Acute exacerbations of COPD are a major driver of the morbidity, mortality, and health care costs of COPD. Because of the greater age of the patients affected and the prevalence of comorbidities, especially cardiovascular disease, the mortality of acute exacerbations is greater than that of exacerbation of asthma, but management does not differ greatly except in the routine use of antibiotics, which are given because exacerbations of COPD frequently involve bacterial infection of the lower airways.
Because of their importance in driving the morbidity and mortality of COPD, much attention has been paid to approaches to prevention of COPD exacerbations. For patients with a history of two or more exacerbations, daily treatment with an ICS is appropriate, and a recent large study showed significant reduction in exacerbation frequency from daily treatment with azithromycin. An innovative, although initially counterintuitive, hypothesis is now also under examination: that treatment with the selective β1-receptor antagonist, metoprolol succinate, will reduce exacerbations in patients with moderate to severe COPD. The hypothesis is counterintuitive because nonselective β-blocker therapy so predictably worsens airflow obstruction in asthmatic patients that it has long been considered contraindicated for patients with COPD. Several developments and observations have changed this view. These include the development of selective β1-receptor antagonists and the recognition that the use of β-blocking agents—once also considered contraindicated for acute myocardial infarction and congestive heart failure—reduces mortality from these conditions. Epidemiologic surveys show significant reductions in overall mortality and exacerbations in COPD patients taking a β-receptor antagonist. Whether these effects reflect the therapeutic effect of β-blockers on mortality from coincident cardiovascular disease or reflect some direct effect on airway function is unknown, but the hypothesis is currently under study in a large, prospective, placebo-controlled study of metoprolol treatment of COPD patients at risk for exacerbations (https://clinicaltrials.gov/ct2/ show/NCT02587351).
• Albuterol Prompt, efficacious bronchodilation Selective β2 agonist • Salmeterol Slow onset, primarily preventive action; potentiates corticosteroid effects Selective β2 agonist
Metaproterenol, terbutaline: Similar to albuterol; terbutaline available as an oral drug
Formoterol, vilanterol: Similar to salmeterol
Asthma, chronic obstructive pulmonary disease (COPD) • drug of choice in acute
Bronchodilation, prevention of asthma exacerbations
Aerosol inhalation • duration several hours • also available for nebulizer and parenteral use • Toxicity: Tremor, tachycardia • Overdose: arrhythmias • Toxicity: Tremor, tachycardia • Overdose:
CORTICOSTEROIDS, INHALED •FluticasoneAlters gene expression Reduces mediators of inflammation •powerfulprophylaxisofexacerbations Asthma•adjunctinCOPD•hayfever(nasal)Aerosol•durationhours•Toxicity: Limitedbyaerosolapplication•candidalinfection, vocal cord changes •Beclomethasone, budesonide, flunisolide, others: Similar to fluticasone •TheophyllineUncertain: •phosphodiesteraseinhibition •adenosinereceptor antagonist Bronchodilation, cardiac stimulation, increased skeletal muscle strength (diaphragm) Asthma, COPD Oral•duration8–12hbutextended-releasepreparationsoftenused•Toxicity: Multiple (see text) •Roflumilast: Similar to theophylline, but with better therapeutic ratio