LOCAL ALLERGEN CHALLENGE AND BRONCHOALVEOLAR LAVAGE OF ALLERGIC ASTHMATIC LUNGS - DESCRIPTION OF THE MODEL AND LOCAL AIRWAY INFLAMMATION

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Abstract
The local mechanisms that result in the cellular inflammation and bronchial airway hyperreactivity that characterize allergic bronchial asthma are poorly defined. In order to study these processes, we developed a method for local allergen challenge using a fiberoptic bronchoscopie and direct observation and bronchoalveolar lavage (BAL) to assess the airway responses to allergen. In these studied, 11 allergic asthmatics (all of whom had previously demonstrated a late-phase asthmatic response to aeroallergen challenge) and 6 healthy, asymptomatic subjects volunteered to undergo bronchoalveolar lavage after local airway challenge via a bronchoscope wedged into subsegmental airways. These studies revealed that asthmatic airways respond to allergen with an immediate pallor followed by reactive hyperemia, edema, and bronchial narrowing. This site and a control site were relavaged at 48 or 96 h after challenge, as did helper T-lymphocytes. Characteristically, at 96 h, neutrophil counts returned to normal values, whereas eosinophiles and helper T-cells remained elevated. Peroxidase-staining cells were also elevated at 48 h after local allergen challenges. Electron microscopy revealed degranulation of mast cells and eosinophils, both immediately and later (48 and 96 h) after local allergen challenge. Macrophages were highly activated and had phagocytized, partially intact granules from both eosinophils and mast cells. There was a significant correlation (p < 0.001) between the concentration of allergen required to produce a visible airway response and a positive end-point skin titration in the asthmatic subjects. The FEV1 decreased 12.9% from baseline (0 < 0.001) after the initial local challenge and bronchoalveolar lavage, but did not change during the repeat bronchoalveolar lavage. Two asthmatics developed localized wheezing, which was easily reversed with locally applied epinephrine. All patients reverted to baseline pulmonary function values within 15 min of challenges. These results suggest that when allergen is introduced into allergic asthmatic airways, there is (1) an immediate local response characterized by blanching, hyperemia, and airway narrowing, and (2) a significant degree of cellular inflammation induced locally, which can persist for as long as 4 days. Local allergen challenge followed by bronchoalveolar lavage is a safe and effective method for examining the consequences of allergen provocation of allergic asthmatic airways and, therefore, the mechanisms of chronic allergic asthma.