Chronic obstructive pulmonary disease (COPD) is a complex disease currently affecting a large number of individuals across the world. Although historically thought of as a disease of older males, the prevalence in females is rising, as are the overall death rates. Patients with COPD primarily suffer from dyspnea, decreased exercise capacity, and chronic cough, which are primarily caused by progressive airflow limitation. The airway obstruction commonly encountered in COPD results from multiple pathophysiological processes, some of which may be preventable and modifiable. Lifestyle modifications, primarily smoking cessation, can have a tremendous impact on slowing the decline of lung function attributed to the disease. The mainstays of treatment are bronchodilators, and as lung function declines, the importance of including lifestyle modifications becomes even more essential. National and international guidelines direct treatment and diagnosis and attempt to increase awareness and educate on the proper care of patients with COPD.
COPD is a respiratory condition affecting 12 million Americans, with an estimated additional 12 million Americans undiagnosed. It is more prevalent in smokers and former smokers and in individuals older than 40 years, and it is more commonly encountered in men than in women. The disease, which was the sixth leading cause of death worldwide approximately a decade ago, is now projected to become the third leading cause of death by the year 2020. In the United States, COPD is the fourth leading cause of death, contributing to a mortality rate of 42.2 per 100,000 individuals and claiming approximately 123,000 lives annually. Direct and indirect health care costs attributed to COPD have topped $37.2 billion yearly. Direct costs of treating COPD totaled $20.9 billion in 2004 and included hospital care, physician services, and prescription medications.
The risk for developing COPD is directly related to the total burden of all inhalational exposures combined, including air pollution and tobacco smoke. Perhaps the greatest risk factor associated with COPD, tobacco smoke, appears to be strongly correlated with increased morbidity and mortality. The risk is present whether the individual is an active smoker or has been repeatedly exposed to secondhand inhalation. However, not all smokers progress to the more severe stages of COPD, suggesting the potential for other contributing factors. Though not definitively identified, α-1 antitrypsin deficiency is a genetic disorder that is characterized by early-onset emphysema, which may potentially be associated with COPD. Furthermore, according to the American Thoracic Society, occupational dust and other environmental exposures are the cause of 10% to 20% of the symptoms of COPD or related functional impairment.
Per the 2007 updated Global Obstructive Lung Disease (GOLD) guidelines, COPD is defined as a preventable and treatable disease with some significant extrapulmonary effects that may contribute to the severity in individual patients. Its pulmonary component is characterized by airflow limitation that is not fully reversible. The airflow limitation is usually progressive and associated with an abnormal inflammatory response of the lungs to noxious particles or gases. Clinical manifestations of COPD generally include persistent and progressive dyspnea, chronic cough, and sputum production. Such symptoms have now been classified into 4 stages, ranging from mild to moderate, severe, and very severe.
The GOLD guidelines outline methods of disease assessment along with counseling points for patients related to the dire need for reducing COPD risk factors. Pharmacological treatment options for the management of COPD include bronchodilators, which may be used intermittently as needed or on a scheduled basis. Bronchodilator therapy, with β-agonists, anticholinergic agents, and methylxanthines, is used to prevent or diminish exacerbations and other COPD-related symptoms. It has also been demonstrated that regular use of a long-acting bronchodilator as compared with a short-acting product is more effective in managing COPD. Bronchodilators may be used alone or in combination. Inhaled corticosteroids (ICSs) may also be added to bronchodilator therapy if disease severity and frequency of exacerbations warrant their use. It is important to note that currently available agents for the management of COPD have not been able to establish a consistent effect in slowing the decline of lung function, especially in the long term. Nonetheless, pharmacological agents are used primarily to diminish general symptoms, such as shortness of breath and airflow obstruction, and the goal of therapy is to improve the patient's overall clinical response.
