Abstract
BackgroundThere is increasing evidence that the small airways contribute significantly to the pathophysiology of asthma. However, due to the difficulty in accessing distal lung regions in clinical settings, functional changes in the peripheral airways are often overlooked in studies of asthmatic patients. The aim of the current study was to characterize progressive changes in small airway function in sheep repeatedly challenged with house dust mite (HDM) allergen.Methodology/Principal FindingsFour spatially separate lung segments were utilized for HDM challenges. The right apical, right medial, right caudal and left caudal lung segments received 0, 8, 16 and 24 weekly challenges with HDM respectively. A wedged-bronchoscope technique was used to assess changes in peripheral resistance (Rp) at rest, and in response to specific and non-specific stimuli throughout the trial. Allergen induced inflammatory cell infiltration into bronchoalveolar lavage and increases in Rp in response to HDM and methacholine were localized to treated lung segments, with no changes observed in adjacent lung segments. The acute response to HDM was variable between sheep, and was significantly correlated to airway responsiveness to methacholine (rs = 0.095, P<0.01). There was no correlation between resting Rp and the number of weeks of HDM exposure. Nor was there a correlation between the magnitude of early-phase airway response and the number of HDM-challenges.ConclusionsOur findings indicate that airway responses to allergic and non-allergic stimuli are localized to specific treated areas of the lung. Furthermore, while there was a decline in peripheral airway function with HDM exposure, this decrease was not correlated with the length of allergen challenge.
Highlights
Asthma is a chronic inflammatory disease involving both the proximal and distal airways
While there was a decline in peripheral airway function with house dust mite (HDM) exposure, this decrease was not correlated with the length of allergen challenge
The Rp in the HDM-challenged segment increased by 2686178% from baseline (Figure 2A), while there was no change in the Rp in the adjacent untreated lung segment (29.764.6%)
Summary
Asthma is a chronic inflammatory disease involving both the proximal and distal airways. There is increasing evidence of chronic inflammation and the presence of structural changes within the small airways of asthmatic patients [1,2,3]. In some cases, these changes are even more severe than what is seen in the large central airways [1]. There is increasing evidence that the small airways contribute significantly to the pathophysiology of asthma. Due to the difficulty in accessing distal lung regions in clinical settings, functional changes in the peripheral airways are often overlooked in studies of asthmatic patients. The aim of the current study was to characterize progressive changes in small airway function in sheep repeatedly challenged with house dust mite (HDM) allergen
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