Fig 1.
Timeline of U.S. Environmental Protection Agency (EPA) action on formaldehyde from September 1990-December 2016, highlighting Integration Risk Information System (IRIS) final assessments releases, reassessments, internal and external reviews, and final rules issued.
Table 1.
Strength of evidence definitions for human evidence.
Fig 2.
PRISMA flowchart showing the literature search and screening process for studies relevant to formaldehyde exposure and asthma outcomes.
Our search was not limited by language or publication date (search was conducted up until April 1, 2020). The search terms used for each database are provided in S1–S7 Tables.
Table 2.
Summary of included studies (n = 90).
Table 3.
Study characteristics, stratified by population health outcome group.
Fig 3.
Cumulative risk of bias ratings (low, probably low, probably high, or high) across all human studies included in our systematic review of formaldehyde exposure and asthma outcomes.
Risk of bias designations for individual studies are assigned by review authors according to criteria provided in S3 Methods (Risk of Bias instructions) and the justifications for each study are provided in S8–S95 Tables.
Fig 4.
Risk of bias ratings (low, probably low, probably high, or high) for all human studies included in our systematic review of formaldehyde exposure and asthma outcomes, organized by study population (children or adult) and outcome (asthma diagnosis, asthma symptoms, or pulmonary measures).
Risk of bias designations for individual studies are assigned by review authors according to criteria provided in S3 Methods (Risk of Bias instructions) and the justifications for each study are provided in S8–S95 Tables.
Fig 5.
Meta-analysis of human studies (n = 9 studies, including a total of 9,049 children) for formaldehyde exposure for asthma diagnosis assessed in children up to 15 years of age: Reported effect estimates and 95% confidence interval (CI) from individual studies (inverse-variance weighted, represented by size of rectangle) and overall pooled estimate from random effects (RE) model per 10 μg/m3 increase in formaldehyde exposure.
Heterogeneity statistics: I2 = 27.2%, p = 0.202.
Table 4.
Meta-analysis and sensitivity analysis of childhood asthma diagnosis (N = 9 studies) pooled ORs and 95% CIs for random-effects models.
Fig 6.
Meta-analysis of human studies (n = 5 studies, including a total of 7,662 children) for formaldehyde exposure for asthma symptoms (wheeze and shortness of breath) assessed in children up to 15 years of age: Reported effect estimates and 95% confidence interval (CI) from individual studies (inverse-variance weighted, represented by size of rectangle) and overall pooled estimate from random effects (RE) model per 10 μg/m3 increase in formaldehyde exposure.
Heterogeneity statistics: I2 = 0%, p = 0.899.
Fig 7.
Dose-response relationship (n = 3 studies, including a total of 3,600 adult participants) between formaldehyde exposure (μg/m3) and relative risk of asthma diagnosis in adults.
Dose-response data from Yeatts et al. 2012 (63), Billionnet et al. 2011 (92), Matsunaga et al. 2008 (93). Data were modeled with random-effects log linear models with restricted cubic splines mixed effects methods with exchangeable covariance structure of multivariable-adjusted relative risks. Lines with long dashes represent the 95% confidence interval (CI) bounds for the fitted nonlinear trend (solid line). Symbols (triangles, circles, and squares) represent point estimates.
Table 5.
Summary of rating quality and strength of the human evidence, by population/outcome group.
Table 6.
Cases reduced and willingness to pay for a reduction in formaldehyde exposure implied by the proposed EPA rule on pressed wood products (once the impacts of the rule have reached steady-state).