COPD as a Self-Sustaining Loop System: A Multi-Target Intervention Framework

Chronic Obstructive Pulmonary Disease (COPD) is maintained by a network of interlocking feedback loops that persist after the initial trigger (smoke, pollution, infection, or occupational dust) has been removed. Current inhaled corticosteroids and bronchodilators suppress inflammatory outputs without addressing the loops themselves. This document proposes a framework in which COPD is organized into six interconnected loops: three amplification loops (1–3) that escalate acute tissue injury, and three persistence loops (4–6) that maintain chronicity. Interventions targeting each of the persistence loops are proposed based on published mechanistic evidence from distinct fields, and a phased research plan is outlined for their evaluation. The synthesis draws on recent (2024–2026) findings across pulmonary immunology, epigenetics, metabolomics, geroscience, and comparative biology.