Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease. 2018 Report. Available at https://goldcopd.org/. Accessed 30 July 2018.
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.
CAS Article PubMed PubMed Central Google Scholar
Hurst JR, Donaldson GC, Perera WR, Wilkinson TM, Bilello JA, Hagan GW, et al. Use of plasma biomarkers at exacerbation of chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2006;174:867–74.
CAS Article PubMed Google Scholar
Spencer S, Jones PW. Time course of recovery of health status following an infective exacerbation of chronic bronchitis. Thorax. 2003;58(7):589–93.
CAS Article PubMed PubMed Central Google Scholar
Suissa S, Dell’Aniello S, Ernst P. Long-term natural history of chronic obstructive pulmonary disease: severe exacerbations and mortality. Thorax. 2012;67(11):957–63.
Article PubMed Google Scholar
Pauwels R, Calverley P, Buist AS, Rennard S, Fukuchi Y, Stahl E, et al. COPD exacerbations: the importance of a standard definition. Respir Med. 2004;98(2):99–107.
CAS Article PubMed Google Scholar
Montes de Oca M, Laucho-Contreras ME. Is It Time to Change the Definition of Acute Exacerbation of Chronic Obstructive Pulmornary Disease? What Do We Need to Add? Med Sci (Basel). 2018;6(2) https://doi.org/10.3390/medsci6020050.
Article PubMed Central Google Scholar
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.
CAS Article PubMed Google Scholar
National Institute for Health and Care Excellence. Chronic obstructive pulmonary disease in over 16s: diagnosis and management. 2010. Available at https://www.nice.org.uk/guidance/CG101. Accessed 30 July 2018.
Wedzicha JA, Miravitlles M, Hurst JR, Calverley PM, Albert RK, Anzueto A, et al. Management of COPD exacerbations: a European Respiratory Society/American Thoracic Society guideline. Eur Respir J. 2017;49(3) https://doi.org/10.1183/13993003.00791-2016.
Article Google Scholar
Noell G, Cosío BG, Faner R, Monsó E, Peces-Barba G, de Diego A, et al. Multi-level differential network analysis of COPD exacerbations. Eur Respir J. 2017;50(3) https://doi.org/10.1183/13993003.00075-2017.
Article Google Scholar
Celli BR. Dissecting COPD exacerbations: time to rethink our definition. Eur Respir J. 2017;50(3) https://doi.org/10.1183/13993003.01432-2017.
Article Google Scholar
Celli BR, Barnes PJ. Exacerbations of chronic obstructive pulmonary disease. Eur Respir J. 2007;29(6):1224–38.
CAS Article PubMed Google Scholar
Antoniu SA, Carone M. Hospitalizations for chronic obstructive pulmonary disease exacerbations and their impact on disease and subsequent morbidity and mortality. Expert Rev Pharmacoecon Outcomes Res. 2013;13(2):187–9.
Article PubMed Google Scholar
Garcia-Aymerich J, Serra Pons I, Mannino DM, Maas AK, Miller DP, Davis KJ. Lung function impairment, COPD hospitalisations and subsequent mortality. Thorax. 2011;66:585–59.
Article PubMed Google Scholar
Kilic H, Kokturk N, Sari G, Cakır M. Do females behave differently in COPD exacerbation? Int J Chron Obstruct Pulmon Dis. 2015;10:823–30.
PubMed PubMed Central Google Scholar
Sadatsafavi M, Xie H, Etminan M, Johnson K, FitzGerald JM. Canadian Respiratory Research Network. The association between previous and future severe exacerbations of chronic obstructive pulmonary disease: Updating the literature using robust statistical methodology. PLoS One. 2018;13(1):e0191243.
Article PubMed PubMed Central Google Scholar
Hurst JR, Vestbo J, Anzueto A, Locantore N, Müllerova H, Tal-Singer R, 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(12):1128–38.
CAS Article PubMed Google Scholar
Müllerova H, Maselli DJ, Locantore N, Vestbo J, Hurst JR, Wedzicha JA, et al. Hospitalized exacerbations of COPD: risk factors and outcomes in the ECLIPSE cohort. Chest. 2015;147(4):999–1007.
Article PubMed Google Scholar
Santibáñez M, Garrastazu R, Ruiz-Nuñez M, Helguera JM, Arenal S, Bonnardeux C, et al. Predictors of hospitalized exacerbations and mortality in chronic obstructive pulmonary disease. PLoS One. 2016;11(6):e0158727.
Article CAS PubMed PubMed Central Google Scholar
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(2):81–9.
Article PubMed Google Scholar
Jeong SH, Lee H, Carriere KC, Shin SH, Moon SM, Jeong BH, et al. Comorbidity as a contributor to frequent severe acute exacerbation in COPD patients. Int J Chron Obstruct Pulmon Dis. 2016;11:1857–65.
Article PubMed PubMed Central Google Scholar
Hoogendoorn M, Hoogenveen RT, Rutten-van Mölken MP, Vestbo J, Feenstra TL. Case fatality of COPD exacerbations: a meta-analysis and statistical modelling approach. Eur Respir J. 2011;37(3):508–15.
CAS Article PubMed Google Scholar
Chalela R, González-García JG, Chillarón JJ, Valera-Hernández L, Montoya-Rangel C, Badenes D, et al. Impact of hyponatremia on mortality and morbidity in patients with COPD exacerbations. Respir Med. 2016;117:237–42.
