Chronic obstructive pulmonary disease

Marc Decramer, Wim Janssens, Marc Miravitlles, Marc Decramer, Wim Janssens, Marc Miravitlles

Abstract

Chronic obstructive pulmonary disease (COPD) is characterised by progressive airflow obstruction that is only partly reversible, inflammation in the airways, and systemic effects or comorbities. The main cause is smoking tobacco, but other factors have been identified. Several pathobiological processes interact on a complex background of genetic determinants, lung growth, and environmental stimuli. The disease is further aggravated by exacerbations, particularly in patients with severe disease, up to 78% of which are due to bacterial infections, viral infections, or both. Comorbidities include ischaemic heart disease, diabetes, and lung cancer. Bronchodilators constitute the mainstay of treatment: β(2) agonists and long-acting anticholinergic agents are frequently used (the former often with inhaled corticosteroids). Besides improving symptoms, these treatments are also thought to lead to some degree of disease modification. Future research should be directed towards the development of agents that notably affect the course of disease.

Copyright © 2012 Elsevier Ltd. All rights reserved.

Figures

Figure 1
Figure 1
Comparison of airway features in a healthy individual and in a patient with chronic obstructive pulmonary disease (A) Normal airway. (B) In chronic obstructive pulmonary disease airways are narrowed by infiltration of inflammatory cells, mucosal hyperplasia, and deposition of connective tissue in the peribronchiolar space.
Figure 2
Figure 2
Schematic representation of the mechanisms involved in the pathogenesis of chronic obstructive pulmonary disease The process is essentially characterised by a decline in FEV1 with increasing age. FEV1=forced expiratory volume in 1 s.
Figure 3
Figure 3
Hypothetical cycle of infection and inflammation in COPD COPD=chronic obstructive pulmonary disease. Reproduced from reference 59 by permission of Massachusetts Medical Society.
Figure 4
Figure 4
Comorbidities of chronic obstructive pulmonary disease
Figure 5
Figure 5
FEV1 decline in relation to increasing age in patients with COPD in GOLD stages 2–4 treated with a combined long-acting β2 agonist and inhaled corticosteroid or tiotropium Data from the TORCH and UPLIFT studies are plotted on a Fletcher-Peto diagram. The black dashed line represents the original Fletcher-Peto curve. GOLD=Global Initiative on Obstructive Lung Disease. SFC=salmeterol and fluticasone combined. FEV1=forced expiratory volume in 1 s. Reproduced from reference 117 by permission of BMJ Publishing Group Ltd.
Figure 6
Figure 6
General approach to management of exacerbations in chronic obstructive pulmonary disease

References

    1. Global Initiative for Chronic Obstructive Lung Disease Global strategy for the diagnosis, management, and prevention of COPD: updated 2010. (accessed Oct 20, 2011).
    1. Buist AS, McBurnie MA, Vollmer WM, et al. International variation in the prevalence of COPD (The BOLD Study): a population-based prevalence study. Lancet. 2007;370:741–750.
    1. Mannino DM, Buist AS. Global burden of COPD: risk factors, prevalence, and future trends. Lancet. 2007;370:765–773.
    1. Menezes AM, Perez-Padilla R, Jardim JR, et al. Chronic obstructive pulmonary disease in five Latin American cities (the PLATINO study): a prevalence study. Lancet. 2005;366:1875–1881.
    1. WHO World health statistics 2008. (accessed Oct 20, 2011).
    1. Jemal A, Ward E, Hao Y, et al. Trends in the leading causes of death in the United States, 1970–2002. JAMA. 2005;294:1255–1259.
    1. Gershon AS, Wang C, Wilton AS, et al. Trends in chronic obstructive pulmonary disease prevalence, incidence, and mortality in Ontario, Canada, 1996 to 2007: a population-based study. Arch Intern Med. 2010;170:560–565.
    1. Soriano JB, Ancochea J, Miravitlles M, et al. Recent trends in COPD prevalence in Spain: a repeated cross-sectional survey 1997–2007. Eur Respir J. 2010;36:758–765.
