Objective:To investigate the effects of montelukast sodium combined with compound methoxyphenamine on airway inflammation, intercellular adhesion molecule-1 (ICAM-1), toll-like receptor 4 (TLR4), and soluble programmed death ligand 1 (sPD-L1) levels in patients with post-infection cough.Methods:A total of 200 patients with post-infection cough who received treatment at The 903 Hospital of the PLA Joint Logistics Support Force from January to December 2023 were included in this randomized controlled study. The patients were divided into an observation group ( n = 100) and a control group ( n = 100) using the random number table method. The control group received oral administration of compound methoxyphenamine capsules, while the observation group received oral administration of montelukast sodium in addition to compound methoxyphenamine capsules. Both groups were treated for 7 days. The therapeutic effects as well as daytime and nighttime cough scores, airway inflammation change, serum ICAM-1, TLR4, and sPD-L1 levels, and Leicester Cough Questionnaire scores were compared between the two groups. Results:The total effective rate in the observation group was 95% (95/100), which was significantly higher than that in the control group [84% (84/100), Z = 2.49, P < 0.05]. After treatment, the daytime and nighttime cough scores in the observation group were (1.24 ± 0.31) points and (1.02 ± 0.31) points, respectively, which were significantly lower than those in the control group [(2.17 ± 0.65) points, (1.94 ± 0.47) points, t = 12.91, 16.34, both P < 0.001]. Serum levels of hypersensitive C-reactive protein, interleukin-8, tumor necrosis factor-alpha in the observation group were (8.84 ± 2.21) mg/L], (82.34 ± 13.24) mg/L, and (78.94 ± 13.24) ng/L, respectively, which were significantly lower than those in the control group [(12.76 ± 2.53) mg/L, (127.18 ± 35.17) mg/L, (102.31 ± 21.08) ng/L, t = 11.67, 11.93, 9.39, all P < 0.001]. The ICAM-1 and TLR4 levels in the observation group were (178.32 ± 21.23) μg/L and (7.45 ± 2.32) ng/L, respectively, which were significantly lower than those in the control group [(247.18 ± 25.64) μg/L, (19.98 ± 4.53) ng/L, t = 20.69, 24.62, both P < 0.001], while sPD-L1 level in the observation group [(2.34 ± 0.37) ng/L] was significantly higher than that in the control group [(1.72 ± 0.41) ng/L, t = -11.23, P < 0.001]. The quality-of-life scores in the observation group for social [(2.61 ± 0.25) points], psychological [(6.56 ± 0.45) points], physical [(7.65 ± 0.72) points], and total score [(16.81 ± 2.51) points] were significantly higher than those in the control group [(2.14 ± 0.30) points, (5.44 ± 0.52) points, (6.07 ± 0.65) points, (13.74 ± 2.68) points, t = 12.04, 16.29, 16.29, 8.36, all P < 0.001]. Conclusion:Montelukast sodium combined with compound methoxyphenamine is highly effective in treating post-infection cough in patients. The combined therapy can reduce airway inflammation, lower ICAM-1 and TLR4 levels, and increase sPD-L1 levels.