Proteogenomics of Non-smoking Lung Cancer in East Asia Delineates Molecular Signatures of Pathogenesis and Progression.

Lung cancer in East Asia is characterized by a high percentage of never-smokers, early onset and predominant EGFR mutations. To illuminate the molecular phenotype of this demographically distinct disease, we performed a deep comprehensive proteogenomic study on a prospectively collected cohort in Taiwan, representing early stage, predominantly female, non-smoking lung adenocarcinoma. Integrated genomic, proteomic, and phosphoproteomic analysis delineated the demographically distinct molecular attributes and hallmarks of tumor progression. Mutational signature analysis revealed age- and gender-related mutagenesis mechanisms, characterized by high prevalence of APOBEC mutational signature in younger females and over-representation of environmental carcinogen-like mutational signatures in older females. A proteomics-informed classification distinguished the clinical characteristics of early stage patients with EGFR mutations. Furthermore, integrated protein network analysis revealed the cellular remodeling underpinning clinical trajectories and nominated candidate biomarkers for patient stratification and therapeutic intervention. This multi-omic molecular architecture may help develop strategies for management of early stage never-smoker lung adenocarcinoma.

Molecular profile of driver genes in lung adenocarcinomas of Brazilian patients who have never smoked: implications for targeted therapies.

INTRODUCTION: Lung cancer in never-smoker (LCINS) patients accounts for 20% of lung cancer cases, and its biology remains poorly understood, particularly in genetically admixed populations. We elucidated the molecular profile of driver genes in Brazilian LCINS. METHODS: The mutational and gene fusion status of 119 lung adenocarcinomas from self-reported never-smoker patients, was assessed using targeted sequencing (NGS), nCounter, and immunohistochemistry. A panel of 46 ancestry-informative markers determined patients' genetic ancestry. RESULTS: The most frequently mutated gene was EGFR (49.6%), followed by TP53 (39.5%), ALK (12.6%), ERBB2 (7.6%), KRAS (5.9%), PIK3CA (1.7%), and less than 1% alterations in RET, NTRK1, MET∆ex14, PDGFRA, and BRAF. Except for TP53 and PIK3CA, all other alterations were mutually exclusive. Genetic ancestry analysis revealed a predominance of European (71.1%), and a higher African ancestry was associated with TP53 mutations. CONCLUSION: Brazilian LCINS exhibited a similar molecular profile to other populations, except the increased ALK and TP53 alterations. Importantly, 73% of these patients have actionable alterations that are suitable for targeted treatments.

New insights into the paradox between smoking and the risk of SARS-CoV-2 infection (COVID-19): Insufficient evidence for a causal association.

AIMS: Previous studies have reported a 'smoker's paradox', where people who smoke appear to be protected against Severe Acute Respiratory Syndrome CoronaVirus-2 (SARS-CoV-2) infection (COVID-19). This conflicts with well-established evidence that people who smoke are generally more vulnerable to respiratory infections. In this study, we aimed to validate the association between smoking and SARS-CoV-2 infection in a general Dutch population, and to evaluate the evidence underlying the possible causal relationship between smoking and SARS-CoV-2 infection by applying a modern adaptation of the Bradford Hill criteria. METHODS: In total, 57,833 participants from the Lifelines Cohort Study were included in the analysis. Smoking status, including never smoker, current smoker, and former smoker, was derived from the Lifelines general assessment between 2014 and 2017, while SARS-CoV-2 infection status was derived from an additional COVID-19 questionnaire from 2021 to 2022. Logistic regressions were used for the association between smoking status and infection status. The adapted Bradford Hill's criteria, including the strength of association (including an analysis of plausible confounding), plausibility, temporality and study design suitability, were applied to evaluate the existing literature. RESULTS: We found, compared with never smokers, an increased risk of SARS-CoV-2 infection for former smokers (odds ratio (OR)=1.07, 95% confidence interval (CI)=1.01-1.13), but a reduced risk for current smokers (OR=0.85, 95% CI=0.79-0.92), after adjusting for several relevant covariates. However, we discerned a possible explanation of the smoker's paradox since we observed that current smokers were more likely to be non-responders to the COVID-19 questions and, more importantly, these non-responders were more likely to have other established risk factors for SARS-CoV-2 infection. CONCLUSIONS: There is insufficient evidence to suggest that smoking protects against SARS-CoV-2 infection. According to the adapted Bradford Hill's criteria, we observed a high inconsistency between study results, a high possibility for residual confounding and no clear evidence for biological plausibility. Future studies should include linkage with the confirmed testing results from national healthcare registries to mitigate avoidable bias.

