Pathophysiology
Clinical meaning
COPD pharmacotherapy follows a stepwise approach guided by the GOLD ABE assessment and blood eosinophil count. LAMA (tiotropium, umeclidinium) provides 24-hour bronchodilation via M3 receptor blockade and reduces exacerbations. LABA (salmeterol, formoterol, vilanterol, indacaterol) provides sustained beta-2-mediated bronchodilation. LAMA + LABA dual bronchodilation is preferred over ICS-LABA for most COPD patients. ICS addition (triple therapy) is reserved for patients with blood eosinophils >= 300 cells/mcL or >= 100 with recurrent exacerbations, as the IMPACT and ETHOS trials demonstrated exacerbation reduction in this phenotype. ICS increases pneumonia risk in COPD (NNH approximately 30 per year) and should be avoided when eosinophils < 100. PDE4 inhibitors (roflumilast) are add-on therapy for chronic bronchitis phenotype with FEV1 < 50%. Azithromycin prophylaxis (250mg daily or 3x/week) reduces exacerbations in former smokers without hearing impairment or QT prolongation.