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IQOS product use in adults who smoke cigarettes daily does not change respiratory inflammatory markers

Thies, J. L.; Appleseth, H. J.; Yamaguchi, N.; Bose, P. G.; Speen, A. M.; Peraza, N.; Cobos-Uribe, C.; Perryman, A. A.; Tackett, A. P.; Rebuli, M. E.

2025-11-19 respiratory medicine
10.1101/2025.11.17.25339937 medRxiv
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IntroductionThe use and availability of heated tobacco products has increased globally. However, the health effects of IQOS product use remain contradictory, and the impact of IQOS product use on respiratory health and immune biomarkers is lacking. Industry sponsored studies suggest IQOS products reduce exposure to harmful chemicals compared to conventional cigarettes and show attenuated inflammatory responses compared to cigarette smoke, yet independent research studies indicate exposure to IQOS is still associated with negative health outcomes similar to conventional cigarettes. Clinical data is needed to understand the respiratory health impacts of IQOS use in people who currently smoke cigarettes. MethodsAdults located in Los Angeles, California were recruited for the Adult IQOS Respiratory Study (AIRS, N = 32; 21-65 years). Nasal epithelial lining fluid (NELF) and saliva collected from adults who were willing to incorporate IQOS into their daily habits, were analyzed by multiplex enzyme linked immunosorbent assays for 29 different inflammatory markers or cotinine, respectively. Repeated measures ANOVA were used to identify changes in immune markers across the weekly visits. Linear mixed modelling was used to identify changes in participant cigarette or IQOS HeetStick use over the study period. Day was added as a fixed effect. ResultsBetween-participants variability in IQOS or cigarette usage was identified (p < 0.0001). IQOS and cigarette use did not significantly change across time and remained stable over the course of the 4-week study period. No significant changes were identified in soluble protein mediators across each week. Cotinine concentrations remained consistent, even when disaggregated by sex and visit. ConclusionsAll together, these data highlight that dual product use may be more likely in individuals who smoke cigarettes, particularly over the first month of incorporation, rather than completely switching to IQOS products when provided. Furthermore, incorporating IQOS did not significantly change nicotine exposure or nasal inflammatory biomarkers, suggesting, at least with nicotine exposure and nasal inflammation, that addition of heated tobacco products may not substantially reduce harm. What is already known on this topicHeated tobacco products are marketed as less harmful and smoke-free alternative products compared to conventional cigarettes; however, lack of respiratory data and contradictory reports suggest they may still pose risks and use may contribute to consequential health impacts. Short-term and industry sponsored studies are available, but limited clinical data exists on the respiratory and immunological impacts of IQOS product use. What this study addsIn the follow repeated measures study, our findings provide clinical evidence there are no significant differences in nasal immune biomarkers in individuals that smoke, who incorporate IQOS into their lifestyles. While each participant varied in their IQOS and cigarette product use, no significant trends were observed over the four-week sampling period in overall IQOS or cigarette use. Additionally, when participants were provided with the IQOS option, they were more inclined to dual use both products rather than switch from cigarettes to only IQOS use in the 4 week period studied. How this study might affect research, practice or policyThe following clinical study suggests there is an increased likelihood of dual use among individuals who are provided alternative tobacco products. Additional studies should consider evaluating health differences, including immunological markers, between individuals who dual use IQOS and other tobacco products, exclusively use IQOS, people who completely switch their product use and people who quit altogether to establish whether IQOS use reduces harmful exposures resulting in differential inflammatory responses when compared to cigarette use.

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