90-3064. Bethesda, MD: US Department of Health and Human Services, Public Health Service, National Institutes of Health, National Cancer Institute; 1990.
87. Stead LF, Buitrago D, Preciado N, Sanchez G, Hartmann-Boyce J, Lancaster T. Physician advice for smoking cessation. Cochrane Database Syst Rev 2013;5:CD000165.
88. Stead LF, Koilpillai P, Fanshawe TR, Lancaster T. Combined pharmacotherapy and behavioural interventions for smoking cessation. Cochrane Database Syst Rev 2016;3:CD008286.
89. Wongsurakiat P, Maranetra KN, Wasi C, Kositanont U, Dejsomritrutai W, Charoenratanakul S. Acute respiratory illness in patients with COPD and the effectiveness of influenza vaccination: a randomized controlled study. Chest 2004;125: 2011-2020.
90. Poole PJ, Chacko E, Wood-Baker RW, Cates CJ. Influenza vaccine for patients with chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2006;1:CD002733.
91. Wongsurakiat P, Lertakyamanee J, Maranetra KN, Jongriratanakul S, Sangkaew S. Economic evaluation of influenza vaccination in Thai chronic obstructive pulmonary disease patients. J Med Assoc Thai 2003;86:497-508.
92. Nichol KL, Margolis KL, Wuorenma J, Von Sternberg T. The efficacy and cost effectiveness of vaccination against influenza among elderly persons living in the community. N Engl J Med 1994;331: 778-784.
93. Fiore AE, Shay DK, Broder K, Iskander JK, Uyeki TM, Mootrey G, Bresee JS, Cox NJ; Centers for Disease Control and Prevention. Prevention and control of seasonal influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2009. MMWR Recomm Rep 2009;58:1-52.
94. Huang CL, Nguyen PA, Kuo PL, Iqbal U, Hsu YH, Jian WS. Influenza vaccination and reduction in risk of ischemic heart disease among chronic obstructive pulmonary elderly. Comput Methods Programs Biomed 2013;111:507-511.
95. Edwards KM, Dupont WD, Westrich MK, Plummer WD Jr, Palmer PS, Wright PF. A randomized controlled trial of cold-adapted and inactivated vaccines for the prevention of influenza A disease. J Infect Dis 1994;169:68-76.
96. Hak E, van Essen GA, Buskens E, Stalman W, de Melker RA. Is immunising all patients with chronic lung disease in the community against influenza cost effective? Evidence from a general practice based clinical prospective cohort study in Utrecht, The Netherlands. J Epidemiol Community Health 1998; 52:120-125.
97. Burge PS, Calverley PM, Jones PW, Spencer S, Anderson JA, Maslen TK. Randomised, double blind, placebo controlled study of fluticasone propionate in patients with moderate to severe chronic obstructive pulmonary disease: the ISOLDE trial. BMJ 2000;320: 1297-1303.
98. Anthonisen NR, Connett JE, Kiley JP, Altose MD, Bailey WC, Buist AS, Conway WA Jr, Enright PL, Kanner RE, O'Hara P, et al. Effects of smoking intervention and the use of an inhaled anticholinergic bronchodilator on the rate of decline of FEV1: the Lung Health Study. JAMA 1994;272:1497-1505.
99. Pauwels RA, Löfdahl CG, Laitinen LA, Schouten JP, Postma DS, Pride NB, Ohlsson SV; European Respiratory Society Study on Chronic Obstructive Pulmonary Disease. Long-term treatment with inhaled budesonide in persons with mild chronic obstructive pulmonary disease who continue smoking. N Engl J Med 1999;340: 1948-1953.
100. Vestbo J, Sørensen T, Lange P, Brix A, Torre P, Viskum K. Long-term effect of inhaled budesonide in mild and moderate chronic obstructive pulmonary disease: a randomised controlled trial. Lancet 1999;353:1819-1823.
101. Tashkin DP, Celli B, Senn S, Burkhart D, Kesten S, Menjoge S, Decramer M; UPLIFT Study Investigators. A 4-year trial of tiotropium in chronic obstructive pulmonary disease. N Engl J Med 2008;359:1543-1554.
102. O'Donnell DE, Flüge T, Gerken F, Hamilton A, Webb K, Aguilaniu B, Make B, Magnussen H. Effects of tiotropium on lung hyperinflation, dyspnoea and exercise tolerance in COPD. Eur Respir J 2004;23: 832-840.
103. O'Donnell DE, Sciurba F, Celli B, Mahler DA, Webb KA, Kalberg CJ, Knobil K. Effect of fluticasone propionate/salmeterol on lung hyperinflation and exercise endurance in COPD. Chest 2006;130: 647-656.
104. Appleton S, Jones T, Poole P, Pilotto L, Adams R, Lasserson TJ, Smith B, Muhammad J. Ipratropium bromide versus long-acting beta-2 agonists for stable chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2006;3:CD006101.
105. Karner C, Chong J, Poole P. Tiotropium versus placebo for chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2014; 7:CD009285.
106. Melani AS. Long-acting muscarinic antagonists. Expert Rev Clin Pharmacol 2015;8:479-501.
107. Kesten S, Casaburi R, Kukafka D, Cooper CB. Improvement in selfreported exercise participation with the combination of tiotropium and rehabilitative exercise training in COPD patients. Int J Chron Obstruct Pulmon Dis 2008;3:127-136.
108. Casaburi R, Kukafka D, Cooper CB, Witek TJ Jr, Kesten S. Improvement in exercise tolerance with the combination of tiotropium and pulmonary rehabilitation in patients with COPD. Chest 2005;127:809-817.
109. Vogelmeier C, Hederer B, Glaab T, Schmidt H, Rutten-van Mölken MP, Beeh KM, Rabe KF, Fabbri LM; POET-COPD Investigators. Tiotropium versus salmeterol for the prevention of exacerbations of COPD. N Engl J Med 2011;364:1093-1103.
110. Decramer ML, Chapman KR, Dahl R, Frith P, Devouassoux G, Fritscher C, Cameron R, Shoaib M, Lawrence D, Young D, et al.; INVIGORATE investigators. Once-daily indacaterol versus tiotropium for patients with severe chronic obstructive pulmonary disease (INVIGORATE): a randomised, blinded, parallel-group study. Lancet Respir Med 2013;1:524-533.
111. Anthonisen NR, Connett JE, Enright PL, Manfreda J; Lung Health Study Research Group. Hospitalizations and mortality in the Lung Health Study. Am J Respir Crit Care Med 2002;166: 333-339.
112. Michele TM, Pinheiro S, Iyasu S. The safety of tiotropium-the FDA's conclusions. N Engl J Med 2010;363:1097-1099.
113. Wise RA, Anzueto A, Cotton D, Dahl R, Devins T, Disse B, Dusser D, Joseph E, Kattenbeck S, Koenen-Bergmann M, et al.; TIOSPIR Investigators. Tiotropium Respimat inhaler and the risk of death in COPD. N Engl J Med 2013;369:1491-1501.
114. Ram FS, Jones PW, Castro AA, De Brito JA, Atallah AN, Lacasse Y, Mazzini R, Goldstein R, Cendon S. Oral theophylline for chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2002; 4:CD003902.
115. ZuWallack RL, Mahler DA, Reilly D, Church N, Emmett A, Rickard K, Knobil K. Salmeterol plus theophylline combination therapy in the treatment of COPD. Chest 2001;119:1661-1670.
116. Zacarias EC, Castro AA, Cendon S. Effect of theophylline associated with short-acting or long-acting inhaled beta2-agonists in patients with stable chronic obstructive pulmonary disease: a systematic review. J Bras Pneumol 2007;33:152-160.
117. Cosío BG, Shafiek H, Iglesias A, Yanez A, Có rdova R, Palou A, Rodriguez-Roisin R, Peces-Barba G, Pascual S, Gea J, et al. Oral low-dose theophylline on top of inhaled fluticasone-salmeterol does not reduce exacerbations in patients with severe COPD: a pilot clinical trial. Chest 2016;150:123-130.
118. Zhou Y, Wang X, Zeng X, Qiu R, Xie J, Liu S, Zheng J, Zhong N, Ran P. Positive benefits of theophylline in a randomized, double-blind, parallel-group, placebo-controlled study of low-dose, slow-release theophylline in the treatment of COPD for 1 year. Respirology 2006; 11:603-610.
119. McKay SE, Howie CA, Thomson AH, Whiting B, Addis GJ. Value of theophylline treatment in patients handicapped by chronic obstructive lung disease. Thorax 1993;48:227-232.
