Precision Medicine within the Institute of Lung Health

Much of the work carried out by the Respiratory Theme falls under the description of Precision Medicine. Examples include:

“Breathomics”

Exhaled breath contains >1500 volatile organic compounds (VOCs) reflecting biological processes occurring within the lung as well as host-environment interactions [1]. Analysis of VOCs in breath is a metabolomic approach that provides a real-time, non-invasive method of diagnosing, phenotyping and stratifying patients with a variety of clinical conditions including respiratory disease and infections (bacterial, fungal, viral). Leicester has unique strengths and strong collaborations between clinical academics and basic scientists and SMEs, delivering novel prognostic tests and targeted therapies.

Key publications:

White IR, Willis KA, Whyte C, Cordell R, Blake RS, Wardlaw AJ, Rao S, Grigg J, Ellis AM, Monks PS. Real-time multi-marker measurement of organic compounds in human breath: towards fingerprinting breath. J Breath Res 2013;7:017112

Brightling CE, Bleecker ER, Panettieri RA Jr, Bafadhel M, She D, Ward CK, Xu X, Birrell C, van der Merwe R. Benralizumab for chronic obstructive pulmonary disease and sputum eosinophilia: a randomised, double-blind, placebo-controlled, phase 2a study. Lancet Respir Med. 2014 (Sept 5) doi: 10.1016/S2213-2600(14)70187-0.

Studies into the role of fungal allergy in respiratory disease involves using appropriate biomarkers to determine which types of asthma are associated with fungal allergy, how this relates to day to day control and prognosis and whether fungal specific interventions are of value in treating these patients.

Key publications:

Agbetile J, Bourne M, Fairs A, Hargadon B, Desai D, Broad C, Morley J, Bradding P, Brightling CE, Green RH, Haldar P, Pashley CH, Pavord ID, Wardlaw AJ. Effectiveness of voriconazole in the treatment of Aspergillus fumigatus-associated asthma (EVITA3 study). J Allergy Clin Immunol. 2014 Jul;134(1):33-9. doi: 10.1016/j.jaci.2013.09.050.

Chronic Obstructive Pulmonary Disease

Exacerbations of chronic obstructive pulmonary disease (COPD) are associated with significant morbidity and mortality. Current guidelines advocate the use of systemic corticosteroids in addition to antibiotics to treat an exacerbation, but these treatments are not universally effective and are not without harm. Individualised treatment may, therefore, be an advance. The Respiratory Medicine group recently showed that patients with a peripheral blood eosinophil count of ≥2% respond promptly and completely to prednisolone, whereas those with a count of <2% had a higher rate of treatment failure compared with placebo. This has led to alrger studies to confirm this stratified treatment approach. 

Key publications:

Bafadhel M1, McKenna S, Terry S, Mistry V, Pancholi M, Venge P, Lomas DA, Barer MR, Johnston SL, Pavord ID, Brightling CE. Blood eosinophils to direct corticosteroid treatment of exacerbations of chronic obstructive pulmonary disease: a randomized placebo-controlled trial. Am J Respir Crit Care Med 2012; 186: 48–55. doi: 10.1164/rccm.201108-1553OC

Haldar P, Brightling CE, Hargadon B, Gupta S, Monteiro W, Sousa A, Marshall RP, Bradding P, Green RH, Wardlaw AJ, Pavord ID. Mepolizumab and exacerbations of refractory eosinophilic asthma. N Engl J Med. 2009;360(10):973-84

Genetics and Genomics of COPD:

Professor Martin Tobin’s work involves identifying individuals with rare genotypes of COPD which will help the Respiratory Science Theme understand the mechanisms of lung function decline in asthma and COPD.

Key publications:

Soler Artigas M, Wain LV, Repapi E, Obeidat M, Sayers I, Burton PR, Johnson T, Zhao JH, Albrecht E, Dominiczak AF, Kerr SM, Smith BH, Cadby G, Hui J, Palmer LJ, Hingorani AD, Wannamethee SG, Whincup PH, Ebrahim S, Smith GD, Barroso I, Loos RJ, Wareham NJ, Cooper C, Dennison E, Shaheen SO, Liu JZ, Marchini J; Medical Research Council National Survey of Health and Development (NSHD) Respiratory Study Team, Dahgam S, Naluai AT, Olin AC, Karrasch S, Heinrich J, Schulz H, McKeever TM, Pavord ID, Heliövaara M, Ripatti S, Surakka I, Blakey JD, Kähönen M, Britton JR, Nyberg F, Holloway JW, Lawlor DA, Morris RW, James AL, Jackson CM, Hall IP, Tobin MD; SpiroMeta Consortium. Effect of five genetic variants associated with lung function on the risk of chronic obstructive lung disease, and their joint effects on lung function. Am J Respir Crit Care Med. 2011 Oct 1;184(7):786-95. doi: 10.1164/rccm.201102-0192OC

 

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