Future cohort studies should incorporate objective

The gap

Evidence profile

Sourced from the future-work section and limitations section and limitations and inline gaps of the source papers, classified as general, spanning 6 journals.

Supporting evidence — 7 representative gaps

• The association between periodontal disease and lung cancer: a re-evaluation of independent causal relationships in the presence of smoking as a confounder and an exploration of potential mechanisms (2026) · Frontiers in Cellular and Infection Microbiology · doi

  Future cohort studies should incorporate objective biomarkers of tobacco exposure, such as serum cotinine or urinary nicotine metabolites, to better control for confounding. Large-scale studies with stringent exclusion of former smokers and secondhand smoke exposure are needed to investigate the association in non-smokers. Advanced causal inference methodologies should be used to investigate whether the observed association reflects a causal relationship.

  generalfuture-work section
  Keywords: future cohort studies incorporate objective biomarkers tobacco exposure
• The association between periodontal disease and lung cancer: a re-evaluation of independent causal relationships in the presence of smoking as a confounder and an exploration of potential mechanisms (2026) · Frontiers in Cellular and Infection Microbiology · doi

  The findings among non-smokers are inconsistent, suggesting possible residual confounding. Current studies predominantly rely on self-reported smoking status or pack-year estimates, which are susceptible to recall bias. The observed association may not reflect a causal relationship, requiring further investigation through advanced causal inference methodologies. Large-scale studies with stringent exclusion of former smokers and secondhand smoke exposure are needed.

  generallimitations section
  Keywords: findings among non-smokers inconsistent suggesting possible residual confounding
• Smoking, alcohol consumption, and psoriasis risk: a systematic review and dose-response meta-analysis of observational studies (2026) · Frontiers in Public Health · doi

  should also be acknowledged. First, substantial between-study heterogeneity remained, particularly in the primary smoking analysis. Although heterogeneity was explored, univariable meta-regression showed that geographic region explained only a limited proportion of the observed variability (Wald χ 2 = 2.01, P = 0.3669; R2 ≈ 10.47%). Additional clinically relevant sources of heterogeneity likely included differences in outcome ascertainment, exposure assessment, and adjustment for major confounders such as body mass index, as well as mutual adjustment for smoking and alcohol exposure. More detailed quantitative exploration of these factors was limited by incomplete and non-uniform reporting across the included studies. Therefore, the pooled estimates should be interpreted as summaries of direction and overall magnitude rather than as precise effect sizes applicable across all study settings. a assumption, HRs Second, although ORs and RRs were considered approximately comparable under are low-incidence conceptually distinct time-to-event measures and may not be fully equivalent to cumulative risk estimates. We therefore performed additional stratified and sensitivity analyses for smoking and a limited alcohol-related supplementary analysis restricted to OR-based studies; however, some cross-measure comparability concerns remain. Accordingly, pooled estimates involving different effect measures should be interpreted with caution despite the supporting sensitivity analyses. Third, smoking and alcohol consumption are closely related index, cardiometabolic to socioeconomic status, body mass status, and psychological or behavioral factors, and residual confounding cannot be excluded despite multivariable adjustment in most included studies. The most plausible direction of residual confounding is overestimation of the observed associations, especially for alcohol, because alcohol consumption frequently co-occurs with smoking and other psoriasis-related risk factors. Given the modest alcohol effect size and attenuation after trim- and-fill adjustment, residual confounding could have a meaningful influence on the alcohol estimate. However, the exact magnitude of this bias could not be quantified because the included studies differed in exposure definitions, adjustment models, and reporting detail. Covariate adjustment patterns are summarized in Supplementary Table 9. Fourth, although the literature search was updated through December 18, 2025, no eligible studies published in 2025 met the inclusion criteria; thus, the quantitative synthesis ultimately reflected the available evidence through 2024. Fifth, we did not systematically search trial registries or other gray literature sources, which may have increased the possibility of publication or reporting bias. Finally, publication bias or small-study effects were suggested in some alcohol-related and residual-risk analyses, indicating that those findings should be interpreted cautiously.

  generallimitationsevidence 5/5
  Keywords: alcohol adjustment smoking included related residual heterogeneity limited exposure factors reporting estimates interpreted risk analyses
• Tobacco smoke exposure and spine fracture risk in US adults: A cross-sectional analysis of the National Health and Nutrition Examination Survey 1999–2010, 2013–2014, 2017–2020 (2026) · Tobacco Induced Diseases · doi