120. Cazzola M, Molimard M. The scientific rationale for combining longacting beta2-agonists and muscarinic antagonists in COPD. Pulm Pharmacol Ther 2010;23:257-267.
121. van der Molen T, Cazzola M. Beyond lung function in COPD management: effectiveness of LABA/LAMA combination therapy on patient-centred outcomes. Prim Care Respir J 2012; 21:101-108.
122. Mahler DA, Decramer M, D'Urzo A, Worth H, White T, Alagappan VK, Chen H, Gallagher N, Kulich K, Banerji D. Dual bronchodilation with QVA149 reduces patient-reported dyspnoea in COPD: the BLAZE study. Eur Respir J 2014;43:1599-1609.
123. Singh D, Ferguson GT, Bolitschek J, Grönke L, Hallmann C, Bennett N, Abrahams R, Schmidt O, Bjermer L. Tiotropium 1 olodaterol shows clinically meaningful improvements in quality of life. Respir Med 2015;109:1312-1319.
124. Bateman ED, Chapman KR, Singh D, D'Urzo AD, Molins E, Leselbaum A, Gil EG. Aclidinium bromide and formoterol fumarate as a fixed-dose combination in COPD: pooled analysis of symptoms and exacerbations from two six-month, multicentre, randomised studies (ACLIFORM and AUGMENT). Respir Res 2015;16:92.
125. Mahler DA, Kerwin E, Ayers T, FowlerTaylor A, Maitra S, Thach C, Lloyd M, Patalano F, Banerji D. FLIGHT1 and FLIGHT2: efficacy and safety of QVA149 (indacaterol/glycopyrrolate) versus its monocomponents and placebo in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2015;192: 1068-1079.
126. Wedzicha JA, Decramer M, Ficker JH, Niewoehner DE, Sandstrom T, Taylor AF, D'Andrea P, Arrasate C, Chen H, Banerji D. Analysis of chronic obstructive pulmonary disease exacerbations with the dual bronchodilator QVA149 compared with glycopyrronium and tiotropium (SPARK): a randomised, double-blind, parallel-group study. Lancet Respir Med 2013;1:199-209.
127. Wedzicha JA, Banerji D, Chapman KR, Vestbo J, Roche N, Ayers RT, Thach C, Fogel R, Patalano F, Vogelmeier CF; FLAME Investigators. Indacaterol-glycopyrronium versus salmeterolfluticasone for COPD. N Engl J Med 2016;374:2222-2234.
128. Nannini LJ, Lasserson TJ, Poole P. Combined corticosteroid and long-acting beta(2)-agonist in one inhaler versus long-acting beta (2)-agonists for chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2012;9:CD006829.
129. Nannini LJ, Poole P, Milan SJ, Kesterton A. Combined corticosteroid and long-acting beta(2)-agonist in one inhaler versus inhaled corticosteroids alone for chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2013;8:CD006826.
130. Calverley PM, Anderson JA, Celli B, Ferguson GT, Jenkins C, Jones PW, Yates JC, Vestbo J; TORCH investigators. Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease. N Engl J Med 2007;356:775-789.
131. Vestbo J, Anderson JA, Brook RD, Calverley PM, Celli BR, Crim C, Martinez F, Yates J, Newby DE; SUMMIT Investigators. Fluticasone furoate and vilanterol and survival in chronic obstructive pulmonary disease with heightened cardiovascular risk (SUMMIT): a double-blind randomised controlled trial. Lancet 2016;387:1817-1826.
132. Yang IA, Clarke MS, Sim EH, Fong KM. Inhaled corticosteroids for stable chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2012;7:CD002991.
133. Crim C, Dransfield MT, Bourbeau J, Jones PW, Hanania NA, Mahler DA, Vestbo J, Wachtel A, Martinez FJ, Barnhart F, et al. Pneumonia risk with inhaled fluticasone furoate and vilanterol compared with vilanterol alone in patients with COPD. Ann Am Thorac Soc 2015; 12:27-34.
134. Johnell O, Pauwels R, Löfdahl CG, Laitinen LA, Postma DS, Pride NB, Ohlsson SV. Bone mineral density in patients with chronic obstructive pulmonary disease treated with budesonide Turbuhaler. Eur Respir J 2002;19:1058-1063.
135. Ferguson GT, Calverley PM, Anderson JA, Jenkins CR, Jones PW, Willits LR, Yates JC, Vestbo J, Celli B. Prevalence and progression of osteoporosis in patients with COPD: results from the TOwards a Revolution in COPD Health study. Chest 2009;136:1456-1465.
136. Dransfield MT, Bourbeau J, Jones PW, Hanania NA, Mahler DA, Vestbo J, Wachtel A, Martinez FJ, Barnhart F, Sanford L, et al. Once-daily inhaled fluticasone furoate and vilanterol versus vilanterol only for prevention of exacerbations of COPD: two replicate double-blind, parallel-group, randomised controlled trials. Lancet Respir Med 2013;1:210-223.
137. Loke YK, Cavallazzi R, Singh S. Risk of fractures with inhaled corticosteroids in COPD: systematic review and meta-analysis of randomised controlled trials and observational studies. Thorax 2011;66:699-708.
138. Suissa S, Kezouh A, Ernst P. Inhaled corticosteroids and the risks of diabetes onset and progression. Am J Med 2010;123:1001-1006.
139. Wang JJ, Rochtchina E, Tan AG, Cumming RG, Leeder SR, Mitchell P. Use of inhaled and oral corticosteroids and the long-term risk of cataract. Ophthalmology 2009;116:652-657.
140. Andréjak C, Nielsen R, Thomsen VO, Duhaut P, Sørensen HT, Thomsen RW. Chronic respiratory disease, inhaled corticosteroids and risk of non-tuberculous mycobacteriosis. Thorax 2013;68: 256-262.
141. Dong YH, Chang CH, Lin Wu FL, Shen LJ, Calverley PM, Löfdahl CG, Lai MS, Mahler DA. Use of inhaled corticosteroids in patients with COPD and the risk of TB and influenza: a systematic review and meta-analysis of randomized controlled trials. Chest 2014;145: 1286-1297.
142. Lee CH, Kim K, Hyun MK, Jang EJ, Lee NR, Yim JJ. Use of inhaled corticosteroids and the risk of tuberculosis. Thorax 2013;68: 1105-1113.
143. Nadeem NJ, Taylor SJ, Eldridge SM. Withdrawal of inhaled corticosteroids in individuals with COPD-a systematic review and comment on trial methodology. Respir Res 2011;12:107.
144. van der Valk P, Monninkhof E, van der Palen J, Zielhuis G, van Herwaarden C. Effect of discontinuation of inhaled corticosteroids in patients with chronic obstructive pulmonary disease: the COPE study. Am J Respir Crit Care Med 2002;166: 1358-1363.
145. Wouters EF, Postma DS, Fokkens B, Hop WC, Prins J, Kuipers AF, Pasma HR, Hensing CA, Creutzberg EC; COSMIC (COPD and Seretide: a Multi-Center Intervention and Characterization) Study Group. Withdrawal of fluticasone propionate from combined salmeterol/fluticasone treatment in patients with COPD causes immediate and sustained disease deterioration: a randomised controlled trial. Thorax 2005;60: 480-487.
146. Kunz LI, Postma DS, Klooster K, Lapperre TS, Vonk JM, Sont JK, Kerstjens HA, Snoeck-Stroband JB, Hiemstra PS, Sterk PJ; GLUCOLD Study Group. Relapse in FEV1 decline after steroid withdrawal in COPD. Chest 2015;148:389-396.
147. Magnussen H, Disse B, Rodriguez-Roisin R, Kirsten A, Watz H, Tetzlaff K, Towse L, Finnigan H, Dahl R, Decramer M, et al.; WISDOM Investigators. Withdrawal of inhaled glucocorticoids and exacerbations of COPD. N Engl J Med 2014; 371:1285-1294.
148. Welte T, Miravitlles M, Hernandez P, Eriksson G, Peterson S, Polanowski T, Kessler R. Efficacy and tolerability of budesonide/formoterol added to tiotropium in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2009; 180:741-750.
149. Singh D, Brooks J, Hagan G, Cahn A, O'Connor BJ. Superiority of "triple" therapy with salmeterol/fluticasone propionate and tiotropium bromide versus individual components in moderate to severe COPD. Thorax 2008;63:592-598.
150. Jung KS, Park HY, Park SY, Kim SK, Kim YK, Shim JJ, Moon HS, Lee KH, Yoo JH, Lee SD; Korean Academy of Tuberculosis and Respiratory Diseases study group; Korea Chronic Obstructive Pulmonary Disease study group. Comparison of tiotropium plus fluticasone propionate/salmeterol with tiotropium in COPD: a randomized controlled study. Respir Med 2012;106:382-389.
