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Cited by 167Smoking Behavior and CessationAir Quality and Health ImpactsChronic Obstructive Pulmonary Disease (COPD) Research

The DOI matches its Crossref record; 470 of the 470 references it cites were found in a registry or an index; 15 of the 20 sources its claims cite were checked for support.

Health effects associated with exposure to secondhand smoke: a Burden of Proof study

Open access
Flor, Luisa S., Anderson, Jason A., Ahmad, Noah, Aravkin, Aleksandr, Carr, Sinclair, Dai, Xiaochen, Gil, Gabriela F., Hay, Simon I., Malloy, Matthew J., McLaughlin, Susan A., Mullany, Erin C., Murray, Christopher J. L., O’Connell, Erin M., Okereke, Chukwuma, Sorensen, Reed J. D., Whisnant, Joanna, Zheng, Peng, Gakidou, Emmanuela·2024·Nature Medicine
DOI 10.1038/s41591-023-02743-4PMC PMC10803272
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Abstract

Despite a gradual decline in smoking rates over time, exposure to secondhand smoke (SHS) continues to cause harm to nonsmokers, who are disproportionately children and women living in low- and middle-income countries. We comprehensively reviewed the literature published by July 2022 concerning the adverse impacts of SHS exposure on nine health outcomes. Following, we quantified each exposure–response association accounting for various sources of uncertainty and evaluated the strength of the evidence supporting our analyses using the Burden of Proof Risk Function methodology. We found all nine health outcomes to be associated with SHS exposure. We conservatively estimated that SHS increases the risk of ischemic heart disease, stroke, type 2 diabetes and lung cancer by at least around 8%, 5%, 1% and 1%, respectively, with the evidence supporting these harmful associations rated as weak (two stars). The evidence supporting the harmful associations between SHS and otitis media, asthma, lower respiratory infections, breast cancer and chronic obstructive pulmonary disease was weaker (one star). Despite the weak underlying evidence for these associations, our results reinforce the harmful effects of SHS on health and the need to prioritize advancing efforts to reduce active and passive smoking through a combination of public health policies and education initiatives.

Overview

AI snapshot

Written from the paper’s full text.

TL;DR

This Burden of Proof meta-analysis synthesized evidence through July 2022 on secondhand smoke (SHS) exposure and nine health outcomes, finding statistically significant associations with all nine when not accounting for between-study heterogeneity. Under conservative BPRF estimates, SHS exposure was associated with at least around 8%, 5%, 1% and 1% higher risk of ischemic heart disease, stroke, type 2 diabetes and lung cancer, respectively, with these four rated two stars and the remaining five outcomes rated one star.

Key findings

  • Across 410 included publications and 623 observations from over 178 locations, all nine outcomes showed statistically significant associations with SHS exposure before accounting for between-study heterogeneity.
  • Conservative BPRF estimates: ischemic heart disease RR 1.26 (1.05–1.52), BPRF 1.08, ROS 0.04, two stars, at least 8% higher risk; stroke RR 1.16 (1.03–1.32), BPRF 1.05, ROS 0.02, two stars, at least 5% higher risk; type 2 diabetes RR 1.16 (0.98–1.37), BPRF 1.01, ROS 0.005, two stars, at least 1% higher risk; lung cancer RR 1.37 (0.94–1.99), BPRF 1.00, ROS 0.001, two stars at the lower threshold, around 1% higher risk.
  • The evidence for otitis media (BPRF 0.95, ROS −0.03), asthma (BPRF 0.93, ROS −0.04), lower respiratory infections (BPRF 0.88, ROS −0.06), breast cancer (BPRF 0.81, ROS −0.11) and COPD (BPRF 0.75, ROS −0.14) was weaker, each rated one star.
  • No publication bias was detected in the primary models; publication bias was found for otitis media in one prospective-cohort sensitivity analysis.

Methods

  • PRISMA systematic review in PubMed and Web of Science for studies published 1 January 1970 to 31 July 2022, plus citation searching; 7,109 unique records and 1,972 additional records were screened, yielding 410 publications. Included designs were mostly case–control (n = 235) and prospective cohort (n = 156), with smaller numbers of nested case–control, retrospective cohort, case–cohort and case-crossover studies.
  • The Burden of Proof Risk Function (BPRF) framework used MR-BRT meta-regression to estimate pooled relative risks for dichotomous SHS exposure, adjust for selected bias covariates, quantify unexplained between-study heterogeneity (gamma), test publication bias with Egger’s regression, and derive BPRF, ROS and star ratings.
  • Sensitivity analyses restricted models to prospective cohort studies, never-smoking samples, and both restrictions combined; asthma also had a children-only sensitivity analysis.

