Data from The Asthma Report - Curated by EPG Health - Last updated 18 September 2018
Professor Sally Wenzel began the session highlighting the current state of phenotyping in asthma. Blood eosinophils have been shown to be one of our best current biomarkers and up to 80% of severe asthmatics are Type 2 high on repeated measures in the SARP (The Severe Asthma Research Program) cohort with higher blood eosinophils likely to imply better response to anti-IL5 therapy. Late onset asthma also seems to confer better response to anti-IL5 therapy. While blood eosinophils predict better response to dupilumab too, there is a 65% exacerbation reduction in those with low blood eosinophils. IL6 in blood predicts increased exacerbation rate independently of BMI, but doesn’t correlate with lung IL6.
Professor Wenzel posed the question of whether a response to treatment should be used as a bio marker. Unbiased approaches to biomarker and pathway identification such as WGCNA are needed.
Professor Peter Gibson presented on the effects of macrolides in airways diseases. Severe and nonsevere asthma both seem to show a 40% reduction in exacerbation with long term macrolides, but treatment needs to be longer than 3 months. Diarrhoea may necessitate dose reduction while statins (simvastatin or atorvastatin) and long QTc (Corrected QT Interval) may be problematic. Macrolides affect macrophage phagocytosis and inflammatory cytokines. Macrolides seem to work in eosinophilia and noneosinophilic asthma without affecting inflammatory cell counts, but bacterial pathogen presence in sputum and mucus hypersecretion predicts better exacerbation reduction. Azithromycin did reduce microbiome variability, but also haemophilus copy number in AMAZES. Azithromycin but not clindamycin improves macrophage clearance of apoptosis cells. Professor Gibson concluded that azithromycin may improve exacerbation frequency through improving dysbiosis or macrophage function, but should be considered in those with “ABBA syndrome” – adults with bacterial bronchitis and asthma.
Director of the Asthma Clinical Research Center at Baylor College of Medicine, Nicola Hanania tried to answer whether we are transforming care with biologics. Biologics should aim to improve short and long term outcomes, reduce airway inflammation, have reliable biomarkers, be simple to administer, be cost effective and modify disease. Challenges include limitations of biomarkers and lack of information on multiple biologic use. Potential targets for biologic therapy include alarmins, traditional cytokines and GATA3. Omalizumab reduces exacerbation by approx 38% in allergic asthma and hospitalisations by over 80%, and this may be through an effect on dendritic cells and well as the IgE receptor. Mepolizumab reduces exacerbations by 50% with blood eos of 0.15 and more with higher counts, and this is maintained over time but may not preserve lung function. Reslizumab and Benralizumab showed similar effects. Dupilumab may affect structural cells as well as inflammatory cells, improves exacerbation rates but also importantly improves lung function. Tezepelumab is in phase 3 but may improve T2 and non T2 asthma. Treatment for non Type 2/allergic disease is needed.