pulmonary disorders
Treatment of Stable COPD
Drug Therapy for Stable COPD
Recommended drug therapy is summarized in the table Pharmacologic Treatment of COPD . Inhaled bronchodilatorsare the mainstay of COPD management; drugs include Beta-agonists Anticholinergics (antimuscarinics) These two classes of drugs are equally effective. Patients with Pulmonary function tests disease are treated only when symptomatic. Patients with The frequency of exacerbations can be reduced with the use of anticholinergics, inhaled corticosteroids, or long-acting beta-agonists. However, there is no convincing evidence that regular bronchodilator use slows deterioration of lung function. The initial choice among short-acting beta-agonists, long-acting beta-agonists, anticholinergics, and combination beta-agonist and anticholinergic therapy is often a matter of tailoring cost and convenience to the patient’s preferences and symptoms. For home treatment of chronic stable disease, drug administration by metered-dose inhaler or dry-powder inhaler is preferred over administration by nebulizer; home nebulizers are prone to contamination due to incomplete cleaning and drying. Therefore, nebulizers should be reserved for people who cannot coordinate activation of the metered-dose inhaler with inhalation or cannot develop enough inspiratory flow for dry powder inhalers. For metered-dose inhalers, patients should be taught to exhale to functional residual capacity, inhale the aerosol slowly to total lung capacity, and hold the inhalation for 3 to 4 seconds before exhaling. Spacers help ensure optimal delivery of drug to the distal airways and reduce the importance of coordinating activation of the inhaler with inhalation. Some spacers alert patients if they are inhaling too rapidly. New or not recently used metered-dose inhalers require 2 to 3 priming doses (different manufacturers have slightly different recommendations for what is considered "not recently used," ranging from 3 to 14 days). Timing of Therapy Dyspnea without exacerbations*, † Exacerbations with or without dyspnea‡ Initial therapy LAC or LABA LAC or LABA Second-line therapy LABA + LAC or LABA + ICS LABA + LAC or LABA + ICS Third-line therapy LABA + LAC + ICS LABA + LAC + ICS * For persistent dyspnea, consider changing the inhalation device or drug. Also evaluate for other causes of dyspnea. † May need to de-escalate ICS if the patient develops pneumonia or does not respond to treatment. ‡ For recurrent exacerbations,add either a PDE4 inhibitor (eg,roflumilast) or long-termazithromycin. ICS is most effective in patients with eosinophilia.Roflumilastis indicated in patients with COPD with chronic bronchitis.Azithromycinis less effective in current smokers. LABA = Long-acting beta agonist; LAC = long-acting anticholinergic; ICS = inhaled corticosteroid; PDE4 = phosphodiesterase-4 inhibitor. Data from Figure 4.4 of the Global Initiative for Chronic Obstructive Lung Disease (GOLD): 2021 Global Strategy for the Diagnosis, Management and Prevention of COPD. Available athttp://www.goldcopd.org. Beta-agonists relax bronchial smooth muscle and increase mucociliary clearance.Albuterolaerosol, 2 puffs (90 to 100 mcg/puff) inhaled from a metered-dose inhaler 4 to 6 times a day as needed, is usually the drug of choice. Long-acting beta-agonistsare preferable for patients with nocturnal symptoms or for those who find frequent dosing inconvenient. Options includesalmeterolpowder, 1 puff (50 mcg) inhaled twice a day, indacaterol 1 puff (75 mcg) inhaled once a day (150 mcg once a day in Europe), andolodaterol2 puffs once a day at the same time each day. Vilanterol is available in combination with an inhaled corticosteroid. Also available are nebulized forms ofarformoterolandformoterol. The dry-powder formulations may be more effective for patients who have trouble coordinating use of a metered-dose inhaler. Patients should be taught the difference between short-acting and long-acting drugs, because long-acting drugs that are used as needed or more than twice a day increase the risk of Overview of Arrhythmias . Adverse effects commonly result from use of any beta-agonist and include tremor, anxiety, tachycardia, and mild, temporary hypokalemia. Anticholinergics (antimuscarinics) relax bronchial smooth muscle through competitive inhibition of muscarinic receptors (M1, M2, and M3). Ipratropiumis a short-acting anticholinergic; dose is 2 to 4 puffs (17 mcg/puff) from a metered-dose inhaler every 4 to 6 hours.Ipratropiumhas a slower onset of action (within 30 minutes; peak effect in 1 to 2 hour), so a beta-agonist is often prescribed with it in a single combination inhaler or as a separate as-needed rescue drug. Tiotropiumis a long-acting quaternary anticholinergic inhaled as a powder formulation (18 mcg/puff) and soft mist inhaler (2.5 mcg/puff). Dose is 1 puff (18 mcg) once