Immediate and Late Airway Response of Allergic Rhinitis Patients to Segmental Antigen Challenge: Characterization of Eosinophil and Mast Cell Mediators

Abstract

Segmental antigen bronchoprovocation was used to define the nature of the inflammatory process in allergic airway disease. Bronchoalveolar lavage fluid obtained from allergic rhinitis patients 12 min after segmental antigen instillation (immediate response) revealed a significant increase in histamine and tryptase, but no cellular response. Repeat segmental lavage 48 h later (late response) showed marked and significant increases in both low and normal density eosinophils as well as striking elevations of eosinophil granular protein levels (major basic protein, eosinophil-derived neurotoxin, eosinophil cationic protein, and eosinophil peroxidase). Leukotriene C4, but not tryptase, concentrations were also consistently elevated in late lavage samples. Further, the late lavage samples showed a significant increase in interleukin-5 concentrations that correlated with the presence of eosinophils and eosinophil granular proteins. Neither eosinophils nor soluble mediators of eosinophils increased when normal subjects were similarly challenged with antigen. These data suggest that eosinophils are attracted to the airway during the late-phase allergic reaction and that IL-5 may produce changes in airway eosinophil density and promote the release of granular proteins to cause airway injury.

Segmental Bronchial Provocation Induces Nasal Inflammation in Allergic Rhinitis Patients

“…Previous studies involving allergic rhinitis and asthma patients have shown a significant increase in IL-5 concentrations in BALF after SBP (11,27,28). We could also demonstrate an increased expression of both IL-5 and eotaxin in the bronchial mucosa of allergic patients 24 h after SBP.…”

“…Generalized pulmonary inflammation cannot be explained by bronchoscopic and biopsy findings, per se (21). To minimize intraluminal spread of antigen from the allergenchallenged bronchial segment to other segments, we held the bronchoscope in the wedged position for 5 min, as has been suggested by other authors (11). It is also very unlikely that allergen spilled into the nose after SBP, since we performed bronchoscopy by the oral route, and it did not lead to excessive coughing.…”

“…It is clear that the condition of the upper airways definitely influences the lower airways. In allergic rhinitis patients without bronchial hyperreactivity (BHR), signs of allergic inflammation of the lower airways have been found in induced sputum, bronchoalveolar lavage fluid (BALF), and bronchial biopsy specimens (10)(11)(12)(13). The nasal-bronchial reflex, an altered breathing pattern, pulmonary aspiration of nasal contents, and increased levels of inflammatory factors in the blood are possible mechanisms for lower airway dysfunction among patients with rhinitis (14).…”

Enhanced peripheral leukocyte leukotriene production and bronchial hyperresponsiveness in asthmatics

“…This suggests that enhanced LTC 4 production is closely related to the pathophysiology of asthma attacks. These results are consistent with a report that showed enhanced LTC 4 production by activated eosinophils during antigen challenge [19]. In addition, SCHAUER et al [20] showed that, upon stimulation with the ionophore A23187, the granulocytes of asthmatic children generated significantly more LTC 4 than those of healthy controls.…”

Lidocaine in bronchoalveolar lavage fluid (BALF) is an inhibitor of eosinophil-active cytokines

“…The gene cluster for IL-3, IL-4, IL-5 and GM-CSF is expressed by bronchoalveolar T lymphocytes in patients with atopic asthma [22], and mRNA for IL-5 has been detected in bronchial tissue biopsies of patients with asthma [23]. In previous studies, IL-5 and, in some cases, GM-CSF and/or IL-3 were detected in BALF from patients with allergic rhinitis who underwent segmental bronchoprovocation with ragweed extract [24,25]. Significant elevations of tumour necrosis factor (TNF), GM-CSF, IL-1 , IL-2, and IL-6 were detected by immunoassay (GM-CSF, IL-1 and IL-6), bioassay (TNF and IL-6), and polymerase chain reaction (PCR) (IL-1 and TNF) in the airways of patients with symptomatic asthma compared with that of patients with asymptomatic asthma [26].…”