Bronchial Neutrophilia in Patients with Noninfectious Status Asthmaticus

Abstract

Cellular events that occur in status asthmaticus (SA) remain poorly investigated. Autopsy studies frequently emphasized about the presence of eosinophils in bronchial airway wall, whereas recent studies reported increased number of neutrophils in patients dying of sudden-onset fatal asthma. Mucus plugs occluding the bronchial lumen are almost constant features during SA. Bronchial lavage (BL) may be useful to remove mucus plugs in cases of atelectasis and/or refractory SA. We investigated the contribution of different cell types and cellular mediators (neutrophil elastase, eosinophil cationic protein [ECP], histamine, interleukin-8 [IL-8]) to the pathogenesis of SA. We studied 16 BL from eight patients undergoing mechanical ventilation (MV) for SA (time interval from onset of MV = Day 0 to Day 11), four BL from patients undergoing MV without preexisting respiratory disease (V), 11 BL from patients with stable asthma (A) and eight BL from healthy controls (C). SA exhibited higher number and percentage of neutrophils (81.5 +/- 4.5%) than V (44.3 +/- 12.2) (p < 0.05), A (6.9 +/- 2.7) and C (9.5 +/- 3.8) (p < 0.0001), and higher number of eosinophils than V, A, and C (p < 0.01). Neutrophil elastase, ECP, and IL-8 levels were dramatically increased in SA. Histamine was higher in SA than in C and V (p < 0.05). Bronchial neutrophilia was not related to concomitant bacterial infection as bacteriological cultures were positive in only three BL. Eosinophils, mast cells and histamine were higher in BL performed within the first 48 h of MV (p < 0.05) than in BL performed later on. Our results indicate that bronchial inflammation in SA differs from bronchial inflammation in mild asthma. Persistent bronchial neutrophilia is associated with increased eosinophils and mast cells in the early phase of SA. Neutrophils may result in tissue damage and participate to the shedding of the epithelium in SA.

Th17 cells: new players in asthma pathogenesis

“…In those patients with asthma in which inflammation is nonatopic, non-IgE-dependent, and noneosinophilic, airway neutrophilia is correlated with asthma severity, suggesting a major role for neutrophils, at least in this subset of patients with asthma (70,71). Neutrophilic inflammation has also been described in sudden-onset fatal asthma and neutrophil numbers are highly elevated in status asthmaticus (72), thus suggesting a possible role for these cells in severe and fatal asthma. As the role of IL-17 in neutrophil recruitment to the airways is well known, in the last years several studies tried to find an association between Th17 lymphocytes and asthma (73)(74)(75)(76)(77).…”

Neutrophilic airway inflammation and IL‐17

“…There is evidence from clinical studies that an exaggerated recruitment and activation of neutrophilic granulocytes in the airways is linked to the clinical course of several inflammatory diseases in the airways and lungs, such as asthma (1)(2)(3)(4)(5)(6)82), nonspecific bronchial hyperreactivity (BHR) (7), chronic bronchitis (3,(8)(9)(10), chronic obstructive pulmonary disease (COPD) (3,(11)(12)(13), cystic fibrosis (14)(15)(16)(17), and acute respiratory distress syndrome (18)(19)(20). The referred evidence has been gathered analysing cellular contents in bronchial tissue, in bronchoalveolar lavage (BAL) fluid, in bronchial biopsies, in induced sputum and in peripheral blood.…”

“…In severe asthma, for example, it can be detected in the submucosa of bronchi, even when no eosinophils are present, underlining the possibility that the neutrophil itself is more pivotal for developing severe asthma than is the eosinophil (6). The concentration of neutrophil elastase within the airway lumen is also increased in severe asthma, even when there is no detectable airway infection present (2)(3)(4). An increase in neutrophil elastase is also detected in the airways in chronic bronchitis and in COPD (3,39).…”

Airway neutrophils and interleukin-17

“…This has been indicated by studies involving bronchoalveolar lavage (BAL) fluid and bronchial biopsy samples as well as induced sputum from patients [1±6]. Recent data suggest that this increased number of airway neutrophils is not associated with detectable airway infection [6].…”