(Chest. 2004;126:93S-95S.)
© 2004
American College of Chest Physicians
Similarities and Differences in Asthma and COPD*
The Dutch Hypothesis
Eugene R. Bleecker, MD, FCCP
* From the Center for Human Genomics, Wake Forest University, Winston-Salem, NC.
Correspondence to: Eugene R. Bleecker, MD, FCCP, Center for Human Genomics, Wake Forest University, Medical Center Blvd, Winston-Salem, NC 27157; e-mail: ebleeck{at}wfubmc.edu
COPD represents an increasingly important chronic debilitating illness in the United States and worldwide.1 Approximately 16 million Americans have received a diagnosis of COPD, but this figure may represent a low estimate, since there is evidence of misclassification and underdiagnosis, with COPD remaining undiagnosed by a physician in as many as 30 million individuals. The National Health and Nutrition Examination Survey2 of 16,084 individuals who were > 17 years of age revealed that 25% of white male smokers had evidence of airway obstruction, as documented by an FEV1/FVC ratio of < 70%.3 Even more impressive was that COPD had not been previously diagnosed in 44% of those with an FEV1/FVC ratio of < 50% predicted. Mortality caused by COPD has increased, and this disease has become the fourth leading cause of death in the United States.45 COPD is the only disease among the top 10 causes of death that is increasing in frequency.67 It is anticipated that the prevalence of COPD will continue to increase through the year 2020 and beyond.
There are many factors responsible for the current level of misclassification or underdiagnosis and the apparent increasing prevalence of COPD. These include the following: the latency period between the initiation of cigarette smoking that causes COPD and the actual onset of this disease; the relatively small fraction of smokers who develop COPD; the physiologically and clinically silent nature of COPD during early stages of its development; and finally, the increasing longevity of the overall population due to improved survival from other medical causes that impact the prevalence of a disease that increases with age.
The most common signs and symptoms of COPD are dyspnea on exertion, often accompanied by cough with sputum production and wheezing.4 Many older individuals experience dyspnea on exertion because of deconditioning and obesity. Cough and sputum production is so common in smokers that it may be considered normal. Wheezing occurs frequently, but often is attributed to asthma or a viral respiratory tract infection, leading to a diagnosis of asthma.5 The clinically silent nature of early COPD and the indolent course of the disease allow patients to accommodate their growing disability with lifestyle changes. Therefore, most patients presenting to their health-care provider for symptoms related to their COPD have an FEV1 that is < 50% predicted. In the past, COPD has been defined in terms of irreversible airway obstruction that is progressive over time,8 but, more recently, the fact that patterns of COPD overlap with those of asthma has been recognized.9 In addition, acute and chronic reversibility of airflow obstruction has been recognized to occur in COPD patients. For example, in 1995 the American Thoracic Society stated "it may be impossible to differentiate patients with asthma whose airflow obstruction does not remit completely from persons with chronic bronchitis and emphysema with partially reversible airflow obstruction and bronchial hyperresponsiveness [BHR]."10 Numerous studies1112 have documented the presence of partial reversibility after short-term and long-term bronchodilator administration in patients with COPD. This partial reversibility contrasts with asthma, which traditionally is characterized by variable and reversible airflow obstruction. More recently, current asthma guidelines513 have emphasized that there may be a fixed or irreversible component to airway obstruction in some patients with asthma. Both asthma and COPD appear to share some clinical features. The use of phenotypic characteristics (eg, symptoms, allergy, and BHR) may be useful to differentiate disease characteristics, as well as helpful in understanding the similarities in the development and progression of both obstructive airways diseases. Figure 1
contrasts and compares some of the features of both of these disorders.14
There is increasing scientific and clinical evidence that asthma and COPD share many common origins (ie, epidemiologic characteristics and clinical manifestations), a theory that is known as the Dutch hypothesis. The Dutch hypothesis was first proposed in 1961 by Orie and coworkers.15 Their conclusions were based on a comparison of signs, laboratory findings, treatment responses, and natural history. The three components of this hypothesis are as follows: (1) various forms of obstructive lung disease (OLD) have overlapping clinical features, and defining the specific clinical phenotype with which to characterize obstructive airways disease (eg, symptoms, allergy, and BHR) was proposed by Orie and coworkers15; (2) one form of OLD (asthma) may evolve into another (COPD); and (3) the development of OLD is based on allergy (ie, inflammation) and BHR, and endogenous (host) factors determined by heredity (genes), but is modulated by exogenous (ie, environmental) factors (eg, allergens, infections, smoking, pollution, age, and airway geometry) [Fig 2
].1516 While some concepts of the Dutch hypothesis have been controversial, none of the three components of the hypothesis have been conclusively disproven.15 A comprehensive review of the Dutch hypothesis will provide a useful platform on which to base future approaches in the assessment and therapy of asthma and COPD. This symposium will include a comprehensive discussion of the similarities and differences in the epidemiology, genetics, and pathophysiology of asthma and COPD. These reviews will be complemented with an in-depth discussion of the therapeutic implications of these concepts.
The specific topics that are discussed include the following: the rationale for the Dutch hypothesis: allergy and airway hyperresponsiveness as genetic factors and their interaction with the environment in the development of asthma and COPD; genetics of asthma and COPD: similar results for different phenotypes; the relationship between asthma and COPD: lessons from transgenic mice; physiologic similarities and differences between COPD and asthma; therapeutic responses in asthma and COPD: bronchodilators; therapeutic responses in asthma and COPD: corticosteroids; and treatment implications on morbidity and mortality in COPD.
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Footnotes
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Abbreviations: BHR = bronchial hyperresponsiveness; OLD = obstructive lung disease
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References
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