Article PubMed Google Scholar
Chen CW, Chen YY, Lu CL, Chen SC, Chen YJ, Lin MS, et al. Severe hypoalbuminemia is a strong independent risk factor for acute respiratory failure in COPD: a nationwide cohort study. Int J Chron Obstruct Pulmon Dis. 2015;10:1147–54.
CAS Article PubMed PubMed Central Google Scholar
Aliyali M, Mehravaran H, Abedi S, Sharifpour A, Yazdani CJ. Impact of comorbid ischemic heart disease on short-term outcomes of patients hospitalized for acute exacerbations of COPD. Tanaffos. 2015;14(3):165–71.
PubMed PubMed Central Google Scholar
Fabbian F, De Giorgi A, Manfredini F, Lamberti N, Forcellini S, Storari A, et al. Impact of renal dysfunction on in-hospital mortality of patients with severe chronic obstructive pulmonary disease: a single-center Italian study. Int Urol Nephrol. 2016;48(7):1121–7.
CAS Article PubMed Google Scholar
Wells JM, Morrison JB, Bhatt SP, Nath H, Dransfield MT. Pulmonary artery enlargement is associated with cardiac injury during severe exacerbations of COPD. Chest. 2016;149(5):1197–204.
Article PubMed PubMed Central Google Scholar
Mantero M, Rogliani P, Di Pasquale M, Polverino E, Crisafulli E, Guerrero M, et al. Acute exacerbations of COPD: risk factors for failure and relapse. Int J Chron Obstruct Pulmon Dis. 2017;12:2687–93.
Article PubMed PubMed Central Google Scholar
Prieto-Centurion V, Markos MA, Ramey NI, Gussin HA, Nyenhuis SM, Joo MJ, et al. Interventions to reduce rehospitalizations after chronic obstructive pulmonary disease exacerbations. A systematic review. Ann Am Thorac Soc. 2014;11:417–24.
Article PubMed PubMed Central Google Scholar
Sharif R, Parekh TM, Pierson KS, Kuo YF, Sharma G. Predictors of early readmission among patients 40 to 64 years of age hospitalized for chronic obstructive pulmonary disease. Ann Am Thorac Soc. 2014;11:685–94.
Article PubMed PubMed Central Google Scholar
Crisafulli E, Torres A, Huerta A, Méndez R, Guerrero M, Martinez R, et al. C-reactive protein at discharge, diabetes mellitus and ≥ 1 hospitalization during previous year predict early readmission in patients with acute exacerbation of chronic obstructive pulmonary disease. COPD. 2015;12(3):306–14.
Article PubMed Google Scholar
Crisafulli E, Ortega S, Torres A. Predictors of readmission in a period of 30 days or less in acute exacerbation of chronic obstructive pulmonary disease. Clin Pulm Med. 2015;22(4):172–6.
Article Google Scholar
Guerrero M, Crisafulli E, Liapikou A, Huerta A, Gabarrús A, Chetta A, et al. Readmission for acute exacerbation within 30 days of discharge is associated with a subsequent progressive increase in mortality risk in COPD patients: a long-term observational study. PLoS One. 2016;11(3):e0150737.
Article CAS PubMed PubMed Central Google Scholar
Crisafulli E, Guerrero M, Chetta A, Torres A. Readmission in COPD patients: should we consider it a marker of quality of care or a marker of a more severe disease with a worse prognosis? Eur Respir J. 2016;48(1):279–81.
Article PubMed Google Scholar
Calverley PM, Anzueto AR, Dusser D, Mueller A, Metzdorf N, Wise RA. Treatment of exacerbations as a predictor of subsequent outcomes in patients with COPD. Int J Chron Obstruct Pulmon Dis. 2018;13:1297–308.
Article PubMed PubMed Central Google Scholar
Crisafulli E, Torres A, Huerta A, Guerrero M, Gabarrús A, Gimeno A, et al. Predicting in-hospital treatment failure (≤ 7 days) in patients with COPD exacerbation using antibiotics and systemic steroids. COPD. 2016;13(1):82–92.
Article PubMed Google Scholar
Kocks JW, van den Berg JW, Kerstjens HA, Uil SM, Vonk JM, de Jong YP, et al. Day-to-day measurement of patient-reported outcomes in exacerbations of chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis. 2013;8:273–86.
PubMed PubMed Central Google Scholar
Amin AN, Bollu V, Stensland MD, Netzer L, Ganapathy V. Treatment patterns for patients hospitalized with chronic obstructive pulmonary disease. Am J Health Syst Pharm. 2018;75(6):359–66.
Article PubMed Google Scholar
Turner MO, Patel A, Ginsburg S, FitzGerald JM. Bronchodilator delivery in acute airflow obstruction. A meta-analysis Arch Intern Med. 1997;157(15):1736–44.
CAS Article PubMed Google Scholar
van Geffen WH, Douma WR, Slebos DJ, Kerstjens HA. Bronchodilators delivered by nebuliser versus pMDI with spacer or DPI for exacerbations of COPD. Cochrane Database Syst Rev. 2016;8:CD011826.
