Neutrophilic inflammation in sputum does not define a clinical distinct asthma phenotype in ATLANTIS

Abstract

It has been suggested that neutrophilic asthma is a clinically distinct phenotype characterized by more airflow obstruction and frequent exacerbations. Within the ATLANTIS study we investigated whether asthmatic participants with neutrophilic inflammation in sputum or blood, have a more severe clinical expression. ATLANTIS included 773 participants with asthma (mean age 44 years, 58% female, 76% never-smoker). We defined sputum (≥70.6%) or blood (≥4.7*109 cells/L) neutrophilia as a percentage or number higher than the upper quartile in asthmatics. Asthmatic participants with sputum neutrophilia did not have more severe disease. The level of symptoms and lung function (FEV1 % predicted mean (SD) 89.2 (10.7) and 90.2 (11.0), p = 0.52) were similar between patients with and without sputum neutrophilia, respectively. No association with sputum neutrophilia and exacerbations was found (HR 1.02, CI 0.49 – 2.15, p = 0.94). Results were similar in a sensitivity analysis performed in patients receiving GINA step 4 or 5 treatment and were independently validated in the U-BIOPRED study. Similar to sputum neutrophilia, the presence of blood neutrophilia was not associated with a worse outcome regarding symptoms (ACQ6), FEV1 %predicted or exacerbation risk. By contrast, blood neutrophilia was independently associated with a higher BMI, female gender, smoking, systemic corticosteroid use and hyperinflation (RV/TLC). The presence of neutrophilia in sputum does not identify a distinct clinical phenotype. Neutrophilic inflammation in blood is associated with hyperinflation suggesting small airways disease in asthma and is affected by higher BMI, smoking, and systemic corticosteroid use.