American Journal of Respiratory and Critical Care Medicine Vol 174. pp. 244, (2006)
© 2006 American Thoracic Society
doi: 10.1164/rccm.2604010
Rebuttal by Dr. Barnes
I did not find Monica Kraft's arguments that asthma and chronic obstructive pulmonary disease (COPD) are the same disease to be very persuasive. Because there may occasionally be difficulties in distinguishing asthma and COPD in the clinic does not mean that they are the same disease! It is very likely that COPD and asthma coexist in some patients, resulting in a mixed clinical picture, requiring treatment of both conditions. It is not surprising that bronchodilators are effective in both asthma and COPD, as they work by relaxing airway smooth muscle. However, there is a striking difference in the bronchodilator response to  2-agonists in asthma and COPD, whereas anticholinergics have a similar effect in both diseases because they only reverse vagal cholinergic tone. The much greater bronchodilator efficacy of 2-agonists in asthma is because they are functional antagonists, which counteract all bronchoconstrictor mechanisms (histamine, cysteinyl leukotrienes, prostaglandins, bradykinin, etc.) that are not involved in COPD. The most striking difference in response to therapy, not discussed by Dr. Kraft, is the poor response to corticosteroids in COPD compared with the striking response in asthma—this marks a fundamental difference in the underlying inflammatory process between these diseases.
Airway hyperresponsiveness (AHR) is a feature of asthma and COPD, but Dr. Kraft fails to distinguish the marked AHR of asthma, which is also seen with indirect challenges like exercise, from the AHR of COPD, which can be accounted for entirely by changes in baseline airway caliber. AHR in asthma and COPD is a manifestation of airway narrowing, but in asthma there are additional mechanisms, such as mast cell mediator release and abnormal behavior of airway smooth muscle, which are not features of COPD.
Although asthma and COPD are clearly different in terms of clinical presentation, physiologic responses, immunopathology, and response to therapy, I agree that there is some convergence in patients with severe asthma who have several of the features seen in classical COPD (summarized in my Table 1). This may indicate common molecular mechanisms that relate to disease severity, and the identification of several genes that are common to severe asthma and COPD (ADAM33, PHF-11, DPP-10, and others) may be showing these are genes that determine inflammation severity. These same genes may also be involved in other chronic inflammatory diseases, such as inflammatory bowel disease and rheumatoid arthritis, but this does not mean that these diseases are the same; rather, the genetic determinants of severity may be common to all. Finally, if we consider asthma and COPD to be a common airway disease, then this becomes the commonest disease in the world. This may give a political advantage in arguing for more research funding and better clinical resources. Thus, although the Dutch hypothesis is incorrect, it has some important political advantages!
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S. K. Chhabra
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M. Kraft and P. J. Barnes
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174(9):
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D. L. Hahn
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Copyright © 2006 American Thoracic Society
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