Tobacco-Related Disease Research Program Funded Publications

Tobacco use remains the single most preventable cause of disease, disability, and death in the United States and in California. The Tobacco-Related Disease Research Program (TRDRP) is one of three entities that constitute California’s program to control tobacco consumption and alleviate the burden of tobacco-related disease. This effort was initiated by Proposition 99, “The Tobacco Tax and Health Protection Act of 1988” which mandated that the Department of Health Services, the Department of Education and the University of California be allocated a portion of the tobacco tax revenue collected to address issues of tobacco consumption and its consequences in the state. Enabling legislation requested that the University of California, in its role as the research arm of the state, “administer a comprehensive grant program to support research efforts related to the prevention, causes, and treatment of tobacco-related diseases” and that “ all qualified investigators, regardless of institutional affiliation, shall have equal access and opportunity to compete for the funds.”

The TRDRP is administered by the University of California and is a program of the Research Grants Program Office (RGPO), Office of Research and Graduate Studies at the University of California, Office of the President.

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Sex differences in cigarette smoking following a mindfulness-based cessation randomized controlled trial

(2025)

Some interventions for smoking cessation such as quit smoking aids show sex-specific effects on outcomes, but behavioral interventions such as mindfulness-based interventions (MBIs) for smoking cessation lack formal reporting of sex-intervention tests of interaction to date. To address this gap, we conducted a secondary analysis of a RCT dataset (N = 213), recruiting participants from California, to statistically test a sex-intervention interaction effect on complete 7-day point prevalence abstinence (PPA), proportion of days abstinent, and daily cigarettes smoked. Smoking was assessed using the timeline follow back method spanning the four weeks following a daily 14-day app-based intervention and a planned smoking quit date immediately following the intervention phase. All models adjusted for baseline nicotine dependence. The study groups had comparable sex proportions (MBI: 56 % female; control: 55 % female) and the ratio of outcome assessment completion by group was not dependent on sex. Adjusted analyses revealed a significant sex-intervention interaction effect for daily cigarettes smoked ([female coded 1]: two-way interaction effect IRR = 0.59, 95 % CI: 0.46-0.77, p < 0.0001; effect for female: IRR = 0.68, 95 % CI: 0.57-0.81, effect for male: IRR = 1.14, 95 % CI: 0.95-1.37), but not for complete 7-day PPA ([female coded 1] two-way interaction effect OR = 1.24, 95 % CI: 0.31-4.89, p = 0.76) or proportion of total days abstinent ([female coded 1] two-way interaction effect OR = 1.97, 95 % CI: 0.53-7.37, p = 0.31). Females, but not males, allocated to a daily app-based MBI with a quit plan and quit aid workbook smoked fewer cigarettes per day compared to females in the control group. Males, but not females, showed significantly less use of the MBI app compared to the control app.

Opioid drug seeking after early-life adversity: a role for delta opioid receptors

(2024)

Opioid use disorder (OUD) is associated with a history of early-life adversity (ELA), an association that is particularly strong in women. In a rodent model, we previously found that ELA enhances risk for opioid addiction selectively in females, but the mechanisms for this effect are unclear. Here, we show that ELA robustly alters cFos responses to opioid drugs in females’ nucleus accumbens (NAc) and basolateral amygdala (BLA), but not elsewhere. We further identify delta opioid receptors (DOR), which mature in the first week of life and thus later than kappa or mu opioid receptors, as a potential mediator of ELA's impacts on reward circuit functions. Accordingly, DOR mRNA in NAc was persistently reduced in adult females with ELA history. Moreover, pharmacological stimulation of NAc DORs increased opioid demand in control females (recapitulating the ELA phenotype), while blocking DORs in ELA females conversely reduced high-effort drug consumption, simulating the control rearing phenotype. These findings support a role for NAc DORs in mediating ELA-induced opioid vulnerability. In contrast, BLA neurons expressing DOR protein do not overlap heroin- responsive cells in ELA rats, arguing against a direct relationship of BLA DORs to heroin's addiction-relevant actions in the brain. Together, these results suggest a novel and selective role for NAc DORs in contributing to enduring, ELA-provoked vulnerability to OUD.

