PT  - JOURNAL ARTICLE
AU  - Timothy S.C. Hinks
AU  - Stewart J. Levine
AU  - Guy G. Brusselle
TI  - Treatment options in type-2 low asthma
AID  - 10.1183/13993003.00528-2020
DP  - 2021 Jan 01
TA  - European Respiratory Journal
PG  - 2000528
VI  - 57
IP  - 1
4099  - http://erj.ersjournals.com/content/57/1/2000528.short
4100  - http://erj.ersjournals.com/content/57/1/2000528.full
SO  - Eur Respir J2021 Jan 01; 57
AB  - Monoclonal antibodies targeting IgE or the type-2 cytokines interleukin (IL)-4, IL-5 and IL-13 are proving highly effective in reducing exacerbations and symptoms in people with severe allergic and eosinophilic asthma, respectively. However, these therapies are not appropriate for 30–50% of patients in severe asthma clinics who present with non-allergic, non-eosinophilic, “type-2 low” asthma. These patients constitute an important and common clinical asthma phenotype, driven by distinct, yet poorly understood pathobiological mechanisms. In this review we describe the heterogeneity and clinical characteristics of type-2 low asthma and summarise current knowledge on the underlying pathobiological mechanisms, which includes neutrophilic airway inflammation often associated with smoking, obesity and occupational exposures and may be driven by persistent bacterial infections and by activation of a recently described IL-6 pathway. We review the evidence base underlying existing treatment options for specific treatable traits that can be identified and addressed. We focus particularly on severe asthma as opposed to difficult-to-treat asthma, on emerging data on the identification of airway bacterial infection, on the increasing evidence base for the use of long-term low-dose macrolides, a critical appraisal of bronchial thermoplasty, and evidence for the use of biologics in type-2 low disease. Finally, we review ongoing research into other pathways including tumour necrosis factor, IL-17, resolvins, apolipoproteins, type I interferons, IL-6 and mast cells. We suggest that type-2 low disease frequently presents opportunities for identification and treatment of tractable clinical problems; it is currently a rapidly evolving field with potential for the development of novel targeted therapeutics.One-third of severe asthma is type-2 low, presenting a challenge to clinicians. This review provides an overview of the currently available treatment options, other treatable traits and a range of therapies in development. https://bit.ly/2YeNOQd