Google Scholar
Papaioannou AI, Herodotou Y, Tomos I, Apollonatou V, Verykokou G, Papathanasiou E, et al. Ability of using different dry powder inhalers during COPD exacerbations. Pulm Pharmacol Ther. 2018;48:211–6.
CAS Article PubMed Google Scholar
Cazzola M, Matera MG. Long-acting β2 agonists as potential option in the treatment of acute exacerbations of COPD. Pulm Pharmacol Ther. 2003;16:197–201.
CAS Article PubMed Google Scholar
Bourbeau J, Sedeno MF, Metz K, Li PZ, Pinto L. Early COPD exacerbation treatment with combination of ICS and LABA for patients presenting with mild-to-moderate worsening of dyspnea. COPD. 2016;13(4):439–47.
Article PubMed Google Scholar
Rogliani P, Ora J, Ciaprini C, Senis L, Stirpe E, Cazzola E. Effect of indacaterol on arterial blood gases in patients suffering from acute exacerbation of COPD. Respir Med. 2014;108:307–13.
Article PubMed Google Scholar
Segreti A, Fiori E, Calzetta L, Sabatini M, Segreti V, Rogliani P, et al. The effect of indacaterol during an acute exacerbation of COPD. Pulm Pharmacol Ther. 2013;26:630–4.
CAS Article PubMed Google Scholar
Wedzicha JA, Banerji D, Chapman KR, Vestbo J, Roche N, Ayers RT, et al. FLAME investigators. Indacaterol-Glycopyrronium versus salmeterol-fluticasone for COPD. N Engl J Med. 2016;374(23):2222–34.
CAS Article PubMed Google Scholar
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(9177):456–60.
CAS Article PubMed Google Scholar
Niewoehner DE, Erbland ML, Deupree RH, Collins D, Gross NJ, Light RW, et al. Effect of systemic glucocorticoids on exacerbations of chronic obstructive pulmonary disease. Department of veterans affairs cooperative study group. N Engl J Med. 1999;340(25):1941–7.
CAS Article PubMed Google Scholar
Aaron SD, Vandemheen KL, Hebert P, Dales R, Stiell IG, Ahuja J, et al. Outpatient oral prednisone after emergency treatment of chronic obstructive pulmonary disease. N Engl J Med. 2003;348(26):2618–25.
CAS Article PubMed Google Scholar
Alía I, de la Cal MA, Esteban A, Abella A, Ferrer R, Molina FJ, 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(21):1939–46.
Article PubMed Google Scholar
Leuppi JD, Schuetz P, Bingisser R, Bodmer M, Briel M, Drescher T, et al. Short-term vs conventional glucocorticoid therapy in acute exacerbations of chronic obstructive pulmonary disease: the REDUCE randomized clinical trial. JAMA. 2013;309(21):2223–31.
CAS Article PubMed Google Scholar
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(6):1741–7.
CAS Article PubMed Google Scholar
Aggarwal P, Wig N, Bhoi S. Efficacy of two corticosteroid regimens in acute exacerbation of chronic obstructive pulmonary disease. Int J Tuberc Lung Dis. 2011;15(5):687–92.
CAS Article PubMed Google Scholar
Walters JA, Tan DJ, White CJ, Wood-Baker R. Different durations of corticosteroid therapy for exacerbations of chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2018;3:CD006897.
PubMed Google Scholar
Abroug F, Ouanes-Besbes L, Fkih-Hassen M, Ouanes I, Ayed S, Dachraoui F, et al. Prednisone in COPD exacerbation requiring ventilatory support: an open-label randomised evaluation. Eur Respir J. 2014;43(3):717–24.
CAS Article PubMed Google Scholar
Ceviker Y, Sayiner A. Comparison of two systemic steroid regimens for the treatment of COPD exacerbations. Pulm Pharmacol Ther. 2014;27(2):179–83.
CAS Article PubMed Google Scholar
Lindenauer PK, Pekow PS, Lahti MC, Lee Y, Benjamin EM, Rothberg MB. Association of corticosteroid dose and route of administration with risk of treatment failure in acute exacerbation of chronic obstructive pulmonary disease. JAMA. 2010;303(23):2359–67.
CAS Article PubMed Google Scholar
Kiser TH, Allen RR, Valuck RJ, Moss M, Vandivier RW. Outcomes associated with corticosteroid dosage in critically ill patients with acute exacerbations of chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2014;189(9):1052–64.
CAS Article PubMed Google Scholar
Sayiner A, Aytemur ZA, Cirit M, Unsal I. Systemic glucocorticoids in severe exacerbations of COPD. Chest. 2001;119(3):726–30.
CAS Article PubMed Google Scholar
Crisafulli E, Guerrero M, Menéndez R, Huerta A, Martinez R, Gimeno A, et al. Inhaled corticosteroids do not influence the early inflammatory response and clinical presentation of hospitalized subjects with COPD exacerbation. Respir Care. 2014;59(10):1550–9.
Article PubMed Google Scholar
Maltais F, Ostinelli J, Bourbeau J, Tonnel AB, Jacquemet N, Haddon J, et al. 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(5):698–703.
Article PubMed Google Scholar
Ding Z, Li X, Lu Y, Rong G, Yang R, Zhang R, et al. A randomized, controlled multicentric study of inhaled budesonide and intravenous methylprednisolone in the treatment on acute exacerbation of chronic obstructive pulmonary disease. Respir Med. 2016;121:39–47.
