azithromycin vs roflumilast

Prophylactic azithromycin has been shown to significantly reduce exacerbations when added to usual care, with this effect being greatest in patients who previously smoked cigarettes (vs those who are still smoking) and in those with an exacerbation history in the previous 12 months (choice A is correct). Azithromycin is a macrolide with antibacterial, anti-inflammatory, and immunomodulating qualities. Global Initiative for Chronic Obstructive Lung Disease guidelines recommend azithromycin at dosages of 250 mg/day or 500 mg three times per week for patients who continue to have exacerbations despite being on triple therapy. Monitoring for long-term adverse events attributed to treatment, including the development of resistant organisms, impaired hearing, and prolongation of corrected QT interval is warranted.

Roflumilast, a phosphodiesterase-4 inhibitor, has been shown to decrease exacerbations in patients with a chronic bronchitis phenotype who have severe to very severe COPD and a history of exacerbations. This patient’s clinical history does not suggest chronic bronchitis. In addition, roflumilast should generally be avoided in underweight patients, such as the patient presented here, based on the association of treatment with unintentional weight loss.

Benralizumab is a monoclonal antibody that is directed against the alpha chain of the IL-5 receptor and causes a depletion of eosinophils. It is estimated that up to 40% of patients with COPD may have eosinophilic inflammation, raising the possibility of a role for biologic therapy. In pooled data from over 2,500 patients with a blood eosinophil count ≥220/μL (≥0.2 ×109/L) who had moderate to very severe COPD and a history of frequent exacerbations on double or triple therapy, those patients who received add-on benralizumab failed to demonstrate a lower annual rate of COPD exacerbations despite a significant reduction in blood eosinophil counts. Studies with mepolizumab, an anti-IL-5 monoclonal antibody, used different inclusion criteria and showed variable results regarding reduction in exacerbations, suggesting a potential role for these agents in selected populations.

The addition of an ICS to long-acting bronchodilator therapy is recommended in patients with moderate to very severe COPD with a history of exacerbations and has been shown to be effective in reducing future exacerbations. Studies exploring the effects of withdrawing ICS in stable patients have yielded conflicting results, with some showing no change in exacerbations and others showing an increase in exacerbations. Studies correlating exacerbation frequency and blood eosinophil count have shown that higher eosinophil counts are associated with a greater frequency of exacerbations following ICS withdrawal (choice D is incorrect). As inhaled steroids can be associated with increased bacterial infections and pneumonia, the inclusion of this class of medication should be based on clinical guidelines.

This patient has chronic bronchitis and is losing weight due to an adverse effect of roflumilast (choice D is correct). Roflumilast is a selective phosphodiesterase-4 (PDE-4) inhibitor that is approved for use in patients with a chronic bronchitis phenotype and a history of at least two COPD exacerbations/year or one requiring hospitalization. The proposed mechanism of action centers on the increase in intracellular cyclic adenosine monophosphate (cAMP) that follows inhibition of PDE-4, leading to decreased inflammation associated with COPD. Clinical studies have demonstrated that the rate of moderate (treated with systemic corticosteroids) and severe (requiring hospitalization) exacerbations of COPD were reduced when roflumilast was added to regimens that included combination inhaled steroid/long-acting beta-agonists with or without a long-acting muscarinic antagonists, in patients who had two or more COPD exacerbations in the prior year. A modest but significant decrease in albuterol was also reported with roflumilast therapy. In post hoc analyses, patients who had more frequent exacerbations in the year prior to roflumilast treatment had an even lower rate of exacerbations and time to rehospitalization on roflumilast. While roflumilast is not a bronchodilator, postbronchodilator FEV1 increases significantly in patients treated with roflumilast compared to placebo.

Adverse effects of roflumilast are most commonly gastrointestinal symptoms including diarrhea (8-9%) and nausea (5%). Weight loss has also been noted in 6 to 12% of patients, as was the case in the patient presented here. An increase in psychiatric reactions has also been reported. Drug interactions occur with inducers and inhibitors of CYP 3A4 (inducers: such as rifampicin and carbamazepine, which may reduce its therapeutic effectiveness, as well as inhibitors such as erythromycin, cimetidine, and protease inhibitors, which may increase roflumilast systemic exposure). Treatment is contraindicated in patients with moderate-to-severe hepatic impairment (Child-Pugh class B or C).

Megesterol acetate is a progesterone derivative that improves appetite and is associated with slight weight gain in patients with cancer. Treatment of the cause of weight loss is more appropriate. There is limited evidence for progesterone therapy in noncancer cachexia (choice A is incorrect).

The 2-mm nodule is unlikely to represent a neoplasm causing cachexia. An abdominal CT scan would not be the next most appropriate step in this individual (choice B is incorrect). A PET scan is not a screening test for unintentional weight loss (choice C is incorrect).