Limitations

  • The paper states that SHS exposure was self-reported or proxy-reported, risking exposure misclassification; most surveys captured current rather than cumulative exposure, so formerly exposed individuals could be misclassified as unexposed; and dichotomous exposure may oversimplify intensity and frequency.
  • The paper also states that input studies used varied exposure definitions and locations, public-setting exposure was not included, modeled RRs were not disaggregated by geography, sex or age group, and the nine outcomes do not capture the full disease burden of SHS.
  • The text makes evident that several associations were sensitive to data restrictions: stroke was downgraded to one star when restricted to prospective cohorts of never smokers, lung cancer to one star in prospective cohorts, breast cancer showed no significant association in prospective cohorts without gamma, and COPD showed no significant association in prospective cohorts or never-smoking populations without gamma.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1038/s41591-023-02743-4

Cites

470 of 470 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Figures

Fig. 1 Modified funnel plots for SHS exposure and two cardiovascular outcomes. a,b, These modified funnel plots show the residuals of the reported mean RR relative to 0, the null value, on the x axis and the residuals of the standard error, as estimated from both the reported standard error and gamma, relative to 0 on the y axis, for IHD (a) and stroke (b). The light-blue vertical interval corresponds to the 95% uncertainty interval incorporating between-study heterogeneity; the dark-blue vertical interval corresponds to the 95% uncertainty interval (UI) without between-study heterogeneity; the dots are each included observation; the red Xs are outliered observations; the gray dotted line reflects the null log(RR); the blue line is the mean log(RR) for SHS and the outcome of interest; and the red line is the Burden of Proof function at the fifth quantile for these harmful risk–outcome associations.
Fig. 1 Modified funnel plots for SHS exposure and two cardiovascular outcomes. a,b, These modified funnel plots show the residuals of the reported mean RR relative to 0, the null value, on the x axis and the residuals of the standard error, as estimated from both the reported standard error and gamma, relative to 0 on the y axis, for IHD (a) and stroke (b). The light-blue vertical interval corresponds to the 95% uncertainty interval incorporating between-study heterogeneity; the dark-blue vertical interval corresponds to the 95% uncertainty interval (UI) without between-study heterogeneity; the dots are each included observation; the red Xs are outliered observations; the gray dotted line reflects the null log(RR); the blue line is the mean log(RR) for SHS and the outcome of interest; and the red line is the Burden of Proof function at the fifth quantile for these harmful risk–outcome associations.CC BY · PubMed Central
Fig. 2 Modified funnel plots for SHS exposure and two cancer outcomes. a,b, These modified funnel plots show the residuals of the reported mean RR relative to 0, the null value, on the x axis and the residuals of the standard error, as estimated from both the reported standard error and gamma, relative to 0 on the y axis, for lung cancer (a) and breast cancer (b). The light-blue vertical interval corresponds to the 95% uncertainty interval incorporating between-study heterogeneity; the dark-blue vertical interval corresponds to the 95% uncertainty interval (UI) without between-study heterogeneity; the dots are each included observation; the red Xs are outliered observations; the gray dotted line reflects the null log(RR); the blue line is the mean log(RR) for SHS and the outcome of interest; the red line is the Burden of Proof function at the fifth quantile for these harmful risk–outcome associations.
Fig. 2 Modified funnel plots for SHS exposure and two cancer outcomes. a,b, These modified funnel plots show the residuals of the reported mean RR relative to 0, the null value, on the x axis and the residuals of the standard error, as estimated from both the reported standard error and gamma, relative to 0 on the y axis, for lung cancer (a) and breast cancer (b). The light-blue vertical interval corresponds to the 95% uncertainty interval incorporating between-study heterogeneity; the dark-blue vertical interval corresponds to the 95% uncertainty interval (UI) without between-study heterogeneity; the dots are each included observation; the red Xs are outliered observations; the gray dotted line reflects the null log(RR); the blue line is the mean log(RR) for SHS and the outcome of interest; the red line is the Burden of Proof function at the fifth quantile for these harmful risk–outcome associations.CC BY · PubMed Central
Fig. 3 Modified funnel plots for SHS exposure and three respiratory outcomes. These modified funnel plots show the residuals of the reported mean RR relative to 0, the null value, on the x axis and the residuals of the standard error, as estimated from both the reported standard error and gamma, relative to 0 on the y axis, for asthma (a), lower respiratory infections (b) and COPD (c). The light-blue vertical interval corresponds to the 95% uncertainty interval incorporating between-study heterogeneity; the dark-blue vertical interval corresponds to the 95% uncertainty interval (UI) without between-study heterogeneity; the dots are each included observation; the red Xs are outliered observations; the gray dotted line reflects the null log(RR); the blue line is the mean log(RR) for SHS and the outcome of interest; the red line is the Burden of Proof function at the fifth quantile for these harmful risk–outcome associations.
