Background Asthma is significantly related to chronic rhinosinusitis (CRS) both in prevalence and severity. However, the clinical patterns of uncontrolled asthma with and without comorbid CRS are still unclear. This study aimed to explore the clinical characteristics and cytokine patterns of patients with uncontrolled asthma, with and without comorbid CRS. Methods 22 parameters associated with demographic characteristics, CRS comorbidity, severity of airflow obstruction and airway inflammation, and inflammation type of asthma were collected and assessed in 143 patients with uncontrolled asthma. Different clusters were explored using two-step cluster analysis. Sputum samples were collected for assessment of Th1/Th2/Th17 and epithelium-derived cytokines. Results Comorbid CRS was identified as the most important variable for prediction of different clusters, followed by pulmonary function parameters and blood eosinophil level. Three clusters of patients were determined: Cluster 1 (n = 46) characterized by non-atopic patients with non-eosinophilic asthma without CRS, demonstrating moderate airflow limitation; Cluster 2 (n = 54) characterized by asthma patients with mild airflow limitation and CRS, demonstrating higher levels of blood eosinophils and immunoglobulin E (IgE) than cluster 1; Cluster 3 (n = 43) characterized by eosinophilic asthma patients with severe airflow limitation and CRS (46.5% with nasal polyps), demonstrating worst lung function, lowest partial pressure of oxygen (PaO2), and highest levels of eosinophils, fraction of exhaled nitric oxide (FeNO) and IgE. Sputum samples from Cluster 3 showed significantly higher levels of Interleukin (IL)-5, IL-13, IL-33, and tumor necrosis factor (TNF)-α than the other two clusters; and remarkably elevated IL-4, IL-17 and interferon (IFN)-γ compared with cluster 2. The levels of IL-10 and IL-25 were not significantly different among the three clusters. Conclusions Uncontrolled asthma may be endotyped into three clusters characterized by CRS comorbidity and inflammatory cytokine patterns. Furthermore, a united-airways approach may be especially necessary for management of asthma patients with Type 2 features.

Background Although 20–60% of patients with chronic rhinosinusitis with nasal polyps (CRSwNP) have asthma, the risk factors associated with comorbid asthma are not clear. The aim of the study was to investigate the factors associated with asthma, and develop a practical scoring system to screen asthma comorbidity in CRSwNP patients. Methods This report describes a cross-sectional study with consecutive CRSwNP patients. Two cohorts of CRSwNP patients named “modelling” group and “validation” group were investigated respectively. Logistic regression analysis was performed based on demographic and clinical data collected from patients in the modelling group to determine the risk factors associated with asthma, and establish a scoring system for screening comorbid asthma. Receiver operating characteristic curve was constructed to evaluate the screening system; the optimal cut-off point was established by means of the Yoden Index. The consistency between the diagnosis of asthma by the Global Initiative for Asthma (GINA) criteria and by the screening system was assessed by Kappa value in the validation group. Results Totally 150 patients in modelling group and 78 patients in validation group were enrolled. Female gender (odds ratio [OR] = 6.4; P < 0.001), allergic rhinitis (OR = 2.9; P = 0.021), serum total (T)-immunoglobulin (Ig) E ≥ 69.0kU/L (OR = 12.0; P < 0.001), and blood eosinophil count  ≥ 0.35 × 109/L (OR = 4.0; P = 0.001) were shown to be independent risk factors for asthma in patients with CRSwNP. Based on these variables, a scoring system (FAIE) ranging from 0(no risk) to 6(high risk); was developed. The area under the receiver operating characteristic curve of the system was 0.823, and the optimal cut-off value was 3 points, with sensitivity 83.8% and specificity 68.6% for screening asthma. The asthma comorbidity determined with FAIE score ≥ 3 points in the validation group, was moderately consistent with that defined by GINA (Kappa = 0.513, P < 0.001), with sensitivity 76.9% and specificity 74.4%. Conclusions Female gender, allergic rhinitis, serum T-IgE level, and blood eosinophil count are independent risk factors for asthma comorbidity in patients with CRSwNP, and the FAIE system may be practical for screening comorbid asthma in these patients.