© 2005 American Thoracic Society
Penh Is Not a Validated Technique for Measuring Airway Function in MiceTo the Editor:We read with interest the recent article by Kumar and colleagues outlining an important benefit of blocking proinflammatory cytokines in a mouse model of chronic asthma (1). The clinical experience with drugs that block Th-2 cytokines, particularly interleukin (IL)-5, has been disappointing, to the point that clinical development of these drugs has essentially been dropped (2). Chronic asthma is essentially a developmental disease that begins in childhood. We have argued that the development of asthma should be considered a two-phase process consisting of an initiation stage, which essentially occurs in childhood and during which allergen-induced Th-2–mediated inflammation is the major driving process, followed by a consolidation phase in which chronic inflammation induces a self-sustaining cycle of airway remodeling, heightened responsiveness, and airway inflammation that results in chronic asthma in adulthood (2). Viewed in this light, the impressive results obtained by Kumar and coworkers (1) are not surprising, in that while the chronicity of exposure in their model (3) is a significant improvement over the relatively acute exposure of many other models, this is still likely to represent the Th-2–driven initiation phase of asthma in childhood. There is, however, one aspect of Kumar and colleagues' report (1) that is potentially open to misinterpretation and on which we wish to comment. They used enhanced pause (Penh) to approximate lung function and bronchial responsiveness in their mice. Penh has fallen into disrepute as a measure of lung function, as elaborated by a group of 22 internationally respected respiratory physiologists (4). Kumar and coworkers do highlight this issue but go on to state: "In our chronic model, we have previously shown that the observed changes in Penh closely correlate with increased specific airway resistance as measured by the forced oscillation technique ... (19)." We would like to point out that the previous study referred to as their Reference 19 (see Reference 5 herein) did not use unrestrained plethysmography and hence did not compare Penh with direct measurements of airway function, using forced oscillations. While that study (5) did show that when inflammation was largely specific to the airways it did result in heightened responsiveness that was confined to the airways, the fact that the two studies (1, 5) both reported similar phenomena cannot, in any way, be taken as supporting the use of Penh as a measure of airway function or bronchial responsiveness. Penh will be influenced by any factor that alters breathing pattern. While this includes changes in airway function, it can also include many other factors, including change in respiratory drive (4). While not detracting in any way from the findings presented by Kumar and coworkers (1), it would be wrong for readers of the Journal, especially those not trained in respiratory physiology, to conclude from their article that Penh was validated by a sophisticated and specific measurement of airway resistance and, consequently, could be used to represent airway function in mouse models of asthma.
a The University of Western Australia, West Perth, Australia FOOTNOTES Conflict of Interest Statement: P.D.S. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript; D.J.T. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript; R.A.C. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript; Z.H. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. Dr. Kumar was given the opportunity to respond to this letter but declined to do so. REFERENCES
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