Invited Review: Complexity of factors modulating airway narrowing in vivo: relevance to assessment of airway hyperresponsiveness

In vivo, the airway response to constrictor stimuli is the net result of a complex array of factors, some facilitating and some opposing airway narrowing, which makes the interpretation of bronchial challenges far from being straightforward

Vito Brusasco; Riccardo Pellegrino

2015

Scholarcy highlights

  • In vivo, the airway response to constrictor stimuli is the net result of a complex array of factors, some facilitating and some opposing airway narrowing, which makes the interpretation of bronchial challenges far from being straightforward
  • No matter how important the release of inflammatory mediators in the pathogenesis of Airway hyperresponsiveness may be, no studies have been able to fully explain how airway inflammation translates into airway narrowing, which is the basic event in bronchial asthma
  • Interesting in this respect is the hypothesis that AHR could result from an individual genetic predisposition to develop an abnormal response to inflammatory stimuli, possibly involving changes in airway smooth muscle
  • Subsequent studies that used different measurements of airway caliber found that a difference in dose-response curve existed between asthmatic and normal subjects even when deep inhalation were prohibited, such a difference was further increased with the DIs taken after each dose of methacholine
  • In the latter study, a series of DIs taken before the airways were exposed to methacholine was unexpectedly associated with a significant decrease of the functional parameters not preceded by a full lung inflation in asthmatic and healthy subjects compared with when DIs were avoided, suggesting paradoxical bronchoconstriction
  • Isolated ASM is able to produce enough force to shorten to 20% of its optimal length
  • Lumping all these variables together is a real challenge if we wish to understand the mechanisms of AHR, but perhaps it is the only realistic approach that offers directions for future effective treatment

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