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JOURNAL CLUB - Respirology

June 2008

Editorial Overview:

Denis E. O’Donnell, MB ChB, FRCPI, FRCPC

Professor of Medicine, Queen’s University, Kingston, Ontario

Many patients with chronic obstructive pulmonary disease (COPD) are not diagnosed until the disease has progressed to a relatively advanced stage and have considerable pulmonary impairment on initial assessment. Consequently, the Canadian Thoracic Society (CTS) has taken a more proactive stance in their updated guidelines for COPD management, including targeted screening to identify at-risk patients with mild COPD; timely introduction of pharmacotherapy to improve dyspnea and activity levels; and anticipatory prevention of acute exacerbations through evidence-based strategies.

To identify COPD at less advanced stages, it is now recommended that current or exsmokers over the age of 40 undergo spirometric testing if they answer yes to any one of a set of questions determined by the CTS (Table 1). A postbronchodilator FEV1/FVC ratio of <0.7 is widely accepted as a diagnosis for COPD. Having established a spirometric diagnosis, management should be guided by symptom severity and level of disability. In milder COPD, key treatment goals include smoking cessation, vaccination to prevent exacerbations, regular physical activity and bronchodilator therapy. Careful follow-up, at least on an annual basis, is mandatory in patients identified with early disease by spirometry. Every smoker should be given smoking cessation advice and encouraged to seek out more intensive counselling accompanied by pharmacotherapy to maximize quit rates.

Available Options

For patients with a FEV1 greater than 65% predicted, little is known about the effect of pharmacotherapy but for those with more advanced disease, bronchodilators are the cornerstone of COPD pharmacotherapy. Three classes of bronchodilators are currently recommended along with combination products in which a long-acting bronchodilator and an inhaled corticosteroid (ICS) are delivered in a single inhaler: the anticholinergics, beta2- agonists and oral theophyllines. According to the new recommendations, a short-acting beta2- agonist (SABA) or a short-acting anticholinergic, used alone or in combination on an as-needed basis, are both acceptable options for patients who experience symptoms only on exertion and who have relatively little disability. Patients with more persistent symptoms and moderate to severe airflow obstruction require a long-acting anticholinergic (LAAC) or a longacting beta2-agonist (LABA). Choices here may include tiotropium as a LAAC or salmeterol or formoterol as a LABA. A SABA can be used for immediate symptom relief. Treatment decisions in moderate to severe COPD differ somewhat, depending on the patient’s history of exacerbations.

Individuals with the same degree of COPD impairment but who have on average one or more exacerbations a year may benefit from a combination of tiotropium plus a combination inhaler containing both an ICS and a LABA—either fluticasone/salmeterol 500/50 µg b.i.d. or budesonide/formoterol 400/12 µg b.i.d.

If patients have less than one exacerbation a year on average for two consecutive years, the CTS recommends a combination of tiotropium 18 µg q.d. plus a LABA. A lower dose of a combination LABA/ICS could be used instead of a LABA alone to maximize bronchodilation in patients with persistent dyspnea despite LABA therapy. Again, a SABA may be used as needed for symptomatic relief.

Presently, two such combination inhalers are available in Canada: salmeterol/fluticasone and formoterol/budesonide. Both combination inhalers improve bronchodilation and lung deflation and reduce the frequency and severity of exacerbations. There is, however, no difference in duration of effect between the two LABAs and no adequate formal head-to-head comparisons of these medications are currently available.

Results from two pivotal trials evaluating combination budesonide/formoterol in moderate to severe COPD showed that at six months, patients receiving the combination inhaler 200/4.5 µg (two puffs b.i.d.) had a significantly greater increase from baseline in average pre- and post-dose FEV1 compared with budesonide 160 µg. Effects were also sustained for both comparisons for six months (Szafranski et al. Eur Respir J 2003;21:74-81, Calverley et al. Eur Respir J 2003;22:912-7).

