- Email: [email protected]
Asthma and COPD
ARTICLE IN PRESS
Experimental and Toxicologic Pathology 57 (2006) S2, 35–40
EXPERIMENTAL ANDTOXICOLOGIC PATHOLOGY www.elsevier.de/etp
Asthma and COPD Tobias Weltea, David A. Groneberga,b, a
Department of Respiratory Medicine, Hannover Medical School, Carl-Neuberg-Straße 1, 30625 Hannover, Germany Allergy-Centre-Charite´, Charite´ School of Medicine, Free University and Humboldt University, Augustenburger Platz 1/OR-1, 13353 Berlin, Germany b
Received 21 October 2005; accepted 16 February 2006
Abstract The two obstructive airway diseases bronchial asthma and chronic obstructive pulmonary disease (COPD) represent major global causes of disability and death, and COPD is estimated to become the third most common cause of death by 2020. The structural and pathophysiologic findings in both diseases appear to be easily differentiated in the extremes of clinical presentation. However, a significant overlap may exist in individual patients regarding features such as airway wall thickening on computer tomography or reversibility and airway hyperresponsiveness in lung function tests. Airway inflammation differs between the two diseases. In bronchial asthma, airway inflammation is characterized in most cases by an increased number of activated T-lymphocytes, particularly CD4+ Th2 cells, and sometimes eosinophils and mast cells. The most notable difference of chronic severe asthma compared with mild to moderate asthma is an increased number of neutrophils. In stable COPD, airway inflammation is characterized by an increased number of T-lymphocytes, particularly CD8+ T cells, macrophages and neutrophils. With the progression of the disease severity, macrophage and neutrophil numbers increase. Although there may be a partial overlap between asthma and COPD in some patients, the differences in functional, structural and pharmacological features clearly demonstrate the consensus that asthma and COPD are different diseases along all their stages of severity. r 2006 Elsevier GmbH. All rights reserved. Keywords: Airways; Asthma; COPD; Drug; Inflammation; Lung; Therapy
Introduction The two airway diseases bronchial asthma and chronic obstructive pulmonary disease (COPD) are chronic conditions that exact an enormous toll on patients, healthcare providers and the society (Chung Corresponding author. Zentrum Innere Medizin, Abteilung Pneumologie, Medizinische Hochschule Hannover, Carl-NeubergStraße 1, 30625 Hannover, Germany. Tel.: +49 511 532 3530; fax: +49 511 532 3353. E-mail address: [email protected] (D.A. Groneberg).
0940-2993/$ - see front matter r 2006 Elsevier GmbH. All rights reserved. doi:10.1016/j.etp.2006.02.004
et al., 2002). There has been a substantial increase in the prevalence of both diseases in the last decades that has led to sizable concerns being expressed from national and international healthcare authorities. The underlying characteristics of both conditions involve inflammatory changes in the respiratory tract, while the specific nature and the reversibility of these processes largely differ in each entity and disease stage (Table 1). In the context of disease management, acute exacerbations are important clinical events in both illnesses that largely contribute to an increase in mortality and morbidity (Skrepnek and Skrepnek, 2004).
ARTICLE IN PRESS 36
Table 1.
T. Welte, D.A. Groneberg / Experimental and Toxicologic Pathology 57 (2006) S2, 35–40
Phenotype differences between COPD and bronchial asthma
Feature
COPD
Asthma
Limitation of airflow Bronchial hyperresponsiveness Parenchymal integrity Steroid response
Largely irreversible Variable (small) Destruction Varying
Largely reversible Significant Intact Present
COPD The clinical diagnosis of COPD relies on abnormal lung function tests and the patient’s history. COPD is characterized by a largely variable pathology and the molecular mechanisms are not completely understood so far. Therefore, it has been difficult to define a simple disease definition. First approaches based on the epidemiological features of chronic cough and sputum production such as duration of symptoms for 3 months over a period of at least 2 years (chronic bronchitis) or on pathological features such as the identification of emphysema in COPD airway tissue. However, these approaches did not prove to be efficient in the clinical management of the disease. Therefore, important approaches towards a rational disease definition were first reports that related death and disability in COPD to a progressive decrease in the forced expiratory volume in 1 s (FEV1) (Fletcher and Peto, 1977; Peto et al., 1983). Today there is a consensus that the diagnosis of COPD relies on the presence of airflow obstruction defined as decreased FEV1 to FVC (forced vital capacity) or vital capacity ratio. Extending these basic functional features, the GOLD guidelines introduced persistent inflammation and the potential presence of noxious stimuli to the disease definition (Pauwels et al., 2001). Also, a classification of COPD disease severity was defined with five stages from risk group to very severe disease (Table 2). With regard to inhalant noxious stimuli, tobacco smoke is regarded as a major cause, but toxic gases or indoor air pollution may also be regarded as major factors leading to COPD (Pandey, 1984; Perez-Padilla et al., 1996).