Article PubMed Google Scholar
Jiang Z, Zhu L. Update on molecular mechanisms of corticosteroid resistance in chronic obstructive pulmonary disease. Pulm Pharmacol Ther. 2016;37:1–8.
Article CAS PubMed Google Scholar
Sethi S, Murphy TF. Infection in the pathogenesis and course of chronic obstructive pulmonary disease. N Engl J Med. 2008;359:2355–65.
CAS Article PubMed Google Scholar
Wedzicha JA, Seemungal TA. COPD exacerbations: defining their cause and prevention. Lancet. 2007;370:786–96.
Article PubMed PubMed Central Google Scholar
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(6):1354–60.
Article PubMed Google Scholar
Huerta A, Crisafulli E, Menéndez R, Martínez R, Soler N, Guerrero M, et al. Pneumonic and nonpneumonic exacerbations of COPD: inflammatory response and clinical characteristics. Chest. 2013;144(4):1134–42.
CAS Article PubMed Google Scholar
Soler N, Torres A, Ewig S, Gonzalez J, Celis R, El-Ebiary M, et al. Bronchial microbial patterns in severe exacerbations of chronic obstructive pulmonary disease (COPD) requiring mechanical ventilation. Am J Respir Crit Care Med. 1998;157:1498–505.
CAS Article PubMed Google Scholar
Estirado C, Ceccato A, Guerrero M, Huerta A, Cilloniz C, Vilaró O, et al. Microorganisms resistant to conventional antimicrobials in acute exacerbations of chronic obstructive pulmonary disease. Respir Res. 2018;19(1):119.
Article PubMed PubMed Central Google Scholar
Stolz D, Christ-Crain M, Bingisser R, Leuppi J, Miedinger D, Müller C, et al. Antibiotic treatment of exacerbations of COPD: a randomized, controlled trial comparing procalcitonin-guidance with standard therapy. Chest. 2007;131(1):9–19.
CAS Article PubMed Google Scholar
Schuetz P, Christ-Crain M, Thomann R, Falconnier C, Wolbers M, Widmer I, et al. Effect of procalcitonin-based guidelines vs standard guidelines on antibiotic use in lower respiratory tract infections: the ProHOSP randomized controlled trial. JAMA. 2009;302(10):1059–66.
CAS Article PubMed Google Scholar
Schuetz P, Wirz Y, Sager R, Christ-Crain M, Stolz D, Tamm M, et al. Procalcitonin to initiate or discontinue antibiotics in acute respiratory tract infections. Cochrane Database Syst Rev. 2017;10:CD007498.
PubMed Google Scholar
Wang JX, Zhang SM, Li XH, Zhang Y, Xu ZY, Cao B. Acute exacerbations of chronic obstructive pulmonary disease with low serum procalcitonin values do not benefit from antibiotic treatment: a prospective randomized controlled trial. Int J Infect Dis. 2016;48:40–5.
CAS Article PubMed Google Scholar
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(6):503–12.
CAS Article PubMed Google Scholar
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.
PubMed Google Scholar
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(9298):2020–5.
CAS Article PubMed Google Scholar
Alonso Martínez JL, Rubio Obanos MT, Sampériz Legarre AL, Escolar Castellón F, Carrasco del Amo ME. Antibiotic treatment for acute episodes of chronic obstructive pulmonary disease. An Med Interna. 1992;9(8):377–80.
PubMed Google Scholar
Pines A, Raafat H, Plucinski K, Greenfield JS, Solari M. Antibiotic regimens in severe and acute purulent exacerbations of chronic bronchitis. Br Med J. 1968;2(5607):735–8.
CAS Article PubMed PubMed Central Google Scholar
Pines A, Raafat H, Greenfield JS, Linsell WD, Solari ME. Antibiotic regimens in moderately ill patients with purulent exacerbations of chronic bronchitis. Br J Dis Chest. 1972;66(2):107–15.
CAS Article PubMed Google Scholar
Daniels JM, Snijders D, de Graaff CS, Vlaspolder F, Jansen HM, Boersma WG. Antibiotics in addition to systemic corticosteroids for acute exacerbations of chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2010;181(2):150–7.
CAS Article PubMed Google Scholar
Nouira S, Marghli S, Besbes L, Boukef R, Daami M, Nciri N, et al. Standard versus newer antibacterial agents in the treatment of severe acute exacerbation of chronic obstructive pulmonary disease: a randomized trial of trimethoprim-sulfamethoxazole versus ciprofloxacin. Clin Infect Dis. 2010;51(2):143–9.
CAS Article PubMed Google Scholar
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.
Article PubMed PubMed Central Google Scholar
Plant PK, Owen JL, Elliott MW. One year period prevalence study of respiratory acidosis in acute exacerbations of COPD: implications for the provision of non-invasive ventilation and oxygen administration. Thorax. 2000;55(7):550–4.
CAS Article PubMed PubMed Central Google Scholar
Lellouche F, Bouchard PA, Roberge M, Simard S, L'Her E, Maltais F, et al. Automated oxygen titration and weaning with FreeO2 in patients with acute exacerbation of COPD: a pilot randomized trial. Int J Chron Obstruct Pulmon Dis. 2016;11:1983–90.