Rennard et al. similarly found the same regimen provided significantly greater increases in pre-dose FEV1 and one-hour postdose FEV1 over baseline compared with formoterol alone and that the effect was again maintained over a 12-month treatment period. The TORCH (Towards a Revolution in COPD Health) study, in turn, in which the combination of fluticasone/salmeterol was compared with placebo and against either drug on its own, showed the combination significantly improved lung function and health status, and reduced exacerbations compared with either agent alone ( N Engl J Med 2006;356:775-801).

Table 1.

Unlike asthma, the CTS advise physicians against using ICS therapy alone in COPD and only in combination with a LABA. For those patients with persistent, severe symptoms despite the use of tiotropium plus an ICS/LABA combination, a long-acting formulation of oral theophylline may be considered, although blood levels need to be monitored and attention paid to side effects and potential drug interactions. The CTS also caution that longterm treatment with oral corticosteroids should not be used in COPD, as there is no real evidence of benefit and there is a high risk of adverse systemic effects.

Prevention of AECOPD

Prevention of acute exacerbations of COPD (AECOPD) is essential to reduce the risk of patients requiring hospital admission. The key here is to target the main triggers of AECOPD (Table 2). Patients who successfully quit smoking have a slower rate of lung function decline than those who do not, and this in turn may reduce their likelihood of developing AECOPD, although there is no direct evidence
rvation.

Table 2.

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In contrast, studies indicate that an annual influenza vaccination reduces morbidity and mortality in elderly COPD patients by as much as 50% and patients should be encouraged to be vaccinated annually. They should also receive the pneumococcal vaccine at least once in their lives.

Another strategy that helps reduce exacerbations is to use tiotropium with or without a LABA in patients with a FEV1 less than 60% predicted. In contrast, ICS monotherapy should not be used to reduce the risk of exacerbations, but for those with a FEV1 less than 60% predicted and who have one or more acute exacer
mbination of an ICS and a LABA should be considered.

Figure 1.

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Regarding AECOPD management, other causes for worsening cough and dyspnea need to be ruled out before initiating treatment. For those who present to the emergency room or who require hospital admission, a chest X-ray may reveal abnormalities that may change management strategies, and for the subset of patients with low arterial oxygen saturation on oximetry, arterial blood gases should be carried out (Figure 1). Gram stain and culture may also be considered for those with very poor lung function, those who have frequent exacerbations, or those who have been on antibiotics in the preceding three months.

There is some evidence that high doses of short-acting inhaled bronchodilators in combination can reduce lung hyperinflation and relieve dyspnea in AECOPD. More solid evidence supports the use of either oral corticosteroids in most individuals with moderate to severe AECOPD, with duration of treatment of between five and 14 days. In severe purulent AECOPD, antibiotics are recognized as useful and they should be considered in this group of patients.

Summary

There are several major objectives in the management of COPD that need to be kept in mind to improve the quality of life and prognosis of patients with the disease. Key among them is smoking cessation, but physicians also need to reduce the frequency and severity of AECOPD; alleviate breathlessness and other respiratory symptoms through modalities with a rapid onset of action; and improve exercise tolerance and the ability to carry out activities of daily living.

With a collective effort and novel therapeutic strategies, treating physicians should be able to reduce both morbidity and mortality from this progressive and increasingly prevalent disease.

questions and answers

Panel

Paul Hernandez, MDCM, FRCPC

Dalhousie University, Halifax, Nova Scotia

Jean Bourbeau, MD, MSc, FRCPC

McGill University, Montreal, Quebec

Darcy Marciniuk, MD, FRCPC, FCCP

Royal University Hospital, Saskatoon, Saskatchewan

Denis E. O’Donnell, MB ChB, FRCPI, FRCPC

Queen's University, Kingston, Ontario

The new guidelines recommend physicians offer diagnostic spirometry to long-term smokers who present with a respiratory tract infection (RTI) once their symptoms subside.

Do you think routine early assessment of at-risk individuals might improve the prognosis of patients with COPD?

