The effects of dual IQOS and cigarette smoke exposure on airway epithelial cells: implications for lung health and respiratory disease pathogenesis

Abstract

BackgroundCigarette smoking (CS) remains the primary cause of chronic lung diseases. After a steady decline, smoking rates have recently increased especially with the introduction of newer electronic nicotine delivery devices, and it is also emerging that dual or poly product usage is on the rise. Additionally, with the introduction of IQOS (a heated tobacco product) globally, its impact on human health needs to be investigated. In this study we tested if dual exposure (CS+IQOS) is detrimental to lung epithelial cells when compared to CS or IQOS exposure alone.MethodsHuman airway epithelial cells (BEAS-2B) cells were exposed to either CS or IQOS or their dual combinations at concentrations 0.1, 1.0, 2.5 and 5.0%. Cytotoxicity, oxidative stress, mitochondrial homeostasis, mitophagy, and effects on epithelial mesenchymal transition (EMT) signaling were assessed.ResultsBoth CS and IQOS alone significantly induced loss of cell viability in a concentration-dependent manner which was further enhanced by dual exposure compared to IQOS alone (p<0.01). Dual exposure significantly increased oxidative stress and perturbed mitochondrial homeostasis when compared to CS or IQOS alone (p<0.05). Additionally, dual exposure induced EMT signaling as shown by increased in mesenchymal (α-SMA and N-cadherin) and decreased epithelial (E-cadherin) markers when compared to CS or IQOS alone (p<0.05).ConclusionCollectively, our study demonstrates that dual exposure enhances pathogenic signaling mediated by oxidative stress and mitochondrial dysfunction leading to EMT activation which is an important regulator of small airway fibrosis in obstructive lung diseases.

Heated tobacco product (IQOS) induced pulmonary infiltrates

“…Transcriptomic changes associated with oxidative stress were more prominent at 4 hours of exposure, suggesting early adaptive mechanisms and antioxidant responses that varied based on the intensity of exposure [ 13 ]. Moreover, in a mouse model exposed to an intensive puffing regime of HTPs, characterized by 5 hours of exposure per day over a 2-week period, significant increases in proinflammatory cytokines, chemokines, and CD4+RORγt + T cells were observed in bronchoalveolar lavage fluid [ [25] , [26] , [27] , [28] , [29] ]. These findings shed light on the underlying cellular mechanisms contributing to various inflammatory pathologies like organizing pneumonia in our case, respiratory infections, inflammation, autoimmune diseases, asthma, and chronic obstructive pulmonary disease (COPD).…”

The Product Science of Electrically Heated Tobacco Products: An Updated Narrative Review of the Scientific Literature

“…Three studies were identified that utilized bubbled smoke/aerosol extracts to compare the in vitro toxicological effects of HTP aerosol with cigarette smoke in respiratory tract cell lines [ 40 , 77 , 78 ]. In the first study, the effects of liquid extracts of aerosol produced from both the Glo and IQOS HTP on oxidative stress in a human lung fibroblast cell line were investigated [ 77 ].…”

“…In the third study, human bronchial epithelial (BEAS-2B) cells were used to investigate the effect of dual product use on a range of in vitro endpoints, including cell viability and oxidative stress [ 78 ]. Liquid extracts were produced by bubbling aerosol or smoke from one IQOS HTP consumable or one Marlboro Red cigarette into phosphate-buffered saline, and the resulting stock solution was used to create serial dilutions for testing.…”

RNA sequencing analysis of early-stage atherosclerosis in vascular-on-a-chip and its application for comparing combustible cigarettes with heated tobacco products

“…Various studies have been conducted to estimate the potential risk of HTPs. The main interests of researchers regarding HTPs are the toxicological concerns and their risk in the respiratory tract ( Dempsey, 2023 , Saha, 2023 , Muratani, 2023 ) because HTPs are inhalable products and have similar behavior of use as cigarettes. To date, several reports related to the reduced risk potential of HTPs for CVD have been published.…”