Abstract
The relationship among airway responsiveness, inflammation and remodelling in asthma is incompletely understood. To investigate potential mechanistic associations, allergen-induced asthma was studied in C57Bl/6 mice. Mice were sensitized and challenged with ovalbumin (OVA) using sub-acute (SA) or chronic (C) protocols. Responsiveness was assessed by measuring respiratory impedence which was partitioned into airway resistance (Raw) and distal lung components (Gti, Hti) during methacholine-induced constriction. Inflammation, airway mucus, airway smooth muscle, collagen, biglycan and decorin were quantified. The airways were sub-divided into central or peripheral. In SA and C OVA, Raw, Gti and Hti responsiveness were significantly increased; the peripheral response was significantly greater in SA vs C OVA. Airway inflammation and mucus were increased in both groups, but more significantly in peripheral airways in SA OVA. In the SA OVA model, inflammation and mucus appear to drive the mechanical response, especially in the lung periphery; airway remodelling seems to contribute to hyper-responsiveness to an equivalent degree, after both challenge protocols.
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