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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Association of race and ethnicity with quality of care among head and neck cancer patients in California

(2025)

Background

There are significant racial disparities in head and neck cancer (HNC) outcomes. Racial differences in survival may be explained by differential access to high-quality care. The goal of this study was to evaluate the association of race and ethnicity with the quality of the treating hospital, and receipt of guideline-compliant care among HNC patients.

Methods

Retrospective cohort study of data from the California Cancer Registry dataset linked with discharge records and hospital characteristics. The study cohort included adult patients with HNC diagnosed between January 1, 2010, and December 31, 2019. Outcome measures included the quality of treating hospital, and NCCN guideline-compliant care.

Results

Black (OR 0.76, 95 % CI 0.67 to 0.85) and Hispanic (OR 0.68, 95 % CI 0.63 to 0.74) patients were less likely to be treated in top-quality hospitals compared with non-Hispanic White patients, after adjusting for demographic, and clinical factors. This association disappeared for Black patients, but persisted for Hispanic patients, after additionally adjusting for socioeconomic status and insurance status. Black patients with advanced-stage disease were less likely to be treated with dual-modality therapy (OR 0.82, 95 % CI 0.70 to 0.96), however, this association disappeared after adjusting for demographic, and clinical factors, and hospital quality.

Conclusion

There are significant racial and ethnic disparities in quality of care for patients with HNC. Our findings suggest that differential access to high-quality care may account for some of the racial disparities in HNC survival, and highlight the need for continued investigation into the drivers of racial disparities in HNC outcomes.

M19 Adult Consequences of Repeated Nicotine and Δ9-Tetrahydrocannabinol (THC) Vapor Inhalation in Adolescent Rats

(2025)

S100A8/A9 innate immune signaling as a distinct mechanism driving progression of smoking-related breast cancers

(2025)

Smoking plays an underappreciated role in breast cancer progression, increasing recurrence and mortality in patients. Here, we show that S100A8/A9 innate immune signaling is a molecular mechanism that identifies smoking-related breast cancers and underlies their enhanced malignancy. In contrast to acute exposure, chronic nicotine increased tumorigenicity and reprogrammed breast cancer cells to express innate immune response genes. This required the α7 nicotinic acetylcholine receptor, which elicited dynamic changes in cell differentiation, proliferation, and expression of secreted cytokines, such as S100A8 and S100A9, as assessed by unbiased scRNA-seq. Indeed, pharmacologic or genetic inhibition of S100A8/A9-RAGE receptor signaling blocked nicotine's tumor-promoting effects. We also discovered Syntaphilin (SNPH) as an S100A8/A9-dependent gene enriched specifically in estrogen receptor-negative (ER^-) cancers from former smokers, linking this response to patient disease. Together, our findings describe a new α7 nAChR-S100A8/A9-Syntaphilin immune signaling module that drives nicotine-induced tumor progression and distinguishes smoking-related patient disease as a distinct subset of aggressive breast cancers.

Cover page of Effect of a minimum floor price law for tobacco products on tobacco sales in Oakland, California, USA: a synthetic difference-in-differences analysis

Effect of a minimum floor price law for tobacco products on tobacco sales in Oakland, California, USA: a synthetic difference-in-differences analysis

(2025)

Background

In May 2020, Oakland became the most populous city in California to implement a minimum floor price law (MFPL), requiring tobacco retailers to sell cigarettes and cigars at $8 or more per pack/package. Policy enforcement began in August 2020.

Methods

We estimated changes in cigarette and cigar prices and unit sales for Oakland versus a matched comparator during the first 20 months following MFPL implementation using a synthetic difference-in-differences approach. We estimated outcome changes overall and by lower-priced (<$8) versus higher-priced (≥$8) segments based on pre-MFPL prices. We also assessed retailer compliance with the MFPL. We further estimated cross-border shopping as a means of price increase avoidance and substitution to electronic nicotine delivery systems (ENDS) and nicotine replacement therapy (NRT) products as alternative consumer responses to the MFPL.

Results

Retailer compliance was high for cigarettes (97.5%) but extremely low for cigars (7.4%). Lower-priced cigarettes in Oakland exhibited: increased median price per pack of 9.0%, a decline in mean monthly sales of 25.2%, and no evidence of significant cross-border shopping (-1.2%) following MFPL enforcement. Lower-priced cigars in Oakland experienced no price change, yet a large sales decline post-enforcement (-58.8%), with a partially-offsetting increase in cross-border shopping (11.0%) post-enforcement. We observed no significant product substitution to higher-priced cigarettes or cigars nor to ENDS or NRT products.

Conclusions

Oakland's MFPL produced an aggregate decline in cigarette sales of 15%. MFPLs hold promise as a complement to tobacco taxation for reducing tobacco use, especially in localities that pre-empt local tobacco taxation.

Clarification Regarding Insurance Disparities Among Patients With Head and Neck Cancer—Reply

(2025)

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.

Targeting Pancreatic Cancer Cell Stemness by Blocking Fibronectin-Binding Integrins on Cancer-Associated Fibroblasts

(2025)

Significance

Simultaneous targeting of two integrins that function as receptors for FN, a protumor ECM protein, can prevent fibroblasts from supporting the malignant behavior of pancreatic cancer cells.

Cigarette smoking is associated with reduced neuroinflammation and better cognitive control in people living with HIV.

