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Department of Medicine, Tufts University; and Pulmonary and Critical Care Division, St. Elizabeth's Medical Center, Boston, Massachusetts
Correspondence and requests for reprints should be addressed to Bartolome R. Celli, M.D., Pulmonary and Critical Care Division, St. Elizabeth's Medical Center, Boston, MA 02135. E-mail: bcelli{at}cchcs.org, bcelli@copdnet.org, bcelli@semc.org
ABSTRACT
Chronic obstructive pulmonary disease (COPD) has been associated with a nihilistic attitude. On the basis of current evidence, this nihilistic attitude is totally unjustified. The disease must be viewed through the lens of a new paradigm: one that accepts COPD as not only a pulmonary disease but also as one with important measurable systemic consequences. COPD is not only preventable but also treatable. Smoking cessation, oxygen for hypoxemic patients, lung reduction surgery for selected patients with emphysema, and noninvasive ventilation during severe exacerbations have all been shown to impact on mortality. In addition, pulmonary rehabilitation, pharmacologic therapy, and lung transplantation improve patient-centered outcomes such as health-related quality of life, dyspnea, exercise capacity, and even exacerbations and hospitalizations. Caregivers should familiarize themselves with the multiple complementary forms of treatment and individualize therapy to the particular situation of each patient. The future for patients with this disease is bright as its pathogenesis and clinical and phenotypic manifestations are unraveled. The advent of newer and more effective therapies will lead to a decline in the contribution of this disease to poor world health.
Key Words: airflow obstruction • bronchitis • chronic obstructive pulmonary disease • emphysema
The American Thoracic Society and European Respiratory Society have defined chronic obstructive pulmonary disease (COPD) as a preventable and treatable disease state characterized by airflow limitation that is not fully reversible. The airflow limitation is usually both progressive and associated with an abnormal response of the lungs to noxious particles or gases, primarily caused by cigarette smoking. Although COPD affects the lungs, it also produces significant systemic consequences (1). This definition changes the paradigm that characterized older definitions (2, 3) in two important aspects. First, it presents a positive attitude toward the disease when it describes it as it is, preventable and treatable, and second, it points out a salient feature of COPD, that is, it is frequently associated with systemic manifestations. This review presents the evidence that COPD is an increasingly important disease and the many problems that make it so, and that have led to a nihilistic attitude on the part of those providing treatment. More importantly, evidence is presented proving that an optimistic attitude is justified, and that there is hope for patients who suffer from this disease.
HIGHLY PREVALENT, UNDERDIAGNOSED, UNDERTREATED, AND UNDERPERCEIVED
COPD causes problems for society because of its direct and indirect costs, but more importantly it affects millions of individuals by limiting their laboring and functional capacity. It has a long subclinical phase but once symptoms develop, COPD usually follows a course of progressive dyspnea at ever lower levels of exercise, gas exchange imbalance, and respiratory failure (1, 3). In the end, death can occur either from the respiratory failure or from the frequently associated comorbidity such as coronary artery disease and lung cancer (4, 5). It is difficult to estimate the exact prevalence of COPD worldwide. Estimates based on the presence of airflow limitation are the most accurate, because symptoms and self-report or clinician diagnosis lack sensitivity and specificity. A postbronchodilator FEV1/FVC less than 70%, in an individual with the appropriate history of exposure to risk factors such as cigarette smoke, or inhaled wood smoke, and/or symptoms of cough, sputum production, or dyspnea, confirms the diagnosis (1). Some of the best data available at present come from two sources, the third National Health and Nutrition Examination Survey (NHANES III), a large national survey conducted in the United States between 1988 and 1994 (6, 7) and the Proyecto Latinoamericano para la Investigación de la Enfermedad Obstructiva Crónica, or PLATINO study (8), conducted in five cities in Latin America (Caracas, Venezuela; Mexico City, Mexico; Montevideo, Uruguay; Santiago, Chile; and São Paulo, Brazil) between 2001 and 2004.
