A Nationwide Framework for Surveillance of Cardiovascular and Chronic Lung Diseases (2011)

3

Chronic Lung Disease

Chronic lung disease includes the conditions of chronic obstructive pulmonary disease (COPD), sleep-disordered breathing, and interstitial lung disease. This report has chosen to focus on COPD because it is the third leading cause of death in the United States (after heart disease and malignant neoplasms) (Kochanek et al., 2011) and is a substantial financial burden for the American economy. Many issues related to surveillance of COPD will apply equally to the other chronic lung conditions.

DEFINITION

Chronic obstructive pulmonary disease is an umbrella term for several conditions, including chronic bronchitis and emphysema as well as a subset of patients with asthma, that impede the flow of air in the bronchi and trachea. COPD has been defined as “a disease state characterized by airflow limitation that is not fully reversible. The airflow limitation is usually both progressive and associated with an abnormal inflammatory response of the lungs to noxious particles or gases” (Crapo et al., 2000; Rabe et al., 2007).

The heterogeneity of COPD has resulted in a variety of different definitions of disease that include components of destruction of the lung parenchyma (emphysema), chronic sputum production (bronchitis), limitation of airflow, and the development of hypoxemia. No single definition is perfect or all-inclusive. For example, some patients will have clinically significant emphysema in the absence of airflow limitation, whereas other patients may have significant airflow limitation in the absence of any emphysema or hypoxemia. In addition, lung function declines with age, resulting in questions about what represents disease versus normal aging. Although there is little debate surrounding moderate or severe disease, a great deal of debate surrounds more mild disease, which, ironically, is probably the most responsive to intervention.

One widely accepted and used classification strategy defines COPD by the presence of obstruction on spirometry: a forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) ratio of less than 70 percent, measured with a post-bronchodilator lung function (Celli et al., 2004b; WHO, 2008). Although this “fixed” ratio is easy to remember and simple, there is some concern that it may underestimate COPD in younger populations, overestimate it in older ones, and misclassify other patients (Celli et al., 2003; Kohler et al., 2003).

The GOLD and ATS/ERS criteria classify COPD into four stages (Celli et al., 2004b; WHO, 2008):

• Stage 1 (FEV1 ≥ 80 percent predicted);
• Stage 2 (FEV1 50 to < 80 percent predicted);
• Stage 3 (FEV1 30 to < 50 percent predicted); and
• Stage 4 (FEV1 < 30 percent predicted).

In addition, an “at risk” stage (formerly known as GOLD Stage 0) consists of patients with chronic respiratory symptoms (cough, sputum, or dyspnea) and normal lung function. Although this stage has been removed from the 2006 GOLD update because of data suggesting this stage may not progress to GOLD Stage 1 and higher COPD (Vestbo and Lange, 2002; WHO, 2008), people with symptoms and normal lung function have a lower quality of life and a higher risk of hospitalizations and mortality in follow-up investigations (Mannino et al., 2006; Stavem et al., 2006).

As noted above, this classification strategy may miss some patients with disease and overestimate the extent of disease in others. In addition, surveillance of disease typically depends on using information from administrative data sets, requiring the use of diagnostic and procedure codes to infer the presence of disease. This can be particularly problematic when looking at mortality related to COPD because most people with severe COPD who die have their death attributed to another cause (Mannino et al., 2006), and most people who die with a diagnosis of COPD listed on their death certificate do not have this attributed as the underlying cause of death. Therefore, the contribution of this chronic lung disease to observed mortality patterns and trends is underestimated.

EPIDEMIOLOGY

COPD is a common chronic disease. Most estimates of COPD place its prevalence in the adult population at 5 to 10 percent, although these estimates vary by the specific criteria used. Data from the Third National Health and Nutrition Examination Survey (NHANES III), the most recent national health survey that included spirometry, showed a prevalence of COPD in adults of 6.8 percent (Mannino and Buist, 2007). Over 50 percent of people with evidence of COPD have never been diagnosed with this disease. This proportion is even higher among people with mild disease, which is most amenable to intervention (Mannino and Braman, 2007).

COPD is responsible for about 700,000 hospitalizations annually in the United States. In recent years, the hospitalization rate among women has increased and is now similar to the rate among men. In 2009, more than 137,000 adults in the United States died from COPD (Kochanek et al., 2011). Age-adjusted mortality rates per 100,000 vary dramatically by state, from a low of 27.1 in Hawaii to a high of 93.6 in Oklahoma (CDC, 2008).

COPD has an enormous financial burden, with estimated direct medical costs in 1993 of $14.7 billion. The estimated indirect costs related to morbidity (loss of work time and productivity) and premature mortality is an additional $9.2 billion, for a total of $23.9 billion. By 2002 the direct and indirect costs were estimated at $32.1 billion (Mannino and Buist, 2007). The overwhelming risk factor for COPD is cigarette smoking. Other important risk factors include a history of asthma; occupational exposures to dusts, gases, vapors, and fumes; exposure to biomass smoke; and respiratory infections such as tuberculosis. In the developing world, exposures to biomass smoke and respiratory infections are particularly important (Buist et al., 2007). Comorbid diseases include cardiovascular disease, osteoporosis, lung cancer, and depression. In addition, diseases such as pneumonia and pulmonary hypertension are often complications of COPD (Decramer et al., 2008; Holguin et al., 2005).

PREVENTION AND TREATMENT

The classification of chronic respiratory disorders is often based on the pattern of physiologic impairment, either obstructive or restrictive, as measured with pulmonary function tests. Obstructive disorders, asthma, and COPD are the most common chronic respiratory diseases. The restrictive disorders are heterogeneous, including diffuse parenchymal lung diseases (e.g., idiopathic pulmonary fibrosis) and disorders that impair chest movement (e.g., morbid obesity, neuromuscular diseases). The focus of this review is on COPD, which provides an example of how surveillance throughout the life span may contribute to the prevention and control of chronic respiratory diseases.

While asthma and COPD are both characterized by airflow obstruction, asthma is reversible and COPD is incompletely reversible. Other differences also exist. For example, asthma most commonly develops in childhood, and COPD usually begins in the fifth decade or later. Moreover, recent evidence suggests that asthma and COPD have a number of distinct phenotypes with substantial overlap (Gibson and Simpson, 2009), and a number of childhood characteristics—including maternal asthma, paternal asthma, childhood asthma, respiratory infections, and maternal smoking—are risk factors for COPD (Salvi and Barnes, 2009; Svanes et al., 2010).

In adulthood there are multiple determinants of lung function level and decline (Gibson and Simpson, 2009), including cigarette smoking (Griffith et al., 2001), age, race, gender, bronchial hyperreactivity, asthma, occupational and environmental exposures, physical inactivity (Garcia-Aymerich et al., 2007; Pelkonen et al., 2003), chest wall deformity (DiBari et al., 2004), and psychological characteristics (Kubzansky et al., 2002).

Strategies for the prevention and control of asthma and COPD include methods for primary, secondary, or tertiary prevention. Primary prevention is accomplished by elimination of exposures that cause these diseases. Secondary prevention involves early detection and intervention among asymptomatic persons. Tertiary prevention is the management of symptomatic disease. Healthy People 2020 has eight objectives related to asthma and four related to COPD.

Determining the effectiveness of these interventions requires surveillance throughout the life span to measure known risk factors, to conduct early detection, and to monitor outcomes. This chapter uses available data sources and evidence relevant to surveillance activities for COPD as an example of how to describe and evaluate the current state of surveillance, and to serve as background for recommendations on a national surveillance system.

Primary Prevention

While elimination of active smoking is the single most important intervention for the primary prevention of COPD in the United States, variation in the population-attributable fraction¹ for smoking suggests that other risk factors (described below) also have a significant public health impact. For example, Ezzati and Lopez (2003) examined the global burden of mortality from COPD. They estimated population-attributable fractions for COPD mortality among industrialized countries were 84 and 77 percent for men 30–69 years and ≥ 70 years, respectively. For women the corresponding estimates were 62 and 61 percent. Among developing countries, the estimates were substantially lower (49 and 45 percent for men, and 20 and 12 percent for women). Globally, the population-attributable fractions were 54 percent for men 30–69 years and 52 percent for men ≥ 70 years, and for women 24 percent and 19 percent, respectively.

Differences in population distributions of other COPD risk factors may partly contribute to variations in population-attributable fractions for smoking. These other factors may include occupational exposures, environmental tobacco smoke, other indoor air pollutants, outdoor air pollution, respiratory tract infections, asthma, low physical activity, poor nutrition, low socioeconomic/educational status, and genetic susceptibility. Moreover, interactions between smoking and these other factors may modify the magnitude of risk for COPD between populations (Hu et al., 2006; Svanes et al., 2010).

Compared to tobacco control, evidence is limited on effectiveness of controlling exposures to other risk factors for COPD, including maternal smoking and nutrition, early childhood exposure to tobacco smoke and infections, outdoor and indoor air pollution, occupational exposures, and other behavioral factors. Recent evidence suggests that maternal and early childhood interventions may offer opportunities at least as large as tobacco control for the prevention of COPD (Svanes et al., 2010). Lower levels of outdoor and indoor air pollution are associated with improved rates of lung growth in children (Avol et al., 2001; Gauderman et al., 2002), reduced rate of lung function decline in adults improved respiratory symptoms in adults (Downs et al., 2007; Menzies et al., 2006), and reduced mortality (Schindler et al., 2009).

____________

¹ The population-attributable fraction “is the proportional reduction in population disease or mortality that would occur if exposure to a risk factor were reduced to an alternative ideal exposure scenario (e.g., no tobacco use).” See http://www.who.int/healthinfo/global_burden_disease/metrics_paf/en/index.html (accessed May 21, 2011).