    1. Halbert RJ, Natoli JL, Gano A, et al. Global burden of COPD: systematic review and meta-analysis. Eur Respir J. 2006;28:523–532.
    1. Vollmer WM, Gislason T, Burney P, et al. Comparison of spirometry criteria for the diagnosis of COPD: results from the BOLD study. Eur Respir J. 2009;34:588–597.
    1. Miravitlles M, Soriano JB, Garcia-Rio F, et al. Prevalence of COPD in Spain: impact of undiagnosed COPD on quality of life and daily life activities. Thorax. 2009;64:863–868.
    1. Hvidsten SC, Storesund L, Wentzel-Larsen T, et al. Prevalence and predictors of undiagnosed chronic obstructive pulmonary disease in a Norwegian adult general population. Clin Respir J. 2010;4:13–21.
    1. Mannino DM, Homa DM, Akinbami LJ, Ford ES, Redd SC. Chronic obstructive pulmonary disease surveillance-United States, 1971–2000. MMWR Surveill Summ. 2002;51:1–16.
    1. Svanes C, Sunyer J, Plana E, et al. Early life origins of chronic obstructive pulmonary disease. Thorax. 2010;65:14–20.
    1. Eisner MD, Anthonisen N, Coultas D, et al. 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.
    1. Gooptu B, Ekeowa UI, Lomas DA. Mechanisms of emphysema in α1-antitrypsin deficiency: molecular and cellular insights. Eur Respir J. 2009;34:475–488.
    1. Hancock DB, Eijgelsheim M, Wilk JB, et al. Meta-analyses of genome-wide association studies identify multiple loci associated with pulmonary function. Nat Genet. 2010;42:45–52.
    1. Pillai SG, Ge D, Zhu G, et al. A genome-wide association study in chronic obstructive pulmonary disease (COPD): identification of two major susceptibility loci. PLoS Genet. 2009;5:e1000421.
    1. Wilk JB, Chen TH, Gottlieb DJ, et al. A genome-wide association study of pulmonary function measures in the Framingham Heart Study. PLoS Genet. 2009;5:e1000429.
    1. Hunninghake GM, Cho MH, Tesfaigzi Y, et al. MMP12, lung function, and COPD in high-risk populations. N Engl J Med. 2009;361:2599–2608.
    1. Lambrechts D, Buysschaert I, Zanen P, et al. The 15q24/25 susceptibility variant for lung cancer and chronic obstructive pulmonary disease is associated with emphysema. Am J Respir Crit Care Med. 2010;181:486–493.
    1. O'Donnell DE. Hyperinflation, dyspnea, and exercise intolerance in chronic obstructive pulmonary disease. Proc Am Thorac Soc. 2006;3:180–184.
    1. Hogg JC, Timens W. The pathology of chronic obstructive pulmonary disease. Annu Rev Pathol. 2009;4:435–459.
    1. Hogg JC, McDonough JE, Gosselink JV, et al. What drives the peripheral lung-remodeling process in chronic obstructive pulmonary disease? Proc Am Thorac Soc. 2009;6:668–672.
    1. MacNee W, Tuder RM. New paradigms in the pathogenesis of chronic obstructive pulmonary disease I. Proc Am Thorac Soc. 2009;6:527–531.
    1. Silverman EK, Spira A, Pare PD. Genetics and genomics of chronic obstructive pulmonary disease. Proc Am Thorac Soc. 2009;6:539–542.
    1. Cosio MG, Saetta M, Agusti A. Immunologic aspects of chronic obstructive pulmonary disease. N Engl J Med. 2009;360:2445–2454.
    1. Opitz B, van Laak V, Eitel J, Suttorp N. Innate immune recognition in infectious and noninfectious diseases of the lung. Am J Respir Crit Care Med. 2010;181:1294–1309.
    1. Demedts IK, Bracke KR, Van Pottelberge G, et al. Accumulation of dendritic cells and increased CCL20 levels in the airways of patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2007;175:998–1005.