In the NHANES III study from the United States (6), for those aged 25–75 yr, the estimated prevalence of COPD was 16%. The prevalence of both mild and moderate COPD was higher among males than females and among white subjects than black subjects, and increased steeply with age. The survey reflects the actual strata of the U.S. population and provides invaluable data in many health aspects.
The prevalence of COPD determined in the PLATINO study is perhaps the best available data because it was a field study representing the cities surveyed. It was designed to evaluate the disease itself and it included questions specifically directed at the causes of COPD. Finally, and importantly, the survey included postbronchodilation FEV1 data. The study was conducted in five cities and the prevalence fluctuated from 7.8% in Mexico City to 19.7% in Montevideo. The prevalence was higher among men than women and among less educated than better educated persons.
Data from other, smaller surveys showed a prevalence of 13.1% in men and 10.5% in Spain (9), 8.4% in Greece (10), and 11.4% in a European study by de Marco and coworkers (11). Taken together, these studies confirm the widely held concept that COPD is highly prevalent. Indeed, if we assume the lowest of these prevalences, 7.8% for the 40% of people more than 40 yr of age, the total number of cases of COPD in the world approximates close to 280 million persons, a daunting number that needs to be controlled. It is estimated that COPD, currently the fourth leading cause of death in the United States, will become the third cause of death worldwide by 2020.
Unfortunately, COPD remains largely underdiagnosed. Indeed, in the same NHANES III survey, it was clear that less than 50% of individuals with COPD based on airflow limitation have a doctor's diagnosis of COPD at all stages of COPD (6), that is, even persons with advanced COPD do not know they suffer from the disease and thus remain untreated.
For many possible reasons, including self-guilt, patients themselves underperceive the magnitude of their problem and tend to accept the limitations associated with disease progression as natural for a person who has smoked. Indeed, in a telephone survey of more than 3,000 patients with COPD, Rennard and coworkers reported that more than 50% of patients with the most severe rating of dyspnea as measured by the Medical Research Council functional scale (dyspneic when dressing) qualified their COPD as mild or moderate (12). This leads to little advocacy from patients and absent recognition in the sufferers, their families, and society of the true magnitude of the problem.
THE AIRFLOW OBSTRUCTION OF COPD
The airflow obstruction of COPD, as expressed by the FEV1, is by definition of the disease poorly reversible (1, 3). In a paradoxical way, we have used this defining physiology as the outcome to determine the effectiveness of interventions. Indeed, we have planned many studies to reverse what we have defined as "not" fully reversible. It is no surprise that the lack of large response in FEV1 to different therapies has resulted in a nihilism that is not deserved (12–23). The evidence accumulated suggests otherwise, and an optimistic attitude toward patients with COPD goes a long way in relieving patient fears and misconceptions. In contrast to many other diseases, some interventions, such as smoking cessation (5, 13), long-term oxygen therapy in hypoxemic patients (24, 25), mechanical ventilation in acute respiratory failure (26, 27), and lung volume reduction surgery (LVRS) for patients with upper lobe emphysema and poor exercise capacity improve survival (28), whereas others, such as pharmacologic therapy, pulmonary rehabilitation, and surgery, improve symptoms and the quality of a patient's life once the diagnosis has been established (1, 3). Table 1 summarizes the available therapeutic options for patients with COPD.
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Conventionally, the severity of COPD has been graded on the basis of the FEV1 (1–3). However, COPD is associated with a range of clinical manifestations not closely related to the severity of airflow limitation, such as a worsening dyspnea, reduction in exercise capacity, pulmonary hypertension, peripheral muscle weakness, and malnutrition (29, 30). Furthermore, several large studies have shown that the FEV1 is not the only determinant of mortality and a number of other risk factors have now been identified. These include hypoxemia, hypercapnia, the timed walking distance (31, 32), and a low body mass index (30). Therefore, grading COPD solely on the basis of the FEV1 does not reflect the clinical manifestations of the disease and its ultimate prognosis.