151. Hanania NA, Crater GD, Morris AN, Emmett AH, O'Dell DM, Niewoehner DE. Benefits of adding fluticasone propionate/salmeterol to tiotropium in moderate to severe COPD. Respir Med 2012;106:91-101.
152. Frith PA, Thompson PJ, Ratnavadivel R, Chang CL, Bremner P, Day P, Frenzel C, Kurstjens N; Glisten Study Group. Glycopyrronium oncedaily significantly improves lung function and health status when combined with salmeterol/fluticasone in patients with COPD: the GLISTEN study, a randomised controlled trial. Thorax 2015;70: 519-527.
153. Siler TM, Kerwin E, Singletary K, Brooks J, Church A. Efficacy and safety of umeclidinium added to fluticasone propionate/salmeterol in patients with COPD: results of two randomized, double-blind studies. COPD 2016;13:1-10.
154. Singh D, Papi A, Corradi M, PavlišováI, Montagna I, Francisco C, Cohuet G, Vezzoli S, Scuri M, Vestbo J. Single inhaler triple therapy versus inhaled corticosteroid plus long-acting b2-agonist therapy for chronic obstructive pulmonary disease (TRILOGY): a doubleblind, parallel group, randomised controlled trial. Lancet 2016;388: 963-973.
155. Aaron SD, Vandemheen KL, Fergusson D, Maltais F, Bourbeau J, Goldstein R, Balter M, O'Donnell D, McIvor A, Sharma S, et al.; Canadian Thoracic Society/Canadian Respiratory Clinical Research Consortium. Tiotropium in combination with placebo, salmeterol, or fluticasone-salmeterol for treatment of chronic obstructive pulmonary disease: a randomized trial. Ann Intern Med 2007;146: 545-555.
156. Calverley PM, Rabe KF, Goehring UM, Kristiansen S, Fabbri LM, Martinez FJ; M2-124 and M2-125 study groups. Roflumilast in symptomatic chronic obstructive pulmonary disease: two randomised clinical trials. Lancet 2009;374:685-694.
157. Chong J, Leung B, Poole P. Phosphodiesterase 4 inhibitors for chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2013;11:CD002309.
158. Seemungal TA, Wilkinson TM, Hurst JR, Perera WR, Sapsford RJ, Wedzicha JA. Long-term erythromycin therapy is associated with decreased chronic obstructive pulmonary disease exacerbations. Am J Respir Crit Care Med 2008;178:1139-1147.
159. Uzun S, Djamin RS, Kluytmans JA, Mulder PG, van't Veer NE, Ermens AA, Pelle AJ, Hoogsteden HC, Aerts JG, van der Eerden MM. Azithromycin maintenance treatment in patients with frequent exacerbations of chronic obstructive pulmonary disease (COLUMBUS): a randomised, double-blind, placebo-controlled trial. Lancet Respir Med 2014;2:361-368.
160. Albert RK, Connett J, Bailey WC, Casaburi R, Cooper JA Jr, Criner GJ, Curtis JL, Dransfield MT, Han MK, Lazarus SC, et al.; COPD Clinical Research Network. Azithromycin for prevention of exacerbations of COPD. N Engl J Med 2011;365:689-698.
161. Sethi S, Jones PW, Theron MS, Miravitlles M, Rubinstein E, Wedzicha JA, Wilson R; PULSE Study group. Pulsed moxifloxacin for the prevention of exacerbations of chronic obstructive pulmonary disease: a randomized controlled trial. Respir Res 2010;11:10.
162. Cazzola M, Calzetta L, Page C, Jardim J, Chuchalin AG, Rogliani P, Matera MG. Influence of N-acetylcysteine on chronic bronchitis or COPD exacerbations: a meta-analysis. Eur Respir Rev 2015;24: 451-461.
163. Poole P, Chong J, Cates CJ. Mucolytic agents versus placebo for chronic bronchitis or chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2015;7:CD001287.
164. Collet JP, Shapiro P, Ernst P, Renzi T, Ducruet T, Robinson A. Effects of an immunostimulating agent on acute exacerbations and hospitalizations in patients with chronic obstructive pulmonary disease: the PARI-IS Study Steering Committee and Research Group. Prevention of Acute Respiratory Infection by an Immunostimulant. Am J Respir Crit Care Med 1997;156: 1719-1724.
165. Li J, Zheng JP, Yuan JP, Zeng GQ, Zhong NS, Lin CY. Protective effect of a bacterial extract against acute exacerbation in patients with chronic bronchitis accompanied by chronic obstructive pulmonary disease. Chin Med J (Engl) 2004;117:828-834.
166. Lee JH, Kim HJ, Kim YH. The Effectiveness of anti-leukotriene agents in patients with COPD: a systemic review and meta-analysis. Lung 2015;193:477-486.
167. Rennard SI, Fogarty C, Kelsen S, Long W, Ramsdell J, Allison J, Mahler D, Saadeh C, Siler T, Snell P, et al.; COPD Investigators. The safety and efficacy of infliximab in moderate to severe chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2007; 175:926-934.
168. Criner GJ, Connett JE, Aaron SD, Albert RK, Bailey WC, Casaburi R, Cooper JA Jr, Curtis JL, Dransfield MT, Han MK, et al.; COPD Clinical Research Network; Canadian Institutes of Health Research. Simvastatin for the prevention of exacerbations in moderate-tosevere COPD. N Engl J Med 2014;370:2201-2210.
169. Ingebrigtsen TS, Marott JL, Nordestgaard BG, Lange P, Hallas J, Vestbo J. Statin use and exacerbations in individuals with chronic obstructive pulmonary disease. Thorax 2015;70:33-40.
170. Lehouck A, Mathieu C, Carremans C, Baeke F, Verhaegen J, Van Eldere J, Decallonne B, Bouillon R, Decramer M, Janssens W. High doses of vitamin D to reduce exacerbations in chronic obstructive pulmonary disease: a randomized trial. Ann Intern Med 2012;156: 105-114.
171. Melani AS, Bonavia M, Cilenti V, Cinti C, Lodi M, Martucci P, Serra M, Scichilone N, Sestini P, Aliani M, et al.; Gruppo Educazionale Associazione Italiana Pneumologi Ospedalieri. Inhaler mishandling remains common in real life and is associated with reduced disease control. Respir Med 2011;105:930-938.
172. Rootmensen GN, van Keimpema AR, Jansen HM, de Haan RJ. Predictors of incorrect inhalation technique in patients with asthma or COPD: a study using a validated videotaped scoring method. J Aerosol Med Pulm Drug Deliv 2010;23:323-328.
173. Dantic DE. A critical review of the effectiveness of "teach-back" technique in teaching COPD patients self-management using respiratory inhalers. Health Educ J 2014;73:41-50.
174. Chapman KR, Stockley RA, Dawkins C, Wilkes MM, Navickis RJ. Augmentation therapy for alpha1 antitrypsin deficiency: a metaanalysis. COPD 2009;6:177-184.
175. Chapman KR, Burdon JG, Piitulainen E, Sandhaus RA, Seersholm N, Stocks JM, Stoel BC, Huang L, Yao Z, Edelman JM, et al.; RAPID Trial Study Group. Intravenous augmentation treatment and lung density in severe a1 antitrypsin deficiency (RAPID): a randomised, double-blind, placebo-controlled trial. Lancet 2015;386:360-368.
176. Dirksen A, Dijkman JH, Madsen F, Stoel B, Hutchison DC, Ulrik CS, Skovgaard LT, Kok-Jensen A, Rudolphus A, Seersholm N, et al. A randomized clinical trial of alpha(1)-antitrypsin augmentation therapy. Am J Respir Crit Care Med 1999;160: 1468-1472.
177. Dirksen A, Piitulainen E, Parr DG, Deng C, Wencker M, Shaker SB, Stockley RA. Exploring the role of CT densitometry: a randomised study of augmentation therapy in alpha1-antitrypsin deficiency. Eur Respir J 2009;33:1345-1353.
178. Schildmann EK, Rémi C, Bausewein C. Levodropropizine in the management of cough associated with cancer or nonmalignant chronic disease-a systematic review. J Pain Palliat Care Pharmacother 2011;25:209-218.
179. Barberà JA, Roger N, Roca J, Rovira I, Higenbottam TW, Rodriguez-Roisin R. Worsening of pulmonary gas exchange with nitric oxide inhalation in chronic obstructive pulmonary disease. Lancet 1996; 347:436-440.
