A one-horse race can have only one winner Kenneth R. Lutchen
J Appl Physiol 116:1119, 2014. doi:10.1152/japplphysiol.00023.2014 You might find this additional info useful... This article cites 4 articles, 2 of which can be accessed free at: /content/116/8/1119.full.html#ref-list-1 Updated information and services including high resolution figures, can be found at: /content/116/8/1119.full.html Additional material and information about Journal of Applied Physiology can be found at: http://www.the-aps.org/publications/jappl
This information is current as of February 14, 2015.
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Journal of Applied Physiology publishes original papers that deal with diverse areas of research in applied physiology, especially those papers emphasizing adaptive and integrative mechanisms. It is published 12 times a year (monthly) by the American Physiological Society, 9650 Rockville Pike, Bethesda MD 20814-3991. Copyright © 2014 by the American Physiological Society. ISSN: 0363-6143, ESSN: 1522-1563. Visit our website at http://www.the-aps.org/.
J Appl Physiol 116: 1119, 2014; doi:10.1152/japplphysiol.00023.2014.
Letter To The Editor
A one-horse race can have only one winner Kenneth R. Lutchen Boston University, Boston, Massachusetts
Address for reprint requests and other correspondence: K. R. Lutchen, Boston Univ., 44 Cummington St., Boston, MA 02215 (e-mail: klutch @bu.edu).
http://www.jappl.org
in lung resistance postchallenge was due to the airways and virtually none was due to changes in the tissue properties. Dr. Noble and colleague’s (see Ref. 4) response raises a legitimate concern of whether transmural pressures for isolated airways compare well to in situ. But Harvey et al. (1) used rather large pressure swings near the limits of what is likely achievable in situ and still was unable to invoke substantive bronchoprotection or bronchodilation. Dr. Skloot and colleagues (see Ref. 4) raise some interesting whole organism data, but perhaps the exercise data and the obesity data can also be explained by length adaptation and/or atelectasis mechanisms rather than the impact of ASM dynamic stretching. So, there remains an understandable propensity to want to design experiments and explain our data with only a single “horse” in the race. I profess that we likely need to run a more challenging and less predictable race with more horses, and I for one might take better odds on some of the others. DISCLOSURES No conflicts of interest, financial or otherwise, are declared by the author(s). AUTHOR CONTRIBUTIONS K.R.L. drafted manuscript; K.R.L. edited and revised manuscript; K.R.L. approved final version of manuscript. REFERENCES 1. Harvey BC, Parameswaran H, Lutchen KR. Can tidal breathing with deep inspirations of intact airways create sustained bronchoprotection or bronchodilation? J Appl Physiol 115: 436 –445, 2013. 2. Lutchen KR, Hantos Z, Petak F, Adamicza A, Suki B. Airway inhomogeneities contribute to apparent lung tissue resistance during constriction. J Appl Physiol 80: 1841–1849, 1996. 3. Lutchen KR. Viewpoint: Airway smooth muscle stretch and airway hyperresponsiveness in asthma: Have we chased the wrong horse? J Appl Physiol; doi:10.1152/japplphysiol.00968.2013. 4. Noble PB, McFawn PK, Mitchell HW, Ansell TK, Bates JHT, Seow CY, Brusasco V, Pellegrino R, Skloot G, Togias A, Schichilone N. Commentaries on Viewpoint: Airway smooth muscle and airway hyperresponsiveness in human asthma: Have we chased the wrong horse? J Appl Physiol; 10.1152/japplphysiol.00025.2014.
8750-7587/14 Copyright © 2014 the American Physiological Society
1119
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TO THE EDITOR: The spectrum of reactions to my Viewpoint (3) regarding the role of the airway smooth muscle (ASM) in creating airway hyperresponsiveness akin to asthma has raised several interesting points (see Ref. 4). First, I must begin with a critical clarification. A few of the responders appear under the impression that I suggested the ASM was the “horse” we should dismount or stop chasing as it is not the main culprit in causing hyperresponsiveness. This is not my claim. The ASM may very well be the main culprit. The horse I referred to was that the causative step leading to airway hyperresponsive is a reduced ability to dynamically stretch the ASM during tidal breathing and a DI, which then triggers the necessary alteration in ASM phenotype. Have we been overly predisposed to design experiments and interpret data singularly along these lines? I provided arguments suggesting that this specific trajectory may be the wrong “leading” horse in the race, that data from intact airway airways are inconsistent with such because the in situ strains during typical transmural pressures are insufficient, and that whole organism data could be explained with other mechanisms and are not exclusively supportive of only this “horse.” Hence, the diminished response to a DI in patients with asthma and the clear evidence that humans with asthma have a diminished capacity to dilate their airways compared with those without asthma may be a consequence rather than a cause. Our inclination for it having been a cause rather than a consequence had been driven, perhaps, by an over willingness to leap from isolated ASM experiments to whole organism ones. There are some other reactions I need to address. Dr. Seow’s (see Ref. 4) response seemed concerned with parenchymal stiffening during airway provocation. However, it is unlikely that this is an important phenomena in the whole lung. Indeed, a study from our group (2) using gases of distinct density affirmed that the preponderance of the changes
J Appl Physiol 116:1119, 2014. doi:10.1152/japplphysiol.00023.2014 You might find this additional info useful... This article cites 4 articles, 2 of which can be accessed free at: /content/116/8/1119.full.html#ref-list-1 Updated information and services including high resolution figures, can be found at: /content/116/8/1119.full.html Additional material and information about Journal of Applied Physiology can be found at: http://www.the-aps.org/publications/jappl
This information is current as of February 14, 2015.