    1. Barnes PJ, Shapiro SD, Pauwels RA. Chronic obstructive pulmonary disease: molecular and cellular mechanisms. Eur Respir J. 2003;22:672–688.
    1. Rahman I, Adcock IM. Oxidative stress and redox regulation of lung inflammation in COPD. Eur Respir J. 2006;28:219–242.
    1. Sullivan AK, Simonian PL, Falta MT, et al. Oligoclonal CD4+ T cells in the lungs of patients with severe emphysema. Am J Respir Crit Care Med. 2005;172:590–596.
    1. van der Strate BW, Postma DS, Brandsma CA, et al. Cigarette smoke-induced emphysema: a role for the B cell? Am J Respir Crit Care Med. 2006;173:751–758.
    1. Lee SH, Goswami S, Grudo A, et al. Antielastin autoimmunity in tobacco smoking-induced emphysema. Nat Med. 2007;13:567–569.
    1. Tang Q, Bluestone JA. The Foxp3+ regulatory T cell: a jack of all trades, master of regulation. Nat Immunol. 2008;9:239–244.
    1. Barcelo B, Pons J, Ferrer JM, et al. Phenotypic characterisation of T-lymphocytes in COPD: abnormal CD4+CD25+ regulatory T-lymphocyte response to tobacco smoking. Eur Respir J. 2008;31:555–562.
    1. Alcorn JF, Crowe CR, Kolls JK. TH17 cells in asthma and COPD. Annu Rev Physiol. 2010;72:495–516.
    1. Di Stefano A, Caramori G, Gnemmi I, et al. T helper type 17-related cytokine expression is increased in the bronchial mucosa of stable chronic obstructive pulmonary disease patients. Clin Exp Immunol. 2009;157:316–324.
    1. Tsuji T, Aoshiba K, Nagai A. Alveolar cell senescence in patients with pulmonary emphysema. Am J Respir Crit Care Med. 2006;174:886–893.
    1. Tsuji T, Aoshiba K, Nagai A. Cigarette smoke induces senescence in alveolar epithelial cells. Am J Respir Cell Mol Biol. 2004;31:643–649.
    1. Ito K, Barnes PJ. COPD as a disease of accelerated lung aging. Chest. 2009;135:173–180.
    1. Tuder RM, Yoshida T, Fijalkowka I, et al. Role of lung maintenance program in the heterogeneity of lung destruction in emphysema. Proc Am Thorac Soc. 2006;3:673–679.
    1. Giangreco A, Arwert EN, Rosewell IR, et al. Stem cells are dispensable for lung homeostasis but restore airways after injury. Proc Natl Acad Sci USA. 2009;106:9286–9291.
    1. Rennard SI, Togo S, Holz O. Cigarette smoke inhibits alveolar repair: a mechanism for the development of emphysema. Proc Am Thorac Soc. 2006;3:703–708.
    1. Crosby LM, Waters CM. Epithelial repair mechanisms in the lung. Am J Physiol Lung Cell Mol Physiol. 2010;298:L715–L731.
    1. Hoogendoorn M, Feenstra TL, Hoogenveen RT, et al. Association between lung function and exacerbation frequency in patients with COPD. Int J Chron Obstruct Pulmon Dis. 2010;5:435–444.
    1. Hurst JR, Vestbo J, Anzueto A, et al. Susceptibility to exacerbation in chronic obstructive pulmonary disease. N Engl J Med. 2010;363:1128–1138.
    1. Doll H, Miravitlles M. Health-related QOL in acute exacerbations of chronic bronchitis and chronic obstructive pulmonary disease: a review of the literature. Pharmacoeconomics. 2005;23:345–363.
    1. Soler-Cataluna JJ, Martinez-Garcia MA, Roman SP, et al. Severe acute exacerbations and mortality in patients with chronic obstructive pulmonary disease. Thorax. 2005;60:925–931.
