Konno Satoshi, Taniguchi Natsuko, Makita Hironi, Nakamaru Yuji, Shimizu Kaoruko, Shijubo Noriharu, Fuke Satoshi, Takeyabu Kimihiro, Oguri Mitsuru, Kimura Hirokazu, Maeda Yukiko, Suzuki Masaru, Nagai Katsura, Ito Yoichi M, Wenzel Sally E, Nishimura Masaharu
1 First Department of Medicine, and.
2 Otolaryngology Head & Neck Surgery, Hokkaido University School of Medicine, Sapporo, Japan.
Ann Am Thorac Soc. 2015 Dec;12(12):1771-80. doi: 10.1513/AnnalsATS.201507-407OC.
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 cigarette smokers.
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. Twelve 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 were identified, including two characterized by high pack-year exposure to cigarette smoking and low FEV1/FVC. There were marked differences between the two clusters of cigarette smokers. One had high levels of circulating eosinophils, high IgE levels, and a high sinus disease score. The other was characterized by low levels of the same parameters. Sputum analysis revealed increased levels of IL-5 in the former cluster and increased levels of IL-6 and osteopontin in the latter. 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 1 year later.
This study reveals two distinct phenotypes of severe asthma in current and former cigarette smokers with potentially different biological pathways contributing to fixed airflow limitation. Clinical trial registered with www.umin.ac.jp (000003254).
吸烟可能对哮喘表型产生多因素影响，尤其是在重度哮喘中。聚类分析已被用于探索新的表型，这些表型并非基于任何先验假设。
在纳入吸烟者的情况下，通过聚类分析探索新的重度哮喘表型。
我们从大学医院及其29家附属医院/肺病诊所共招募了127名重度哮喘患者，其中包括59名现吸烟者或既往吸烟者。在为期2天的住院期间获得的12项临床变量用于聚类分析。使用临床变量进行聚类后，测量14种分子的痰液水平以对临床聚类进行生物学特征描述。
识别出5个临床聚类，其中两个聚类的特征是吸烟包年数高且FEV1/FVC低。这两个吸烟者聚类之间存在显著差异。一个聚类的循环嗜酸性粒细胞水平高、IgE水平高且鼻窦疾病评分高。另一个聚类的特征是相同参数水平低。痰液分析显示，前一个聚类中IL-5水平升高，后一个聚类中IL-6和骨桥蛋白水平升高。其他三个聚类与先前报道的聚类相似：早发型/特应性、非吸烟者/嗜酸性粒细胞较少、女性/肥胖。关键临床变量在1年后被证实是稳定且一致的。
本研究揭示了现吸烟者和既往吸烟者中重度哮喘的两种不同表型，可能有不同的生物学途径导致固定性气流受限。临床试验在www.umin.ac.jp注册（000003254）。
