Profiling of sputum inflammatory mediators in asthma and chronic obstructive pulmonary disease

Introduction: Asthma and chronic obstructive pulmonary disease (COPD) display features of overlap in airway physiology and airway inflammation. The relationship between mediator expression and airway inflammation was explored within these airway diseases. Methods: Patients with asthma (54 patients: 21 men) and COPD (49 patients: 36 men) were studied. Clinical characteristics and sputum was collected at entry into the study. A two-step sputum processing method was performed for supernatant and cytospin preparation. The Meso Scale Discovery and Luminex platforms were used to measure cytokines, chemokines and matrix metalloproteinase levels. Results: Analytes sensitive to dithiothreitol (DTT) that had increased recovery in the two step sputum process were IL-1b, 4, 5, 10, 13, IFN-g, TNFRI, GM-CSF, CCL2, 3, 4, 5, 13 and 17. There was a differential expression in IL-8, TNFRI and TNFRII between asthma and COPD (mean fold difference (95% confidence interval) IL-8, 2.6 (1.3 to 5.4), p=0.01; TNFRI, 2.1 (1.3 to 5.4), p=0.03; and TNFRII, 2.6 (1.2 to 5.6), p=0.02). In neutrophilic and eosinophilic airway inflammation, TNFα, TNFRI, TNFRII, IL-6, IL-8 and IL-5 could differentiate between these phenotypes. However, these phenotypes were unrelated to the diagnosis of asthma or COPD. Conclusion: Recovery of sputum mediators sensitive to DTT can be improved using a new sputum processing technique. Within airway inflammatory sub-phenotypes there is a differential pattern of mediator expression that is independent of disease. Whether these inflammatory phenotypes in asthma and COPD confer distinct pathogenesis, therapeutic responses and clinical phenotypes needs to be further evaluated.