The RASP-UK consortium is a dynamic, inter-linking project comprising four work-strands.
Work-strand 1 aims to provide a clinical stratification of patient cohorts and will serve as a platform for investigative programmes in the other work-strands.
Aim 1: Identify non-adherence
Non-adherence to steroid treatment is often unintentional and is poorly detected by clinicians and enrolment of non-adherent patients into clinical trials complicates the interpretation of the results. Work-strand 1 aims to develop and validate biomarkers as objective tools for assessing non-adherence to steroid treatment.
Patients will be tested for inhaled steroid adherence, using the fractional exhaled nitric oxide (FeNO) suppression test combined with remote inhaler monitoring technology. This test identifies inhaled steroid responsiveness and patients who are adherent but inhaled corticosteroid resistant and remain T2-biomarker high despite adequate adherence with high dose inhaled steroids (T2-high asthma) require additional treatment. Other novel biomarkers will also be studied as a means to assess adherence.
Aim 2: Evaluation of a composite T2 biomarker score to optimise steroid treatment
Although individual Type 2 biomarkers (blood eosinophil count, FeNO and serum periostin) correlate with risk of asthma exacerbation and steroid response, a composite score using all these biomarkers may offer greater predictive power. RASP-UK will compare a composite biomarker strategy with standard care to identify if steroids can be better targeted in severe asthma.
Aim 3: Characterise and follow up the T2-low cohort
It is now recognised that not all facets of severe asthma are driven by Type 2 effector cytokines (such as interleukins-4, -5 and -13). It is anticipated that using the composite biomarker strategy described above, we will identify patients with “T2-Low asthma”. A key focus of RASP-UK will to phenotypically characterise and compare this population with (i) the T2-high cohort and (ii) subjects with stable asthma and good symptom control on low dose corticosteroids. It is hoped that by characterising and comparing patient phenotypes, important structure/function/symptom relationships will be defined. The T2-Low cohort will be followed-up at 6 and 12 months to identify exacerbation pattern and phenotype stability.
Aim 1: Define Bronchoscopic sampling procedures
The analysis of expressed genes in airway epithelial cells is useful for defining subsets of asthma. Bronchoscopic samples from patients with T2-Low asthma will enable the analysis and identification of differentially expressed genes and other differences and thus allow us to interrogate the factors driving T2-Low severe asthma. It is probable that T2-Low severe asthma is heterogeneous and we do not currently know what drives disease in this phenotype, although ‘non-inflammatory’ structural changes may be involved. Therefore, a detailed immunopathological analysis will be performed coupled with gene expression data.
Aim: To identify novel biomarkers to predict response to Omalizumab treatment
Omalizumab is an approved treatment for severe atopic asthma which reduces asthma exacerbations. There are currently no reliable biomarkers that predict which patients will respond positively to omalizumab, however the Unbiased BIOmarkers for the Prediction of Respiratory Disease Outcomes (U-BIOPRED) programme has identified novel biomarkers in patients with severe asthma. These urinary biomarkers will be investigated for their predictive value with omalizumab treatment in subjects suitable for omalizumab.
Aim: Proof of concept clinical trials in stratified cohorts
RASP-UK will explore the effects of novel compounds as ‘add on therapies’ to standard care in subjects with both T2-High and T2-Low asthma.