Adair Dionne, Bagheri AmirBehzad, Yosef Matheos, Khalatbari Shokoufeh, Lewis Toby, Mohan Arjun, Lugogo Njira
Division of Pediatric Pulmonary, Medical College of Georgia, Augusta, GA, USA.
Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, MI, USA.
Pulm Ther. 2025 Mar;11(1):41-54. doi: 10.1007/s41030-024-00281-z. Epub 2024 Dec 23.
Asthma is a complex condition characterized by airway inflammation. Interleukin-6 (IL-6) plays a significant role in asthma pathogenesis through its effects on T cells and its association with pro-inflammatory responses. Both lung and circulating IL-6 levels are elevated in asthma. IL-6 is positively associated with disease severity, frequent exacerbations, and impaired lung function, all of which can be observed clinically. We developed an IL-6 cut-off model to examine the association between high IL-6, race, high body mass index (BMI), metabolic disease, and asthma severity as assessed by reduced lung function.
This study utilized the Coronary Artery Risk Development in Young Adults (CARDIA) database, comprised of 5115 adults, to investigate the relationship between IL-6 levels, asthma, race, and metabolic dysfunction. A "healthy" subset of 427 patients was used to compute the IL-6 cut-off. IL-6 levels within detection limits (0.15-12 pg/mL) were analyzed. The IL-6 cut-off was determined using the 95th percentile of log-transformed IL-6 values for lean (BMI < 25) and healthy individuals. Specific cut-offs were established for racial groups. Statistical analyses involved comparing patient characteristics between high and low IL-6 groups, regression analyses, and assessment of factors influencing lung function changes.
Using an IL-6 cut-off of 4.979 pg/mL, the cohort was divided into high and low IL-6 groups. High IL-6 correlated with Black race, higher BMI, hypertension, and markers of metabolic dysfunction, e.g., elevated HbA1c, C-reactive protein (CRP), and reduced lung function. Multivariable analysis linked high IL-6 with male gender, high BMI, Black race, HbA1c, CRP, and inversely with lung function and total cholesterol. Obesity showed a consistent positive association with elevated IL-6, regardless of the presence or absence of asthma. Patients with asthma and high IL-6 were more likely to be Black and showed increased CRP. Lung function was lowest in non-lean, high IL-6 patients with asthma, with similar trends in non-lean (BMI ≥ 25) patients without asthma.
This study underscores the significant association between IL-6, asthma, obesity, and metabolic dysfunction. Elevated IL-6 correlates with asthma severity, particularly in individuals with obesity. Future research should explore anti-IL-6 therapies for specific phenotypes, such as obesity-related asthma. These findings advance our understanding of asthma and the role of IL-6 in its pathogenesis.
哮喘是一种以气道炎症为特征的复杂病症。白细胞介素-6（IL-6）通过其对T细胞的作用及其与促炎反应的关联，在哮喘发病机制中发挥重要作用。哮喘患者的肺部和循环中的IL-6水平均会升高。IL-6与疾病严重程度、频繁发作以及肺功能受损呈正相关，所有这些在临床上均可观察到。我们开发了一种IL-6临界值模型，以研究高IL-6、种族、高体重指数（BMI）、代谢疾病与通过肺功能降低评估的哮喘严重程度之间的关联。
本研究利用了包含5115名成年人的青年成人冠状动脉风险发展（CARDIA）数据库，来研究IL-6水平、哮喘、种族和代谢功能障碍之间的关系。使用427名患者的“健康”子集来计算IL-6临界值。分析检测限内（0.15 - 12 pg/mL）的IL-6水平。使用瘦（BMI < 25）且健康个体的对数转换后IL-6值的第95百分位数来确定IL-6临界值。为不同种族群体确定了特定的临界值。统计分析包括比较高IL-6组和低IL-6组之间的患者特征、回归分析以及对影响肺功能变化因素的评估。
使用4.979 pg/mL的IL-6临界值，将队列分为高IL-6组和低IL-6组。高IL-6与黑人种族、较高的BMI、高血压以及代谢功能障碍标志物相关，例如糖化血红蛋白（HbA1c）升高、C反应蛋白（CRP）升高以及肺功能降低。多变量分析将高IL-6与男性、高BMI、黑人种族、HbA1c、CRP相关联，并且与肺功能和总胆固醇呈负相关。无论是否患有哮喘，肥胖均与IL-6升高呈一致的正相关。患有哮喘且IL-6高的患者更可能是黑人并且CRP升高。在非瘦且患有哮喘的高IL-6患者中肺功能最低，在非瘦（BMI≥25）且无哮喘的患者中也有类似趋势。
本研究强调了IL-6、哮喘、肥胖和代谢功能障碍之间的显著关联。IL-6升高与哮喘严重程度相关，尤其是在肥胖个体中。未来的研究应探索针对特定表型（如肥胖相关哮喘）的抗IL-6疗法。这些发现增进了我们对哮喘以及IL-6在其发病机制中作用的理解。
