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Updated: Jan 11, 2026
Methodology for Sputum Induction and Laboratory Processing
Published on: December 17, 2017
Identification of two distinct molecular endotypes in cough-variant asthma based on sputum transcriptomics and
Wenzhi Zhan1,2, Wei Luo1,2, Feng Wu3
1Guangzhou Institute of Respiratory Health, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Rationale:
Asthmatic cough may not respond well to corticosteroids. The underlying mechanisms and heterogeneity of cough variant asthma (CVA) remain poorly understood. The objectives of the present study were to explore airway immunological mechanisms and identify molecular endotypes in CVA by analysing sputum transcriptomics, clinical and pathophysiological characteristics.
Methods:
RNA sequencing and cytokine measurement were performed on sputum samples from newly diagnosed patients with CVA (n=72), classic asthma (CA) (n=28) and healthy controls (HC) (n=28). Patients with CVA were treated and followed-up for 6 months.
Results:
The majority of differentially expressed genes in CVA versus HC overlapped with those identified in CA versus HC. However, the type 2 immunity co-expression network in CVA was lower than that in CA. Based on sputum transcriptomics profiles, two endotypes of CVA were identified: mixed-inflammatory CVA (n=40) and pauci-inflammatory CVA (n=32). Mixed-inflammatory CVA showed higher inflammation-related gene set signatures compared to both pauci-inflammatory CVA and HC. Mixed-inflammatory CVA also showed elevated levels of eosinophils, neutrophils, type 2, type 1 and type 3 cytokines in sputum compared to HC. Conversely, pauci-inflammatory CVA had slightly elevated sputum eosinophils, but no significant gene signatures and cytokine differences compared to HC. During 6 months' follow-up, pauci-inflammatory CVA showed a trend of less complete resolution in cough (56.2% versus 80.0%, p=0.0553) compared to mixed-inflammatory CVA. Kaplan-Meier analysis found significantly higher cough persistence in pauci-inflammatory versus mixed-inflammatory CVA.
Conclusions:
CVA exhibits overlapping but distinct airway transcriptomics profiles compared to CA. Two distinct molecular endotypes are identified in CVA, presenting different clinical and pathophysiological features.
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