Management of Stable Chronic Obstructive Pulmonary Disease

The currently available long-acting beta agonists include salmeterol, formoterol, aformoterol, olodatetol, and indacaterol. The last two have the advantage of once-daily dosing rather than twice [22,23]. LABAs have been shown to improve lung function, exacerbation rate, and quality of life in multiple clinical trials [22–24]. Vilanterol is another LABA that has a long duration of action and can be used once daily [25], but is only available in a combination with umeclidinium, a LAMA. Several LAMAs are approved for use in COPD, including the prototype tiotropium in addition to aclidinium, umeclidinium, and glycopyrronium. These have been shown in clinical trials to improve lung function, symptoms, and exacerbation rate [26–29].

Patients can be started on either a LAMA or LABA depending on patient needs and side effects [7]. Both have comparable side effects and efficacy as detailed below. Concerning side effects, there is conflicting data concerning an association of cardiovascular events with both classes of long-acting bronchodilators. While clinical trials failed to show an increased risk [24,30,31], several retrospective studies showed an increased risk of emergency room visits and hospitalizations due to tachyarrhythmias, heart failure, myocardial infarction, and stroke upon initiation of long-acting bronchodilators [32,33]. There was no difference in risk for adverse cardiovascular events between LABA and LAMA in one Canadian study, and slightly more with LABA in a study using an American database [32,33]. Urinary retention is another possible complication of LAMA supported by evidence from meta-analyses and retrospective studies but not clinical trials and should be discussed with patients upon initiation [34,35]. There have been concerns about increased mortality with the soft mist formulation of tiotropium that were put to rest by the tiotropium safety and performance in Respimat (TIOSPIR) trial, which showed no increased mortality compared to Handihaler [36].

As far as efficacy and benefits, tiotropium and salmeterol were compared head-to-head in a clinical trial, and tiotropium increased the time before developing first exacerbation and decreased the overall rate of exacerbations [37]. No difference in hospitalization rate or mortality was noted in one meta-analysis, although tiotropium was more effective in reducing exacerbations [38]. The choice of agent should be made based on patient comorbidities and side effects. For example, an elderly patient with severe benign prostatic hyperplasia and urinary retention should try a LABA while for a patient with severe tachycardia induced by albuterol, LAMA would be a better first agent.

• What is the role of inhaled corticosteroids in COPD?

Inhaled corticosteroids (ICS) are believed to work in COPD by reducing airway inflammation [39]. ICS should not be used alone for COPD management and are always combined with LABA [7]. Several inhaled corticosteroid formulations are approved for use in COPD, including budesonide and fluticasone. ICS has been shown to decrease symptoms and exacerbations with modest effect on lung function and no change in mortality [40]. Side effects include oral candidiasis, dysphonia, and skin bruising [41]. There is also an increased risk of pneumonia [42]. ICS are best reserved for patients with a component of asthma or asthma–COPD overlap syndrome (ACOS) [43]. ACOS is characterized by persistent airflow limitation with several features usually associated with asthma and several features usually associated with COPD [44].