Reprint of: Smoking and pulmonary health in women: A narrative review and behavioral health perspective.

OBJECTIVE: Cigarette smoking prevalence has declined slower among women than men, and smoking-related pulmonary disease (PD) has risen among women. Given these trends, there is a critical need to understand and mitigate PD risk among women who smoke. The purpose of this narrative review and commentary is to highlight important evidence from the literature on smoking and PD among women. METHODS: This review focuses broadly on examining cigarette smoking and PD among women within six topic areas: (1) demographic characteristics and prevalence of smoking, (2) smoking behavior, (3) lung cancer, (4) obstructive PD, (5) diagnostic and treatment disparities, and (6) gaps in the literature and potential directions for future research and treatment. RESULTS: Growing evidence indicates that compared to men, women are at increased risk for developing smoking-related PD and poorer PD outcomes. Gender disparities in smoking-related PD may be largely accounted for by genetic differences and sex hormones contributing to PD pathogenesis and presentation, smoking behavior, nicotine dependence, and pathogen/carcinogen clearance. Moreover, gender disparities in smoking-related PD may be exacerbated by important social determinants (e.g., women with less formal education and those from minoritized groups may be at especially high risk for poor PD outcomes due to higher rates of smoking). CONCLUSION: Rising rates of smoking-related PD among women risk widening diagnostic and treatment disparities. Ongoing research is needed to explore potentially complex relationships between sex, gender, and smoking-related PD processes and outcomes, and to improve smoking-cessation and PD treatment for women.

Smoking and pulmonary health in women: A narrative review and behavioral health perspective.

OBJECTIVE: Cigarette smoking prevalence has declined slower among women than men, and smoking-related pulmonary disease (PD) has risen among women. Given these trends, there is a critical need to understand and mitigate PD risk among women who smoke. The purpose of this narrative review and commentary is to highlight important evidence from the literature on smoking and PD among women. METHODS: This review focuses broadly on examining cigarette smoking and PD among women within six topic areas: (1) demographic characteristics and prevalence of smoking, (2) smoking behavior, (3) lung cancer, (4) obstructive PD, (5) diagnostic and treatment disparities, and (6) gaps in the literature and potential directions for future research and treatment. RESULTS: Growing evidence indicates that compared to men, women are at increased risk for developing smoking-related PD and poorer PD outcomes. Gender disparities in smoking-related PD may be largely accounted for by genetic differences and sex hormones contributing to PD pathogenesis and presentation, smoking behavior, nicotine dependence, and pathogen/carcinogen clearance. Moreover, gender disparities in smoking-related PD may be exacerbated by important social determinants (e.g., women with less formal education and those from minoritized groups may be at especially high risk for poor PD outcomes due to higher rates of smoking). CONCLUSION: Rising rates of smoking-related PD among women risk widening diagnostic and treatment disparities. Ongoing research is needed to explore potentially complex relationships between sex, gender, and smoking-related PD processes and outcomes, and to improve smoking-cessation and PD treatment for women.

"It's a cause I believe in": factors motivating participation and engagement in longitudinal, respiratory-focused research studies.

BACKGROUND: Key to the success of any prospective cohort study is the effective recruitment and retention of participants, but the specific factors that influence younger adults of the Millennial generation to participate in research are not well-understood. The objective of this qualitative study was to identify factors that motivated participation and engagement in longitudinal research studies focused on respiratory health among a diverse group of young adults. METHODS: We conducted qualitative, semi-structured interviews with 50 younger adult participants (aged 25-35 years) regarding factors influencing their participation in longitudinal research studies. Thematic analysis was used to develop, organize, and tabulate the frequency of key themes. In exploratory analyses, we examined for patterns in the distribution of key themes across racial, ethnic, or socioeconomic groups. RESULTS: Participants identified several key themes that affected their willingness to participate in longitudinal studies. These included the health-related benefits generated by research (both to the individual and to society at-large), factors related to the institution and study team conducting the research, concerns regarding unethical and/or unrepresentative study design, and barriers to participation in research. Certain factors may be more impactful to underrepresented groups, including concerns regarding data privacy and confidentiality. CONCLUSIONS: In this diverse group of younger adults, we identified specific factors that motivated participation and predicted high engagement in longitudinal research studies focused on respiratory health. Implementing and integrating these factors into study protocols may improve recruitment and retention, including among participants who are historically underrepresented in research.

Therapeutic efficacy of IL-17A neutralization with corticosteroid treatment in a model of antigen-driven mixed-granulocytic asthma.

