A 58-year-old man with a 40 pack-year smoking history presents with progressive dyspnea, chronic productive cough, and recurrent respiratory tract infections. Spirometry shows FEV₁ 35% predicted with poor bronchodilator response. He is already on inhaled corticosteroids and long-acting beta-2 agonists. What is the drug of choice to reduce exacerbation frequency and mortality in this patient?