Comprehensive Physiology Wiley Online Library

Pathogenesis of E‐Cigarette Vaping Product Use‐Associated Lung Injury (EVALI)

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EVALI is an acute inflammatory disease in response to lung cell injury induced by electronic cigarettes and vaping devices (EV) frequently containing Vitamin E Acetate or tetrahydrocannabinol additives, in the context of risk factors such as microbial exposure. EVALI resembles a respiratory viral illness that may progress to acute respiratory failure and acute respiratory distress syndrome (ARDS) but can also affect extra pulmonary organs. Manifestations may be severe, leading to death or long‐term morbidity and current treatments are largely supportive. While COVID‐19 has demanded public and research attention, EVALI continues to affect young individuals and its better understanding via research remains a priority. Although clinical research led to improved recognition of triggers, clinical and pathological manifestations, and natural course of EVALI, important questions remain that require a better understanding of disease pathogenesis. Preclinical models utilizing laboratory animals and cell or tissue culture platforms provide insight into the physiologic and mechanistic consequences of acute and chronic EV exposure, including the characteristics of the respiratory dysfunction and inflammatory response. However, a key limitation in the field is the absence of an established animal model of EVALI. Important areas of research emphasis include identifying triggers and risk factors to understand why only certain vapers develop EVALI, the role of specific lung immune and structural cells in the pathogenesis of EVALI, and the most important molecular mediators and therapeutic targets in EVALI. © 2023 American Physiological Society. Compr Physiol 13:4617‐4630, 2023.

Figure 1. Figure 1. Schematic of triggers and pathways involved in EVALI pathogenesis. Made in © BioRender ‐
Figure 2. Figure 2. Effect of EV on lung cell barriers. (A) Measurement system for barrier measurement using Electric Cell‐Substrate Impedance Sensing (ECIS) using the 8WFilter and TEER24 units. (B) Effect of EV Juul brand juice, containing 10% nicotine on barrier function in small airway epithelial cells (SAEC) grown on air‐liquid interface; shown for comparison is TER of SAEC exposed to cigarette smoke (CS) extract (10%) and TER of human bronchial epithelial cell line Beas2B exposed to vitamin E acetate. Effect of Juul juice containing 5% (low) or 10% nicotine on primary human lung microvascular cells (HLMVEC). Trans‐cellular electrical resistance (TER) was measured in real time using ECIS and normalized by baseline resistance. A decrease in TER signifies loss of barrier function. Note that EV weakens the barrier of lung microvascular barrier in a nicotine‐dose‐dependent manner, but not that of lung epithelial barrier, which in turn is weakened by vitamin E acetate. Each tracing reflects one experiment that is representative of n = 3–10.

Figure 1. Schematic of triggers and pathways involved in EVALI pathogenesis. Made in © BioRender ‐

Figure 2. Effect of EV on lung cell barriers. (A) Measurement system for barrier measurement using Electric Cell‐Substrate Impedance Sensing (ECIS) using the 8WFilter and TEER24 units. (B) Effect of EV Juul brand juice, containing 10% nicotine on barrier function in small airway epithelial cells (SAEC) grown on air‐liquid interface; shown for comparison is TER of SAEC exposed to cigarette smoke (CS) extract (10%) and TER of human bronchial epithelial cell line Beas2B exposed to vitamin E acetate. Effect of Juul juice containing 5% (low) or 10% nicotine on primary human lung microvascular cells (HLMVEC). Trans‐cellular electrical resistance (TER) was measured in real time using ECIS and normalized by baseline resistance. A decrease in TER signifies loss of barrier function. Note that EV weakens the barrier of lung microvascular barrier in a nicotine‐dose‐dependent manner, but not that of lung epithelial barrier, which in turn is weakened by vitamin E acetate. Each tracing reflects one experiment that is representative of n = 3–10.
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Irina Petrache, Arnav Gupta, Patrick S. Hume, Tanner Rivera, Kelly S. Schweitzer, Hong Wei Chu. Pathogenesis of E‐Cigarette Vaping Product Use‐Associated Lung Injury (EVALI). Compr Physiol 2023, 13: 4617-4630. doi: 10.1002/cphy.c220022