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J Appl Physiol 103: 1466, 2007; doi:10.1152/japplphysiol.00822.2007
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LETTER TO THE EDITOR

Last Word on Viewpoint "The role of the large airways on smooth muscle contraction in asthma"

To the Editor: Macklem (3) and Pellegrino and Brusasco (4) suggest that the change in lung volume from the baseline smooth muscle tone (BSMT) might be largely an artifact. Whatever proportion of the increase in FRC from the BSMT was due to an artifact had no significant effect on the results of our study (2). The artifact causes an equal overestimation of the change in RV and FRC, but it is the change in FRC relative to the change in RV, as reflected by the FRCratio, that was the major determinant of the magnitude of the hyperresponsiveness to the BSMT (1). We recalculated the FRCratio with the assumption that there was an increase in FRC from an artifact proportional to the resistance of the large airways that averaged nearly 80% of the measured increase in FRC. None of the effects of FRCratio on lung volumes or hyperresponsiveness was significantly altered.

The points that were raised by Thompson et al. (6) that the methods used in our study were not sufficiently sensitive to detect an effect of small airways on the increase in RV from BSMT are certainly valid. Nevertheless, the methods we used were sufficiently sensitive to detect a highly significant decrease from BSMT in the diameter of the small airways of 15% that was nearly fourfold greater than the decrease in the diameter of the large airways (1). While the significant changes in the diameter of the small airways had no effect on the variance of the change in RV, the ratio of the wall thickness to the diameter of the large airways and the diameter of the medium airways accounted for more than 70% of the variance of the increase in RV (1).

Perhaps the most surprising and important finding in our study is that the magnitude of the structural response of the airways to smooth muscle tone was not a determinant of the magnitude of the response in pulmonary function. Thus hyperresponsiveness of the change in FVC or FEV1 to smooth muscle tone occurred with the same degree of airways narrowing; and it is, therefore, a nonsequitur to consider the exaggerated response in pulmonary function as a manifestation of airways hyperresponsiveness. These findings are compatible with the study of Schueller et al. (5) who found that the difference in airway luminal area between baseline and postalbuterol or between baseline and histamine challenge was the same for three groups: a group of healthy volunteers and two groups of asthmatic subjects, those with or without a significant decrease in FEV1 with the histamine challenge.

We suggest that the hyperresponsiveness of the change in pulmonary function is determined by the attenuation of the compensatory response in FRC and TLC to the change in RV that, in turn, is a function of the degree of dynamic hyperinflation that results from narrowing of the relaxed large airways.

FOOTNOTES


Address for reprint requests and other correspondence: S. Permutt, 5501 Hopkins Bayview Circle, Baltimore, MD 21224 (e-mail: spermut{at}jhmi.edu)

REFERENCES

  1. Brown RH, Pearse DB, Pyrgos G, Liu MC, Togias A, Permutt S. The structural basis of airways hyperresponsiveness in asthma. J Appl Physiol 101: 30–39, 2006.[Abstract/Free Full Text]
  2. Brown RH, Pearse DB, Pyrgos G, Liu MC, Togias A, Permutt S. Reply from Drs. Brown, Pearse, Pyrgos, Liu, Togias, and Permutt. J Appl Physiol 101: 1813, 2006.[Free Full Text]
  3. Macklem P. Commentary on "The role of large airways on smooth muscle contraction in asthma." J Appl Physiol; doi:10.1152/japplphysiol.00646.2007.
  4. Pellegrino R, Brusasco V. Commentary on "The role of large airways on smooth muscle contraction in asthma." J Appl Physiol; doi:10.1152/japplphysiol.00684.2007.
  5. Schueller G, Neumann K, Helbich T, Riemer H, Backfrieder W, Sertl K, Herold CJ. Bronchial reactivity in hyperresponsive patients and healthy individuals: demonstration with high resolution computed tomography. Eur J Radiol 52: 151–156, 2004.[CrossRef][Web of Science][Medline]
  6. Thompson B, King G, Harding R. Commentary on "The role of large airways on smooth muscle contraction in asthma." J Appl Physiol; doi:10.1152/japplphysiol.00696.2007.

Solbert Permutt
 Division of Pulmonary and Critical Care Medicine, Johns Hopkins University Asthma and Allergy Center, Baltimore, Maryland





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