Many mouse models of allergic asthma exhibit eosinophil-predominant cellularity rather than the mixed-granulocytic cytology in steroid-unresponsive severe disease. Therefore, we sought to implement a novel mouse model of antigen-driven, mixed-granulocytic, severe allergic asthma to determine biomarkers of the disease process and potential therapeutic targets. C57BL/6J wild-type, interleukin-6 knockout (IL-6-/-), and IL-6 receptor knockout (IL-6R-/-), mice were injected with an emulsion of complete Freund's adjuvant and house dust mite antigen (CFA/HDM) on day 1. Dexamethasone, a lymphocyte-depleting biological, or anti-IL-17A was administered during the intranasal HDM challenge on days 19-22. On day 23, the CFA/HDM model elicited mixed bronchoalveolar lavage (BAL) cellularity (typically 80% neutrophils and 10% eosinophils), airway hyperresponsiveness (AHR) to methacholine, diffusion impairment, lung damage, body weight loss, corticosteroid resistance, and elevated levels of serum amyloid A (SAA), pro-inflammatory cytokines, and T helper type 1/ T helper type 17 (Th1/Th17) cytokines compared with eosinophilic models of HDM-driven allergic airway disease. BAL cells in IL-6- or IL-6R-deficient mice were predominantly eosinophilic and associated with elevated T helper type 2 (Th2) and reduced Th1/Th17 cytokine production, along with an absence of SAA. Nevertheless, AHR remained in IL-6-deficient mice even when dexamethasone was administered. However, combined administration of anti-IL-17A and systemic corticosteroid significantly attenuated both overall and neutrophilic airway inflammation and also reduced AHR and body weight loss. Inhibition of IL-17A combined with systemic corticosteroid treatment during antigen-driven exacerbations may provide a novel therapeutic approach to prevent the pathological pulmonary and constitutional changes that greatly impact patients with the mixed-granulocytic endotype of severe asthma.

Examining Associations Between Baseline Health-Related Quality of Life and Depression and Physical Functioning Improvement Following Pulmonary Rehabilitation.

PURPOSE: This study examined whether health-related quality of life (HRQL) and depression assessed prior to pulmonary rehabilitation (PR) participation (ie, at baseline) predicted change in 6-min walk distance (6MWD) from baseline to end of PR. METHODS: Patients with pulmonary disease were consecutively referred/enrolled in a PR program from 2009-2022 (N = 503). Baseline 6MWD was assessed along with self-report measures of HRQL (St George's Respiratory Questionnaire [SGRQ]) and depression (Geriatric Depression Scale [GDS]). The SGRQ total score was used to assess overall HRQL, and SGRQ subscales assessed pulmonary symptoms, activity limitations, and psychosocial impacts of pulmonary disease. Multiple linear regression was used to examine whether baseline SGRQ scores and depression predicted Δ6MWD. RESULTS: Baseline SGRQ total score ( F(1,389) = 8.4, P = .004) and activity limitations ( F(1,388) = 4.8, P = .03) predicted Δ6MWD. Patients with an SGRQ activity limitation score ≤ 25th percentile showed the most 6MWD improvement (mean = 79.7 m, SE = 6.7), and significantly more improvement than participants scoring between the 50-75th percentiles (mean = 54.4 m, SE = 6.0) or >75th percentile (mean = 48.7 m, SE = 7.5). Patients scoring between the 25-50th percentiles (mean = 70.2 m, SE = 6.1) did not differ significantly from other groups. The SGRQ symptoms and impacts subscales were unrelated to Δ6MWD ( F(1,388) = 1.2-1.9, P > .05), as was depression ( F(1,311) = 0.0, P  > .85). CONCLUSIONS: Patients with greater HRQL at baseline may experience greater physical functioning improvement following PR. Additional support for patients with lower HRQL (eg, adjunctive self-management interventions) may enhance PR outcomes, particularly for patients who report greater activity limitations. Alternatively, early referral to PR (ie, when less symptomatic) may also benefit physical function outcomes.

Reduced Nicotine Cigarettes and E-Cigarettes in High-Risk Populations: 3 Randomized Clinical Trials.

