Treatment
Several modalities of treatment—used either individually or in combination—are available for patients with COPD. Although bronchoconstriction in these patients is considerably less than in patients with bronchial asthma, bronchodilators remain an important part of the treatment of many patients with COPD. The agents used are identical to those discussed in Chapter 5, including sympathomimetic agents (β2- agonists), anticholinergic drugs, and methylxanthines. Short-acting inhaled β2-agonists (e.g., albuterol), short-acting anticholinergic agents (e.g., ipratropium), or both are most commonly used as needed for patients with mild disease who require only infrequent therapy. For patients with more severe disease who require regular therapy, either a long-acting β2-agonist (e.g., salmeterol, formoterol, arformoterol, indacaterol), a long-acting anticholinergic (antimuscarinic) agent (e.g., tiotropium, aclidinium, umeclidinium), or both are commonly used, although regular use of short-acting agents is an alternative. The methylxanthine theophylline is another option, but concern for systemic side effects has relegated it to a secondary role in comparison with the inhaled bronchodilators.
Corticosteroid use for COPD treatment is dependent on the clinical setting. A 5- to 14-day course of systemic corticosteroids is frequently administered at the time of an acute exacerbation, and most studies suggest the benefit of improved pulmonary function and reduced treatment failure in this setting. On the other hand, only a minority of patients with chronic, stable, but severe disease show improved pulmonary function after a regimen of oral corticosteroids. Inhaled corticosteroids have little use in the setting of acute exacerbations of COPD. However, a trial of inhaled corticosteroids should be considered in patients with moderate to severe COPD who have frequent exacerbations, because some evidence indicates that inhaled corticosteroids may reduce the frequency or severity of exacerbations. In patients with frequent exacerbations, an alternative to combination therapy with a long-acting β2-agonist and an inhaled corticosteroid is combination therapy with a long-acting β2-agonist and a long-acting anticholinergic (antimuscarinic) agent, or a combination of all three drug classes.
Roflumilast, a phosphodiesterase-4 inhibitor, represents a relatively new class of medications for COPD. Phosphodiesterase-4 inhibitors decrease inflammation and promote airway smooth muscle relaxation and bronchodilation. Roflumilast is typically used in patients with more severe disease and frequent exacerbations.
Modalities available for treatment of COPD are as follows:
1.Bronchodilators
2.Antibiotics
3.Corticosteroids
4.Phosphodiesterase-4 inhibitors
5.Supplemental oxygen
6.Exercise rehabilitation
7.Chest physiotherapy
8.Surgery (selected cases)
Patients with COPD who develop an acute respiratory tract infection, or patients with an exacerbation of their disease without a clear precipitant, are often treated with antibiotics. The primary usefulness of antibiotics is treatment of bacterial infections. However, a bacterial cause is difficult to document with certainty, and many exacerbations are thought to be either noninfectious or triggered by viral respiratory
infections. In practice, patients are frequently treated with antibiotics when a change in quantity, color, and/or thickness of sputum is noted in comparison with the usual pattern of sputum production, regardless of whether a bacterial infection is documented. Of the potential bacterial pathogens, those most frequently implicated are Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. As a result, the choice of an empiric antibiotic should provide coverage for these organisms. An area of investigation is the use of C-reactive protein levels and other biomarkers to help guide the use of antibiotics.
More recently, there has also been interest in the chronic use of a macrolide antibiotic (e.g., azithromycin) for its anti-inflammatory as well as antibacterial properties as another option for decreasing exacerbations in patients with COPD and a history of frequent exacerbations. However, as with chronic use of virtually any antibiotic, there is an associated risk of selecting out more resistant bacterial strains.
An important therapy for patients with significant hypoxemia (i.e., systemic arterial oxygen saturation ≤ 88% or arterial PO2 ≤ 55 mm Hg) is administration of supplemental O2. Fortunately, the PO2 of hypoxemic patients with COPD usually responds quite well to relatively small amounts of supplemental O2 (range, 24%-28% O2). A low flow rate of O2 (1-2 L/min) given by nasal prongs is an effective, well-tolerated method for achieving these concentrations of inspired O2. Oxygen is particularly important in patients with pulmonary hypertension and in those with secondary polycythemia, because each of these complications is largely due to hypoxemia and is responsive to treatment for it. For significantly hypoxemic patients, as defined earlier, administering supplemental O2 has been shown to alter the natural history of the disease and improve long-term survival. However, no such benefit appears to accrue in patients with less severe or episodic hypoxemia.
