Intrapulmonary activation of leukocytes and release of cellular mediators and enzymes are involved in the pathophysiology of the adult respiratory distress syndrome (ARDS). To investigate a possible role of local cytokines, we measured bronchoalveolar fluid (BALF) and plasma levels of tumor necrosis factor alpha (TNF-alpha) and its soluble inhibitors (sTNF-RI + RII), interleukin-1 beta (IL-1 beta), interferon-alpha (IFN-alpha), and granulocyte elastase in 14 patients at risk for ARDS and in 35 patients developing ARDS after trauma, sepsis, or shock. During clinical development of severe ARDS, BALF cytokines increased markedly: TNF-alpha from 116 +/- 36 to 10,731 +/- 5,048 pg/ml (mean +/- SEM), p = 0.001; sTNF-RI + RII from 3.7 +/- 1.4 to 24.6 +/- 2.6 ng/ml, p less than 0.05; and IL-1 beta from 7,746 +/- 5,551 to 42,255 +/- 19,176 pg/ml, p = 0.01. Plasma cytokines were not increased in most patients, nor were they correlated with the development or severity of ARDS. BALF elastase was higher in patients developing ARDS than in those at risk but not going into pulmonary failure (0.97 +/- 0.26 versus 0.28 +/- 0.13 U/ml, p = 0.026), and the highest values were observed in the early stages of severe ARDS (1.85 +/- 0.39 U/ml). BALF elastase levels correlated with IFN-alpha (r = 0.72, p less than 0.001). In conclusion, local release of TNF-alpha and IL-1 beta, possibly by pulmonary macrophages or other cells, and/or accumulation in the lung is associated with the development of ARDS.(ABSTRACT TRUNCATED AT 250 WORDS)

Compared to commonly used screening methods such as the McCarthy score, leucocyte count and other inflammatory markers such as interleukin-6, interleukin-8 and interleukin- receptor antagonist, procalcitonin and C-reactive protein offer a better sensitivity and specificity in predicting serious bacterial infection in children with fever without localising signs.

We studied the possible role of granulocyte neutral proteases as mediators of airway destruction in patients with cystic fibrosis (CF) who were infected with Pseudomonas aeruginosa. We measured the enzymatic activities of bronchial secretions on purified radioactively labeled complement component three (C3), elastin, and a granulocyte elastase-specific substrate. Bronchial secretions from 18 patients with CF who were infected with P aeruginosa had a significantly higher mean value for C3 cleaving, elastolytic, and granulocyte elastase-like activity than did two control groups. High enzymatic activities were observed in patients with CF who have advanced bronchial disease (that had been determined by a clinical scoring system). Kinetics of proteolysis of radioactively labeled C3 and inhibition profiles of the activities of the three enzymatic activities studied suggest that they are mainly derived from granulocytes. In addition, 20 of 31 strains of P aeruginosa isolated from patients with CF inactivated purified o l-antiprotease in vitro. We postulate that granulocyte neutral proteases and P aeruginosa may act synergistically in the airways of patients with CF and may contribute to the destruction of elastin and inactivation of C3.Cystic fibrosis is a fatal hereditary disease, in which the leading cause of death is respiratory failure [I]. Patients with cystic fibrosis (CF) usually have a long history of purulent bronchitis leading to progressive destruction of small bronchioles and followed by involvement of the large airways [2]. The pathogens most frequently associated with these respiratory-tract infections are Staphylococcus aureus and Pseudomonas aeruginosa [2,3]. Clinical and pathological observations suggest that progressive airway destruction is accelerated during infections with P aeruginosa [2]. However, little information is available regarding the mechanisms involved in progressive bronchiolar and bronchial damage and the persistence of P aeruginosa in bronchial secretions.Bronchial secretions from patients with CF con- [4,5]. These enzymes are indeed able to destroy important structural proteins of the lung and its airways such as elastin, collagen, and proteoglycans [4,5] in vitro; in addition, they can inactivate important opsonins such as complement component C3 [6][7][8] and IgG and IgM immunoglobulins [9][10][11]. It is also well established that they are released extracellularly during phagocytosis [12]. Furthermore, P aeruginosa may secrete an elastase that destroys the two main inhibitors protecting the lung and its airways from the activity of PMN neutral proteases: al-antiprotease [13][14][15][16] and the bronchial mucosal proteinase inhibitor [17]. In addition, this bacterial elastase is also active on C3[18] and elastin [15].We therefore measured the enzymatic activities of bronchial secretions from patients with CF (who were infected with P aeruginosa) on purified human C3, bovine elastin, and a granulocyte elastase-specific substrate. Two groups of patients with bronchial secretions r...

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A rapid determination of procalcitonin concentration could be useful for the management of children with febrile UTI in the emergency room.