Phenotypic Variations of Mild-to-Moderate Obstructive Pulmonary Diseases According to Airway Inflammation and Clinical Features

PURPOSE: Asthma and chronic obstructive pulmonary disease (COPD) are complex and heterogeneous inflammatory diseases. We sought to investigate distinct disease profiles based on clinical, cellular and molecular data from patients with mild-to-moderate obstructive pulmonary diseases. PATIENTS AND METHODS: Patients with mild-to-moderate allergic asthma (n=30) and COPD (n=30) were prospectively recruited. Clinical characteristics and induced sputum were collected. In total, 35 mediators were assessed in induced sputum. Logistic regression analysis was conducted to identify the optimal factors that were able to discriminate between asthma and COPD. Further, the data were explored using hierarchical clustering in order to discover and compare clusters of combined samples of asthma and COPD patients. Clinical parameters, cellular composition, and sputum mediators of asthma and COPD were assessed between and within obtained clusters. RESULTS: We found five clinical and biochemical variables, namely IL-6, IL-8, CCL4, FEV(1)/VC ratio pre-bronchodilator (%), and sputum neutrophils (%) that differentiated asthma and COPD and were suitable for discrimination purposes. A combination of those variables yielded high sensitivity and specificity in the differentiation between asthma and COPD, although only FEV(1)/VC ratio pre-bronchodilator (%) proven significant in the combined model. In cluster analysis, two main clusters were identified: cluster 1, asthma predominant with evidence of eosinophilic airway inflammation and low level of Th1 and Th2 cytokines; and cluster 2, COPD predominant with elevated levels of Th1 and Th2 mediators. CONCLUSION: The inflammatory profile of sputum samples from patients with stable mild-to-moderate asthma and COPD is not disease specific, varies within the disease and might be similar between these diseases. This study highlights the need for phenotyping the mild-to-moderate stages according to their clinical and molecular features.