Importance: Prohibiting the sale of commonly preferred e-cigarette flavors (eg, fruity and sweet) to discourage use among youths poses a risk of diminishing efforts to decrease smoking in adults. Objective: To compare reductions in smoking achieved in adults with psychiatric conditions or lower educational level using very low nicotine content (VLNC) cigarettes alone, combined with e-cigarettes limited to tobacco flavor (TF), or combined with e-cigarettes in participant-preferred flavors. Design, Setting, and Participants: Three randomized clinical trials were conducted for 16 weeks from October 2020 through November 2023 at the University of Vermont, Brown University, and Johns Hopkins University. Participants were adults who smoked daily and were not planning to quit in the next 30 days. These participants were from 3 at-risk populations: those with affective disorders, exemplifying mental illness; those with opioid use disorder, exemplifying substance use disorders; and females of reproductive age with a high-school education or less, exemplifying lower educational level. Participants were randomly assigned to 1 of 4 experimental conditions: (1) normal nicotine content (NNC) cigarettes only; (2) VLNC cigarettes only; (3) VLNC cigarettes plus e-cigarettes with classic TF (hereafter, VLNC + TF); and (4) VLNC cigarettes plus e-cigarettes with preferred flavors (hereafter, VLNC + PF). Interventions: The NNC cigarettes contained 15.8 mg nicotine/g tobacco, the VLNC cigarettes contained 0.4 mg nicotine/g tobacco, the VLNC + TF had pods containing 5% nicotine by weight and only classic TF, and the VLNC + PF had pods containing 5% nicotine in 8 flavors (including fruity and sweet) from which participants selected 3 flavors. Main Outcomes and Measures: The primary outcome was mean total cigarettes smoked per day (CPD) during week 16. Tobacco-related biomarkers were assessed, including total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), a tobacco-specific carcinogen. Results: A total of 326 participants (mean [SD] age, 40.09 [10.79] years; 243 females [74.5%]) from 3 randomized clinical trials were included. The VLNC cigarettes decreased total CPD, with least square (LS) means (SEMs) of 22.54 (1.59) in the NNC, 14.32 (1.32) in the VLNC, 11.76 (1.18) in the VLNC + TF, and 7.63 (0.90) in the VLNC + PF conditions. Each VLNC condition differed significantly from NNC, with an adjusted mean difference (AMD) of -8.21 (95% CI, -12.27 to -4.16; P < .001) in the VLNC, -10.78 (95% CI, -14.67 to -6.90; P < .001) in the VLNC + TF, and -14.91 (95% CI, -18.49 to -11.33; P < .001) in the VLNC + PF conditions. Participants in the VLNC + PF condition also decreased smoking below the VLNC and the VLNC + TF conditions (AMDs, -6.70 [95% CI, -9.84 to -3.55; P < .001] and -4.13 [95% CI, -7.05 to -1.21; P = .02]); the VLNC and VLNC + TF conditions did not differ significantly. Consistent with decreases in CPD, NNAL levels in the VLNC + PF condition were lower than in all other conditions, with AMDs (in pmol/mg creatinine) of -0.94 (95% CI, -1.41 to -0.47; P < .001) compared with the NNC condition, -0.47 (95% CI, -0.87 to -0.08; P = .03) compared with the VLNC condition, and -0.46 (95% CI, -0.83 to -0.10; P = .04) compared with the VLNC + TF condition. Conclusions and Relevance: These results provide further evidence that a reduced-nicotine standard for cigarettes has the potential to decrease smoking and tobacco-toxicant exposure in high-risk populations and that these effects may be enhanced when adults can access e-cigarettes in commonly preferred flavors. Trial Registration: ClinicalTrials.gov Identifiers: NCT04092387, NCT04090879, NCT04092101.

Smoking Cessation Interventions for Patients With Chronic Obstructive Pulmonary Disease: A NARRATIVE REVIEW WITH IMPLICATIONS FOR PULMONARY REHABILITATION.

PURPOSE: Reducing disease burden in patients with chronic obstructive pulmonary disease (COPD) focuses, in part, on helping patients become more functional through programs such as pulmonary rehabilitation (PR). Smoking cessation may be a prerequisite or component of PR, and determining which smoking interventions (eg, behavioral, pharmacotherapy, combination) are most effective can help guide efforts to extend them to patients with COPD. The purpose of this narrative review was to summarize evidence from studies testing smoking cessation interventions in patients with COPD and discuss how these interventions may be integrated into PR programs. REVIEW METHODS: Searches were conducted in the PubMed and Web of Science databases. Search terms included "(smoking cessation) AND (RCT OR clinical trial OR intervention) AND (pulmonary OR chronic bronchitis OR emphysema OR COPD)." Published original studies were included if they used a prospective, experimental design, tested a smoking cessation intervention, reported smoking cessation rate, and included patients with COPD or a subgroup analysis focused on smokers with COPD. SUMMARY: Twenty-seven distinct studies were included in the review. Most studies tested multitreatment smoking cessation interventions involving some form of counseling in combination with pharmacotherapy and/or health education. Overall, smoking cessation interventions may help promote higher rates of smoking abstinence in patients with COPD, particularly multifaceted interventions that include intensive counseling (eg, individual, group, and telephone support), smoking cessation medication or nicotine replacement therapy, and health education.