Fig. 3 Modified funnel plots for SHS exposure and three respiratory outcomes. These modified funnel plots show the residuals of the reported mean RR relative to 0, the null value, on the x axis and the residuals of the standard error, as estimated from both the reported standard error and gamma, relative to 0 on the y axis, for asthma (a), lower respiratory infections (b) and COPD (c). The light-blue vertical interval corresponds to the 95% uncertainty interval incorporating between-study heterogeneity; the dark-blue vertical interval corresponds to the 95% uncertainty interval (UI) without between-study heterogeneity; the dots are each included observation; the red Xs are outliered observations; the gray dotted line reflects the null log(RR); the blue line is the mean log(RR) for SHS and the outcome of interest; the red line is the Burden of Proof function at the fifth quantile for these harmful risk–outcome associations.CC BY · PubMed Central
Fig. 4 Modified funnel plots for SHS exposure and type 2 diabetes and otitis media. a,b, These modified funnel plots show the residuals of the reported mean RR relative to 0, the null value, on the x axis and the residuals of the standard error, as estimated from both the reported standard error and gamma, relative to 0 on the y axis, for type 2 diabetes (a) and otitis media (b). The light-blue vertical interval corresponds to the 95% uncertainty interval incorporating between-study heterogeneity; the dark-blue vertical interval corresponds to the 95% uncertainty interval (UI) without between-study heterogeneity; the dots are each included observation; the red Xs are outliered observations; the gray dotted line reflects the null log(RR); the blue line is the mean log(RR) for SHS and the outcome of interest; the red line is the Burden of Proof function at the fifth quantile for these harmful risk–outcome associations.
Fig. 4 Modified funnel plots for SHS exposure and type 2 diabetes and otitis media. a,b, These modified funnel plots show the residuals of the reported mean RR relative to 0, the null value, on the x axis and the residuals of the standard error, as estimated from both the reported standard error and gamma, relative to 0 on the y axis, for type 2 diabetes (a) and otitis media (b). The light-blue vertical interval corresponds to the 95% uncertainty interval incorporating between-study heterogeneity; the dark-blue vertical interval corresponds to the 95% uncertainty interval (UI) without between-study heterogeneity; the dots are each included observation; the red Xs are outliered observations; the gray dotted line reflects the null log(RR); the blue line is the mean log(RR) for SHS and the outcome of interest; the red line is the Burden of Proof function at the fifth quantile for these harmful risk–outcome associations.CC BY · PubMed Central
Extended Data Fig. 1 Forest plot of the association between secondhand smoke exposure and ischemic heart disease. This forest plot presents the estimated mean relative risk, its 95% uncertainty intervals (UI), and the data points underlying the estimates for ischemic heart disease in association with secondhand smoke exposure (two-star rating of the risk-outcome relationship). The color of the point indicates whether the point was detected and trimmed as an outlier. The light blue interval corresponds to the 95% UI incorporating between-study heterogeneity; the dark blue interval corresponds to the 95% UI without between-study heterogeneity. The black vertical dotted line reflects the null relative risk value (one) and the red vertical line is the burden of proof function at the 5th quantile for this harmful risk-outcome association. The black data points and horizontal lines each correspond to a mean effect size and 95% UI from the included study identified on the y-axis. We included multiple observations from a single study when effects were reported by location or source of exposure and/or separately by sex or other subgroups. See Supplementary Table 4 for more details on included observations from each study (n = 37 studies).
Extended Data Fig. 1 Forest plot of the association between secondhand smoke exposure and ischemic heart disease. This forest plot presents the estimated mean relative risk, its 95% uncertainty intervals (UI), and the data points underlying the estimates for ischemic heart disease in association with secondhand smoke exposure (two-star rating of the risk-outcome relationship). The color of the point indicates whether the point was detected and trimmed as an outlier. The light blue interval corresponds to the 95% UI incorporating between-study heterogeneity; the dark blue interval corresponds to the 95% UI without between-study heterogeneity. The black vertical dotted line reflects the null relative risk value (one) and the red vertical line is the burden of proof function at the 5th quantile for this harmful risk-outcome association. The black data points and horizontal lines each correspond to a mean effect size and 95% UI from the included study identified on the y-axis. We included multiple observations from a single study when effects were reported by location or source of exposure and/or separately by sex or other subgroups. See Supplementary Table 4 for more details on included observations from each study (n = 37 studies).CC BY · PubMed Central
