Perfluoroalkyl substances are linked to incident chronic spontaneous urticaria: A nested case-control study

Previous studies suggested immunotoxicity of perfluoroalkyl substances (PFASs), but contradictory findings were reported for the associations of PFASs with allergies. The current study aimed to investigate the association of serum PFASs with incident chronic spontaneous urticaria (CSU) in adults. A nested case-control study within a longitudinal cohort of 7051 government employees in China was conducted. Participants with urticaria at the baseline were excluded. During the first follow-up, 70 incident CSU cases were included, and 70 matched healthy controls were randomly selected. In serum samples collected at the baseline, eight PFASs were determined using the UHPLC-MS/MS approach. The median serum concentrations of perfluorobutanoic acid (PFBA) and perfluoroheptanoic acid (PFHpA) were significantly higher in participants with incident CSU. The area under the receiver operating characteristic curve was 0.714 (95% CI: 0.60-0.83) based on the joint prediction by PFBA and PFHpA. The Bayesian kernel machine regression showed a nonlinear positive overall effect of the mixture of PFASs, and identified significant single effects of PFBA and PFHpA. Serum interleukin-4 was significantly higher in the case group at baseline, and was positively associated with PFHpA (r = 0.24). Causal mediation analysis indicated interleukin-4 as a partial mediator (14.8%) in the association of PFHpA with CSU. In conclusion, serum PFASs are associated with an increased risk of incident CSU, and PFBA and PFHpA might be the effective compounds.