Airway eosinophilic inflammation, epithelial damage, and bronchial hyperresponsiveness in patients with mild?moderate, stable asthma

Abstract

Allergic asthma is characterized by chronic recruitment of eosinophils in the airways. Once activated, eosinophils release toxic products, including eosinophil cationic protein (ECP), able to damage airway epithelial cells. To test the hypothesis that also in mild‐moderate stable asthma, a significant eosinophil activation could occur, we studied 25 asthmatic patients (34 ± 19 years old), of whom 18 were allergic (27 ± 12 years) and seven nonallergic (42±10 years), with FEV1 values ±70% of predicted, and eight normal volunteers (controls, 33 ±11 years). All subjects underwent methacholine (MCh) challenge on the first visit, and bronchoalveolar lavage (BAL) on the second visit (approximately 3–4 days later). BAL cells were counted and albumin (Alb) (as index of protein dilution in BAL fluid) and ECP levels (as index of eosinophil activation) in BAL fluid were measured. As compared to controls, a significant increase in BAL eosinophil and in BAL epithelial cell numbers was observed in asthmatic patients (P>0.05, each comparison), with no differences between the two asthmatic patient subgroups. Detectable ECP levels (>2 μg/1) were found in BAL of 18 asthmatic patients (14 allergic and four nonallergic asthmatic patients), while Alb levels were measurable in 25 BAL fluids and found to be similar in controls and asthmatic patients, and in the two asthmatic patient subgroups (P>0.05, each comparison). In BAL of asthmatic patients, positive correlations were found between eosinophil numbers and 1) ECP/Alb levels (r= 0.50, P = 0.020); 2) epithelial cell numbers (r = 0.S0, P = 0.014). In asthmatic patients, a significant negative correlation was found between bronchial reactivity to MCh (log Pd15) and ECP/Alb levels in BAL fluid (r=‐0.6, P= 0.005), whereas no correlation was found between log Pd15 MCh and BAL eosinophil or epithelial cell number (P>0.1, each correlation). These data suggest that bronchial eosinophil recruitment and activation may occur also in mild‐moderate stable asthma and that bronchial epithelium damage and airway responsiveness may be partially associated with the eosinophilic inflammatory reaction.

Correlation between reversibility of airway obstruction and exhaled nitric oxide levels in children with stable bronchial asthma

“…Studies have attempted to establish the relationship between exhaled nitric oxide (eNO) and more direct measures of airway inflammation from airway biopsies and bronchoalveolar lavages which require invasive procedures, such as bronchoscopy and bronchial biopsy. 15 Markers of inflammation, such as eosinophils from induced sputum and airway biopsy specimens, are elevated in patients with asthma 16,17 and have been found to correlate with eNO in patients not taking inhaled corticosteroids (ICS). 15 In addition, decreases in eNO correlated with a decrease in bronchial hyperresponsiveness, as measured by methacholine challenge and after initiating ICS therapy.…”

Airway Eosinophilic Inflammation and Bronchial Hyperresponsiveness after Allergen Inhalation Challenge in Asthma

“…Because oxygen radicals and granule-associated proteins released by eosinophils can be toxic to epithelial cells [9,18,19] and because epithelial damage is a described feature in the pathology of asthma [18,24], recruitment and activation of eosinophils may indeed represent a relevant destructive mechanism for epithelial cells in this disorder. In addition, in evaluating asthmatic subjects in stable conditions, a positive correlation was demonstrated between bronchoalveolar lavage (BAL), eosinophil number, and eosinophilic cationic protein (ECP) levels, suggesting that an ongoing activation of these cells parallels their migration [27]. In the same study, the demonstration of weak correlations between the number of BAL eosinophils and ciliated epithelial cells and between BAL ECP levels and bronchial reactivity to methacholine (MCh) supported the hypothesis that bronchial epithelial damage and airway hyperresponsiveness ''at baseline'' may be partially associated with the release of ECP [27].…”

“…In addition, in evaluating asthmatic subjects in stable conditions, a positive correlation was demonstrated between bronchoalveolar lavage (BAL), eosinophil number, and eosinophilic cationic protein (ECP) levels, suggesting that an ongoing activation of these cells parallels their migration [27]. In the same study, the demonstration of weak correlations between the number of BAL eosinophils and ciliated epithelial cells and between BAL ECP levels and bronchial reactivity to methacholine (MCh) supported the hypothesis that bronchial epithelial damage and airway hyperresponsiveness ''at baseline'' may be partially associated with the release of ECP [27]. With this background, the present study was designed to evaluate whether ECP levels in BAL fluid could reflect, better than BAL eosinophil counts, the cellular activation that follows allergen exposure in atopic asthmatics.…”

Bronchial and Bronchoalveolar Inflammation in Single Early and Dual Responders after Allergen Inhalation Challenge

“…Eosinophils have been implicated as one of the primary effector cells in the tissue damage observed in severe bronchial asthma [14], since they can produce leukotrienes and oxygen radicals at two to three times the rate of similarly activated neutrophils and a variety of cytotoxic cationic proteins, including ECP [17]. In this context, epithelial damage or loss is a well known characteristic finding in biopsies [16] and BAL fluids obtained from patients with asthma [26]. In addition, it has been reported that granule cationic proteins, including ECP, can cause dose-related damage to guinea pig tracheal epithelium [24].…”