Age-related differences in associations between uncontrolled asthma, comorbidities and biomarkers in adult-onset asthma

Adult-onset asthma is a recognized but heterogeneous phenotype and has been described to associate with poor asthma control. Knowledge about associations between clinical characteristics including comorbidities and control of adult-onset asthma is limited, especially in older populations. We aimed to study how clinical biomarkers and comorbidities are associated with uncontrolled asthma among middle-aged and older individuals with adult-onset asthma. Clinical examinations including structured interview, asthma control test (ACT), spirometry, skin prick test (SPT), blood sampling, and measurement of exhaled fractional nitric oxide (FeNO) was performed in a population-based adult-onset asthma cohort in 2019–2020 (<i>n</i> = 227, 66.5% female). Analyses were performed among all included, and separately in middle-aged (37–64 years, <i>n</i> = 120) and older (≥65 years, <i>n</i> = 107) participants. In bivariate analysis, uncontrolled asthma (ACT ≤ 19) was significantly associated with a blood neutrophil count ≥5/µl, BMI ≥30, and several comorbidities. In multivariable regression analysis, uncontrolled asthma was associated with neutrophils ≥5/µl (OR 2.35; 95% CI 1.11–4.99). In age-stratified analysis, BMI ≥30 (OR 3.04; 1.24–7.50), eosinophils ≥0.3/µl (OR 3.17; 1.20–8.37), neutrophils ≥5/µl (OR 4.39; 1.53–12.62) and allergic rhinitis (OR 5.10; 1.59–16.30) were associated with uncontrolled asthma among the middle-aged. Among the older adults, uncontrolled asthma was only associated with comorbidities: chronic rhinitis (OR 4.08; 1.62–10.31), ischemic heart disease (OR 3.59; 1.17–10.98), malignancy (OR 3.10; 1.10–8.73), and depression/anxiety (OR 16.31; 1.82–146.05). In adult-onset asthma, comorbidities were strongly associated with uncontrolled asthma among older adults, while clinical biomarkers including eosinophils and neutrophils in blood were associated with uncontrolled asthma among middle-aged.

成人起病哮喘（adult-onset asthma）是一种已被临床认知但表型异质的疾病，既往研究证实其与哮喘控制不佳存在关联。目前针对包括合并症在内的临床特征与成人起病哮喘控制情况之间关联的认知仍较为有限，在老年人群中尤为如此。本研究旨在探讨中老年成人起病哮喘患者的临床生物标志物与合并症分别与未控制哮喘的关联。2019-2020年，我们在一项基于人群的成人起病哮喘队列（cohort）中开展了临床检查，包括结构化访谈、哮喘控制测试（Asthma Control Test, ACT）、肺量测定法（spirometry）、皮肤点刺试验（skin prick test, SPT）、血液采样以及呼出气一氧化氮分数（exhaled fractional nitric oxide, FeNO）检测，共纳入227名受试者，其中女性占比66.5%。我们对全部入组受试者进行了整体分析，并分别对中年（37~64岁，n=120）与老年（≥65岁，n=107）两个亚组开展了单独分析。双变量分析结果显示，未控制哮喘（ACT≤19）与外周血中性粒细胞计数≥5/µl、体重指数（body mass index, BMI）≥30以及多种合并症存在显著关联。多变量回归分析结果显示，未控制哮喘与中性粒细胞计数≥5/µl显著相关（比值比（odds ratio, OR）=2.35，95%置信区间（confidence interval, CI）：1.11~4.99）。年龄分层分析结果显示，在中年亚组中，BMI≥30（OR=3.04，95%CI：1.24~7.50）、嗜酸性粒细胞计数≥0.3/µl（OR=3.17，95%CI：1.20~8.37）、中性粒细胞计数≥5/µl（OR=4.39，95%CI：1.53~12.62）以及变应性鼻炎（OR=5.10，95%CI：1.59~16.30）与未控制哮喘显著相关。在老年亚组中，未控制哮喘仅与以下合并症存在显著关联：慢性鼻炎（OR=4.08，95%CI：1.62~10.31）、缺血性心脏病（OR=3.59，95%CI：1.17~10.98）、恶性肿瘤（OR=3.10，95%CI：1.10~8.73）以及抑郁/焦虑障碍（OR=16.31，95%CI：1.82~146.05）。本研究结果表明，在成人起病哮喘患者中，老年人群的未控制哮喘与合并症密切相关，而中年人群的未控制哮喘则与包括血液嗜酸性粒细胞、中性粒细胞在内的临床生物标志物存在显著关联。