The goal of O2 therapy is to shift PO2 into the range where hemoglobin is almost fully saturated (i.e., Po2 > 60-65 mm Hg). Ideally, O2 saturation should be well maintained on a continuous basis throughout the day and night. In some COPD patients who are not significantly hypoxemic during the day, a substantial drop in PO2 and O2 saturation can occur at night. In these patients, nocturnal O2 theoretically may be of benefit, although this has not been proven. In addition to oxygen therapy, there is also an emerging role for nocturnal noninvasive positive pressure ventilation in some patients with severe COPD, particularly if hypercapnia is present.
For patients in whom airway secretions cause significant symptoms, chest physiotherapy and postural drainage are sometimes used to help mobilize and clear secretions. These techniques use percussion of the chest wall to loosen secretions and induce cough, followed by positional changes to allow gravity to aid in the drainage of secretions. Hand-held mucus-clearing devices are also available. To use these devices, the patient exhales into the apparatus, which applies oscillatory positive end-expiratory pressure, allowing more efficient clearance of secretions. However, the general usefulness of chest physiotherapy, postural drainage, or mucus-clearing devices is not generally accepted because outcome studies have not clearly supported their benefit.
In a small subgroup of patients with COPD who have α1-antitrypsin deficiency, therapy is available in the form of intravenous α1-antitrypsin concentrate, which is prepared from pooled human plasma. The rationale for this therapy is to replace the deficient protease inhibitor and attempt to inhibit or prevent unchecked proteolytic destruction of alveolar tissue. Although intravenous infusions of α1-antitrypsin have been shown to increase concentrations of this antiprotease in alveolar epithelial lining fluid, whether such replacement therapy alters the accelerated decline in pulmonary function is less definitively known.
In patients with impaired exercise tolerance secondary to COPD, a rehabilitation program focusing on education and a regimen of exercise training is often quite beneficial. Most patients participating in such a
Данная книга находится в списке для перевода на русский язык сайта https://meduniver.com/
program report an improved sense of well-being at the same time they experience an improvement in exercise tolerance. Smoking cessation education and assistance are absolutely critical parts of any comprehensive therapeutic program. Pharmacologic assistance to ameliorate the effects of nicotine withdrawal—nicotine replacement therapy, bupropion, or varenicline—is often a valuable component of smoking cessation efforts. Vaccination against influenza, SARS-CoV-2, and pneumococcus is indicated for all patients as a preventive strategy and a component of the overall therapeutic regimen.
Two surgical approaches have been used for patients with severe COPD who remain markedly symptomatic despite optimal therapy. One approach, lung volume reduction surgery, initially seems counterintuitive because it involves removing portions of both lungs from patients whose pulmonary reserve is marginal at best. However, two interesting pathophysiologic rationales underlie this approach. First, removal of some lung tissue diminishes overall intrathoracic volume, allowing the flattened and foreshortened diaphragm to return toward its normal position and resume its usual curved configuration. A flattened, foreshortened diaphragm is an inefficient respiratory muscle, and the changes in its position and shape following surgery facilitate its effectiveness during inspiration. Second, when the most diseased regions of lung are selectively removed (i.e., the regions with the least elastic recoil), the overall elastic recoil of the lung improves. Lung elastic recoil is an important determinant of expiratory flow and airway collapse, and improving elastic recoil has secondary benefits on airway patency and expiratory flow. Although lung volume reduction, either via surgery or via implantation of endobronchial valves through a bronchoscope, is a novel and potentially attractive approach, it appears to be beneficial only in wellselected patients. Critical aspects of patient selection include the severity of disease and the anatomic distribution of emphysematous changes.
The other surgical approach to treatment of end-stage COPD is lung transplantation. However, this approach is limited for large numbers of individuals because of the resources needed, the shortage of donor organs, the age of most patients with COPD, and the presence of disqualifying comorbid conditions. Patients whose emphysema is due to α1-antitrypsin deficiency, in whom the disease occurs at an early age, may be a particularly appropriate subgroup to consider for lung transplantation.
When acute respiratory failure supervenes as a part of COPD, mechanical ventilation may be necessary to support gas exchange and maintain acceptable arterial blood gas values. Such ventilatory assistance with intermittent positive pressure may be delivered via either a mask (noninvasive positive-pressure ventilation) or an endotracheal tube, but the former noninvasive method is preferred. More detailed information about the treatment of acute respiratory failure superimposed on chronic disease of the obstructive variety is covered in Chapter 28. Mechanical ventilation is discussed in Chapter 30.