  The nationwide and multi-ethnic scope of our study, based on the NHANES database with its complex sampling design, enhances the applicability and generalizability of our findings to the noninstitutionalized US adult population. Furthermore, the large sample size (N=31124) provided adequate statistical power to detect the association of interest. In addition, a key methodological strength is the use of serum cotinine, an objective and quantitative biomarker, to assess tobacco smoke exposure. To our knowledge, this represents the first large-scale, population-based study to examine the specific relationship between tobacco smoke exposure (objectively measured by serum cotinine) and spine fracture risk. This approach minimizes misclassification bias inherent in self-reported smoking data and strengthens the internal validity of our exposure-outcome association. Finally, the application of complex survey weights in all analyses ensured that our estimates are representative of the non-institutionalized US adult population, further bolstering the external validity of our results. However, several limitations should be noted. Firstly, the generalizability of our results may be constrained by the exclusive focus on the US population; external validation in diverse international cohorts is necessary. Secondly, the inherent constraints of the cross-sectional design preclude definitive causal inference regarding the relationship between tobacco smoke exposure and spine fracture. Thirdly, the assessment of serum cotinine at a single timepoint may not accurately reflect long-term Tob. Induc. Dis. 2026;24(June):83 https://doi.org/10.18332/tid/217959 10 Tobacco Induced Diseases Research Paperexposure patterns, as it cannot account for intraindividual variability over time. Fourth, despite adjusting for a comprehensive set of covariates, residual confounding from unmeasured or imperfectly measured variables remains possible. Specifically, we lacked data on important potential confounders such as physical activity levels, dietary calcium and vitamin D intake, bone mineral density (BMD), history of falls, and use of medications affecting bone metabolism (e.g. glucocorticoids, bisphosphonates). Previous studies have identified these factors as significant predictors of fracture risk and may also be associated with smoking behavior, thus potentially confounding the observed association28. Fifth, the use of self-reported data for several variables, including spine fracture status and comorbidities, introduces the potential for recall bias and outcome misclassification.

  generallimitationsevidence 5/5
  Keywords: exposure fracture population cotinine tobacco association serum smoke spine bias based complex design generalizability institutionalized
• Exercise Interventions for Reducing Nicotine Dependence and Craving in E-Cigarette Users: A Narrative Review (2026) · Quality in Sport · doi

  Several limitations should be acknowledged. First, evidence evaluating exercise interventions specifically among exclusive e-cigarette users remains limited, and part of the interpretation relied on findings derived from studies involving conventional cigarette smokers. Consequently, direct extrapolation of current observations to vaping populations should be approached cautiously. Second, heterogeneity was observed across the included studies regarding intervention design, exercise characteristics, outcome assessment, and participant populations. These differences limited direct comparisons and complicated interpretation of the available evidence. Finally, only studies published in English were included, which may have resulted in omission of relevant findings reported in other languages.

  generallimitationsevidence 5/5
  Keywords: evidence exercise cigarette limited interpretation direct populations included several limitations acknowledged first evaluating interventions specifically
• A Systematic Review and Meta-Analysis Evaluating the Role of GLP-1 Receptor Agonists in Substance Use Disorders (2026) · Cureus · doi

  This meta-analysis has some limitations. First, the small number of included RCTs (n = 5 in quantitative synthesis) substantially limits statistical power for subgroup analyses, increases the influence of each study on pooled estimates, and precludes assessment of small-study effects via formal regression tests. Second, marked clinical and methodological heterogeneity limits the clinical interpretability of pooled estimates, particularly for alcohol outcomes. Third, most included trials were short (6-26 weeks), so whether GLP-1RA effects on substance use are maintained with longer treatment or after discontinuation is entirely unknown. Assessment of publication bias was also limited because the number of included studies was too small for reliable funnel plot interpretation or formal asymmetry testing.

  generallimitationsevidence 5/5
  Keywords: small included number limits pooled estimates assessment effects formal clinical meta limitations first rcts quantitative
• Smoking-Attributable Gastrointestinal Cancer Burden in Brazil, Russia, India, China, and South Africa (BRICS) and Associated Economies (1990-2023): A Global Burden of Disease Study Analysis (2026) · Tobacco Prevention & Cessation · doi

  Strengths and limitations This study has several strengths. Second, limited by the GBD framework, there was no analysis of gender differences and details such as the amount of cigarettes smoked per day, smoking duration and whether they had quit were not included, so it was impossible to explore dose-response relationships25,26. SUPPLEMENTARY FILE DISCLAIMER The content has been provided by the author(s) and has not been reviewed, verified, or endorsed by European Publishing.

  generalinline gapsevidence 5/5
  Keywords: strengths limitations several second limited framework there gender differences details amount cigarettes smoked smoking duration

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