PhD: Blood eosinophil count as a means of stratifying COPD management
3rd Supervisor: Dr Rachel Jordan
Chronic obstructive pulmonary disease (COPD) is a chronic respiratory condition characterised by airflow obstruction that is not fully reversible. Typically the disease occurs in people aged >40 with a history of cigarette smoking. Inhaled corticosteroids (ICS) are currently a key component of pharmacological management of COPD.(1) British guidance recommends use of ICS in combination with a long acting beta agonist (LABA) for COPD patients with a forced expiratory volume in one second (FEV1) <50% of predicted, although history of exacerbation is also important (2). 27% of patients are started on ICS and 30% on ICS/LABA combination around diagnosis, suggesting this treatment class is overused.(3) ICS have a modest effect on reducing COPD exacerbations and decline in health-related quality of life (HRQoL) but do not reduce risk of mortality(4) and are associated with important adverse effects including an increased risk of pneumonia (5), bruising and oral candidiasis (4). Other than a low FEV1 and history of recurrent exacerbations there are no biomarkers available to guide clinicians towards more rational and tailored use of ICS.
Eosinophilic inflammation has been shown through sputum induction to be present in 20-40% of cases of COPD.(6-8) and could characterise a distinct phenotype of COPD.(9) Measuring sputum eosinophil counts is largely only undertaken for research. However blood eosinophil counts, routinely available in clinical practice, may be a good biomarker of bronchial eosinophilia.(10) In an analysis of routine primary care data 10% of COPD patients had a blood eosinophil count ≥0.5 x 109/L and patients with eosinophilia had a higher exacerbation rate.(11). This project will examine the potential for blood eosinophil count to aid stratification of treatment for ICS use in COPD by way of literature review and validation work using primary care data. If possible an algorithm to determine selection for ICS therapy will be developed by the end of the project.
Environment for study
This project is jointly supervised between respiratory medicine and primary care, both supervisors having experience of systematic reviews and epidemiological work in COPD. The successful student will be placed in the respiratory medicine group, where there are typically 3 clinical PhD/MD students and 1 non-clinical PhD at any given time. Our group has weekly laboratory meetings and presentation of research. Training will be available through University courses on relevant areas for the PhD, and attendance at relevant primary care or public health seminars will be encouraged.
Applicants should have a strong background in medical sciences, and ideally a background in public health or epidemiology. They should have a commitment to research in respiratory medicine and/or primary care, and hold or realistically expect to obtain at least an Upper Second Class Honours Degree in a relevant subject.
How to apply
Informal enquiries should be directed to Dr Alice Turner (email@example.com or firstname.lastname@example.org )
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 certificates with transcripts;
• Evidence of your proficiency in the English language, if applicable.
The required funding for this PhD will consist of standard University PhD fees, and consumable costs of £5000 per annum, to cover costs of database access, study retrieval, printing and anticipated dissemination and publication costs.
1. Global Initiative for Chronic Obstructive Lung Disease: Global strategy for the diagnosis, managment, and prevention of chronic obstructive pulmonary disease Global Initiative for Chronic Obstructive Lung Disease, 2013.
2. Chronic obstructive pulmonary disease : management of chronic obstructive pulmonary disease in adults in primary and secondary care. London: National Institute for Health and Clinical Excellence; 2010.
3. Gruffydd-Jones K, Brusselle G, Jones R, Miravitlles M, Baldwin M, Stewart R, et al. Changes in initial COPD treatment choice over time and factors influencing prescribing decisions in UK primary care: in UK primary care: a real-world, retrospective, observational. Npj Primary Care Respiratory Medicine. 2016;26:16002.
4. Yang IA, Clarke MS, Sim EHA, Fong KM. Inhaled corticosteroids for stable chronic obstructive pulmonary disease. Cochrane Db Syst Rev. 2012(7).
5. Kew KM, Seniukovich A. Inhaled steroids and risk of pneumonia for chronic obstructive pulmonary disease. The Cochrane database of systematic reviews. 2014;3:CD010115.
6. Saetta M, Distefano A, Maestrelli P, Turato G, Ruggieri MP, Roggeri A, et al. Airway Eosinophilia in Chronic-Bronchitis during Exacerbations. Am J Resp Crit Care. 1994;150(6):1646-52.
7. Pizzichini E, Pizzichini MMM, Gibson P, Parameswaran K, Gleich GJ, Berman L, et al. Sputum eosinophilia predicts benefit from prednisone in smokers with chronic obstructive bronchitis. Am J Resp Crit Care. 1998;158(5):1511-7.
8. Brightling CE, Monteiro W, Ward R, Parker D, Morgan MDL, Wardlaw AJ, et al. Sputum eosinophilia and short-term response to prednisolone in chronic obstructive pulmonary disease: a randomised controlled trial. Lancet. 2000;356(9240):1480-5.
9. Cosio BG, Soriano JB, Lopez-Campos JL, Calle-Rubio M, Soler-Cataluna JJ, de-Torres JP, et al. Defining the Asthma-COPD Overlap Syndrome in a COPD Cohort. Chest. 2016;149(1):45-52.
10. Eltboli O, Mistry V, Barker B, Brightling CE. Relationship between blood and bronchial submucosal eosinophilia and reticular basement membrane thickening in chronic obstructive pulmonary disease. Respirology. 2015;20(4):667-70.
11. Price D, Rigazio A, Postma D, Papi A, Guy B, Agusti A, et al. Blood eosinophilia and the number of exacerbations in COPD patients. European Respiratory Journal. 2014;44(Suppl 58).
12. IMS Health: Our data London: IMS Health; 2016 [Available from: http://www.epic-uk.org/our-data/our-data.shtml.
13. Pascoe S, Locantore N, Dransfield MT, Barnes NC, Pavord ID. Blood eosinophil counts, exacerbations, and response to the addition of inhaled fluticasone furoate to vilanterol in patients with chronic obstructive pulmonary disease: a secondary analysis of data from two parallel randomised controlled trials. The lancet Respiratory medicine. 2015;3(6):435-42.