Severe Asthma Phenotypes — How Should They Guide Evaluation and Treatment?

Abstract

Although patients with “severe” asthma tend to be characterized by ongoing symptoms and airway inflammation despite treatment with high doses of inhaled and systemic corticosteroids, there is increasing recognition of marked phenotypic heterogeneity within affected patients. While “precision medicine” approaches for patients with severe asthma are needed, there are many hurdles that must be overcome in daily practice. The National Heart, Lung and Blood Institute's Severe Asthma Research Program (SARP) has been at the forefront of phenotype discovery in severe asthma for the past decade. SARP, along with other international groups, have described clinical severe asthma phenotypes in both adults and children that can be evaluated in the clinical setting. While these clinical phenotypes provide a good “starting point” for addressing disease heterogeneity in severe asthma in everyday practice, more efforts are needed to understand how these phenotypes relate to underlying disease mechanisms and pharmacological treatment responses. This review highlights the clinical asthma phenotypes identified to date, their associations with underlying endotypes and potential biomarkers, and remaining knowledge gaps that must be addressed before precision medicine can become a reality for patients with severe asthma.

Asthma diagnosis using integrated analysis of eosinophil microRNAs

“…Asthma pathogenesis depends on numerous factors, including genetic predisposition and environmental agents (allergens, infections, and air pollutants) . It can be classified into different phenotypes and endotypes, which further complicates diagnosis in the absence of fully effective treatment . Asthma symptoms are accompanied by T helper (Th)2–driven inflammatory cell infiltrate of eosinophils and T lymphocytes …”

The Severe Heterogeneous Asthma Research collaboration, Patient-centred (SHARP) ERS Clinical Research Collaboration: a new dawn in asthma research

“…These issues of key importance to people with asthma, their clinicians, the laboratory scientists, the pharmaceutical industry, regulators and payers, gain even more importance with the recognition that severe asthma is heterogeneous both in clinical and pathological terms [14]. In Europe, the effort to stratify asthma was led by the Innovative Medicines Initiative (IMI)-funded consortium U-BIOPRED (Unbiased BIOmarkers for the Prediction of REspiratory Disease outcomes) resulting in major discoveries that, together with those from the US consortium, SARP (Severe Asthma Research Program), have transformed our understanding of asthma mechanisms and provided new clinical asthma phenotypes [15][16][17]. They open up the possibility of discovering the underlying driving molecular endotypes behind these variants.…”

Immunologic and Non-Immunologic Mechanisms Leading to Airway Remodeling in Asthma

“…These two categories often correlate with the presence of eosinophils or neutrophils, respectively. However, airway wall remodeling occurs in most asthma patients and does not correlate with specific pheno-or endo-types [15,16].…”

“…The only new aspect that seems to show up in many studies was the important role of the interaction between the environment and the lung, based on epigenetic gene regulation. Many of the "-omic" studies indicated that tissue remodeling is a major pathology and against previous assumption occurs independent from inflammation [15][16][17]. Furthermore, many studies reported that the different asthma phenotypes, which were described based on patient symptoms, could not be well separated by specific cellular pathologies [18][19][20].…”