Association between phthalate exposure and asthma risk: A meta-analysis of observational studies

Background: Phthalates are ubiquitously found in numerous environments and have been related to a variety of adverse health effects. Previous studies have suggested that phthalate exposure is associated with asthma risk in humans; however, such findings are inconsistent. Methods: The aim of the present meta-analysis was to clarify the association between phthalate exposure and asthma risk. A literature search was conducted using PubMed, EMBASE and Web of Science for relevant studies published up to January 5, 2020. Fixed-effects or random-effects models were applied to combine the results, and several subgroup analyses were used to explore the sources of heterogeneity. Results: A total of 14 studies containing more than 14,000 participants were included in the present study. A positive, significant association between mono-benzyl phthalate (MBzP) levels and asthma risk was found, and the overall odds ratio (OR) was 1.17 (95% confidence interval [CI]: 1.06-1.28, P-value for overall effect [P-z]= 0.001), with a low heterogeneity (P-value for heterogeneity [Phet]= 0.193, I-2= 23.6%). The pooled ORs for mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) and mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP) concentrations were 1.13 (95% CI: 1.03-1.24, P-z = 0.011) and 1.20 (95% CI: 1.00-1.42, P-z = 0.045), respectively. Children with high levels of MBzP or mono-(carboxynonyl) phthalate (MCNP) were suggested to have increased odds of asthma compared to older populations. In the subgroup analysis by study location, an increased risk for asthma in relation to levels of the sum of di-2-ethylhexyl phthalate (SDEHP) was observed in European studies (OR = 1.16, 95% CI: 1.00-1.34, P-z = 0.048) compared to Asia and North America. Conclusions: Urinary levels of MBzP, MEHHP, MECPP, MCNP, and DEHP were positively related to asthma risk. No significant association was observed for the other phthalate metabolites in relation to asthma risk. Further research is needed to verify these findings and shed light on the molecular mechanism by which phthalates are associated with asthma.