Predictors of quitting support from nonsmoking mothers for smoking fathers: a cross-sectional study from Chinese pupils' families.

BACKGROUND: Quitting support from smokers' partners can predict quit attempts and smoking abstinence but research on factors that predict such support has been limited. To add more evidence for partner support and the improved interventions for smoking cessation, we analyzed some new potential predictors of quitting support from smokers' spouses. METHOD: This cross-sectional study was conducted in in 2022 and 2023, selecting the students' families in which fathers smoked and mothers didn't smoke from grade 1-5 of 13 primary schools in Qingdao, China. Parents who met the criteria completed the online questionnaires and 1018 families were included in the analysis. We measured personal information related to smokers and their spouses such as age, education and nicotine dependence, and variables related to family and marital relationship such as family functioning, perceived responsiveness and power in decision-making of quitting smoking. Quitting support from smokers' spouses was measured by Partner Interaction Questionnaire and generalized linear model was used to explore the potential predictors of partner support. RESULTS: In this study, the mean age of smokers was 39.97(SD = 5.57) and the mean age of smokers' spouses was 38.24(SD = 4.59). The regression analysis showed that for smokers and their spouses, the older age groups showed the lower ratio of positive/negative support(P < 0.05) and smokers with high education showed the less positive and negative partner support(P < 0.05). Nicotine dependence was positively associated with negative support (ß = 0.120, P < 0.01), and perceived responsiveness (ß = 0.124, P < 0.05) as well as family functioning (ß = 0.059, P < 0.05) was positively associated with positive support. These three factors were associated with ratio of positive/negative support(P < 0.05). In addition, power of smoker's spouse in decision-making of quitting smoking was positively associated with the positive (ß = 0.087, P < 0.001) and negative support (ß = 0.084, P < 0.001). CONCLUSIONS: Nicotine dependence, family functioning, power in decision-making of quitting smoking and perceived responsiveness were found to be the predictors of quitting support from smokers' spouses. By incorporating predictors of partner support and integrating some established theories that can improve family functioning and marital relationships, smoking cessation interventions can be further improved.

Effect of Adding Personalized Instant Messaging Apps to a Brief Smoking Cessation Model in Community Smokers in Hong Kong: Pragmatic Randomized Clinical Trial.

BACKGROUND: While text messaging has proven effective for smoking cessation (SC), engagement in the intervention remains suboptimal. OBJECTIVE: This study aims to evaluate whether using more interactive and adaptive instant messaging (IM) apps on smartphones, which enable personalization and chatting with SC advisors, can enhance SC outcomes beyond the provision of brief SC advice and active referral (AR) to SC services. METHODS: From December 2018 to November 2019, we proactively recruited 700 adult Chinese daily cigarette users in Hong Kong. Participants were randomized in a 1:1 ratio. At baseline, all participants received face-to-face brief advice on SC. Additionally, they were introduced to local SC services and assisted in selecting one. The intervention group received an additional 26 personalized regular messages and access to interactive chatting through IM apps for 3 months. The regular messages aimed to enhance self-efficacy, social support, and behavioral capacity for quitting, as well as to clarify outcome expectations related to cessation. We developed 3 sets of messages tailored to the planned quit date (within 30 days, 60 days, and undecided). Participants in the intervention group could initiate chatting with SC advisors on IM themselves or through prompts from regular messages or proactive inquiries from SC advisors. The control group received 26 SMS text messages focusing on general health. The primary outcomes were smoking abstinence validated by carbon monoxide levels of <4 parts per million at 6 and 12 months after the start of the intervention. RESULTS: Of the participants, 505/700 (72.1%) were male, and 450/648 (69.4%) were aged 40 or above. Planning to quit within 30 days was reported by 500/648 (77.2%) participants, with fewer intervention group members (124/332, 37.3%) reporting previous quit attempts compared with the control group (152/335, 45.4%; P=.04). At the 6- and 12-month follow-ups (with retention rates of 456/700, 65.1%, and 446/700, 63.7%, respectively), validated abstinence rates were comparable between the intervention (14/350, 4.0%, and 19/350, 5.4%) and control (11/350, 3.1% and 21/350, 6.0%) groups. Compared with the control group, the intervention group reported greater utilization of SC services at 12 months (RR 1.26, 95% CI 1.01-1.56). Within the intervention group, engaging in chat sessions with SC advisors predicted better validated abstinence at 6 months (RR 3.29, 95% CI 1.13-9.63) and any use of SC services (RR 1.66, 95% CI 1.14-2.43 at 6 months; RR 1.67, 95% CI 1.26-2.23 at 12 months). CONCLUSIONS: An IM-based intervention, providing support and assistance alongside brief SC advice and AR, did not yield further increases in quitting rates but did encourage the utilization of SC services. Future research could explore whether enhanced SC service utilization leads to improved long-term SC outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT03800719; https://clinicaltrials.gov/ct2/show/NCT03800719.

