Repeated Inhalation of Low Doses of Cat Allergen That Do Not Induce Clinical Symptoms Increases Bronchial Hyperresponsiveness and Eosinophil Cationic Protein Levels

Abstract

The aim of this study was to investigate whether repeated exposure to subclinical doses of cat allergens, not inducing asthma symptoms, could affect eosinophil cationic protein (ECP) levels in bronchoalveolar lavage (BAL) or in peripheral blood, without the appearance of clinical symptoms. Twelve patients with mild asthma, all sensitized to cats and not exposed to cat allergen at home, underwent a series of inhalations of cat allergen or placebo for 8 days over 2 weeks. A methacholine challenge was performed before and after the allergen and saline exposures, and BAL and blood were sampled for ECP measurements and eosinophil counts. No patients experienced asthma symptoms. However, PD20 methacholine (geometric mean) decreased significantly from 263 μg before to 126 μg after inhalation of allergen. Inhalation of saline did not induce any significant change in PD20. The change in log PD20 before and after cat allergen exposure was statistically different from the change in log PD20 before and after saline. Median ECP levels in BAL and serum increased significantly after allergen exposure, from 0.8 to 3.1 μg/l (p<0.02) and from 15.9 to 31.4 μg/l (p<0.05), respectively. No change was observed after saline inhalations. The change in BAL and serum ECP levels was statistically significant compared to that in the control group. The number of eosinophils did not change, however, nor did IL–5 and RANTES levels in BAL and serum. In conclusion, our results show that (1) exposure of asthma patients to repeated low doses of allergen, which did not provoke any clinical symptoms, is capable of inducing a local eosinophil activation associated with an increase in nonspecific bronchial hyperresponsiveness and (2) the increase in serum ECP levels due to eosinophil activation precedes the occurrence of asthma symptoms and may thus be a marker of allergen exposure in allergic asthma.

Nerve growth factor levels and localisation in human asthmatic bronchi

“…Selection criteria for the asthmatic patients included a well-documented history of asthma and bronchial hyperresponsiveness, as assessed by a methacholine challenge test (18-2,340 mg) at a screening visit, according to a standardised procedure, as described previously [30].…”

Early rise in exhaled nitric oxide and mast cell activation in repeated low-dose allergen challenge

“…However, investigations of mechanisms of airway inflammation in this particular model have been rather limited so far, and findings in peripheral blood are largely negative [5,7,9]. In a diluent controlled evaluation of the challenge, the percentage of eosinophils, interleukin-5 and eosinophil cationic protein in induced sputum were shown to increase [2], and early effects on eosinophils and macrophages in bronchoalveolar lavage fluid have also been reported [9,10].…”

“…In this challenge setting, patients with atopic asthma were subjected to inhalations of fixed doses of allergen, titrated to cause minimal bronchoconstriction and administered once daily on 4-10 consecutive weekdays [1][2][3][4][5][6]. The procedure generates a distinct increase in airway hyperresponsiveness (AHR) to direct bronchoconstrictors [1][2][3][4][5][6].…”

Variants in TGFB1, Dust Mite Exposure, and Disease Severity in Children with Asthma

“…Animal models have demonstrated the importance of TGF-b1 in allergen-induced T helper type 2 (Th2)-mediated airway inflammation (7), but the precise role of TGF-b1 in asthma has been difficult to define. In murine models, overexpression of the gene for TGF-b1 (TGFB1) leads to increased airway inflammation and subepithelial fibrosis (8,9).…”

“…In humans, levels of TGF-b1 are higher in the bronchoalveolar lavage (BAL) fluid of subjects with asthma than in that of control subjects (11). Moreover, TGFB1 expression is increased in the asthmatic airway upon repeated exposure to low-dose allergen, suggesting that TGFB1 is involved in the late phase of airway inflammation (7). Given these observations, we hypothesized that variants in TGFB1 would influence disease severity in children with asthma.…”