To determine whether a link exists between the recruitment of inflammatory cells in the airways and the development of the late-phase asthmatic reaction, we studied with bronchoalveolar lavage 54 asthmatic patients either at baseline (10 patients) or 4 h (11 patients), 24 h (13 patients), and 72 h (20 patients) after allergen inhalation challenge. Among the patients studied 4 h after allergen challenge, five were known to have a late-phase asthmatic response and showed a significant increase in the number and percentage of eosinophils in bronchoalveolar lavage compared with either patients without late-phase response (p less than 0.05) or unchallenged patients (p less than 0.01). Both the number and the percentage of eosinophils in bronchoalveolar lavage were also increased (p less than 0.05) in patients without a late-phase asthmatic reaction studied 24 h but not in those studied 4 h after allergen challenge. The numbers and the percentages of macrophages, neutrophils, or lymphocytes did not differ significantly among the different groups of patients. Of the patients studied 4 and 24 h after allergen challenge, only those with a late-phase asthmatic response showed an increased airway responsiveness to methacholine 1 h before bronchoalveolar lavage. We conclude that the development of the late-phase asthmatic response to allergen inhalation challenge and the allergen-induced increase in airway responsiveness are associated with an early recruitment of eosinophils in the airways.
The relationship between airway responsiveness to methacholine and inflammatory cells in bronchoalveolar lavage (BAL) was determined in patients with history of rhinitis and/or mild bronchial asthma either at baseline (10 patients) or 3-4 h after allergen inhalation challenge (11 patients). At baseline, airway responsiveness did not correlate with any BAL cell population. When data obtained after allergen challenge were included in the analysis, 44% of the variability of airway responsiveness was explained by a multiple regression model with BAL eosinophils as a directly correlated (P = 0.002) independent variable and with BAL macrophages as an inversely correlated (P = 0.045) independent variable. Changes in airway responsiveness after allergen challenge were predicted (82% of variance explained) by a model with BAL eosinophils and BAL lymphocytes as directly correlated (P = 0.0002 and P = 0.03, respectively) independent variables. We conclude that, in stable asymptomatic asthma, baseline airway responsiveness does not correlate with the presence in the airways of inflammatory and immunoeffector cells that can be recovered by BAL. Nevertheless the allergen-induced increase in airway responsiveness is associated with an influx of eosinophils and lymphocytes in the bronchial lumen.
Nonspecific bronchial responsiveness was studied in 23 allergic patients with a history of rhinitis and/or bronchial asthma who underwent fiberoptic bronchoscopy with bronchoalveolar and bronchial lavage (BAL-BL) 4h (Group A) or 24 h (Group B) after an allergen inhalation challenge. In all patients, the dose of methacholine causing an FEV1 fall of 15% (PD15) was determined at baseline, 24 h before allergen challenge. Methacholine bronchial challenge was repeated 1 h before BAL-BL in patients of both groups and again 12 to 14 h after BAL-BL in Group A and 24 h after BAL-BL in Group B. In patients of Group A, the values of methacholine PD15 after BAL-BL were not significantly different from those determined before BAL-BL. This was also the case in patients in whom bronchial responsiveness was increased after allergen challenge. In patients of Group B, methacholine PD15 was significantly decreased after allergen challenge, and this decrease was correlated with the occurrence and the severity of the late asthmatic reaction. Even in patients who showed dual asthmatic reactions and an increased responsiveness after allergen challenge, methacholine PD15 was not further decreased after BAL-BL. These data support the safety of a procedure combining bronchial allergen challenge with BAL-BL, which can be used for studies on the pathophysiology of bronchial asthma.
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