Extended Data Fig. 2 Forest plot of the association between secondhand smoke exposure and stroke. This forest plot presents the estimated mean relative risk, its 95% uncertainty intervals (UI), and the data points underlying the estimates for ischemic heart disease in association with secondhand smoke exposure (two-star rating of the risk-outcome relationship). The color of the point indicates whether the point was detected and trimmed as an outlier. The light blue interval corresponds to the 95% UI incorporating between-study heterogeneity; the dark blue interval corresponds to the 95% UI without between-study heterogeneity. The black vertical dotted line reflects the null relative risk value (one) and the red vertical line is the burden of proof function at the 5th quantile for this harmful risk-outcome association. The black data points and horizontal lines each correspond to a mean effect size and 95% UI from the included study identified on the y-axis. We included multiple observations from a single study when effects were reported by location or source of exposure and/or separately by sex or other subgroups. See Supplementary Table 5 for more details on included observations from each study (n = 20 studies).
Extended Data Fig. 2 Forest plot of the association between secondhand smoke exposure and stroke. This forest plot presents the estimated mean relative risk, its 95% uncertainty intervals (UI), and the data points underlying the estimates for ischemic heart disease in association with secondhand smoke exposure (two-star rating of the risk-outcome relationship). The color of the point indicates whether the point was detected and trimmed as an outlier. The light blue interval corresponds to the 95% UI incorporating between-study heterogeneity; the dark blue interval corresponds to the 95% UI without between-study heterogeneity. The black vertical dotted line reflects the null relative risk value (one) and the red vertical line is the burden of proof function at the 5th quantile for this harmful risk-outcome association. The black data points and horizontal lines each correspond to a mean effect size and 95% UI from the included study identified on the y-axis. We included multiple observations from a single study when effects were reported by location or source of exposure and/or separately by sex or other subgroups. See Supplementary Table 5 for more details on included observations from each study (n = 20 studies).CC BY · PubMed Central
Extended Data Fig. 3 Forest plot of the association between secondhand smoke exposure and lung cancer. This forest plot presents the estimated mean relative risk, its 95% uncertainty intervals (UI), and the data points underlying the estimates for ischemic heart disease in association with secondhand smoke exposure (two-star rating of the risk-outcome relationship). The color of the point indicates whether the point was detected and trimmed as an outlier. The light blue interval corresponds to the 95% UI incorporating between-study heterogeneity; the dark blue interval corresponds to the 95% UI without between-study heterogeneity. The black vertical dotted line reflects the null relative risk value (one) and the red vertical line is the burden of proof function at the 5th quantile for this harmful risk-outcome association. The black data points and horizontal lines each correspond to a mean effect size and 95% UI from the included study identified on the y-axis. We included multiple observations from a single study when effects were reported by location or source of exposure and/or separately by sex or other subgroups. See Supplementary Table 6 for more details on included observations from each study (n = 104 studies).
Extended Data Fig. 3 Forest plot of the association between secondhand smoke exposure and lung cancer. This forest plot presents the estimated mean relative risk, its 95% uncertainty intervals (UI), and the data points underlying the estimates for ischemic heart disease in association with secondhand smoke exposure (two-star rating of the risk-outcome relationship). The color of the point indicates whether the point was detected and trimmed as an outlier. The light blue interval corresponds to the 95% UI incorporating between-study heterogeneity; the dark blue interval corresponds to the 95% UI without between-study heterogeneity. The black vertical dotted line reflects the null relative risk value (one) and the red vertical line is the burden of proof function at the 5th quantile for this harmful risk-outcome association. The black data points and horizontal lines each correspond to a mean effect size and 95% UI from the included study identified on the y-axis. We included multiple observations from a single study when effects were reported by location or source of exposure and/or separately by sex or other subgroups. See Supplementary Table 6 for more details on included observations from each study (n = 104 studies).CC BY · PubMed Central
Extended Data Fig. 4 Forest plot of the association between secondhand smoke exposure and breast cancer. This forest plot presents the estimated mean relative risk, its 95% uncertainty intervals (UI), and the data points underlying the estimates for ischemic heart disease in association with secondhand smoke exposure (one-star rating of the risk-outcome relationship). The color of the point indicates whether the point was detected and trimmed as an outlier. The light blue interval corresponds to the 95% UI incorporating between-study heterogeneity; the dark blue interval corresponds to the 95% UI without between-study heterogeneity. The black vertical dotted line reflects the null relative risk value (one) and the red vertical line is the burden of proof function at the 5th quantile for this harmful risk-outcome association. The black data points and horizontal lines each correspond to a mean effect size and 95% UI from the included study identified on the y-axis. We included multiple observations from a single study when effects were reported by location or source of exposure and/or separately by sex or other subgroups. See Supplementary Table 7 for more details on included observations from each study (n = 51 studies).
