Eosinophilic Asthma Resource Centre

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Unmet Needs and Challenges In Uncontrolled Severe Asthma

Speaker: Nicola A. Hanania, MD, MS

Unmet Needs and Challenges In Uncontrolled Severe Asthma

In this webcast by Dr Hanania the definition of severe asthma, the underlying mechanisms of disease, and the current treatment guidelines are discussed.


In this webcast, Dr Hanania reviews the correct definition for severe asthma, discusses its underlying mechanisms, explains the current treatment guidelines and highlights the need for improving treatment in this patient population.

The GINA recommendation goals are to achieve current control and reduce future risk (of worsening, of lung-function loss, or adverse treatment effects and of exacerbations). Despite these and other guidelines, asthma remains uncontrolled in about 40% of patient, and of these 5-10% are considered severe cases that fail to respond to conventional therapy. The result is substantial morbidity and mortality and a high economic burden. 

The ATS/ERS defines severe asthma as asthma that has required medication suggested in the GINA guidelines Step 4 and 5 over the previous year, or systemic corticosteroids for ≥50% of the previous year to prevent it becoming uncontrolled, or which remains uncontrolled despite this therapy.

Asthma is a heterogeneous disease with several pathophysiological mechanisms (TH2-high and TH2-low subgroups, for example). This results in different responses to different treatments.

Dr Hanania describes the difference between asthma phenotypes (disease attributes that describe differences between individuals) and endotypes (the specific biological pathway that explains the observable properties of a phenotype). He describes emerging phenotypes (e.g., obesity-associated asthma, smooth-muscle-mediated paucigranulocytic asthma, and smoking-related neutrophilic asthma) and their relation to age of onset, and highlights the importance of phenotyping (using biomarkers if possible) in order to give the right treatment to the individual.

Asthma phenotyping is complicated however, by the overlap of phenotypes. Atopic + eosinophilic can occur in the same individual, as can Atopic + TH2-high or TH2-high + eosinophilic. This complicates treatment decisions, particularly with administering biologics.

The approach to uncontrolled asthma is to revisit the diagnosis to rule out asthma mimickers, to avoid potential triggers, to treat aggravating conditions and asthma education (e.g., compliance, proper inhaler use).

The GINA guidelines lay out a stepwise approach to asthma treatment and management, but about 10-15% of asthma patients remain uncontrolled no matter what is done. Progress in understanding asthma phenotypes along with the continued development of targeted therapies may help to change patient management.