Mitochondrial dysfunction in the airway epithelium is associated with Chronic Obstructive Pulmonary Disease (COPD). However, the mechanisms of how mitochondrial dysfunction might be contributing to COPD are poorly understood.

This study aims to identify whether there are changes in mitochondrial function in the bronchial epithelium of COPD patients compared to healthy ex-smokers (H-ES).

We analysed an RNAseq dataset derived from bronchial brushes from a cohort of healthy ex-smokers (n=17) and COPD (n=31) (Hristova et al., ERJ 2023) for differentially expressed mitochondrial associated genes using DESeq and EdgeR. We also used primary bronchial epithelial cells (PBEC) from H-ES (n=6) and COPD (n=7) donors to generate airway organoids. We analysed the cellular bioenergetics of these organoids using a Seahorse XF analyser.

The RNAseq analysis identified 27 mitochondrial associated differentially expressed genes in COPD, the top hit was AKR1B10 (p<0.0001). We also showed that COPD organoids have a 1.77-fold reduction in mitochondrial spare respiratory capacity compared to H-ES (p-value = 0.035). There were no significant differences between COPD and H-ES in basal respiration, mitochondrial ATP production or glycolysis rates.

Spare respiratory capacity is essential for cells under stress which increases energy demands. This reduced reserve could make the COPD epithelium more susceptible to acute stressors like pathogens and pollutants as well as impacting on tissue repair and remodelling following damage. Further investigations are needed to understand whether the reduced mitochondrial reserve and changes in gene expression are connected.