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Effects of Cannabis Use on Cigarette Smoking Cessation in LGBTQ+ Individuals

(2024)

Objective

Sexual and gender minority individuals are more likely to use tobacco and cannabis and have lower cigarette cessation. This study examined cannabis use associations with daily cigarettes smoked in sexual and gender minority individuals before and during a quit attempt.

Method

Participants included dual smoking same-sex/gender couples from California that were willing to make a quit attempt (individual n = 205, 68.3% female sex). Participants reported baseline past 30-day cannabis use and number of cigarettes smoked and cannabis use (yes/no) during 35 nightly surveys. Individuals with current cannabis use reported baseline cannabis use and/or nightly survey cannabis use. Multilevel linear models predicted number of cigarettes smoked by cannabis use.

Results

Number of cigarettes decreased from before to during a quit attempt, but this decrease was smaller in individuals with current cannabis use compared to no current cannabis use (p < .001). In individuals with current cannabis use, number of cigarettes smoked was greater on days with cannabis use (p < .001). Furthermore, cannabis use that day increased overall number of cigarettes in those with relatively high overall cannabis use but only during a quit attempt in those with relatively low cannabis use (Within-Subject Cannabis Use × Between-Subject Cannabis Use × Quit Attempt interaction; p < .001).

Conclusions

Sexual and gender minority individuals with cannabis and cigarette use may have a harder time quitting smoking than those who do not use cannabis. For those with cannabis use, guidance on not using cannabis during a quit attempt may improve cigarette cessation outcomes. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Cover page of Policy-relevant differences between secondhand and thirdhand smoke: strengthening protections from involuntary exposure to tobacco smoke pollutants

Policy-relevant differences between secondhand and thirdhand smoke: strengthening protections from involuntary exposure to tobacco smoke pollutants

(2024)

Starting in the 1970s, individuals, businesses and the public have increasingly benefited from policies prohibiting smoking indoors, saving thousands of lives and billions of dollars in healthcare expenditures. Smokefree policies to protect against secondhand smoke exposure, however, do not fully protect the public from the persistent and toxic chemical residues from tobacco smoke (also known as thirdhand smoke) that linger in indoor environments for years after smoking stops. Nor do these policies address the economic costs that individuals, businesses and the public bear in their attempts to remediate this toxic residue. We discuss policy-relevant differences between secondhand smoke and thirdhand smoke exposure: persistent pollutant reservoirs, pollutant transport, routes of exposure, the time gap between initial cause and effect, and remediation and disposal. We examine four policy considerations to better protect the public from involuntary exposure to tobacco smoke pollutants from all sources. We call for (a) redefining smokefree as free of tobacco smoke pollutants from secondhand and thirdhand smoke; (b) eliminating exemptions to comprehensive smoking bans; (c) identifying indoor environments with significant thirdhand smoke reservoirs; and (d) remediating thirdhand smoke. We use the case of California as an example of how secondhand smoke-protective laws may be strengthened to encompass thirdhand smoke protections. The health risks and economic costs of thirdhand smoke require that smokefree policies, environmental protections, real estate and rental disclosure policies, tenant protections, and consumer protection laws be strengthened to ensure that the public is fully protected from and informed about the risks of thirdhand smoke exposure.

Early-life tobacco exposure is causally implicated in aberrant RAG-mediated recombination in childhood acute lymphoblastic leukemia

(2024)

“I’m both smoking and vaping”: a longitudinal qualitative study of US young adults who tried to quit smoking cigarettes by using electronic cigarettes

(2024)

Objective

To describe how young adults use electronic cigarettes (electronic nicotine delivery systems (ENDS)) for smoking cessation and reasons why they may or may not successfully quit smoking.

Methods

Longitudinal qualitative data were collected annually from 2017 to 2019 for 25 young adult tobacco users (aged 18-29 years) in California (USA) who used ENDS to quit/reduce smoking. Thematic and trajectory analyses were used to identify key within-person and between-person changes in tobacco/nicotine use over time.

