Clinical and phenotypic characteristics of chronic cough patients without sputum eosinophilia

Corticosteroid treatment has no effect in patients without sputum eosinophilia. Sputum neutrophils and lymphocytes contribute to chronic cough hypersensitivity. The characteristics of chronic cough patients without sputum eosinophilia have not been investigated. This study included a total of 1061 patients at the First Affiliated Hospital of Guangzhou Medical University between July 2021 and June 2024 (Approval number: ES-2024-K117-02). We analyzed clinical characteristics, sputum cell profiles, spirometry, and pulmonary lesions across four groups: chronic cough patients with normal sputum (n = 180), lymphocytotic sputum (n = 270), neutrophilic sputum (n = 349), and mixed leukocytotic sputum (n = 262). Gastroesophageal reflux cough was the most prevalent disease in chronic cough patients with normal sputum. Atopic cough was more common in patients with lymphocytotic sputum. COPD and bronchiectasis were more prevalent in both neutrophilic and leukocytotic sputum groups. Advanced age was a characteristic of patients with neutrophilic or leukocytotic sputum. Patients with neutrophilic sputum had a higher prevalence of smoking history and a longer smoking duration. Pulmonary lesions were less severe in patients with lymphocytotic sputum but more severe in those with neutrophilic or leukocytotic sputum. Compared to patients with normal sputum, both neutrophilic and leukocytotic sputum groups exhibited marked reductions in overall lung function (FVC% of predicted, FEV1% of predicted, FEV1/FVC% of predicted, and PEF% of predicted) and small airway function (MMEF% of predicted, FEF75% of predicted, and FEF50% of predicted). Associations were observed among age, smoking history, sputum neutrophil percentages, pulmonary lesions, and declined lung functions. Elevated sputum neutrophils were independently associated with reduced lung function across multiple parameters (FVC% of predicted, FEV1/FVC% predicted, FEV1/VCmax% predicted, PEF% predicted, MMEF% of predicted, and FEF50% of predicted), despite robust adjustment for age and the presence of COPD, bronchiectasis, and interstitial lung disease. Advanced age and smoking history are risk factors for elevated sputum neutrophils in chronic cough patients. Neutrophil-mediated airway inflammation is associated with pulmonary lesions and declined lung functions in chronic cough patients.