Expression of microRNA-223 and microRNA-214 in gingival crevicular fluid of smoker and nonsmoker periodontitis patients, an observational diagnostic accuracy study.

OBJECTIVE: Periodontitis is a multifactorial disease that affects a wide range of populations. However, its pathogenesis remains unclear. miRNAs are now considered potential diagnostic markers for many inflammatory diseases. Thus, the aim of this study was to assess the expression of microRNA-223(miRNA-223) and microRNA-214 (miRNA-214) in gingival crevicular fluid (GCF) of smoker and nonsmoker with periodontitis. MATERIALS AND METHODS: We conducted a prospective study among 42 participants: 14 healthy controls, 14 nonsmoker periodontitis participants, and 14 smokers with periodontitis. Eligibility criteria for inclusion were consecutive adults, aged 20-60 years, with stage III periodontitis grade B/C and no systemic diseases. All consenting participants had gingival crevicular fluid samples collected after diagnosis to assess miRNA-214 and -223 by quantitative real-time polymerase chain reaction assay. RESULTS: ROC curve analyses for the non-smoker periodontitis group showed that miR-214 as a predictor in comparison to miR-223 had higher sensitivity [92.86%-64.29%], same specificity [100%], and a significantly higher area under the curve [0.974-0.796] respectively (p = 0.036). As for the smoker periodontitis group, a ROC curve with miR-214 as predictor in comparison to miR-223 had higher sensitivity [100%-71.43%], same specificity [100%], and a non-significantly higher area under the curve [1-0.872], respectively (p = 0.059). CONCLUSION: Both miRNA-214 and 223 are reliable potential diagnostic markers for periodontitis, with miRNA-214 being more accurate for smokers with periodontitis. CLINICAL RELEVANCE: Both miRNA-214 and 223 could be considered for potential chair-side diagnostics, by simply collecting GCF detecting the disease in its first steps and aid in preventing unrepairable damage.

Female reproductive and hormonal factors and lung cancer mortality among never-smokers: A prospective cohort study of 287 408 Chinese women.

There is growing, but inconsistent evidence suggesting oestrogen may play a key role in lung cancer development, especially among never-smoking women for whom lung cancer risk factors remain largely elusive. Using the China Kadoorie Biobank, a large-scale prospective cohort with 302 510 women aged 30 to 79 years recruited from 10 regions in China during 2004 to 2008, we assessed the risk of lung cancer death among self-reported never-smoking women who were cancer-free at baseline, in relation to age at menarche, age at menopause, time since menopause, prior use of oral contraceptives (OCP), number of livebirths, breastfeeding and age at first livebirth. Women were followed up to December 31, 2016 with linkage to mortality data. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox regression, adjusting for key confounders including several socio-demographic, environmental and lifestyle factors. Among 287 408 never-smoking women, 814 died from lung cancer with a median follow-up of 10.3 years. Women who had used OCP within 15 years prior to baseline had a significantly higher hazard of lung cancer death compared with never-users: HR = 1.85 (95% CI: 1.14-3.00) and risk increased by 6% with each additional year of use: HR = 1.06 (1.01-1.10). Among parous women, the hazard of lung cancer death increased by 13% with each single livebirth: HR = 1.13 (1.05-1.23); and among post-menopausal women, the risk increased by 2% with each year since menopause: HR = 1.02 (1.01-1.04). These results suggest that reproductive factors which were proxies for lower endogenous oestrogen level, for example, longer duration of OCP use, could play a role in lung cancer development.

New Evidence of Microplastics in the Lower Respiratory Tract: Inhalation through Smoking.