Bronchial asthma Bronchial asthma is defined as chronic inflammatory disorder of the airways (Caramori et al., 2005). The chronically inflamed airways of patients with bronchial asthma are hyperresponsive and become obstructed due to bronchoconstriction and mucus hypersecretion (Caramori et al., 2005). Clinically, asthma is characterized by wheezing, breathlessness, chest tightness and coughing particularly at night or in the early morning. Common risk factors of the disease include the exposure to seasonal or perennial allergens including pollens,
Table 2. Inflammatory cell population differences between COPD and bronchial asthma COPD
Asthma
Neutrophils Macrophages CD8-T-lymphocytes Eosinophils (exacerbations)
Eosinophils Mast cells CD4-T-lymphocytes Macrophages, neutrophils
Ranked in relative order of importance.
molds, animal allergens or domestic dust mites. Other risk factors can be tobacco smoke, air pollution, respiratory infections, exercise, occupational irritants, physical and chemical irritants and drugs including aspirin or beta blockers. There is also good evidence of a genetic component in asthma since the disease often occurs in families. The severity of the disease can be intermittent, persistently mild, moderate or severe.
Inflammation Important features of both diseases are ongoing chronic inflammatory processes in the airways as indicated by the current GINA and GOLD guidelines (Pauwels et al., 2001). There are great differences between COPD and bronchial asthma (Groneberg and Chung, 2004): while mast cells and eosinophils represent prominent cell types in allergic diseases such as asthma or atopic dermatitis (Groneberg et al., 2005), the major inflammatory cell types in COPD are different (Table 2) (Saetta et al., 1998). Neutrophils play a crucial role in the pathophysiology of COPD. They release multiple mediators and tissue-degrading enzymes such as elastases that orchestrate tissue destruction and chronic inflammation (Chung, 2001; Stockley, 2002). Neutrophil and macrophage numbers are also increased in bronchoalveolar lavage fluids from cigarette smokers (Hunninghake and Crystal, 1983). COPD patients with a high degree of airflow limitation have a higher level of induced sputum neutrophilia than COPD patients with a milder airflow limitation. In this respect, increased sputum neutrophilia is related to an accelerated decrease in the FEV1 and more prevalent in subjects with the symptoms of chronic cough and sputum production (Stanescu et al., 1996).
