PhD Studentship: Blood eosinophilia as a biomarker of response and side effects of inhaled corticos

Details
Chronic Obstructive Pulmonary Disease (COPD) is an important cause of morbidity and mortality [1-3]. Smoking cessation is currently the only known disease modifying intervention. Pharmacotherapy is mainly symptomatic, aiming to reduce dyspnoea, increase exercise tolerance and improve perceived health [2]. Bronchodilators (BD) are the cornerstone of pharmacotherapy, with inhaled corticosteroids (ICS) being additionally prescribed for those with frequent exacerbations to reduce recurrence [4]. COPD exacerbations are associated with greater lung function decline, poor health status and increased mortality [5].

Although commonly prescribed, there is an ongoing debate about the role of ICS in patients with COPD [6]. Growing evidence supports the association between ICS and risk of pneumonia and fracture [6-8], particularly among older patients [9]. While it remains unclear whether this is a class effect [10], this has certainly challenged the role of ICS in COPD. In COPD, ICS are not as effective as in asthmatics [11], which may be related to the more neutrophilic, rather than eosinophilic inflammatory airway response in COPD compared with asthma.

Recent evidence from two double-blind randomized controlled trials (RCTs) with 1 year follow-up suggest that blood eosinophil count is a promising biomarker of response to ICS in patients with COPD. One RCT compared daily vilanterol (BD) with a vilanterol /fluticasone (BD/ICS) combination in patients with moderate-to-severe COPD and one or more exacerbations in the previous year. Peripheral blood eosinophilia (≥2%) was observed among 68% of COPD patients. Compared with BD alone, combination treatment reduced exacerbations by 29% in patients with eosinophilia, and by 10% in patients without (Figure 1 [12]). This has been confirmed in other clinical studies including post-hoc analyses of RCTs [13-16]. However, it is unclear whether this is true for other ICS, and large population-based studies are lacking. Also, the usefulness of eosinophil count as a biomarker in patients without an exacerbation in the past year remains to be studied.

Aims
The aim will be to assess differential response to ICS in COPD patients with or without eosinophilia regarding exacerbations, pneumonia, fracture, COPD-related hospitalisation, all-cause mortality and COPD-related mortality

Enquiries should be directed to the College MDS Graduate School at mds-gradschool@contacts.bham.ac.uk

To apply, please send:

• A Detailed CV, including your nationality and country of birth;
• Names and addresses of two referees;
• A covering letter highlighting your research experience/capabilities;
• Copies of your degree transcripts;
• Evidence of your proficiency in the English language, if applicable.

Funding Notes

This PhD Studentship is jointly supported by University of Birmingham (UK) and the Maastricht University (Netherlands) and provides a three year stipend and consumables costs.