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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.

Local immunotherapy (LIT) with Dermatophagoides extract or placebo were administered to two groups of 11 patients with allergic asthma in a double-blind fashion. All patients received cromolyn sodium (20 mg four times a day) during treatments. Bronchial provocation tests with allergen and methacholine were performed before, 1 week, and 4 weeks after the end of treatments. Symptom score, drug consumption, and peak expiratory flow were monitored daily from 2 weeks before to 4 weeks after treatments. Compared to baseline, early bronchial sensitivity to allergen was significantly reduced both 1 week (p less than 0.0005) and 4 weeks (p less than 0.01) after LIT but not after placebo administration. Late bronchial reaction to allergen occurred similarly after placebo administration and LIT. However, in the group with LIT, the severity of late reaction was unchanged after treatment in spite of the significantly larger doses of allergen administered to provoke the early asthmatic reaction. Neither symptom score, nor drug consumption, nor peak expiratory flow were significantly different in the two groups before and during the treatment period even though both symptom score and drug consumption tended to be reduced after LIT. We conclude that LIT may be an effective and safe alternative to traditional immunotherapy.

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.

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.

Twelve patients with asthma sensitized to Dermatophagoides pteronyssinus and Parietaria judaica were studied. Patients were challenged before (winter), during (summer), and after (autumn) Parietaria-pollen season. Early asthmatic reaction was positive for both allergens, and the provocative dose causing a 15% decrease of FEV1 was similar in all seasons. The provocative dose of methacholine causing a 15% decrease of FEV1 and specific IgEs for both allergens were also not significantly different throughout the time of study. Late asthmatic reaction (LAR) to Dermatophagoides occurred in eight of 12 patients in winter, in six of nine in summer, and in five of six patients in autumn. The severity of LAR, expressed as the maximum fall of FEV1 3 to 8 hours after challenge, was not significantly different between seasons. LAR to Parietaria occurred in only one of 12 patients in winter, in six of 11 in summer, and in one of six patients in autumn. In summer, LAR to Parietaria was significantly more severe than in winter. In both winter and autumn, but not in summer, LAR to Dermatophagoides was significantly more severe than to Parietaria. We conclude that LAR is allergen specific, and natural exposure has a priming effect on LAR.