Altered innate immune responses in neutrophils from patients with well- and suboptimally controlled asthma

Background: Respiratory infections are a major cause of asthma exacerbations where neutrophilic inflammation dominates and is associated with steroid refractory asthma. Structural airway cells in asthma differ from nonasthmatics; however it is unknown if neutrophils differ. We investigated neutrophil immune responses in patients who have good (AGood) and suboptimal (ASubopt) asthma symptom control. Methods: Peripheral blood neutrophils from AGood (ACQ < 0.75, n=11), ASubopt (ACQ > 0.75, n=7), and healthy controls (HC) (n=9) were stimulated with bacterial (LPS (1 g/mL), fMLF (100 nM)), and viral (imiquimod (3 g/mL), R848 (1.5 g/mL), and poly I:C (10 g/mL)) surrogates or live rhinovirus (RV) 16 (MOI1). Cell-free supernatant was collected after 1 h for neutrophil elastase (NE) and matrix metalloproteinase- (MMP-) 9 measurements or after 24 h for CXCL8 release. Results: Constitutive NE was enhanced in AGood neutrophils compared to HC. fMLF stimulated neutrophils from ASubopt but not AGood produced 50% of HC levels. fMLF induced MMP-9 was impaired in ASubopt and AGood compared to HC. fMLF stimulated CXCL8 but not MMP-9 was positively correlated with FEV1 and FEV1/FVC. ASubopt and AGood responded similarly to other stimuli. Conclusions: Circulating neutrophils are different in asthma; however, this is likely to be related to airflow limitation rather than asthma control.