Smoker's Lungs: Quo Vadis? Exploring the Shared and Individual Smoking-Related Molecular Pathways of Emphysema, Carcinoma, and Fibrosis - An Illustrative Review.

Cigarette smoking is a major preventable risk factor for the development of lung cancer and chronic obstructive pulmonary disease (COPD); furthermore, it is also associated with idiopathic pulmonary fibrosis (IPF). Cigarette smoke primarily induces chronic epithelial injury in the lungs, initiating a cascade of interconnected molecular responses within the pulmonary microenvironment. Aiming to explore the common and individual important pathways in the processes of malignant alteration (non-small cell carcinoma), lung tissue destruction (emphysema in the context of COPD), and aberrant healing (IPF), we conducted a narrative review in which we explore the roles of various selected processes, including NFκB activation, mitochondrial dysfunction, the role of reactive oxygen species, and the antioxidant response via Keap1/Nrf2 and TGFβ-mediated signaling, in the context of their respective disease. This review is not meant to represent an exhaustive reference of pathophysiologic processes involved in the pathogenesis of these diseases, but to illustrate the common features and specific differences among the selected disease processes. Given the persistent global burden of tobacco use, further research into the interconnected molecular consequences of cigarette smoke exposure remains essential for advancing both preventive and therapeutic approaches in pulmonary medicine.