Early Detection and Intervention

Airflow obstruction is common among asymptomatic persons (Mannino et al., 2000), and spirometry offers a feasible method for early detection and intervention to prevent or limit progression to symptomatic disease. An extensive review of available evidence concerning spirometry screening for COPD, conducted by the U.S. Preventive Services Task Force (USPSTF) and published in 2008, addressed eight questions (see Table 3-1) (Lin et al., 2008). While spirometry offers a feasible method for early detection and intervention, available evidence does not support the routine use of spirometry for screening. Results are inconclusive on the use of spirometry as a tool to enhance smoking cessation, and they are not available on the use of pharmacological treatments among asymptomatic persons with chronic airflow obstruction. A major limitation of spirometry screening is the low

TABLE 3-1 Questions and Conclusions on Screening for Chronic Obstructive Pulmonary Disorder (COPD) from U.S. Preventive Services Task Force

SOURCE: Lin et al. (2008).

prevalence of severe and very severe airflow obstruction (FEV1 < 50 percent predicted) in the general population, which is the group most likely to benefit from available medical interventions. Using COPD exacerbation as the primary health outcome, the USPSTF (Lin et al., 2008) estimated that among current smokers and never smokers, 833 and 2,000 persons, respectively, would have to be screened with spirometry to prevent one exacerbation over 6–36 months. The number needed to screen decreased with advancing age and was lowest among persons 70–74 years of age at 400.

While available evidence does not support the routine use of spirometry for screening, evidence from population-based and clinical studies (discussed in the next section) shows that diagnostic spirometry is underused and contributes to substantial diagnostic misclassification. Using NHANES III data, Mannino and colleagues (2000) found an overall prevalence of spirometry-defined obstructive lung disease of 8.5 percent, and an additional 4.3 percent of the population reported a diagnosis of obstructive lung disease, but did not have spirometric evidence. In a population-based household survey in England, Shahab and colleagues (2006) found spirometry-defined COPD among 13.3 percent of participants over 35 years of age, but only 18.8 percent of these volunteers reported any diagnosis of lung disease, which was lowest for mild impairment (6.4 percent) and increased with moderate (21.3 percent) and severe impairment (46.8 percent). Miravitlles and colleagues (2009) conducted a population-based survey in Spain and found an overall prevalence of spirometry-defined COPD of 10.2 percent, and of these patients only 26.9 percent reported a previous diagnosis of COPD, with 16 percent, 35.2 percent, and 85 percent for mild, moderate, and severe or very severe impairment, respectively.

Treatment of Diagnosed Disease

Management or tertiary prevention of COPD has the goals of reducing morbidity and mortality among persons with symptomatic COPD, and has been extensively described elsewhere (Rodriguez-Roisen et al., 2009). Four main components of management are diagnosis and monitoring, reduction of risk factors, management of stable COPD, and management of exacerbations (Rodriguez-Roisen et al., 2009). To raise awareness about the optimal management of COPD, a number of evidence-based guidelines have been developed in recent years (Celli et al., 2004a; National Collaborating Centre for Chronic Conditions, 2004; Rodriguez-Roisen et al., 2009). However, physician knowledge and adherence to these guidelines is limited, particularly among primary care physicians who provide the majority of care for patients with COPD (Barr et al., 2005; Rutschmann et al., 2004).

Diagnosis and Monitoring

This component of management refers to accurately diagnosing COPD, assessing disease severity and complications, and diagnosing comorbid conditions. Furthermore, as a chronic progressive condition, COPD requires ongoing monitoring for diagnosis and treatment of complications and comorbid conditions. While spirometric evidence of “airflow limitation that is not fully reversible” (Rodriguez-Roisen et al., 2009) is the hallmark for diagnosing COPD, clinicians infrequently use spirometry and most often diagnose chronic lung diseases based solely on respiratory symptoms and current or past cigarette smoking (Han et al., 2007; Joo et al., 2008a).

Severity and complications In addition to the findings on spirometry, which is used to classify the severity of airflow obstruction, a number of other factors influence the prognosis of patients with COPD. These factors include age, severity of dyspnea, body mass index (BMI), 6-minute walk distance (Celli et al., 2004a; Puhan et al., 2009c), and complications (e.g., hypoxemia, hypoventilation, right heart failure). Although awareness of these factors may be used to tailor management practices, limited evidence is available about the effectiveness of their use in clinical practice. One example is undertreatment of hypoxemia, with only 32 percent of patients with baseline hypoxia receiving home oxygen as part of routine management (Mularski et al., 2006).

Comorbid conditions Patients with COPD frequently have other illnesses with similar symptoms. This may further contribute to diagnostic misclassification and may affect prognosis and management (Schneider et al., 2010a). On average, persons aged 65 and older have three or more chronic conditions (Boyd et al., 2005), and patients with

COPD also commonly have cardiovascular disease, lung cancer, depression, cognitive impairment, osteoporosis, and gastroesophageal reflux (Hung et al., 2009; Rascon-Aguilar et al., 2006; Schneider et al., 2010a,b; Sin et al., 2006; Soriano et al., 2005). The co-occurrence of multiple chronic illnesses presents a number of diagnostic and management challenges. Delay in diagnosis of COPD or cardiovascular disease may result because of the non-specificity of respiratory symptoms. The use of many different medications to treat multiple conditions may contribute to adverse drug interactions (Boyd et al., 2005). Moreover, polypharmacy combined with underlying depression and cognitive impairment may cause problems with medication adherence. Identification of single or combined treatments for two or more conditions offers a potential solution to polypharmacy. Targeting chronic systemic inflammation, a common pathophysiological pathway between COPD and cardiovascular disease, offers the potential for a common therapeutic agent. For example, limited evidence suggests that the use of statins to treat systemic inflammation reduces morbidity and mortality in patients with COPD (Alexeeff et al., 2007; Frost et al., 2007; Keddissi et al., 2007; Søyseth et al., 2007; van Gestel et al., 2009). Addressing the clinical challenges of comorbid illnesses in patients with COPD is an ongoing area of investigation.

Reduce risk factors Smoking cessation is a critical component in the management of patients with COPD. Cessation is associated with reduced rate of decline in lung function, improved symptoms, and lower mortality (Anthonisen et al., 2005a; HHS, 2004). The comparative effectiveness of smoking cessation interventions among patients with COPD was recently examined by Strassmann and colleagues (2009), who conducted a meta-analysis of eight clinical trials that included 7,372 patients. Overall, smoking cessation counseling combined with a pharmacological agent (i.e., nicotine replacement, antidepressant) had the greatest benefit compared to counseling alone or to usual care. High-intensity counseling combined with nicotine replacement had the greatest success when compared to usual care (OR = 5.22; 95 percent CI, 4.43–6.15). By contrast, low-intensity counseling without a pharmacological agent compared to usual care had no significant effect (OR = 1.17; 95 percent CI, 0.39–3.54). All other combinations of counseling and pharmacological agents had intermediate effects.

Compared to smoking cessation, evidence is limited on the effectiveness of controlling exposures to other risk factors for COPD-related morbidity and mortality, including outdoor and indoor air pollution, occupational exposures, and nutrition (e.g., BMI). However, control of outdoor and indoor particulate pollution may have a number of benefits for patients with COPD, including reduced rate of lung function decline (Downs et al., 2007; Menzies et al., 2006), improved chronic respiratory symptoms (Menzies et al., 2006; Schindler et al., 2009), and reduced mortality (Goodman et al., 2007; Pope et al., 2009).

Management of stable COPD Strong evidence suggests that the management of patients with COPD is often suboptimal and many patients are undertreated (Barr et al., 2005; Mularski et al., 2006). The optimal management of patients with COPD is composed of self-management education, medications, influenza/pneumococcal vaccination, and pulmonary rehabilitation (Rodriguez-Roisen et al., 2009; Wilt et al., 2005). Each of these components of routine care is reviewed below.

Self-management education refers to the process of informing, motivating, and preparing patients to control their disease and improve their health status through medical treatments and health behavior change (Bourbeau et al., 2004; Epping-Jordan et al., 2004). Available evidence suggests gaps in patient knowledge for effective self-management (Barr et al., 2005; Hernandez et al., 2009). Self-management programs have been part of center-based pulmonary rehabilitation programs (Troosters et al., 2005) and stand-alone programs (Effing et al., 2007; Shahab et al., 2006), with three main components: (1) lifestyle change (e.g., smoking cessation, exercise, nutrition); (2) dyspnea management (e.g., medication adherence/inhalation technique, breathing technique, energy conservation, relaxation); and (3) exacerbation action plan. Because programs often target more than one of these topics, the relative importance of each component is unknown. Overall, results of self-management programs in settings other than pulmonary rehabilitation have demonstrated limited benefit, probably because of methodological issues (e.g., patient selection, small sample size) and variation in the quality of the interventions (Effing et al., 2007; Monninkhof et al., 2003; Shahab et al., 2006). Most programs have emphasized patient education, which is not effective for changing health-related behavior (Nieuwenhuijsen et al., 2006). Limited attention has been given to theory-based health behavior interventions that address not only patient knowledge but also motivation

and behavioral support (Effing et al., 2007; Shabab et al., 2006). Moreover, while self-management interventions may be necessary for improving outcomes, results are inconsistent and alone may be insufficient for improving quality-of-life or healthcare use among patients with COPD.

A growing literature strongly suggests that a number of psychosocial factors have a wide-range of influence on functional and health status among patients with COPD (Katz et al., 2010; Simpson and Rocker, 2008). For example, depression, cognitive impairment, self-efficacy, and social support may all affect adherence to medical management of COPD, and subsequent functional and health status (Antonelli-Incalzi et al., 2007; Bourbeau et al., 2004; Davis et al., 2006; Wong et al., 2005).

