We conclude that UEX in pediatric patients is associated with longer length of mechanical ventilation and length of stay in the PICU. A continuous quality improvement monitoring and educational program that identified high-risk patients for UEX (younger patients) and patients who were at low risk for subsequent reintubation (weaning patients) contributed to a reduction of these potentially adverse events.

Idiopathic pneumonia syndrome (IPS) refers to a diffuse, noninfectious, acute lung injury after hematopoietic stem cell transplantation. Historically, IPS is associated with respiratory failure and mortality rates exceeding 50%. Preclinical studies have implicated tumor necrosis factor-␣ as an important effector molecule in the development of disease. We studied the tumor necrosis factor-␣ inhibitor, etanercept, combined with corticosteroids in treating 15 patients (median age, 18 years; range, 1-60 years) with IPS. Eight of 15 patients required mechanical ventilation at therapy onset. Etanercept was administered subcutaneously at a dose of 0.4 mg/kg (maximum 25 mg) twice weekly, for a maximum of 8 doses. Therapy was well tolerated with no infectious pulmonary complications noted. Ten of 15 patients had a complete response, defined as the ability to discontinue supplemental oxygen support during study therapy. The median time to complete response was 7 days (range, 3-18 days), with a day 28 survival of 73%. IPS onset was associated with elevations of several inflammatory proteins in the bronchoalveolar lavage fluid and plasma, and response to therapy correlated with reductions in pulmonary and systemic inflammation. The combination of etanercept and corticosteroids is safe and is associated with high response rates and improved survival in patients with IPS. IntroductionNoninfectious lung injury is a frequent and severe complication of hematopoietic stem cell transplantation (HCT) both in the immediate posttransplantation period and in the months and years that follow. In the acute setting, a diffuse interstitial process, termed idiopathic pneumonia syndrome (IPS), may develop. [1][2][3] In 1993, a panel convened by the National Institutes of Health (NIH) proposed a broad working definition of IPS to include widespread alveolar injury in the absence of active lower respiratory tract infection after HCT. 1 The NIH panel stressed that they considered this definition to be that of a clinical syndrome, with variable histopathologic correlates and several potential etiologies. Diagnostic criteria of IPS include signs and symptoms of pneumonia, nonlobar radiographic infiltrates, abnormal pulmonary function, and the absence of infectious organisms in the lower respiratory tract. 1 Published reports indicate that IPS develops in 7% to 15% of allogeneic HCT patients, a median of 14 to 42 days after transplantation. Survival after onset is poor, with mortality rates of 50% to 80% reported. 1,[4][5][6] The typical clinical course involves a rapid onset of respiratory failure leading to death, underscoring the critical nature of this transplantation-related complication. 4 Potential etiologies for IPS include direct toxic effects of HCT conditioning regimens, the presence of occult pulmonary infections, and damage from inflammatory cytokines that have been implicated in other forms of pulmonary injury. 1,2,6-8 Although IPS has been reported after autologous HCT, it is primarily a complication of allogeneic transplantations...

Acute pulmonary dysfunction remains a frequent and severe complication of hematopoietic stem cell transplantation (SCT). Almost half of the pulmonary insults that occur in this seating are noninfectious in origin and are referred to as idiopathic pneumonia syndrome (IPS). In this series of 3 patients, etanercept (Enbrel; Immunex, Seattle, WA), a soluble, dimeric tumor necrosis factor alpha-binding protein, was administered to 3 consecutive pediatric allogeneic BMT recipients with IPS. The administration of etanercept, in combination with standard immunosuppressive therapy, was well tolerated and associated with significant improvements in pulmonary dysfunction within the first week of therapy. These data suggest that etanercept may represent a safe, non-cross-reactive, therapeutic option for patients with IPS and that clinical trials studying etanercept for this indication are warranted.

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