Extended Data Fig. 4 Forest plot of the association between secondhand smoke exposure and breast cancer. This forest plot presents the estimated mean relative risk, its 95% uncertainty intervals (UI), and the data points underlying the estimates for ischemic heart disease in association with secondhand smoke exposure (one-star rating of the risk-outcome relationship). The color of the point indicates whether the point was detected and trimmed as an outlier. The light blue interval corresponds to the 95% UI incorporating between-study heterogeneity; the dark blue interval corresponds to the 95% UI without between-study heterogeneity. The black vertical dotted line reflects the null relative risk value (one) and the red vertical line is the burden of proof function at the 5th quantile for this harmful risk-outcome association. The black data points and horizontal lines each correspond to a mean effect size and 95% UI from the included study identified on the y-axis. We included multiple observations from a single study when effects were reported by location or source of exposure and/or separately by sex or other subgroups. See Supplementary Table 7 for more details on included observations from each study (n = 51 studies).CC BY · PubMed Central
Extended Data Fig. 5 Forest plot of the association between secondhand smoke exposure and asthma. This forest plot presents the estimated mean relative risk, its 95% uncertainty intervals (UI), and the data points underlying the estimates for ischemic heart disease in association with secondhand smoke exposure (one-star rating of the risk-outcome relationship). The color of the point indicates whether the point was detected and trimmed as an outlier. The light blue interval corresponds to the 95% UI incorporating between-study heterogeneity; the dark blue interval corresponds to the 95% UI without between-study heterogeneity. The black vertical dotted line reflects the null relative risk value (one) and the red vertical line is the burden of proof function at the 5th quantile for this harmful risk-outcome association. The black data points and horizontal lines each correspond to a mean effect size and 95% UI from the included study identified on the y-axis. We included multiple observations from a single study when effects were reported by location or source of exposure and/or separately by sex or other subgroups. See Supplementary Table 8 for more details on included observations from each study (n = 125 studies).
Extended Data Fig. 5 Forest plot of the association between secondhand smoke exposure and asthma. This forest plot presents the estimated mean relative risk, its 95% uncertainty intervals (UI), and the data points underlying the estimates for ischemic heart disease in association with secondhand smoke exposure (one-star rating of the risk-outcome relationship). The color of the point indicates whether the point was detected and trimmed as an outlier. The light blue interval corresponds to the 95% UI incorporating between-study heterogeneity; the dark blue interval corresponds to the 95% UI without between-study heterogeneity. The black vertical dotted line reflects the null relative risk value (one) and the red vertical line is the burden of proof function at the 5th quantile for this harmful risk-outcome association. The black data points and horizontal lines each correspond to a mean effect size and 95% UI from the included study identified on the y-axis. We included multiple observations from a single study when effects were reported by location or source of exposure and/or separately by sex or other subgroups. See Supplementary Table 8 for more details on included observations from each study (n = 125 studies).CC BY · PubMed Central
Extended Data Fig. 6 Forest plot of the association between secondhand smoke exposure and lower respiratory infections. This forest plot presents the estimated mean relative risk, its 95% uncertainty intervals (UI), and the data points underlying the estimates for ischemic heart disease in association with secondhand smoke exposure (one-star rating of the risk-outcome relationship). The color of the point indicates whether the point was detected and trimmed as an outlier. The light blue interval corresponds to the 95% UI incorporating between-study heterogeneity; the dark blue interval corresponds to the 95% UI without between-study heterogeneity. The black vertical dotted line reflects the null relative risk value (one) and the red vertical line is the burden of proof function at the 5th quantile for this harmful risk-outcome association. The black data points and horizontal lines each correspond to a mean effect size and 95% UI from the included study identified on the y-axis. We included multiple observations from a single study when effects were reported by location or source of exposure and/or separately by sex or other subgroups. See Supplementary Table 9 for more details on included observations from each study (n = 50 studies).
Extended Data Fig. 6 Forest plot of the association between secondhand smoke exposure and lower respiratory infections. This forest plot presents the estimated mean relative risk, its 95% uncertainty intervals (UI), and the data points underlying the estimates for ischemic heart disease in association with secondhand smoke exposure (one-star rating of the risk-outcome relationship). The color of the point indicates whether the point was detected and trimmed as an outlier. The light blue interval corresponds to the 95% UI incorporating between-study heterogeneity; the dark blue interval corresponds to the 95% UI without between-study heterogeneity. The black vertical dotted line reflects the null relative risk value (one) and the red vertical line is the burden of proof function at the 5th quantile for this harmful risk-outcome association. The black data points and horizontal lines each correspond to a mean effect size and 95% UI from the included study identified on the y-axis. We included multiple observations from a single study when effects were reported by location or source of exposure and/or separately by sex or other subgroups. See Supplementary Table 9 for more details on included observations from each study (n = 50 studies).CC BY · PubMed Central