Downloaded from on February 14, 2015
Journal of Applied Physiology publishes original papers that deal with diverse areas of research in applied physiology, especially those papers emphasizing adaptive and integrative mechanisms. It is published 12 times a year (monthly) by the American Physiological Society, 9650 Rockville Pike, Bethesda MD 20814-3991. Copyright © 2014 by the American Physiological Society. ISSN: 0363-6143, ESSN: 1522-1563. Visit our website at http://www.the-aps.org/.
J Appl Physiol 116: 1119, 2014; doi:10.1152/japplphysiol.00023.2014.
Letter To The Editor
A one-horse race can have only one winner Kenneth R. Lutchen Boston University, Boston, Massachusetts
Address for reprint requests and other correspondence: K. R. Lutchen, Boston Univ., 44 Cummington St., Boston, MA 02215 (e-mail: klutch @bu.edu).
http://www.jappl.org
in lung resistance postchallenge was due to the airways and virtually none was due to changes in the tissue properties. Dr. Noble and colleague’s (see Ref. 4) response raises a legitimate concern of whether transmural pressures for isolated airways compare well to in situ. But Harvey et al. (1) used rather large pressure swings near the limits of what is likely achievable in situ and still was unable to invoke substantive bronchoprotection or bronchodilation. Dr. Skloot and colleagues (see Ref. 4) raise some interesting whole organism data, but perhaps the exercise data and the obesity data can also be explained by length adaptation and/or atelectasis mechanisms rather than the impact of ASM dynamic stretching. So, there remains an understandable propensity to want to design experiments and explain our data with only a single “horse” in the race. I profess that we likely need to run a more challenging and less predictable race with more horses, and I for one might take better odds on some of the others. DISCLOSURES No conflicts of interest, financial or otherwise, are declared by the author(s). AUTHOR CONTRIBUTIONS K.R.L. drafted manuscript; K.R.L. edited and revised manuscript; K.R.L. approved final version of manuscript. REFERENCES 1. Harvey BC, Parameswaran H, Lutchen KR. Can tidal breathing with deep inspirations of intact airways create sustained bronchoprotection or bronchodilation? J Appl Physiol 115: 436 –445, 2013. 2. Lutchen KR, Hantos Z, Petak F, Adamicza A, Suki B. Airway inhomogeneities contribute to apparent lung tissue resistance during constriction. J Appl Physiol 80: 1841–1849, 1996. 3. Lutchen KR. Viewpoint: Airway smooth muscle stretch and airway hyperresponsiveness in asthma: Have we chased the wrong horse? J Appl Physiol; doi:10.1152/japplphysiol.00968.2013. 4. Noble PB, McFawn PK, Mitchell HW, Ansell TK, Bates JHT, Seow CY, Brusasco V, Pellegrino R, Skloot G, Togias A, Schichilone N. Commentaries on Viewpoint: Airway smooth muscle and airway hyperresponsiveness in human asthma: Have we chased the wrong horse? J Appl Physiol; 10.1152/japplphysiol.00025.2014.
8750-7587/14 Copyright © 2014 the American Physiological Society
1119
Downloaded from on February 14, 2015
TO THE EDITOR: The spectrum of reactions to my Viewpoint (3) regarding the role of the airway smooth muscle (ASM) in creating airway hyperresponsiveness akin to asthma has raised several interesting points (see Ref. 4). First, I must begin with a critical clarification. A few of the responders appear under the impression that I suggested the ASM was the “horse” we should dismount or stop chasing as it is not the main culprit in causing hyperresponsiveness. This is not my claim. The ASM may very well be the main culprit. The horse I referred to was that the causative step leading to airway hyperresponsive is a reduced ability to dynamically stretch the ASM during tidal breathing and a DI, which then triggers the necessary alteration in ASM phenotype. Have we been overly predisposed to design experiments and interpret data singularly along these lines? I provided arguments suggesting that this specific trajectory may be the wrong “leading” horse in the race, that data from intact airway airways are inconsistent with such because the in situ strains during typical transmural pressures are insufficient, and that whole organism data could be explained with other mechanisms and are not exclusively supportive of only this “horse.” Hence, the diminished response to a DI in patients with asthma and the clear evidence that humans with asthma have a diminished capacity to dilate their airways compared with those without asthma may be a consequence rather than a cause. Our inclination for it having been a cause rather than a consequence had been driven, perhaps, by an over willingness to leap from isolated ASM experiments to whole organism ones. There are some other reactions I need to address. Dr. Seow’s (see Ref. 4) response seemed concerned with parenchymal stiffening during airway provocation. However, it is unlikely that this is an important phenomena in the whole lung. Indeed, a study from our group (2) using gases of distinct density affirmed that the preponderance of the changes