Results

Five types of tobacco use transition were identified among baseline dual users of cigarettes and ENDS: sustained dual use without reduced smoking (n=8), transition to exclusive daily ENDS use (n=6), sustained dual use with reduced smoking (n=5), transition back to exclusive smoking (n=4) and transition to neither smoking nor vaping (n=2). Participants' ENDS use behaviour varied over time in terms of vaping quantity and device characteristics (eg, changing nicotine concentrations/flavours, switching between multiple devices). Three themes that related to successfully replacing cigarettes with ENDS were perceived positive physical effects, perceived satisfaction and enjoyment and context changes. Four themes for unsuccessful replacement were perceived negative physical discomforts, perceived addictiveness and harm, unsatisfactory substitution for cigarettes and device malfunction.

Conclusions

Young adults' experiences with using ENDS as a smoking cessation aid were highly variable. Adequate nicotine delivery and perceived safety and benefits contributed to successfully reducing or quitting cigarettes. Providing behavioural counselling and standardising ENDS products may enhance cessation for young adults.

Cover page of Nicotine inhalant via E‐cigarette facilitates sensorimotor function recovery by upregulating neuronal BDNF–TrkB signalling in traumatic brain injury

Nicotine inhalant via E‐cigarette facilitates sensorimotor function recovery by upregulating neuronal BDNF–TrkB signalling in traumatic brain injury

(2024)

Background and purpose

Traumatic brain injury (TBI) causes lifelong physical and psychological dysfunction in affected individuals. The current study investigated the effects of chronic nicotine exposure via E-cigarettes (E-cig) (vaping) on TBI-associated behavioural and biochemical changes.

Experimental approach

Adult C57/BL6J male mice were subjected to controlled cortical impact (CCI) followed by daily exposure to E-cig vapour for 6 weeks. Sensorimotor functions, locomotion, and sociability were subsequently evaluated by nesting, open field, and social approach tests, respectively. Immunoblots were conducted to examine the expression of mature brain-derived neurotrophic factor (mBDNF) and associated downstream proteins (p-Erk, p-Akt). Histological analyses were performed to evaluate neuronal survival and neuroinflammation.

Key results

Post-injury chronic nicotine exposure significantly improved nesting performance in CCI mice. Histological analysis revealed increased survival of cortical neurons in the perilesion cortex with chronic nicotine exposure. Immunoblots revealed that chronic nicotine exposure significantly up-regulated mBDNF, p-Erk and p-Akt expression in the perilesion cortex of CCI mice. Immunofluorescence microscopy indicated that elevated mBDNF and p-Akt expression were mainly localized within cortical neurons. Immunolabelling of Iba1 demonstrated that chronic nicotine exposure attenuated microglia-mediated neuroinflammation.

Conclusions and implications

Post-injury chronic nicotine exposure via vaping facilitates recovery of sensorimotor function by upregulating neuroprotective mBDNF/TrkB/Akt/Erk signalling. These findings suggest potential neuroprotective properties of nicotine despite its highly addictive nature. Thus, understanding the multifaceted effects of chronic nicotine exposure on TBI-associated symptoms is crucial for paving the way for informed and properly managed therapeutic interventions.

Thirdhand smoke exposure promotes gastric tumor development in mouse and human

(2024)

The pollution of indoor environments and the consequent health risks associated with thirdhand smoke (THS) are increasingly recognized in recent years. However, the carcinogenic potential of THS and its underlying mechanisms have yet to be thoroughly explored. In this study, we examined the effects of short-term THS exposure on the development of gastric cancer (GC) in vitro and in vivo. In a mouse model of spontaneous GC, CC036, we observed a significant increase in gastric tumor incidence and a decrease in tumor-free survival upon THS exposure as compared to control. RNA sequencing of primary gastric epithelial cells derived from CC036 mice showed that THS exposure increased expression of genes related to the extracellular matrix and cytoskeletal protein structure. We then identified a THS exposure-induced 91-gene expression signature in CC036 and a homologous 84-gene signature in human GC patients that predicted the prognosis, with secreted phosphoprotein 1 (SPP1) and tribbles pseudokinase 3 (TRIB3) emerging as potential targets through which THS may promote gastric carcinogenesis. We also treated human GC cell lines in vitro with media containing various concentrations of THS, which, in some exposure dose range, significantly increased their proliferation, invasion, and migration. We showed that THS exposure could activate the epithelial-mesenchymal transition (EMT) pathway at the transcript and protein level. We conclude that short-term exposure to THS is associated with an increased risk of GC and that activation of the EMT program could be one potential mechanism. Increased understanding of the cancer risk associated with THS exposure will help identify new preventive and therapeutic strategies for tobacco-related disease as well as provide scientific evidence and rationale for policy decisions related to THS pollution control to protect vulnerable subpopulations such as children.