Medication management The cornerstone of medical management has been the use of inhaled medications, including short- and long-acting bronchodilators and anti-inflammatory agents. Both classes of medications provide symptom relief, improve quality of life, and decrease exacerbations in selected patients (Wilt et al., 2007). However, a number of factors may contribute to suboptimal use of medications, including lack of physician knowledge (Rutschmann et al., 2004), underuse (Anthonisen et al., 2005b; Joo et al., 2008a), poor adherence, and the fact that even under ideal circumstances, fewer than half of the patients in randomized trials benefit from potent pharmacological interventions (e.g., tiotropium) (Vincken et al., 2002). These observations may partly explain the finding that fewer than 60 percent of patients with COPD receive recommended medications (Mularski et al., 2006). Among 21,529 Medicare beneficiaries with obstructive lung disease, the majority of whom had COPD, Craig and colleagues (2008) found that only 30.8 percent received some form of pharmacotherapy. Similarly, Bourbeau and coworkers (2004) found that only 34 percent of patients in primary care settings received medications consistent with guideline recommendations, and the patterns of treatment inconsistency included both under- and overtreatment. While the use of medications increases with the severity of COPD impairment, both under- and overtreatment have been described in a number of investigations (Anthonisen et al., 2005b; Chavez and Shokar, 2009; Craig et al., 2008; Diette et al., 2010; Jones et al., 2008; Joo et al., 2008b; Miravitlles et al., 2008).

Influenza and pneumococcal vaccination The use of these vaccinations in the management of patients with COPD has been reviewed extensively elsewhere (Mannino et al., 2000). Briefly, influenza vaccination reduces exacerbations in patients with COPD, but the evidence regarding pneumococcal vaccination is insufficient (see Table 3-1). Moreover, data do not support prioritizing vaccination based on severity of spirometric impairment.

Pulmonary rehabilitation Compared to the healthy elderly, patients with COPD are markedly inactive (Pitta et al., 2005). This inactivity from dyspnea leads to deconditioning and further decline in functional performance, which, in turn, may lead to social isolation, poor quality of life, and depression. The available evidence strongly suggests that disruption of this cycle of physical inactivity and deconditioning is necessary to substantially improve functional performance and health status for patients with COPD. Pulmonary rehabilitation programs have been designed to address this problem and are cost-effective (American Thoracic Society, 1999; Griffiths et al., 2001; Lacasse et al., 2006).

However, despite the available evidence on the benefits of pulmonary rehabilitation, surveys conducted in the United States, United Kingdom, and Canada have consistently estimated that fewer than 2 percent of patients with COPD receive pulmonary rehabilitation (Bickford et al., 1995; Brooks et al., 2007; Yohannes and Connolly, 2004).

Manage exacerbations Patients with COPD suffer from chronic respiratory symptoms, including dyspnea, cough, and fatigue, and frequently have episodic acute worsening of their symptoms that may require an escalation of medical therapies and, in severe episodes, emergency room treatment or hospitalization. In a cohort of 198,981 U.S. veterans with COPD, Joo and colleagues (2007) used inpatient, outpatient, and pharmacy databases to identify all exacerbations and found that 44 percent had at least one exacerbation or more over a 2-year follow-up period. Moreover, the rate of exacerbations varied widely between regions, ranging from 0.34 to 0.75 exacerbations per person per year, which may be underestimates because patients underreport episodes of exacerbation (Xu et al., 2010). Of all exacerbations, about 15 to 40 percent are severe enough to result in an emergency room visit or hospitalization (FitzGerald et al., 2007; Oostenbrink et al., 2004; Xu et al., 2010). A number of factors have been associated with hospitalization for a COPD exacerbation, including lower socioeconomic status (Disano et al., 2010), interruption of health insurance coverage (Bindman et al., 2008), and fewer primary care visits (Kronman et al., 2008). Clinical predictors associated with hospitalization for COPD exacerbation have included older age,

comorbidity, chronic oxygen therapy, lower FEV1, hypoventilation, hospitalization in previous year, greater number of respiratory medications prescribed, regular use of corticosteroids, and depression (Bahadori and FitzGerald, 2007; FitzGerald et al., 2007; Xu et al., 2008).

Findings by Laditka and Laditka (2006) demonstrated that hospitalization for an exacerbation of COPD is considered preventable and a marker for suboptimal access to or effectiveness of primary care, also known as an ambulatory sensitive condition. Using a nationwide sample of community hospital discharge data, the researchers found that compared to non-Hispanic whites, African American males (adjusted relative rates of 1.9 and 1.6 for ages 19–64 and 65+, respectively) and Hispanic males (2.6 and 2.3, respectively) and females (1.6 and 2.1, respectively) had higher rates of hospitalizations for COPD, adjusted for disease prevalence. In an analysis of admission rates in North Carolina among Medicare beneficiaries for ambulatory-care sensitive conditions including COPD, Howard and colleagues (2007) found that African Americans had lower admission rates for COPD compared to whites (OR = 0.67, 95 percent CI 0.65–0.69). Population and methodological differences may partly explain the conflicting results between these two studies.

Disease exacerbations, whether reported or not, substantially impact patients’ health status, including morbidity and mortality. Reductions in quality of life have been found after exacerbations for up to a year after an exacerbation. While the greatest reductions are among patients with more severe reported exacerbations, even patients who do not report their worsening symptoms have clinically significant declines in quality of life (Xu et al., 2010). In addition to the impact of exacerbations on quality of life, these episodes are associated with increased mortality (Agabiti et al., 2010). While a number of factors may contribute to variation in outcomes after an exacerbation, this remains an area of active investigation, with a focus on quality of care provided during an exacerbation.

Lindenauer and colleagues (2006) analyzed clinical data from 69,820 patients hospitalized for an exacerbation at 360 U.S. hospitals. They compared actual treatment to recommended management guidelines developed by the American College of Physicians and the American College of Chest Physicians, and found that 66 percent received all five components of recommended care (i.e., chest radiography, supplemental oxygen, bronchodilators, systemic corticosteroids, and antibiotics); 45 percent received at least one non-recommended measure (i.e., acute spirometry, methylxanthine bronchodilator, sputum testing, mucolytic therapy, or chest physiotherapy); and only 33 percent received ideal care (i.e., all five recommended and none of the non-recommended measures). In a recent analysis of this same database that included 84,621 patients with a COPD exacerbation, Rothberg and colleagues (2010) found that antibiotic use was associated with a decreased risk (odds ratio [OR] 0.87; 95 percent confidence interval [CI], 0.82–0.92) of treatment failure (i.e., mechanical ventilation, inpatient mortality, and readmission). Furthermore, treatment failure was no more likely with low-dose oral compared to high-dose intravenous corticosteroids (OR = 0.93, 95 percent CI, 0.84–1.02) (Lindenauer et al., 2010). In addition to the quality of COPD-specific management potentially affecting outcomes of COPD exacerbations, outcomes may also be adversely affected by comorbid conditions and associated complications. Diastolic dysfunction is associated with more frequent and prolonged exacerbations in patients with COPD (Abusaid et al., 2009). Moreover, following an exacerbation patients are at increased risk for myocardial infarction within 1–5 days (OR = 2.27; 95 percent CI, 1.1–4.7) and stroke within 1–49 days (OR = 1.26; 95 percent CI, 1.0–1.6) (Donaldson et al., 2010).

Because of the morbidity and mortality associated with exacerbations, there has been growing interest in prevention and early recognition and control of exacerbations. A number of methods to prevent or limit exacerbations have been examined, including pharmacological measures, self-management education, pulmonary rehabilitation, and control of exposures that cause exacerbations. To examine the comparative effectiveness of four categories of inhaled medications for preventing exacerbations, Puhan and colleagues (2009a) conducted a meta-analysis of 35 clinical trials with 26,786 patients. Overall, all categories of inhaled medications decreased the risk of exacerbation by 29 percent compared to placebo (OR = 0.71; 95 percent CI, 0.64–0.80), and when compared to long-acting beta-agonists alone, there were no differences with long-acting anti-cholinergic, corticosteroids, or combination long-acting bronchodilators and corticosteroids. However, when the FEV1 percent predicted was less than 40 percent, these three categories of inhaled medications significantly decreased the risk of exacerbation compared to long-acting beta-agonists alone. In an observational study of managed-care Medicare beneficiaries, Simoni-Wastila and colleagues (2009) examined inhaled medication use on COPD-related hospitalizations and emergency department visits. They found that a combination long-acting bronchodilator and corticosteroid was

more effective when compared to anticholinergic treatments in decreasing emergency department visits (OR = 0.82; 95 percent CI, 0.76–0.89) and hospitalizations (OR = 0.82; 95 percent CI, 0.75–0.89).

In addition to inhaled medications for COPD, treatment of comorbid conditions may also prevent exacerbations. The cardioprotective benefits of beta-blockers may explain the recent observation that chronic use of these medications decreases the risk of exacerbations of COPD (OR = 0.71; 95 percent CI, 0.60–0.83) and mortality (OR = 0.68; 95 percent CI, 0.56–0.83) (Rutten et al., 2010).

Integrated care models Integration of the necessary management components for providing optimal delivery of health care to patients with chronic illnesses presents many challenges and has been an active area of investigation (Peikes et al., 2009). Results from a large, multicenter randomized trial of care coordination programs among more than 18,000 Medicare beneficiaries—which included patients treated for such common chronic conditions as coronary artery disease (60.5 percent), congestive heart failure (48.3 percent), diabetes (39 percent), COPD (32.1 percent), cancer (20.8 percent), and stroke (13.5 percent)—showed no overall reduction in hospitalizations, improvement in quality of care, or reduction in healthcare costs. However, results from selected programs in the trial suggested potential program characteristics (e.g., in-person contact between care coordinators and patients, close collaboration between the care coordinator and patient’s physician) that may be helpful for the design of future programs (Ayanian, 2009).

