Therapeutic Routes of Drug Administration in Chronic Obstructive Pulmonary Disease: Evidence-based Evaluation.

Abstract

Chronic obstructive pulmonary disease (COPD) remains a major global healthcare burden, necessitating multimodal pharmacologic strategies optimized for effective drug delivery. Inhalation is the preferred route due to targeted pulmonary deposition, rapid onset, reduced systemic exposure, and lower dose requirements. Pressurized metered-dose inhalers, dry-powder inhalers, soft-mist inhalers, and nebulizers demonstrate proven efficacy; however, effectiveness is limited by patient technique, inspiratory capacity, and device-dependent variability. Oral agents, including corticosteroids, phosphodiesterase-4 inhibitors, and theophylline, provide systemic anti-inflammatory and bronchodilator effects but are constrained by adverse event profiles and narrow therapeutic windows. Parenteral therapy, such as intravenous corticosteroids and bronchodilators, remains primarily reserved for severe exacerbations; however, evidence suggests limited superiority over oral corticosteroids. Intravenous alpha-1 antitrypsin replacement offers a disease-modifying benefit in genetically deficient populations, slowing emphysema progression and improving survival. Transdermal nicotine replacement therapy contributes indirectly to COPD management via smoking cessation support. Collectively, inhalation continues to dominate COPD maintenance therapy, while systemic routes are reserved for specific indications. The optimal outcomes depend on individualized route selection based on disease severity, patient ability, and therapeutic goals.