Dr. O’Donnell: Yes, I think it will, especially if it is targeted screening of patients with a high pre-test probability of having the disease. If these patients are identified and smoking cessation is successful, there is very good evidence that we can change the natural history of the disease and improve survival. We also strongly suspect that modern pharmacotherapy will have an impact on the natural history of the disease as well. We are now able to relieve symptoms as never before and when you look at modern therapies in conjunction, there may be a survival advantage as well. In September (2008), we’ll have our first glimpse of data from the UPLIFT study looking at the effect of a LAAC on rate of decline in lung function. This is the first definitive prospective study designed to see if modern bronchodilators change the natural history of COPD and if the study shows that they do, there will be a very persuasive argument for more aggressive, early intervention.

Dr. Hernandez: I think it needs to start with the recognition that COPD, although common, is under-diagnosed; many patients are unaware they have COPD or they are being detected at a fairly late stage of the disease. Unfortunately, history and physical exam are not specific enough to identify airflow obstruction early in the course of the illness; we need objective measurements that will allow physicians to detect COPD earlier. The CTS has therefore suggested a simple strategy that family physicians and others can use to screen patients: any patient who is 40 years of age and older with a smoking history and any respiratory symptoms, such as frequent or severe RTIs being the most common symptoms in mild COPD patients, should be suspected of having COPD and clinical suspicion should be confirmed with spirometry. If they are still smoking, smoking cessation is important to prevent disease progression. There is weak evidence that providing patients with information about their spirometry results may increase smoking quit rates.

Dr. Marciniuk: I do. There are a number of interventions that can be offered to patients with mild COPD, most notably smoking cessation, but other pharmacological and non-pharmacological interventions can be implemented and they have been shown to be effective (Figure 2). In the guidelines, we specifically indicate patients with symptomatic milder COPD be educated about the disease and engage in a smoking cessation program, and should be encouraged to participate in regular physical activity. Treatment with bronchodilator therapy should also be initiated for those who are symptomatic and exacerbations prevented through vacci
nza and pneumococcus. And we recommend that such patients be closely followed on a regular basis.

Figure 2.

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Dr. Bourbeau: Clearly, we feel that there is a problem with under-diagnosis of COPD in the Canadian population but that is also true worldwide. So the Canadian guidelines recommend patients who are symptomatic be the main target for screening and in that population, it is really key to do spirometry and make sure the diagnosis of COPD is confirmed. That would certainly help improve the management of patients who have the disease but who are undiagnosed and undertreated. For those who have respiratory symptoms but in whom spirometry does not confirm the diagnosis, we should look for an alternative diagnosis.

Does inflammation contribute to the pathogenesis and progression of COPD?

Dr. O’Donnell: Certainly, COPD is an inflammatory disease, its first manifestation being fairly intense, small airway bronchiolitis. So the nature of the inflammation in COPD is understood, but it’s a completely different inflammation from that in asthma. As well, response to ICS therapy is extremely good in eosinophilic inflammation as in asthma but as monotherapy, ICS hasn’t been shown to have a consistent effect in COPD. However, if the inhaled steroid is combined with a LABA, a few studies did show a consistent effect of treatment on markers of inflammation. So while evidence is limited, biopsy studies did show the combination product (ICS/LABA) consistently affected some markers of airway inflammation.

Dr. Hernandez: COPD is an inflammatory disease of the airway and the lung parenchyma so inflammation is key in its development and progression. The typical trigger for inflammation in Canadian patients is cigarette smoke, which activates a number of inflammatory cells that release inflammatory mediators and result in airway and lung parenchymal damage. We are also learning that COPD is not just a lung disease, but rather a systemic illness, with evidence of systemic inflammation which contributes to some of the comorbidities seen in COPD, such as cachexia and skeletal muscle dysfunction.

Dr. Marciniuk: I think our understanding of the etiology of COPD continues to grow. There is now enhanced recognition of the role of inflammation in COPD and evidence on a number of fronts that inflammatory mechanisms contribute to the disease as well as some of the consequences of the disease. Right now, there is a bit of disconnect in terms of our understanding of inflammation in COPD and the clinical effects of ICS monotherapy but we know that when you add a LABA to an ICS, there is an incremental and very meaningful effect on a variety of patient-centred outcomes. So while monotherapy with ICS has not been shown to be very effective, significant benefit has been noted when ICS is given in combination with a LABA.