In addition to generic care coordination programs for chronic illness, a number of COPD-specific programs have been investigated to address the complexities of COPD management through better integration of care, including delivery system design, decision support, and clinical information systems. In a systematic review of 32 studies, Adams and colleagues (2007) did not find improvements in symptoms or quality of life with any of the interventions, but did find statistically significant improvements in emergency/unscheduled visits and hospitalizations when two or more of the components were used. Peytremann-Birdevaux and colleagues (2008) reviewed 13 studies of disease management defined as an intervention that “included two or more different components (e.g., physical exercise, self-management, and structured follow-up), two or more health professionals actively involved in patient care, patient education was considered, and at least one component of the intervention lasted a minimum of 12 months.” Overall, disease management was associated with improved quality of life, lower risk of hospitalization, and improved exercise capacity.

ROLE OF SURVEILLANCE

Although there have been a number of investigations of outcome-specific data for COPD, there is no U.S. surveillance system that is characterized by data collection, analysis, and interpretation that is ongoing and systematic. Apart from the use of vital statistics for describing mortality from COPD, the use of other data sources to examine COPD-specific outcome data has been a relatively recent phenomenon. Moreover, concerns about the available outcome measures and data limitations (discussed in greater detail below) may contribute to delays in progress (Heffner et al., 2010). Therefore, there has been limited time for dissemination and consensus about results, with little opportunity to link these results to planning, implementation, and evaluation of public health and clinical programs to improve COPD prevention and control.

Data relevant to surveillance of COPD are currently available from a number of national and international sources. In the United States, these sources include vital statistics (Lewis et al., 2009), hospital data reporting (http://www.healthgrades.com; Lindenauer et al., 2006), Medicare (Wennberg et al., 2004; http://www.hospitalcompare.hhs.gov), Medicaid (Bindman et al., 2008), Veterans Administration (Joo et al.. 2007, 2008a; Singh, 2009), population-based surveys (Mannino et al., 2000), and health insurance claims databases (Mapel et al., 2006; McKnight et al., 2005). Examples of international sources of COPD surveillance have been published from meta-analyses of clinical trials (Puhan et al., 2009a,b; Strassmann et al., 2009), the U.K. General Practice Research Database (Khan et al., 2010; Levy et al., 2007; Smith et al., 2008; Soriano et al., 2001), and health administrative data in Canada (Gershon et al., 2009).

Available evidence supports the feasibility of these data sources for surveillance and suggests potential opportunities for their use to guide public health policy and other interventions to improve various components

of prevention and healthcare delivery for COPD. For example, Wennberg and colleagues (2004) used Medicare claims data for more than 90,000 patients with COPD, congestive heart failure, and cancer to examine patterns of care at the hospital level, including length of stay, intensive care unit (ICU) days, and physician visits. They found wide variation in healthcare use, ranging from 2.9 to 7.3 times the number of hospital or ICU days used between the lowest and highest use hospitals, respectively. These results suggest the potential for large opportunities to improve efficiency of care.

A number of other recent examples show potential uses of these data sources in a surveillance system for COPD. U.S. examples include:

• use of state Medicaid claims data to identify COPD patients with high healthcare use to target for case management (Yarger et al., 2008),
• use of Medicare claims to identify patient and physician characteristics associated with potentially preventable hospitalizations (O’Malley et al., 2007),
• use of Medicare managed-care data to examine cost of illness and comorbidities (Menzin et al., 2008) and monitoring trends in quality-of-care and healthcare disparities (Trivedi et al., 2005),
• use of Medicaid (Rascati et al., 2007) and Medicare managed-care (Simoni-Wastila et al., 2009) claims data to examine comparative effectiveness of different inhaled medications for COPD,
• voluntary reporting of hospital data for comparative effectiveness research of corticosteroid dose and route of administration during exacerbation of COPD (Lindenauer et al., 2010), and
• use of data on variations in preventable hospitalization rates for COPD and other chronic conditions to target continuing medical education topics (Sumner et al., 2008).

International examples of surveillance activities relevant to COPD have been conducted to monitor quality of primary care and drug safety. In the United Kingdom, the Health Improvement Network was used to demonstrate improvement of spirometry use and combination inhaler use among primary care physicians after release of management guidelines and pay-for-performance incentives (Smith et al., 2008). In another analysis using data from 7,456 general practices in the United Kingdom, higher levels of nurse staffing were associated with improved performance on a number of clinical performance measures for COPD, coronary heart disease, hypertension, and diabetes (Griffiths et al., 2010). Furthermore, surveillance has been conducted to monitor the safety of pharmacological treatments for COPD, albeit with conflicting results (Jara et al., 2007; Johansson et al., 2010; Lee et al., 2008, 2009; Loke et al., 2010; Pujades-Rodriguez et al., 2007; Salpeter, 2009).

A major goal of surveillance is to promote interventions for the prevention and control of COPD, and to evaluate the effectiveness of these interventions through ongoing surveillance of various process and health outcomes. This process may happen at the national, regional, and local levels. Although hospitals do not report quality-of-care indicators for COPD to the Joint Commission and the Centers for Medicare & Medicaid Services—they do for acute myocardial infarction, heart failure, and pneumonia—limited evidence suggests that such reporting, with quarterly feedback on performance to hospitals, has been associated with performance improvement (Jha et al., 2005; Williams et al., 2005). Despite the lack of national reporting, the reporting and feedback process for other diseases may be contributing to a growing interest in local performance improvement initiatives for COPD (Deprez et al., 2009; Roberts et al., 2009).

While a number of data sources for surveillance of COPD are available as discussed above and throughout the chapter, there is no comprehensive surveillance system that contributes to the prevention and control of COPD. Except for the COPD optional module in Behavioral Risk Factor Surveillance System (BRFSS) and some data collected by NHANES, most available data sources have been one-time investigations and are not part of a larger system that is ongoing. However, because these data sources provide evidence of the feasibility and potential usefulness for enhanced surveillance and decision making, they could serve as the basis for developing a system of COPD surveillance. A summary of the current state of surveillance relevant to the primary, secondary, and tertiary prevention of COPD follows.

In terms of primary prevention, cigarette smoking is the major risk factor for COPD. This factor is regularly monitored population-wide through the BRFSS. However, there is no population-based monitoring of other risk factors for COPD such as occupations that expose workers to high levels of dust.

Identifying individuals early in the course of their disease is important to secondary prevention efforts. Although current evidence suggests that widespread screening with spirometry is not effective, this nevertheless remains an important consideration. An analogy to the cardiovascular diseases is identification of increased cholesterol levels, which predict cardiovascular disease. These elevated levels can be followed and targeted for specific interventions. COPD does not, at this point, have such a biomarker available, although several candidates, such as C-reactive protein, fibrinogen, and radiographic changes, are currently being investigated. Filling this gap would result in a better understanding of disease progression and give an additional means of monitoring progression, both in individuals and the population. This may become more important in future years as the prevalence of smoking decreases and the other risk factors for COPD become more important.

The major gap in the surveillance of COPD for tertiary prevention is the lack of pulmonary function data in most databases, which contributes to misdiagnosis. When these data do exist, they may not be accessible or may be in a format that is not easily usable in surveillance activities. Moreover, the underutilization of spirometry in the diagnosis of COPD results in sub-optimal management. To address this gap, the Center for Medicare and Medicaid Services has proposed spirometry evaluation as an indicator of quality of care for patients with a diagnosis of COPD, along with bronchodilator therapy based on FEV1 level and smoking cessation counseling (Berwick, 2011). This policy should contribute to an improvement in the current gaps in diagnosis and management of patients with COPD.

Another gap is the lack or heterogeneity of other objective measures of COPD, such as imaging information, that can better define the presence of bronchial wall thickening or emphysema and are predictors of poor outcomes. Current studies, such as COPDGene, MESA COPD, and Spiromics, will be addressing the scientific aspect of these gaps, such as what may be the best imaging measures to follow over time. Additional studies are needed to assess whether these measures can be routinely used in the clinical evaluation of patients. Filling these gaps would result in a better picture of the true burden of disease and how COPD relates to morbidity and mortality in the population.

The available evidence provides strong support for the feasibility and potential usefulness of a national surveillance system for COPD. A number of limitations, however, need to be considered and addressed to fully realize the benefits of surveillance. As previously discussed, the diagnosis of COPD is under- and overdiagnosed, which limits the usefulness of diagnostic codes from administrative data. While the specificity of diagnostic algorithms show promise for selected applications (Mapel et al., 2006; Yarger et al., 2008), their sensitivity and positive predictive value for COPD are low (Rector et al., 2004; Singh, 2009). Moreover, variations in patterns of diagnostic practices may further bias claims data (Song et al., 2010). A major gap in the surveillance of COPD is the relative paucity of and scant evidence for the effectiveness of COPD-specific performance measures that are currently in use (Heffner et al., 2010). For example, Medicare process performance measures are not strongly associated with hospital risk-adjusted mortality rates (Werner and Bradlow, 2006).

In summary, while components of a surveillance system for COPD are available in the United States and have provided evidence of the need for improvement of the prevention and control of COPD, the committee concluded that further development is needed to create an effective surveillance system. Such development will require the participation of experts from a variety of disciplines to address the important limitations described above. Effectiveness will be determined by the quality of the data; the ongoing, systematic collection, analysis, and interpretation of the data; and the ongoing use of the results to plan and implement prevention and control interventions. None of these characteristics currently exist in the United States for the surveillance of COPD. As previously discussed, the quality of data needs to be improved, with standards for diagnosis to minimize diagnostic misclassification and better COPD-specific outcome data (Heffner et al., 2010). While a number of data sources have been used to examine outcomes, most analyses conducted to date have been one-time studies, and there is no structured or systematic use of these sources for ongoing analyses. Finally, health policy advocates and federal and private institutions in the United States need more well-defined organizational structures and processes for disseminating and using the results from chronic disease surveillance in order to enhance the prevention and control of COPD.

