Phenotyping severe asthma: a rationale for biologic therapy

ABSTRACT

Introduction

Asthma is a complex disease with heterogeneity in etiology, triggers, clinical characteristics and different responses to pharmacological therapies.

Areas covered

Patients with severe uncontrolled asthma constitute a relatively small percentage, ranging from 5 to 10% of all asthmatics. These patients can benefit from targeted biological therapies developed in recent years. In fact, a better understanding of the etiopathological mechanisms of different phenotypes and endotypes of severe asthma have led to the availability of innovative biological therapies, able to modify the natural history of the disease by targeting molecules involved in airway inflammation. Several phenotypes based on clinical and physiologic variables and on inflammatory markers have been reported.

Expert opinion

The priority is to define the molecular process underlying the disease. In this context the recognition of T2 and non T2 inflammatory pathways, so called molecular phenotypes, represents the most reliable approach to drive the use of novel biological therapies. For this purpose, several biomarkers have been validated for identifying severe asthma phenotypes and for guiding the choice of the most appropriate treatment. The purpose of this review is to discuss the current knowledge about the molecular phenotypes of severe asthma, as well as the rationale underlying the use of existing biological drugs.

KEYWORDS:

• Severe asthma
• biomarkers
• biologic drugs
• asthma phenotypes
• T2 inflammation
• asthma therapy
• asthma endotypes
• precision medicine

Article highlights

• Asthma is a complex disease with heterogeneity in etiology, triggers, clinical characteristics and different responses to pharmacological therapies.

• A minority of patients experience poor disease control despite the maximum standard therapy, with reduced quality of life and higher exacerbation, hospitalization and mortality rates.

• In recent years, the discovery of different asthma phenotypes and endotypes has laid the foundation for a profound change in treatment of severe asthma, moving from a ‘one-size-fits-all’ approach to a more precise and personalized one.

• All the various cellular and molecular factors of immunophlogistic processes in asthma may represent a target for potential pharmacological approaches with biological molecules.

• Currently available biomarkers are useful tools for identifying severe asthma phenotypes and allow to identify the presence of type 2 inflammation.

• The potential molecular targets of different biological treatments are based on the inflammatory phenotype.

• Currently, there are only biological medications available against T2 inflammation.

• In the clinical context, a correct approach to define the most suitable biological therapy should take in consideration clinical and physiological variables, other than biological characterization based on biomarkers.

• A greater knowledge of molecular endotypes of asthma will allow a more precise definition of several clinical and biologic phenotypes, in order to address patients towards tailored therapies with the highest probability of success.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewers disclosure

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.