    1. Hurst JR, Donaldson GC, Perera WR, et al. Use of plasma biomarkers at exacerbation of chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2006;174:867–874.
    1. Bozinovski S, Hutchinson A, Thompson M, et al. Serum amyloid A is a biomarker of acute exacerbations of chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2008;177:269–278.
    1. Papi A, Bellettato CM, Braccioni F, et al. Infections and airway inflammation in chronic obstructive pulmonary disease severe exacerbations. Am J Respir Crit Care Med. 2006;173:1114–1121.
    1. Stockley RA, O'Brien C, Pye A, et al. Relationship of sputum color to nature and outpatient management of acute exacerbations of COPD. Chest. 2000;117:1638–1645.
    1. Soler N, Agusti C, Angrill J, et al. Bronchoscopic validation of the significance of sputum purulence in severe exacerbations of chronic obstructive pulmonary disease. Thorax. 2007;62:29–35.
    1. Stolz D, Christ-Crain M, Bingisser R, et al. Antibiotic treatment of exacerbations of COPD: a randomized, controlled trial comparing procalcitonin-guidance with standard therapy. Chest. 2007;131:9–19.
    1. Daniels JM, Schoorl M, Snijders D, et al. Procalcitonin vs C-reactive protein as predictive markers of response to antibiotic therapy in acute exacerbations of COPD. Chest. 2010;138:1108–1115.
    1. Monso E, Ruiz J, Rosell A, et al. Bacterial infection in chronic obstructive pulmonary disease. A study of stable and exacerbated outpatients using the protected specimen brush. Am J Respir Crit Care Med. 1995;152:1316–1320.
    1. Miravitlles M, Marin A, Monso E, et al. Colour of sputum is a marker for bacterial colonisation in chronic obstructive pulmonary disease. Respir Res. 2010;11:58.
    1. Sethi S, Murphy TF. Infection in the pathogenesis and course of chronic obstructive pulmonary disease. N Engl J Med. 2008;359:2355–2365.
    1. Sethi S, Evans N, Grant BJ, et al. New strains of bacteria and exacerbations of chronic obstructive pulmonary disease. N Engl J Med. 2002;347:465–471.
    1. Sethi S, Wrona C, Eschberger K, et al. Inflammatory profile of new bacterial strain exacerbations of chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2008;177:491–497.
    1. Wilkinson TM, Patel IS, Wilks M, et al. Airway bacterial load and FEV1 decline in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2003;167:1090–1095.
    1. Marin A, Monso E, Garcia-Nunez M, et al. Variability and effects of bronchial colonisation in patients with moderate COPD. Eur Respir J. 2010;35:295–302.
    1. Miravitlles M, Espinosa C, Fernandez-Laso E, et al. Relationship between bacterial flora in sputum and functional impairment in patients with acute exacerbations of COPD. Study Group of Bacterial Infection in COPD. Chest. 1999;116:40–46.
    1. Murphy TF, Brauer AL, Eschberger K, et al. Pseudomonas aeruginosa in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2008;177:853–860.
    1. Ewig S, Soler N, Gonzalez J, et al. Evaluation of antimicrobial treatment in mechanically ventilated patients with severe chronic obstructive pulmonary disease exacerbations. Crit Care Med. 2000;28:692–697.
    1. Montero M, Dominguez M, Orozco-Levi M, et al. Mortality of COPD patients infected with multi-resistant Pseudomonas aeruginosa: a case and control study. Infection. 2009;37:16–19.
    1. Monso E, Garcia-Aymerich J, Soler N, et al. Bacterial infection in exacerbated COPD with changes in sputum characteristics. Epidemiol Infect. 2003;131:799–804.
    1. Allegra L, Blasi F, Diano P, et al. Sputum color as a marker of acute bacterial exacerbations of chronic obstructive pulmonary disease. Respir Med. 2005;99:742–747.
    1. Mallia P, Message SD, Gielen V, et al. Experimental Rhinovirus infection as a human model of chronic obstructive pulmonary disease exacerbation. Am J Respir Crit Care Med. 2011;183:734–742.