The focus of this chapter has been on COPD, yet the same kinds of data (e.g., those related to risk factors, screening, environmental exposures, availability of care, access to care, patient education, treatments, quality of life, etc.) are needed for other chronic lung diseases, including asthma. In fact, collection of these data on asthma, for example, could lead to improved understanding of the relationship between asthma and COPD. This has

important implications not only for improved understanding of the pathophysiology of both diseases but also for improved understanding of corresponding health disparities. An effective surveillance system that encompasses chronic lung disease more broadly could enhance efforts aimed at prevention, diagnosis, treatment, and improved health outcomes.

REFERENCES

Abusaid, G. H., A. Barbagelata, E. Tuero, A. Mahmood, and G. Sharma. 2009. Diastolic dysfunction and COPD exacerbation. Postgraduate Medicine 121(4):76-81.

Adams, S. G., P. K. Smith, P. F. Allan, A. Anzueto, J. A. Pugh, and J. E. Cornell. 2007. Systematic review of the chronic care model in chronic obstructive pulmonary disease prevention and management. Archives of Internal Medicine 167(6):551-561.

Agabiti, N., V. Belleudi, M. Davoli, F. Forastiere, A. Faustini, R. Pistelli, D. Fusco, and C. A. Perucci. 2010. Profiling hospital performance to monitor the quality of care: The case of COPD. European Respiratory Journal 35(5):1031-1038.

Alexeeff, S. E., A. A. Litonjua, D. Sparrow, P. S. Vokonas, and J. Schwartz. 2007. Statin use reduces decline in lung function: VA normative aging study. American Journal of Respiratory and Critical Care Medicine 176(8):742-747.

American Thoracic Society. 1999. Pulmonary rehabilitation—1999. American Journal of Respiratory and Critical Care Medicine 159(5):1666-1682.

Anthonisen, N. R., M. A. Skeans, R. A. Wise, J. Manfreda, R. E. Kanner, and J. E. Connett, for the Lung Health Study Research Group. 2005a. The effects of a smoking cessation intervention on 14.5-year mortality. Annals of Internal Medicine 142(4):233-239.

Anthonisen, N. R., K. Woodlrage, and J. Manfreda. 2005b. Use of spirometry and respiratory drugs in Manitobans over 35 years of age with obstructive lung diseases. Canadian Respiratory Journal 12(2):69-74.

Antonelli-Incalzi, R., A. Corsonello, L. Trojano, C. Pedone, D. Acanfora, A. Spada, O. Izzo, and F. Rengo. 2007. Screening of cognitive impairment in chronic obstructive pulmonary disease. Dementia and Geriatric Cognitive Disorders 23(4):264-270.

Avol, E. L., W. J. Gauderman, S. M. Tan, S. J. London, and J. M. Peters. 2001. Respiratory effects of relocating to areas of differing air pollution levels. American Journal of Respiratory and Critical Care Medicine 164(11):2067-2072.

Ayanian, J. Z. 2009. The elusive quest for quality and cost savings in the Medicare program. JAMA: The Journal of the American Medical Association 301(6):668-670.

Bahadori, K., and J. M. FitzGerald. 2007. Risk factors of hospitalization and readmission of patients with COPD exacerbation—systematic review. International Journal of Chronic Obstructive Pulmonary Disease 2(3):241-251.

Barr, R. G., B. R. Celli, F. J. Martinez, A. L. Ries, S. I. Rennard, J. J. Reilly, F. C. Sciurba, B. M. Thomashow, and R. A. Wise. 2005. Physician and patient perceptions in COPD: The COPD resource network needs assessment survey. The American Journal of Medicine 118(12):1415.e1419-1415.e1417.

Berwick, D. M. 2011. Launching accountable care organizations—the proposed rule for the Medicare shared savings program. New England Journal of Medicine 364(16):e32.

Bickford, L. S., J. E. Hodgkin, and S. L. McInturff. 1995. National pulmonary rehabilitation survey update. Journal of Cardiopulmonary Rehabilitation and Prevention 15(6):406-411.

Bindman, A. B., A. Chattopadhyay, and G. M. Auerback. 2008. Interruptions in Medicaid coverage and risk for hospitalization for ambulatory care-sensitive conditions. Annals of Internal Medicine 149(12):854-860.

Bourbeau, J., D. Nault, and T. Dang-Tan. 2004. Self-management and behaviour modification in COPD. Patient Education and Counseling 52(3):271-277.

Boyd, C. M., J. Darer, C. Boult, L. P. Fried, L. Boult, and A. W. Wu. 2005. Clinical practice guidelines and quality of care for older patients with multiple comorbid diseases. JAMA: The Journal of the American Medical Association 294(6):716-724.

Brooks, D., R. Sottana, B. Bell, M. Hanna, L. Laframboise, S. Selvanayagarajah, and R. Goldstein. 2007. Characterization of pulmonary rehabilitation programs in Canada in 2005. Canadian Respiratory Journal 14(2):87-92.

Buist, A. S., M. A. McBurnie, W. M. Vollmer, S. Gillespie, P. Burney, D. M. Mannino, A. M. B. Menezes, S. D. Sullivan, T. A. Lee, K. B. Weiss, R. L. Jensen, G. B. Marks, A. Gulsvik, and E. Nizankowska-Mogilnicka. 2007. International variation in the prevalence of COPD (The BOLD Study): A population-based prevalence study. The Lancet 370(9589):741-750.

CDC (Centers for Disease Control and Prevention). 2008. Deaths from chronic obstructive pulmonary disease—United States, 2000-2005. MMWR: Morbidity and Mortality Weekly Report 57(45):1229-1232.

Celli, B. R., R. J. Halbert, S. Isonaka, and B. Schau. 2003. Population impact of different definitions of airway obstruction. European Respiratory Journal 22(2):268-273.

Celli, B. R., C. G. Cote, J. M. Marin, C. Casanova, M. Montes de Oca, R. A. Mendez, V. Pinto Plata, and H. J. Cabral. 2004a. The body-mass index, airflow obstruction, dyspnea, and exercise capacity index in chronic obstructive pulmonary disease. New England Journal of Medicine 350(10):1005-1012.

Celli, B. R., W. MacNee, A. Agusti, A. Anzueto, B. Berg, A. S. Buist, P. M. A. Calverley, N. Chavannes, T. Dillard, B. Fahy, A. Fein, J. Heffner, S. Lareau, P. Meek, F. Martinez, W. McNicholas, J. Muris, E. Austegard, R. Pauwels, S. Rennard, A. Rossi, N. Siafakas, B. Tiep, J. Vestbo, E. Wouters, and R. ZuWallack. 2004b. Standards for the diagnosis and treatment of patients with COPD: A summary of the ATS/ERS position paper. European Respiratory Journal 23(6):932-946.

Chavez, P. C., and N. K. Shokar. 2009. Diagnosis and management of chronic obstructive pulmonary disease (COPD) in a primary care clinic. COPD 6(6):446-451.

Craig, B., C. Kraus, B. Chewning, and J. Davis. 2008. Quality of care for older adults with chronic obstructive pulmonary disease and asthma based on comparisons to practice guidelines and smoking status. BMC Health Services Research 8(1):144.

Crapo, R. O., R. Casaburi, A. L. Coates, P. L. Enright, J. L. Hankinson, C. G. Irvin, N. R. MacIntyre, R. T. McKay, J. S. Wanger, S. D. Anderson, D. W. Cockcroft, J. E. Fish, and P. J. Sterk. 2000. Guidelines for methacholine and exercise challenge testing—1999. This official statement of the American Thoracic Society was adopted by the ATS board of directors, July 1999. American Journal of Respiratory and Critical Care Medicine 161(1):309-329.

Davis, A. H. T., V. Carrieri-Kohlman, S. L. Janson, W. M. Gold, and M. S. Stulbarg. 2006. Effects of treatment on two types of self-efficacy in people with chronic obstructive pulmonary disease. Journal of Pain and Symptom Management 32(1):60-70.

Decramer, M., S. Rennard, T. Troosters, D. W. Mapel, N. Giardino, D. Mannino, E. Wouters, S. Sethi, and C. B. Cooper. 2008. COPD as a lung disease with systemic consequences—clinical impact, mechanisms, and potential for early intervention. COPD 5(4):235-256.

Deprez, R., A. Kinner, P. Millard, L. Baggott, J. Mellett, and J. L. Loo. 2009. Improving quality of care for patients with chronic obstructive pulmonary disease. Population Health Management 12(4):209-215.

Di Bari, M., M. Chiarlone, D. Matteuzzi, S. Zacchei, C. Pozzi, V. Bellia, F. Tarantini, R. Pini, G. Masotti, and N. Marchionni. 2004. Thoracic kyphosis and ventilatory dysfunction in unselected older persons: An epidemiological study in Dicomano, Italy. Journal of the American Geriatrics Society 52(6):909-915.

Diette, G. B., P. Orr, M. C. McCormack, W. Gandy, and B. Hamar. 2010. Is pharmacologic care of chronic obstructive pulmonary disease consistent with the guidelines? Population Health Management 13(1):21-26.

Disano, J., J. Goulet, N. Muhajarine, C. Neudorf, and J. Harvey. 2010. Social-economic status and rates of hospital admission for chronic disease in urban Canada. Canadian Nurse 106(1):24-29.

Donaldson, G. C., J. R. Hurst, C. J. Smith, R. B. Hubbard, and J. A. Wedzicha. 2010. Increased risk of myocardial infarction and stroke following exacerbation of COPD. Chest 137(5):1091-1097.

