Changes in the “U-Shaped” Distribution of Airway Hyperresponsiveness and Characterization of Inflammatory Phenotypes in Different Age Groups

Fei Hu, Xi Ning Li, Pei Qi Li, Chuan Chuan Dong, Ru Jie Huo, Er Jing Cheng, Min Huang, Xin Rui Tian Department of Respiratory and Critical Care Medicine, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of ChinaCorrespondence: Xin Rui Tian, The Second Hospital of Shanxi Medical University, No. 382, Wuyi Road,Xinghualing District, Taiyuan, Shanxi, People’s Republic of China, Tel +86 13834575570, Email [email protected]: This study investigated age-related variations in airway hyperresponsiveness (AHR) based on pulmonary function, fractional exhaled nitric oxide (FeNO), total immunoglobulin E (IgE), eosinophils, basophils, neutrophils, monocytes, and lymphocytes.Methods: A total of 1,500 patients treated at the Second Hospital of Shanxi Medical University from 2021 to July–September 2023 were enrolled and stratified into four age groups. General information, smoking history, pulmonary function, FeNO (including FeNO50, FeNO200, and CaNO), and blood biomarkers (total IgE, eosinophils, basophils, neutrophils, monocytes, lymphocytes) were collected. Intergroup comparisons and correlation analyses were performed.Results: Pulmonary function: The positive rate of bronchial provocation test and the decline rate of FEV1 were higher in adolescents and the elderly, exhibiting a “U-shaped” distribution. FEV1, FVC, MEF50, and MEF25 increased with age until 18 years old and then declined. FEV1/FVC showed an overall decline with age. Exhaled nitric oxide test: The positive rate of type 2 inflammation in small airways showed a “U-shaped” distribution. CaNO was highest in the elderly group, overall displaying a “U-shaped” trend. No age-related differences were observed in FeNO50 and FeNO200. Laboratory indicators: Eosinophils, total IgE, and lymphocytes decreased with age. Basophils were highest in the young adult group. Neutrophils were lower in adolescents and higher in the elderly. Monocytes were elevated in both adolescent and elderly groups.Conclusion: AHR is more prominent in adolescents and the elderly, showing a “U-shaped” age distribution. Adolescents exhibited Th2-type inflammation (mainly eosinophil-driven), while the elderly showed non-Th2-type inflammation (mainly neutrophil- and monocyte-driven). Pulmonary function peaks in young adulthood and declines more rapidly after middle age, with small airway obstruction worsening in the elderly. The elevated CaNO in the elderly group dissociated from decreased blood eosinophils, suggesting localized eosinophilic inflammation or impaired migration, potentially indicating an eosinophil non-dependent inflammatory phenotype.Keywords: age-dependent, airway hyperresponsiveness, lung function, inflammatory phenotype