EDITORIAL |
https://doi.org/10.4103/ijrc.ijrc_177_22 |
Managing Acute Exacerbation of Chronic Obstructive Pulmonary Disease: What's New?
Department of Critical Care Medicine, Narayana Hrudayalaya, Bengaluru, Karnataka, India
E-mail: dr.harishmm@rocketmail.com
How to cite this article: Raman RA, Maheswarappa HM. Managing acute exacerbation of chronic obstructive pulmonary disease: What's new? Indian J Respir Care 2022;11:287-90.
Received: 29-09-2022
Revised: 09-10-2022
Accepted: 12-10-2022
Published: 12-11-2022
INTRODUCTION
Chronic obstructive pulmonary disease (COPD) is the third-leading cause of death worldwide causing a major health-care burden. With a global prevalence of 10.1%, it not only affects low/middle-income countries but also wealthy countries.[1] COPD is a constellation of clinical entities such as chronic respiratory symptoms, structural pulmonary abnormalities, and airflow limitation, which is poorly reversible.[2] A COPD exacerbation event can be defined as a worsening of respiratory symptoms that warrants additional therapy.[3] Exacerbations are significant events in COPD management due to their negative impact on health status and disease progression. COPD can be categorized as “stable” when symptoms are well controlled with minimal pulmonary decline and “unstable” when there are frequent/severe exacerbations with a faster pulmonary decline.[4] Acute exacerbation of COPD requiring hospitalization is associated with an increased 1-year mortality risk of at least 18%.[5] This review will focus on the management of acute exacerbation of COPD, recent advances in management, and newer emerging therapies.
EXACERBATION AND ITS IMPACT
Exacerbations in COPD patients are associated with increased airway inflammation, increased mucus production, and increased gas trapping. These changes contribute to dyspnea, which is the predominant complaint of these patients. Numerous studies have documented the association between exacerbation history and future exacerbation events.[6,7] The prevention of acute exacerbation plays a vital role in COPD management as it is associated with an increase in mortality.[8] Many of these exacerbation events are not reported to the health-care personnel. Although some events are shorter in duration, their impact on health status is huge.
EXACERBATION-HOW TO APPROACH
Exacerbations are classified[3] as:
- Mild - Treated with short-acting bronchodilators only
- Moderate - Treated with short-acting bronchodilators + antibiotics and/or oral corticosteroids
- Severe - Requiring hospitalization/visit to the emergency room.
Triggers for exacerbation mainly include respiratory viral infections, bacterial infections, and environmental factors such as pollution and ambient temperature. Sudden worsening of respiratory symptoms, hypoxemia, acute mental changes, nonresponders to initial medical management, insufficient home support, and the presence of serious comorbidities are indications of hospitalization during an acute exacerbation episode. In COPD patients, other comorbidities which can worsen respiratory symptoms should also be ruled out, before labeling them as acute exacerbation, such as pulmonary embolism, pneumothorax, pulmonary edema due to cardiac causes, and pneumonia.
Pharmacological management
The cornerstone of treatment of an acute exacerbation event is the administration of short-acting inhaled beta-2 agonists with or without short-acting anticholinergics. The mode of delivery of these agents should be individualized to each patient, as studies demonstrate that there is no significant difference in benefit between metered dose inhalers and nebulizers.[9] In cases where nebulizer is preferred, air-driven nebulization is more beneficial than oxygen-driven nebulization as PaCO2 levels always increase with the latter one.[10]
Systemic glucocorticoids shorten recovery time, improve forced expiratory volume in 1 s (FEV1), improve oxygenation, and decrease the length of hospitalization.[11,12] Treatment for 5 days with 40 mg of prednisone or its equivalent daily is equally effective as a 10-day course.[13] Nebulized budesonide is also an alternative, which can be used comfortably in some patients. Recent studies demonstrate that corticosteroids may be ineffective in treating acute exacerbation in COPD patients for whom blood eosinophil count is lower,[14,15] and thus, more steroid-sparing regimens are needed to treat them. Methylxanthines are not recommended in these patients due to their significant side effects, such as nausea, vomiting, frequent tremors, palpitations, and arrhythmias.[16]
Antibiotics are beneficial in patients with purulent sputum and severe exacerbation requiring mechanical ventilation and duration of 5-14 days will suffice in most of the cases.[13] Other adjunctive therapeutic measures include maintaining fluid balance, thromboembolism prophylaxis, ensuring adequate nutrition, and treatment of other comorbidities.
