Kim Joo Hee, Chang Hun Soo, Shin Seung Woo, Baek Dong Gyu, Son Ji Hye, Park Choon Sik, Park Jong Sook
Division of Pulmonology, Allergy and Critical Care, Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Korea.
Genome Research Center for Allergy and Respiratory Diseases, Bucheon, Korea.
Allergy Asthma Immunol Res. 2018 Nov;10(6):614-627. doi: 10.4168/aair.2018.10.6.614.
Asthma is a heterogeneous disease that responds to medications to varying degrees. Cluster analyses have identified several phenotypes and variables related to fixed airway obstruction; however, few longitudinal studies of lung function have been performed on adult asthmatics. We investigated clinical, demographic, and inflammatory factors related to persistent airflow limitation based on lung function trajectories over 1 year.
Serial post-bronchodilator forced expiratory volume (FEV) 1% values were obtained from 1,679 asthmatics who were followed up every 3 months for 1 year. First, a hierarchical cluster analysis was performed using Ward's method to generate a dendrogram for the optimum number of clusters using the complete post-FEV1 sets from 448 subjects. Then, a trajectory cluster analysis of serial post-FEV1 sets was performed using the k-means clustering for the longitudinal data trajectory method. Next, trajectory clustering for the serial post-FEV1 sets of a total of 1,679 asthmatics was performed after imputation of missing post-FEV1 values using regression methods.
Trajectories 1 and 2 were associated with normal lung function during the study period, and trajectory 3 was associated with a reversal to normal of the moderately decreased baseline FEV1 within 3 months. Trajectories 4 and 5 were associated with severe asthma with a marked reduction in baseline FEV1. However, the FEV1 associated with trajectory 4 was increased at 3 months, whereas the FEV1 associated with trajectory 5 was persistently disturbed over 1 year. Compared with trajectory 4, trajectory 5 was associated with older asthmatics with less atopy, a lower immunoglobulin E (IgE) level, sputum neutrophilia and higher dosages of oral steroids. In contrast, trajectory 4 was associated with higher sputum and blood eosinophil counts and more frequent exacerbations.
Trajectory clustering analysis of FEV1 identified 5 distinct types, representing well-preserved to severely decreased FEV1. Persistent airflow obstruction may be related to non-atopy, a low IgE level, and older age accompanied by neutrophilic inflammation and low baseline FEV1 levels.
哮喘是一种异质性疾病，对药物的反应程度各不相同。聚类分析已确定了几种与固定性气道阻塞相关的表型和变量；然而，针对成年哮喘患者的肺功能纵向研究较少。我们基于1年的肺功能轨迹，研究了与持续性气流受限相关的临床、人口统计学和炎症因素。
从1679名哮喘患者中获取支气管扩张剂后用力呼气容积（FEV）1%的系列值，这些患者每3个月随访1年。首先，使用Ward法进行层次聚类分析，利用448名受试者的完整FEV1后数据集生成聚类最优数量的树状图。然后，使用纵向数据轨迹方法的k均值聚类对系列FEV1后数据集进行轨迹聚类分析。接下来，在使用回归方法对缺失的FEV1后值进行插补后，对总共1679名哮喘患者的系列FEV1后数据集进行轨迹聚类。
轨迹1和2与研究期间的正常肺功能相关，轨迹3与基线FEV1中度下降在3个月内恢复正常相关。轨迹4和5与严重哮喘相关，基线FEV1显著降低。然而，与轨迹4相关的FEV1在3个月时增加，而与轨迹5相关的FEV1在1年内持续受损。与轨迹4相比，轨迹5与年龄较大、特应性较少、免疫球蛋白E（IgE）水平较低、痰液中性粒细胞增多和口服类固醇剂量较高的哮喘患者相关。相比之下，轨迹4与痰液和血液嗜酸性粒细胞计数较高以及更频繁的急性加重相关。
FEV1的轨迹聚类分析确定了5种不同类型，代表FEV1从保存良好到严重下降。持续性气流阻塞可能与非特应性、低IgE水平、老年以及中性粒细胞炎症和低基线FEV1水平有关。