To investigate the relation of smoking and microplastic inhalation, we conducted a prospective study combining population-based and experimental work. Bronchoalveolar lavage fluid (BALF) samples from 17 smokers and 15 nonsmokers were collected in Zhuhai City, China. We simulated an active smoking model to explore the contribution of smoking to inhaled microplastics. The characteristics of microplastics in BALF samples and cigarette smoke were determined using laser direct infrared spectroscopy. We compared the differences between smokers and nonsmokers as well as between cigarette smoke and control groups. Microplastics were identified positive in all BALF samples. Smokers had higher concentrations of total microplastics (25.86 particles/g), polyurethane (11.34 particles/g), and silicone (1.15 particles/g) than nonsmokers. In the cigarette smoking simulation model, higher concentrations of total microplastics (9.99 particles/L), polyurethane (4.66 particles/L), and silicone (2.78 particles/L) were present in the cigarette smoke than those in the control group. We confirmed and extended the evidence on the presence of microplastics in the lower respiratory tract. These findings also provide new evidence on the relation between cigarette smoking and microplastic inhalation.

Biomarkers of exposure in urine of active smokers, non-smokers, and vapers.

The exposure to smoking related products has been evaluated through urine illness risk marker determination through the analysis of urine samples of smokers and vapers. Biomarkers and their metabolites such as N-acetyl-S-(2-cyanoethyl)-L-cysteine (CEMA), N-acetyl-S-(3,4-dihydroxybutyl)-L-cysteine (DHBMA), N-acetyl-S-[1-(hydroxymethyl)-2-propen-1-yl)-L-cysteine (MHBMA), N-acetyl-S-(3-hydroxypropyl)-L-cysteine (3HPMA), 2R-N-acetyl-S-(4-hydroxybutan-2-yl)-L-cysteine (HMPMA), and N-acetyl-S-(3-carboxy-2-propyl)-L-cysteine (CMEMA) together with nicotine and cotinine were identified and quantified by LC-HRMS and LC-MS/MS, and data found normalized to the creatinine level. One hundred two urine samples were collected from smokers, non-smokers, and vapers, spanning an age range from 16 to 79 years. Results obtained showed that CEMA was only detected in urine samples from smokers and MHBMA was in the same order of magnitude in all the urine samples analyzed. HMPMA was found in the urine of vapers at the same order of concentration as in non-smokers. 3HPMA in vapers was lower than in the urine of smokers, presenting an intermediate situation between smokers and non-smokers. On the other hand, DHBMA in vapers can reach similar values to those found for smokers, while CMEMA shows concentrations in the urine of vapers higher than in the case of non-smokers and traditional smokers, requiring new research to link this metabolite to the use of electronic cigarettes and possible alternative metabolomic routes. In general, this study seems to verify that traditional smoking practice constitutes a major source of carcinogenic chemicals compared with substitutive practices, although those practices are not free of potential harm.

Isoflavone and soy food intake and risk of lung cancer in never smokers: report from prospective studies in Japan and China.

PURPOSE: Evidence from several cohorts has suggested that a higher intake of isoflavone is associated with lower risk of lung cancer in never smokers, but the association has not been investigated by histologic type of lung cancer. Adenocarcinoma is a common histologic type found in never smokers. We hypothesized that a higher intake of isoflavone is associated with a lower risk of lung adenocarcinoma among never smokers. Here, we examined the associations of isoflavone and soy food intake with lung cancer and its histologic types in never smokers. METHODS: We performed a pooled analysis using data from the Japan Public Health Center-based Prospective Study, Shanghai Women's Health Study and Shanghai Men's Study with 147,296 never smokers aged 40-74 years with no history of cancer. During 1,990,040 person-years of follow-up, 1247 lung cancer cases were documented. Dietary isoflavone and soy food intake were assessed using a food-frequency questionnaire. Multivariable Cox proportional hazards models assessed the associations between isoflavone and soy intake with incidence of lung cancer by histologic type. RESULTS: A higher intake of dietary isoflavone and soy food were associated with reduced risk of lung adenocarcinoma. The multivariable hazard ratios (HRs) (95% CI) of risk of lung adenocarcinoma for the highest versus lowest intakes of isoflavone and soy food were 0.74 (0.60-0.92) and 0.78 (0.63-0.96), respectively. The multivariable HRs of risk of lung adenocarcinoma associated with each 10 mg/day increase in isoflavone and each 50 g/day increase in soy food intake were 0.81 (0.70-0.94) and 0.84 (0.73-0.96), respectively. CONCLUSION: Higher intake of isoflavone and soy food was associated with lower risk of lung adenocarcinoma in never smokers.

Urinary cotinine and exposure to passive smoke in children and adolescents in Germany - Human biomonitoring results of the German Environmental Survey 2014-2017 (GerES V).