a day by dry powder inhaler and 2 puffs (5 mcg) once a day by soft mist inhaler.Aclidiniumbromide is available as a multidose dry-powder inhaler. Dose is 1 puff (400 mcg/puff) twice a day.Aclidiniumis also available in combination with a long-acting beta-agonist as a dry-powder inhaler.Umeclidiniumcan be used as a once a day combination with vilanterol (a long-acting beta-agonist) in a dry-powder inhaler.Glycopyrrolate(an anticholinergic) can be used twice a day in combination with indacaterol orformoterol(long-acting beta-agonists) in a dry-powder or metered-dose inhaler.Revefenacinis given once a day via nebulizer. Adverse effects of all anticholinergics are pupillary dilation (and risk of triggering or worsening acute Angle-Closure Glaucoma ), urinary retention, and dry mouth. Corticosteroids are often part of treatment. Inhaled corticosteroids seem to reduce airway inflammation, reverse beta-receptor down-regulation, and inhibit leukotriene and cytokine production. They do not alter the course of pulmonary function decline in patients with COPD who continue to smoke, but they do relieve symptoms and improve short-term pulmonary function in some patients, are additive to the effect of bronchodilators, and diminish the frequency of COPD exacerbations. They are indicated for patients who have repeated exacerbations or symptoms despite optimal bronchodilator therapy. Inhaled corticosteroids are of greatest benefit in patients who have Eosinophilia . In patients with exacerbations, addition of an inhaled corticosteroid reduces exacerbation frequency and prolongs survival ( The long-term risks of inhaled corticosteroids in older people are not proved but probably include Osteoporosis , De-escalation of inhaled corticosteroid therapy may be necessary if patients develop pneumonia or do not respond to treatment. Combinations of a long-acting beta-agonist and an inhaled corticosteroid are more effective than either drug alone in the treatment of chronic stable disease. Oral or systemic corticosteroids should usually not be used to treat chronic stable COPD. Theophyllineplays only a small role in the treatment of chronic stable COPD now that safer, more effective drugs are available.Theophyllinedecreases smooth muscle spasm, enhances mucociliary clearance, improves right ventricular function, and decreases pulmonary vascular resistance and arterial pressure. Its mode of action is poorly understood but appears to differ from that of beta-2-agonists and anticholinergics. Its role in improving diaphragmatic function and dyspnea during exercise is controversial. Theophyllinecan be used for patients who have not adequately responded to inhaled drugs and who have shown symptomatic benefit from a trial of the drug. Serum levels need not be monitored unless the patient does not respond to the drug, develops symptoms of toxicity, or is questionably adherent; slowly absorbed oraltheophyllinepreparations, which require less frequent dosing, enhance adherence. Toxicity is common and includes sleeplessness and gastrointestinal upset, even at low blood levels. More serious adverse effects, such as supraventricular and ventricular arrhythmias and seizures, tend to occur at blood levels>20 mg/L (111 micromol/L). Hepatic metabolism oftheophyllinevaries greatly and is influenced by genetic factors, age, cigarette smoking, hepatic dysfunction, diet, and some drugs, such as macrolide and fluoroquinolone antibiotics and nonsedating histamine 2 blockers. Phosphodiesterase-4 inhibitors are more specific thantheophyllinefor pulmonary phosphodiesterase and have fewer adverse effects. They have anti-inflammatory properties and are mild bronchodilators. Phosphodiesterase-4 inhibitors such asroflumilastcan be used in addition to other bronchodilators for reduction of exacerbations in patients who have COPD with chronic bronchitis.Roflumilastshould be started at a oral dose of 250 mcg once a day and increased to 500 mcg once a day as tolerated. Common adverse effects include nausea, headache, and weight loss, but these effects may subside with continued use. Long-termazithromycintherapy is an effective adjunct to prevent COPD exacerbations in patients who are prone to repeated or severe exacerbations, particularly those who are not currently smoking. A dose of 250 mg orally once a day has demonstrated efficacy.Erythromycin250 mg orally twice or 3 times a day has also been found effective. 1.Lipson DA, Crim C, Criner GJ, et al: Reduction in all-cause mortality withfluticasonefuroate/umeclidinium/vilanterolin patients with chronic obstructive pulmonary disease.Am J Respir Crit Care Med201(12):1508–1516, 2020. doi: 10.1164/rccm.201911-2207OC 2.Rabe KF, Martinez FJ, Ferguson GT, et al: Triple inhaled therapy at two glucocorticoid doses in moderate-to-very-severe COPD.N Engl J Med383(1):35–48, 2020. doi: 10.1056/NEJMoa1916046 