1 First Department of Medicine and.
2 Department of Otolaryngology-Head and Neck Surgery, Hokkaido University School of Medicine, Sapporo, Japan.
Ann Am Thorac Soc. 2018 Jan;15(1):33-41. doi: 10.1513/AnnalsATS.201701-065OC.
Smoking may have multifactorial effects on asthma phenotypes, particularly in severe asthma. Cluster analysis has been applied to explore novel phenotypes, which are not based on any a priori hypotheses.
To explore novel severe asthma phenotypes by cluster analysis when including smoking patients with asthma.
We recruited a total of 127 subjects with severe asthma, including 59 current or ex-smokers, from our university hospital and its 29 affiliated hospitals/pulmonary clinics. Clinical variables obtained during a 2-day hospital stay were used for cluster analysis. After clustering using clinical variables, the sputum levels of 14 molecules were measured to biologically characterize the clinical clusters.
Five clinical clusters, including two characterized by low forced expiratory volume in 1 second/forced vital capacity, were identified. When characteristics of smoking subjects in these two clusters were compared, there were marked differences between the two groups: one had high levels of circulating eosinophils, high immunoglobulin E levels, and a high sinus score, and the other was characterized by low levels of the same parameters. Sputum analysis revealed intriguing differences of cytokine/chemokine pattern in these two groups. The other three clusters were similar to those previously reported: young onset/atopic, nonsmoker/less eosinophilic, and female/obese. Key clinical variables were confirmed to be stable and consistent 3 years later.
This study reveals two distinct phenotypes with potentially different biological pathways contributing to fixed airflow limitation in cigarette smokers with severe asthma.
吸烟可能对哮喘表型产生多因素影响，尤其是在重症哮喘中。聚类分析已被用于探索新的表型，这些表型不是基于任何先验假设。
当纳入吸烟的哮喘患者时，通过聚类分析来探索新的重症哮喘表型。
我们共招募了 127 名重症哮喘患者，包括 59 名目前或曾经吸烟的患者，他们来自我们的大学医院及其 29 家附属医院/肺诊所。在 2 天的住院期间获得的临床变量用于聚类分析。在使用临床变量进行聚类后，测量了 14 种分子的痰液水平，以对临床聚类进行生物学特征描述。
确定了五个临床聚类，包括两个以低用力呼气量/用力肺活量为特征的聚类。当比较这两个聚类中吸烟患者的特征时，两组之间存在明显差异：一组循环嗜酸性粒细胞水平高、免疫球蛋白 E 水平高、鼻窦评分高，另一组则具有相同参数的低水平。痰液分析揭示了这两组细胞因子/趋化因子模式的有趣差异。另外三个聚类与之前报道的相似：发病年龄早/特应性、不吸烟/嗜酸性粒细胞较少、女性/肥胖。关键临床变量在 3 年后被证实是稳定且一致的。
本研究揭示了两种不同的表型，它们可能具有不同的生物学途径，导致吸烟的重症哮喘患者出现固定气流受限。