Insurance Disparities in Quality of Care Among Patients With Head and Neck Cancer

(2024)

Importance

Significant insurance status disparities have been demonstrated in head and neck cancer (HNC) outcomes. The effects of insurance status on HNC outcomes may be explained by differential access to high-quality care.

Objective

To evaluate the association of insurance status with the quality of the treating hospital and receipt of guideline-compliant care among patients with HNC.

Design, setting, and participants

This retrospective cohort study of data from the California Cancer Registry dataset linked with discharge records and hospital characteristics from the California Department of Health Care Access and Information included adult patients with HNC diagnosed between January 1, 2010, and December 31, 2019. Data were analyzed from May 10, 2023, to March 25, 2024.

Exposures

Insurance status: commercial, Medicare, Medicaid, uninsured, other, or unknown.

Main outcomes and measures

Quality of the treating hospital (tertiles), receipt of National Comprehensive Cancer Network guideline-compliant care, and overall survival.

Results

A total of 23 933 patients (mean [SD] age, 64.8 [12.3] years; 75.3% male) met the inclusion criteria. Treatment in top-tertile hospitals (hazard ratio, 0.87; 95% CI, 0.79-0.95) was associated with improved overall survival compared with treatment in bottom-tertile hospitals. Medicare (odds ratio [OR], 0.78; 95% CI, 0.73-0.84), Medicaid (OR, 0.60; 95% CI, 0.54-0.66), and uninsured (OR, 0.38; 95% CI, 0.29-0.49) status were associated with lower likelihood of treatment in high-quality hospitals compared with commercial insurance. Among patients with advanced disease, Medicaid (OR, 0.72; 95% CI, 0.62-0.83) and uninsured (OR, 0.64; 95% CI, 0.44-0.93) patients were less likely to receive dual-modality therapy. Among patients with surgically resected advanced disease, Medicaid coverage (OR, 0.73; 95% CI, 0.58-0.93) was associated with lower likelihood of receiving adjuvant radiotherapy.

Conclusions and relevance

This study found significant insurance disparities in quality of care among patients with HNC. These findings highlight the need for continued health insurance reform in the US to improve the quality of insurance coverage, in addition to expanding access to health insurance.

An Exploration of Rural Housing Insecurity as a Public Health Problem in California’s Rural Northern Counties

(2024)

Although widely acknowledged as an important social determinant of health, until recently researchers and policymakers have primarily approached housing insecurity as an urban issue, obscuring the visibility of its impacts in rural contexts, including the ways in which housing insecurity intersects with other health and structural inequities facing rural populations. Working to address this gap in the existing literature, this paper explores the experiences of housing insecurity in a rural context by reporting on an analysis of 210 in-depth interviews with 153 adults between the ages of 18-35, living in California's rural North State, a relatively overlooked far northern region of the state comprised of 12 north central and north eastern counties. Using in-depth qualitative interview data, we conducted an exploratory pattern-level analysis of participants' narratives structured by four dimensions of housing insecurity defined in the literature (housing affordability, housing stability, housing conditions, and neighborhood context). Drawing attention to the pervasiveness of rural housing insecurity within our sample, this analysis highlights the unique ways in which rurality creates distinct experiences not currently captured in the existing literature. Further research is needed across different types of rural communities to better understand the various ways that housing insecurity affects the everyday lives and health of rural residents. By grounding research within the experiences of rural residents, we are better able to respond to the crisis of rural housing insecurity and develop solutions that are tailored to rural residents' unique needs.