180. Blanco I, Santos S, Gea J, Güell R, Torres F, Gimeno-Santos E, Rodriguez DA, Vilaró J, Gómez B, Roca J, et al. Sildenafil to improve respiratory rehabilitation outcomes in COPD: a controlled trial. Eur Respir J 2013;42:982-992.
181. Goudie AR, Lipworth BJ, Hopkinson PJ, Wei L, Struthers AD. Tadalafil in patients with chronic obstructive pulmonary disease: a randomised, double-blind, parallel-group, placebo-controlled trial. Lancet Respir Med 2014;2:293-300.
182. Spruit MA, Singh SJ, Garvey C, ZuWallack R, Nici L, Rochester C, Hill K, Holland AE, Lareau SC, Man WD, et al.; ATS/ERS Task Force on Pulmonary Rehabilitation. An official American Thoracic Society/European Respiratory Society statement: key concepts and advances in pulmonary rehabilitation. Am J Respir Crit Care Med 2013;188:e13-e64.
183. Puhan MA, Gimeno-Santos E, Scharplatz M, Troosters T, Walters EH, Steurer J. Pulmonary rehabilitation following exacerbations of chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2011;10:CD005305.
184. Greening NJ, Williams JE, Hussain SF, Harvey-Dunstan TC, Bankart MJ, Chaplin EJ, Vincent EE, Chimera R, Morgan MD, Singh SJ, et al. An early rehabilitation intervention to enhance recovery during hospital admission for an exacerbation of chronic respiratory disease: randomised controlled trial. BMJ 2014;349:g4315.
185. Vogiatzis I, Rochester CL, Spruit MA, Troosters T, Clini EM; American Thoracic Society/European Respiratory Society Task Force on Policy in Pulmonary Rehabilitation. Increasing implementation and delivery of pulmonary rehabilitation: key messages from the new ATS/ERS policy statement. Eur Respir J 2016;47: 1336-1341.
186. Zwerink M, Brusse-Keizer M, van der Valk PD, Zielhuis GA, Monninkhof EM, van der Palen J, Frith PA, Effing T. Self management for patients with chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2014;3:CD002990.
187. Fan VS, Gaziano JM, Lew R, Bourbeau J, Adams SG, Leatherman S, Thwin SS, Huang GD, Robbins R, Sriram PS, et al. A comprehensive care management program to prevent chronic obstructive pulmonary disease hospitalizations: a randomized, controlled trial. Ann Intern Med 2012;156:673-683.
188. Peytremann-Bridevaux I, Taffe P, Burnand B, Bridevaux PO, Puhan MA. Mortality of patients with COPD participating in chronic disease management programmes: a happy end? Thorax 2014;69: 865-866.
189. Kruis AL, Smidt N, Assendelft WJ, Gussekloo J, Boland MR, Rutten-van Mölken M, Chavannes NH. Integrated disease management interventions for patients with chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2013;10: CD009437.
190. Kruis AL, Boland MR, Assendelft WJ, Gussekloo J, Tsiachristas A, Stijnen T, Blom C, Sont JK, Rutten-van Mölken MP, Chavannes NH. Effectiveness of integrated disease management for primary care chronic obstructive pulmonary disease patients: results of cluster randomised trial. BMJ 2014;349:g5392.
191. Cartwright M, Hirani SP, Rixon L, Beynon M, Doll H, Bower P, Bardsley M, Steventon A, Knapp M, Henderson C, et al.; Whole Systems Demonstrator Evaluation Team. Effect of telehealth on quality of life and psychological outcomes over 12 months (Whole Systems Demonstrator telehealth questionnaire study): nested study of patient reported outcomes in a pragmatic, cluster randomised controlled trial. BMJ 2013;346:f653.
192. American Academy of Hospice and Palliative Medicine; Center to Advance Palliative Care; Hospice and Palliative Nurses Association; Last Acts Partnership; National Hospice and Palliative Care Organization. National Consensus Project for Quality Palliative Care: Clinical Practice Guidelines for quality palliative care, executive summary. J Palliat Med 2004;7:611-627.
193. Halpin DMG, Seamark DA, Seamark CJ. Palliative and end-of-life care for patients with respiratory diseases. Eur Respir Monograph 2009; 43:327-353.
194. Weber C, Stirnemann J, Herrmann FR, Pautex S, Janssens JP. Can early introduction of specialized palliative care limit intensive care, emergency and hospital admissions in patients with severe and very severe COPD? A randomized study. BMC Palliat Care 2014; 13:47.
195. Ek K, Andershed B, Sahlberg-Blom E, Ternestedt BM. "The unpredictable death"-The last year of life for patients with advanced COPD: relatives' stories. Palliat Support Care 2015;13:1213-1222.
196. Cranston JM, Crockett AJ, Moss JR, Alpers JH. Domiciliary oxygen for chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2005;4:CD001744.
197. Albert RK, Au DH, Blackford AL, Casaburi R, Cooper JA Jr, Criner GJ, Diaz P, Fuhlbrigge AL, Gay SE, Kanner RE, et al.; Long-Term Oxygen Treatment Trial Research Group. A randomized trial of long-term oxygen for COPD with moderate desaturation. N Engl J Med 2016;375:1617-1627.
198. Galli JA, Krahnke JS, James Mamary A, Shenoy K, Zhao H, Criner GJ. Home non-invasive ventilation use following acute hypercapnic respiratory failure in COPD. Respir Med 2014;108:722-728.
199. Coughlin S, Liang WE, Parthasarathy S. Retrospective assessment of home ventilation to reduce rehospitalization in chronic obstructive pulmonary disease. J Clin Sleep Med 2015;11:663-670.
200. Clini E, Sturani C, Rossi A, Viaggi S, Corrado A, Donner CF, Ambrosino N; Rehabilitation and Chronic Care Study Group, Italian Association of Hospital Pulmonologists (AIPO). The Italian multicentre study on noninvasive ventilation in chronic obstructive pulmonary disease patients. Eur Respir J 2002;20:529-538.
201. Köhnlein T, Windisch W, Köhler D, Drabik A, Geiseler J, Hartl S, Karg O, Laier-Groeneveld G, Nava S, Schönhofer B, et al. Noninvasive 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.
202. Struik FM, Sprooten RT, Kerstjens HA, Bladder G, Zijnen M, Asin J, Cobben NA, Vonk JM, Wijkstra PJ. Nocturnal non-invasive ventilation in COPD patients with prolonged hypercapnia after ventilatory support for acute respiratory failure: a randomised, controlled, parallel-group study. Thorax 2014;69:826-834.
203. Casanova C, Celli BR, Tost L, Soriano E, Abreu J, Velasco V, Santolaria F. Long-term controlled trial of nocturnal nasal positive pressure ventilation in patients with severe COPD. Chest 2000;118: 1582-1590.
204. Marin JM, Soriano JB, Carrizo SJ, Boldova A, Celli BR. Outcomes in patients with chronic obstructive pulmonary disease and obstructive sleep apnea: the overlap syndrome. Am J Respir Crit Care Med 2010;182:325-331.
205. Fishman A, Martinez F, Naunheim K, Piantadosi S, Wise R, Ries A, Weinmann G, Wood DE; National Emphysema Treatment Trial Research Group. A randomized trial comparing lung-volumereduction surgery with medical therapy for severe emphysema. N Engl J Med 2003;348:2059-2073.
206. National Emphysema Treatment Trial Research Group. Patients at high risk of death after lung-volume-reduction surgery. N Engl J Med 2001;345:1075-1083.
207. Marchetti N, Criner GJ. Surgical approaches to treating emphysema: lung volume reduction surgery, bullectomy, and lung transplantation. Semin Respir Crit Care Med 2015;36:592-608.
208. Christie JD, Edwards LB, Kucheryavaya AY, Benden C, Dipchand AI, Dobbels F, Kirk R, Rahmel AO, Stehlik J, Hertz MI; International Society of Heart and Lung Transplantation. The Registry of the International Society for Heart and Lung Transplantation: 29th adult lung and heart-lung transplant report-2012. J Heart Lung Transplant 2012;31:1073-1086.
209. Stavem K, Bjørtuft Ø, Borgan Ø, Geiran O, Boe J. Lung transplantation in patients with chronic obstructive pulmonary disease in a national cohort is without obvious survival benefit. J Heart Lung Transplant 2006;25:75-84.
210. Thabut G, Christie JD, Ravaud P, Castier Y, Brugiè re O, Fournier M, Mal H, Lesè che G, Porcher R. Survival after bilateral versus single lung transplantation for patients with chronic obstructive pulmonary disease: a retrospective analysis of registry data. Lancet 2008;371: 744-751.
