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Epidemiology, Clinical and Economic Burden, and Natural History of Chronic Obstructive Pulmonary Disease and Asthma
Grant H. Skrepnek, PhD, RPh; and Stan V. Skrepnek, MD

Epidemiology, Clinical and Economic Burden, and Natural History of Chronic Obstructive Pulmonary Disease and Asthma

Grant H. Skrepnek, PhD, RPh; and Stan V. Skrepnek, MD

Chronic obstructive pulmonary disease (COPD) and asthma are conditions that exact a tremendous toll on patients, providers, and society. The substantial increase in the prevalence of both conditions in recent decades has generated sizable concern from both domestic and global perspectives. The underlying characteristics of both conditions involve inflammation of the respiratory tract, although the specific nature and reversibility of these processes differ according to each illness. Within the context of disease management, acute exacerbations are important clinical events that contribute to an increase in morbidity and mortality, and may occur in any patient suffering from the disease. Because these conditions are highly important to clinical practice and healthcare systems, this article will highlight key aspects of epidemiology, burden of illness, and clinical presentation of COPD and asthma. A review of the definition, classification, and natural history is also offered, emphasizing the role of acute exacerbations. In general, the natural history of both COPD and asthma is highly variable and not precisely defined because of their heterogeneous clinical courses. Continued inquiry concerning the epidemiology, etiology, classification, and prognosis of each condition and related exacerbations may offer clinicians improved decision-making information to optimize interventions for affected patient populations.

(Am J Manag Care. 2004;10:S129-S138)

In 2001, approximately 12.1 million adults older than 25 years of age were reportedly diagnosed with chronic obstructive pulmonary disease (COPD) in the United States. Another 24 million presented with impaired lung function that may suggest a marked underdiagnosis of the disease.1,2 COPD has been identified as the fourth leading cause of morbidity and mortality domestically, and projections estimate that the condition will rise globally to be the fifth most common cause for morbidity and the third most frequent cause of mortality by the year 2020.2-4 Asthma is estimated to affect 300 million people worldwide and 11% of the US population. By 2025, 400 million people are expected to suffer from the illness globally.5 In the United States, more than 11 million individuals reported having an asthma attack in 2000; more than 5% were children under 18 years of age.6

The economic burden of COPD is considerable, with direct medical costs in the United States estimated at $18 billion in 2002, and indirect costs associated with morbidity and mortality were approximately $14.1 billion.7 In asthma, direct medical costs were estimated to be $9.4 billion, with indirect costs comprising an additional $4.6 billion.7 Hospital costs are a large single contributor to expenditures in both illnesses. In 2002, costs of hospitalization constituted 40.6% ($7.3 billion) of direct COPD costs and 33.0% ($3.1 billion) of direct asthma costs.7 Prescription drugs constituted 20.6% ($3.7 billion) of direct COPD costs and 39.4% ($3.7 billion) of direct asthma costs.7 Recent findings from The Epidemiological and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR) study have also found a significantly higher burden and resource utilization (eg, higher absenteeism rates, increased healthcare visits) in patients with more severe or difficult-to-treat cases of asthma.8

Exacerbations in COPD and asthma are a primary contributor to morbidity, mortality, and cost of illness in both hospital and outpatient settings.5,9 An estimated 25% of cases presenting in emergency departments for dyspnea have been attributed to COPD-related exacerbations.10 In 2000, 16 million physician office visits and 1.5 million COP-Drelated emergency department visits were reported; 726 000 hospitalizations and 119 000 deaths also occurred secondary to the disease.11,12 Approximately 2 million emergency department visits, 478 000 hospitalizations, and 4400 deaths were attributed to asthma in 1999; 10.8 million physician office visits placed asthma as a primary diagnosis in the same year.6,13,14 Beyond the discussion of the epidemiology and burden of illness, the purpose of this article is to present the definition, classification, clinical presentation, and natural history of COPD, asthma, and related exacerbations in each condition.

Definitions and Classifications

COPD is a disease state characterized by progressive airflow obstruction that is often accompanied by airway hyperreactivity.15 The development of COPD has been suggested to be linked to several systemic sequelae, especially in advanced stages.16,17 Both chronic bronchitis and emphysema are included within the definition of COPD; bronchitis involves a definition relating to clinical presentation (eg, long-term cough or sputum production extending over 3 months for a period of at least 2 years) whereas emphysema centers on the pathology of the lung itself.18 In 2001, chronic bronchitis accounted for 76% (9.2 million) of COPD cases whereas emphysema accounted for 17% (2 million); the remainder involved both conditions.1,19

Following the endorsement of the American Thoracic Society, the National Heart, Lung, and Blood Institute of the National Institutes of Health, and the World Health Organization's (NHLBI/WHO) Global Initiative for Chronic Obstructive Lung Disease (GOLD) identified COPD as "characterized by airflow limitation that is not fully reversible. The airflow limitation is in most cases both progressive and associated with an abnormal inflammatory response of the lungs to noxious particles or gases."20,21 Typical symptomatic manifestations of COPD include cough, increased sputum production, and dyspnea on exertion. Although the condition is often considered to be irreversible because a complete remission of airflow limitation does not typically occur, reversible components may also be present.

