Pulmonary alveolar proteinosis (PAP) is a rare lung disorder in which surfactant-derived lipoproteins accumulate excessively within pulmonary alveoli, causing severe respiratory distress. The importance of granulocyte/macrophage colony-stimulating factor (GM-CSF) in the pathogenesis of PAP has been confirmed in humans and mice, wherein GM-CSF signaling is required for pulmonary alveolar macrophage catabolism of surfactant. PAP is caused by disruption of GM-CSF signaling in these cells, and is usually caused by neutralizing autoantibodies to GM-CSF or is secondary to other underlying diseases. Rarely, genetic defects in surfactant proteins or the common β chain for the GM-CSF receptor (GM-CSFR) are causal. Using a combination of cellular, molecular, and genomic approaches, we provide the first evidence that PAP can result from a genetic deficiency of the GM-CSFR α chain, encoded in the X-chromosome pseudoautosomal region 1.

No abstract

Risk factors for PFI include Grade A2 rejection, repeated acute rejection, CMV-positive donor, tacrolimus-based regimen and pre-transplant colonization.

To characterize epidemiology and risk factors for respiratory viral infections (RVI) in pediatric lung transplant recipients within the first post-transplant year, a retrospective multicenter study of pediatric lung transplant recipients from 1988 to 2005 was conducted at 14 centers in the United States and Europe. Data were recorded for 1 year post transplant. Associations between RVI and continuous and categorical risk factors were assessed using Wilcoxon's rank-sum and chi(2) tests, respectively. Associations between time to RVI and risk factors or survival were assessed by multivariable Cox proportional hazards models. Of 576 subjects, 79 subjects (14%) had 101 RVI in the first year post transplant. Subjects with RVI were younger than those without RVI (median ages 9.7, 13; P<0.01). Viruses detected included adenovirus (n=25), influenza (n=9), respiratory syncytial virus (n=21), parainfluenza virus (n=19), enterovirus (n=4), and rhinovirus (n=22). In a multivariable model for time to first RVI, etiology other than cystic fibrosis (CF), younger age, and no induction therapy were independently associated with risk of RVI. Cytomegalovirus serostatus and acute rejection were not associated with RVI. RVI was independently associated with decreased 12-month survival (hazard ratio 2.6, 95% confidence interval 1.6-4.4). RVI commonly occurs after pediatric lung transplantation with risk factors including younger age and non-CF diagnosis. RVI is associated with decreased 1-year survival.

Background A retrospective review of pediatric lung transplant recipients at 14 centers in North America and Europe was conducted to characterize the epidemiology and risk factors for cytomegalovirus (CMV) and to explore the impact of preventative antiviral therapy. Methods Data were recorded for one year post-transplant. Associations between CMV and continuous and categorical risk factors were assessed using Wilcoxon rank-sum and Chi-square tests, respectively. Associations between time to CMV and risk factors or survival were assessed by multivariable Cox proportional hazards models. Results Within 12 months posttransplant, 172 of 577 subjects (29.8%) developed 218 CMV episodes (90 asymptomatic infection, 25 syndrome, 103 disease). Forty-one subjects developed more than one episode of CMV. Donor or recipient CMV seropositivity was associated with increased risk of CMV episodes. Except for decreased prophylaxis in CMV D-/R- subjects, duration of prophylaxis did not vary by D/R serostatus. For CMV D+ subjects, not being on prophylaxis at the time of CMV episode increased the risk of CMV (D+/R+ HR 3.5: 95% CI 1.4, 8.4; D+/R- 1.9: 1.02, 3.7). CMV was associated with increased mortality within the first posttransplant year among those with donor or recipient CMV seropositivity (HR 2.0: 95% CI 1.1, 3.6; p=0.024). Conclusions CMV remains a serious complication after pediatric lung transplant, and the impact of prophylaxis is complex.

Mycobacterium abscessus is increasingly recognized as an important pathogen in some individuals with advancing lung disease related to cystic fibrosis (CF). Because of its resistance to antimicrobial agents and virulence, its presence in the lungs of potential lung transplant recipients can be problematic. We present 2 cases of individuals with CF in whom M. abscessus was present in the preoperative sputum cultures. The organism manifested different degrees of invasiveness in the 2 cases after transplantation with different outcomes, suggesting an approach to future candidates for lung transplantation that may be of clinical significance to their physicians and surgeons.

No abstract

To evaluate the epidemiology and investigate the impact of colonization and pulmonary fungal infections (PFI), we performed a retrospective analysis of 55 pediatric lung transplant recipients from 2002-2007 at a single institution. While 29 had positive pretransplant colonization, thirty-three (60%) were colonized post-transplant and 20% (11 subjects) developed proven or probable PFI. In a multivariable model, posttransplant fungal colonization was associated with older age (HR 2.9; 95% CI 1.1-7.6), CMV prophylaxis (5.6; 1.3-24.6) and respiratory viral infection prior to fungal colonization (2.9; 1.0-8.3). Neither fungal colonization nor PFI were associated with the development of chronic allograft rejection or death.