Effects of treatment changes on asthma phenotype prevalence and airway neutrophil function

Abstract

Background: Asthma inflammatory phenotypes are often defined by relative cell counts of airway eosinophils/neutrophils. However, the importance of neutrophilia remains unclear, as does the effect of ICS treatment on asthma phenotypes and airway neutrophil function. The purpose of this study was to assess asthma phenotype prevalence/characteristics in a community setting, and, in a nested preliminary study, determine how treatment changes affect phenotype stability and inflammation, with particular focus on airway neutrophils.

Methods: Fifty adult asthmatics and 39 non-asthmatics were assessed using questionnaires, skin prick tests, spirometry, exhaled nitric oxide (FENO) measurement, and sputum induction. Twenty-one asthmatics underwent further assessment following treatment optimisation (n = 11) or sub-optimisation (n = 10).

Results: Forty percent (20/50) had eosinophilic asthma (EA) and 8% had neutrophilic asthma. EA was associated with increased FENO, bronchodilator reversibility (BDR) and reduced lung function (p < 0.05). Following optimisation/sub-optimisation, the EA/NEA (non-eosinophilic asthma) phenotype changed in 11/21 (52%) asthmatics. In particular, fewer subjects had EA post treatment optimisation, but this was not statistically significant. However, a significant (p < 0.05) reduction in FENO, ACQ7 score, and BDR was observed after treatment optimisation, as well as an increase in FEV₁-% predicted (p < 0.05). It was also associated with reduced eosinophils (p < 0.05) and enhanced neutrophil phagocytosis (p < 0.05) in EA only, and enhanced neutrophil oxidative burst in both EA and NEA (p < 0.05).

Conclusions: In this community based population, non-eosinophilic asthma was common, less severe than EA, and at baseline most asthmatics showed no evidence of inflammation. In the nested change in treatment study, treatment optimisation was associated with reduced sputum eosinophils, improved symptoms and lung function, and enhanced neutrophil function, but a significant reduction in EA could not be demonstrated.

Trial registration: The nested change in treatment component of this study is registered at the Australia and New Zealand Clinical Trial Registry ( www.ANZCTR.org.au ) ACTRN12617001356358 . Registration date 27/09/2017. Retrospectively registered.

Keywords: Asthma; Eosinophils; Induced sputum; Inflammatory phenotype; Neutrophils.

Fig. 1

Study plan flow chart. Recruitment of participants, and the assessments involved in the phenotype prevalence and change in treatment components of the study

Fig. 2

Clinical and sputum sample inflammatory parameters for all CIT participants (n = 21). Data represent the assessment in which treatment was considered as sub-optimised or optimised. a – FEV1% predicted, b- change in FEV1% predicted post-bronchodilator (BDR), c – ACQ7, d- exhaled NO levels, e – change in % sputum eosinophils, f-change in % sputum neutrophils. Median data values are expressed at the top of each group

Fig. 3

Sputum neutrophil functional parameters (as assessed using flow cytometry). Data represent CIT participants who produced an adequate sample for neutrophil oxidative burst (n = 7) or phagocytosis measurement (n = 16) at both visits. Groups are stratified on the basis of treatment status (sub-optimised or optimised). a – change in % sputum neutrophils undergoing oxidative burst after stimulation with PMA, b – change in % sputum neutrophils that are capable of phagocytosing fluorescent zymosan beads in culture at 37 °C, c- change in % sputum neutrophils that are capable of phagocytosing fluorescent zymosan beads in culture at 37 °C when stratified into EA/NEA. Median values are expressed at the top of each group