Bronchodilators are instrumental in COPD therapy because they allow for bronchial smooth muscle relaxation. All patients with COPD should receive a bronchodilator to be used for “rescue therapy” on an as-needed basis. The GOLD guidelines recommend either a short-acting β-2 agonist (albuterol, levalbuterol, or pirbuterol) or an anticholinergic (ipratropium). To date, there have been no published clinical trials that have demonstrated that one therapy is more clinically beneficial or safer than another, so either may be selected as initial therapy. Should patients not respond adequately to monotherapy, combination therapy with albuterol and ipratropium can be used on an as-needed basis or scheduled and is available in a single-inhaler device.
For patients with stages II and beyond (moderate to very severe) or for those who do not respond adequately to short-acting bronchodilators, therapy with scheduled long-acting bronchodilators may be added. Currently available treatment options include tiotropium, salmeterol, and formoterol. Again, no study has demonstrated any overwhelming benefit of one therapy over another. The GOLD guidelines suggest that any of the above may be selected, and these agents may also be used in combination should patients not respond adequately to monotherapy. Tiotropium, a long-acting anticholinergic, is administered as a once-daily dose via a dry powder inhaler. Recent concerns relating to the use of anticholinergics and increased stroke risk and cardiovascular events in patients with COPD have not led to any changes in FDA labeling, and until further data are published, it is recommended that patients continue these therapies if they are currently receiving them.
The decision to initiate therapy should be made on a case-by-case basis after discussion between patients and prescribers outlining the risks and benefits. Formoterol and salmeterol, both long-acting β-2 agonists (LABAs), are administered twice daily, typically 12 hours apart. Ultra-long-acting β-2 agonists (uLABAs) are currently under development and may provide an additional once-daily administration option for patients with COPD in the near future. Combination therapy with uLABAs and ICSs as well as with other bronchodilators is also being evaluated. Although the use of LABAs in patients with asthma has been linked to an increase in mortality, studies have not suggested the same risk in patients with COPD. Both classes of long-acting bronchodilators have demonstrated improved outcomes for multiple clinical markers in patients with COPD, including exercise tolerance, lung function, exacerbation rates, and quality of life (as typically measured by the St. George's Respiratory Questionnaire). Theophylline is not typically used, as the toxicity profile and potential for drug interactions make it less desirable than other available options.
An ICS may provide therapeutic benefit because of its ability to reduce airway inflammation, which contributes to the airflow limitation encountered in patients with COPD. However, the controversy that has been noted with ICSs is related to the absence of improved clinical outcomes when they are used in the general management of COPD. A meta-analysis has supported this suggestion, demonstrating that the regular use of ICSs was not associated with a reduction in the rate of forced expiratory volume (FEV1) decline. The GOLD guidelines suggest that patients with stages III and IV COPD who suffer from continuous symptoms and have repeated exacerbations (>3 per year) are those most likely to benefit from therapy with an ICS.
The combination product with fluticasone and salmeterol is often used in patients with COPD. Well-designed clinical trials have shown that the combined use of an ICS with a bronchodilator may improve lung function in patients with COPD. More recently, additional trials have suggested benefits in the reduction of exacerbations as well as a potential effect in reducing the decline of lung function (FEV1). It is anticipated that more data will be published over the next few years, solidifying the role of combination therapy with an ICS and a LABA, specifically in those in the earlier stages of COPD. Until that time, or until the GOLD guidelines are updated with new recommendations, prescribers should strongly consider using combination therapy only in patients who are candidates for an ICS and have not responded adequately to therapy with one or more long-acting bronchodilators or their combination.
Patients with COPD can take an active role in optimizing their therapy. Lifestyle modifications are fundamental in the overall management of COPD and may reduce symptoms and avoid the complications associated with the disease. The adoption of healthy behaviors can have a positive impact on COPD-related morbidity. Smoking cessation, engaging in physical activity, and maintaining a proper diet are just a few ways in which patients can maximize their quality of life. Chronic exposure to tobacco smoke, in addition to other environmental irritants, can trigger an inflammatory response in the lungs, leading to the destruction of lung tissue. It is projected that between 80% and 90% of COPD is a direct result of cigarette smoking and/or exposure to secondhand smoke. Smoking cessation can not only prevent the onset of COPD, but it is one of the few known interventions that can actually slow the progression of lung impairment. To date, no pharmacological treatment has been able to duplicate that effect. As a general rule, smoking cessation should be implemented in all patients diagnosed with COPD.