Respiratory support
Oxygen supplementation is crucial in patients with hypoxemia, and a target saturation of 88%-92% is accepted. The high-flow nasal cannula did not exhibit any benefit in these patients.[17] Noninvasive ventilation (NIV) has been the preferred mode of ventilation to treat acute respiratory failure in these patients. NIV improves oxygenation, decreases tachypnea, decreases the work of breathing, and decreases mortality and intubation rates in these cases.[18,19] Invasive ventilation is only used as a rescue therapy in those who do not respond to NIV, patients in shock, and in those unable to protect the airway.
Long-acting beta2-agonists VS long-acting muscarinic antagonists
Ultra-long-acting beta2-agonists (LABAs) improve lung function, decrease symptoms, and help in preventing exacerbations.[20,21] Many “once-daily dosing LABA” have been available over the past years and indacaterol, olodaterol and vilanterol are the newest drugs available. In symptomatic individuals, there is no significant difference between LABA and long-acting muscarinic antagonists (LAMA). Whereas in frequent exacerbators, LAMA is more effective than LABA.[22,23]
Tiotropium was the only available LAMA worldwide, of which effectiveness is supported by a multitude of studies. Over the years, new drugs have emerged with efficacy being established by various trials such as aclidinium (ACCLAIM trial[24] and ATTAIN trial).[25] Similarly, umeclidinium also had promising results with increase in FEV1, dyspnea, and quality of life scores.[26] Another promising agent was glycopyrronium, of which efficacy was established by the GEM study.[27]
LONG-ACTING BETA2-AGONISTS LONG-ACTING MUSCARINIC ANTAGONISTS
Aclidinium + formoterol combination helped in reducing exacerbations, as demonstrated by AUGMENT and ACLIFORM studies.[28] Umeclidinium + vilanterol combination also had a favorable outcome in some studies.[29,30] Similarly, glycopyrronium/indacaterol reduced the rate of mild-to-severe COPD exacerbations compared to fluticasone/salmeterol.[31] Recent studies suggest that single-inhaler triple therapy (LABA + LAMA + inhaled corticosteroids [ICS]) provides a significant symptom relief and decreased rate of exacerbation compared to single-inhaler separate therapy.[32,33]
THE “GOLD” GUIDELINES
The global initiative for chronic obstructive lung disease suggests the flowchart [Figure 1] for the management of exacerbation in COPD.[34] The withdrawal of inhaled corticosteroids (ICS) is recommended in cases where eosinophil counts are less than 100, there is a poor response and occurrence of pneumonia. Roflumilast (PDE4 inhibitor) can be added in patients with FEV1 <50% and chronic bronchitis.[35,36] Adding a macrolide antibiotic like azithromycin to the treatment can decrease the rate of exacerbations in a year and improve the quality of life in patients, especially who are not current smokers.[37]
PREVENTION AND FOLLOW-UP
After an episode of exacerbation, measures should be taken for the prevention of further episodes. Smoking cessation, rehabilitation, Vitamin D supplementation, and shielding measures (masks, social distancing and frequent hand washing) are some of the methods which can prevent further exacerbation episodes.[34]
Figure 1: *Withdraw ICS: Pneumonia, lack of response. ICS: Inhaled corticosteroids. The Global Initiative for Chronic Obstructive Lung Disease Guidelines on exacerbation management
At the time of discharge, ensure adequate patient education, optimize medication, correct technique of using inhalers, optimize other comorbidities, and continue patient contact. Early follow-up (within 4 weeks) is associated with less exacerbation-related readmissions.[38] Additional follow-up at 12 weeks to review patient's lung function, assessment of long-term oxygen therapy, the status of other comorbidities, and prognostication is recommended.[34]
EMERGING THERAPIES
Lung volume reduction surgeries are the only surgical option available for patients with severe emphysema. Recent years saw the development of novel bronchoscopic interventions to treat severe emphysema, such as coils and endobronchial valves. The REVOLENS[39] and RENEW[40] randomized controlled trials evaluated the effect of bronchoscopic lung volume reduction in severe emphysema patients; however, further studies are required in this to establish a definitive clinical role. Bronchoscopic lung volume reduction with the use of one-way endobronchial valves is another potential treatment for patients with severe emphysema with modest results, but it needs further studies in the future.[41]
CONCLUSION
COPD exacerbations, particularly those that require hospitalization, lead to substantial financial burden. Patients who are frequent exacerbators have decreased quality of life and quick disease progression. Appropriate therapy with maintenance bronchodilators has been shown to reduce exacerbation frequency but is underused, highlighting a need for increased awareness of treatment recommendations among treating patients, physicians, and health-care organizations. Emerging evidence of LAMA + LABA therapy, single inhaler with dual/triple medication, and withdrawal of ICS is showing promising results in managing acute exacerbations. Proper patient education, appropriate training to use inhalers, and pulmonary rehabilitation improve patients' quality of life of those with frequent exacerbation.
