Effect of airway remodeling and hyperresponsiveness on complexity of breathing pattern in rat.

The complexity of respiratory dynamics is decreased, in association with disease severity, in patients with asthma. However, the pathophysiological basis of decreased complexity of breathing pattern in asthma is not clear. In the present study, we investigated the effect of airway remodeling and hyperresponsiveness induced by repeated bronchoconstriction (using methacholine) on breathing pattern in rats with or without allergen-induced sensitization. Entropy analysis of respiratory variability showed decreased irregularity (less complexity) of respiratory rhythm in this rat model of asthma. Airway remodeling and hyperresponsiveness induced by repeated bronchoconstriction also led to increased regularity of respiratory dynamics in sensitized rats. However, these airway alterations had no significant effect on the complexity of breathing pattern in non-sensitized rats. Our results indicate that mechanical respiratory alterations cannot per se attenuate the complexity of respiratory dynamics, unless there is an underlying inflammation. We suggest further studies on underlying mechanisms of breathing variability with focus on respiratory control alterations due to airway inflammation.

Bronchoconstriction Induces Structural and Functional Airway Alterations in Non-sensitized Rats.

The impact of mechanical forces on pathogenesis of airway remodeling and the functional consequences in asthma remains to be fully established. In the present study, we investigated the effect of repeated bronchoconstriction induced by methacholine (MCh) on airway remodeling and airway hyperresponsiveness (AHR) in rats with or without sensitization to an external allergen. We provide evidence that repeated bronchoconstriction, using MCh, alone induces airway inflammation and remodeling as well as AHR in non-allergen-sensitized rats. Also, we found that the airways are structurally and functionally altered by bronchoconstriction induced by either allergen or MCh in allergen-sensitized animals. This finding provides a new animal model for the development of airway remodeling and AHR in mammals and can be used for studying the complex reciprocal relationship between bronchoconstriction and airway inflammation. Further studies on presented animal models are required to clarify the exact mechanisms underlying airway remodeling due to bronchoconstriction and the functional consequences.