The Effects of Dual IQOS and Cigarette Smoke Exposure on Airway Epithelial Cells: Implications for Lung Health and Respiratory Disease Pathogenesis

Background Cigarette 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.

Methods Human 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.

Results Both 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).

Conclusion Collectively, 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.