Chronic obstructive pulmonary disease (COPD) patients frequently suffer from multiple comorbidities, resulting in poor outcomes for these patients. Diabetes is observed at a higher frequency in COPD patients than in the general population. Both type 1 and 2 diabetes mellitus are associated with pulmonary complications, and similar therapeutic strategies are proposed to treat these conditions. Epidemiological studies and disease models have increased our knowledge of these clinical associations. Several recent genome-wide association studies have identified positive genetic correlations between lung function and obesity, possibly due to alterations in genes linked to cell proliferation; embryo, skeletal, and tissue development; and regulation of gene expression. These studies suggest that genetic predisposition, in addition to weight gain, can influence lung function. Cigarette smoke exposure can also influence the differential methylation of CpG sites in genes linked to diabetes and COPD, and smoke-related single nucleotide polymorphisms are associated with resting heart rate and coronary artery disease. Despite the vast literature on clinical disease association, little direct mechanistic evidence is currently available demonstrating that either disease influences the progression of the other, but common pharmacological approaches could slow the progression of these diseases. Here, we review the clinical and scientific literature to discuss whether mechanisms beyond preexisting conditions, lifestyle, and weight gain contribute to the development of COPD associated with diabetes. Specifically, we outline environmental and genetic confounders linked with these diseases.

Alpha-1 antitrypsin (AAT) has established anti-inflammatory and immunomodulatory effects in chronic obstructive pulmonary disease but there is increasing evidence of its role in other inflammatory and immune-mediated conditions, like diabetes mellitus (DM). AAT activity is altered in both developing and established type 1 diabetes mellitus (T1DM) as well in established type 2 DM (T2DM). Augmentation therapy with AAT appears to favorably impact T1DM development in mice models and to affect β-cell function and inflammation in humans with T1DM. The role of AAT in T2DM is less clear, but AAT activity appears to be reduced in T2DM. This article reviews these associations and emerging therapeutic strategies using AAT to treat DM.

The safety of electronic cigarettes (e-cigarettes) is a major topic of discussion. The key goals of this study were to examine the contents of e-cigarette vapor and determine if nicotine altered inflammatory responses against respiratory syncytial virus (RSV) infection. E-cigarette vapor was passed through a hollow 3D-model of an adult lung, and gas chromatography detected over 50 compounds passed through the 3D model, including nicotine, propylene glycol (PG), ethanol, methanol, and diacetyl. The murine alveolar macrophage cell line MH-S cells were exposed to nicotine and e-cigarette vapor with and without nicotine. Nicotine significantly induced the expression of matrix metalloprotease (Mmp) 12 and reduced expression of Ifnβ and Tnfα. To examine the role of nicotine in lung defense against RSV infection, A/J mice were exposed to PBS, e-cigarette vapor with and without nicotine for 2 months before RSV infection. E-cigarette vapor did not influence RSV infection-induced animal weight loss, RSV infectivity, airway hyperresponsiveness during methacholine challenge, or immune cell infiltration into the lungs. However, e-cigarette vapor containing nicotine enhanced obstruction and induced secretion of MMP12 and reduced levels of Ifnβ and TNFα. In conclusion, nicotine in vaping products modulates immune responses that may impact the lungs during a respiratory infection.