Similarity of sputum mediator signatures between e-cigarette users and COPD depends on GOLD stage and type of e-cigarette: a pilot study

There is overlap in symptoms and airway pathobiology between COPD and e-cigarette (e-cig) users. We sought to determine if young adult e-cig users have similar sputum soluble mediator profiles to COPD and if this is related to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage and generation of e-cig device. Experimental groups (n = 20-30/group) included non-smokers, smokers at risk of COPD ("pre-COPD"), mild/moderate COPD (GOLD 1/2), and severe COPD (GOLD 3) from the SPIROMICS cohort and healthy e-cig users of 3rd and 4th generation devices (previously published). Sputum soluble mediator profiles were compared between COPD GOLD stages and then between e-cig users of both generation devices and COPD participants by GOLD stage using a suite of computational approaches, including correlation analyses, unsupervised machine learning, and multivariate distance metrics. Inflammatory mediators were significantly increased in pre-COPD and GOLD 3 versus non-smokers and GOLD 1/2. Soluble mediator profiles of e-cig users showed patterns of overlap with COPD that were GOLD stage specific and based on shared biological functions that included proteases (MMP9, MMP2) and elastases (neutrophil elastase, myeloperoxidase). These findings indicate similarities in soluble mediator profiles between e-cig users and patients with COPD, highlighting potentially similar biological mechanisms relating to inflammation and tissue remodeling. Future studies with younger COPD cohorts, and those with preserved ratio impaired spirometry (PRISm) or bronchitis versus apical emphysema are needed to fully understand the extent of biological mechanisms that are shared between e-cig users and COPD. This pilot study represents a first step in understanding potential similarities between mediator changes in the airways of COPD patients and otherwise healthy young adult e-cig users.