Proteomic analysis of sputum reveals novel biomarkers for various presentations of asthma

Chao Cao, Wen Li, Wen Hua, Fugui Yan, Hao Zhang, Huaqiong Huang, Yinghua Ying, Na Li, Fen Lan, Shaobin Wang, Xiao Chen, Jing Li, Jinkai Liu, Tianwen Lai, Zhengqiang Bao, Yuan Cao, Yun Zhao, Gang Huang, Lili Huang, Yaqing Huang, Ping Wu, Chao Peng, Zhihua Chen, Kian Fan Chung, Nanshan Zhong, Songmin Ying, Huahao Shen

It is now recognized that asthma can present in different forms. Typically, asthma present with symptoms of wheeze, breathlessness and cough. Atypical forms of asthma such as cough variant asthma (CVA) or chest tightness variant asthma (CTVA) do not wheeze. We hypothesize that these different forms of asthma may have distinctive cellular and molecular features. 30 patients with typical or classical asthma (CA), 27 patients with CVA, 30 patients with CTVA, and 30 healthy control adults were enrolled in this prospective study. We measured serum IgE, lung function, sputum eosinophils, nitric oxide in exhaled breath (FeNO). We performed proteomic analysis of induced-sputum supernatants by mass spectrometry. There were no significant differences in atopy and FEV1 among patients with CA, CVA, and CTVA. Serum IgE, sputum eosinophil percentages, FeNO, anxiety and depression scores were significantly increased in the three presentations of asthmatic patients as compared with healthy controls but there was no difference between the asthmatic groups. Comprehensive mass spectrometric analysis revealed more than a thousand proteins in the sputum from patients with CA, CVA, and CTVA, among which 23 secreted proteins were higher in patients than that in controls. Patients with CA, CVA, or CTVA share common clinical characteristics of eosinophilic airway inflammation. And more importantly, their sputum samples were composed with common factors with minor distinctions. These findings support the concept that these three different presentations of asthma have similar pathogenetic mechanism in terms of an enhanced Th2 associated with eosinophilia. In addition, this study identified a pool of novel biomarkers for diagnosis of asthma and to label its subtypes. Trial registration http://www.chictr.org.cn (ChiCTR-OOC-15006221).