211. Criner GJ, Cordova F, Sternberg AL, Martinez FJ. The National Emphysema Treatment Trial (NETT) Part II: lessons learned about lung volume reduction surgery. Am J Respir Crit Care Med 2011; 184:881-893.
212. Shah PL, Slebos DJ, Cardoso PF, Cetti E, Voelker K, Levine B, Russell ME, Goldin J, Brown M, Cooper JD, et al.; EASE trial study group. Bronchoscopic lung-volume reduction with Exhale Airway Stents for Emphysema (EASE trial): randomised, sham-controlled, multicentre trial. Lancet 2011;378:997-1005.
213. Come CE, Kramer MR, Dransfield MT, Abu-Hijleh M, Berkowitz D, Bezzi M, Bhatt SP, Boyd MB, Cases E, Chen AC, et al. A randomised trial of lung sealant versus medical therapy for advanced emphysema. Eur Respir J 2015;46:651-662.
214. Sciurba FC, Ernst A, Herth FJ, Strange C, Criner GJ, Marquette CH, Kovitz KL, Chiacchierini RP, Goldin J, McLennan G; VENT Study Research Group. A randomized study of endobronchial valves for advanced emphysema. N Engl J Med 2010;363:1233-1244.
215. Davey C, Zoumot Z, Jordan S, Carr DH, Polkey MI, Shah PL, Hopkinson NS. Bronchoscopic lung volume reduction with endobronchial valves for patients with heterogeneous emphysema and intact interlobar fissures (the BeLieVeR-HIFi trial): study design and rationale. Thorax 2015;70:288-290.
216. Klooster K, ten Hacken NH, Hartman JE, Kerstjens HA, van Rikxoort EM, Slebos DJ. Endobronchial valves for emphysema without interlobar collateral ventilation. N Engl J Med 2015;373: 2325-2335.
217. Deslée G, Mal H, Dutau H, Bourdin A, Vergnon JM, Pison C, Kessler R, Jounieaux V, Thiberville L, Leroy S, et al.; REVOLENS Study Group. Lung volume reduction coil treatment vs usual care in patients with severe emphysema: the REVOLENS Randomized Clinical Trial. JAMA 2016;315:175-184.
218. Sciurba FC, Criner GJ, Strange C, Shah PL, Michaud G, Connolly TA, Deslée G, Tillis WP, Delage A, Marquette CH, et al.; RENEW Study Research Group. Effect of endobronchial coils vs usual care on exercise tolerance in patients with severe emphysema: the RENEW randomized clinical trial. JAMA 2016;315:2178-2189.
219. Barr RG, Bourbeau J, Camargo CA, Ram FS. Inhaled tiotropium for stable chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2005;2:CD002876.
220. Karner C, Cates CJ. Long-acting beta(2)-agonist in addition to tiotropium versus either tiotropium or long-acting beta(2)-agonist alone for chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2012;4:CD008989.
221. Martinez FJ, Calverley PM, Goehring UM, Brose M, Fabbri LM, Rabe KF. Effect of roflumilast on exacerbations in patients with severe chronic obstructive pulmonary disease uncontrolled by combination therapy (REACT): a multicentre randomised controlled trial. Lancet 2015;385:857-866.
222. Martinez FJ, Rabe KF, Sethi S, Pizzichini E, McIvor A, Anzueto A, Alagappan VK, Siddiqui S, Rekeda L, Miller CJ, et al. Effect of roflumilast and inhaled corticosteroid/long-acting b2-agonist on chronic obstructive pulmonary disease exacerbations (RE(2) SPOND): a randomized clinical trial. Am J Respir Crit Care Med 2016;194:559-567.
223. Garvey C, Bayles MP, Hamm LF, Hill K, Holland A, Limberg TM, Spruit MA. Pulmonary rehabilitation exercise prescription in chronic obstructive pulmonary disease: review of selected guidelines: an official statement from the American Association of Cardiovascular and Pulmonary Rehabilitation. J Cardiopulm Rehabil Prev 2016;36: 75-83.
224. Ortega F, Toral J, Cejudo P, Villagomez R, Sánchez H, Castillo J, Montemayor T. Comparison of effects of strength and endurance training in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2002;166:669-674.
225. Bernard S, Whittom F, Leblanc P, Jobin J, Belleau R, BérubéC, Carrier G, Maltais F. Aerobic and strength training in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1999;159:896-901.
226. Velloso M, do Nascimento NH, Gazzotti MR, Jardim JR. Evaluation of effects of shoulder girdle training on strength and performance of activities of daily living in patients with chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis 2013;8: 187-192.
227. Au DH, Udris EM, Engelberg RA, Diehr PH, Bryson CL, Reinke LF, Curtis JR. A randomized trial to improve communication about end-of-life care among patients with COPD. Chest 2012;141: 726-735.
228. Tomczyk S, Bennett NM, Stoecker C, Gierke R, Moore MR, Whitney CG, Hadler S, Pilishvili T; Centers for Disease Control and Prevention (CDC). Use of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine among adults aged >65 years: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep 2014;63:822-825.
229. Struik FM, Lacasse Y, Goldstein RS, Kerstjens HA, Wijkstra PJ. Nocturnal noninvasive positive pressure ventilation in stable COPD: a systematic review and individual patient data meta-analysis. Respir Med 2014;108:329-337.
230. Tiong LU, Davies R, Gibson PG, Hensley MJ, Hepworth R, Lasserson TJ, Smith B. Lung volume reduction surgery for diffuse emphysema. Cochrane Database Syst Rev 2006;4:CD001001.
231. Weill D, Benden C, Corris PA, Dark JH, Davis RD, Keshavjee S, Lederer DJ, Mulligan MJ, Patterson GA, Singer LG, et al. A consensus document for the selection of lung transplant candidates: 2014-an update from the Pulmonary Transplantation Council of the International Society for Heart and Lung Transplantation. J Heart Lung Transplant 2015;34:1-15.
232. The International Society for Heart and Lung Transplantation. Slide sets: overall lung transplantation statistics; 2015 [accessed 2016 Sept 18]. Available from: https://www.ishlt.org/downloadables/slides/2015/lung-adult.pptx
233. Wedzicha JA, Seemungal TA. COPD exacerbations: defining their cause and prevention. Lancet 2007;370:786-796.
234. Seemungal TA, Donaldson GC, Paul EA, Bestall JC, Jeffries DJ, Wedzicha JA. Effect of exacerbation on quality of life in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1998;157:1418-1422.
235. Anthonisen NR, Manfreda J, Warren CP, Hershfield ES, Harding GK, Nelson NA. Antibiotic therapy in exacerbations of chronic obstructive pulmonary disease. Ann Intern Med 1987;106:196-204.
236. Woodhead M, Blasi F, Ewig S, Huchon G, Ieven M, Ortqvist A, Schaberg T, Torres A, van der Heijden G, Verheij TJ; European Respiratory Society; European Society of Clinical Microbiology and Infectious Diseases. Guidelines for the management of adult lower respiratory tract infections. Eur Respir J 2005;26:1138-1180.
237. White AJ, Gompertz S, Stockley RA. Chronic obstructive pulmonary disease. 6: The aetiology of exacerbations of chronic obstructive pulmonary disease. Thorax 2003;58:73-80.
238. Papi A, Bellettato CM, Braccioni F, Romagnoli M, Casolari P, Caramori G, Fabbri LM, Johnston SL. Infections and airway inflammation in chronic obstructive pulmonary disease severe exacerbations. Am J Respir Crit Care Med 2006;173:1114-1121.
239. Bafadhel M, McKenna S, Terry S, Mistry V, Pancholi M, Venge P, Lomas DA, Barer MR, Johnston SL, Pavord ID, et al. Blood eosinophils to direct corticosteroid treatment of exacerbations of chronic obstructive pulmonary disease: a randomized placebocontrolled trial. Am J Respir Crit Care Med 2012;186:48-55.
240. Seemungal TA, Donaldson GC, Bhowmik A, Jeffries DJ, Wedzicha JA. Time course and recovery of exacerbations in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2000; 161:1608-1613.
241. Hurst JR, Donaldson GC, Quint JK, Goldring JJ, Baghai-Ravary R, Wedzicha JA. Temporal clustering of exacerbations in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2009; 179:369-374.
242. Wells JM, Washko GR, Han MK, Abbas N, Nath H, Mamary AJ, Regan E, Bailey WC, Martinez FJ, Westfall E, et al.; COPDGene Investigators; ECLIPSE Study Investigators. Pulmonary arterial enlargement and acute exacerbations of COPD. N Engl J Med 2012;367:913-921.
