Cardiopulmonary Consequences of Vaping in Adolescents: A Scientific Statement From the American Heart Association.

Although the US Food and Drug Administration has not approved e-cigarettes as a cessation aid, industry has at times positioned their products in that way for adults trying to quit traditional cigarettes; however, their novelty and customizability have driven them into the hands of unintended users, particularly adolescents. Most new users of e-cigarette products have never smoked traditional cigarettes; therefore, understanding the respiratory and cardiovascular consequences of e-cigarette use has become of increasing interest to the research community. Most studies have been performed on adult e-cigarette users, but the majority of these study participants are either former traditional smokers or smokers who have used e-cigarettes to switch from traditional smoking. Therefore, the respiratory and cardiovascular consequences in this population are not attributable to e-cigarette use alone. Preclinical studies have been used to study the effects of naive e-cigarette use on various organ systems; however, almost all of these studies have used adult animals, which makes translation of health effects to adolescents problematic. Given that inhalation of any foreign substance can have effects on the respiratory and cardiovascular systems, a more holistic understanding of the pathways involved in toxicity could help to guide researchers to novel therapeutic treatment strategies. The goals of this scientific statement are to provide salient background information on the cardiopulmonary consequences of e-cigarette use (vaping) in adolescents, to guide therapeutic and preventive strategies and future research directions, and to inform public policymakers on the risks, both short and long term, of vaping.

Agonistic induction of PPARγ reverses cigarette smoke-induced emphysema.

The development of emphysema in humans and mice exposed to cigarette smoke is promoted by activation of an adaptive immune response. Lung myeloid dendritic cells (mDCs) derived from cigarette smokers activate autoreactive Th1 and Th17 cells. mDC-dependent activation of T cell subsets requires expression of the SPP1 gene, which encodes osteopontin (OPN), a pleiotropic cytokine implicated in autoimmune responses. The upstream molecular events that promote SPP1 expression and activate mDCs in response to smoke remain unknown. Here, we show that peroxisome proliferator-activated receptor γ (PPARG/Pparg) expression was downregulated in mDCs of smokers with emphysema and mice exposed to chronic smoke. Conditional knockout of PPARγ in APCs using Cd11c-Cre Pparg(flox/flox) mice led to spontaneous lung inflammation and emphysema that resembled the phenotype of smoke-exposed mice. The inflammatory phenotype of Cd11c-Cre Pparg(flox/flox) mice required OPN, suggesting an antiinflammatory mechanism in which PPARγ negatively regulates Spp1 expression in the lung. A 2-month treatment with a PPARγ agonist reversed emphysema in WT mice despite continual smoke exposure. Furthermore, endogenous PPARγ agonists were reduced in the plasma of smokers with emphysema. These findings reveal a proinflammatory pathway, in which reduced PPARγ activity promotes emphysema, and suggest that targeting this pathway in smokers could prevent and reverse emphysema.

A protease-activated pathway underlying Th cell type 2 activation and allergic lung disease.

The respiratory allergens that induce experimental Th cell type 2-dependent allergic lung inflammation may be grouped into two functional classes. One class of allergens, in this study termed type I, requires priming with adjuvants remote from the lung to overcome airway tolerogenic mechanisms that ordinarily preclude allergic responses to inhaled Ags. In contrast, the other, or type II, allergen class requires neither remote priming nor additional adjuvants to overcome airway tolerance and elicit robust allergic lung disease. In this study, we show in an experimental model that diverse type II allergens share in common proteolytic activity that is both necessary and sufficient for overcoming airway tolerance and induction of pulmonary allergic disease. Inactivated protease and protease-free Ag fragments showed no allergenic potency, demonstrating that only active protease acting on endogenous substrates was essential. Furthermore, induction of airway tolerance could be aborted and allergic lung disease established by simply adding purified protease to a type I allergen. Thus, exogenous proteases are common to type II allergens and may be generally required to overcome the innate resistance of the airway to Th cell type 2 activation and allergic inflammation, raising concern for their potential contribution to diseases such as asthma.