COPD is often associated with a history of tobacco smoking and occasionally with a predisposition to respiratory illness in childhood; approximately 10% to 15% of smokers develop the illness.16,22,23 As such, the most critical risk factor of COPD is considered to be smoking, although genetic factors (eg, α1- antitrypsin deficiency) have been linked to the condition.24 In older populations, mucus hypersecretion, respiratory infections, and concomitant cardiovascular conditions (eg, ventricular or atrial arrhythmias) are also of importance in the prognosis of COPD.25 COPD is classified according to severity and often emphasizes pulmonary function based on forced expiratory volume in 1 second (FEV1), although symptoms and other factors are of importance. The staging of COPD offered by GOLD appears in Table 1.21



Asthma is a chronic inflammatory disease wherein airflow obstruction is reversible and bronchial hyperresponsiveness is often manifested symptomatically by increased sputum production, shortness of breath, wheezing, coughing, and chest tightness.26-28 The most universally accepted definition of asthma was proposed by the National Institutes of Health National Asthma Education and Prevention Program (NAEPP) at the NHLBI and has been subsequently used by the NHLBI/WHO Global Initiative for Asthma (GINA):

"Asthma is a chronic inflammatory disorder of the airways in which many cells and cellular elements play a role, in particular, mast cells, eosinophils, T lymphocytes, neutrophils, and epithelial cells. In susceptible individuals, this inflammation causes recurrent episodes of wheezing, breathlessness, chest tightness, and cough, particularly at night and in early morning. These episodes are usually associated with widespread but variable airflow obstruction that is often reversible either spontaneously or with treatment. The inflammation also causes an associated increase in the existing bronchial hyperresponsiveness to a variety of stimuli."26,27

Asthma often develops in childhood, although adult onset is not infrequent, especially because of occupational exposure to potential irritants. In children, risk factors for asthma have been identified as wheezing not related to rhinovirus infection, male sex, parenteral history of asthma, atopy, obesity, peripheral eosinophilia, severe infections of the lower respiratory tract, and increased serum immunoglobulin E (IgE).29,30 Key risk factors for asthma in adults include cigarette smoking, rhinitis, atopy, family history of asthma, and female sex.30 The susceptibility to asthma that may be attributable to genetic predisposition has been estimated to be as high as half of all cases.31

The classification of asthma is based on severity, which considers general symptoms (eg, intermittent, long term), nighttime symptoms, and pulmonary function. NAEPP uses the following schema relating to stepwise therapy, beginning with the mildest forms and building in terms of severity: Step 1–Mild intermittent; Step 2–Mild persistent; Step 3–Moderate persistent; and Step 4–Severe persistent.6,27 Specific cases of asthma may also be described as seasonal, allergic, nocturnal, or cough variant and may involve exercise-induced bronchospasm.6,27 Further classification may include an indicator of the severity of an acute exacerbation. Table 2 presents more detailed information concerning the general classification of asthma based on severity that was developed by NAEPP.27



Although COPD and asthma similarly involve airflow limitation and chronic inflammatory processes, the pathophysiology of COPD contrasts with asthma concerning the exact nature of inflammation. The obstruction of airflow in COPD occurs secondary to hypertrophy of smooth muscle, decreased elastic recoil pressure in emphysema, and peribronchiolar fibrosis.19 The presence of neutrophils, macrophages, and CD8+ T lymphocytes is considered to be of primary importance in COPD.32 In contrast, asthma predominantly involves eosinophils, mast cells, and CD4+-related mechanisms; IgE antibodies play a key role in immune responses associated with asthma.33

Exacerbations

An exacerbation is a clinical event of both COPD and asthma that may result in hospitalizations, treatment within intensive care units, or death. Although these episodes are most commonly associated with uncontrolled or severe conditions, all individuals with COPD or asthma are at risk.34 To illustrate the morbidity and mortality associated with exacerbations in COPD, patients with an FEV1 below 50% predicted (ie, moderate-to-severe COPD) have been reported to experience 1 to 2 exacerbations on a yearly basis.35,36 Furthermore, exacerbations in COPD worsen the natural history of disease and lower quality of life to a greater degree than the accompanied decreased lung function based on clinical function parameters.36-38 Complete recovery in pulmonary function does not occur quickly, with an estimated 25% of patients reported not to have regained preexacerbation lung function 35 days after the event, and approximately half of patients have been found to be readmitted within 6 months after discharge.39-41 Although many investigations have found inpatient mortality rates associated with COPD exacerbations to be between 2.5% and 4%, GOLD has reported an overall rate of 10%, which increases to 40% in 1 year.21,42 In patients older than 65 years of age, the 1-year mortality rate has been observed to be as high as 59%.43 In emergency departments in the United States, asthma constitutes the eleventh most diagnosed condition, and mortality for acute asthma in intensive care settings was found in one investigation to be as high as 22%, although rates are most often observed to be between 0% and 6%.44-46

 
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