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REFERENCES
1. GBD 2017 Causes of Death Collaborators. Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980-2017: A systematic analysis for the Global Burden of Disease Study 2017. Lancet 2018;392:1736-88.
2. Celli BR, Agustí A. COPD: Time to improve its taxonomy? ERJ Open Res 2018;4:00132-2017.
3. Wedzicha JA, Seemungal TA. COPD exacerbations: Defining their cause and prevention. Lancet 2007;370:786-96.
4. Bollmeier SG, Hartmann AP. Management of chronic obstructive pulmonary disease: A review focusing on exacerbations. Am J Health Syst Pharm 2020;77:259-68.
5. Rosenberg SR, Kalhan R. Recent advances in the management of chronic obstructive pulmonary disease. F1000Res 2017;6:863.
6. Hurst JR, Vestbo J, Anzueto A, Locantore N, Müllerova H, Tal-Singer R, et al. Susceptibility to exacerbation in chronic obstructive pulmonary disease. N Engl J Med 2010;363:1128-38.
7. Huseb0 GR, Bakke PS, Aanerud M, Hardie JA, Ueland T, Gr0nseth R, et al. Predictors of exacerbations in chronic obstructive pulmonary disease-results from the Bergen COPD cohort study. PLoS One 2014;9:e109721.
8. Soler-Cataluña JJ, Martíez-García MA, Roman Sanchez P, Salcedo E, Navarro M, Ochando R. Severe acute exacerbations and mortality in patients with chronic obstructive pulmonary disease. Thorax 2005;60:925-31.
9. 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;2016:CD011826.
10. Bardsley G, Pilcher J, McKinstry S, Shirtcliffe P, Berry J, Fingleton J, et al. Oxygen versus air-driven nebulisers for exacerbations of chronic obstructive pulmonary disease: A randomised controlled trial. BMC Pulm Med 2018;18:157.
11. 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;340:1941-7.
12. 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;354:456-60.
13. Wedzicha JA, Calverley PM, Albert RK, Anzueto A, Criner GJ, Hurst JR, et al. Prevention of COPD exacerbations: A European Respiratory Society/American Thoracic Society guideline. Eur Respir J 2017;50:1602265.
14. Bafadhel M, McKenna S, Terry S, Mistry V, Pancholi M, Venge P, et al. Blood eosinophils to direct corticosteroid treatment of exacerbations of chronic obstructive pulmonary disease: A randomized placebo-controlled trial. Am J Respir Crit Care Med 2012;186:48-55.
15. Sivapalan P, Lapperre TS, Janner J, Laub RR, Moberg M, Bech CS, et al. Eosinophil-guided corticosteroid therapy in patients admitted to hospital with COPD exacerbation (CORTICO-COP): A multicentre, randomised, controlled, open-label, non-inferiority trial. Lancet Respir Med 2019;7:699-709.
16. Barr RG, Rowe BH, Camargo CA. Methylxanthines for exacerbations of chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2003;(2):CD002168.
17. Fu C, Liu X, Zhu Q, Wu X, Hao S, Xie L, et al. Efficiency of high-flow nasal cannula on pulmonary rehabilitation in COPD patients: A meta-analysis. Biomed Res Int 2020;2020:7097243.
18. 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.
19. 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;333:817-22.
20. Calverley PM, Anderson JA, Celli B, Ferguson GT, Jenkins C, Jones PW, et al. Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease. N Engl J Med 2007;356:775-89.
21. Decramer M, Celli B, Kesten S, Lystig T, Mehra S, Tashkin DP, 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;374:1171-8.
22. Vogelmeier C, Magnussen H, LaForce C, Owen R, Kramer B. Profiling the bronchodilator effects of the novel ultra-long-acting β2-agonist indacaterol against established treatments in chronic obstructive pulmonary disease. Ther Adv Respir Dis 2011;5:345-57.