Passive smoking is a preventable and significant cause of many serious health problems, with children being particularly at risk. In the fifth German Environmental Survey (GerES V), conducted from 2014 to 2017, information reflecting the extent of passive smoke exposure in children and adolescents was collected by interview-based questionnaires and human biomonitoring (HBM) analyses of cotinine in urine from 2260 participants, aged 3-17 years. Based on these population-representative data, we describe current passive smoke exposure stratified by different subgroups and identify specific exposure determinants using multivariate logistic regression. The questionnaire data revealed that 42% of children and adolescents lived with at least one smoker in the household. Quantifiable concentrations of cotinine could be detected in 56% of the participants. The overall median concentration of cotinine was 0.2 µg/L, with children and adolescents of low socioeconomic status found to be a group particularly affected by passive smoke with higher cotinine concentrations (median = 1.2 µg/L). In the multiple analysis, the most significant predictor of cotinine levels derived from the questionnaire was passive smoking at home (odds ratio (OR) 13.07 [95CI: 4.65, 36.70]). However, parental smoking and passive smoking among friends and relatives could also be identified as independent factors influencing elevated cotinine levels. The comparison between the previous cycle GerES IV (2003-2006) on 3-14-year-olds and GerES V shows that tobacco smoke exposure of children decreased significantly. This decrease is likely an effect of extensive non-smoker protection laws being enforced 2007-2008 on federal and state level. This is reflected by a halving of urinary cotinine concentrations. Nevertheless, our results indicate that passive smoke is still a relevant source of harmful pollutants for many children and adolescents in Germany, and thus support the need for further efforts to reduce passive smoke exposure, especially in the private environment.

Lung Cancer in Never Smokers: Delving into Epidemiology, Genomic and Immune Landscape, Prognosis, Treatment, and Screening.

Lung cancer in never smokers (LCINS) represents a growing and distinct entity within the broader landscape of lung malignancies. This review provides a comprehensive overview of LCINS, encompassing its epidemiologic trends, risk factors, distinct genomic alterations, clinical outcomes and the ongoing initiative aimed at formulating screening guidelines tailored to this unique population. As LCINS continues to gain prominence, understanding its intricate genomic landscape has become pivotal for tailoring effective therapeutic strategies. Moreover, LCINS does not meet the criteria for lung cancer screening as per the current guidelines. Hence, there is an urgent need to explore its heterogeneity in order to devise optimal screening guidelines conducive to early-stage detection. This review underscores the vital importance of detailed research to elucidate the multifaceted nature of LCINS, with the potential to shape future clinical management and screening recommendations for this unique and growing patient cohort.

Serum zinc and periodontitis in non-diabetic smoking and non-smoking adults: NHANES 2011-2014.

OBJECTIVE: This study aimed to evaluate the association of serum zinc with periodontitis in non-diabetics based on smoking status, using a representative sample of adults in the United States. METHODS: A total of 1051 participants who underwent full-mouth periodontal examination and serum zinc testing were enrolled from NHANES 2011 to 2014. The covariate-adjusted association of serum zinc concentrations with periodontitis was explored using multivariable logistic regression, restricted cubic spines, and sensitivity analysis. RESULTS: The mean age of the 1051 adults was 54.5 years, 59.37% were male, and 20.65% had periodontitis. Analysis of the results showed that serum zinc was associated with periodontitis. The overall adjusted odds of periodontitis were 9% (odds ratio [OR]: 0.91; 95% confidence interval [CI]: 0.83-1.00) and 14% (OR: 0.86; 95% CI: 0.75-0.98) for nonsmokers and smokers, respectively. Smokers with T3 serum zinc exhibited a 53% reduction in the fully adjusted odds of periodontitis (OR: 0.47; 95% CI: 0.23-0.96), when compared to the reference group (T1 serum zinc), with serum zinc as the categorical variable. CONCLUSIONS: Serum zinc levels were associated with the risk of periodontitis in non-diabetic smokers but not non-smokers.

Cigarette smoke exposure of hospitalised children: Prevalence of smoking in parents or carers and admission practices of health services.

