Abstract and Introduction
Abstract
The last 5 years have seen a proliferation of data about the best way to treat chronic obstructive pulmonary disease (COPD). New long-acting inhaled β-agonist and antimuscarinic drugs have been developed as a once-daily inhaled corticosteroid. Studies have tested whether these agents are safe and effective alone or in combination. Alternative strategies to treatment including phosphodiesterase-4 inhibition and long-term antibiotic treatment have become reasonable alternatives to more established approaches, at least in terms of preventing COPD exacerbations. New data are beginning to define which patients benefit from which treatments and this will help us develop more appropriate treatment regimes. These topics are considered in this review which provides an overview of the latest data and some direction as to how these findings can be applied in practice.
Introduction
The appropriate management of the chronic obstructive pulmonary disease (COPD) patient involves more than just choosing the best drug. The most recent revision of the Global Initiative for Chronic Obstructive Lung Disease (GOLD) strategy emphasizes the need to assess current symptoms, ideally using a global assessment scores, such as the COPD Assessment Test, the degree of spirometric impairment, and the likelihood of future exacerbations. This approach has limitations, not least the spontaneous variation in exacerbation status, but it does provide a clinically useful way of defining different groups of patients with different outcomes. Its introduction represents an important change in our treatment strategy, but at present the allocation of evidence to support the effectiveness of treatment in the new scheme involves "retrofitting" data collected in patients who were stratified by spirometry alone. Despite this it is clear that changing exposures to risk factors such as tobacco, offering preventative immunization, and increasing the level of daily exercise have value to all COPD patients. By contrast, widely used treatments such as ambulatory oxygen maybe less effective than first thought, while approaches to lung function reduction have now largely switched to endoscopic treatment and remain relatively experimental.
Thus, for most COPD patients, drug treatment is an essential part of their management which will help them cope with rather than reverse their disease. The drug therapy of acute exacerbations has changed little over the past 20 years, although there are now good data that oral corticosteroids are just as effective when given for 5 days, as they are when a longer treatment period is offered. Antibiotics improve the outcome in many cases and patients treated in this way may be less likely to subsequently develop pneumonia. However, most changes in our approach to COPD have occurred in the management of stable disease. The goals of maintenance treatment are shown in Table 1.
Ideally, the clinician seeks evidence that the drug is working, or at least is being taken and changes in spirometry can be reassuring in that respect. Spirometric change can be a useful intermediate marker when the treatment involves a bronchodilator and some anti-inflammatory drugs, but it is harder to assess whether treatment is working when lung function is unaffected, that is, with long-term antibiotics. Likewise, reductions in breathlessness and increase in exercise tolerance are usually noticed by the patient while treatment designed to reduce exacerbation frequency is taken on a probabilistic basis, that is, the treatment is known to do good in general rather than in the individual. Approaches that might increase the clinician's confidence that this treatment will work are discussed at the end of this review.
As yet, drug treatment is not generally accepted as changing disease progression or reducing mortality, although there are data that suggest this is likely to happen. Conducting studies of a size and duration to establish these points conclusively is difficult when the same treatments are used for more immediate symptoms relief, but possibly investigations earlier in the natural history when the rate of decline of lung function is faster would give stronger evidence for this.
For practical reasons, most data have been collected about how treatment affects spirometry, breathlessness, exercise performance, and exacerbations, both in the community and when hospitalized. The main targets for treatment have not changed substantially with bronchodilators focusing on reducing airway smooth muscle tone and a range of anti-inflammatory agents producing secondary changes in lung function and diminishing the likelihood of the patient exacerbating. More recently, attempts at decreasing the microbial burden that might trigger COPD exacerbations have also been explored.
In this review, we consider what new approaches have been tested and how useful they appear to be in terms of changing our current treatment paradigms. This is a rapidly moving field with a degree of "built in obsolescence" and so the studies cited should be considered indicative rather than comprehensive given the evolving literature. The treatment approaches studied reflect the drugs which have been developed and inevitably the agenda of the pharmaceutical companies who have developed them. Despite this inherent bias, useful insights into how we should best treat COPD are emerging. We will begin by considering the least explored approach to improving treatment—changing the way in which a drug is delivered.