Article PubMed PubMed Central Google Scholar
Frat JP, Coudroy R, Marjanovic N, Thille AW. High-flow nasal oxygen therapy and noninvasive ventilation in the management of acute hypoxemic respiratory failure. Ann Transl Med. 2017;5(14):297.
Article PubMed PubMed Central Google Scholar
Sztrymf B, Messika J, Bertrand F, Hurel D, Leon R, Dreyfuss D, et al. Beneficial effects of humidified high flow nasal oxygen in critical care patients: a prospective pilot study. Intensive Care Med. 2011;37(11):1780–6.
CAS Article PubMed Google Scholar
Sztrymf B, Messika J, Mayot T, Lenglet H, Dreyfuss D, Ricard JD. Impact of high-flow nasal cannula oxygen therapy on intensive care unit patients with acute respiratory failure: a prospective observational study. J Crit Care. 2012;27(3):324.e9–13. https://doi.org/10.1016/j.jcrc.2011.07.075.
Article PubMed Google Scholar
Riera J, Pérez P, Cortés J, Roca O, Masclans JR, Rello J. Effect of high-flow nasal cannula and body position on end-expiratory lung volume: a cohort study using electrical impedance tomography. Respir Care. 2013;58(4):589–96.
Article PubMed Google Scholar
Lin SM, Liu KX, Lin ZH, Lin PH. Does high-flow nasal cannula oxygen improve outcome in acute hypoxemic respiratory failure? A systematic review and meta-analysis. Respir Med. 2017;131:58–64.
Article PubMed Google Scholar
Corley A, Rickard CM, Aitken LM, Johnston A, Barnett A, Fraser JF, et al. High-flow nasal cannulae for respiratory support in adult intensive care patients. Cochrane Database Syst Rev. 2017;5:CD010172. https://doi.org/10.1002/14651858.CD010172.pub2.
Article PubMed Google Scholar
Vogelsinger H, Halank M, Braun S, Wilkens H, Geiser T, Ott S, et al. Efficacy and safety of nasal high-flow oxygen in COPD patients. BMC Pulm Med. 2017;17(1):143.
Article CAS PubMed PubMed Central Google Scholar
Bräunlich J, Köhler M, Wirtz H. Nasal highflow improves ventilation in patients with COPD. Int J Chron Obstruct Pulmon Dis. 2016;11:1077–85.
Article PubMed PubMed Central Google Scholar
Pilcher J, Eastlake L, Richards M, Power S, Cripps T, Bibby S, et al. Physiological effects of titrated oxygen via nasal high-flow cannulae in COPD exacerbations: a randomized controlled cross-over trial. Respirology. 2017;22(6):1149–55.
Article PubMed Google Scholar
Lee MK, Choi J, Park B, Kim B, Lee SJ, Kim SH, et al. High flow nasal cannulae oxygen therapy in acute-moderate hypercapnic respiratory failure. Clin Respir J. 2018;12(6):2046–56.
CAS Article PubMed Google Scholar
Soo Hoo GW, Esquinas AM, Karim HMR. High flow nasal cannulae versus non-invasive ventilation in moderate hypercapnic respiratory failure: different roads, same destination but doubtful equality. Clin Respir J. 2018; https://doi.org/10.1111/crj.12942. [Epub ahead of print]
Roberts CM, Stone RA, Buckingham RJ, Pursey NA, Lowe D. National Chronic Obstructive Pulmonary Disease Resources and outcomes project implementation group. Acidosis, non-invasive ventilation and mortality in hospitalised COPD exacerbations. Thorax. 2011;66(1):43–8.
CAS Article PubMed Google Scholar
Jeffrey AA, Warren PM, Flenley DC. Acute hypercapnic respiratory failure in patients with chronic obstructive lung disease: risk factors and use of guidelines for management. Thorax. 1992;47(1):34–40.
CAS Article PubMed PubMed Central Google Scholar
Brochard L, Mancebo J, Wysocki M, Lofaso F, Conti G, Rauss A, et al. Noninvasive ventilation for acute exacerbations of chronic obstructive pulmonary disease. N Engl J Med. 1995;333(13):817–22.
CAS Article PubMed Google Scholar
Celikel T, Sungur M, Ceyhan B, Karakurt S. Comparison of noninvasive positive pressure ventilation with standard medical therapy in hypercapnic acute respiratory failure. Chest. 1998;114(6):1636–42.
CAS Article PubMed Google Scholar
Thys F, Roeseler J, Reynaert M, Liistro G, Rodenstein DO. Noninvasive ventilation for acute respiratory failure: a prospective randomised placebo-controlled trial. Eur Respir J. 2002;20(3):545–55.
CAS Article PubMed Google Scholar
Carrera M, Marín JM, Antón A, Chiner E, Alonso ML, Masa JF, et al. A controlled trial of noninvasive ventilation for chronic obstructive pulmonary disease exacerbations. J Crit Care. 2009;24(3):473. e7–14
Article PubMed Google Scholar
Martin TJ, Hovis JD, Costantino JP, Bierman MI, Donahoe MP, Rogers RM, et al. A randomized, prospective evaluation of noninvasive ventilation for acute respiratory failure. Am J Respir Crit Care Med. 2000;161(3 Pt 1):807–13.