ARTICLE IN PRESS T. Welte, D.A. Groneberg / Experimental and Toxicologic Pathology 57 (2006) S2, 35–40
The second major cell type that plays a crucial role in COPD are macrophages (Shapiro, 1999). Similar to neutrophils, they release tissue-degrading enzymes such as matrix metalloproteinases (MMPs). Neutrophils and macrophages communicate with other cells such as airway smooth muscle cells, endothelial cells or sensory neurons, and release inflammatory mediators that propagate the events of bronchoconstriction (O’Byrne and Inman, 2003), airway remodeling (Vignola et al., 2002), and mucus hypersecretion involving the induction of mucin genes (Groneberg et al., 2002b, c, 2003b, 2004c). As in bronchial asthma, lymphocytes are also involved in cellular mechanisms underlying COPD (Majo et al., 2001). However, the T-cell-associated inflammatory processes largely differ from those in allergic asthma, which is characterized by increased numbers of CD4-positive T-lymphocytes (Fabbri et al., 2003; Sutherland and Martin, 2003) (Table 2). In COPD, there are increased numbers of CD8-positive T-lymphocytes present in the airways (Saetta et al., 1999). The degree of airflow obstruction is correlated with the numbers of CD8-positive T-lymphocytes (O’Shaughnessy et al., 1997). In contrast to asthma, eosinophils may only play a major role in acute exacerbations of COPD (Saetta et al., 1994). However, their presence in stable COPD has been shown to be an indicator of steroid responsiveness (Pizzichini et al., 1998; Fujimoto et al., 1999). Features such as mucus hypersecretion, basing on mucin gene induction (Groneberg et al., 2002b, c, 2003b, 2004c; Chung et al., 2004) or chronic cough basing on an increased expression of transient receptor potential vanilloid-1 (VR1 or TRPV1) (Groneberg et al., 2004b), may be found both in bronchial asthma and COPD as well as in other respiratory diseases.
Bronchodilator reversibility One of the main features used to distinguish bronchial asthma from COPD is the acute bronchodilator reversibility of the FEV1. Historically, asthma has been defined as an obstructive disease with bronchodilator reversibility in most patients while definitions of COPD emphasized little or no bronchodilator reversibility. However, there has been increasing evidence in the past few years that COPD patients have a large variability of reversibility that may vary day-to-day (Nisar et al., 1990, p. 457). It can be assumed that acute bronchodilator reversibility may be present in a significant proportion of COPD patients depending on definitions and nature and dosing of drugs (Kerstjens et al., 1993). A problem lies within the lack of clarity concerning the term ‘irreversibility’. This is due to the inappropriate restriction of the bronchodilator reversibility to the
37
FEV1 since the COPD definition also requires an obstructive forced expiratory ratio that is the ratio of the FEV1 to the FVC. A FEV1/FVC ratio of o0.7 is essential for the diagnosis of airway obstruction and it remains o0.7 after bronchodilator use in COPD patients. It is therefore particularly the FEV1/FVC ratio in COPD that is ‘irreversible’ after bronchodilator use (McKenzie et al., 2003). The definition of COPD, diagnosis and severity grading according to spirometric parameters are critical issues that even affect COPD prevalence, burden of disease and the effects of interventions. Recently, a 200% variation in COPD prevalence was reported that resulted from applying different definitions of airway obstruction from widely used guidelines (Celli et al., 2003). Patients with COPD who presented reversibility are often classified as having an ‘asthmatic’ component in contrast to the ‘pure’ or ‘true’ COPD. A serious consequence is that certain therapeutic options may not be taken into consideration for the ‘true COPD’ group. In this respect, small-scaled clinical trials assessing inhaled steroids in COPD and the use of FEV1 as main end-point suggested the commonly held view that inhaled steroids should not be prescribed for patients with COPD with no acute response to inhaled bronchodilators or oral corticosteroids (van Schayck, 2000). In this respect, it is not logic to solely define the disease by its lack of reversibility to bronchodilators while therapeutic studies are then conducted using spirometry as the primary outcome. However, larger studies with multiple end-points including quality of life, exercise capacity and exacerbations demonstrated that neither bronchodilator nor oral steroid response tests can be used to predict the benefit of inhaled steroids (Weir and Burge, 1993; Burge et al., 2000; Calverley et al., 2003). It is now also clear that there is a large variability and that an acute bronchodilator reversibility may be present on one occasion and not another, within a short period of time. Also, several definitions used to calculate acute bronchodilator reversibility of the FEV1 can result in different proportions of patients being classified as having reversibility, and studies have shown that the reversibility is affected by many factors (O’Donnell, 2000). Therefore, the currently accepted disease definitions do not state that COPD is a disease characterized by a completely irreversible airflow limitation but state that the obstruction cannot be fully reversed, referring in particular to the persistence of an abnormal FEV1/FVC ratio (o0.7) after bronchodilator use. Also, the recognition that clinical improvements in symptoms, exercise capacity and quality of life can occur in the presence of minimal changes in FEV1 is a crucial feature with regard to therapeutic options (Hay et al., 1992; Paggiaro et al., 1998). However, the FEV1 remains a very important test
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T. Welte, D.A. Groneberg / Experimental and Toxicologic Pathology 57 (2006) S2, 35–40
despite its limitations when used as isolated diagnostic tool and the risk of death from COPD is closely related to the degree of impairment of the FEV1 (Thomason and Strachan, 2000). It can be stated that the bronchodilator reversibility should not be used as an isolated parameter to define two completely separate classes of COPD patients since this is an artificial and misleading representation. It is now generally accepted that patients with COPD may benefit from a broad range of treatments including long-acting bronchodilators, pulmonary rehabilitation or inhaled steroids. While some of these benefits may be measured by spirometric parameters, real-life outcomes such as quality of life or walking distance may also be important indexes to quantify the benefit (O’Donnell et al., 1999).