Dr. Bourbeau: Inflammation is key in the pathogenesis of the disease. Many studies have shown that it is present early and it’s certainly a normal response to any insult to the lung such as smoking, but in people who are susceptible to smoking, an amplification of the inflammatory response to smoking might explain why some patients develop COPD while others don’t. Until now, no treatment has been shown to change the natural course of the disease except smoking cessation. But we have medications that have anti-inflammatory effects; it remains to be shown if the effects of these medications could change the course of the disease.

Some have suggested that it is difficult to differentiate between COPD and asthma. What are the key distinguishing features between them?

Dr. O’Donnell: In certain circumstances such as an asthmatic smoker, it can be difficult to unravel the two and I refer to the table in the guidelines as it captures the main differences between them (Table 3). Asthma appears at an earlier age; symptoms are more intermittent; there is often a family history of asthma or a personal history of atopy; spirometric reversibility measurements are of greater magnitude than in COPD; and response to inhaled steroids is much more impressive in asthma than in COPD. In contrast, the older patient with a smoking history who has progressive symptoms where wheeze is not a dominant feature nor a history of atopy but who does have frequent RTIs which linger—all these features are more consistent with COPD. But in some patients there is mixed disease and it can be hard to tell the relative i
ease. If you see large fluctuations in lung function, it’s more likely to be asthma as well, as you do not see these wide fluctuations in COPD.

Table 3.

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Dr. Hernandez: It is sometimes difficult for family physicians and specialists alike to differentiate between the two conditions. In fact, a minority of COPD patients also suffer from asthma. However, the CTS has identified key features to distinguish both in recently published guidelines, including early age of onset being typical of asthma; the necessity of having a history of inhaled noxious substances, which usually means smoking, for COPD; allergy or atopy being characteristic of asthma, and so on. In terms of how spirometry helps distinguish between the two conditions, it can be confusing and part of the fault lies in the way in which pulmonary function tests are reported. Results are reported as “evidence of reversibility” to the administration of a bronchodilator and that “reversibility” in the lab is often misinterpreted to mean asthma. But the majority of COPD patients will show enough reversibility to be labelled “reversible” because you only need a small degree of reversibility—200 mL and 12% of FEV1—to meet this criterion and this doesn’t help differentiate COPD and asthma. If there are larger degrees of reversibility to a bronchodilator or to an ICS trial, then a clinician would be more suspicious that they’re dealing with asthma and not COPD.

Dr. Marciniuk: In the guidelines, we point out a number of the clinical differences between asthma and COPD, key among them being age of onset, usually under 40 for asthma and usually over 40 for COPD; smoking history, which is not causal in asthma but which usually is in COPD; production of sputum, which is infrequent in asthma but which often occurs in COPD; and the presence of allergies that often occurs in asthma but which is infrequent in COPD. Other differences include the course of disease, which tends to be stable with asthma and progressively worsening with COPD (although exacerbations are present in both diseases); spirometry, which often normalizes in patients with asthma but which never does in COPD; and the presence of symptoms which are intermittent and variable in asthma but which tend to be persistent in COPD.

Dr. Bourbeau: There is unfortunately no single feature that differentiates the two conditions unless patients have complete reversibility of airflow obstruction with treatment. So if you document airflow obstruction first and it is completely reversible after treatment, that is pathognomic for asthma. Clinically, there are features of either condition that are more characteristic of one over the other: you are more likely to have asthma, for example, in the presence of allergy or atopy, or if someone is a non-smoker with respiratory symptoms. That said, we probably underestimate environmental risk factors in the development of COPD such as working in a dirty industry, so smoking is not the only cause of COPD.

How are you recommending physicians assess disease severity?

Dr. O’Donnell: Our position was for physicians to first make a firm diagnosis with spirometry and then let treatment decisions be influenced by symptoms and disability, as well as the number of exacerbations. It can be difficult to evaluate disability and you need to do a probing interview, but the simple Medical Research Council (MRC) Dyspnea Scale will allow physicians to stratify disease severity and treat accordingly (Table 4). So a patient with a MRC score of >3 has clinically important, activityrelated shortness of breath and needs treatment with a bronchodilator. Those with a MRC of 5 require a chronic-care model be in place where they receive both nonpharmacologic and pharmacologic interventions. It’s also important to assess patients for the presence of comorbidities. But for family physicians, we would like to see a firm diagnosis, first with spirometry, and then have them rate symptomatology and the risk of acute exacerbations, both of which are incredibly important to help guide decision management.