Extended Data Fig. 7 Forest plot of the association between secondhand smoke exposure and chronic obstructive pulmonary disease. This forest plot presents the estimated mean relative risk, its 95% uncertainty intervals (UI), and the data points underlying the estimates for ischemic heart disease in association with secondhand smoke exposure (one-star rating of the risk-outcome relationship). The color of the point indicates whether the point was detected and trimmed as an outlier. The light blue interval corresponds to the 95% UI incorporating between-study heterogeneity; the dark blue interval corresponds to the 95% UI without between-study heterogeneity. The black vertical dotted line reflects the null relative risk value (one) and the red vertical line is the burden of proof function at the 5th quantile for this harmful risk-outcome association. The black data points and horizontal lines each correspond to a mean effect size and 95% UI from the included study identified on the y-axis. We included multiple observations from a single study when effects were reported by location or source of exposure and/or separately by sex or other subgroups. See Supplementary Table 10 for more details on included observations from each study (n = 21 studies).
Extended Data Fig. 7 Forest plot of the association between secondhand smoke exposure and chronic obstructive pulmonary disease. This forest plot presents the estimated mean relative risk, its 95% uncertainty intervals (UI), and the data points underlying the estimates for ischemic heart disease in association with secondhand smoke exposure (one-star rating of the risk-outcome relationship). The color of the point indicates whether the point was detected and trimmed as an outlier. The light blue interval corresponds to the 95% UI incorporating between-study heterogeneity; the dark blue interval corresponds to the 95% UI without between-study heterogeneity. The black vertical dotted line reflects the null relative risk value (one) and the red vertical line is the burden of proof function at the 5th quantile for this harmful risk-outcome association. The black data points and horizontal lines each correspond to a mean effect size and 95% UI from the included study identified on the y-axis. We included multiple observations from a single study when effects were reported by location or source of exposure and/or separately by sex or other subgroups. See Supplementary Table 10 for more details on included observations from each study (n = 21 studies).CC BY · PubMed Central
Extended Data Fig. 8 plot of the association between secondhand smoke exposure and type 2 diabetes mellitus. This forest plot presents the estimated mean relative risk, its 95% uncertainty intervals (UI), and the data points underlying the estimates for ischemic heart disease in association with secondhand smoke exposure (two-star rating of the risk-outcome relationship). The color of the point indicates whether the point was detected and trimmed as an outlier. The light blue interval corresponds to the 95% UI incorporating between-study heterogeneity; the dark blue interval corresponds to the 95% UI without between-study heterogeneity. The black vertical dotted line reflects the null relative risk value (one) and the red vertical line is the burden of proof function at the 5th quantile for this harmful risk-outcome association. The black data points and horizontal lines each correspond to a mean effect size and 95% UI from the included study identified on the y-axis. We included multiple observations from a single study when effects were reported by location or source of exposure and/or separately by sex or other subgroups. See Supplementary Table 11 for more details on included observations from each study (n = 9 studies).
Extended Data Fig. 8 plot of the association between secondhand smoke exposure and type 2 diabetes mellitus. This forest plot presents the estimated mean relative risk, its 95% uncertainty intervals (UI), and the data points underlying the estimates for ischemic heart disease in association with secondhand smoke exposure (two-star rating of the risk-outcome relationship). The color of the point indicates whether the point was detected and trimmed as an outlier. The light blue interval corresponds to the 95% UI incorporating between-study heterogeneity; the dark blue interval corresponds to the 95% UI without between-study heterogeneity. The black vertical dotted line reflects the null relative risk value (one) and the red vertical line is the burden of proof function at the 5th quantile for this harmful risk-outcome association. The black data points and horizontal lines each correspond to a mean effect size and 95% UI from the included study identified on the y-axis. We included multiple observations from a single study when effects were reported by location or source of exposure and/or separately by sex or other subgroups. See Supplementary Table 11 for more details on included observations from each study (n = 9 studies).CC BY · PubMed Central
