Characteristics of the Inflammatory response in bronchial lavage fluids from patients with status asthmaticus

Abstract

Status asthmaticus (SA) is a sudden respiratory failure characterized by an acute bronchospasm with a severe inflammation, requiring in some cases mechanical ventilation (MV). Initial postmortem studies emphasized the presence of eosinophils in the bronchial wall and of mucus plugs filling the bronchi. More recently a prominent neutrophil influx was observed in patients with fatal or near fatal asthma. The aim of our study was to evaluate characteristics of bronchial inflammation in terms of cellular influx, mediators, cytokines and chemokines. Ten patients with SA were compared with 11 patients with chronic asthma, 4 without preexisting pulmonary disease requiring MV and 8 healthy subjects. Bronchial lavages in SA were indicated to remove bronchial plugs in case of atelectasis and/or refractory SA. The main findings in patients with SA were a massive influx of neutrophils (81.5 +/- 4.5%) with a dramatic increase of neutrophil elastase. Although more limited than the neutrophil influx, eosinophils were present and associated with high levels of eosinophil cationic protein (ECP), which suggested that a part of the eosinophils were activated and degranulated. In parallel to the neutrophil and eosinophil influx, we observed elevated amounts of proinflammatory (IL-1beta, IL-5, IL-6, TNFalpha) and anti-inflammatory (IL-10, IL-1 receptor antagonist, soluble TNF receptors) cytokines with a balance in favor of a net proinflammatory activity. Chemokines were also present in large quantities with a predominance of MCP-1, MIP-alpha and RANTES with a significant correlation between MCP-1, RANTES, IL-5 and both eosinophil and ECP values. In addition an acute 10- to 160-fold increase of 92-kD gelatinase (MMP9) was detected in bronchial lavage fluid from patients with SA associated with a free metallogelatinolytic activity, suggesting an imbalance in the local production of proteases and antiproteases. Therefore, our results indicate that the bronchi in SA are the site of an intense production of pro- and anti-inflammatory cytokines and chemokines that are implicated in the influx of eosinophils and neutrophils. The inflammatory pattern in SA clearly differs from the usual profile observed in chronic asthma.