Abstract Rationale Cough and sputum are common symptoms in patients with asthma, affecting both quality of life and disease control. Although Type 2 inflammation plays a central role in asthma pathophysiology, its involvement in persistent cough and sputum symptoms among patients receiving inhaled corticosteroid (ICS) therapy remains unclear. This study aimed to identify clinical characteristics and serum biomarkers associated with cough and sputum symptoms in ICS-treated asthma patients. Methods In this single-center cross-sectional study, 182 patients with physician-diagnosed asthma receiving ICS treatment at Teikyo University Hospital between June and November 2023 were enrolled. Cough and sputum symptoms were assessed using the validated Cough and Sputum Assessment Questionnaire (CASA-Q). Clinical characteristics, asthma control (Asthma Control Test; ACT), pulmonary function, and serum biomarkers were evaluated, including Type 2-related markers (periostin, FeNO, blood eosinophils), eosinophil-derived proteins (galectin-10, eosinophil-derived neurotoxin EDN), and inflammatory markers (TNF-α, IL-6, C-reactive protein CRP). Patients were classified into Type 2 and Type 2-low phenotypes based on blood eosinophil count (150 /μL) and FeNO (35 ppb). Univariable and multivariable logistic regression analyses identified factors associated with cough and sputum symptoms. Results Among the 182 patients, 130 (71.4%) reported cough, and 97 of these (74.6%) had concurrent sputum symptoms (productive cough). Patients with cough or sputum had significantly lower ACT scores and higher blood neutrophil counts than those without symptoms (p 0.05). No significant differences were observed in FeNO, blood eosinophil counts, or Type 2-related biomarkers between groups. FEV1 did not differ by symptom presence. Multivariable analysis revealed that elevated serum CRP was independently associated with cough in the overall population, while gastroesophageal reflux disease (GERD) was related to cough in Type 2-low asthma. Galectin-10 was associated with sputum symptoms in the Type 2 asthma subgroup. Patients with productive cough had lower ACT scores and higher neutrophil counts than those with dry cough, although biomarker profiles were similar. Conclusions Persistent cough and sputum symptoms in ICS-treated asthma appear to be driven by mechanisms other than Type 2 inflammation or airflow limitation. Neutrophilic inflammation and comorbidities such as GERD may represent treatable traits. These findings underscore the need for novel therapeutic strategies targeting non-Type 2 pathways. This abstract is funded by: none
Hattori et al. (Fri,) studied this question.