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In the last 8 years the FEV1 (forced expiratory volume in 1 s) of a ‘typical’ patient with chronic obstructive pulmonary disease (COPD) has fallen by ∼400 ml. However, the knowledge of those caring for this hypothetical patient has grown rapidly in this same period and Thorax has played a vital role in this change of fortune. In 2003 there were 1698 citations to COPD articles in PubMed, compared with 1494 in the first 6 months of 2010 alone, a remarkable growth in the interest in and perhaps quality of research in this field.
Many themes have been considered in this last 8 years, not least how to diagnose the disease. Swanney et al1 defined population norms for the lower limit of normal of the FEV1/forced vital capacity (FVC) ratio to avoid overdiagnosis of airflow obstruction in the elderly. However, not all were convinced, especially when there appeared to be no difference in mortality when the definition was varied in this way.2 The absence of bronchodilator reversibility proved to be an unreliable defining feature in COPD,3 and the treatment guidelines changed to reflect this new research.4 Classifying patients with GOLD (global initiative for chronic obstructive lung disease) stage 1 disease (reduced FEV1/FVC but FEV1 >80% predicted) proved difficult as some patients were not reproducibly obstructed. However, those with symptoms did show more rapid decline in lung function,5 were more likely to have previous bronchitic symptoms6 and responded physiologically to inhaled bronchodilators.7 So, contrary to earlier views, GOLD stage 1 may be a clinically relevant entity after all.
COPD is normally thought of as a ‘smokers' illness’, and some have argued that it should only be diagnosed in smokers. Powerful arguments against this view have come from the elegant laboratory and epidemiological studies from South China where a clear relationship between symptomatic airflow limitation and biomass fuel exposure has been demonstrated,8 not to mention the clear associations between COPD and occupation reviewed by Blanc and colleagues.9 Moreover, early life events such as parental asthma, maternal smoking and respiratory infections play an unexpectedly large part in determining who will subsequently lose lung function.10 Ideally we would be able just to take blood, and a serum biomarker would give us some clinical certainty. A comprehensive review by Gan et al showed that there is growing evidence for systemic inflammation in COPD but at the patient level there is too much variability in any of the potential biomarkers of inflammation to make them suitable for clinical decision making.11
Sometimes you cannot see what is in front of you and it is embarrassing to realise just how many co-morbid conditions affect our patients with COPD, as shown in a large Italian study of people undergoing pulmonary rehabilitation.12 These are not just chance occurrences. Mills et al showed that increased arterial stiffness and raised blood pressure were associated with COPD independently of age and smoking.13 Patel et al reported an association between wrinkling as a surrogate of elastin destruction and COPD,14 while the Edinburgh group subsequently completed the argument by relating arterial stiffness to CT-defined emphysema. These observations add to the growing evidence that COPD is best seen as a disease of accelerated ageing, a fruitful new area for research in the coming years. Clearly COPD is not just a lung disease but is, at the least, a marker for other important conditions. This helps explain the elegant data from the TORCH study which showed that many patients with clinically significant COPD die from non-respiratory causes and especially cardiovascular disease.15
Respiratory physiology staged a comeback as new methods allowed us to ask new clinically relevant questions. For the first time we could measure chest wall movement directly using opto-electronic plethysmography. This showed that although the lungs may hyperinflate as exercise begins the chest wall does not always change in parallel and, when patients activate their abdominal muscles in the face of airflow obstruction, they may stop sooner than expected.16 Similar techniques showed that the timing of hyperinflation varied between patients and that rehabilitation was associated with less chest wall overinflation during exercise.17 Non-invasive measurements of lung mechanics by forced oscillation methods identified significant falls in inspiratory resistance and lung volume as COPD exacerbations resolved18 while measurements of quadriceps muscle strength became the latest independent prognostic marker for patients with more severe COPD.19
Exacerbations of COPD are now recognised as key events in the natural history of the disease with exacerbating patients having not only a worse health status but a worse prognosis.20 Infection, both viral and bacterial, is accepted as a key trigger to these events, but we now have evidence that gastro-oesophageal reflux21 and changes in atmospheric air pollution22 also precipitate these episodes. Old treatments may be more valuable than we thought. Roede and colleagues reported a provocative pharmaco-epidemiological study suggesting that the addition of antibiotics to steroids at exacerbation prolonged time not only to the next exacerbation, but also to the exacerbation after that.23 Intravenous xanthines fared less well as they failed to influence the outcome of hospitalised patients in the largest randomised controlled trial to date of this treatment.24
There has been much debate about the use of long-acting bronchodilators with and without inhaled corticosteroids in the management of stable disease, and Thorax has published important papers from both sides of this debate. As a result, there is now a consensus on when and how these drugs should be used, and this has been recently reviewed in the limited update of the National Institute for Health and Clinical Excellence (NICE) guidance. It is also evident that we need new treatment approaches to make further progress. Theophyllines have been available for years, but the suggestion from Cosio and colleagues in 2009 that they may reduce the apparent corticosteroid insensitivity observed in COPD has led to a resurgence of interest in these drugs—and at low dose too.25 Non-drug treatment has been evaluated with mixed results. Short-burst oxygen therapy to relieve breathlessness has proven ineffective physiologically,26 although the suspicion lingers that occasional patients may benefit to a minor degree.27 Eight years ago non-invasive ventilation at exacerbation was becoming widely available, and McEvoy and colleagues have recently conducted a challenging trial in patients with stable hypercapnia who lived longer with this treatment but felt worse,28 making its routine use at present an unattractive prospect.
The last 8 years has shown us that we used to frequently miss the diagnosis of COPD even in those with severe airflow limitation29 and that our healthcare system often failed them when they were acutely ill.30 However, recent survey data from the Royal College of Physicians show that we are doing better and encouragingly our patients seem to be living longer.31 The past is a foreign country, they do things differently there as LP Hartley said, and this is just as true for COPD as for any area of life. Building on what we have learnt using new tools and new treatment approaches sometimes applied to old drugs but often to the new agents just entering clinical trials is sure to drive forward our understanding of the causes, consequences and impacts of COPD. Often the biggest effect comes from a change in how we deliver care rather than the components of the care we deliver. Changing how the patient behaves can have dramatic effects on their outcome. Perhaps the most surprising paper of the last 8 years was the report from the TORCH study showing that patients who took their treatment had substantial and highly significant differences in hospitalisation and death rates compared with those who did not—even when randomised to placebo!32
Whatever the results of these new studies, we are confident that the best of them will be published in Thorax, which will remain at the heart of respiratory research in the decade ahead.
Competing interests None.
Provenance and peer review Commissioned; not externally peer reviewed.