My principal area of research is the study of the development and impact of chronic obstructive pulmonary disease (COPD). I am involved in the day-to-day running of the London COPD cohort. This is an observational cohort of approximately 200 moderate to very severe COPD patients started in November 1995. We have shown a relationship between COPD exacerbations and quality of life and disease progression, and that early treatment of exacerbations reduces the severity and prevents hospital admission. This has led to the development of early intervention strategies that is one of the objectives of the COPD National Services Framework. Our research has strong clinical and basic components and we have shown the importance of infection at exacerbation, the interaction of bacteria and viruses and the rationale for the use of antibiotics at COPD exacerbation in collaboration with Microbiology and Virology at the Royal Free Hospital. We were the first to show the relationship between airway inflammatory markers and decline in lung function. We were also the first group to define the presence of COPD patients with a history of frequent exacerbations and these patients are most prone to have recurrent COPD admissions which impose considerable costs on the NHS. The division of patients into frequent and infrequent exacerbation phenotypes has been incorporated into disease management guidelines for the prescription of maintenance therapy. An analysis of a pharma-epidemiological database (2010) showed the relationship between COPD exacerbation and acute myocardial infarction, and this work has been a stimulus for better treatment of cardiovascular disease in COPD.
The cohort is currently involved in a number of commercial and non-commercial studies. It is currently participating in the AZ funded Novelty study, EU-IMI RESCEU study and a NIHR funded Programme Grant which is a study involving the innovative use of antibiotics to reduce exacerbations and involves two active randomized control trials (RCT). There are also active academic and pharma company collaborations
Over my 22 years of involvement with the cohort, it has participated in the TREAT study (a RCT of Roflumilast at acute exacerbation) funded by Takeda, ECLIPSE (3 years observational study) funded by GSK, an infection susceptibility study funded by AZ, a study of macrophage phagocytosis funded by Astra-Zeneca, LTB4 proof of concept study funded by GSK, REACT (1 yr RCT of long-term Roflumilast) funded by Takeda, a combination bronchodilator therapy study funded by Novartis, Forward (RCT of Foster) funded by Chiesi, and a RCT of broncho-vaxom for Vifor-Pharma.
I have also been involved in the collaborative study of the development of bronchitis (mucus hyper-secretion) and early life smoking on later adult lung development in the MRC1947 Birth cohort. This work has focused the development of the BLF early COPD development partnership. I am a key member of the lead team at Imperial establishing the cohort with funding for £3.4 million from 5 pharmaceutical companies (GSK, Novartis, BI, AZ, Cheisi). The partnership involves 8 academic institutions (Imperial, Southampton, Leicester, Nottingham, Liverpool, Belfast, Edinburgh and Birmingham) and the British Lung Foundation (BLF). He has been involved from the start in study design, grant writing and planning for data management. I sit on the consortium management committee board as a permanent, co-opted member
My other research interest has been the study of the physiological effects of cold and heat on the body. In a series of human experiments, we showed that cold increases the concentration of clotting factors in the blood and thus explain the rise in cardiovascular deaths in winter. This lead to an interest into the effects of climate on UK mortality and Hospital admissions. The results showed the delay between falls in temperature and death from various categories of disease. Much cold exposure is due to person behavior and we studied this with a pan-European survey of home heating and outdoor clothing (Eurowinter project). Our findings have been incorporated into Department of Health heat-wave and winter planning strategies for the UK. I have also published work on the confounding between temperature and atmospheric pollutants.
I was a co-author of two commissioned briefing documents for the Department of Health on the health implications of heat-waves in the UK. I have also examined the effects of cold weather on mortality and COPD exacerbations (1999). This work showed that respiratory disease had the steepest negative relationship to temperature, a finding used as the rational for the Meteorological Office’s health forecasting service for COPD. I have also been consulted by the Overheating Thresholds Experts' Roundtable run by the London Climate Change Partnership concerning temperature threshold for advising vulnerable groups not to travel on the London Underground, and the Health Protection Agency and the Department of Health, in association with the National House Building Council Foundation and the Building Research Establishment (BRE) concerning the health effects of over-heating.
I have been involved in a number of health service studies including the provision of non-invasive ventilation across Europe (Eurovent project), the use of Home-Oxygen in England and Wales (with the Department of Health and the British Thoracic Society), and the health-economics of COPD in collaboration with Astra-Zeneca. I have designed and built two web-sites for the Eurovent project and for the EU funded COST initiation on exacerbations.
et al., 2020, Bacteria and sputum inflammatory cell counts; a COPD cohort analysis., Respir Res, Vol:21
et al., 2020, Immunological and inflammatory biomarkers of susceptibility and severity in adult respiratory syncytial virus infections, Journal of Infectious Diseases, Vol:222, ISSN:0022-1899, Pages:S584-S591
et al., 2020, Pharmacologic Management of Chronic Obstructive Pulmonary Disease. An Official American Thoracic Society Clinical Practice Guideline (vol 201, pg e56, 2020), American Journal of Respiratory and Critical Care Medicine, Vol:202, ISSN:1073-449X, Pages:910-910
et al., 2020, Targeted retreatment of incompletely recovered COPD exacerbations with ciprofloxacin: a double-blind, randomised, placebo-controlled, multicentre phase III trial, American Journal of Respiratory and Critical Care Medicine, Vol:202, ISSN:1073-449X, Pages:549-557
et al., 2020, The sputum microbiome is distinct between COPD and health, independent of smoking history, Respiratory Research, Vol:21, ISSN:1465-9921, Pages:1-12