Significant Increase of IL-8 Sputum Levels in Treatment Resistant Severe Asthma Compared with Difficult to Treat Severe Asthma Patients

Abstract

The spectrum of severe asthma includes different groupings and phenotypes. World Health Organization proposes to differentiate two categories: difficult-to-treat-severe asthma (DTTSA) and treatment-resistant-severe asthma (TRSA). DTTSA includes controllable severe asthma and TRSA includes patient’s not achieving adequate levels of control and persisting indicators of severity despite receiving and using maximum levels of inhaled medications. We hypothesized that granulocyte counts from sputum samples could differentiate pathogenic differences between both groups. We analyzed the number of sputum neutrophils and eosinophils in both categories of severe asthma patients admitted for an asthma exacerbation in a respiratory-based hospital. We also compared our results with mild to moderate asthma patients (MMA) and healthy controls (HC). We measured cytokines levels relevant to neutrophil recruitment (IL-8 and IL17-A) and inflammatory cytokines. We found a significant increase in neutrophil numbers in TRSA compared to DDTSA, MMA and HC; moreover, we detected a significant increase of IL-8 levels in sputum samples of TRSA patients. However we found no differences in exhaled FeNO and IL17-A levels among groups. This study shows that the sputum neutrophilic profile predominates in patients with TRSA, could be useful in distinguishing from DTTSA, and may provide insight into the pathogenic differences between both groups.