Increases in airway eosinophils and interleukin-5 with minimal bronchoconstriction during repeated low-dose allergen challenge in atopic asthmatics

Abstract

Asthma induced by the inhalation of various allergens in the clinical research laboratory, has been a model for studying pathophysiology and pathogenesis of this disease for many years [1][2][3][4]. The inhalation of a specific allergen by asthmatic subjects can cause three types of airway responses [5]: the isolated response, that develops within 10-30 min after allergen challenge; the isolated late response that develops 3-8 h after the challenge; and the dual response, where subjects develop both early and late airway responses. The late response is associated with allergeninduced increases in airway responsiveness [6] and with eosinophilic airway inflammation [7].The doses of allergen usually used to study experimentally induced asthma are of a magnitude that causes an early response of at least a 15% reduction in forced expiratory volume in one second (FEV1) and a late response of at least 20% [5]. A shortcoming of this method is that these doses of allergen may be much higher than those to which patients with asthma are exposed in their natural environments. This shortcoming has been addressed by IHRE and co-workers [8,9], who used airway challenge with a low-dose of allergen. At first, these investigators studied early and late responses after a single challenge with low-dose allergen [8]. Later, they used repeated lowdose allergen challenge and demonstrated a significant increase in airway hyperresponsiveness [9]. However, the role of airway inflammation in causing these changes, as well as the time course of these events, has not been studied previously.The purposes of the present study were: 1) to determine the effects of repeated low-dose allergen challenge on airway inflammation as measured by numbers of eosinophils and metachromatic cells in induced sputum, as well as markers of eosinophil activation and level of the eosinopoietic cytokine IL-5; 2) to evaluate the effects of repeated low-dose allergen challenge on the development of late responses and methacholine airway hyperresponsiveness and to examine the time course of the changes; and 3) to evaluate the effects of repeated low-dose challenge on asthma symptoms and β 2 -agonist use. Increases in airway eosinophils and interleukin-5 with minimal bronchoconstriction during repeated low-dose allergen challenge in atopic asthmatics. I. Sulakvelidze, M.D. Inman, T. Rerecich, P.M. O'Byrne. ©ERS Journals Ltd 1998.ABSTRACT: Repeated low-dose allergen challenge increases airway hyperresponsiveness in atopic asthmatics. However, it is not known whether low-dose allergen challenge increases airway inflammation.Eight atopic asthmatics were enrolled in a controlled, cross-over study to evaluate the effect and time course of repeated low-dose allergen challenge on airway inflammation and hyperresponsiveness. The dose of allergen to reduce forced expiratory volume in one second (FEV1) by approximately 5% was selected in a screening allergen challenge. The subjects then were challenged for five consecutive days with either diluent or the selected low-dose of a...

Eosinophilopoiesis in A Murine Model of Allergic Airway Eosinophilia: Involvement of Bone Marrow IL-5 and IL-5 Receptor α

“…Repeated allergen exposure results in an accumulation of eosinophils in the airways over several days, both in humans (36) and in sensitized mice (Table I). In the present experiments in a murine model of allergic airway inflammation, eosinophils are already evident in the airways 24 h after two allergen exposures on consecutive days, and after the third exposure, newly produced eosinophils significantly contribute to this inflammatory response (Table I and Fig.…”

Definitions and types of work-related asthma: a nosological approach

“…Although it is not invariably the case, late reactions are associated with an increase in NSBH and in airway inflammation, more often than immediate reactions [11][12][13][14]. Furthermore, exposure to inducers at doses that do not elicit airflow obstruction can provoke an increase in NSBH and airway inflammation, which can be assumed to result in a worsening of the asthma condition [15,16]. Viral infections, particularly in children, can induce asthma in a similar way to that of allergens [17].…”

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

“…For example, the allergen-induced early and late asthmatic response in the conventional highdose allergen challenge is associated with an increase in urinary levels of 9a11b-PGF 2 [12]. While the activation of eosinophils has been shown to occur in the low-dose challenge [2,7,8], the activation of mast cells has been less explored. It is becoming increasingly evident that the pathogenetic role of the eosinophil in asthmatic airway inflammation is uncertain [13].…”

“…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]. The aim of the current study was to further characterise the influence of repeated low-dose allergen challenge on the development of airway inflammation.…”

“…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].…”