CAS Article PubMed Google Scholar
Chandra D, Stamm JA, Taylor B, Ramos RM, Satterwhite L, Krishnan JA, et al. 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(2):152–9.
Article PubMed PubMed Central Google Scholar
Rochwerg B, Brochard L, Elliott MW, Hess D, Hill NS, Nava S, et al. Official ERS/ATS clinical practice guidelines: noninvasive ventilation for acute respiratory failure. Eur Respir J. 2017;50(2). https://doi.org/10.1183/13993003.02426-2016.
Article Google Scholar
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(7382):185.
Article PubMed PubMed Central Google Scholar
Osadnik CR, Tee VS, Carson-Chahhoud KV, Picot J, Wedzicha JA, Smith BJ. Non-invasive ventilation for the management of acute hypercapnic respiratory failure due to exacerbation of chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2017;7:CD004104.
PubMed Google Scholar
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(9219):1931–5.
CAS Article PubMed Google Scholar
Bott J, Carroll MP, Conway JH, Keilty SE, Ward EM, Brown AM, et al. Randomised controlled trial of nasal ventilation in acute ventilatory failure due to chronic obstructive airways disease. Lancet. 1993;341(8860):1555–7.
CAS Article PubMed Google Scholar
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(6):1799–806.
CAS Article PubMed Google Scholar
Plant PK, Owen JL, Elliott MW. Non-invasive ventilation in acute exacerbations of chronic obstructive pulmonary disease: long term survival and predictors of in-hospital outcome. Thorax. 2001;56(9):708–12.
CAS Article PubMed PubMed Central Google Scholar
Plant PK, Owen JL, Parrott S, Elliott MW. Cost effectiveness of ward based non-invasive ventilation for acute exacerbations of chronic obstructive pulmonary disease: economic analysis of randomised controlled trial. BMJ. 2003;326(7396):956.
CAS Article PubMed PubMed Central Google Scholar
Nava S, Hill N. Non-invasive ventilation in acute respiratory failure. Lancet. 2009;374(9685):250–9.
Article PubMed PubMed Central Google Scholar
Nava S, Navalesi P, Gregoretti C. Interfaces and humidification for noninvasive mechanical ventilation. Respir Care. 2009;54(1):71–84.
PubMed Google Scholar
Pisani L, Mega C, Vaschetto R, Bellone A, Scala R, Cosentini R, et al. Oronasal mask versus helmet in acute hypercapnic respiratory failure. Eur Respir J. 2015;45(3):691–9.
Article PubMed Google Scholar
Antonaglia V, Ferluga M, Molino R, Lucangelo U, Peratoner A, Roman-Pognuz E, et al. Comparison of noninvasive ventilation by sequential use of mask and helmet versus mask in acute exacerbation of chronic obstructive pulmonary disease: a preliminary study. Respiration. 2011;82(2):148–54.
Article PubMed Google Scholar
Nicolini A, Santo M, Ferrari-Bravo M, Barlascini C. Open-mouthpiece ventilation versus nasal mask ventilation in subjects with COPD exacerbation and mild to moderate acidosis: a randomized trial. Respir Care. 2014;59(12):1825–31.
Article PubMed Google Scholar
Di Marco F, Centanni S, Bellone A, Messinesi G, Pesci A, Scala R, et al. Optimization of ventilator setting by flow and pressure waveforms analysis during noninvasive ventilation for acute exacerbations of COPD: a multicentric randomized controlled trial. Crit Care. 2011;15(6):R283.
Article PubMed PubMed Central Google Scholar
Jaber S, Fodil R, Carlucci A, Boussarsar M, Pigeot J, Lemaire F, et al. Noninvasive ventilation with helium-oxygen in acute exacerbations of chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2000;161(4 Pt 1):1191–200.
CAS Article PubMed Google Scholar
Jolliet P, Ouanes-Besbes L, Abroug F, Ben Khelil J, Besbes M, Garnero A, et al. A multicenter randomized trial assessing the efficacy of helium/oxygen in severe exacerbations of chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2017;195(7):871–80.
CAS Article PubMed Google Scholar
Abroug F, Ouanes-Besbes L, Hammouda Z, Benabidallah S, Dachraoui F, Ouanes I, et al. Noninvasive ventilation with helium-oxygen mixture in hypercapnic COPD exacerbation: aggregate meta-analysis of randomized controlled trials. Ann Intensive Care. 2017;7(1):59.
Article CAS PubMed PubMed Central Google Scholar
Ferrer M, Torres A. Noninvasive ventilation with helium/oxygen in chronic obstructive pulmonary disease exacerbations. When physiologic improvement does not translate into clinical benefit. Am J Respir Crit Care Med. 2017;195(7):843–4.
Article PubMed Google Scholar
Maggiore SM, Richard JC, Abroug F, Diehl JL, Antonelli M, Sauder P, et al. A multicenter, randomized trial of noninvasive ventilation with helium-oxygen mixture in exacerbations of chronic obstructive lung disease. Crit Care Med. 2010;38(1):145–51.
Article PubMed Google Scholar
Ambrosino N, Foglio K, Rubini F, Clini E, Nava S, Vitacca M. Non-invasive mechanical ventilation in acute respiratory failure due to chronic obstructive pulmonary disease: correlates for success. Thorax. 1995;50(7):755–7.
