Inhaled bronchodilator therapy with long-acting muscarinic antagonists (LAMAs) and long-acting β2-agonists (LABAs) in combination is currently the mainstay of treatment for chronic obstructive pulmonary disease (COPD). Treatment guidelines recommend the addition of inhaled corticosteroids (ICS) to LABA/LAMA only in patients with a history of frequent/severe exacerbations and high blood eosinophil counts, or in those with concomitant asthma. Despite this, real-world data suggest that clinicians are not adhering to this guidance and that ICS are frequently overused. This is possibly due to the incorrect assumption that when LABA/LAMA therapy is not sufficient, adding an ICS to the treatment regimen is the logical next step. In this narrative review, we describe global and country-specific guideline recommendations from Germany, Spain, and Japan and compare these with real-world data on LABA/LAMA and ICS use in clinical practice. We also provide a clinical guide to the use of add-on therapies with LABA/LAMA for different patient phenotypes, including (1) patients still symptomatic (but not exacerbating) despite LABA/LAMA treatment; (2) patients still exacerbating despite LABA/LAMA treatment who have high blood eosinophil counts; and (3) patients still exacerbating despite LABA/LAMA treatment who do not have high blood eosinophils or concomitant asthma.
Keywords: COPD; dyspnoea; eosinophils; exacerbations; inhaled corticosteroids; long-acting beta-agonists.
What are the options for patients with COPD when LABA/LAMA is not enough?Treatment guidelines for chronic obstructive pulmonary disease (COPD) recommend dual bronchodilator therapy for the majority of patients, consisting of an inhaled combination of long-acting β2-agonist (LABA) and long-acting muscarinic antagonist (LAMA). Patients whose COPD is not well controlled on LABA/LAMA require further clinical intervention, which may or may not involve treatment with additional drugs.Data from observational studies reflecting routine clinical practice suggest that inhaled corticosteroids (ICS) are often added to LABA/LAMA, even though treatment guidelines recommend only adding ICS in a specific group of patients with a history of exacerbations and high levels of eosinophils (a type of inflammatory cell) in the blood, or in those with current asthma. As long-term ICS use may be associated with an increased risk of side effects such as pneumonia, it is important to avoid overuse of ICS. When a patient’s COPD is not well controlled on LABA/LAMA, other treatable conditions should first be ruled out, and factors such as medication adherence, inhaler technique, and co-existing health conditions should also be considered.This review gives advice on what follow-up options physicians should consider when LABA/LAMA is not providing adequate control of a patient’s COPD. Specifically, recommendations are given for three different patient profiles:1. Patients who still have symptoms of COPD (but no acute/sudden worsenings of symptoms, known as exacerbations).2. Patients who have exacerbations, as well as high levels of eosinophils in the blood.3. Patients who have exacerbations, but without high levels of eosinophils in the blood or current asthma.