    1. Quint JK, Donaldson GC, Goldring JJ, et al. Serum IP-10 as a biomarker of human rhinovirus infection at exacerbation of COPD. Chest. 2010;137:812–822.
    1. McManus TE, Marley AM, Baxter N, et al. Respiratory viral infection in exacerbations of COPD. Respir Med. 2008;102:1575–1580.
    1. Decramer M, Rennard S, Troosters T, et al. COPD as a lung disease with systemic consequences-clinical impact, mechanisms, and potential for early intervention. COPD. 2008;5:235–256.
    1. Fabbri LM, Luppi F, Beghe B, et al. Complex chronic comorbidities of COPD. Eur Respir J. 2008;31:204–212.
    1. Mannino DM, Thorn D, Swensen A, et al. Prevalence and outcomes of diabetes, hypertension and cardiovascular disease in COPD. Eur Respir J. 2008;32:962–969.
    1. Sin DD, Anthonisen NR, Soriano JB, et al. Mortality in COPD: role of comorbidities. Eur Respir J. 2006;28:1245–1257.
    1. Celli BR, Cote CG, Marin JM, et al. The body-mass index, airflow obstruction, dyspnea, and exercise capacity index in chronic obstructive pulmonary disease. N Engl J Med. 2004;350:1005–1012.
    1. Edwards R. The problem of tobacco smoking. BMJ. 2004;328:217–219.
    1. Pitta F, Troosters T, Spruit MA, et al. Characteristics of physical activities in daily life in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2005;171:972–977.
    1. Booth FW, Gordon SE, Carlson CJ, et al. Waging war on modern chronic diseases: primary prevention through exercise biology. J Appl Physiol. 2000;88:774–787.
    1. Heath GW. Physical activity transitions and chronic disease. Am J Lifestyle Med. 2009;3:27S–31S.
    1. Boyd CM, Darer J, Boult C, et al. Clinical practice guidelines and quality of care for older patients with multiple comorbid diseases: implications for pay for performance. JAMA. 2005;294:716–724.
    1. Burgel PR, Paillasseur JL, Caillaud D, et al. Clinical COPD phenotypes: a novel approach using principal component and cluster analyses. Eur Respir J. 2010;36:531–539.
    1. Fabbri LM, Rabe KF. From COPD to chronic systemic inflammatory syndrome? Lancet. 2007;370:797–799.
    1. Mora S, Cook N, Buring JE, et al. Physical activity and reduced risk of cardiovascular events: potential mediating mechanisms. Circulation. 2007;116:2110–2118.
    1. Yanbaeva DG, Dentener MA, Creutzberg EC, et al. Systemic effects of smoking. Chest. 2007;131:1557–1566.
    1. Broekhuizen R, Wouters EF, Creutzberg EC, et al. Raised CRP levels mark metabolic and functional impairment in advanced COPD. Thorax. 2006;61:17–22.
    1. Barnes PJ, Celli BR. Systemic manifestations and comorbidities of COPD. Eur Respir J. 2009;33:1165–1185.
    1. Sinden NJ, Stockley RA. Systemic inflammation and comorbidity in COPD: a result of ‘overspill’ of inflammatory mediators from the lungs? Review of the evidence. Thorax. 2010;65:930–936.
    1. Anthonisen NR, Connett JE, Kiley JP, 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.
    1. Anthonisen NR, Connett JE, Murray RP. Smoking and lung function of Lung Health Study participants after 11 years. Am J Respir Crit Care Med. 2002;166:675–679.
    1. Anthonisen NR, Skeans MA, Wise RA, et al. The effects of a smoking cessation intervention on 14.5-year mortality: a randomized clinical trial. Ann Intern Med. 2005;142:233–239.
    1. Lacasse Y, Goldstein R, Lasserson TJ, et al. Pulmonary rehabilitation for chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2006;4 CD003793.
    1. Troosters T, Casaburi R, Gosselink R, et al. Pulmonary rehabilitation in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2005;172:19–38.