Extended Data Fig. 9 plot of the association between secondhand smoke exposure and otitis media. This forest plot presents the estimated mean relative risk, its 95% uncertainty intervals (UI), and the data points underlying the estimates for ischemic heart disease in association with secondhand smoke exposure (one-star rating of the risk-outcome relationship). The color of the point indicates whether the point was detected and trimmed as an outlier. The light blue interval corresponds to the 95% UI incorporating between-study heterogeneity; the dark blue interval corresponds to the 95% UI without between-study heterogeneity. The black vertical dotted line reflects the null relative risk value (one) and the red vertical line is the burden of proof function at the 5th quantile for this harmful risk-outcome association. The black data points and horizontal lines each correspond to a mean effect size and 95% UI from the included study identified on the y-axis. We included multiple observations from a single study when effects were reported by location or source of exposure and/or separately by sex or other subgroups. See Supplementary Table 12 for more details on included observations from each study (n = 24 studies).
Extended Data Fig. 9 plot of the association between secondhand smoke exposure and otitis media. This forest plot presents the estimated mean relative risk, its 95% uncertainty intervals (UI), and the data points underlying the estimates for ischemic heart disease in association with secondhand smoke exposure (one-star rating of the risk-outcome relationship). The color of the point indicates whether the point was detected and trimmed as an outlier. The light blue interval corresponds to the 95% UI incorporating between-study heterogeneity; the dark blue interval corresponds to the 95% UI without between-study heterogeneity. The black vertical dotted line reflects the null relative risk value (one) and the red vertical line is the burden of proof function at the 5th quantile for this harmful risk-outcome association. The black data points and horizontal lines each correspond to a mean effect size and 95% UI from the included study identified on the y-axis. We included multiple observations from a single study when effects were reported by location or source of exposure and/or separately by sex or other subgroups. See Supplementary Table 12 for more details on included observations from each study (n = 24 studies).CC BY · PubMed Central
Extended Data Fig. 10 Summarized results of the primary model and sensitivity analyses conducted across all nine health outcomes. This heatmap reports the summarized results of the main model and the sensitivity analyses (columns) conducted for each of the nine health outcomes (rows) reported in this study. Detailed results for each of the sensitivity models are presented in the Supplementary Information (Supplementary Tables 13–16). Sensitivity analyses reflect the impact of restricting the input data to 1) prospective cohort studies, 2) observations associated with never-smokers, and 3) both prospective cohort studies and never-smoking samples. For asthma, we additionally restrict the data to children population aged 16 or less. General model parameters remained constant across models; we trimmed 10% of the data if more than 10 observations were available for the specific model. The color of the blue boxes and the number depicted in each box corresponds to the resulting risk-outcome score (ROS) calculated for models in which the estimates of association without incorporating between-study heterogeneity were statistically significant. Grey boxes depict models that did not pass this threshold and, thus, ROS did not apply (NA). For models that did pass this threshold, the ROS reflects a conservative interpretation of the data that aligns with the Burden of Proof approach incorporating between-study heterogeneity and other sources of uncertainty. The ROS is translated into a star rating from 1 to 5 stars based on thresholds outlined in Zheng et al. The star rating for each model result is reported as the yellow stars in each box. A one-star association suggests that there is weak evidence supporting estimates of an association between the risk and the outcome. A two-star association reflects that there is weak-to-moderate evidence suggesting an association between the risk and outcome, and additional stars illustrate increasing strength of evidence.
Extended Data Fig. 10 Summarized results of the primary model and sensitivity analyses conducted across all nine health outcomes. This heatmap reports the summarized results of the main model and the sensitivity analyses (columns) conducted for each of the nine health outcomes (rows) reported in this study. Detailed results for each of the sensitivity models are presented in the Supplementary Information (Supplementary Tables 13–16). Sensitivity analyses reflect the impact of restricting the input data to 1) prospective cohort studies, 2) observations associated with never-smokers, and 3) both prospective cohort studies and never-smoking samples. For asthma, we additionally restrict the data to children population aged 16 or less. General model parameters remained constant across models; we trimmed 10% of the data if more than 10 observations were available for the specific model. The color of the blue boxes and the number depicted in each box corresponds to the resulting risk-outcome score (ROS) calculated for models in which the estimates of association without incorporating between-study heterogeneity were statistically significant. Grey boxes depict models that did not pass this threshold and, thus, ROS did not apply (NA). For models that did pass this threshold, the ROS reflects a conservative interpretation of the data that aligns with the Burden of Proof approach incorporating between-study heterogeneity and other sources of uncertainty. The ROS is translated into a star rating from 1 to 5 stars based on thresholds outlined in Zheng et al. The star rating for each model result is reported as the yellow stars in each box. A one-star association suggests that there is weak evidence supporting estimates of an association between the risk and the outcome. A two-star association reflects that there is weak-to-moderate evidence suggesting an association between the risk and outcome, and additional stars illustrate increasing strength of evidence.CC BY · PubMed Central