Dr. Hernandez: A complex disease like COPD can’t be fully characterized simply by looking at a number such as per cent of predicted FEV1. The degree of airflow obstruction is important but we also need to understand the impact of symptoms on patients and for this, we use the MRC Dyspnea Scale which measures symptom limitations and better characterizes overall disease severity. The degree of airflow obstruction and symptoms are also important in predicting prognosis and mortality risk, as are measures of exercise performance, body mass index, and frequency and severity of acute exacerbations. All of these features are important, independent predictors of prognosis, and all but the six-minute walk test are readily available to family physicians to assess overall severity of the illness as well as mortality risk.

Dr. Marciniuk: We’ve offered physicians a choice of using either lung function with spirometry and/or assessing the severity of symptoms and disability. Disease severity can be assessed based on the level of impairment of lung function as measured by spirometry, but it can also be assessed according to the MRC Dyspnea Scale, as outlined in the guidelines. What physicians will use will likely depend on the patient and the physician’s interest and comfort level with either of these classification offerings.

Dr. Bourbeau: Traditionally, assessment of disease severity was based on the degree of airflow obstruction, but there is a poor correlation of symptoms of dyspnea and exercise intolerance with FEV1. So we strongly recommend that physicians assess disability based on patient-centred outcomes. The main symptom of COPD is dyspnea on exertion so we recommend physicians assess disability according to the MRC Dyspnea Scale. It’s easy to use and it’s a very good discriminatory scale as well as a good predictive scale in terms of survival. The scale is actually similar to the New York Heart Association (NYHA) scale that rates severity of congestive heart failure, and we hope that physicians come to use the MRC Dyspnea Scale just as they use the NYHA scale for heart failure.

The guidelines recommend physicians consider a number of pharmacological aids to help patients quit smoking. What interventions have you found work best?

Dr. O’Donnell: As specialists, we don’t get as involved in front-line smoking cessation programs as family physicians do, so they probably know what works a lot more than we do. Since varenicline has been available, we are having significan
oking cessation attempts, so varenicline seems to be superior to nicotine replacement products, as well as bupropion, although it needs to be used in the setting of supportive counselling.

Table 4.

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Dr. Hernandez: I think the most important thing we can do is take the time at each visit to discuss smoking with patients, to document their smoking status, to assess patients’ readiness to quit and their level of addiction, and then use brief counselling methods to help motivate patients to move along the stages of readiness for change. Any counselling will be more effective if it is also combined with the appropriate pharmacotherapy. There are a number of medications, including nicotine replacement therapy, bupropion and varenicline, to offer patients, the best one depending on considerations of comorbidities, cost, side effects, access and drug interactions.

Dr. Marciniuk: Right now, evidence suggests a combination of counselling plus pharmacotherapy works best, but the main messages that physicians need to keep in mind regarding smoking is that smoking cessation is vital; that it makes a difference; that it often requires repeated attempts; and that physicians should not quit trying to get patients to quit until patients actually quit.

Dr. Bourbeau: The use of various medications for smoking cessation is detailed in the guidelines and we encourage physicians to use this information. At the same time, we as physicians have an important role in making sure patients understand that their condition is due to smoking and that they are at risk for adverse consequences if they continue to smoke. We also have to offer our help not in a confrontational way, but in a way that indicates we are concerned about their smoking-related health problems. We have to work with patients, assess their stage of readiness to quit, and then, as often as we can, when they come back to see us, reassess whether they are closer to be ready to quit. So we need to invest time with patients, but certainly, many medications can be used to help patients quit and given together with proper counselling, the combination can be more effective than counselling alone.

How do you explain the lack of consistent evidence for ICS monotherapy when inflammation is an underlying element in COPD?

