REGULATORYSCIENCE
Improving Public Health With Tobacco Regulatory Science Anesthesiologists recognized early that smoking cessation greatly improves surgical outcomes. The Jordt laboratory in the department’s Center for Translational Pain Medicine (CTPM) has become a major contributor to regulatory science supporting smoking cessation and tobacco control. Regulatory science helps agencies like the US Food and Drug Administration (FDA) to assess the safety of pharmaceuticals, medical devices, foods, and the public health impact of tobacco products. Dr. Sven-Eric Jordt, director of the Chemical Sensing, Pain and Inflammation Laboratory within the CTPM, contributed to breakthrough discoveries in pain research in the laboratory of Nobel Laureate David Julius. In 2004, Jordt discovered a receptor in pain-sensing nerves, TRPA1, activated by many noxious chemicals, including irritants in tobacco smoke, toxic chlorine gas and tear gas agents that cause severe pain and nerve-mediated inflammation. Jordt continued to study these mechanisms in his own laboratory, established at Yale in 2005 and relocated to Duke in 2014, in collaboration with Duke Anesthesiology’s Drs. Satya Achanta and Anabel Caceres.
facilitated the inhalation of cigarette smoke and increased nicotine blood levels in mice, proving that menthol cigarettes are more addictive. These findings were cited in the FDA’s 2022 proposal to ban menthol cigarettes and in state bans that led to a significant drop in smoking rates. When Jordt learned that the tobacco industry had launched “non-menthol” versions of menthol cigarette brands banned in California, he and Duke Anesthesiology’s Dr. Sairam Jabba, sprung into action. They detected a cooling synthetic menthol derivative in “non-menthol” cigarettes, added by tobacco manufacturers to circumvent California’s menthol ban. This study, published in the Journal of the American Medical Association (JAMA), caught the eye of California legislators who, in consultation with Jordt, passed a new law that bans any cooling agents in cigarettes, closing this regulatory loophole. Funded by the FDA/NIH Tobacco Regulatory Science Program, the Jordt lab continues to investigate the effects of chemical additives in tobacco products, including the increasingly popular electronic cigarettes. As reported in the journals Tobacco Control and JAMA, Jordt, Jabba and collaborators identified a new strategy by makers of electronic Contributing Authors of the cigarettes, bypassing regulations by 35TH SURGEON GENERAL’S REPORT ON SMOKING AND HEALTH replacing nicotine with a more potent “Eliminating Tobacco-Related Disease and Death: Addressing Disparities” analogue, 6-methyl nicotine. In • Jordt and Jabba contributed their expertise on the pharmacological and behavioral effects of response, California rapidly closed this menthol and other flavor chemicals in tobacco products. loophole, and other states are closely behind. • Their studies revealed that menthol’s cooling and pain-relieving effects make it easier to inhale Jordt has expanded his regulatory irritating tobacco smoke. advisory activities as a member of the • These effects are mediated by TRPM8, a cold- and menthol-activated ion channels in FDA’s Tobacco Product Scientific sensory nerves innervating the airways and lungs. Advisory Committee and an advisor to the World Health Organization’s Study Group on Tobacco Product Previously, Jordt studied the analgesic effects Regulation. For a basic scientist like Jordt, used to of menthol, the natural cooling compound found the often decades-long periods between scientific in peppermint. When Jordt learned in 2009 discovery and clinical translation, “the rapid that Congress had exempted menthol cigarettes translation of scientific findings into new tobacco from a ban on flavored cigarettes, he became control regulations is a breath of fresh air,” he concerned that this decision overlooked the potent says, “however, setbacks also happen.” This was pharmacological effects of menthol. Menthol has illustrated by the cancellation of the FDA’s effort proven anti-tussive effects suppressing the cough to ban menthol cigarettes nationwide in January reflex, leading Jordt to hypothesize that menthol of 2025. Committed for the long term and guided reduces the harshness of cigarette smoke. Teaming by his lab's research, Jordt persists in advocating up with Dr. John Morris, a renowned inhalation for a ban on menthol cigarettes and other flavored toxicologist, the labs reported that menthol tobacco products. 26
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