CAS Article PubMed PubMed Central Google Scholar
Confalonieri M, Garuti G, Cattaruzza MS, Osborn JF, Antonelli M, Conti G, et al. Italian noninvasive positive pressure ventilation (NPPV) study group. A chart of failure risk for noninvasive ventilation in patients with COPD exacerbation. Eur Respir J. 2005;25(2):348–55.
CAS Article PubMed Google Scholar
Marchioni A, Castaniere I, Tonelli R, Fantini R, Fontana M, Tabbì L, et al. Ultrasound-assessed diaphragmatic impairment is a predictor of outcomes in patients with acute exacerbation of chronic obstructive pulmonary disease undergoing noninvasive ventilation. Crit Care. 2018;22(1):109.
Article PubMed PubMed Central Google Scholar
https://clinicaltrials.gov/ct2/show/NCT03014869?term=NCT03014869&rank=1. Accessed 30 July 2018.
https://clinicaltrials.gov/ct2/show/NCT03033251?term=NCT03033251&rank=1. Accessed 30 July 2018.
Spruit MA, Singh SJ, Garvey C, ZuWallack R, Nici L, Rochester C, et al. An official American Thoracic Society/European Respiratory Society statement: key concepts and advances in pulmonary rehabilitation. Am J Respir Crit Care Med. 2013;188(8):e13–64.
Article PubMed Google Scholar
Clini EM, Crisafulli E. Exercise capacity as a pulmonary rehabilitation outcome. Respiration. 2009;77(2):121–8.
Article PubMed Google Scholar
Crisafulli E, Clini EM. Measures of dyspnea in pulmonary rehabilitation. Multidiscip Respir Med. 2010;5(3):202–10.
Article PubMed PubMed Central Google Scholar
Garrod R, Malerba M, Crisafulli E. Determinants of success. Eur Respir J. 2011;38(5):1215–8.
CAS Article PubMed Google Scholar
Vogiatzis I, Terzis G, Stratakos G, Cherouveim E, Athanasopoulos D, Spetsioti S, et al. Effect of pulmonary rehabilitation on peripheral muscle fiber remodeling in patients with COPD in GOLD stages II to IV. Chest. 2011;140(3):744–52.
Article PubMed Google Scholar
Crisafulli E, Venturelli E, Biscione G, Vagheggini G, Iattoni A, Lucic S, et al. Exercise performance after standard rehabilitation in COPD patients with lung hyperinflation. Intern Emerg Med. 2014;9(1):23–31.
Article PubMed Google Scholar
Crisafulli E, Morandi A, Olivini A, Malerba M, Clini EM. Rehabilitation and supportive therapy in elderly patients with chronic obstructive pulmonary disease. Eur J Intern Med. 2014;25(4):329–35.
Article PubMed Google Scholar
Crisafulli E, Costi S, Luppi F, Cirelli G, Cilione C, Coletti O, et al. Role of comorbidities in a cohort of patients with COPD undergoing pulmonary rehabilitation. Thorax. 2008;63(6):487–92.
CAS Article PubMed Google Scholar
Crisafulli E, Gorgone P, Vagaggini B, Pagani M, Rossi G, Costa F, et al. Efficacy of standard rehabilitation in COPD outpatients with comorbidities. Eur Respir J. 2010;36(5):1042–8.
CAS Article PubMed Google Scholar
Maddocks M, Kon SS, Canavan JL, Jones SE, Nolan CM, Labey A, et al. Physical frailty and pulmonary rehabilitation in COPD: a prospective cohort study. Thorax. 2016;71(11):988–95.
Article PubMed Google Scholar
Vogiatzis I, Simoes DC, Stratakos G, Kourepini E, Terzis G, Manta P, et al. Effect of pulmonary rehabilitation on muscle remodelling in cachectic patients with COPD. Eur Respir J. 2010;36(2):301–10.
CAS Article PubMed Google Scholar
Clini EM, Crisafulli E, Costi S, Rossi G, Lorenzi C, Fabbri LM, et al. Effects of early inpatient rehabilitation after acute exacerbation of COPD. Respir Med. 2009;103(10):1526–31.
Article PubMed Google Scholar
Troosters T, Probst VS, Crul T, Pitta F, Gayan-Ramirez G, Decramer M, et al. Resistance training prevents deterioration in quadriceps muscle function during acute exacerbations of chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2010;181(10):1072–7.
Article PubMed Google Scholar
Borges RC, Carvalho CR. Impact of resistance training in chronic obstructive pulmonary disease patients during periods of acute exacerbation. Arch Phys Med Rehabil. 2014;95(9):1638–45.
Article PubMed Google Scholar
Torres-Sánchez I, Valenza MC, Cabrera-Martos I, López-Torres I, Benítez-Feliponi Á, Conde-Valero A. Effects of an exercise intervention in frail older patients with chronic obstructive pulmonary disease hospitalized due to an exacerbation: a randomized controlled trial. COPD. 2017;14(1):37–42.
Article PubMed Google Scholar
Eaton T, Young P, Fergusson W, Moodie L, Zeng I, O'Kane F, et al. Does early pulmonary rehabilitation reduce acute health-care utilization in COPD patients admitted with an exacerbation? A randomized controlled study. Respirology. 2009;14(2):230–8.