243. Han MK, Kazerooni EA, Lynch DA, Liu LX, Murray S, Curtis JL, Criner GJ, Kim V, Bowler RP, Hanania NA, et al.; COPDGene Investigators. Chronic obstructive pulmonary disease exacerbations in the COPDGene study: associated radiologic phenotypes. Radiology 2011;261:274-282.
244. Kim V, Han MK, Vance GB, Make BJ, Newell JD, Hokanson JE, Hersh CP, Stinson D, Silverman EK, Criner GJ; COPDGene Investigators. The chronic bronchitic phenotype of COPD: an analysis of the COPDGene Study. Chest 2011;140:626-633.
245. Burgel PR, Nesme-Meyer P, Chanez P, Caillaud D, CarréP, Perez T, Roche N; Initiatives Bronchopneumopathie Chronique Obstructive Scientific Committee. Cough and sputum production are associated with frequent exacerbations and hospitalizations in COPD subjects. Chest 2009;135:975-982.
246. Martinez FJ, Han MK, Flaherty K, Curtis J. Role of infection and antimicrobial therapy in acute exacerbations of chronic obstructive pulmonary disease. Expert Rev Anti Infect Ther 2006;4:101-124.
247. Celli BR, Thomas NE, Anderson JA, Ferguson GT, Jenkins CR, Jones PW, Vestbo J, Knobil K, Yates JC, Calverley PM. Effect of pharmacotherapy on rate of decline of lung function in chronic obstructive pulmonary disease: results from the TORCH study. Am J Respir Crit Care Med 2008;178:332-338.
248. Tashkin DP, Celli B, Decramer M, Liu D, Burkhart D, Cassino C, Kesten S. Bronchodilator responsiveness in patients with COPD. Eur Respir J 2008;31:742-750.
249. Hoogendoorn M, Hoogenveen RT, Rutten-van Mölken MP, Vestbo J, Feenstra TL. Case fatality of COPD exacerbations: a metaanalysis and statistical modelling approach. Eur Respir J 2011;37: 508-515.
250. Piquet J, Chavaillon JM, David P, Martin F, Blanchon F, Roche N; French College of General Hospital Respiratory Physicians (CPHG). High-risk patients following hospitalisation for an acute exacerbation of COPD. Eur Respir J 2013;42:946-955.
251. Singanayagam A, Schembri S, Chalmers JD. Predictors of mortality in hospitalized adults with acute exacerbation of chronic obstructive pulmonary disease. Ann Am Thorac Soc 2013;10:81-89.
252. Garcia-Aymerich J, Serra Pons I, Mannino DM, Maas AK, Miller DP, Davis KJ. Lung function impairment, COPD hospitalisations and subsequent mortality. Thorax 2011;66:585-590.
253. National Institute for Health and Care Excellence. Chronic obstructive pulmonary disease in over 16s: diagnosis and management. 2010 [accessed 2017 Feb 8]. https://www.nice.org.uk/guidance/CG101
254. Celli BR, MacNee W; ATS/ERS Task Force. Standards for the diagnosis and treatment of patients with COPD: a summary of the ATS/ERS position paper. Eur Respir J 2004;23:932-946.
255. Turner MO, Patel A, Ginsburg S, FitzGerald JM. Bronchodilator delivery in acute airflow obstruction: a meta-analysis. Arch Intern Med 1997;157:1736-1744.
256. Barr RG, Rowe BH, Camargo CA Jr. Methylxanthines for exacerbations of chronic obstructive pulmonary disease: metaanalysis of randomised trials. BMJ 2003;327:643.
257. Duffy N, Walker P, Diamantea F, Calverley PM, Davies L. Intravenous aminophylline in patients admitted to hospital with non-acidotic exacerbations of chronic obstructive pulmonary disease: a prospective randomised controlled trial. Thorax 2005;60:713-717.
258. Davies L, Angus RM, Calverley PM. Oral corticosteroids in patients admitted to hospital with exacerbations of chronic obstructive pulmonary disease: a prospective randomised controlled trial. Lancet 1999;354:456-460.
259. Maltais F, Ostinelli J, Bourbeau J, Tonnel AB, Jacquemet N, Haddon J, Rouleau M, Boukhana M, Martinot JB, Duroux P. Comparison of nebulized budesonide and oral prednisolone with placebo in the treatment of acute exacerbations of chronic obstructive pulmonary disease: a randomized controlled trial. Am J Respir Crit Care Med 2002;165:698-703.
260. Niewoehner DE, Erbland ML, Deupree RH, Collins D, Gross NJ, Light RW, Anderson P, Morgan NA; Department of Veterans Affairs Cooperative Study Group. Effect of systemic glucocorticoids on exacerbations of chronic obstructive pulmonary disease. N Engl J Med 1999;340:1941-1947.
261. Thompson WH, Nielson CP, Carvalho P, Charan NB, Crowley JJ. Controlled trial of oral prednisone in outpatients with acute COPD exacerbation. Am J Respir Crit Care Med 1996;154:407-412.
262. Alía I, de la Cal MA, Esteban A, Abella A, Ferrer R, Molina FJ, Torres A, Gordo F, Elizalde JJ, de Pablo R, et al. Efficacy of corticosteroid therapy in patients with an acute exacerbation of chronic obstructive pulmonary disease receiving ventilatory support. Arch Intern Med 2011;171:1939-1946.
263. Aaron SD, Vandemheen KL, Hebert P, Dales R, Stiell IG, Ahuja J, Dickinson G, Brison R, Rowe BH, Dreyer J, et al. Outpatient oral prednisone after emergency treatment of chronic obstructive pulmonary disease. N Engl J Med 2003;348:2618-2625.
264. Leuppi JD, Schuetz P, Bingisser R, Bodmer M, Briel M, Drescher T, Duerring U, Henzen C, Leibbrandt Y, Maier S, et al. Short-term vs conventional glucocorticoid therapy in acute exacerbations of chronic obstructive pulmonary disease: the REDUCE randomized clinical trial. JAMA 2013;309:2223-2231.
265. de Jong YP, Uil SM, Grotjohan HP, Postma DS, Kerstjens HA, van den Berg JW. Oral or IV prednisolone in the treatment of COPD exacerbations: a randomized, controlled, double-blind study. Chest 2007;132:1741-1747.
266. Bafadhel M, McKenna S, Terry S, Mistry V, Reid C, Haldar P, McCormick M, Haldar K, Kebadze T, Duvoix A, et al. Acute exacerbations of chronic obstructive pulmonary disease: identification of biologic clusters and their biomarkers. Am J Respir Crit Care Med 2011;184:662-671.
267. Vollenweider DJ, Jarrett H, Steurer-Stey CA, Garcia-Aymerich J, Puhan MA. Antibiotics for exacerbations of chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2012;12: CD010257.
268. Miravitlles M, Kruesmann F, Haverstock D, Perroncel R, Choudhri SH, Arvis P. Sputum colour and bacteria in chronic bronchitis exacerbations: a pooled analysis. Eur Respir J 2012;39:1354-1360.
269. Stockley RA, O'Brien C, Pye A, Hill SL. Relationship of sputum color to nature and outpatient management of acute exacerbations of COPD. Chest 2000;117:1638-1645.
270. Ram FS, Rodriguez-Roisin R, Granados-Navarrete A, Garcia-Aymerich J, Barnes NC. Antibiotics for exacerbations of chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2006; 2:CD004403.
271. Schuetz P, Christ-Crain M, Thomann R, Falconnier C, Wolbers M, Widmer I, Neidert S, Fricker T, Blum C, Schild U, et al.; ProHOSP Study Group. Effect of procalcitonin-based guidelines vs standard guidelines on antibiotic use in lower respiratory tract infections: the ProHOSP randomized controlled trial. JAMA 2009; 302:1059-1066.
272. Schuetz P, Müller B, Christ-Crain M, Stolz D, Tamm M, Bouadma L, Luyt CE, Wolff M, Chastre J, Tubach F, et al. Procalcitonin to initiate or discontinue antibiotics in acute respiratory tract infections. Cochrane Database Syst Rev 2012;9:CD007498.
273. Nouira S, Marghli S, Belghith M, Besbes L, Elatrous S, Abroug F. Once daily oral ofloxacin in chronic obstructive pulmonary disease exacerbation requiring mechanical ventilation: a randomised placebo-controlled trial. Lancet 2001;358:2020-2025.
