As part of the updated 2019 ERS/ATS asthma guidelines, two important questions have been reached in relation to biomarkers:
- Whether measurement of a specific biomarker should be used to guide the initiation of treatment with a monoclonal anti-IL-5 or IL-5rα antibody in adults and children with severe asthma. The task force has suggested that a blood eosinophil cut-off of > 150/μL can be used to guide anti-IL-5 initiation in adult patients with severe asthma and a history of prior asthma exacerbations. Although the recommendation is conditional, due to low quality of evidence, we place high value on reducing exacerbations and the feasibility of the measurement of the biomarker, together with a lower value on cost and invasiveness.
- Whether measurement of a specific biomarker should be used, in addition to total IgE level, to guide initiation of treatment with a monoclonal anti-IgE antibody in adults and children with severe asthma. The conditional recommendation was to use a blood eosinophilic cut-off of >260/μL, or a FeNO cut-off of 19.5 ppb, to identify patients over 12 years old with severe allergic asthma, who are more likely to benefit from anti-IgE treatment. This recommendation is of great value in increasing treatment response when both, blood eosinophils and FeNO, are used to select patients.
The use of biomarkers can help to reach the current objective to personalise the approach of managing asthma treatment. GINA consider an add-on biologic type-2 targeted treatment depending on anti-IgE, anti-IL-5/IL-5r and anti-IL-4R status. The level of type-2 mechanisms/pathways has been related to clinical patterns: T2-high with TAC1 and T2-low/non-T2 with TAC2 and TAC3, in relation with TAC status, like blood eosinophil counts.
In summary, the system's biology (exposome, lifestyle and genome) condition biological responses, endotypes and clinical phenotypes, which in the end relate to a precision medicine combining targeted treatment and biomarkers.
Other speeches have covered other clinical approaches of severe and non-eosinophilic asthma, illustrated with clinical cases.
- Summarising from the speech of Dr Nair: There is a rationale to consider that most patients with asthma do not need a biologic. Inadequate airway IL-5 neutralisation with monoclonal antibody can worsen severe prednisone-dependent asthma by autoimmune mechanisms. Targeting IL-4R may be helpful in predominantly non-eosinophil patients. Thermoplasty is an option for severe AHR. Novel imaging may be useful outcome measures.
- Dr Schleich has pointed out that non-eosinophilic asthma is not responsive to ICS and that there are large unmet needs for patients with severe asthma without significant Th2 inflammation. LAMA is useful in moderate-to-severe asthma and macrolides decrease exacerbations and improve quality of life.