(2025)

People living with HIV (HIV+) are roughly twice as likely to smoke cigarettes (Smok+) as the general population. With the advent of effective antiretroviral therapies, it is increasingly important to understand the effects of chronic HIV infection and cigarette smoking on brain function and cognition since HIV+ individuals have heightened neuroinflammation and cognitive deficits even with such therapies. Based on prior studies demonstrating that smoking reduces a marker for neuroinflammation in HIV- individuals, we hypothesized that HIV+/Smok+ individuals would have less neuroinflammation and better cognitive control than HIV+/Smok- individuals. Fifty-nine participants (HIV-/Smok- [n = 16], HIV-/Smok+ [n=14], HIV+/Smok- [n = 18], and HIV+/Smok+ [n = 11]) underwent baseline eligibility tests, positron emission tomography (PET) scanning to determine levels of a marker for neuroinflammation, and assessment of cognitive control with the reverse-translated 5-choice continuous performance test (5C-CPT), with smokers having smoked to satiety prior to testing. For the PET data, a significant effect of smoking status on whole brain (WB) standardized uptake value (SUV) was found between HIV+/Smok+ and HIV+/Smok- participants (due to 18.8% lower WB SUV in the HIV+/Smok+ group). HIV+/Smok- participants exhibited a mean 13.5% higher WB SUV than HIV-/Smok- participants. For the 5C-CPT, HIV+/Smok+ participants performed significantly better than HIV+/Smok- participants (d prime), and HIV+/Smok- participants performed worse than HIV-/Smok- participants. Thus, HIV+/Smok+ individuals demonstrated lower levels of the neuroinflammation marker and better cognitive control than HIV+/Smok- individuals. Given that HIV+ individuals whose HIV is well-controlled can still have chronic neurocognitive complications, study results suggest possible paths for future research into nicotine-related treatments to prevent such complications.

Autologous precision-cut lung slice co-culture models for studying macrophage-driven fibrosis

(2025)

Precision-cut lung slices (PCLS) are commonly used as an ex vivo model to study lung fibrosis; however, traditional models lack immune cell infiltration, including the recruitment of monocytes and macrophages, which are critical for inflammation and fibrosis. To address this limitation, we developed novel autologous PCLS-immune co-culture models that better replicate the processes of inflammation, repair, and immune cell recruitment associated with fibrosis. Fibrotic responses to nicotine, cigarette smoke extract (CSE), and a fibrosis-inducing cocktail (FC) were first evaluated in PCLS containing only tissue-resident macrophages, with upregulation of α-SMA-expressing fibroblasts confirmed by immunofluorescence and Western blotting, and collagen deposition quantified using Sirius Red staining. To study macrophage recruitment, we employed an indirect co-culture model using transwells to approximate blood vessel function. Chemotactic studies revealed increased migration of autologous bone marrow-derived macrophages (BMDMs) toward and infiltration into CSE-injured PCLS. In a direct co-culture model simulating the repair phase of fibrosis, PCLS exposed to CSE and FC showed further increased collagen deposition in the presence of autologous BMDMs, but not heterologous ones. These findings suggest that our novel PCLS-immune co-culture models provide a platform for studying macrophage involvement in fibrosis and offer potential for developing macrophage-targeted therapeutic strategies in pulmonary fibrosis.

Cover page of Material hardship, forced displacement, and negative health outcomes among unhoused people who use drugs in Los Angeles, California and Denver, Colorado: a latent class analysis

Material hardship, forced displacement, and negative health outcomes among unhoused people who use drugs in Los Angeles, California and Denver, Colorado: a latent class analysis

(2025)

Background

Homelessness is a growing concern in the United States, especially among people who use drugs (PWUD). The degree of material hardship among this population may be linked to worse health outcomes. PWUD experiencing homelessness in urban areas are increasingly subjected to policies and social treatment, such as forced displacement, which may worsen material hardship. It is critical to describe hardship among PWUD and examine if it is linked to health outcomes.

Methods

Data were collected as part of a prospective cohort study of PWUD in Los Angeles, California and Denver, Colorado (n = 476). Analysis sample size was smaller (N = 395) after selecting for people experiencing homelessness and for whom data were complete. Five indicators assessing hardship (difficulty finding food, clothing, restrooms, places to wash/shower, and shelter) in the past three months were obtained from participants at baseline and were used in latent class analysis (LCA). We chose a base latent class model after examination of global fit statistics. We then built three auxiliary models using the three-step Bolck-Croon-Hagenaars (BCH) method to test the relationship of latent class membership to several hypothesized social and health variables in this same three month time period.

Results

Fit statistics, minimum classification probabilities, and ease of interpretation indicated a three-class solution for level of material difficulty. We termed these classes "High Difficulty" (n = 82), "Mixed Difficulty" (n = 215), and "Low Difficulty" (n = 98). Average classification probabilities indicated good class separability. "High Difficulty" participants had high probabilities of usually having difficulty accessing all five resources. "Mixed Difficulty" participants indicated a range of difficulty accessing all resources, with restrooms and bathing facilities being the most difficult. "Low Difficulty" participants were defined by high probabilities of never having access difficulty. In auxiliary analyses, there were significant (p < 0.05) differences in experiences of displacement, opioid withdrawal symptoms, nonfatal overdose, and violent victimization between classes.

Conclusions

This LCA indicates that among PWUD experiencing homelessness there exist distinct differences in resource access and material hardship, and that these differences are linked with political, social, substance use, and other health outcomes. We add to the literature on the relationship between poverty and health among PWUD. Policies which increase difficulty accessing necessary material resources may negatively impact health in this population.