Treatment of the Stable Patient with Chronic Obstructive Pulmonary Disease

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Chapter 42 Treatment of the Stable Patient with Chronic Obstructive Pulmonary Disease

The airflow obstruction of chronic obstructive pulmonary disease (COPD), as defined by the forced expiratory volume in 1 second (FEV1), is thought to be only partially irreversible. This physiologic fact has been perpetuated over the years and has generated an unjustified negativist therapeutic attitude in many health care providers. The evidence suggests that the airflow obstruction of COPD does reverse with therapy, and that therapies aimed at the extrapulmonary manifestations of the disease do improve patient outcomes. An optimistic attitude toward these patients helps relieve fears and misconceptions. In contrast to many other diseases, some forms of intervention in COPD improve survival, such as smoking cessation, long-term oxygen therapy in hypoxemic patients, lung volume reduction surgery in certain patients with inhomogeneous upper lobe emphysema, and even pharmacologic therapy. Other interventions, such as pulmonary rehabilitation, lung transplantation, and bronchodilator therapy, improve symptoms and the quality of a patient’s life once the diagnosis of COPD has been established.

Box 42-1 summarizes the available therapeutic options for patients with COPD. This chapter reviews medical management of COPD that centers on three goals: (1) prevent deterioration in lung function, (2) alleviate symptoms, and (3) treat complications as they arise. Once diagnosed, patients with COPD should be encouraged to participate actively in their management; collaborative management improves their self-reliance and self-esteem. All patients should be encouraged to lead a healthy life and exercise regularly. Preventive care is extremely important, and all patients should receive immunizations, including pneumococcal vaccine every 5 years and yearly influenza vaccine. Figure 42-1 provides an algorithm detailing this comprehensive approach.

Multicomponent Disease

Increasing evidence shows that independent of the degree of airflow limitation, the lung volumes are important in the development of symptoms in patients with more advanced COPD. Studies have demonstrated that dyspnea perceived during exercise, including walking, more closely relates to development of dynamic hyperinflation than to changes in FEV1. Further, the improvement in exercise brought about by several therapies, including bronchodilators, oxygen, lung reduction surgery, and even rehabilitation, is more closely related to delaying dynamic hyperinflations than by changing the degree of airflow obstruction. Hyperinflation, expressed as the ratio of inspiratory capacity to total lung capacity, was shown to predict survival better than the FEV1. This not only provides new insights into pathogenesis, but also opens the door for novel ways to alter lung volumes and perhaps impact COPD progression.

The association between COPD and important systemic manifestations in patients with more advanced disease is now accepted. Because of a persistent systemic inflammatory state or other, yet-unproven mechanisms (e.g., imbalanced oxidative stress, abnormal immunologic or reparative response), many patients with COPD may have decreased fat-free mass (FFM), impaired systemic muscle function, anemia, osteoporosis, depression, pulmonary hypertension, and cor pulmonale, all of which are important determinants of outcome. Indeed, dyspnea measured with a simple tool such as the UK Modified Medical Research Council (MMRC) scale, the body mass index (BMI; kg/m2), and the 6-minute walking distance (6MWD) are all better predictors of mortality than the FEV1. The incorporation of these variables into the multidimensional BODE index (BMI, airflow obstruction, dyspnea, exercise capacity) predicts survival even better. The BODE index is also responsive to exacerbations and, more importantly, acts as a surrogate marker of future outcome after interventions, thus providing clinicians with a useful tool to help determine the comprehensive severity of the disease. Other multidimensional indices (e.g., age, dyspnea, and obstruction [ADO]; dyspnea, obstruction, smoking, and exacerbation [DOSE]), have also shown important outcome predictive capacity and could be used to test novel forms of therapy.

Based on the multidimensional nature of COPD and the availability of multiple effective therapies, the approach shown in Figure 42-1 may more accurately help clinicians evaluate patients and choose therapies than the current approach, using primarily the FEV1 percentage from reference values.

Respiratory Manifestations

Once diagnosed, the patient with COPD should be encouraged to participate in disease management, confident that if not cured, COPD can certainly be treated.

Pharmacologic Therapy of Airflow Obstruction

Most patients with COPD require pharmacologic therapy. This should be organized according to the severity of symptoms, the degree of lung dysfunction, and the tolerance of the patient to specific drugs. A stepwise approach similar to that developed for systemic hypertension may be helpful, because medications alleviate symptoms, improve exercise tolerance and QOL, and may decrease mortality. Tables 42-1 and 42-2 summarize the evidence supporting the effect of individual and combined therapies on outcomes of importance in patients with COPD. Because most patients with COPD are elderly, care must be taken when prescribing drugs for this population. Comorbidities are frequently present in patients with COPD, mandating caution to ensure that therapy takes these into account.

Bronchodilators

Several important concepts guide the use of bronchodilators. In some patients, changes in FEV1 may be small, and the symptomatic benefit may result from other mechanisms, such as a decrease in hyperinflation of the lung. Some older COPD patients cannot effectively activate metered dose inhalers (MDIs), and clinicians should work with the patient to achieve mastery of the MDI. If this is not possible, use of a spacer or nebulizer to facilitate inhalation of the medication will help achieve the desired results. Mucosal deposition in the mouth will result in local side effects (e.g., thrush with inhaled steroids) or general absorption and its consequences (e.g., tremor after β2-agonists). The inhaled route is preferred over oral administration, and long-acting bronchodilators are more effective than short-acting agents. The currently available bronchodilators are described next.

Corticosteroids

Glucocorticoids act at multiple points within the inflammatory cascade, although their effects in COPD appear to be more modest compared with bronchial asthma. In outpatients, COPD exacerbations necessitate a course of oral steroids, as discussed later, but it is important to wean patients quickly; older COPD patients are susceptible to complications such as skin damage, cataracts, diabetes, osteoporosis, and secondary infections. These risks do not accompany standard doses of inhaled corticosteroid aerosols, which may cause thrush but pose a negligible risk for other outcomes, such as cataract and osteoporosis.

Several large multicenter trials evaluated the role of inhaled corticosteroids (ICS) in preventing or slowing the progressive course of symptomatic COPD. The results of these earlier studies showed minimal, if any, benefits in the rate of decline of lung function. On the other hand, in the one study that evaluated it, inhaled fluticasone decreased exacerbations and the rate of loss of health-related QOL. Recent retrospective analysis of large databases suggesting a possible effect of ICS on improving survival was not confirmed in the TORCH trial, in which the ICS-only arm did not show improved survival compared with placebo, whereas the combination arm was significantly more effective than ICS alone. In TORCH the combination was superior in terms of all outcomes evaluated. Along with the more frequent development of pneumonia in the patients receiving ICS, this suggests that ICS should not be prescribed alone but rather with a long-acting β2-agonist (LABA).