Metabolic reprogramming: A driver of cigarette smoke-induced inflammatory lung diseases

Cigarette smoking is a well-known risk factor for pulmonary diseases, including chronic obstructive pulmonary disease (COPD), asthma and pulmonary fibrosis. Despite major progress in dissecting the mechanisms associated with disease development and progression, findings only represent one aspect of multifaceted disease. A crucial consequence of this approach is that many therapeutic treatments often fail to improve or reverse the disease state as other conditions and variables are insufficiently considered. To expand our understanding of pulmonary diseases, omics approaches, particularly metabolomics, has been emerging in the field. This strategy has been applied to identify putative biomarkers and novel mechanistic insights. In this review, we discuss metabolic profiles of patients with COPD, asthma, and idiopathic pulmonary fibrosis (IPF) with a focus on the direct effects of cigarette smoking in altering metabolic regulation. We next present cell- and animal-based experiments and point out the therapeutic potential of targeting metabolic reprogramming in inflammatory lung diseases. In addition, the obstacles in translating these findings into clinical practice, including potential adverse effects and limited pharmacological efficacy, are also addressed. [Display omitted] •Smoke exposure causes inflammatory response and multiple pathophysiological processes via metabolic dysregulation.•The alteration of mitochondrial functions drives emphysema for chronic obstructive pulmonary disease.•Arginine reprogramming and mitochondrial fragmentation promote airway remodeling in allergic asthma.•TGF-β1 upregulates metabolic flux for lung fibroblast activation in pulmonary fibrosis.