AIM: The aim of this study is to understand the exposure to second-hand tobacco smoke in the homes of hospitalised children through: (i) understanding the prevalence of smoking in adults or carers and (ii) examining the health services' approach to identifying parental smoking status. METHODS: This prospective observational study consisted of two surveys: one administered to parents/carers of hospitalised children and one to health services. The first cross-sectional survey aimed to elicit the proportion of children requiring admission to a regional Victorian general paediatric unit who live with adults who smoke cigarettes. The survey was delivered to participating parents/carers during the standard nursing admission process. The second survey was administered across 15 public health services to determine if identification of parent/carer's smoking status is a routine part of their standard paediatric admission practice. RESULTS: For the parental survey, 453 responses were obtained from 782 consecutive new admissions. Nearly a third (n = 136, 30%) requiring hospital admission were found to be living with at least one parent/carer who identified as a current cigarette smoker. Of the 15 health services surveyed, only four (27%) nursing units reported routinely asking parents/carers about their smoking status as part of their standard admission process. CONCLUSION: Admission to hospital provides an opportunity to enhance care for children by addressing nicotine dependence within their families. Findings suggest routine recording of smoking status can be improved, to drive smoking cessation and brief intervention conversations with parents and carers of children admitted to hospital.

Evaluating Declines in Compliance With Ecological Momentary Assessment in Longitudinal Health Behavior Research: Analyses From a Clinical Trial.

BACKGROUND: Ecological momentary assessment (EMA) is increasingly used to evaluate behavioral health processes over extended time periods. The validity of EMA for providing representative, real-world data with high temporal precision is threatened to the extent that EMA compliance drops over time. OBJECTIVE: This research builds on prior short-term studies by evaluating the time course of EMA compliance over 9 weeks and examines predictors of weekly compliance rates among cigarette-using adults. METHODS: A total of 257 daily cigarette-using adults participating in a randomized controlled trial for smoking cessation completed daily smartphone EMA assessments, including 1 scheduled morning assessment and 4 random assessments per day. Weekly EMA compliance was calculated and multilevel modeling assessed the rate of change in compliance over the 9-week assessment period. Participant and study characteristics were examined as predictors of overall compliance and changes in compliance rates over time. RESULTS: Compliance was higher for scheduled morning assessments (86%) than for random assessments (58%) at the beginning of the EMA period (P<.001). EMA compliance declined linearly across weeks, and the rate of decline was greater for morning assessments (2% per week) than for random assessments (1% per week; P<.001). Declines in compliance were stronger for younger participants (P<.001), participants who were employed full-time (P=.03), and participants who subsequently dropped out of the study (P<.001). Overall compliance was higher among White participants compared to Black or African American participants (P=.001). CONCLUSIONS: This study suggests that EMA compliance declines linearly but modestly across lengthy EMA protocols. In general, these data support the validity of EMA for tracking health behavior and hypothesized treatment mechanisms over the course of several months. Future work should target improving compliance among subgroups of participants and investigate the extent to which rapid declines in EMA compliance might prove useful for triggering interventions to prevent study dropout. TRIAL REGISTRATION: ClinicalTrials.gov NCT03262662; https://clinicaltrials.gov/ct2/show/NCT03262662.

Use of the Smoking Cessation App Ex-Smokers iCoach and Associations With Smoking-Related Outcomes Over Time in a Large Sample of European Smokers: Retrospective Observational Study.

BACKGROUND: Digital interventions are increasingly used to support smoking cessation. Ex-smokers iCoach was a widely available app for smoking cessation used by 404,551 European smokers between June 15, 2011, and June 21, 2013. This provides a unique opportunity to investigate the uptake of a freely available digital smoking cessation intervention and its effects on smoking-related outcomes. OBJECTIVE: We aimed to investigate whether there were distinct trajectories of iCoach use, examine which baseline characteristics were associated with user groups (based on the intensity of use), and assess if and how these groups were associated with smoking-related outcomes. METHODS: Analyses were performed using data from iCoach users registered between June 15, 2011, and June 21, 2013. Smoking-related data were collected at baseline and every 3 months thereafter, with a maximum of 8 follow-ups. First, group-based modeling was applied to detect distinct trajectories of app use. This was performed in a subset of steady users who had completed at least 1 follow-up measurement. Second, ordinal logistic regression was used to assess the baseline characteristics that were associated with user group membership. Finally, generalized estimating equations were used to examine the association between the user groups and smoking status, quitting stage, and self-efficacy over time. RESULTS: Of the 311,567 iCoach users, a subset of 26,785 (8.6%) steady iCoach users were identified and categorized into 4 distinct user groups: low (n=17,422, 65.04%), mild (n=4088, 15.26%), moderate (n=4415, 16.48%), and intensive (n=860, 3.21%) users. Older users and users who found it important to quit smoking had higher odds of more intensive app use, whereas men, employed users, heavy smokers, and users with higher self-efficacy scores had lower odds of more intensive app use. User groups were significantly associated with subsequent smoking status, quitting stage, and self-efficacy over time. For all groups, over time, the probability of being a smoker decreased, whereas the probability of being in an improved quitting stage increased, as did the self-efficacy to quit smoking. For all outcomes, the greatest change was observed between baseline and the first follow-up at 3 months. In the intensive user group, the greatest change was seen between baseline and the 9-month follow-up, with the observed change declining gradually in moderate, mild, and low users. CONCLUSIONS: In the subset of steady iCoach users, more intensive app use was associated with higher smoking cessation rates, increased quitting stage, and higher self-efficacy to quit smoking over time. These users seemed to benefit most from the app in the first 3 months of use. Women and older users were more likely to use the app more intensively. Additionally, users who found quitting difficult used the iCoach app more intensively and grew more confident in their ability to quit over time.