Downs, S. H., C. Schindler, L. J. Liu, D. Keidel, L. Bayer-Oglesby, M. H. Brutsche, M. W. Gerbase, R. Keller, N. Kunzli, P. Leuenberger, N. M. Probst-Hensch, J. M. Tschopp, J. P. Zellweger, T. Rochat, J. Schwartz, and U. Ackermann-Liebrich. 2007. Reduced exposure to pm10 and attenuated age-related decline in lung function. New England Journal of Medicine 357(23):2338-2347.

Effing, T., E. M. Monninkhof, P. D. van der Valk, J. van der Palen, C. L. van Herwaarden, M. R. Partidge, E. H. Walters, and G. A. Zielhuis. 2007. Self-management education for patients with chronic obstructive pulmonary disease. Cochrane Database Systematic Reviews(4):CD002990.

Epping-Jordan, J. E., S. D. Pruitt, R. Bengoa, and E. H. Wagner. 2004. Improving the quality of health care for chronic conditions. Quality and Safety in Health Care 13(4):299-305.

Ezzati, M., and A. D. Lopez. 2003. Estimates of global mortality attributable to smoking in 2000. The Lancet 362(9387):847-852.

FitzGerald, J. M., J. M. Haddon, C. Bradly-Kennedy, L. Kuramoto, and G. T. Ford. 2007. Resource use study in COPD (rusic): A prospective study to quantify the effects of COPD exacerbations on health care resource use among COPD patients. Canadian Respiratory Journal 14(3):145-152.

Frost, F. J., H. Petersen, K. Tollestrup, and B. Skipper. 2007. Influenza and COPD mortality protection as pleiotropic, dose-dependent effects of statins*. Chest 131(4):1006-1012.

Garcia-Aymerich, J., P. Lange, M. Benet, P. Schnohr, and J. M. Anto. 2007. Regular physical activity modifies smoking-related lung function decline and reduces risk of chronic obstructive pulmonary disease: A population-based cohort study. American Journal of Respiratory and Critical Care Medicine 175(5):458-463.

Gauderman, W. J., G. F. Gilliland, H. Vora, E. Avol, D. Stram, R. McConnell, D. Thomas, F. Lurmann, H. G. Margolis, E. B. Rappaport, K. Berhane, and J. M. Peters. 2002. Association between air pollution and lung function growth in southern California children: Results from a second cohort. American Journal of Respiratory and Critical Care Medicine 166(1):76-84.

Gershon, A. S., C. Wang, J. Guan, J. Vasilevska-Ristovska, L. Cicutto, and T. To. 2009. Identifying individuals with physician diagnosed COPD in health administrative databases. COPD 6(5):388-394.

Gibson, P. G., and J. L. Simpson. 2009. The overlap syndrome of asthma and COPD: What are its features and how important is it? Thorax 64(8):728-735.

Goodman, P., M. Agnew, M. McCaffrey, G. Paul, and L. Clancy. 2007. Effects of the Irish smoking ban on respiratory health of bar workers and air quality in Dublin pubs. American Journal of Respiratory and Critical Care Medicine 175(8):840-845.

Griffith, K. A., D. L. Sherrill, E. M. Siegel, T. A. Manolio, H. W. Bonekat, and P. L. Enright. 2001. Predictors of loss of lung function in the elderly: The cardiovascular health study. American Journal of Respiratory and Critical Care Medicine 163(1):61-68.

Griffiths, P., T. Murrells, J. Maben, S. Jones, and M. Ashworth. 2010. Nurse staffing and quality of care in UK general practice: Cross-sectional study using routinely collected data. British Journal of General Practice 60:e36-e48.

Griffiths, T. L., C. J. Phillips, S. Davies, M. L. Burr, and I. A. Campbell. 2001. Cost effectiveness of an outpatient multidisciplinary pulmonary rehabilitation programme. Thorax 56(10):779-784.

Han, M. K., M. G. Kim, R. Mardon, P. Renner, S. Sullivan, G. B. Diette, and F. J. Martinez. 2007. Spirometry utilization for COPD: How do we measure up? Chest 132(2):403-409.

Heffner, J. E., R. A. Mularski, and P. M. Calverley. 2010. COPD performance measures: Missing opportunities for improving care. Chest 137(5):1181-1189.

Hernandez, P., M. Balter, J. Bourbeau, and R. Hodder. 2009. Living with chronic obstructive pulmonary disease: A survey of patients’ knowledge and attitudes. Respiratory Medicine 103(7):1004-1012.

HHS (U.S. Department of Health and Human Services). 2004. The health consequences of smoking: A report of the surgeon general. Atlanta, GA: US Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health.

Holguin, F., E. Folch, S. C. Redd, and D. M. Mannino. 2005. Comorbidity and mortality in COPD-related hospitalizations in the United States, 1979 to 2001*. Chest 128(4):2005-2011.

Howard, D. L., F. B. Hakeem, C. Njue, T. Carey, and Y. Jallah. 2007. Racially disproportionate admission rates for ambulatory care sensitive conditions in North Carolina. Public Health Reports 122(3):362-372.

Hu, Y., B. Chen, Z. Yin, L. Jia, Y. Zhou, and T. Jin. 2006. Increased risk of chronic obstructive pulmonary diseases in coke oven workers: Interaction between occupational exposure and smoking. Thorax 61(4):290-295.

Hung, W. W., J. P. Wisnivesky, A. L. Siu, and J. S. Ross. 2009. Cognitive decline among patients with chronic obstructive pulmonary disease. American Journal of Respiratory and Critical Care Medicine 180(2):134-137.

Jara, M., S. F. Lanes, C. Wentworth, 3rd, C. May, and S. Kesten. 2007. Comparative safety of long-acting inhaled bronchodilators: A cohort study using the UK thin primary care database. Drug Safety 30(12):1151-1160.

Jha, A. K., Z. Li, E. J. Orav, and A. M. Epstein. 2005. Care in U.S. hospitals—the hospital quality alliance program. New England Journal of Medicine 353(3):265-274.

Johansson, S., M. A. Wallander, F. J. de Abajo, and L. A. Garcia Rodriguez. 2010. Prospective drug safety monitoring using the UK primary-care general practice research database: Theoretical framework, feasibility analysis and extrapolation to future scenarios. Drug Safety 33(3):223-232.

Jones, R., M. Dickson-Spillmann, M. Mather, D. Marks, and B. Shackell. 2008. Accuracy of diagnostic registers and management of chronic obstructive pulmonary disease: The Devon primary care audit. Respiratory Research 9(1):62.

Joo, M. J., T. A. Lee, and K. B. Weiss. 2007. Geographic variation in chronic obstructive pulmonary disease exacerbation rates. Journal of General Internal Medicine 22(11):1560-1565.

Joo, M. J., T. A. Lee, D. H. Au, M. L. Fitzgibbon, and K. B. Weiss. 2008a. Medication use patterns associated with spirometry in diagnosing COPD. COPD 5(6):360-368.

Joo, M. J., T. A. Lee, B. Bartle, W. B. van de Graaff, and K. B. Weiss. 2008b. Patterns of healthcare utilization by COPD severity: A pilot study. Lung 186(5):307-312.

Joo, M. J., T. A. Lee, and K. B. Weiss. 2008c. Geographic variation of spirometry use in newly diagnosed COPD. Chest 134(1):38-45.

Katz, P. P., L. J. Julian, T. A. Omachi, S. E. Gregorich, M. D. Eisner, E. H. Yelin, and P. D. Blanc. 2010. The impact of disability on depression among individuals with COPD. Chest 137(4):838-845.

Keddissi, J. I., W. G. Younis, E. A. Chbeir, N. N. Daher, T. A. Dernaika, and G. T. Kinasewitz. 2007. The use of statins and lung function in current and former smokers*. Chest 132(6):1764-1771.

Khan, N. F., S. E. Harrison, and P. W. Rose. 2010. Validity of diagnostic coding within the general practice research database: A systematic review. British Journal of General Practice 60(572):e128-136.

Kochanek, K., J. Xu, S. Murphy, A. Minnino, and H. Kung. 2011. Deaths: Preliminary data for 2009. National Vital Statistics Reports 59(4).

Kohler, D., J. Fischer, F. Raschke, and B. Schonhofer. 2003. Usefulness of GOLD classification of COPD severity. Thorax 58(9):825.

Kronman, A. C., A. S. Ash, K. M. Freund, A. Hanchate, and E. J. Emanuel. 2008. Can primary care visits reduce hospital utilization among Medicare beneficiaries at the end of life? Journal of General Internal Medicine 23(9):1330-1335.

Kubzansky, L. D., R. J. Wright, S. Cohen, S. Weiss, B. Rosner, and D. Sparrow. 2002. Breathing easy: A prospective study of optimism and pulmonary function in the normative aging study. Annals of Behavioral Medicine 24(4):345-353.

Lacasse, Y., R. Goldstein, T. J. Lasserson, and S. Martin. 2006. Pulmonary rehabilitation for chronic obstructive pulmonary disease. Cochrane Database Systematic Reviews (4):CD003793.

Laditka, J. N., and S. B. Laditka. 2006. Race, ethnicity and hospitalization for six chronic ambulatory care sensitive conditions in the USA. Ethnicity & Health 11(3):247-263.

Lee, T. A., A. S. Pickard, D. H. Au, B. Bartle, and K. B. Weiss. 2008. Risk for death associated with medications for recently diagnosed chronic obstructive pulmonary disease. Annals of Internal Medicine 149(6):380-390.

Lee, T. A., C. Wilke, M. Joo, K. T. Stroupe, J. A. Krishnan, G. T. Schumock, and A. S. Pickard. 2009. Outcomes associated with tiotropium use in patients with chronic obstructive pulmonary disease. Archives of Internal Medicine 169(15):1403-1410.

