© 2007 American Thoracic Society
Airway Responsiveness Should Be a Measurement of the Responsiveness of AirwaysFrom the Authors:
We thank Mitzner and colleagues for their interest in our recent article (1). While one can argue about our terminology and interpretations, it is important to note that our main conclusions that
We are puzzled by their statement that we rely heavily on Penh when this variable was only used in two figures (1). Due to controversies surrounding Penh, we took additional in vivo and ex vivo approaches. We could have made inferences from single compartment model data (R and E) about airway responsiveness, an approach that has been taken by many investigators, including Dr. Mitzner (2). However, because the constant phase model allows one to partition responsiveness within the lung, we included data on Rn, G, and H. Several publications from Dr. Irvin infer airway hyperresponsiveness (AHR) from collective changes in constant phase model parameters (3, 4). As illustrated by Dr. Irvin's group, AHR can be the result of diverse physiological mechanisms including increased heterogeneity of airway narrowing (4). If the differences in G we observed in Figures 2, 4, 9, and 10 are due to differences in airway narrowing, then there is a correlation between our in vivo and ex vivo data. While we agree that Rn is the best measure of airway resistance in vivo, we are perplexed as to why Mitzner and colleagues chose to ignore our data in Figures 9 and 10, which clearly demonstrate that Mitzner and colleagues state that "the defect in asthma is with airway narrowing." We respectfully disagree. Airway narrowing is not the only factor that can contribute to AHR in asthma. As discussed by Wagers and colleagues, AHR can be attributed to airway wall thickening, exaggerated airway closure, and plugging/closure of small airways and alveoli, and is thus a manifestation of a multitude of events in the lung (4).
National Institute of Environmental Health Sciences/National Institutes of Health, Research Triangle Park, North Carolina
Medical College of Wisconsin, Milwaukee, Wisconsin
National Jewish Medical and Research Center, Denver, Colorado
National Institute of Environmental Health Sciences/National Institutes of Health, Research Triangle Park, North Carolina FOOTNOTES Conflict of Interest Statement: None of the authors has a financial relationship with a commercial entity that has an interest in the subject of this manuscript. REFERENCES
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ERKO mice have altered responsiveness associated with M2 muscarinic receptor dysfunction are indisputable. We demonstrate dysfunction by plethysmography (Buxco) and invasive analysis (Flexivent), with two different agonists, both in vivo and ex vivo, under both basal and allergic conditions.