Behavioral Activation-Based Digital Smoking Cessation Intervention for Individuals With Depressive Symptoms: Randomized Clinical Trial.

BACKGROUND: Depression is common among adults who smoke cigarettes. Existing depression-specific cessation interventions have limited reach and are unlikely to improve smoking prevalence rates among this large subgroup of smokers. OBJECTIVE: This study aimed to determine whether a mobile app-based intervention tailored for depression paired with a mailed sample of nicotine replacement therapy (NRT) is efficacious for treating depression and promoting smoking cessation. METHODS: A 2-arm nationwide remote randomized clinical trial was conducted in the United States. Adults (N=150) with elevated depressive symptoms (Patient Health Questionnaire-8≥10) who smoked were enrolled. The mobile app ("Goal2Quit") provided behavioral strategies for treating depression and quitting smoking based on Behavioral Activation Treatment for Depression. Goal2Quit participants also received a 2-week sample of combination NRT. Treatment as usual participants received a self-help booklet for quitting smoking that was not tailored for depression. Primary end points included Goal2Quit usability, change in depression (Beck Depression Inventory-II) across 12 weeks, and smoking cessation including reduction in cigarettes per day, incidence of 24-hour quit attempts, floating abstinence, and 7-day point prevalence abstinence (PPA). RESULTS: In total, 150 participants were enrolled between June 25, 2020, and February 23, 2022, of which 80 were female (53.3%) and the mean age was 38.4 (SD 10.3) years. At baseline, participants on average reported moderate depressive symptoms and smoked a mean of 14.7 (SD 7.5) cigarettes per day. Goal2Quit usability was strong with a mean usability rating on the System Usability Scale of 78.5 (SD 16.9), with 70% scoring above the ≥68 cutoff for above-average usability. Retention data for app use were generally strong immediately following trial enrollment and declined in subsequent weeks. Those who received Goal2Quit and the NRT sample reported lower mean depressive symptoms over the trial duration as compared to treatment as usual (difference of mean 3.72, SE 1.37 points less; P=.01). Across time points, all cessation outcomes favored Goal2Quit. Regarding abstinence, Goal2Quit participants reported significantly higher rates of 7-day PPA at weeks 4 (11% vs 0%; P=.02), 8 (7-day PPA: 12% vs 0%; P=.02), and 12 (16% vs 2%; P=.02). CONCLUSIONS: A mobile app intervention tailored for depression paired with a sample of NRT was effective for depression treatment and smoking cessation. Findings support the utility of this intervention approach for addressing the currently unmet public health treatment need for tailored, scalable depression-specific cessation treatments. TRIAL REGISTRATION: ClinicalTrials.gov NCT03837379; https://clinicaltrials.gov/ct2/show/NCT03837379.

Smartphone Apps for Smoking Cessation: Systematic Framework for App Review and Analysis.