There is increasing evidence that lung volumes are important in the genesis of the symptoms and limitations of patients with more advanced disease. A series of elegant studies has demonstrated that the dyspnea perceived during exercise, even during walking by patients with COPD, more closely relates to the development of dynamic hyperinflation than to the severity of obstruction (23, 33). Furthermore, 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. One study also showed that hyperinflation, expressed as the ratio of inspiratory capacity to total lung capacity (IC/TLC), predicted survival better than the FEV1 (34) This not only provides us with new insights into pathogenesis but also opens the door for new, imaginative ways to alter lung volumes and perhaps impact on disease progression.
Equally exciting is the increasing number of studies documenting the presence of systemic abnormalities associated with the disease. Patients with COPD frequently develop skeletal muscle dysfunction, malnutrition with low body mass index and loss of muscle mass, osteoporosis, anemia, and depression along with the better known pulmonary hypertension and heart failure (5, 32, 33). The systemic involvement of COPD is extremely important because it may become the object of therapeutic interventions that could influence outcomes independent of our capacity to modify lung function. As an analogy, patients with diabetes mellitus who develop microalbuminuria and are treated with angiotensin-converting enzyme inhibitors improve their survival. Thus, a treatment that has little to do with the pancreas or the blood sugar impacted on the long-term survival of patients. It is entirely conceivable that as we explore the presence and levels of systemic biomarkers in patients with COPD and their relation to the systemic manifestations of the disease, we can develop and apply novel strategies that will in the end improve the outcome of our patients.
COPD can be described as affecting at least three domains: the respiratory, perceptive, and systemic domains. We have integrated the body mass index (B), degree of obstruction (O), dyspnea (D), and exercise performance (E) scores, using the 6-min walk test to generate a multidimensional index (BODE) that predicts survival better than the current "gold standard," the FEV1 (5). The multicomponent nature is graphically represented in Figure 1, in which the pathophysiologic mechanisms of airflow obstruction are represented within a circle and related to hyperinflation. In addition, related to both but with some independent features we see the systemic and perceptive domains.
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The overall goals of treatment of COPD are to prevent further deterioration in lung function, to alleviate symptoms, and to treat complications as they arise (1, 3). Once diagnosed, the patient should be encouraged to actively participate in disease management. This concept of collaborative management may improve self-reliance and esteem. All patients should be encouraged to lead a healthful lifestyle and exercise regularly. Preventive care is extremely important at this time and all patients should receive immunizations, including pneumococcal vaccine and yearly influenza vaccines (1, 3).
Smoking Cessation
Because smoking is the major cause of COPD, smoking cessation is the most important component of therapy for patients who still smoke (1, 3). Smoking cessation advice should be provided to all patients who smoke. Because second-hand smoking is known to damage lung function, limitation of exposure to involuntary smoke, particularly in children, should be encouraged. Although most patients agree that smoking is risky, many seem unaware of its true significance. The factors that cause patients to smoke include the addictive potential of nicotine; conditional responses to stimuli surrounding smoking; psychosocial problems such as depression, poor education, and low income; and forceful advertising campaigns. Because the causes that drive the patient to smoke are multifactorial, smoking cessation programs should also involve multiple interventions. The clinician should always express strong interest in smoking cessation because a physician's advice to quit smoking may be the difference between successful and unsuccessful results (35–37).
Pharmacologic Therapy of Airflow Obstruction
The pharmacologic therapy of COPD should be organized according to the severity of the disease, and the tolerance of the patient for specific drugs (1, 3, 14–19). In the outpatient setting, a stepwise approach similar in concept to that developed for asthma and systemic hypertension may be helpful. There is no current evidence that the regular use of any pharmacologic agent alters the progressive deterioration of lung function in COPD. However, bronchodilators do provide significant alleviation of symptoms, improve exercise tolerance, and improve quality of life—all worthwhile goals in COPD.
Bronchodilators.
