Mechanism of hyperresponsive airways

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Abstract

It has been known for many years that the response of asthmatic subjects to a deep inspiration differs from that observed in normal healthy subjects. A deep inspiration causes a decrease in airway resistance in normal subjects, whereas asthmatics demonstrate either no change or a slight increase in airway resistance. It has been suggested by several investigators that the inability to dilate airways during lung inflation may be a primary defect in asthma. One study (Skloot and colleagues, J. Clin. Invest. 1995;96:2393-2403) showed that in the absence of a deep inspiration during methacholine (MCh) challenge, normal subjects had a greatly exaggerated and sustained response to this agonist. It was suggested that asthmatic airways could be modeled by this condition in normal, subjects. Other investigators, however, suggest that there are more intrinsic differences between the responses to lung inflation in airways from asthmatic and normal subjects (Brusasco and colleagues, J. Appl. Physiol. 1999;87:567-573). Resolution of this controversy requires the ability to assess the responses of airways directly, but unfortunately conventional pulmonary function tests in human subjects are not specific enough to allow this evaluation. In the present study, we have performed experiments using a direct imaging approach that allows us to obtain measurements of airway and parenchymal dimensions that can be used to test the responses of individual airways to deep inspiration in vivo. Our results show that the presence of normal tidal stresses allows airway smooth muscle to respond normally to deep inspirations. Removing tidal stresses at FRC after MCh challenge is sufficient to change the normal dilatory response to deep inspiration into an abnormal one of contraction. Altered sensitivity of airway smooth muscle to normal tidal stresses thus may be operative in the development of the asthmatic pathology.

Original languageEnglish (US)
Pages (from-to)1619-1623
Number of pages5
JournalAmerican journal of respiratory and critical care medicine
Volume161
Issue number5
DOIs
StatePublished - Jan 1 2000

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ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

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