BACKGROUND: Cigarette smoking is a leading cause of preventable death, and identifying novel treatment approaches to promote smoking cessation is critical for improving public health. With the rise of digital health and mobile apps, these tools offer potential opportunities to address smoking cessation, yet the functionality of these apps and whether they offer scientifically based support for smoking cessation are unknown. OBJECTIVE: The goal of this research was to use the American Psychiatric Association app evaluation model to evaluate the top-returned apps from Android and Apple app store platforms related to smoking cessation and investigate the common app features available for end users. METHODS: We conducted a search of both Android and iOS app stores in July 2021 for apps related to the keywords "smoking," "tobacco," "smoke," and "cigarette" to evaluate apps for smoking cessation. Apps were screened for relevance, and trained raters identified and analyzed features, including accessibility (ie, cost), privacy, clinical foundation, and features of the apps, using a systematic framework of 105 objective questions from the American Psychiatric Association app evaluation model. All app rating data were deposited in mindapps, a publicly accessible database that is continuously updated every 6 months given the dynamic nature of apps available in the marketplace. We characterized apps available in July 2021 and November 2022. RESULTS: We initially identified 389 apps, excluded 161 due to irrelevance and nonfunctioning, and rated 228, including 152 available for Android platforms and 120 available for iOS platforms. Some of the top-returned apps (71/228, 31%) in 2021 were no longer functioning in 2022. Our analysis of rated apps revealed limitations in accessibility and features. While most apps (179/228, 78%) were free to download, over half had costs associated with in-app purchases or full use. Less than 65% (149/228) had a privacy policy addressing the data collected in the app. In terms of intervention features, more than 56% (128/228) of apps allowed the user to set and check in on goals, and more than 46% (106/228) of them provided psychoeducation, although few apps provided evidence-based support for smoking cessation, such as peer support or skill training, including mindfulness and deep breathing, and even fewer provided evidence-based interventions, such as acceptance and commitment therapy or cognitive behavioral therapy. Only 12 apps in 2021 and 11 in 2022 had published studies supporting the feasibility or efficacy for smoking cessation. CONCLUSIONS: Numerous smoking cessation apps were identified, but analysis revealed limitations, including high rates of irrelevant and nonfunctioning apps, high rates of turnover, and few apps providing evidence-based support for smoking cessation. Thus, it may be challenging for consumers to identify relevant, evidence-based apps to support smoking cessation in the app store, and a comprehensive evaluation system of mental health apps is critically important.

Comparison of a Tobacco-Specific Carcinogen in Tobacco Cigarette, Electronic Cigarette, and Dual Users.

BACKGROUND: 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) is known as a lung carcinogen. The objective of this study was to investigate associations of urine NNAL concentrations and smoking status. METHODS: This was a cross-sectionally designed study based on data from the 2016-2018 Korean National Health and Nutrition Examination Survey. A total of 2,845 participants were classified into past-smoker, electronic cigarette (e-cigar) only, dual-user, and cigarette only smoker groups. All sampling and weight variables were stratified and analysis was conducted accounting for the complex sampling design. Analysis of covariance was used to compare the geometric mean of urine NNAL concentrations and log-transformed urine NNAL level among smoking status with weighted survey design. Post hoc paired comparisons with Bonferroni adjustment was performed according to smoking status. RESULTS: The estimated geometric mean concentrations of urine NNAL were 1.974 ± 0.091, 14.349 ± 5.218, 89.002 ± 11.444, and 117.597 ± 5.459 pg/mL in past-smoker, e-cigar only, dual-user, and cigarette only smoker groups, respectively. After fully adjusting, log-transformed urine NNAL level was significantly different among groups (P < 0.001). Compared with the past-smoker group, e-cigar only, dual-user, and cigarette only smoker groups showed significantly higher log-transformed urine NNAL concentrations in post hoc test (all P < 0.05). CONCLUSION: E-cigar only, dual-user, and cigarette only smoker groups showed significantly higher geometric mean concentrations of urine NNAL than the past-smoker group. Conventional cigarette, dual users, and e-cigar users can potentially show harmful health effects from NNAL.

Longitudinal Assessment of Multimorbidity Medication Patterns among Smokers in the COPDGene Cohort.

Background and objectives: Chronic obstructive pulmonary disease (COPD) is usually comorbid with other chronic diseases. We aimed to assess the multimorbidity medication patterns and explore if the patterns are similar for phase 1 (P1) and 5-year follow-up phase 2 (P2) in the COPDGene cohort. Materials and Methods: A total of 5564 out of 10,198 smokers from the COPDGene cohort who completed 2 visits, P1 and P2 visits, with complete medication use history were included in the study. We conducted latent class analysis (LCA) among the 27 categories of chronic disease medications, excluding COPD treatments and cancer medications at P1 and P2 separately. The best number of LCA classes was determined through both statistical fit and interpretation of the patterns. Results: We found four classes of medication patterns at both phases. LCA showed that both phases shared similar characteristics in their medication patterns: LC0: low medication; LC1: hypertension (HTN) or cardiovascular disease (CVD)+high cholesterol (Hychol) medication predominant; LC2: HTN/CVD+type 2 diabetes (T2D) +Hychol medication predominant; LC3: Hychol medication predominant. Conclusions: We found similar multimorbidity medication patterns among smokers at P1 and P2 in the COPDGene cohort, which provides an understanding of how multimorbidity medication clustered and how different chronic diseases combine in smokers.