Conclusion Bronchial asthma and chronic obstructive pulmonary disease (COPD) represent major global causes of disability and death. While there may be a significant overlap in individual patients, the structural and pathophysiologic findings in both diseases can be easily differentiated. Regarding pharmacotherapy, COPD should no longer be viewed as a disease for which nothing can be done. In view of the wide range of bronchodilator reversibility in COPD patients and the limitations of FEV1 reversibility as a sole marker of benefit, new treatment options (Groneberg et al., 2003d, 2004a) may be evaluated on the basis of more real-life or combined outcome parameters (Celli et al., 2004). Concerning novel treatment options, future studies addressing the molecular, biochemical and pathophysiological characteristics of asthma and COPD need to be performed applying modern techniques of morphology (Groneberg et al., 2002a, 2002d, 2003a; Heppt et al., 2004; Springer et al., 2005), molecular biology (Groneberg et al., 2003c; Springer et al., 2004b, 2004c) and physiology (Quarcoo et al., 2004; Springer et al., 2004a).
Acknowledgements This study was supported by the German Academic Exchange Service (DAAD, D/00/10559), and the Deutsche Forschungsgemeinschaft (DFG, GR 2014/2-1).
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Experimental and Toxicologic Pathology 57 (2006) S2, 35–40
EXPERIMENTAL ANDTOXICOLOGIC PATHOLOGY www.elsevier.de/etp
Asthma and COPD Tobias Weltea, David A. Groneberga,b, a
Department of Respiratory Medicine, Hannover Medical School, Carl-Neuberg-Straße 1, 30625 Hannover, Germany Allergy-Centre-Charite´, Charite´ School of Medicine, Free University and Humboldt University, Augustenburger Platz 1/OR-1, 13353 Berlin, Germany b
Received 21 October 2005; accepted 16 February 2006
Abstract The two obstructive airway diseases bronchial asthma and chronic obstructive pulmonary disease (COPD) represent major global causes of disability and death, and COPD is estimated to become the third most common cause of death by 2020. The structural and pathophysiologic findings in both diseases appear to be easily differentiated in the extremes of clinical presentation. However, a significant overlap may exist in individual patients regarding features such as airway wall thickening on computer tomography or reversibility and airway hyperresponsiveness in lung function tests. Airway inflammation differs between the two diseases. In bronchial asthma, airway inflammation is characterized in most cases by an increased number of activated T-lymphocytes, particularly CD4+ Th2 cells, and sometimes eosinophils and mast cells. The most notable difference of chronic severe asthma compared with mild to moderate asthma is an increased number of neutrophils. In stable COPD, airway inflammation is characterized by an increased number of T-lymphocytes, particularly CD8+ T cells, macrophages and neutrophils. With the progression of the disease severity, macrophage and neutrophil numbers increase. Although there may be a partial overlap between asthma and COPD in some patients, the differences in functional, structural and pharmacological features clearly demonstrate the consensus that asthma and COPD are different diseases along all their stages of severity. r 2006 Elsevier GmbH. All rights reserved. Keywords: Airways; Asthma; COPD; Drug; Inflammation; Lung; Therapy
Introduction The two airway diseases bronchial asthma and chronic obstructive pulmonary disease (COPD) are chronic conditions that exact an enormous toll on patients, healthcare providers and the society (Chung Corresponding author. Zentrum Innere Medizin, Abteilung Pneumologie, Medizinische Hochschule Hannover, Carl-NeubergStraße 1, 30625 Hannover, Germany. Tel.: +49 511 532 3530; fax: +49 511 532 3353. E-mail address: [email protected] (D.A. Groneberg).