Dr. O’Donnell: The nature of inflammation in COPD is such that it doesn’t respond to ICS therapy alone. However, the information we now have shows that the addition of a LABA to an ICS in combination products seems to amplify the anti-inflammatory effects of ICS, so delivering both molecules to the same site in the airways seems to suppress inflammation, according to several well-conducted smaller studies.

Dr. Hernandez: There has been a small but variable impact in studies with ICS when looking at lung function, symptoms and effect on acute exacerbation. Interestingly, four large studies showed ICS had no impact on the rate of decline of lung function. However, we know that when combined with a LABA, ICS has a more consistent and positive effect on clinical and physiological outcomes. The reason why ICS doesn’t work as well as we would predict in an inflammatory lung disease is that the type of inflammation in the airways is quite different than that in asthma where ICS therapy has a primary role.

Dr. Marciniuk: Again, it is an evolving area in terms of our understanding, but what current evidence shows is that ICS therapy does have a positive effect on symptoms, quality of life, exacerbations and lung function when given in combination with a LABA and that recommendation is reflected in the guidelines.

Dr. Bourbeau: Evidence is clear that ICS use has little or no place in the primary treatment of COPD and that when ICS is used in COPD, it is more effective when it is used in combination with a LABA. This is somewhat contradictory because we know that inflammation is a key feature in the pathogenesis of COPD and corticosteroids are clearly anti-inflammatory in nature; however, the type of inflammation in COPD is quite resistant to ICS therapy, likely because inflammation is primarily neutrophilic in COPD and eosinophilic in asthma. So it is likely that the LABA potentiates the antiinflammatory effects of the ICS. On bronchial biopsy, for example, a Canadian study showed that the combination does have anti-inflammatory effects in COPD, where ICS alone had minimal or no effect. These new data confirm the biological plausibility that combination therapy (ICS combined with LABA) is superior to monotherapy (ICS).

In which patients or in which situations would you preferentially use a combination inhaler containing both an ICS and a LABA?

Dr. O’Donnell: We reserve the combination inhaler for patients with moderate to severe COPD as there is no evidence that they work in earlier disease. So if patients have moderate to severe COPD and they are prone to getting annual flare-ups, they need triple therapy consisting of a LAAC given in conjunction with a combined ICS/LABA. That is one specific group where evidence supports their use. In patients who don’t get recurrent exacerbations— and at least 40% of COPD patients do not—but who remain symptomatic despite being on a LAAC and a LABA, physicians can consider substituting the combination of the lower-dose ICS/LABA product for the LABA alone, as evidence again suggests that the combination improves small airway function and lung hyperinflation.

Dr. Hernandez: In patients with moderate to severe disease, the combination ICS/LABA should be considered in two situations. First, there may be patients who have frequent exacerbations, in which case the combination should be used optimally in combination with a LAAC and a SABA; secondly, even in patients who are not experiencing frequent exacerbations, those with persistent dyspnea and poor exercise tolerance, despite optimal use of long-acting bronchodilator, should be transitioned to an ICS/LABA combination, again given in combination with a LAAC and a SABA.

Dr. Marciniuk: There are two indications in the CTS guidelines where ICS/LABA therapy would apply. The first is in patients with persistent disability despite combination longacting bronchodilator therapy and pulmonary rehabilitation, if available; the second indication is for those patients with moderate to severe disease who have a history of frequent exacerbations, where there is compelling evidence that combination ICS/LABA therapy, together with a LAAC, is effective in reducing the frequency and severity of exacerbations.

Dr. Bourbeau: Based on evidence from two large and well designed trials—Towards a Revolution in COPD Health Study (TORCH) and the Canadian Optimal Therapy of COPD trial— we established a new treatment algorithm to help with decision-making. The Optimal Therapy study—a Canadian study supported by the Canadian Institutes of Health Research (CIHR)— very clearly showed that you can prevent hospitalizations due to exacerbations, and improve quality of life and FEV1 when you use the combination of a LAAC and an ICS/LABA over either a LAAC alone or a LAAC combined with a LABA. So we now recommend patients with moderate to severe COPD and significant exacerbations receive triple therapy with LAAC plus ICS/LABA, as well as those who have rare or no exacerbations but in whom symptoms and disability persist despite optimal therapy, for whom we recommend physicians take a stepwise approach from long-acting bronchodilators to LAAC plus an ICS/LABA and a SABA for immediate symptom relief.