Levy, M. L., P. Stephenson, P. Barritt, D. Bellamy, J. Haughney, S. Hilton, S. Holmes, K. Jones, R. Neville, D. Price, D. Ryan, and A. Smith. 2007. The UK general practice airways group (GPIAG): Its formation, development, and influence on the management of asthma and other respiratory diseases over the last twenty years. Primary Care Respiratory Journal 16(3):132-139.

Lewis, D. R., L. X. Clegg, and N. J. Johnson. 2009. Lung disease mortality in the United States: The national longitudinal mortality study. International Journal of Tuberculosis and Lung Disease 13(8):1008-1014.

Lin, K., B. Watkins, T. Johnson, J. A. Rodriguez, and M. B. Barton. 2008. Screening for chronic obstructive pulmonary disease using spirometry: Summary of the evidence for the U.S. Preventive services task force. Annals of Internal Medicine 148(7):535-543.

Lindenauer, P. K., P. Pekow, S. Gao, A. S. Crawford, B. Gutierrez, and E. M. Benjamin. 2006. Quality of care for patients hospitalized for acute exacerbations of chronic obstructive pulmonary disease. Annals of Internal Medicine 144(12):894-903.

Lindenauer, P. K., P. S. Pekow, M. C. Lahti, Y. Lee, E. M. Benjamin, and M. B. Rothberg. 2010. Association of corticosteroid dose and route of administration with risk of treatment failure in acute exacerbation of chronic obstructive pulmonary disease. JAMA: The Journal of the American Medical Association 303(23):2359-2367.

Loke, Y. K., C. S. Kwok, and S. Singh. 2010. Risk of myocardial infarction and cardiovascular death associated with inhaled corticosteroids in COPD. European Respiratory Journal 35(5):1003-1021.

Mannino, D. M., and S. Braman. 2007. The epidemiology and economics of chronic obstructive pulmonary disease. Proceedings of the American Thoracic Society 4(7):502-506.

Mannino, D. M., and A. S. Buist. 2007. Global burden of COPD: Risk factors, prevalence, and future trends. Lancet 370(9589):765-773.

Mannino, D. M., R. C. Gagnon, T. L. Petty, and E. Lydick. 2000. Obstructive lung disease and low lung function in adults in the United States: Data from the national health and nutrition examination survey, 1988-1994. Archives of Internal Medicine 160(11):1683-1689.

Mannino, D. M., D. E. Doherty, and A. Sonia Buist. 2006. Global initiative on obstructive lung disease (GOLD) classification of lung disease and mortality: Findings from the Atherosclerosis Risk in Communities (ARIC) study. Respiratory Medicine 100(1):115-122.

Mapel, D. W., F. J. Frost, J. S. Hurley, H. Petersen, M. Roberts, J. P. Marton, and H. Shah. 2006. An algorithm for the identification of undiagnosed COPD cases using administrative claims data. Journal of Managed Care Pharmacy 12(6):457-465.

McKnight, J., A. Scott, D. Menzies, J. Bourbeau, L. Blais, and C. Lemiere. 2005. A cohort study showed that health insurance databases were accurate to distinguish chronic obstructive pulmonary disease from asthma and classify disease severity. Journal of Clinical Epidemiology 58(2):206-208.

Menzies, D., A. Nair, P. A. Williamson, S. Schembri, M. Z. H. Al-Khairalla, M. Barnes, T. C. Fardon, L. McFarlane, G. J. Magee, and B. J. Lipworth. 2006. Respiratory symptoms, pulmonary function, and markers of inflammation among bar workers before and after a legislative ban on smoking in public places. JAMA: The Journal of the American Medical Association 296(14):1742-1748.

Menzin, J., L. Boulanger, J. Marton, L. Guadagno, H. Dastani, R. Dirani, A. Phillips, and H. Shah. 2008. The economic burden of chronic obstructive pulmonary disease (COPD) in a U.S. Medicare population. Respiratory Medicine 102(9):1248-1256.

Miravitlles, M., C. Murio, G. Tirado-Conde, G. Levy, H. Muellerova, J. B. Soriano, A. Ramirez-Venegas, F. W. Ko, B. Canelos-Estrella, E. Giugno, M. Bergna, I. Cherrez, and A. Anzueto. 2008. Geographic differences in clinical characteristics and management of COPD: The epoca study. International Journal of Chronic Obstructive Pulmonary Disease 3(4):803-814.

Miravitlles, M., J. B. Soriano, F. García-Río, L. Muñoz, E. Duran-Tauleria, G. Sanchez, V. Sobradillo, and J. Ancochea. 2009. Prevalence of COPD in Spain: Impact of undiagnosed COPD on quality of life and daily life activities. Thorax 64(10):863-868.

Monninkhof, E., P. van der Valk, J. van der Palen, C. van Herwaarden, M. R. Partridge, and G. Zielhuis. 2003. Self-management education for patients with chronic obstructive pulmonary disease: A systematic review. Thorax 58(5):394-398.

Mularski, R. A., S. M. Asch, W. H. Shrank, E. A. Kerr, C. M. Setodji, J. L. Adams, J. Keesey, and E. A. McGlynn. 2006. The quality of obstructive lung disease care for adults in the United States as measured by adherence to recommended processes*. Chest 130(6):1844-1850.

National Collaborating Centre for Chronic Conditions. 2004. Chronic obstructive pulmonary disease. National clinical guideline on management of chronic obstructive pulmonary disease in adults in primary and secondary care. Thorax 59 (Suppl) 1:1-232.

Nieuwenhuijsen, E. R., E. Zemper, K. R. Miner, and M. Epstein. 2006. Health behavior change models and theories: Contributions to rehabilitation. Disability and Rehabilitation 28(5):245-256.

O’Malley, A. S., H. H. Pham, D. Schrag, B. Wu, and P. B. Bach. 2007. Potentially avoidable hospitalizations for COPD and pneumonia: The role of physician and practice characteristics. Medical Care 45(6):562-570.

Oostenbrink, J. B., and M. P. M. H. Rutten-van Mölken. 2004. Resource use and risk factors in high-cost exacerbations of COPD. Respiratory Medicine 98(9):883-891.

Peikes, D., A. Chen, J. Schore, and R. Brown. 2009. Effects of care coordination on hospitalization, quality of care, and health care expenditures among Medicare beneficiaries: 15 randomized trials. JAMA: The Journal of the American Medical Association 301(6):603-618.

Pelkonen, M., I.-L. Notkola, T. Lakka, H. O. Tukiainen, P. Kivinen, and A. Nissinen. 2003. Delaying decline in pulmonary function with physical activity: A 25-year follow-up. American Journal of Respiratory and Critical Care Medicine 168(4):494-499.

Peytremann-Bridevaux, I., P. Staeger, P.-O. Bridevaux, W. A. Ghali, and B. Burnand. 2008. Effectiveness of chronic obstructive pulmonary disease-management programs: Systematic review and meta-analysis. American Journal of Medicine 121(5):433-443.e434.

Pitta, F., T. Troosters, M. A. Spruit, V. S. Probst, M. Decramer, and R. Gosselink. 2005. Characteristics of physical activities in daily life in chronic obstructive pulmonary disease. American Journal of Respiratory and Critical Care Medicine 171(9):972-977.

Pope, C. A., M. Ezzati, and D. W. Dockery. 2009. Fine-particulate air pollution and life expectancy in the United States. New England Journal of Medicine 360(4):376-386.

Puhan, M., L. Bachmann, J. Kleijnen, G. ter Riet, and A. Kessels. 2009a. Inhaled drugs to reduce exacerbations in patients with chronic obstructive pulmonary disease: A network meta-analysis. BMC Medicine 7(1):2.

Puhan, M., M. Scharplatz, T. Troosters, E. H. Walters, and J. Steurer. 2009b. Pulmonary rehabilitation following exacerbations of chronic obstructive pulmonary disease. Cochrane Database Systematic Reviews (1):CD005305.

Puhan, M. A., J. Garcia-Aymerich, M. Frey, G. ter Riet, J. M. Antó, A. G. Agustí, F. P. Gómez, R. Rodríguez-Roisín, K. G. M. Moons, A. G. Kessels, and U. Held. 2009c. Expansion of the prognostic assessment of patients with chronic obstructive pulmonary disease: The updated BODE index and the ADO index. The Lancet 374(9691):704-711.

Pujades-Rodriguez, M., C. J. Smith, and R. B. Hubbard. 2007. Inhaled corticosteroids and the risk of fracture in chronic obstructive pulmonary disease. QJM : Monthly Journal of the Association of Physicians 100(8):509-517.

Rabe, K. F., S. Hurd, A. Anzueto, P. J. Barnes, S. A. Buist, P. Calverley, Y. Fukuchi, C. Jenkins, R. Rodriguez-Roisin, C. van Weel, and J. Zielinski. 2007. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: Gold executive summary. American Journal of Respiratory and Critical Care Medicine 176(6):532-555.

Rascati, K. L., M. Akazawa, M. Johnsrud, R. H. Stanford, and C. M. Blanchette. 2007. Comparison of hospitalizations, emergency department visits, and costs in a historical cohort of Texas Medicaid patients with chronic obstructive pulmonary disease, by initial medication regimen. Clinical Therapeutics 29(6):1203-1213.

Rascon-Aguilar, I. E., M. Pamer, P. Wludyka, J. Cury, D. Coultas, L. R. Lambiase, N. S. Nahman, and K. J. Vega. 2006. Role of gastroesophageal reflux symptoms in exacerbations of COPD*. Chest 130(4):1096-1101.

Rector, T. S., S. L. Wickstrom, M. Shah, N. Thomas Greeenlee, P. Rheault, J. Rogowski, V. Freedman, J. Adams, and J. J. Escarce. 2004. Specificity and sensitivity of claims-based algorithms for identifying members of Medicare+choice health plans that have chronic medical conditions. Health Services Research 39(6p1):1839-1858.