23. Decramer ML, Chapman KR, Dahl R, Frith P, Devouassoux G, Fritscher C, et al. Once-daily indacaterol versus tiotropium for patients with severe chronic obstructive pulmonary disease (INVIGORATE): A randomised, blinded, parallel-group study. Lancet Respir Med 2013;1:524-33.
24. Jones PW, Rennard SI, Agusti A, Chanez P, Magnussen H, Fabbri L, et al. Efficacy and safety of once-daily aclidinium in chronic obstructive pulmonary disease. Respir Res 2011;12:55.
25. Jones PW, Singh D, Bateman ED, Agusti A, Lamarca R, de Miquel G, et al. Efficacy and safety of twice-daily aclidinium bromide in COPD patients: The ATTAIN study. Eur Respir J 2012;40:830-6.
26. Trivedi R, Richard N, Mehta R, Church A. Umeclidinium in patients with COPD: A randomised, placebo-controlled study. Eur Respir J 2014;43:72-81.
27. LaForce C, Feldman G, Spangenthal S, Eckert JH, Henley M, Patalano F, et al. Efficacy and safety of twice-daily glycopyrrolate in patients with stable, symptomatic COPD with moderate-to-severe airflow limitation: The GEM1 study. Int J Chron Obstruct Pulmon Dis 2016;11:1233-43.
28. Bateman ED, Chapman KR, Singh D, D'Urzo AD, Molins E, Leselbaum A, et al. 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.
29. Decramer M, Anzueto A, Kerwin E, Kaelin T, Richard N, Crater G, et al. Efficacy and safety of umeclidinium plus vilanterol versus tiotropium, vilanterol, or umeclidinium monotherapies over 24 weeks in patients with chronic obstructive pulmonary disease: Results from two multicentre, blinded, randomised controlled trials. Lancet Respir Med 2014;2:472-86.
30. Celli B, Crater G, Kilbride S, Mehta R, Tabberer M, Kalberg CJ, et al. Once-daily umeclidinium/vilanterol 125/25 mcg in COPD: A randomized, controlled study. Chest 2014;145:981-91.
31. Wedzicha JA, Banerji D, Chapman KR, Vestbo J, Roche N, Ayers RT, et al. Indacaterol-glycopyrronium versus salmeterol-fluticasone for COPD. N Engl J Med 2016;374:2222-34.
32. Lai CC, Chen CH, Lin CY, Wang CY, Wang YH. The effects of single inhaler triple therapy vs. single inhaler dual therapy or separate triple therapy for the management of chronic obstructive pulmonary disease: A systematic review and meta-analysis of randomized controlled trials. Int J Chron Obstruct Pulmon Dis 2019;14:1539-48.
33. Rabe KF, Martinez FJ, Ferguson GT, Wang C, Singh D, Wedzicha JA, et al. Triple inhaled therapy at two glucocorticoid doses in moderate-to-very-severe COPD. N Engl J Med 2020;383:35-48.
34. Global Initiative for Chronic Obstructive Lung Disease. Global Strategy for the Diagnosis, Management and Prevention of COPD 2022 Report; 2022.
35. 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;385:857-66.
36. Rabe KF, Calverley PM, Martinez FJ, Fabbri LM. Effect of roflumilast in patients with severe COPD and a history of hospitalisation. Eur Respir J 2017;50:1700158.
37. Albert RK, Connett J, Bailey WC, Casaburi R, Cooper JA Jr., Criner GJ, et al. Azithromycin for prevention of exacerbations of COPD. N Engl J Med 2011;365:689-98.
38. 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;148:375-81.
39. Deslée G, Mal H, Dutau H, Bourdin A, Vergnon JM, Pison C, et al. Lung volume reduction coil treatment vs. usual care in patients with severe emphysema: The REVOLENS Randomized Clinical Trial. JAMA 2016;315:175-84.
40. Sciurba FC, Criner GJ, Strange C, Shah PL, Michaud G, Connolly TA, et al. Effect of endobronchial coils vs. usual care on exercise tolerance in patients with severe emphysema: The RENEW Randomized Clinical Trial. JAMA 2016;315:2178-89.
41. Davey C, Zoumot Z, Jordan S, McNulty WH, Carr DH, Hind MD, et al. Bronchoscopic lung volume reduction with endobronchial valves for patients with heterogeneous emphysema and intact interlobar fissures (the BeLieVeR-HIFi study): A randomised controlled trial. Lancet 2015;386:1066-73.
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