LAUSR

The goal of systems or personalized medicine is to deliver the optimal drug to the right patient at the right time.1,2 A prerequisite for this is the correct identification of asthma clinical phenotypes that possess mechanisms that can be targeted by specific drugs. Eosinophilic asthma is one such phenotype which is characterized by elevated levels of circulating eosinophils. These patients have an underlying type 2 T-helper cell (Th2) mechanism, are more responsive to treatment with inhaled corticosteroids (ICS) but conversely appear more susceptible to exacerbations.1,2 The appreciation of the Th2-based driver mechanism of these patients has driven the use of biological therapies targeted Th2 cytokines. For example, anti-IL-5-directed drugs used to block eosinophil differentiation and activation are effective in patients with high blood eosinophils, severe and recurrent exacerbations already requiring high dose ICS and oral corticosteroids (OCS) 1,2. Unfortunately, only 40-50% of asthmatics have this phenotype and there is a need to define non-Th2 asthma along with their associated driver mechanisms. Neutrophilic asthma was first reported in bronchial biopsies 3but is more often defined as patients with high (40-70%) sputum neutrophil counts. Sputum neutrophilia is linked to severe asthma, a relative lack of response to corticosteroid therapy and chronic airflow obstruction, 3and is reported to occur in acute exacerbations3. A neutrophilic asthma phenotype may arise from the presence of enhanced levels of neutrophilic chemokines such as GRO , interleukin 8, CXCL10, and CCL2 which are all elevated in sputum of these patients.3 However, a number of clinical trials directed against neutrophilassociated mediators have not been successful in moderate to severe asthma. These studies include an antibody against TNF (golimumab), an anti-IL-17 receptor antibody (brodalumab) and with a CXCR2 antagonist.3 In the latter study, involving 640 patients with uncontrolled persistent asthma, treatment for 6 months with the CXCR2 antagonist AZD5069, that blocks the effects of interleukin 8, had no effect on the rate of severe exacerbations, asthma symptoms, or lung function compared with placebo despite significantly reducing mean blood neutrophil counts.4