Verification

Claims the paper makes

53 Own result · 41 Own method · 9 Own interpretation · 5 No basis given · 3 Supported · 2 Supported so far · 2 Partly supported · 2 No full text of the sources · 1 Sources not found · accuracy not yet measured

  • Probably not a substantial claim. 24
  • It may state two separate claims as one. 15
  • The quote only partly states this claim. 2
36 of 36

  • The paper relies on this without support.

    Substantial heterogeneity exists across and within SHS risk–outcome assessments in terms of quantity and quality of studies and reported strength of associations.

    “Despite these findings, substantial heterogeneity is detected across and within SHS risk–outcome assessments in terms of quantity and quality of studies and reported strength of associations.”

  • The paper relies on this without support.

    Variation across studies in definitions of risk exposure used is observed.

    “Variation across studies in the definitions of risk exposure used is also observed, with some reporting the risk associated with SHS exposure in specific settings16 or from specific sources (that is, maternal, paternal)17.”

  • The paper relies on this without support.

    The units and dose categories reported across studies vary widely due to limited availability of studies with environmental and biological samples and lack of a standard measure of SHS exposure.

    “Furthermore, given the limited availability of studies that assess exposure to tobacco smoke on the basis of environmental and biological samples, and the lack of a standard measure of SHS exposure, the units and dose categories reported across studies vary widely.”

  • The paper relies on this without support.

    These inconsistencies limit the comparability and consolidation of evidence concerning the health effects of SHS.

    “Together, these inconsistencies can limit the comparability and consolidation of evidence concerning the health effects of SHS.”
4 of 4

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

1 of 1

Citations

Cites

Show all 469 references

Research works printed but not linked: 4

  1. Salama, B. M., Abukanna, A. & Hegazy, A. Risk factors associated with chronic obstructive pulmonary disease in Arar, Saudi Arabia: a case–control study. Med. Sci. 24, 2487–2493 (2020).
  2. Janghorbani, M. & Sadeghigolmakani, N. Passive smoking and the risk of coronary heart disease among married non-smoking women. Med. J. Islam. Repub. Iran 11, 203–208 (1997).
  3. Woo, C. et al. A prospective study of passive cigarette smoke exposure and breast cancer. Am. J. Epidemiol. 151, 11 (2000).
  4. Dina, A. D. & Djuwita, R. The role of exclusive breastfeeding in reducing pneumonia prevalence in children under five. J. Gizi dan Pangan 16, 89–98 (2021).

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Metadata

Authors
Flor, L. S., Anderson, J. A., Ahmad, N., Aravkin, A., Carr, S., Dai, X., Gil, G. F., Hay, S. I., Malloy, M. J., McLaughlin, S. A., Mullany, E. C., Murray, C. J. L., O’Connell, E. M., Okereke, C., Sorensen, R. J. D., Whisnant, J., Zheng, P., & Gakidou, E.
Affiliations
University of Washington (US)
ORCID
Venue
Nature Medicine
Publisher
Springer Science and Business Media LLC
Published
2024-01
Volume
30
Issue
1
Pages
149-167
ISSN
  • 1078-8956 (ISSN-L)
  • 1546-170X
DOI
10.1038/s41591-023-02743-4
PMC
PMC10803272
OpenAlex
W4390706631
Semantic Scholar
b2594595aa44eea39d24b194c85ea97e6be58be7
Cited by
167
References
469
Citations by year
2026: 75 · 2025: 71 · 2024: 21
FWCI
47.64
Type
journal article
Language
en
Update notices
correction (2024-01-30)
Open access
Licence
Locations
  • Nature Medicine (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion, cc-by)
Funders
Bloomberg Family Foundation
Topics
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Smoking Behavior and Cessation
  • Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Air Quality and Health Impacts
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Chronic Obstructive Pulmonary Disease (COPD) Research
Keywords
passive smoking, non-smokers, health outcomes, ischemic heart disease, stroke, type 2 diabetes, lung cancer, otitis media, asthma, lower respiratory tract infection, breast cancer, chronic obstructive pulmonary disease, quality of evidence
MeSH terms
Asthma, Breast Neoplasms, Child, Diabetes Mellitus, Type 2, Female, Humans, Respiratory Tract Infections, Tobacco Smoke Pollution

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

A language model drew the claims from the paper on 2026-10-29, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).

A second model labelled each claim on 2026-10-29 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).

Cited sources are checked with a language model’s help (gpt-6-sol).

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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