Suggested readings
Reviews
Celli B.R. & Wedzicha J.A. Update on clinical aspects of chronic obstructive pulmonary disease New England Journal of Medicine 2019;381: 1257-1266.
Decramer M, Janssens W. & Miravitlles M. Chronic obstructive pulmonary disease Lancet 2012;379: 1341-1351.
Global Initiative for Chronic Obstructive Lung Disease. (2023). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease [report]. https://goldcopd.org/2023-gold-report-2/.
Miravitlles M, Dirksen A, Ferrarotti I, Koblizek V, Lange P, Mahadeva R., et al. European Respiratory Society statement: Diagnosis and treatment of pulmonary disease in ɑ1-
antitrypsin deficiency European Respiratory Journal 2017;50: 1700610.
Riley C.M. & Sciurba F.C. Diagnosis and outpatient management of chronic obstructive pulmonary disease: A review JAMA 2019;321: 786-797.
Singh D, Agusti A, Anzueto A, Barnes P.J, Bourbeau J, Celli B.R., et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive lung disease: The GOLD science committee report 2019 European Respiratory Journal 2019;53: 1900164.
Strnad P, McElvaney N.G. & Lomas D.A. Alpha1-antitrypsin deficiency New England Journal of Medicine 2020;382: 1443-1455.
Vogelmeier C.F, Criner G.J, Martinez F.J, Anzueto A, Barnes P.J, Bourbeau J., et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive lung disease 2017 report. GOLD executive summary American Journal of Respiratory and Critical Care Medicine 2017;195: 557-582.
Etiology and pathogenesis
Agustí A. & Hogg J.C. Update on the pathogenesis of chronic obstructive pulmonary disease New England Journal of Medicine 2019;381: 1248-1256.
Barnes P.J. Cellular and molecular mechanisms of chronic obstructive pulmonary disease
Clinics in Chest Medicine 2014;35: 71-86.
Brusselle G.G, Joos G.F. & Bracke K.R. New insights into the immunology of chronic obstructive pulmonary disease Lancet 2011;378: 1015-1026.
Cosio M.G, Saetta M. & Agusti A. Immunologic aspects of chronic obstructive pulmonary disease New England Journal of Medicine 2009;360: 2445-2454.
Criner G.J, Cordova F, Sternberg A.L. & Martinez F.J. The National Emphysema Treatment Trial (NETT): Part I: Lessons learned about emphysema American Journal of Respiratory and Critical Care Medicine 2011;184: 763-770.
Djukanovic R. & Gadola S.D. Virus infection, asthma, and chronic obstructive pulmonary disease New England Journal of Medicine 2008;359: 2062-2064.
Eisner M.D, Anthonisen N, Coultas D, Kuenzli N, Perez-Padilla R, Postma D., et al. An official American Thoracic Society public policy statement: Novel risk factors and the global burden of chronic obstructive pulmonary disease American Journal of Respiratory and Critical Care Medicine 2010;182: 693-718.
Hogg J.C, Paré P.D. & Hackett T.L. The contribution of small airway obstruction to the pathogenesis of chronic obstructive pulmonary disease Physiological Reviews 2017;97: 529-552.
Martin R.J, Bel E.H, Pavord I.D, Price D. & Reddel H.K. Defining severe obstructive lung disease in the biologic era: An endotype-based approach European Respiratory Journal 2019;54: 1900108.
Maselli D.J, Bhatt S.P, Anzueto A, Bowler R.P, DeMeo D.L, Diaz A.A., et al. Clinical epidemiology of COPD: Insights from 10 years of the COPDGene Study Chest 2019;156: 228-238.
Postma D.S, Bush A. & van den Berge M. Risk factors and early origins of chronic obstructive pulmonary disease Lancet 2015;385: 899-909.
Sethi S. & Murphy T.F. Infection in the patho-genesis and course of chronic obstructive pulmonary disease New England Journal of Medicine 2008;359: 2355-2365.
Smith BM, Kirby M, Hoffman EA, Kronmal R.A, Aaron S.D, Allen N.B., et al. Association of dysanapsis with chronic obstructive pulmonary disease among older adults JAMA
Данная книга находится в списке для перевода на русский язык сайта https://meduniver.com/
2020;323: 2268-2280.