Patients seeking to quit tobacco use should be treated with a combination of both behavioral modification and medication therapy. Nicotine replacement products and non-nicotine-based therapies such as sustained-release bupropion, varenicline, clonidine, topiramate, and tricyclic antidepressants have all been used to promote and support tobacco abstinence. Nicotine replacement products are generally recommended as first-line therapy and are available in various formulations: transdermal patch, nasal spray, oral inhaler, gum, and lozenge. Patient preference is the predominant factor in determining which agent to use. The typical duration of therapy varies among products. Once-daily dosing is an advantage of the transdermal patch, although dose titration is difficult and skin irritation may occur with use. Nicotine gum may satisfy oral cravings, but patients must be counseled on its appropriate use, with an emphasis on the need to chew intermittently as continuous use negates the therapeutic effect. The patch, gum, and lozenge formulations are available over the counter, which increases patient accessibility.
The U.S. Public Health Service guideline for the treatment of tobacco use and dependence recognizes sustained-release bupropion and varenicline as first-line options, whereas clonidine and nortriptyline are designated as second-line therapies. Bupropion may be of added benefit in patients with a comorbid diagnosis of depression, but it is contraindicated in patients with a preexisting seizure disorder. As a partial nicotine agonist, varenicline can curb nicotine cravings and ameliorate withdrawal symptoms. However, behavioral changes and suicidality have been linked to the use of this medication; therefore, the safety of this product has been brought into question. Cognitive issues such as blackouts and loss of consciousness have also been reported. Both clonidine and nortriptyline have fewer data to support their use in smoking cessation and are limited by significant side effects. The intensity of a smoking cessation program is directly related to successful quit rates, and a comprehensive regimen should include behavioral counseling and social support in addition to pharmacotherapy.
Pulmonary rehabilitation should be considered for all COPD patients who remain symptomatic despite pharmacological treatment and for those who exhibit manifestations of the disease. Exercise, in the form of endurance and strength training, is a key component of any program and serves to improve patient outcomes by strengthening respiratory muscles and peripheral musculature and enhancing the ability to perform activities of daily living. Any form of physical activity should be encouraged, even in those who are not able to follow a structured program.
A pulmonary rehabilitation program should also involve psychosocial counseling, education, and a nutritional counseling component. Adherence to a proper diet is beneficial in both overweight and underweight patients with COPD because excess weight may lead to further breathing difficulties and decreased body mass is a known risk factor for mortality. Additionally, individuals who experience reflux should avoid foods that aggravate the condition as this may also exacerbate COPD symptoms. Furthermore, the incorporation of nutritional supplements into the dietary regimen may be considered in patients who have difficulty eating, secondary to breathing issues.
Simple activities such as relaxation and the adoption of alternative techniques, such as pursed-lip breathing, improve breathing efficiency and comfort. Adherence to health care follow-up appointments and staying up-to-date with vaccinations are vital. An annual influenza vaccine should be administered to all COPD patients, and pneumococcal vaccine is recommended in individuals older than 65 years. Additionally, increasing fluid intake to keep mucus thin, use of a humidifier, and reducing exposure to irritants are all behaviors that may enhance response to medications and improve overall quality of life. Finally, being mindful of poor air quality, extremes in temperature, and close contact with people who are ill is imperative.
To date, no medication therapy has been proven to slow the decline of lung function associated with COPD. Lifestyle modifications, specifically smoking cessation, are one of the few interventions conclusively proven to reduce the decline of FEV1. Patients should also be encouraged to participate in regular exercise and to follow a reasonable diet. Medications are used primarily to reduce the symptoms associated with COPD, and some have also been proven to improve quality of life and to reduce exacerbations. Combinations of different classes of medications are typically used as the disease progresses, and ICSs should be added in those with repeated exacerbations in the later stages of the disease.
Smoking Cessation Therapies and Programs, Tobacco Use and Disease, Epidemiology of
Abbreviations ATS American Thoracic Society BMI body mass index COPD chronic obstructive pulmonary...
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