Asthma triggered by extreme temperatures: From epidemiological evidence to biological plausibility

There is rapidly growing evidence indicating that extreme temperature is a crucial trigger and potential activator of asthma; however, the effects of extreme temperature on asthma are inconsistently reported and the its potential mechanisms remain undefined.This review aims to estimate the impacts of extreme heat, extreme cold, and temperature variations on asthma by systematically summarizing the existing studies from epidemiological evidence to biological plausibility.We conducted a systematic search in PubMed, Embase, and Web of Science from inception to June 30, 2022, and we retrieved articles of epidemiology and biological studies which assessed associations between extreme temperatures and asthma. This protocol was registered with PROSPERO (CRD42021273613).From 12,435 identified records, 111 eligible studies were included in the qualitative synthesis, and 37 articles were included in the meta-analysis (20 for extreme heat, 16 for extreme cold, and 15 for temperature variations). For epidemiological evidence, we found that the synergistic effects of extreme temperatures, indoor/outdoor environments, and individual vulnerabilities are important triggers for asthma attacks, especially when there is extreme heat or cold. Meta-analysis further confirmed the associations, and the pooled relative risks for asthma attacks in extreme heat and extreme cold were 1.07 (95%CI: 1.03-1.12) and 1.20 (95%CI: 1.12-1.29), respectively. Additionally, this review discussed the potential inflammatory mechanisms behind the associations between extreme temperatures and asthma exacerbation, and highlighted the regulatory role of immunological pathways and transient receptor potential ion channels in asthma triggered by extreme temperatures.We concluded that both extreme heat and cold could significantly increase the risk of asthma. Additionally, we proposed a potential mechanistic framework, which is important for understanding the disease pathogenesis that uncovers the complex mechanisms of asthma triggered by extreme temperatures and protects the sensitive individuals from impacts of extreme weather events and climate change.