Smolonska J, Wijmenga C, Postma D.S. & Boezen H.M. Meta-analyses on suspected chronic obstructive pulmonary disease genes: A summary of 20 years’ research American Journal of Respiratory and Critical Care Medicine 2009;180: 618-631.
Tuder R.M. & Petrache I. Pathogenesis of chronic obstructive pulmonary disease Journal of Clinical Investigation 2012;122: 2749-2755.
Clinical features
van den Berge M, Ten Hacken N.H.T, Cohen J, Douma W.R. & Postma D.S. Small airway disease in asthma and COPD: Clinical implications Chest 2011;139: 412-423.
Criner G.J, Bourbeau J, Diekemper R.L, Ouellette D.R, Goodridge D, Hernandez P., et al.
Executive summary. Prevention of acute exacerbation of COPD: American College of Chest Physicians and Canadian Thoracic Society guideline Chest 2015;147: 883-893.
Labaki W.W, Martinez C.H, Martinez F.J, Galbán C.J, Ross B.D, Washko G.R., et al. The role of chest computed tomography in the evaluation and management of the patient with chronic obstructive pulmonary disease American Journal of Respiratory and Critical Care Medicine 2017;196: 1372-1379.
Nussbaumer-Ochsner Y. & Rabe K.F. Systemic manifestations of COPD Chest 2011;139: 165-173.
Peinado V.I, Pizarro S. & Barberà J.A. Pulmonary vascular involvement in COPD Chest 2008;134: 808-814.
Postma D.S. & Rabe K.F. The asthma-COPD overlap syndrome New England Journal of Medicine 2015;373: 1241-1249.
Press V.G, Cifu A.S. & White S.R. Screening for chronic obstructive pulmonary disease
JAMA 2017;318: 1702-1703.
US Preventive Services Task Force. Screening for chronic obstructive pulmonary disease
US Preventive Services Task Force reaffirmation recommendation statement 2022;327: 1806-1811.
Treatment
Beghè B, Rabe K.F. & Fabbri L.M. Phosphodiesterase-4 inhibitor therapy for lung diseases
American Journal of Respiratory and Critical Care Medicine 2013;188: 271-278.
Butler C.C, Gillespie D, White P, Bates J, Lowe R, Thomas-Jones E., et al. C-reactive protein testing to guide antibiotic prescribing for COPD exacerbations New England Journal of Medicine 2019;381: 111-120.
Casaburi R. & ZuWallack R. Pulmonary rehabilitation for management of chronic obstructive pulmonary disease New England Journal of Medicine 2009;360: 1329-1335.
Cazzola M, Rogliani P, Calzetta L. & Matera M.G. Triple therapy versus single and dual long-acting bronchodilator therapy in COPD: A systematic review and meta-analysis
European Respiratory Journal 2018;52: 1801586.
Celli B.R. Pharmacological therapy of COPD: Reasons for optimism Chest 2018;154: 14041415.
Criner G.J. Alternatives to lung transplantation: Lung volume reduction for COPD Clinics in Chest Medicine 2011;32: 379-397.
Criner G.J, Cordova F, Sternberg A.L. & Martinez F.J. The National Emphysema Treatment
Trial (NETT): Part I: Lessons learned about emphysema American Journal of Respiratory and Critical Care Medicine 2011;184: 763-770.
Dobler C.C, Morrow A.S, Beuschel B, Farah M.H, Majzoub A.M, Wilson M.E., et al.
Pharmacologic therapies in patients with exacerbation of chronic obstructive pulmonary disease: A systematic review with meta-analysis Annals of Internal Medicine 2020;172: 413-422.
Horita N, Nagashima A. & Kaneko T. Long-acting β-agonists (LABA) combined with longacting muscarinic antagonists or LABA combined with inhaled corticosteroids for patients with stable COPD JAMA 2017;318: 1274-1275.
Khor Y.H, Dudley K.A, Herman D, Jacobs S.S, Lederer D.J, Krishnan J.A., et al. Summary for clinicians: Clinical practice guideline on home oxygen therapy for adults with chronic lung disease Annals of the American Thoracic Society 2021;18: 1444-1449. Lacasse Y, Sériès F, Corbeil F, Baltzan M, Paradis B, Simão P., et al. Randomized trial of nocturnal oxygen in chronic obstructive pulmonary disease New England Journal of
Medicine 2020;383: 1129-1138.
