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Respiratory diseases are the most common cause of death in the UK but, while targets are set for every other major disease category, lung diseases do not get a mention.
Respiratory diseases are the most common cause of death with a 16% higher mortality rate than with coronary heart disease. Chronic obstructive pulmonary disease (COPD) is the most common chronic respiratory illness. At the end of its long course over 30 000 people die from COPD each year in the UK. It is a disease of the poor, with a death rate in men of working age 14 times higher in unskilled manual workers than in professionals.1
The burden to the health service is enormous. In the UK acute respiratory admissions account for 25% of all emergency medical admissions2 and cost £1.1 billion.3 COPD exacerbations account for more than half of these admissions,2 so are likely to cost in excess of £500 million per annum. In planning for service delivery, COPD admissions throw a spanner in the works. During the summer there is a steady number of admissions but in winter this rises by up to threefold (unpublished data, Mater Hospital). This is the time of year when images of patients waiting on trolleys in A&E departments fill our television screens. The domino effect of admissions with COPD goes beyond A&E departments; beds in medical wards are filled to capacity, beds in surgical wards are filled with medical patients, surgical patients are turned away with their operations cancelled, and politically sensitive waiting list targets are not met.
Respiratory diseases are not on government targets for action. Breathlessness and the most common cause of death is hardly on the political radar. This is only going to get worse. Deaths from COPD are set to rise from the sixth to the third most common cause of death by 2020.4
ROLE OF BACTERIAL INFECTION
The East London COPD study has done much to help our understanding of the condition. In this edition of Thorax Patel and colleagues have reported another aspect of their study group. They examined the sputum for the presence of bacteria and compared colonised and non-colonised subjects for the frequency of COPD exacerbations.5 They divided the group into frequent and infrequent exacerbators and found that patients who had pathogens in their sputum were more likely to be frequent exacerbators with an odds ratio of 6.25. They also found that there was an increased level of interleukin-8 (IL-8) in the sputum of the frequent exacerbators, but this just failed to reach statistical significance. However, the levels of IL-8 correlated with the bacterial count.
“[COPD] . . . will continue . . . as the “Cinderella” of medicine”
The study design was such that the sputum assay was obtained in the middle of the study period and exacerbations were identified from diary cards before and after the sputum assay. As such it is not a prospective study. While the East London COPD study was ongoing, others have shown that more than a quarter of patients with a primary care diagnosis of COPD have CT evidence of bronchiectasis.6 This is an area of significant interest because it will change future investigation and treatment strategies in patients with COPD. It is, however, beyond the scope of this current study to determine the extent of bronchiectasis in their population.
ROLE OF VIRUS INFECTION
In previous work published from the East London COPD study Seemungal et al found that one third of exacerbations of COPD were associated with common respiratory viruses, using molecular techniques.7 Similar findings were reported using traditional virological methods on a mixed population of patients with COPD and heart failure.8 The principal advantages of molecular techniques are their increased sensitivity and higher detection rate of rhinoviruses which can be difficult to culture or identify serologically.
Epidemic viruses may not be the only viruses involved in COPD. Hogg's group in Vancouver have identified the presence of adenovirus E1A early antigens in patients with COPD.9 Infection early in life may lead to latent infection which may be important in priming cells for a subsequent role in the development of COPD. Their findings indicate that E1A continues to be expressed within the epithelial cell and, given the right circumstances such as smoke exposure, COPD will result.
A role for viral infection in the pathogenesis of COPD has been supported by the finding of raised titres to common respiratory viruses (CMV and adenoviruses) in a Norwegian population with COPD.10 By comparing umbilical cord blood samples at birth and heel prick samples, we have confirmed that infection with adenovirus is the commonest respiratory virus in early infancy, with up to 23% of children undergoing seroconversion by 6 months of age.11 In an elaborate study by Gilmour et al a cultured epithelial cell line (A549) was transfected with adenovirus E1A gene and exposed to pollution particles (PM10) resulting in a significant rise in IL-8.12
MECHANISMS OF DISEASE
Patel et al5 identified a correlation between IL-8 levels and bacterial count. IL-8 is secreted by epithelial cells and causes neutrophils to transmigrate the airway epithelium. The principal mechanism of this process is via intercellular adhesion molecule 1 (ICAM-1) on the epithelium which binds to the counter ligand CD18/CD11b on the neutrophil. This process can be enhanced by the addition of tumour necrosis factor α (TNFα) and interferon γ (IFNγ) to epithelial cells in vitro.13
Bacterial colonisation of the airways is associated with increased levels of TNFα,14 and infection with viruses causes a rise in lymphocyte derived IFNγ. Both of these chemokines significantly increase epithelial ICAM-1, thereby compounding the effect of IL-8 in enhancing neutrophil accumulation in the airways. Furthermore, ICAM-1 is the major surface receptor for rhinovirus infecting epithelial cells,15 and rhinovirus is the most common viral infection in COPD exacerbations.7 This sets the scene for a vicious circle of increased adhesion of viruses, increased cytokine expression, and increased neutrophil accumulation in the airway.
While each step in this inflammatory “catch 22” is established, we can only await pharmaceutical development and trials to try to break the cycle. Until that time we have to watch as COPD increases year on year and is expected to rise from its current sixth to the third most common cause of death in 2020.4 We also have to watch as targets are set for every other major disease category, yet lung diseases which kill most people do not get a mention. COPD will continue to fill the A&E departments, shut the hospitals, close the operating theatres due to a lack of beds, and break every target in every acute hospital service. Ironically, it will continue its lonely position as the “Cinderella” of medicine.
Respiratory diseases are the most common cause of death in the UK but, while targets are set for every other major disease category, lung diseases do not get a mention.