0940-2993/$ - see front matter r 2006 Elsevier GmbH. All rights reserved. doi:10.1016/j.etp.2006.02.004
et al., 2002). There has been a substantial increase in the prevalence of both diseases in the last decades that has led to sizable concerns being expressed from national and international healthcare authorities. The underlying characteristics of both conditions involve inflammatory changes in the respiratory tract, while the specific nature and the reversibility of these processes largely differ in each entity and disease stage (Table 1). In the context of disease management, acute exacerbations are important clinical events in both illnesses that largely contribute to an increase in mortality and morbidity (Skrepnek and Skrepnek, 2004).
ARTICLE IN PRESS 36
Table 1.
T. Welte, D.A. Groneberg / Experimental and Toxicologic Pathology 57 (2006) S2, 35–40
Phenotype differences between COPD and bronchial asthma
Feature
COPD
Asthma
Limitation of airflow Bronchial hyperresponsiveness Parenchymal integrity Steroid response
Largely irreversible Variable (small) Destruction Varying
Largely reversible Significant Intact Present
COPD The clinical diagnosis of COPD relies on abnormal lung function tests and the patient’s history. COPD is characterized by a largely variable pathology and the molecular mechanisms are not completely understood so far. Therefore, it has been difficult to define a simple disease definition. First approaches based on the epidemiological features of chronic cough and sputum production such as duration of symptoms for 3 months over a period of at least 2 years (chronic bronchitis) or on pathological features such as the identification of emphysema in COPD airway tissue. However, these approaches did not prove to be efficient in the clinical management of the disease. Therefore, important approaches towards a rational disease definition were first reports that related death and disability in COPD to a progressive decrease in the forced expiratory volume in 1 s (FEV1) (Fletcher and Peto, 1977; Peto et al., 1983). Today there is a consensus that the diagnosis of COPD relies on the presence of airflow obstruction defined as decreased FEV1 to FVC (forced vital capacity) or vital capacity ratio. Extending these basic functional features, the GOLD guidelines introduced persistent inflammation and the potential presence of noxious stimuli to the disease definition (Pauwels et al., 2001). Also, a classification of COPD disease severity was defined with five stages from risk group to very severe disease (Table 2). With regard to inhalant noxious stimuli, tobacco smoke is regarded as a major cause, but toxic gases or indoor air pollution may also be regarded as major factors leading to COPD (Pandey, 1984; Perez-Padilla et al., 1996).
Bronchial asthma Bronchial asthma is defined as chronic inflammatory disorder of the airways (Caramori et al., 2005). The chronically inflamed airways of patients with bronchial asthma are hyperresponsive and become obstructed due to bronchoconstriction and mucus hypersecretion (Caramori et al., 2005). Clinically, asthma is characterized by wheezing, breathlessness, chest tightness and coughing particularly at night or in the early morning. Common risk factors of the disease include the exposure to seasonal or perennial allergens including pollens,
Table 2. Inflammatory cell population differences between COPD and bronchial asthma COPD
Asthma
Neutrophils Macrophages CD8-T-lymphocytes Eosinophils (exacerbations)
Eosinophils Mast cells CD4-T-lymphocytes Macrophages, neutrophils
Ranked in relative order of importance.
molds, animal allergens or domestic dust mites. Other risk factors can be tobacco smoke, air pollution, respiratory infections, exercise, occupational irritants, physical and chemical irritants and drugs including aspirin or beta blockers. There is also good evidence of a genetic component in asthma since the disease often occurs in families. The severity of the disease can be intermittent, persistently mild, moderate or severe.