Several important concepts guide the use of bronchodilators. In some patients, the changes in FEV1 may be small and symptomatic benefit may be experienced through other mechanisms, such as a decrease in the hyperinflation of the lung that occurs as a consequence of increased ventilatory demand, as during exercise or an exacerbation (23, 33, 38). Older patients with COPD may have side effects produced by these drugs. Some older patients with COPD cannot effectively activate metered-dose inhalers, and we should work with these patients to achieve mastery of the metered-dose inhaler. If this is not possible, use of a spacer 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 ß-agonists). Finally, the inhaled route is preferred over oral administration (1, 3) and longer acting bronchodilators may improve compliance and do provide longer bronchodilation and symptom relief.
The currently available bronchodilators are as follows:ß-Agonists: ß-Agonists increase cAMP within many cells and promote airway smooth muscle relaxation. Other nonbronchodilator effects have been observed but their significance is uncertain. In patients with intermittent symptoms, it is reasonable to initiate drug therapy with a metered-dose inhaler of a short-acting ß-agonist as needed for relief of symptoms (1). Albuterol should be taken up to a maximum of four to six times per day or as prophylaxis. In more advanced disease, it is indicated to use long-acting ß-agonists (1, 3, 39, 40), at a dose of one or two puffs twice daily. They prevent nocturnal bronchospasm, increase exercise endurance, and improve quality of life (18). The effect of salmeterol on survival is being evaluated in a long-term, large multicenter trial (41).
Anticholinergics: Anticholinergics act by blocking muscarinic receptors that are known to be functional in COPD. The appropriate dosage of the short-acting ipratropium bromide is two to four puffs three or four times per day, but some patients require and tolerate larger dosages (1, 3). The therapeutic effect is a consequence of a decrease in exercise-induced increased lung inflation or dynamic hyperinflation (23). The long-acting quaternary ammonium compound (tiotropium) has been effective in inducing long-term bronchodilation in patients with COPD (14). In addition, tiotropium shows a beneficial effect on dyspnea, recurrence of exacerbations, and health-related quality of life when compared with placebo and even with ipratropium bromide (14, 17). The results of further clinical trials evaluating its potential role as a disease-modifying agent (42) will determine its place in the overall armamentarium of treatments for patients with COPD. At present, there is an available inhaled combination of ipratropium and a ß-agonist that has proven effective in the management of COPD (43).
Phosphodiesterase inhibitors: Theophylline is a nonspecific phosphodiesterase inhibitor that increases intracellular cAMP within airway smooth muscle. The bronchodilator effects of these drugs are best seen at high doses, with which there is also a higher risk of toxicity. Its potential for toxicity has led to a decline in its popularity. Theophylline is of particular value for less compliant or less capable patients who cannot use aerosol therapy optimally. The previously recommended therapeutic serum levels of 15 to 20 mg/dl are too close to the toxic range and are frequently associated with side effects. Therefore, a lower target range of 8 to 13 mg/dl is safer and still therapeutic (1, 3). The combination of two or more bronchodilators (theophylline, albuterol, and ipratropium) has some logical rationale as they seem to have additive effects and can result in maximum benefit in stable COPD (18, 44).
The specific phosphodiesterase E4 inhibitors cilomilast and roflumilast may have an antiinflammatory and bronchodilator effect but less gastrointestinal irritation and thus prove extremely useful if their theoretical advantages are clinically confirmed. Data from studies during the first 6 mo show modest bronchodilation effects and some effect on quality of life (45).
Antiinflammatory therapy.
In contrast to their value in asthma management, antiinflammatory drugs have not been documented to have a significant role in the routine treatment of patients with stable COPD (1). Cromolyn and nedocromil have not been established as useful agents, although they could possibly be helpful if the patient has associated respiratory tract allergy. The groups of leukotriene inhibitors that have proven useful in asthma have not been adequately tested in COPD, so that a final conclusion about their potential use cannot be drawn.
Corticosteroids.