What is the physiological basis for the use of ICS/LABA in patients with persistently symptomatic COPD with frequent exacerbations?

Dr. O’Donnell: The combination improves small airway function and lung overinflation, which is the root cause of shortness of breath. We also hope that physiological suppression of inflammation with ICS/LABA may reduce the rate of decline of airway function. So with the combination product, there are the mechanical improvements for immediate symptomatic relief and then, hopefully, long-term suppression of inflammation will improve airway function. But if you are using the combination product to improve symptoms and activity limitation, be sure to use the lower dose, as the lower dose looks as good as the higher dose in terms of bronchodilation and lung deflation.

Dr. Hernandez: From two biopsy studies, we know the combination seems to have a better impact in reducing lung inflammation than ICS or placebo alone. We also know that the ICS/LABA combination is quite an effective bronchodilator which translates into improved exercise performance and symptoms for patients. A number of studies have also shown that this combination seems to reduce the frequency of severe exacerbations, although the mechanism by which it does so is less well understood: is it because patients have a high level of baseline lung function on these medications and therefore become less symptomatic during exacerbations and are less likely to seek medical attention, or is it that improvement in lung function results in better clearance of micro-organisms from the lungs and less frequent exacerbations? The mechanism by which the ICS/LABA combination reduces the frequency and severity of exacerbations needs to be further studied.

Dr. Marciniuk: There is an inflammatory response to exacerbations and this response may potentially contribute to further exacerbations in a number of different ways. For the most part, acute exacerbations are infective in etiology but for this particular group of patients, there is strong evidence that the ICS/LABA combination is effective in reducing the frequency of future exacerbations, suggesting that inflammation also plays an important role in this adverse consequence.

Dr. Bourbeau: Long-acting bronchodilators improve both static and dynamic hyperinflation which are closely correlated with dyspnea. They also improve exercise tolerance, and we also know that when we combine ICS with LABA, the LABA may potentiate the effects of ICS and vise versa, which might explain why the combination is more effective than LABAs alone.

How do you encourage patients to exercise when they are often extremely deconditioned and are already short of breath without exercising?

Dr. O’Donnell: We know that avoidance of exercise has disastrous consequences in the long term as patients spiral into deconditioning and muscle wasting, which places great stress on the breathing apparatus. Level one evidence shows that exercise training strengthens endurance in peripheral muscles even in the elderly with debilitating COPD. Unfortunately, only about 1.6% of all COPD patients have access to a structured multidisciplinary rehabilitation program, so we advocate patients be encouraged to exercise regularly, as much as possible. Pharmacotherapeutic drugs are “performance-enhancing” so patients are able to exercise longer and they should be exercising in conjunction with taking the drugs. Walking in particular is good but patients can do any exercise that they enjoy. Physicians need to prescribe the frequency, duration and intensity of exercise. At first, patients need to exercise only until they get short of breath, then rest to recover their breath (interval training), and begin again. The aim is to gradually increase their walking distance over time. Patients with advanced COPD might begin at only five minutes of exercise every day but eventually should aim to achieve 30 minutes per day of exercise at least three times a week.

Dr. Hernandez: It starts by letting patients know what the benefits of exercise are and those benefits include fewer symptoms, an improvement in dyspnea and fatigue, a better quality of life, and much less time spent in hospital when they do suffer an acute exacerbation. Many patients with COPD have comorbidities and exercise often helps with these comorbidities as well—control of body weight, blood pressure, lipids and diabetes. Ideally, advice about how best to exercise should be given in a supervised rehabilitation program but these programs are not widely available. I use the frequency-intensity-type-time (FITT) principle, where I tell patients to build up to a frequency of three to five times a week at an intensity that leaves them moderately short of breath; ideally, this is done for 30 to 45 minutes a session, although they can break this into shorter separate sessions to achieve this goal; and to engage in some form of aerobic exercise that they enjoy—cycling, walking and swimming all being good. Before you advise patients to exercise, it’s often a good idea to consider a cardiac or cardiopulmonary stress test to ensure it’s safe for them to exercise and to help guide advice about exercise intensity and the need for supplemental oxygen.