Leone F.T, Zhang Y, Evers-Casey S, Evins A.E, Eakin M.N, Fathi J., et al. Initiating pharmacologic treatment in tobacco-dependent adults. An official American Thoracic Society clinical practice guideline American Journal of Respiratory and Critical Care Medicine 2020;202: e5e31.
Leuppi J.D, 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: 2223-2231.
Lipson D.A, Barnhart F, Brealey N, Brooks J, Criner G.J, Day N.C., et al. Once-daily singleinhaler triple versus dual therapy in patients with COPD New England Journal of Medicine 2018;378: 1671-1680.
Mackay A.J. & Hurst J.R. COPD exacerbations: Causes, prevention, and treatment Medical Clinics of North America 2012;96: 789-809.
Mammen M.J, Lloyd D.R, Kumar S, Ahmed A.S, Pai V, Kunadharaju R., et al. Triple therapy versus dual or monotherapy with long-acting bronchodilators for chronic obstructive pulmonary disease. A systematic review and meta-analysis Annals of the American Thoracic Society 2020;17: 1308-1318.
Miravitlles M. & Anzueto A. Antibiotics for acute and chronic respiratory infection in patients with chronic obstructive pulmonary disease American Journal of Respiratory and Critical Care Medicine 2013;188: 1052-1057.
Nici L, Mammen M.J, Charbek E, Alexander P.E, Au D.H, Boyd C.M., et al. Pharmacologic management of chronic obstructive pulmonary disease. An official American Thoracic Society clinical practice guideline American Journal of Respiratory and Critical Care Medicine 2020;201: e56e69.
Qaseem A, Wilt T.J, Weinberger S.E, Hanania N.A, Criner G, van der Molen T., et al.
Diagnosis and management of stable chronic obstructive pulmonary disease: A clinical practice guideline update from the American College of Physicians, American College of Chest Physicians, American Thoracic Society, and European Respiratory Society Annals of Internal Medicine 2011;155: 179-191.
Ries A.L, Bauldoff G.S, Carlin B.W, Casaburi R, Emery C.F, Mahler D.A., et al. Pulmonary rehabilitation: Joint ACCP/AACVPR evidence-based clinical practice guidelines Chest 2007;131: 4S42S.
Shah P.L, Herth F.J, van Geffen W.H, Deslee G. & Slebos D.J. Lung volume reduction for
Данная книга находится в списке для перевода на русский язык сайта https://meduniver.com/
emphysema Lancet. Respiratory Medicine 2017;5: 147-156.
Singh D, Roche N, Halpin D, Agusti A, Wedzicha J.A. & Martinez F.J. Current controversies in the pharmacological treatment of chronic obstructive pulmonary disease American Journal of Respiratory and Critical Care Medicine 2016;194: 541-549.
Stoller J.K, Panos R.J, Krachman S, Doherty D.E. & Make B. Oxygen therapy for patients with COPD: Current evidence and the long-term oxygen treatment trial Chest 2010;138: 179-187.
Wedzicha J.A. Choice of bronchodilator therapy for patients with COPD New England Journal of Medicine 2011;364: 1167-1168.
Wedzicha J.A, Banerji D, Chapman K.R, Vestbo J, Roche N, Ayers R.T., et al. Indacaterolglycopyrronium versus salmeterol-fluticasone for COPD New England Journal of Medicine 2016;374: 2222-2234.
Wenzel R.P, Fowler A.A,III. & Edmond M.B. Antibiotic prevention of acute exacerbations of COPD New England Journal of Medicine 2012;367: 340-347.
Wilson M.E, Dobler C.C, Morrow A.S, Beuschel B, Alsawas M, Benkhadra R., et al.
Association of home noninvasive positive pressure ventilation with clinical outcomes in chronic obstructive pulmonary disease: A systematic review and meta-analysis JAMA 2020;323: 455-465.
Woodruff P.G, Agusti A, Roche N, Singh D. & Martinez F.J. Current concepts in targeting chronic obstructive pulmonary disease pharmacotherapy: Making progress towards personalised management Lancet 2015;385: 1789-1798.
Zhou Y, Zhong N, Li X, Chen S, Zheng J, Zhao D., et al. Tiotropium in early-stage chronic obstructive pulmonary disease New England Journal of Medicine 2017;377: 923-935.