    1. Ries AL, Bauldoff GS, Carlin BW, et al. Pulmonary rehabilitation: joint ACCP/AACVPR evidence-based clinical practice guidelines. Chest. 2007;131:4S–42S.
    1. Calverley PM, Anderson JA, Celli B, et al. Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease. N Engl J Med. 2007;356:775–789.
    1. Tashkin DP, Celli B, Senn S, et al. A 4-year trial of tiotropium in chronic obstructive pulmonary disease. N Engl J Med. 2008;359:1543–1554.
    1. Casaburi R, Mahler DA, Jones PW, et al. A long-term evaluation of once-daily inhaled tiotropium in chronic obstructive pulmonary disease. Eur Respir J. 2002;19:217–224.
    1. Niewoehner DE, Rice K, Cote C, et al. Prevention of exacerbations of chronic obstructive pulmonary disease with tiotropium, a once-daily inhaled anticholinergic bronchodilator: a randomized trial. Ann Intern Med. 2005;143:317–326.
    1. Dusser D, Bravo ML, Iacono P. The effect of tiotropium on exacerbations and airflow in patients with COPD. Eur Respir J. 2006;27:547–555.
    1. Wedzicha JA, Calverley P, Seemungal T, et al. The prevention of chronic obstructive pulmonary disease exacerbations by salmeterol/fluticasone propionate or tiotropium bromide. Am J Respir Crit Care Med. 2008;177:19–26.
    1. Kesten S, Celli B, Decramer M, et al. Tiotropium HandiHaler in the treatment of COPD: a safety review. Int J Chron Obstruct Pulmon Dis. 2009;4:397–409.
    1. Pauwels RA, Lofdahl CG, Laitinen LA, et al. Long-term treatment with inhaled budesonide in persons with mild chronic obstructive pulmonary disease who continue smoking. European Respiratory Society Study on Chronic Obstructive Pulmonary Disease. N Engl J Med. 1999;340:1948–1953.
    1. Decramer M, Ferguson G. Clinical safety of long-acting β2-agonist and inhaled corticosteroid combination therapy in COPD. COPD. 2006;3:163–171.
    1. Singh S, Loke YK, Furberg CD. Inhaled anticholinergics and risk of major adverse cardiovascular events in patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis. JAMA. 2008;300:1439–1450.
    1. Celli B, Decramer M, Leimer I, et al. Cardiovascular safety of tiotropium in patients with COPD. Chest. 2010;137:20–30.
    1. Michele TM, Pinheiro S, Iyasu S. The safety of tiotropium—the FDA's conclusions. N Engl J Med. 2010;363:1097–1099.
    1. Crim C, Calverley PM, Anderson JA, et al. Pneumonia risk in COPD patients receiving inhaled corticosteroids alone or in combination: TORCH study results. Eur Respir J. 2009;34:641–647.
    1. Nannini LJ, Cates CJ, Lasserson TJ, et al. Combined corticosteroid and long-acting beta-agonist in one inhaler versus inhaled steroids for chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2007;4 CD006826.
    1. Singh S, Amin AV, Loke YK. Long-term use of inhaled corticosteroids and the risk of pneumonia in chronic obstructive pulmonary disease: a meta-analysis. Arch Intern Med. 2009;169:219–229.
    1. Drummond MB, Dasenbrook EC, Pitz MW, et al. Inhaled corticosteroids in patients with stable chronic obstructive pulmonary disease: a systematic review and meta-analysis. JAMA. 2008;300:2407–2416.
    1. Ernst P, Gonzalez AV, Brassard P, et al. Inhaled corticosteroid use in chronic obstructive pulmonary disease and the risk of hospitalization for pneumonia. Am J Respir Crit Care Med. 2007;176:162–166.
    1. Sin DD, Tashkin D, Zhang X, et al. Budesonide and the risk of pneumonia: a meta-analysis of individual patient data. Lancet. 2009;374:712–719.
