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Vol. 124, No. 1-3, 2001
Issue release date: January–March 2001
Int Arch Allergy Immunol 2001;124:267–271
(DOI:10.1159/000053729)

Characteristics of the Inflammatory Response in Bronchial Lavage Fluids from Patients with Status asthmaticus

Tonnel A.B. · Gosset P. · Tillie-Leblond I.
aUnité INSERM No. 416, Institut Pasteur de Lille, and bClinique des Maladies Respiratoires, CHRU de Lille, Lille, France

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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 atelectasia 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-1β, IL-5, IL-6, TNFα) 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-α 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.



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References

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  4. Lamblin C, Gosset P, Tillie-Leblond I, Saulnier F, Marquette CH, Wallaert B, Tonnel AB: Bronchial neutrophilia in patients with noninfectious status asthmaticus. Am J Respir Crit Care Med 1998;157:359–402.
  5. Tillie-Leblond I, Hammad H, Desurmont S, Pugin J, Walllaert B, Tonnel AB, Gosset P: CC chemokines and IL-5 in bronchial lavages from status asthmaticus patients: Potential implication in eosinophil recruitment. Am J Respir Crit Care Med 2000;162:582–592.
  6. Gonzalo JA, Lloyd CM, Wen D, Albar JP, Wells TN, Proudfoot A, Martinez AC, Dorf M, Bjerke T, Coyle AJ, Gutierrez-Ramos JC: The coordinated action of C-C chemokines in the lung orchestrates allergic inflammation. J Exp Med 1998;188:157–167.
  7. Tillie-Leblond I, Pugin J, Marquette CH, Lamblin C, Saulnier F, Brichet A, Wallaert B, Tonnel AB, Gosset P: Balance between proinflammatory cytokines and their inhibitors in bronchial lavages from patients with status asthmaticus. Am J Respir Crit Care Med 1999;159:487–494.
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    External Resources

  9. Gosset P, Tsicopoulos A, Wallaert B, Vannimenus C, Joseph M, Tonnel AB, Capron A: Increased secretion of TNF alpha and IL-6 by alveolar macrophages consecutive to the development of the late asthmatic reaction. J Allergy Clin Immunol 1991;88:561–572.
  10. Lemjabbar H, Gosset P, Lamblin C, Tillie I, Hartmann D, Wallaert B, Tonnel AB, Lafuma C: Contribution of 92 kDa gelatinase/type IV collagenase in bronchial inflammation during status asthmaticus. Am J Respir Crit Care Med 1999;159:1298–1307.
  11. Yao PM, Buhler JM, D’Ortho MP, Lebargy F, Delclaux C, Harf A, Lafuma C: Expression of matrix metalloproteinase gelatinase A and B by cultured epithelial cells from human bronchial explants. J Biol Chem 1996;271:15580–15589.


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