© 2005 American Thoracic Society
Dissociation of Lung Function and Airway Inflammation in Chronic Obstructive Pulmonary DiseaseIs It a Real or Statistical Phenomenon?From the Authors:We thank Drs. Kostianev and Marinov for their letter discussing some of the potential limitations of our study, thereby questioning our conclusion that "airflow limitation, airway inflammation, and features commonly associated with asthma are separate and largely independent factors in the pathophysiology of COPD" (1). We fully agree that the results of factor analysis are dependent on the selected set of variables (2), and we purposely addressed this in the article. For this reason, we also performed additional factor analyses, including different sets of variables, such as pack-years smoked, or neutrophil and eosinophil numbers instead of percentages. As mentioned in the article, these additional analyses resulted in similar factor structures, all suggestive of the independence of inflammatory and functional variables. Nevertheless, repeating the analysis with inclusion of more direct markers of airway inflammation known to be involved in chronic obstructive pulmonary disease (COPD), such as CD8+ lymphocytes, B lymphocytes, or macrophages in the airway wall or parenchyma, may be very valuable. However, histology was not available when we performed the present analysis. We would like to emphasize that standard criteria about factor structure were applied. However, the factor structure does not exclude associations between parameters in different factors. As shown in the article, there were linear relationships between some of the functional and inflammatory markers in our study. We performed the factor analysis on cross-sectional data of a large group of well-characterized patients. Because exacerbations do indeed influence the inflammatory response, the measurements were postponed if patients experienced a respiratory tract infection within the previous 2 weeks, or an exacerbation requiring oral steroids within the previous 2 months. The patients are presently being followed up longitudinally for 2.5 years, and we intend to monitor the variables included in the factor analysis during this period. We agree with Drs. Kostianev and Marinov that longitudinal studies are needed to investigate whether changes in lung function are associated with changes in inflammation in COPD. We hope to be able to report on this in the future. Factor analysis is an exploratory analysis, serving to generate hypotheses rather than testing them. Our results do suggest that, although there are univariate linear correlations between functional and inflammatory parameters in stable COPD (as have been reported by many others [3]), these entities represent different dimensions in the pathophysiology of COPD. This may have consequences for the development of therapy, which seems to require more than an antiinflammatory strategy alone.
Leiden University Medical Center, Leiden, The Netherlands FOOTNOTES Conflict of Interest Statement: T.S.L. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript; P.J.S. is a member of the Department of Pulmonology at Leiden University Medical Center, which has received grants from AltanaPharma ($222,616), Novartis ($90,640), Bayer ($61,762), AstraZeneca ($113,155), Pfizer ($406,000), Merck, Sharp & Dohme ($118,000), Exhale Therapeutics ($90,000), and GlaxoSmithKline ($299,495) in 2001–2004. REFERENCES
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