© 2008 American Thoracic Society
Mucous Obstruction and Airway Hyperresponsiveness in MiceFrom the Authors:We would like to thank Dr. Agrawal for his appreciation of our article (1). In his letter, Dr. Agrawal suggests that mucus formation could be the cause of airway closure in allergic mice (2). This is certainly a possibility, although we suspect that airway closure may be caused by more than a single mechanism. In particular, we have previously shown, using the forced oscillation technique in allergically inflamed mice, that airway hyperresponsiveness can be ascribed to both a thickening of the airway wall and an increased propensity for the airways to close (3). The latter could be caused either by excess mucus or an increased surface tension due to fibrin or other plasma proteins accumulating at the air–liquid interface. Indeed, we have previously found strong evidence that fibrin formation takes place in inflamed airways, and that this may play an important role in airway closure (4). Interestingly, we also found that methacholine given as an aerosol induces significant airway closure, whereas methacholine given intravenously does not (5). These results suggest that intravenous methacholine constricts only the central airways, whereas aerosolized methacholine also induces a significant increase in the mechanical impedance of the lung periphery. Perhaps these differences are due to a greater amount of mucus production when the methacholine is delivered as an aerosol. In any case, as the phenotype of human asthma appears to be highly variable between individuals, the particular mouse model and route of contractile agonist delivery chosen for any given study should depend on the phenotype of interest (5). Dr. Agrawal also alludes to the differences in the techniques used in his study and ours to assess lung function. The forced oscillation technique we used has the advantage of precision and specificity, albeit at the expense of invasiveness. By contrast, the double-chamber plethysmograph used by Dr. Agrawal allows nonterminal measurements of airway mechanics to be made in mice with somewhat less resolution, and therefore represents a different trade-off between the competing attributes of precision and noninvasiveness (6). We think it is important to point out that while the techniques are different, both are soundly based on first principles of the physics of the lung.
University of Vermont 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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