Modeling COPD in <i>Drosophila melanogaster</i> by cigarette smoke inhalation: functional changes and alterations in the expression of COPD-relevant orthologous genes

Chronic obstructive pulmonary disease (COPD) ranks as the fourth leading cause of mortality worldwide. Long-term exposure to airway irritants such as smoking and air pollution is the main risk factor for developing the disease. Expanding on previous in silico findings on COPD-relevant orthologous genes between humans and <i>Drosophila melanogaster</i>, we experimentally investigated the contribution of cigarette smoke (CS) inhalation exposure to the induction of COPD-related physiological and transcriptomic modifications. Adult flies 2-4 days old were exposed to CS via inhalation for 20 min over five consecutive days. The metabolic rate, locomotor activity, body mass, total body length, and the expression of COPD-specific genes were measured and compared between the exposed and unexposed groups. CS inhalation exposure significantly increased the metabolic rate and decreased the locomotor activity, body weight, and total body length. Transcriptomic changes were more profound in females, indicating sex-specific differences in CS-induced molecular responses. Functional enrichment analyses of the differentially expressed COPD-relevant genes in females pointed toward ABC transporters, miR-313 microRNA, abnormal developmental rate, DNA repair, and cell differentiation. Our results indicate that <i>D. melanogaster</i> is a powerful model organism for studying the pathophysiological changes associated with COPD. Future work should focus on establishing tracheolar-related changes that would reflect histopathological perturbations similar to COPD patients' airways.<b>NEW & NOTEWORTHY</b> Inhalation exposure of adult <i>D. melanogaster</i> to cigarette smoke induced changes in physiological parameters and the expression of COPD-associated orthologous genes. Transcriptomic responses were more profound in females, indicating sex-specific responses to inhaled toxicants. Furthermore, enrichment analyses of the differentially expressed genes in females pointed to biomolecules associated with response to nicotine and detoxification. <i>D. melanogaster</i> thus provides a powerful model system to test the efficacy of new potential drugs for COPD treatment.