Dr. Marciniuk: It’s very tough and indeed, it seems almost counterintuitive to ask patients to become more short of breath by exercising. Nevertheless, evidence strongly suggests that patients who exercise regularly, particularly in a rehabilitation program, experience less shortness of breath and can walk further with fewer adverse outcomes than those who don’t. So exercise allows patients to use what remaining lung function they have better. A lot of the benefits also relate to reversing the long-term effects of deconditioning that we see in COPD. And when you combine optimal pharmacotherapy with rehabilitation, the benefits are striking for the patients. This is the most powerful and effective combination of therapies for optimizing the management of COPD.

Dr. Bourbeau: Exercise and pulmonary rehabilitation are essential in the management of COPD; they are part of a comprehensive approach we are advocating in the guidelines and they should be combined with optimal medical therapy. For patients with moderate to severe disability, it is much better for them to participate in a structured exercise program such as a pulmonary rehabilitation program, where they can increase exercise tolerance gradually and gradually gain more confidence that the program can improve exercise tolerance, quality of life and dyspnea. So we should be referring all our patients with level 3 to 5 MRC dyspnea to a rehabilitation program. That said, fewer than 2% of COPD patients have access to a rehabilitation program per year, which is clearly unacceptable. We need to build waiting lists for COPD patients as we have for cardiac patients; this might help to convince authorities that more pulmonary rehabilitation programs are needed across the country.

What impact do you hope these guidelines will have on the management of COPD?

Dr. O’Donnell: What we are hoping is that spirometry will be used both for early diagnosis and to confirm suspicion of the diagnosis in symptomatic patients. A recent survey of practice behaviour in Quebec and Ontario suggests that only 56% of physicians use confirmatory spirometry to diagnose COPD and we are hoping the guidelines will increase that. We also hope the guidelines will encourage physicians to take an aggressive approach to the prevention and treatment of exacerbations, as we know that exacerbations cause significant morbidity and even mortality, so tracking, preventing and promptly treating them is another goal. And then we’d like to see symptomatic control optimized. Modern pharmacotherapy achieves consistent improvement in airway function and exercise tolerance and reduces exacerbations, so we are in a better position now to meaningfully impact on quality of life for patients. We are very hopeful that effective knowledge translation of the CTS guidelines will prevent COPD and at the very least improve the health of Canadians suffering from this devastating disease.

Dr. Hernandez: Unfortunately, we know from many examples in the past that guidelines themselves do not result in change in patient care. That is why the CTS has invested resources from the start in a committee responsible for COPD guideline dissemination and implementation. The committee uses the guidelines as a benchmark to try to change practitioner behaviour and improve COPD care. We do this through educational initiatives for family physicians and specialists, and we provide tools that the practitioner can use at point of care to make it easier to implement the guidelines in their practice. We know family physicians are faced with numerous guidelines, so it’s a matter of translating key messages into user-friendly formats to make it easier for physicians to make the right decisions regarding COPD management. The CTS is currently evaluating the best strategy to implement COPD and asthma guidelines to primary care physicians.

Dr. Marciniuk: The disease burden from COPD continues to grow and we are going to see more and more of it in the future. There is a growing body of evidence showing that treatment of COPD is effective and that when it is appropriately and aggressively utilized to optimize management, outcomes for patients can also be optimized. So the guidelines provide us with an evidence-based template that allows physicians to navigate their patients through the various treatment strategies with the goal of optimizing COPD management for the benefit of each patient.

Dr. Bourbeau: We have clear evidence now that we can make a difference with a comprehensive treatment approach to COPD that combines drug therapy with nonpharmacological strategies. It’s true we have made some progress in COPD but that progress will only be translated into real change if we all apply the guidelines in our practice. If the guidelines are implemented, they will certainly improve the overall management of COPD. These are actions we can take now!