Our study highlights the gene signature of the airway epithelium, and specifically observed changes in Cma1 and Tiam2 expression in extreme high temperature, increased Sftpc and Nxnl expression in extreme low temperature, and decreased Wfdc21, Cib3, Gpr171, and Cttnbp2 in extreme temperature fluctuation of mice and asthma patients. Here, GPR171 is linked to asthma.