Title: Predicting inhaled steroid responsiveness using near-patient testing: personalising long-term management of COPD in primary care
Funder: Department of Health and Social Care

Abstract: Background Current management of chronic obstructive pulmonary disease (COPD) in primary care is often based on a one-size-fits-all' approach to monitoring and treatment, including initiation of inhaled steroids (ICS) when symptoms deteriorate. Although ICS carry some benefit in long-term management of COPD, they have not consistently been shown to reduce rate of lung function decline, and their use has been associated with side-effects including increased risk of pneumonia. ICS are expensive drugs, costing up to 700 annually per patient. Research in secondary care populations has found that distinct disease phenotypes may exist, which can be identified by biomarkers of inflammation in blood, breath and sputum, and which respond differently to treatment with inhaled steroids (ICS). Specifically, patients with raised sputum eosinophils have improved lung function and symptoms following ICS treatment. However, this has never been studied in a primary care population using less invasive measurement techniques or steroid-nave patients who have not yet commenced ICS treatment. I hypothesise that these phenotypes also exist in a primary care COPD population and that the underlying disease state in the non-eosinophilic subgroup may deteriorate more quickly with inhaled steroids while inhaled steroids may help the eosinophilic subgroup remain more stable for longer. These phenotypes can be identified by biomarkers which have shown promise in a secondary care research environment, some of which could guide treatment decisions at the point of care in general practice and enable better targeting of inhaled steroid treatment to individual patient characteristics. Point-of-care or near-patient testing refers to medical testing at or near the site of patient care. GPs identify COPD as a high priority area for developing near-patient testing in disease monitoring. Aim I aim to identify whether selected near-patient inflammatory biomarkers which have shown promise in a secondary care population can be used to identify disease phenotypes in patients with COPD in primary care, and whether these can identify which patients will receive overall meaningful benefit from inhaled steroids and therefore support more effective and personalised management of this common and important condition. Research objectives 1)To systematically identify and appraise published evidence for the use of selected biomarkers (including blood eosinophil count, C-reactive protein (CRP) and fraction of exhaled nitric oxide (FeNO)) for predicting disease outcomes and steroid responsiveness in long-term management of COPD 2)To investigate biomarker levels in a primary care COPD population, and whether biomarkers predict steroid responsiveness and disease outcomes 3)To characterise biomarker levels, stable state variability and how they relate to each other to establish whether they are useful as single tests and whether there is added benefit to using them in combination for long-term disease monitoring. This will be used to develop plans for subsequent longer term studies. Methods 1)Systematic literature review of current evidence for the use of biomarkers to predict disease outcomes in long-term management of COPD in primary care 2)Database cohort study using routinely collected consultation data of primary care patients to assess association between biomarkers (where assessed) and disease outcomes and steroid responsiveness 3)Prospective observational cohort study of inhaled steroid-nave patients in primary care with clinically stable COPD with monitoring of biomarkers at multiple time points Potential benefits to patients and the NHS Using individual characteristics to tailor treatment more effectively to patients with COPD using near-patient testing will lead to earlier management and therapy initiation, avoid unnecessary prescriptions and may reduce harm. This has the potential to reduce disease burden by helping some patients to remain stable for longer, reduce treatment burden for other patients and reduce associated health care costs, both by decreasing prescriptions of expensive inhalers and patient morbidity.

Lay abstract: Current management of chronic obstructive pulmonary disease (COPD) in primary care is generally a one-size-fits-all' approach, based on guidelines, which recommend inhaled steroid treatment when symptoms deteriorate. I plan to investigate whether health care professionals can use a blood and/or breath test to identify which patients will respond to inhaled steroids. I plan to do this through a literature review, a database study of GP records, and a study monitoring these blood and breath markers in COPD patients. This will help facilitate a more personalised approach to starting inhaled steroid treatment, and improve the care of patients with COPD.

Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: RESPIRATORY