Inflammation Important features of both diseases are ongoing chronic inflammatory processes in the airways as indicated by the current GINA and GOLD guidelines (Pauwels et al., 2001). There are great differences between COPD and bronchial asthma (Groneberg and Chung, 2004): while mast cells and eosinophils represent prominent cell types in allergic diseases such as asthma or atopic dermatitis (Groneberg et al., 2005), the major inflammatory cell types in COPD are different (Table 2) (Saetta et al., 1998). Neutrophils play a crucial role in the pathophysiology of COPD. They release multiple mediators and tissue-degrading enzymes such as elastases that orchestrate tissue destruction and chronic inflammation (Chung, 2001; Stockley, 2002). Neutrophil and macrophage numbers are also increased in bronchoalveolar lavage fluids from cigarette smokers (Hunninghake and Crystal, 1983). COPD patients with a high degree of airflow limitation have a higher level of induced sputum neutrophilia than COPD patients with a milder airflow limitation. In this respect, increased sputum neutrophilia is related to an accelerated decrease in the FEV1 and more prevalent in subjects with the symptoms of chronic cough and sputum production (Stanescu et al., 1996).
ARTICLE IN PRESS T. Welte, D.A. Groneberg / Experimental and Toxicologic Pathology 57 (2006) S2, 35–40
The second major cell type that plays a crucial role in COPD are macrophages (Shapiro, 1999). Similar to neutrophils, they release tissue-degrading enzymes such as matrix metalloproteinases (MMPs). Neutrophils and macrophages communicate with other cells such as airway smooth muscle cells, endothelial cells or sensory neurons, and release inflammatory mediators that propagate the events of bronchoconstriction (O’Byrne and Inman, 2003), airway remodeling (Vignola et al., 2002), and mucus hypersecretion involving the induction of mucin genes (Groneberg et al., 2002b, c, 2003b, 2004c). As in bronchial asthma, lymphocytes are also involved in cellular mechanisms underlying COPD (Majo et al., 2001). However, the T-cell-associated inflammatory processes largely differ from those in allergic asthma, which is characterized by increased numbers of CD4-positive T-lymphocytes (Fabbri et al., 2003; Sutherland and Martin, 2003) (Table 2). In COPD, there are increased numbers of CD8-positive T-lymphocytes present in the airways (Saetta et al., 1999). The degree of airflow obstruction is correlated with the numbers of CD8-positive T-lymphocytes (O’Shaughnessy et al., 1997). In contrast to asthma, eosinophils may only play a major role in acute exacerbations of COPD (Saetta et al., 1994). However, their presence in stable COPD has been shown to be an indicator of steroid responsiveness (Pizzichini et al., 1998; Fujimoto et al., 1999). Features such as mucus hypersecretion, basing on mucin gene induction (Groneberg et al., 2002b, c, 2003b, 2004c; Chung et al., 2004) or chronic cough basing on an increased expression of transient receptor potential vanilloid-1 (VR1 or TRPV1) (Groneberg et al., 2004b), may be found both in bronchial asthma and COPD as well as in other respiratory diseases.