274. Masterton RG, Burley CJ. Randomized, double-blind study comparing 5-and 7-day regimens of oral levofloxacin in patients with acute exacerbation of chronic bronchitis. Int J Antimicrob Agents 2001; 18:503-512.
275. Adams SG, Melo J, Luther M, Anzueto A. Antibiotics are associated with lower relapse rates in outpatients with acute exacerbations of COPD. Chest 2000;117:1345-1352.
276. Miravitlles M, Espinosa C, Fernández-Laso E, Martos JA, Maldonado JA, Gallego M; Study Group of Bacterial Infection in COPD. Relationship between bacterial flora in sputum and functional impairment in patients with acute exacerbations of COPD. Chest 1999;116:40-46.
277. Soler N, Torres A, Ewig S, Gonzalez J, Celis R, El-Ebiary M, Hernandez C, Rodriguez-Roisin R. Bronchial microbial patterns in severe exacerbations of chronic obstructive pulmonary disease (COPD) requiring mechanical ventilation. Am J Respir Crit Care Med 1998;157:1498-1505.
278. Austin MA, Wills KE, Blizzard L, Walters EH, Wood-Baker R. Effect of high flow oxygen on mortality in chronic obstructive pulmonary disease patients in prehospital setting: randomised controlled trial. BMJ 2010;341:c5462.
279. Brochard L, Mancebo J, Wysocki M, Lofaso F, Conti G, Rauss A, Simonneau G, Benito S, Gasparetto A, Lemaire F, et al. Noninvasive ventilation for acute exacerbations of chronic obstructive pulmonary disease. N Engl J Med 1995;333:817-822.
280. Lightowler JV, Wedzicha JA, Elliott MW, Ram FS. Non-invasive positive pressure ventilation to treat respiratory failure resulting from exacerbations of chronic obstructive pulmonary disease: Cochrane systematic review and meta-analysis. BMJ 2003;326: 185.
281. Meyer TJ, Hill NS. Noninvasive positive pressure ventilation to treat respiratory failure. Ann Intern Med 1994;120:760-770.
282. Chandra D, Stamm JA, Taylor B, Ramos RM, Satterwhite L, Krishnan JA, Mannino D, Sciurba FC, Holguín F. Outcomes of noninvasive ventilation for acute exacerbations of chronic obstructive pulmonary disease in the United States, 1998-2008. Am J Respir Crit Care Med 2012;185:152-159.
283. Consensus development conference committee. Clinical indications for noninvasive positive pressure ventilation in chronic respiratory failure due to restrictive lung disease, COPD, and nocturnal hypoventilation-a consensus conference report. Chest 1999;116: 521-534.
284. Bott J, Carroll MP, Conway JH, Keilty SE, Ward EM, Brown AM, Paul EA, Elliott MW, Godfrey RC, Wedzicha JA, et al. Randomised controlled trial of nasal ventilation in acute ventilatory failure due to chronic obstructive airways disease. Lancet 1993;341:1555-1557.
285. Kramer N, Meyer TJ, Meharg J, Cece RD, Hill NS. Randomized, prospective trial of noninvasive positive pressure ventilation in acute respiratory failure. Am J Respir Crit Care Med 1995;151: 1799-1806.
286. Plant PK, Owen JL, Elliott MW. Early use of non-invasive ventilation for acute exacerbations of chronic obstructive pulmonary disease on general respiratory wards: a multicentre randomised controlled trial. Lancet 2000;355:1931-1935.
287. Conti G, Antonelli M, Navalesi P, Rocco M, Bufi M, Spadetta G, Meduri GU. Noninvasive vs. conventional mechanical ventilation in patients with chronic obstructive pulmonary disease after failure of medical treatment in the ward: a randomized trial. Intensive Care Med 2002;28:1701-1707.
288. Jennings JH, Thavarajah K, Mendez MP, Eichenhorn M, Kvale P, Yessayan L. Predischarge bundle for patients with acute exacerbations of COPD to reduce readmissions and ED visits: a randomized controlled trial. Chest 2015;147:1227-1234.
289. Singh G, Zhang W, Kuo YF, Sharma G. Association of psychological disorders with 30-day readmission rates in patients with COPD. Chest 2016;149:905-915.
290. Ringbæk T, Green A, Laursen LC, Frausing E, Brøndum E, Ulrik CS. Effect of tele health care on exacerbations and hospital admissions in patients with chronic obstructive pulmonary disease: a randomized clinical trial. Int J Chron Obstruct Pulmon Dis 2015;10: 1801-1808.
291. Hartl S, Lopez-Campos JL, Pozo-Rodriguez F, Castro-Acosta A, Studnicka M, Kaiser B, Roberts CM. Risk of death and readmission of hospital-admitted COPD exacerbations: European COPD Audit. Eur Respir J 2016;47:113-121.
292. Jordan RE, Majothi S, Heneghan NR, Blissett DB, Riley RD, Sitch AJ, Price MJ, Bates EJ, Turner AM, Bayliss S, et al. Supported selfmanagement for patients with moderate to severe chronic obstructive pulmonary disease (COPD): an evidence synthesis and economic analysis. Health Technol Assess 2015;19:1-516.
293. Gavish R, Levy A, Dekel OK, Karp E, Maimon N. The association between hospital readmission and pulmonologist follow-up visits in patients with COPD. Chest 2015;148:375-381.
294. Oga T, Tsukino M, Hajiro T, Ikeda A, Nishimura K. Predictive properties of different multidimensional staging systems in patients with chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis 2011;6:521-526.
295. Martínez-García MA, de la Rosa Carrillo D, Soler-Cataluña JJ, Donat-Sanz Y, Serra PC, Lerma MA, Ballestín J, Sanchez IV, Selma Ferrer MJ, Dalfo AR, et al. Prognostic value of bronchiectasis in patients with moderate-to-severe chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2013;187:823-831.
296. Barnes PJ, Celli BR. Systemic manifestations and comorbidities of COPD. Eur Respir J 2009;33:1165-1185.
297. Mannino DM, Thorn D, Swensen A, Holguin F. Prevalence and outcomes of diabetes, hypertension and cardiovascular disease in COPD. Eur Respir J 2008;32:962-969.
298. Sin DD, Anthonisen NR, Soriano JB, Agusti AG. Mortality in COPD: role of comorbidities. Eur Respir J 2006;28:1245-1257.
299. Iversen KK, Kjaergaard J, Akkan D, Kober L, Torp-Pedersen C, Hassager C, Vestbo J, Kjoller E; ECHOS Lung Function Study Group. The prognostic importance of lung function in patients admitted with heart failure. Eur J Heart Fail 2010;12: 685-691.
300. Almagro P, Soriano JB, Cabrera FJ, Boixeda R, Alonso-Ortiz MB, Barreiro B, Diez-Manglano J, Murio C, Heredia JL; Working Group on COPD, Spanish Society of Internal Medicine. Short-and medium-term prognosis in patients hospitalized for COPD exacerbation: the CODEX index. Chest 2014;145:972-980.
301. Miller J, Edwards LD, Agustí A, Bakke P, Calverley PM, Celli B, Coxson HO, Crim C, Lomas DA, Miller BE, et al.; Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) Investigators. Comorbidity, systemic inflammation and outcomes in the ECLIPSE cohort. Respir Med 2013;107: 1376-1384.
302. Campo G, Napoli N, Serenelli C, Tebaldi M, Ferrari R. Impact of a recent hospitalization on treatment and prognosis of STsegment elevation myocardial infarction. Int J Cardiol 2013; 167:296-297.
303. Fabbri LM, Luppi F, BeghéB, Rabe KF. Complex chronic comorbidities of COPD. Eur Respir J 2008;31:204-212.
304. Bhatt SP, Dransfield MT. Chronic obstructive pulmonary disease and cardiovascular disease. Transl Res 2013;162:237-251.
305. Matamis D, Tsagourias M, Papathanasiou A, Sineffaki H, Lepida D, Galiatsou E, Nakos G. Targeting occult heart failure in intensive care unit patients with acute chronic obstructive pulmonary disease exacerbation: effect on outcome and quality of life. J Crit Care 2014;29:315.e7-315.e14.
306. MacDonald MI, Shafuddin E, King PT, Chang CL, Bardin PG, Hancox RJ. Cardiac dysfunction during exacerbations of chronic obstructive pulmonary disease. Lancet Respir Med 2016; 4:138-148.
307. Lipworth B, Wedzicha J, Devereux G, Vestbo J, Dransfield MT. Beta-blockers in COPD: time for reappraisal. Eur Respir J 2016; 48:880-888.