Corticosteroids should be considered in individual patients who continue to have symptoms while receiving adequate bronchodilator therapy (1, 3). Glucocorticoids act at multiple points within the inflammatory cascade, although their effects in COPD are more modest compared with bronchial asthma. Among outpatients, exacerbations necessitate a course of oral steroids, as we discuss later in this article, but it is important to wean patients quickly because the older COPD population is susceptible to complications such as skin damage, cataracts, diabetes, osteoporosis, and secondary infection. These risks do not accompany standard doses of inhaled corticosteroid aerosols, which may cause thrush but pose a negligible risk for causing pulmonary infection. Several large multicenter trials evaluated the role of inhaled corticosteroids in preventing or slowing the progressive course of symptomatic COPD (19, 20, 46–50). The results showed minimal if any benefits in the rate of decline of lung function. On the other hand, in the one study in which it was evaluated, inhaled fluticasone decreased the rate of loss of health-related quality of life and the exacerbations (19) that are characteristic of patients with severe COPD. In addition, its regular use was also associated with a decreased rate of exacerbations. Finally, retrospective analyses of large databases suggest a possible effect of inhaled corticosteroids on increased mortality (51, 52). This has prompted the initiation of a large prospective trial to explore the effect of inhaled corticosteroids on mortality (41). Results of this trial could influence how and when to use corticosteroids. Patients with moderate to severe COPD who have had repeated episodes of acute exacerbation may be the best candidates for chronic inhaled corticosteroids.
Mucokinetics.
Mucokinetics, a loosely defined group of drugs, aim to decrease sputum viscosity and adhesiveness to facilitate expectoration. The only controlled study in the United States suggesting a value for these drugs in the chronic management of bronchitis was a multicenter evaluation of organic iodide (53). This study demonstrated symptomatic benefits. Oral acetylcysteine is favored in Europe for its antioxidant effects in addition to its mucokinetic properties. One large trial failed to document any substantial benefit (54). Genetically engineered ribonuclease seems to be useful in cystic fibrosis, but is of no value in COPD.
Antibiotics.
In patients with evidence of respiratory tract infection, such as fever, leukocytosis, and a change in chest radiograph, antibiotics have proven effective (55). If recurrent infections occur, particularly in winter, continuous or intermittent prolonged courses of antibiotics may be useful (56, 57). When an acute bacterial infection is believed to be present, antibiotic therapy may be justified, but the decision is usually made clinically. In prescribing treatment, fiscal concerns should be a consideration, because older, less costly agents are often effective—for example, tetracycline, doxycycline, amoxicillin, or erythromycin (1). The major bacteria to be considered are Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. The antibiotic choice will depend on local experience, supported by sputum culture and sensitivities if the patient is moderately ill or needs to be admitted to hospital (56). The introduction of oral fluoroquinolones and macrolides has increased our capacity to effectively treat patients with acute respiratory tract infections. Quinolones may be favored for patients with more severe disease and for whom gram-negative bacteria with resistance to many antibiotics seem to be a growing problem (56).
1-Antitrypsin.
Although supplemental weekly or monthly administration of the enzyme 1-antitrypsin may be indicated in nonsmoking, younger patients with genetically determined emphysema, in practice such therapy is difficult to initiate. There is evidence that the administration of 1-antitrypsin is relatively safe, but the appropriate selection of the candidate for such therapy is not clear (1, 3, 58). The most likely candidates for replacement therapy would be patients with mild to moderate COPD.
Vaccination.
Ideally, infectious complications of the respiratory tract should be prevented in patients with COPD by using effective vaccines (59, 60). Thus, routine prophylaxis with pneumococcal and influenza vaccines is recommended (1, 3).
