© 2008 American Thoracic Society
Mucous Obstruction and Airway Hyperresponsiveness in MiceTo the Editor:Mucous obstruction may be an important component of airway hyperresponsiveness (AHR), an idea that has received support by Dr. Lundblad and colleagues, in their article on airway closure and AHR (1). They used input impedance analysis and CT imaging to prove that airway closure at the dorsal base of the lung importantly determined AHR in a mouse model of asthma. In a similar model, we found that inhibition of methacholine-induced mucin secretion by a MARCKS protein–related peptide attenuated AHR measured by double-chamber plethysmography (DCP) (2). Even after eliminating the nasal component of airway resistance change, the effect of mucus hypersecretion on AHR remained (2, 3). Since DCP and input impedance analysis are very different techniques, our results are not directly comparable. However, there are some interesting similarities to our findings. First, Lundblad and coworkers found the dominant anatomic location of airway closure to be at the dorsal base of the lung, possibly related to the dominant large central airways that track far into the base of each lung in mice. Mucus production in allergic asthma models is restricted to the central airways of mice (4), suggesting that maximal mucus secretion would be along the long central airway tracking into the bases. Distal occlusion of this airway by mucus would result in a pattern of airway closure similar to that reported. While we did not see histological evidence of this post mortem, that does not exclude temporary airway closure during methacholine challenge. Perhaps future studies examining airway closure will include a group with deficient mucin secretion. Second, we both find that the experimental basis of AHR may not reflect the common understanding of AHR. Lundblad and coworkers have taken an important step forward by questioning the use and implications of the term AHR. This should be applauded and certainly merits further discussion.
Institute of Genomics and Integrative Biology FOOTNOTES Conflict of Interest Statement: A.A. received $15,000 in 2006 as unrestricted grants from Biomarck Pharmaceuticals for conducting animal trials. REFERENCES
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