Investigating human lung resilience, its evolutionary history and its relation to COPD.

Abstract

A subset of long-term smokers remain free of chronic obstructive pulmonary disease or lung cancer, a phenomenon termed "lung resilience." Understanding this resilience could reveal protective mechanisms that preserve respiratory health, yet conceptual and methodological precision is required. Importantly, resilience is not merely the inverse of vulnerability, but a process that can be investigated in its own. In this review, we clarify this concept of resilience and its distinction from tolerance and resistance, and situate human lung resilience within a cross-organ and cross-species framework. We also critically assess the hypothesis that evolutionary processes may have influenced human resilience to smoke exposure. Finally, we advocate for rigorous clinical phenotyping and mechanistic approaches to dissect the interplay between genetics, physiology, and evolution. A refined conceptual framework will establish resilience as a productive paradigm in respiratory medicine, with potential to advance our understanding of disease susceptibility and to inform novel therapeutic strategies.