    1. Celli BR, Thomas NE, Anderson JA, et al. 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.
    1. Decramer M, Celli B, Kesten S, et al. Effect of tiotropium on outcomes in patients with moderate chronic obstructive pulmonary disease (UPLIFT): a prespecified subgroup analysis of a randomised controlled trial. Lancet. 2009;374:1171–1178.
    1. Troosters T, Celli B, Lystig T, et al. Tiotropium as a first maintenance drug in COPD: secondary analysis of the UPLIFT trial. Eur Respir J. 2010;36:65–73.
    1. Decramer M, Cooper CB. Treatment of COPD: the sooner the better? Thorax. 2010;65:837–841.
    1. Jenkins CR, Jones PW, Calverley PM, et al. Efficacy of salmeterol/fluticasone propionate by GOLD stage of chronic obstructive pulmonary disease: analysis from the randomised, placebo-controlled TORCH study. Respir Res. 2009;10:59.
    1. Fletcher C, Peto R. The natural history of chronic airflow obstruction. BMJ. 1977;1:1645–1648.
    1. Weiss ST. Lung function and airway diseases. Nat Genet. 2010;42:14–16.
    1. Mancini GB, Etminan M, Zhang B, et al. Reduction of morbidity and mortality by statins, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers in patients with chronic obstructive pulmonary disease. J Am Coll Cardiol. 2006;47:2554–2560.
    1. Rutten FH, Zuithoff NP, Hak E, et al. β-Blockers may reduce mortality and risk of exacerbations in patients with chronic obstructive pulmonary disease. Arch Intern Med. 2010;170:880–887.
    1. van Gestel YR, Hoeks SE, Sin DD, et al. Effect of statin therapy on mortality in patients with peripheral arterial disease and comparison of those with versus without associated chronic obstructive pulmonary disease. Am J Cardiol. 2008;102:192–196.
    1. Suissa S. Co-morbidity in COPD: the effects of cardiovascular drug therapies. Respiration. 2010;80:3–7.
    1. Seemungal TA, Wilkinson TM, Hurst JR, et al. Long-term erythromycin therapy is associated with decreased chronic obstructive pulmonary disease exacerbations. Am J Respir Crit Care Med. 2008;178:1139–1147.
    1. Albert RK, Connett J, Bailey WC, et al. COPD Clinical Research Network Azithromycin for prevention of exacerbations of COPD. N Engl J Med. 2011;365:689–698.
    1. Hodge S, Hodge G, Jersmann H, et al. Azithromycin improves macrophage phagocytic function and expression of mannose receptor in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2008;178:139–148.
    1. Taylor AE, Finney-Hayward TK, Quint JK, et al. Defective macrophage phagocytosis of bacteria in COPD. Eur Respir J. 2010;35:1039–1047.
    1. Sethi S, Jones PW, Theron MS, et al. Pulsed moxifloxacin for the prevention of exacerbations of chronic obstructive pulmonary disease: a randomized controlled trial. Respir Res. 2010;11:10.
    1. Decramer M, Janssens W. Mucoactive therapy in COPD. Eur Respir Rev. 2010;19:134–140.
    1. Poole P, Black PN. Mucolytic agents for chronic bronchitis or chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2010;2 CD001287.
    1. Zheng JP, Kang J, Huang S-G, et al. Effect of carbocisteine on acute exacerbation of chronic obstructive pulmonary disease (PEACE Study): a randomised placebo-controlled study. Lancet. 2008;371:2013–2018.
    1. Decramer M, Rutten-van Mölken M, Dekhuijzen PNR, et al. Effects of N-acetylcysteine on outcomes in chronic obstructive pulmonary disease (Bronchitis Randomized on NAC Cost-Utility Study, BRONCUS): a randomised placebo-controlled trial. Lancet. 2005;365:1552–1560.
    1. Chronic obstructive pulmonary disease National clinical guideline on management of chronic obstructive pulmonary disease in adults in primary and secondary care. Thorax. 2004;59(suppl 1):1–232.
