There are numerous pharmacological options for treating COPD, and Figure 2 highlights the different approaches based on severity assessment (Global Initiative for Chronic Obstructive Lung Disease, 2018). Ultimately, the choice of inhaler device must be patient centered and depend on access, cost, prescriber, and, most importantly, the patient's ability to use it. Prescribers should be open to speaking with patients to determine preferences, taking into consideration methods to increase efficacy and decrease toxicity.
Treatment approaches for chronic obstructive pulmonary disease based on severity assessment.
Note. LAMA = long-acting muscarinic antagonists; LABA = long-acting beta2-agonists; ICS = inhaled corticosteroid; FEV = forced expiratory volume.
Reprinted with permission from Global Initiative for Chronic Obstructive Lung Disease. (2017). Pocket guide to COPD diagnosis, management, and prevention. Retrieved from https://goldcopd.org/wp-content/uploads/2016/12/wms-GOLD-2017-Pocket-Guide.pdf
According to the GOLD guidelines (Global Initiative for Chronic Obstructive Lung Disease, 2018), long-acting muscarinic antagonists (LAMAs) are preferred over long-acting beta2-agonists (LABAs) due to superior effects in exacerbation prevention. Yet, LABAs have been shown to “significantly improve FEV1 and lung volumes, dyspnea, health status, exacerbation rate and number of hospitalizations, but have no effect on mortality or rate of decline of lung function” (Global Initiative for Chronic Obstructive Lung Disease, 2018, p. 48). Although oral glucocorticoid agents play a role in the acute management of exacerbations, they have no role in the chronic daily treatment of COPD because of a lack of benefit balanced against a high rate of systemic complications (e.g., impaired glucose, bone health).
Referring to the case study, AB is already using Advair, a LABA + inhaled corticosteroid (ICS), along with Spiriva®, a LAMA. This is the preferred therapeutic regimen according to the treatment algorithm above; however, she continues to have worsening symptoms. At this time, a trained medical professional (e.g., physician, pharmacist, nurse practitioner) should assess AB's inhaler technique and adherence. She should be counseled on proper technique, as well as the importance of taking maintenance medications daily as indicated. Medication adherence should always be addressed before prescribing additional medications. Barriers to optimal medication adherence may include, but are not limited to: cost, concurrent health conditions (e.g., tremors or arthritis, which make inhaler coordination more difficult), and cognitive impairment. AB should be administered her annual flu vaccine and both pneumonia vaccines as appropriate. In addition, deep breathing exercises may be recommended for the potential anxiety component of her COPD.
As the efficacy aspects are balanced, it is imperative to monitor for side effects that may impede adherence to treatment approaches or exacerbation of comorbidities. For instance, in a patient like AB, the stimulation of beta2-adrenergic receptors can produce resting sinus tachycardia and has the potential to precipitate cardiac rhythm disturbances. Inhaled anticholinergic drugs can cause xerostomia, which can affect appetite and lead to failure to thrive. Routine follow up and involvement of the patient in the care plan is essential for effective medication management.
Trelegy Ellipta®. The U.S. Food and Drug Administration approved fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) (Trelegy Ellipta) for maintenance treatment of patients with COPD (Pharmacy Times, 2017). This treatment is a combination of an ICS, LAMA, and LABA and the first once-daily product approved in the United States that combines three active molecules in a single inhaler for the treatment of COPD.
Roflumilast (Daliresp®). Roflumilast and the active metabolite, roflumilast N-oxide, selectively inhibit phosphodiesterase 4, a major cyclic adenosine monophosphate (AMP) metabolizing enzyme in lung tissue. The specific mechanism of roflumilast activity in COPD is not well defined; it is thought to be associated with increased levels of intracellular cyclic AMP in lung cells and reduced neutrophil and eosinophil cell counts in the lungs. Roflumilast reduces moderate and severe exacerbations treated with systemic corticosteroids in patients with chronic bronchitis, severe to very severe COPD, and a history of exacerbations. The effects on lung function are also seen when roflumilast is added to long-acting bronchodilators, and in patients who are not controlled on fixed dose LABA/ICS combinations. In the intention-to-treat population, the frequency of moderate-to-severe exacerbations was 13.2% lower in the roflumilast group than in the placebo group in the Poisson regression analysis (rate ratio [RR] = 0.868, 95% confidence interval (CI) [0.735–1.002], p = 0.0529), and was 14.2% lower (RR = 0.858, 95% CI [0.740–0.995], p = 0.0424) in the negative binomial regression analysis (Martinez et al., 2015). No study has compared roflumilast with an ICS.
The most frequent adverse effects of this once daily oral agent are diarrhea, nausea, reduced appetite, weight loss, abdominal pain, sleep disturbance, and headache. Adverse effects seem to occur early during treatment, are reversible, and diminish over time with continued treatment. In controlled studies, an average unexplained weight loss of 2 kg (4.4 lb) has been seen and weight monitoring during treatment is advised in addition to avoiding roflumilast treatment in underweight patients (Global Initiative for Chronic Obstructive Lung Disease, 2018). Roflumilast should also be used with caution in patients with depression.