Article PubMed Google Scholar
He M, Yu S, Wang L, Lv H, Qiu Z. Efficiency and safety of pulmonary rehabilitation in acute exacerbation of chronic obstructive pulmonary disease. Med Sci Monit. 2015;21:806–12.
Article PubMed PubMed Central Google Scholar
Tang CY, Blackstock FC, Clarence M, Taylor NF. Early rehabilitation exercise program for inpatients during an acute exacerbation of chronic obstructive pulmonary disease: a randomized controlled trial. J Cardiopulm Rehabil Prev. 2012;32(3):163–9.
Article PubMed Google Scholar
Clini E, Venturelli E, Crisafulli E. Rehabilitation in COPD patients admitted for exacerbation. Pneumonol Alergol Pol. 2011;79(2):116–20.
PubMed Google Scholar
Alahmari AD, Patel AR, Kowlessar BS, Mackay AJ, Singh R, Wedzicha JA, et al. Daily activity during stability and exacerbation of chronic obstructive pulmonary disease. BMC Pulm Med. 2014;14:98.
Article PubMed PubMed Central Google Scholar
Torres-Sánchez I, Cabrera-Martos I, Díaz-Pelegrina A, Valenza-Demet G, Moreno-Ramírez MP, Valenza MC. Physical and functional impairment during and after hospitalization in subjects with severe COPD exacerbation. Respir Care. 2017;62(2):209–14.
Article PubMed Google Scholar
Spruit MA, Gosselink R, Troosters T, Kasran A, Gayan-Ramirez G, Bogaerts P, et al. Muscle force during an acute exacerbation in hospitalised patients with COPD and its relationship with CXCL8 and IGF-I. Thorax. 2003;58(9):752–6.
CAS Article PubMed PubMed Central Google Scholar
Carr SJ, Hill K, Brooks D, Goldstein RS. Pulmonary rehabilitation after acute exacerbation of chronic obstructive pulmonary disease in patients who previously completed a pulmonary rehabilitation program. J Cardiopulm Rehabil Prev. 2009;29(5):318–24.
CAS Article PubMed Google Scholar
Miravitlles M, Ferrer M, Pont A, Zalacain R, Alvarez-Sala JL, Masa F, et al. Effect of exacerbations on quality of life in patients with chronic obstructive pulmonary disease: a 2 year follow up study. Thorax. 2004;59(5):387–95.
CAS Article PubMed PubMed Central Google Scholar
Clini E, Roversi P, Crisafulli E. Early rehabilitation: much better than nothing. Am J Respir Crit Care Med. 2010;181(10):1016–7.
Article PubMed Google Scholar
Chaplin EJ, Houchen L, Greening NJ, Harvey-Dunstan T, Morgan MD, Steiner MC, et al. Neuromuscular stimulation of quadriceps in patients hospitalised during an exacerbation of COPD: a comparison of low (35 Hz) and high (50 Hz) frequencies. Physiother Res Int. 2013;18(3):148–56.
Article PubMed Google Scholar
Giavedoni S, Deans A, McCaughey P, Drost E, MacNee W, Rabinovich RA. Neuromuscular electrical stimulation prevents muscle function deterioration in exacerbated COPD: a pilot study. Respir Med. 2012;106(10):1429–34.
Article PubMed Google Scholar
Greening NJ, Williams JE, Hussain SF, Harvey-Dunstan TC, Bankart MJ, Chaplin EJ, 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.
Article PubMed PubMed Central Google Scholar
Spruit MA, Singh SJ, Rochester CL, Greening NJ, Franssen FME, Pitta F, et al. Pulmonary rehabilitation for patients with COPD during and after an exacerbation-related hospitalisation: back to the future? Eur Respir J. 2018;51:1701312.
Article PubMed Google Scholar
Sheikh Motahar Vahedi H, Mahshidfar B, Rabiee H, Saadat S, Shokoohi H, Chardoli M, et al. The adjunctive effect of nebulized furosemide in COPD exacerbation: a randomized controlled clinical trial. Respir Care. 2013;58(11):1873–7.
Article PubMed Google Scholar
Abreu González J, Hernández García C, Abreu González P, Martín García C, Jiménez A. Effect of intravenous magnesium sulfate on chronic obstructive pulmonary disease exacerbations requiring hospitalization: a randomized placebo-controlled trial. Arch Bronconeumol. 2006;42(8):384–7.
Article PubMed Google Scholar
Woodruff PG, Albert RK, Bailey WC, Casaburi R, Connett JE, Cooper JA Jr, et al. Randomized trial of zileuton for treatment of COPD exacerbations requiring hospitalization. COPD. 2011;8(1):21–9.
Article PubMed Google Scholar
Page 2
GOLD document
Acute worsening of respiratory symptoms that results in additional therapy.
NICE guidelines
A worsening of the patient’s symptoms from their usual stable state which is beyond normal day-to-day variations, and is acute in onset. Commonly reported symptoms are worsening breathlessness, cough, increased sputum production and change in sputum colour. The change in these symptoms often necessitates a change in medication.
ERS/ATS guidelines
Episodes of increasing respiratory symptoms, particularly dyspnea, cough and sputum production, and increased sputum purulence
