Increased Airway Inflammation with Segmental versus Aerosol Antigen Challenge

Abstract

Airway inflammation is increasingly recognized as a pivotal component of asthma. Because allergens provoke bronchial constriction and inflammation in allergic subjects, bronchial antigen challenge has emerged as a powerful technique for evaluating mechanisms involved in this process. In this study, we compare whole lung antigen challenge (WLAC) with segmental bronchoprovocation (SBP) in eight allergic, non-asthmatic, non-smoking subjects, and evaluated the response by bronchoalveolar lavage (BAL) prior to, and 48 h after antigen challenge. Both challenge techniques evoked airway inflammation, manifest as an increase in total cells and eosinophils recovered by BAL, an increase in total protein concentration, and enhanced production of superoxide anion by airspace cells. The degree to which these changes occurred was significantly greater with SBP than WLAC, and only SBP evoked persistent measurable change in alveolar macrophage density and eosinophil granule protein concentrations. Moreover, although both techniques were associated with a comparable immediate fall in FEV1, only WLAC resulted in statistically significant persistent physiologic changes 48 h afterwards. We conclude that, as anticipated, SBP produces more intense airway inflammation in allergic subjects, does not result in late airway obstruction, and offers specific advantages in studying allergen-driven airway inflammation.

Up-Regulation and Activation of Eosinophil Integrins in Blood and Airway after Segmental Lung Antigen Challenge

“…The purpose of the present study was to define changes in the expression levels and activation states of blood and airway eosinophil integrins 48 h following segmental allergen challenge in asthmatic subjects, thus reflecting the development of allergic inflammation. Segmental Ag challenge induces a strong local recruitment of eosinophils (27). We found characteristic integrin changes on blood and airway eosinophils, differences between single and dual responder asthmatics, and associations among integrin changes, magnitude of eosinophil recruitment to airway, and IL-5 concentration in bronchoalveolar lavage (BAL) 3 fluid.…”

“…Bronchoscopy, segmental bronchoprovocation with allergen, and subsequent BAL were performed in two different bronchopulmonary segments as described (27,28,30). Baseline BAL at 0 h immediately before segmental bronchoprovocation was performed in two segments.…”

The allergen bronchoprovocation model: an important tool for the investigation of new asthma anti‐inflammatory therapies

“…Local (segmental) airway challenges have also been safely performed in subjects with asthma (61)(62)(63). This method requires direct instillation of allergen to selected segmental airways using a bronchoscope.…”

Allergic Rhinitis and its Impact on Asthma (ARIA) 2008*

“…Allergy as a local disease. Endobronchial allergen challenge carried out on nonasthmatic patients with seasonal rhinitis induced bronchoconstriction (1989) and the secretion of proinflammatory mediators and cytokines as well as the recruitment of inflammatory cells in the lavage fluid (1990)(1991)(1992). These studies combine to indicate that patients with nasal symptoms can develop asthma only if the allergen is properly administered into the airways.…”