308. Høiseth AD, Neukamm A, Karlsson BD, Omland T, Brekke PH, Søyseth V. Elevated high-sensitivity cardiac troponin T is associated with increased mortality after acute exacerbation of chronic obstructive pulmonary disease. Thorax 2011;66:775-781.
309. Singh S, Loke YK, Enright P, Furberg CD. Pro-arrhythmic and proischaemic effects of inhaled anticholinergic medications. Thorax 2013;68:114-116.
310. Wilchesky M, Ernst P, Brophy JM, Platt RW, Suissa S. Bronchodilator use and the risk of arrhythmia in COPD: part 2: reassessment in the larger Quebec cohort. Chest 2012;142:305-311.
311. Salpeter SR, Ormiston TM, Salpeter EE. Cardiovascular effects of beta-agonists in patients with asthma and COPD: a meta-analysis. Chest 2004;125:2309-2321.
312. Tashkin DP, Fabbri LM. Long-acting beta-agonists in the management of chronic obstructive pulmonary disease: current and future agents. Respir Res 2010;11:149.
313. Calverley P, Pauwels R, Vestbo J, Jones P, Pride N, Gulsvik A, Anderson J, Maden C; TRial of Inhaled STeroids ANd long-acting beta2 agonists study group. Combined salmeterol and fluticasone in the treatment of chronic obstructive pulmonary disease: a randomised controlled trial. Lancet 2003;361:449-456.
314. Szafranski W, Cukier A, Ramirez A, Menga G, Sansores R, Nahabedian S, Peterson S, Olsson H. Efficacy and safety of budesonide/formoterol in the management of chronic obstructive pulmonary disease. Eur Respir J 2003;21:74-81.
315. Calverley PM, Boonsawat W, Cseke Z, Zhong N, Peterson S, Olsson H. Maintenance therapy with budesonide and formoterol in chronic obstructive pulmonary disease. Eur Respir J 2003;22:912-919.
316. Calverley PM, Anderson JA, Celli B, Ferguson GT, Jenkins C, Jones PW, Crim C, Willits LR, Yates JC, Vestbo J; TORCH Investigators. Cardiovascular events in patients with COPD: TORCH study results. Thorax 2010;65:719-725.
317. Houben-Wilke S, Jörres RA, Bals R, Franssen FM, Glä ser S, Holle R, Karch A, Koch A, Magnussen H, Obst A, et al. Peripheral artery disease and its clinical relevance in patients with COPD in the Systemic Consequences-Comorbidities Network study. Am J Respir Crit Care Med 2017;195:189-197.
318. Divo M, Cote C, de Torres JP, Casanova C, Marin JM, Pinto-Plata V, Zulueta J, Cabrera C, Zagaceta J, Hunninghake G, et al.; BODE Collaborative Group. Comorbidities and risk of mortality in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2012;186:155-161.
319. Bon J, Fuhrman CR, Weissfeld JL, Duncan SR, Branch RA, Chang CC, Zhang Y, Leader JK, Gur D, Greenspan SL, et al. Radiographic emphysema predicts low bone mineral density in a tobaccoexposed cohort. Am J Respir Crit Care Med 2011;183:885-890.
320. McAllister DA, Maclay JD, Mills NL, Mair G, Miller J, Anderson D, Newby DE, Murchison JT, Macnee W. Arterial stiffness is independently associated with emphysema severity in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2007;176:1208-1214.
321. Bolton CE, Cannings-John R, Edwards PH, Ionescu AA, Evans WD, Pettit RJ, Faulkner TA, Stone MD, Shale DJ. What community measurements can be used to predict bone disease in patients with COPD? Respir Med 2008;102:651-657.
322. Bolton CE, Ionescu AA, Shiels KM, Pettit RJ, Edwards PH, Stone MD, Nixon LS, Evans WD, Griffiths TL, Shale DJ. Associated loss of fatfree mass and bone mineral density in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2004;170: 1286-1293.
323. Jaramillo JD, Wilson C, Stinson DS, Lynch DA, Bowler RP, Lutz S, Bon JM, Arnold B, McDonald ML, Washko GR, et al.; COPDGene Investigators. Reduced bone density and vertebral fractures in smokers: men and COPD patients at increased risk. Ann Am Thorac Soc 2015;12:648-656.
324. Jaramillo J, Wilson C, Stinson D, et al. Erratum: reduced bone density and vertebral fractures in smokers: men and COPD patients at increased risk. Ann Am Thorac Soc 2015;12:1112.
325. Ng TP, Niti M, Tan WC, Cao Z, Ong KC, Eng P. Depressive symptoms and chronic obstructive pulmonary disease: effect on mortality, hospital readmission, symptom burden, functional status, and quality of life. Arch Intern Med 2007;167:60-67.
326. Eisner MD, Blanc PD, Yelin EH, Katz PP, Sanchez G, Iribarren C, Omachi TA. Influence of anxiety on health outcomes in COPD. Thorax 2010;65:229-234.
327. de Torres JP, Bastarrika G, Wisnivesky JP, Alcaide AB, Campo A, Seijo LM, Pueyo JC, Villanueva A, Lozano MD, Montes U, et al. Assessing the relationship between lung cancer risk and emphysema detected on low-dose CT of the chest. Chest 2007; 132:1932-1938.
328. Wilson DO, Leader JK, Fuhrman CR, Reilly JJ, Sciurba FC, Weissfeld JL. Quantitative computed tomography analysis, airflow obstruction, and lung cancer in the Pittsburgh Lung Screening Study. J Thorac Oncol 2011;6:1200-1205.
329. Wilson DO, Weissfeld JL, Balkan A, Schragin JG, Fuhrman CR, Fisher SN, Wilson J, Leader JK, Siegfried JM, Shapiro SD, et al. Association of radiographic emphysema and airflow obstruction with lung cancer. Am J Respir Crit Care Med 2008; 178:738-744.
330. de-Torres JP, Wilson DO, Sanchez-Salcedo P, Weissfeld JL, Berto J, Campo A, Alcaide AB, García-Granero M, Celli BR, Zulueta JJ. Lung cancer in patients with chronic obstructive pulmonary disease: development and validation of the COPD Lung Cancer Screening Score. Am J Respir Crit Care Med 2015;191: 285-291.
331. Aberle DR, Adams AM, Berg CD, Black WC, Clapp JD, Fagerstrom RM, Gareen IF, Gatsonis C, Marcus PM, Sicks JD; National Lung Screening Trial Research Team. Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med 2011;365:395-409.
332. Infante M, Cavuto S, Lutman FR, Passera E, Chiarenza M, Chiesa G, Brambilla G, Angeli E, Aranzulla G, Chiti A, et al.; DANTE Study Group. Long-term follow-up results of the DANTE trial, a randomized study of lung cancer screening with spiral computed tomography. Am J Respir Crit Care Med 2015;191: 1166-1175.
333. Cebron Lipovec N, Beijers RJ, van den Borst B, Doehner W, Lainscak M, Schols AM. The prevalence of metabolic syndrome in chronic obstructive pulmonary disease: a systematic review. COPD 2016; 13:399-406.
334. Martinez CH, Okajima Y, Murray S, Washko GR, Martinez FJ, Silverman EK, Lee JH, Regan EA, Crapo JD, Curtis JL, et al.; COPDGene Investigators. Impact of self-reported gastroesophageal reflux disease in subjects from COPDGene cohort. Respir Res 2014;15:62.
335. Ingebrigtsen TS, Marott JL, Vestbo J, Nordestgaard BG, Hallas J, Lange P. Gastro-esophageal reflux disease and exacerbations in chronic obstructive pulmonary disease. Respirology 2015;20: 101-107.
336. Patel IS, Vlahos I, Wilkinson TM, Lloyd-Owen SJ, Donaldson GC, Wilks M, Reznek RH, Wedzicha JA. Bronchiectasis, exacerbation indices, and inflammation in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2004;170:400-407.
337. Shepard JW Jr, Garrison MW, Grither DA, Evans R, Schweitzer PK. Relationship of ventricular ectopy to nocturnal oxygen desaturation in patients with chronic obstructive pulmonary disease. Am J Med 1985;78:28-34.
338. Bradley TD, Rutherford R, Grossman RF, Lue F, Zamel N, Moldofsky H, Phillipson EA. Role of daytime hypoxemia in the pathogenesis of right heart failure in the obstructive sleep apnea syndrome. Am Rev Respir Dis 1985;131:835-839.
339. Weitzenblum E, Krieger J, Apprill M, Vallée E, Ehrhart M, Ratomaharo J, Oswald M, Kurtz D. Daytime pulmonary hypertension in patients with obstructive sleep apnea syndrome. Am Rev Respir Dis 1988;138:345-349.