Bronchodilator reversibility One of the main features used to distinguish bronchial asthma from COPD is the acute bronchodilator reversibility of the FEV1. Historically, asthma has been defined as an obstructive disease with bronchodilator reversibility in most patients while definitions of COPD emphasized little or no bronchodilator reversibility. However, there has been increasing evidence in the past few years that COPD patients have a large variability of reversibility that may vary day-to-day (Nisar et al., 1990, p. 457). It can be assumed that acute bronchodilator reversibility may be present in a significant proportion of COPD patients depending on definitions and nature and dosing of drugs (Kerstjens et al., 1993). A problem lies within the lack of clarity concerning the term ‘irreversibility’. This is due to the inappropriate restriction of the bronchodilator reversibility to the
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FEV1 since the COPD definition also requires an obstructive forced expiratory ratio that is the ratio of the FEV1 to the FVC. A FEV1/FVC ratio of o0.7 is essential for the diagnosis of airway obstruction and it remains o0.7 after bronchodilator use in COPD patients. It is therefore particularly the FEV1/FVC ratio in COPD that is ‘irreversible’ after bronchodilator use (McKenzie et al., 2003). The definition of COPD, diagnosis and severity grading according to spirometric parameters are critical issues that even affect COPD prevalence, burden of disease and the effects of interventions. Recently, a 200% variation in COPD prevalence was reported that resulted from applying different definitions of airway obstruction from widely used guidelines (Celli et al., 2003). Patients with COPD who presented reversibility are often classified as having an ‘asthmatic’ component in contrast to the ‘pure’ or ‘true’ COPD. A serious consequence is that certain therapeutic options may not be taken into consideration for the ‘true COPD’ group. In this respect, small-scaled clinical trials assessing inhaled steroids in COPD and the use of FEV1 as main end-point suggested the commonly held view that inhaled steroids should not be prescribed for patients with COPD with no acute response to inhaled bronchodilators or oral corticosteroids (van Schayck, 2000). In this respect, it is not logic to solely define the disease by its lack of reversibility to bronchodilators while therapeutic studies are then conducted using spirometry as the primary outcome. However, larger studies with multiple end-points including quality of life, exercise capacity and exacerbations demonstrated that neither bronchodilator nor oral steroid response tests can be used to predict the benefit of inhaled steroids (Weir and Burge, 1993; Burge et al., 2000; Calverley et al., 2003). It is now also clear that there is a large variability and that an acute bronchodilator reversibility may be present on one occasion and not another, within a short period of time. Also, several definitions used to calculate acute bronchodilator reversibility of the FEV1 can result in different proportions of patients being classified as having reversibility, and studies have shown that the reversibility is affected by many factors (O’Donnell, 2000). Therefore, the currently accepted disease definitions do not state that COPD is a disease characterized by a completely irreversible airflow limitation but state that the obstruction cannot be fully reversed, referring in particular to the persistence of an abnormal FEV1/FVC ratio (o0.7) after bronchodilator use. Also, the recognition that clinical improvements in symptoms, exercise capacity and quality of life can occur in the presence of minimal changes in FEV1 is a crucial feature with regard to therapeutic options (Hay et al., 1992; Paggiaro et al., 1998). However, the FEV1 remains a very important test
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despite its limitations when used as isolated diagnostic tool and the risk of death from COPD is closely related to the degree of impairment of the FEV1 (Thomason and Strachan, 2000). It can be stated that the bronchodilator reversibility should not be used as an isolated parameter to define two completely separate classes of COPD patients since this is an artificial and misleading representation. It is now generally accepted that patients with COPD may benefit from a broad range of treatments including long-acting bronchodilators, pulmonary rehabilitation or inhaled steroids. While some of these benefits may be measured by spirometric parameters, real-life outcomes such as quality of life or walking distance may also be important indexes to quantify the benefit (O’Donnell et al., 1999).
Conclusion Bronchial asthma and chronic obstructive pulmonary disease (COPD) represent major global causes of disability and death. While there may be a significant overlap in individual patients, the structural and pathophysiologic findings in both diseases can be easily differentiated. Regarding pharmacotherapy, COPD should no longer be viewed as a disease for which nothing can be done. In view of the wide range of bronchodilator reversibility in COPD patients and the limitations of FEV1 reversibility as a sole marker of benefit, new treatment options (Groneberg et al., 2003d, 2004a) may be evaluated on the basis of more real-life or combined outcome parameters (Celli et al., 2004). Concerning novel treatment options, future studies addressing the molecular, biochemical and pathophysiological characteristics of asthma and COPD need to be performed applying modern techniques of morphology (Groneberg et al., 2002a, 2002d, 2003a; Heppt et al., 2004; Springer et al., 2005), molecular biology (Groneberg et al., 2003c; Springer et al., 2004b, 2004c) and physiology (Quarcoo et al., 2004; Springer et al., 2004a).
Acknowledgements This study was supported by the German Academic Exchange Service (DAAD, D/00/10559), and the Deutsche Forschungsgemeinschaft (DFG, GR 2014/2-1).
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