Lung Volume Reduction
Multiple operations have been suggested to improve symptoms in patients with COPD (61–64). Of these, bullectomy has proven useful in patients with large bullae and relatively preserved lung function (61). Lung transplantation results in normalization of pulmonary function, exercise capacity, and quality of life, but its effect on survival remains controversial (65). Several issues must be considered when evaluating a candidate for lung transplantation. These include the patient's pulmonary disability, projected survival without transplantation, comorbid conditions, and patient preferences. General guidelines include that the patient be younger than 65 yr without any other medical condition that could shorten predicted survival; not be addicted to substances such as alcohol, drugs, or cigarettes; be free of persistent bacterial or fungal infections; have no thoracic malformations; or need high-dose corticosteroids.
The other surgical procedure that has received attention is pneumoplasty, or LVRS. Initially developed by Brantigan and colleagues (66), Cooper and coworkers (67) reintroduced it as a valid alternative for selected patients with severe inhomogeneous emphysema who remained severely symptomatic after optimal comprehensive medical therapy. However, evidence shows that LVRS improves FEV1 by close to 10%, with larger improvements in exercise tolerance, dyspnea, and health-related quality of life (68–73). The effect on survival is restricted to a small group with upper lobe disease and limited exercise performance after rehabilitation (18). There are difficulties in patient selection for LVRS (74–77). Current evidence suggests that patients with hyperinflation and inhomogeneous emphysema, those with poor but not extremely severe lung function, and those with limited exercise capacity are the best candidates for this procedure. LVRS offers new hope to selected patients who have few other alternatives. Reports evaluating techniques capable of achieving lung volume reduction, without the surgical risk, open exciting new avenues of treatment. Indeed, the bronchoscopic placement of one-way valves (78) or biological substances (79) capable of inducing closure of emphysematous areas may add to an already exciting armamentarium to treat selected patients with advanced COPD.
THERAPIES THAT ARE EFFECTIVE FOR THE NONRESPIRATORY MANIFESTATIONS OF COPD
As we have seen above, the most exciting changes in the way we conceptualize COPD is the recognition of the extrapulmonary manifestations of COPD. Some of the most important advances in the therapy of COPD center around our capacity to impact on the disease without altering lung function. Two of the most proven forms of therapy for COPD fall within this category: pulmonary rehabilitation and oxygen therapy. If we add mechanical ventilation during exacerbations, the field is open to explore even more exciting therapies.
Pulmonary Rehabilitation
Pulmonary rehabilitation is increasingly recognized as an important component in the comprehensive management of patients with symptomatic lung disease. A somewhat nihilistic approach became widespread when multiple studies evaluating this therapeutic tool in patients with severe lung disease failed to show any improvement in conventional pulmonary function tests. Carefully conducted research studies have shown that pulmonary rehabilitation offers the best treatment option for patients with symptomatic lung disease (80–90). Any patient symptomatic from respiratory disease is a candidate for rehabilitation (80–82). Patients with moderate to moderately severe disease are preferred targets for treatment to prevent the disabling effects of end-stage respiratory failure. The rehabilitation program should have resources available to teach and supervise respiratory therapy techniques (oxygen, use of inhalers, nebulizers, etc.), physical therapy (breathing techniques, chest physical therapy, postural drainage), exercise conditioning (upper and lower extremities), and activities of daily living (work simplification, energy conservation). Also desirable are services to evaluate and advise on nutritional needs, psychologic evaluation, and vocational counseling. Exercise training is the most important component of a pulmonary rehabilitation program. Maltais and coworkers (91) documented that the muscle biopsies of trained patients, but not control subjects, manifested significant increases in all enzymes responsible for oxidative muscle function. Pulmonary rehabilitation can change outcomes that predict survival. Indeed, in one observational study, rehabilitation improved the BODE score and the change induced reflected outcome prognosis (92).
Home Oxygen Therapy
Results of the Nocturnal Oxygen Therapy Trial and Medical Research Council studies have established that continuous home oxygen improves survival in hypoxemic COPD and that survival is related to the number of hours of supplemental oxygen per day (25, 26). Other beneficial effects of long-term oxygen include reduction in polycythemia, in pulmonary artery pressures, dyspnea, and rapid eye movement–related hypoxemia during sleep. Oxygen also improves sleep, and may reduce nocturnal arrhythmias. Importantly, oxygen can also improve neuropsychiatric testing (93, 94) and exercise tolerance (95–97). The beneficial effects of oxygen are the first proof that outcomes can be improved without necessarily changing the degree of airflow obstruction, providing evidence that the disease can be modified without changing the rate of decline of FEV1.