Roberts, D. H., G. S. Gilmartin, N. Neeman, J. E. Schulze, S. Cannistraro, L. H. Ngo, M. D. Aronson, and J. W. Weiss. 2009. Design and measurement of quality improvement indicators in ambulatory pulmonary care. Chest 136(4):1134-1140.

Rodriguez-Roisen, R., A. Anzueto, J. Bourbeau, P. M. Calverley, T. de Guia, F. Yoshinosuke, D. S. C. Hui, C. Jenkins, A. Kocabas, F. Martinez, M. Montes de Oca, C. van Weel, and J. Vestbo. 2009. Global initiative for chronic obstructive lung disease. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease (updated 2009). http://www.goldcopd.com/download.asp?intId=554 (accessed July 7, 2010).

Rothberg, M. B., P. S. Pekow, M. Lahti, O. Brody, D. J. Skiest, and P. K. Lindenauer. 2010. Antibiotic therapy and treatment failure in patients hospitalized for acute exacerbations of chronic obstructive pulmonary disease. JAMA: The Journal of the American Medical Association 303(20):2035-2042.

Rutschmann, O. T., J.-P. Janssens, B. Vermeulen, and F. P. Sarasin. 2004. Knowledge of guidelines for the management of COPD: A survey of primary care physicians. Respiratory Medicine 98(10):932-937.

Rutten, F. H., N. P. A. Zuithoff, E. Hak, D. E. Grobbee, and A. W. Hoes. 2010. Beta-blockers may reduce mortality and risk of exacerbations in patients with chronic obstructive pulmonary disease. Archives of Internal Medicine 170(10):880-887.

Salpeter, S. R. 2009. Do inhaled anticholinergics increase or decrease the risk of major cardiovascular events?: A synthesis of the available evidence. Drugs 69(15):2025-2033.

Salvi, S. S., and P. J. Barnes. 2009. Chronic obstructive pulmonary disease in non-smokers. The Lancet 374(9691):733-743.

Schindler, C., D. Keidel, M. W. Gerbase, E. Zemp, R. Bettschart, O. Brandli, M. H. Brutsche, L. Burdet, W. Karrer, B. Knopfli, M. Pons, R. Rapp, L. Bayer-Oglesby, N. Kunzli, J. Schwartz, L.-J. S. Liu, U. Ackermann-Liebrich, T. Rochat, and the SAPALDIA Team. 2009. Improvements in pm10 exposure and reduced rates of respiratory symptoms in a cohort of Swiss adults (SAPALDIA). American Journal of Respiratory and Critical Care Medicine 179(7):579-587.

Schneider, C., S. S. Jick, U. Bothner, and C. R. Meier. 2010a. COPD and the risk of depression. Chest 137(2):341-347.

Schneider, C., U. Bothner, S. S. Jick, and C. R. Meier. 2010b. Chronic obstructive pulmonary disease and the risk of cardiovascular diseases. European Journal of Epidemiology 25(4):253-260.

Shahab, L., M. J. Jarvis, J. Britton, and R. West. 2006. Prevalence, diagnosis and relation to tobacco dependence of chronic obstructive pulmonary disease in a nationally representative population sample. Thorax 61(12):1043-1047.

Simoni-Wastila, L., K. Yang, Hui-wen, C. Blanchette, L. Zhao, J. Qian, and A. A. Dalal. 2009. Hospital and emergency department utilization associated with treatment for chronic obstructive pulmonary disease in a managed-care Medicare population. Current Medical Research and Opinion 25(11):2729-2735.

Simpson, A. C., and G. M. Rocker. 2008. Advanced chronic obstructive pulmonary disease: Rethinking models of care. QJM 101(9):697-704.

Sin, D. D., N. R. Anthonisen, J. B. Soriano, and A. G. Agusti. 2006. Mortality in COPD: Role of comorbidities. European Respiratory Journal 28(6):1245-1257.

Singh, J. A. 2009. Accuracy of Veterans Affairs databases for diagnoses of chronic diseases. Preventing Chronic Disease 6(4):A126.

Smith, C. J. P., J. Gribbin, K. B. Challen, and R. B. Hubbard. 2008. The impact of the 2004 nice guideline and 2003 general medical services contract on COPD in primary care in the UK. QJM 101(2):145-153.

Song, Y., J. Skinner, J. Bynum, J. Sutherland, J. E. Wennberg, and E. S. Fisher. 2010. Regional variations in diagnostic practices. New England Journal of Medicine 363(1):45-53.

Soriano, J. B., W. C. Maier, G. Visick, and N. B. Pride. 2001. Validation of general practitioner-diagnosed COPD in the UK general practice research database. European Journal of Epidemiology 17(12):1075-1080.

Soriano, J. B., G. T. Visick, H. Muellerova, N. Payvandi, and A. L. Hansell. 2005. Patterns of comorbidities in newly diagnosed COPD and asthma in primary care. Chest 128(4):2099-2107.

Søyseth, V., P. H. Brekke, P. Smith, and T. Omland. 2007. Statin use is associated with reduced mortality in COPD. European Respiratory Journal 29(2):279-283.

Stavem, K., L. Sandvik, and J. Erikssen. 2006. Can global initiative for chronic obstructive lung disease stage 0 provide prognostic information on long-term mortality in men? Chest 130(2):318-325.

Strassmann, R., B. Bausch, A. Spaar, J. Kleijnen, O. Braendli, and M. A. Puhan. 2009. Smoking cessation interventions in COPD: A network meta-analysis of randomised trials. European Respiratory Journal 34(3):634-640.

Sumner, W., M. Schootman, P. Asaro, Y. Yan, and M. D. Hagen. 2008. Using county-level public health data to prioritize medical education topics. Journal of Continuing Education in the Health Professions 28(4):197-204.

Svanes, C., J. Sunyer, E. Plana, S. Dharmage, J. Heinrich, D. Jarvis, R. de Marco, D. Norbäck, C. Raherison, S. Villani, M. Wjst, K. Svanes, and J. M. Antó. 2010. Early life origins of chronic obstructive pulmonary disease. Thorax 65(1):14-20.

Trivedi, A. N., A. M. Zaslavsky, E. C. Schneider, and J. Z. Ayanian. 2005. Trends in the quality of care and racial disparities in Medicare managed care. New England Journal of Medicine 353(7):692-700.

Troosters, T., R. Casaburi, R. Gosselink, and M. Decramer. 2005. Pulmonary rehabilitation in chronic obstructive pulmonary disease. American Journal of Respiratory and Critical Care Medicine 172(1):19-38.

van Gestel, Y. R., S. E. Hoeks, D. D. Sin, V. Huzeir, H. Stam, F. W. Mertens, R. T. van Domburg, J. J. Bax, and D. Poldermans. 2009. COPD and cancer mortality: The influence of statins. Thorax 64(11):963-967.

Vestbo, J., and P. Lange. 2002. Can GOLD stage 0 provide information of prognostic value in chronic obstructive pulmonary disease? American Journal of Respiratory and Critical Care Medicine 166(3):329-332.

Vincken, W., J. A. van Noord, A. P. M. Greefhorst, T. A. Bantje, S. Kesten, L. Korducki, and P. J. G. Cornelissen. 2002. Improved health outcomes in patients with COPD during 1 yr’s treatment with tiotropium. European Respiratory Journal 19(2):209-216.

Wennberg, J. E., E. S. Fisher, T. A. Stukel, and S. M. Sharp. 2004. Use of Medicare claims data to monitor provider-specific performance among patients with severe chronic illness. Health Affairs (Millwood) (Suppl):5-18.

Werner, R. M., and E. T. Bradlow. 2006. Relationship between Medicare’s hospital compare performance measures and mortality rates. JAMA: The Journal of the American Medical Association 296(22):2694-2702.

WHO (World Health Organization). 2008. Global strategy for diagnosis, management, and prevention of COPD. http://www.goldcopd.com/Guidelineitem.asp?l1=2&l2=1&intId=989 (accessed February 3, 2008).

Williams, S. C., S. P. Schmaltz, D. J. Morton, R. G. Koss, and J. M. Loeb. 2005. Quality of care in U.S. hospitals as reflected by standardized measures, 2002-2004. New England Journal of Medicine 353(3):255-264.

Wilt, T. J., D. Niewoehner, C. Kim, R. L. Kane, A. Linabery, J. Tacklind, R. Macdonald, and I. Rutks. 2005. Use of spirometry for case finding, diagnosis, and management of chronic obstructive pulmonary disease (COPD). Evidence Report/Technology Assessment (Summary)(121):1-7.

Wong, K. W., F. K. Y. Wong, and M. F. Chan. 2005. Effects of nurse-initiated telephone follow-up on self-efficacy among patients with chronic obstructive pulmonary disease. Journal of Advanced Nursing 49(2):210-222.

Xu, W., J.-P. Collet, S. Shapiro, Y. Lin, T. Yang, R. W. Platt, C. Wang, and J. Bourbeau. 2008. Independent effect of depression and anxiety on chronic obstructive pulmonary disease exacerbations and hospitalizations. American Journal of Respiratory and Critical Care Medicine 178(9):913-920.

Xu, W., J.-P. Collet, S. Shapiro, Y. Lin, T. Yang, C. Wang, and J. Bourbeau. 2010. Negative impacts of unreported COPD exacerbations on health-related quality of life at 1 year. European Respiratory Journal 35(5):1022-1030.

Yarger, S., K. Rascati, K. Lawson, J. Barner, and R. Leslie. 2008. Analysis of predictive value of four risk models in Medicaid recipients with chronic obstructive pulmonary disease in texas. Clinical Therapeutics 30:1051-1057.

Yohannes, A. M., and M. J. Connolly. 2004. Pulmonary rehabilitation programmes in the UK: A national representative survey. Clinical Rehabilitation 18(4):444-449.