    1. Celli BR, MacNee W. 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.
    1. Hurst JR, Wedzicha JA. Management and prevention of chronic obstructive pulmonary disease exacerbations: a state of the art review. BMC Med. 2009;7:40.
    1. Ram FS, Picot J, Lightowler J, et al. Non-invasive positive pressure ventilation for treatment of respiratory failure due to exacerbations of chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2004;3 CD004104.
    1. McCrory DC, Brown CD. Anticholinergic bronchodilators versus beta2-sympathomimetic agents for acute exacerbations of chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2003;4 CD003900.
    1. Walters JA, Gibson PG, Wood-Baker R, et al. Systemic corticosteroids for acute exacerbations of chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2009;1 CD001288.
    1. Ram FS, Rodriguez-Roisin R, Granados-Navarrete A, et al. Antibiotics for exacerbations of chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2006;2 CD004403.
    1. Barr RG, Rowe BH, Camargo CA., Jr Methylxanthines for exacerbations of chronic obstructive pulmonary disease: meta-analysis of randomised trials. BMJ. 2003;327:643.
    1. Barnes PJ. Immunology of asthma and chronic obstructive pulmonary disease. Nat Rev Immunol. 2008;8:183–192.
    1. Calverley PM, Rabe KF, Goehring UM, et al. Roflumilast in symptomatic chronic obstructive pulmonary disease: two randomised clinical trials. Lancet. 2009;374:685–694.
    1. Fabbri LM, Calverley PM, Izquierdo-Alonso JL, et al. Roflumilast in moderate-to-severe chronic obstructive pulmonary disease treated with longacting bronchodilators: two randomised clinical trials. Lancet. 2009;374:695–703.
    1. Beeh KM, Beier J. Indacaterol, a novel inhaled, once-daily, long-acting beta2-agonist for the treatment of obstructive airways diseases. Adv Ther. 2009;26:691–699.
    1. Tashkin DP. Indacaterol maleate for the treatment of chronic obstructive pulmonary disease. Expert Opin Pharmacother. 2010;11:2077–2085.
    1. Ray NC, Alcaraz L. Muscarinic antagonist-beta-adrenergic agonist dual pharmacology molecules as bronchodilators: a patent review. Expert Opin Ther Pat. 2009;19:1–12.
    1. Bracke KR, Demedts IK, Joos GF, et al. CC-chemokine receptors in chronic obstructive pulmonary disease. Inflamm Allergy Drug Targets. 2007;6:75–79.
    1. Singh D, Smyth L, Borrill Z, et al. A randomized, placebo-controlled study of the effects of the p38 MAPK inhibitor SB-681323 on blood biomarkers of inflammation in COPD patients. J Clin Pharmacol. 2010;50:94–100.
    1. Janssens W, Lehouck A, Carremans C, et al. Vitamin D beyond bones in chronic obstructive pulmonary disease: time to act. Am J Respir Crit Care Med. 2009;179:630–636.
    1. Chishimba L, Thickett DR, Stockley RA, et al. The vitamin D axis in the lung: a key role for vitamin D-binding protein. Thorax. 2010;65:456–462.
    1. Janssens W, Bouillon R, Claes B, et al. Vitamin D deficiency is highly prevalent in COPD and correlates with variants in the vitamin D-binding gene. Thorax. 2010;65:215–220.
    1. Lehouck A, Mathieu C, Carremans C, et al. High doses of vitamin D to reduce exacerbations in COPD: a randomized controlled trial. Ann Intern Med. 2012;156:105–114.
    1. Bourbeau J, Julien M, Maltais F, et al. Reduction of hospital utilization in patients with chronic obstructive pulmonary disease: a disease-specific self-management intervention. Arch Intern Med. 2003;163:585–591.
    1. Casas A, Troosters T, Garcia-Aymerich J, et al. Integrated care prevents hospitalisations for exacerbations in COPD patients. Eur Respir J. 2006;28:123–130.

Source: PubMed

スポンサーと協力者

医学的状態

薬物療法

3
購読する