Exacerbations
An exacerbation of COPD is an event in the natural course of the disease characterized by a change in the patient's baseline dyspnea, cough, and/or sputum beyond day-to-day variability and sufficient to warrant a change in management (1, 3, 98). In the case of an acute exacerbation, pharmacologic therapy is initiated with the same therapeutic agents available for its chronic management (1, 3). Care must be taken to rule out heart failure, myocardial infarction, arrhythmias, and pulmonary embolism, all of which may present with clinical signs and symptoms similar to exacerbation of COPD.
The most important agents for acute exacerbation of COPD are anticholinergic and ß-agonist aerosols as an inhalant solution by nebulization. Systemic corticosteroids should be added to the regimen. Two smaller trials (99, 100) and one large randomized trial (101) proved the usefulness of corticosteroids. It is important to avoid prolonged (> 2 wk) or high-dose therapy because older patients are susceptible to severe complications such as psychosis, fluid retention, and vascular necrosis of bones.
Antibiotics such as amoxicillin, doxycycline, erythromycin, quinolones, and macrolides (clarithromycin and azithromycin) have been helpful in purulent exacerbations of COPD (52). The antibiotics used in severe exacerbation must be guided by knowledge of the prevalent pathogens in that area (102). Exacerbations are to be prevented and treated aggressively because they have a prolonged and intense effect on health-related quality of life and can result in accelerated loss of lung function (103, 104).
Ventilatory support should be considered if patients have persistent hypoxemia and/or hypercapnia with low pH (< 7.35) despite maximal medical therapy (1). Several randomized trials have shown that noninvasive positive pressure ventilation is beneficial in selected patients with respiratory failure, decreasing the need for invasive mechanical ventilation and its complications and, possibly, improving survival (105, 106). Certain conditions would make patients less likely to respond to noninvasive positive-pressure ventilation. These conditions include respiratory arrest, medical instability (shock, cardiac ischemia), inability to protect the airway, excessive secretions, agitation or uncooperativeness, craniofacial trauma, or deformity.
CONCLUSIONS
Over the years, our knowledge about COPD and the capacity to treat it have increased significantly. Smoking cessation campaigns have resulted in a significant decrease in smoking prevalence in the United States. Similar efforts in the rest of the world should have the same impact. The fight against cigarette smoking should results in a drop in incidence of COPD in the years to come. The widespread application of long-term oxygen therapy for hypoxemic patients has resulted in increased survival. During this time we have expanded our drug therapy armamentarium and have used drugs to effectively improve dyspnea and quality of life. Studies have documented the benefits of pulmonary rehabilitation. Noninvasive ventilation has offered new alternatives for patients with acute or chronic failure. The revival of surgery for emphysema or, in the immediate future, endobronchial lung volume reduction should provide an alternative to lung transplantation for those patients with severe COPD who are still symptomatic while receiving maximal medical therapy. With all these options as shown in Figure 2, a nihilistic attitude toward the patient with COPD is not justified. The evidence justifies a positive and constructive attitude.
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Conflict of Interest Statement: B.R.C. received $3,000 in 2005 and $4,000 in 2003 and 2004 for speaking at conferences sponsored by GlaxoSmithKline (GSK). He received $3,000 in 2004 and 2005 for serving on an advisory board for GSK. He has a financial relationship in the laboratory that they direct and work, and received $180,000 from GSK for 3 yr as research grants for conducting this research.
(Received in original form October 19, 2005; accepted in final form October 23, 2005)
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1-antitrypsin augmentation therapy. Am J Respir Crit Care Med 1999;160:1468–1472.This article has been cited by other articles:
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