COPD inhaler therapy: A path to success
Keys to therapeutic success include choosing the right device and drug regimen, providing rigorous patient education, and reducing environmental exposures.
PRACTICE RECOMMENDATIONS
› Follow guideline advice that (1) in general, short-acting beta-agonists (SABAs) are not for daily use in stable chronic obstructive pulmonary disease (COPD) but (2) agents in this class of drugs might have a role in relieving occasional COPD-associated dyspnea. C
› Prescribe albuterol over levalbuterol when a SABA is indicated because of the lower cost of albuterol, its comparative efficacy, and its lower incidence of tachycardia and palpitations, even in patients with cardiovascular disease. B
› Avoid the use of an inhaled corticosteroid, or consider withdrawing inhaled corticosteroid therapy, in patients with COPD whose blood eosinophil count is < 100 cells/μL or who have repeated bouts of pneumonia or a history of mycobacterial infection. B
Strength of recommendation (SOR)
A Good-quality patient-oriented evidence
B Inconsistent or limited-quality patient-oriented evidence
C Consensus, usual practice, opinion, disease-oriented evidence, case series
LABA + LAMA. In a trial of patients with moderate-to-severe COPD, combining a LABA and a LAMA did not reduce the risk of exacerbations or hospitalizations, compared to LABA or LAMA monotherapy, but did improve subjects’ reported daily symptoms and quality of life scores (using the St. George’s Respiratory Questionnaireb; NNT = 14 [LAMA monotherapy] and NNT = 9 [LABA monotherapy], both in a 3 to 12–month period).24 However, another study that looked at patients with moderate-to-severe COPD found that combining a LABA and a LAMA led to fewer exacerbations (NNT = 22, to prevent 1 exacerbation in a 3 to 12–month period) and a lower risk of pneumonia (NNT = 93, to prevent 1 case of pneumonia in a 3 to 12–month period) than LABA + ICS.25
LABA + ICS. This dual therapy is falling out of favor, compared to treatment with LABA + LAMA, because LABA + ICS formulations are less effective at reducing exacerbations and increase the risk of pneumonia in patients with moderate-to-severe COPD.1,25 However, LABA + ICS therapy still has a role in a subset of patients with COPD (discussed in the section on ICS). A LABA combined with an ICS does reduce exacerbations in patients with severe COPD (NNT = 22, to prevent 1 exacerbation per year).18 Expect that the reported rates of candidiasis, hoarseness, and pneumonia associated with an ICS will be similar with LABA + ICS.18
LABA + LAMA + ICS. These are the newest combination inhaled agents approved for clinical use. It is recommended that escalation to such triple therapy be reserved for patients with persistent dyspnea on LAMA + LABA therapy and who have the factors (previously described) that suggest benefit from adding an ICS.1 Several clinical trials have provided guidance:
- In the 2018 TRIBUTE trial,26 beclometasone (ICS) + formoterol (LABA) + glycopyrronium (LAMA) c outperformed indacaterol (LABA) + glycopyrronium for preventing moderate-to-severe exacerbations (NNT = 11, to prevent 1 exacerbation per year) in patients with symptomatic COPD who have severe or very severe airflow resistance and a history of a moderate-to-severe exacerbation during the previous year.
- In the 2017 TRINITY trial,27 beclometasone + formoterol + glycopyrroniumc outperformed tiotropium (LAMA) in preventing moderate-to-severe exacerbations (NNT = 9, to prevent 1 exacerbation per year) in patients with an FEV1 < 50% and a history of ≥ 1 moderate-to-severe exacerbation during the previous year.
- In the 2020 ETHOS trial,28 budesonide + formoterol + glycopyrronium (approved by the FDA in 2020 under the brand name Breztri) outperformed both glycopyrrolate + formoterol (LABA) and budesonide (ICS) + formoterol in preventing moderate-to-severe exacerbations (NNT = 56 and 34, respectively, to prevent 1 exacerbation per year) in patients with moderate-to-severe COPD who had a history of ≥ 1 exacerbation in the previous year. Additionally, higher-dose budesonide + formoterol + glycopyrronium reduced 1-year mortality to a modest degree compared to glycopyrrolate + formoterol (NNT = 100, to prevent 1 death in a 12-month period).
- A 2016 Cochrane review that compared tiotropium + LABA + ICS to tiotropium monotherapy29 showed improvement in FEV1 and patient-reported symptoms and quality of life scores. However, the review showed no difference in exacerbations or hospitalizations over a 1-year period.
Mitigating environmental exposures that affect inhaler medication efficacy
Tobacco smoke. Emphasizing smoking cessation is highly relevant in patients who are still smoking. Smoking impedes the efficacy of ICSs in reducing exacerbations of COPD.30 Along with improved lung function, former smokers with COPD experience fewer exacerbations (NNT = 73, to prevent 1 exacerbation in a 4-year period for all former smokers; NNT = 33, to do so for smokers who quit > 10 years ago).31,32
A 2005 Veterans Health Administration study showed reduced mortality in smokers who were enrolled in a 10-week smoking cessation program, had access to nicotine replacement therapy, and received strong physician messaging.33 Despite a 20% to 25% quit rate, the NNT was 56 to prevent 1 death in 14.5 years across the entire group. It is worth having patients take advantage of this 3-pronged approach if it is available in your community or health system.
Continue to: Exposure to air pollution
