Are there more lungs available than currently meet the eye?
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Humans↗
Biomedical subjects
Jonathan B Orens
Publications and source records attributed to Jonathan B Orens.
Persistent cytomegalovirus-specific memory responses in the lung allograft and blood following primary infection in lung transplant recipients.
Primary CMV infection in lung transplant recipients (LTRs) is associated with increased mortality. We studied 22 donor CMV-positive, recipient-negative (D(+)R(-)) LTRs for the development of posttransplant CMV-specific immunity. We found that 13 of 22 D(+)R(-) LTRs (59.1%) seroconverted (CMV IgG Ab(+)). Using pooled peptides of the immunodominant CMV Ags pp65 and IE1, we detected CMV-specific CD8(+)IFN-gamma(+) T cells in the PBMC of 90% of seroconverted individuals following primary infection by intracellular cytokine staining. In contrast, few seroconverters had detectable CMV-specific CD4(+)IFN-gamma(+) T cells during viral latency. However, the majority of IgG(+) LTRs demonstrated CMV-specific CD4(+) and CD8(+) T cell proliferative responses from PBMC, with CD4(+)IFN-gamma(+) T cells detectable upon re-expansion. Examination of lung allograft mononuclear cells obtained by bronchoalveolar lavage revealed both CMV-specific CD4(+) and CD8(+)IFN-gamma(+) T cells, including patients from whom CD4(+)IFN-gamma(+) T cells were simultaneously undetectable in the PBMC, suggesting differential effector memory populations between these compartments. Moreover, both responses in the PBMC and lung allograft were found to persist, despite substantial immunosuppression, long after primary infection. Clinical correlation in this cohort demonstrated that the acquisition of CMV immunity was associated with freedom from CMV disease (p < or = 0.009) and preservation of allograft function (p < or = 0.02) compared with those who failed to develop CMV immunity. Together, our data reveal immunologic heterogeneity in D(+)R(-) LTRs, with the development and persistence of primary CMV responses that may provide clinical benefit.
Adolescent↗
Lung transplantation in scleroderma compared with idiopathic pulmonary fibrosis and idiopathic pulmonary arterial hypertension.
OBJECTIVE: Lung transplantation is a viable, life-saving intervention for several primary pulmonary disorders complicated by severe lung dysfunction. This study was undertaken to evaluate whether patients with systemic sclerosis (scleroderma), a systemic autoimmune rheumatic disorder, would receive similar benefit from this intervention. METHODS: Survival following lung transplantation was examined at 2 university medical centers among 29 patients with scleroderma as compared with 70 patients with idiopathic pulmonary fibrosis (IPF) and 38 with idiopathic pulmonary arterial hypertension (IPAH), the latter groups representing pathologically related primary pulmonary disorders. The end point was death from any cause. Risk of mortality in patients with scleroderma was compared with that in patients with IPF or IPAH, with adjustment for demographic and clinical parameters. RESULTS: During 2 years of followup, 11 patients with scleroderma (38%), 23 with IPF (33%), and 14 with IPAH (37%) died. Cumulative survival at 6 months posttransplantation was 69% in the scleroderma group compared with 80% in the IPF group (log-rank P = 0.21) and 79% in the IPAH group (P = 0.38). The estimated risk of mortality at 6 months was increased in patients with scleroderma compared with those with IPF (relative risk [RR] 1.70, 95% confidence interval [95% CI] 0.74-3.93) and those with IPAH (RR 1.52, 95% CI 0.59-3.96), but the differences were not statistically significant. Over the following 18 months, there was convergence in the survival rates such that cumulative survival at 2 years was comparable, at approximately 64%, among all 3 groups. CONCLUSION: Patients with scleroderma who are recipients of lung transplantation experience similar rates of survival 2 years after the procedure compared with those with IPF or IPAH. Lung transplantation may represent a viable therapeutic option to consider for patients with end-stage lung disease due to scleroderma.
Adult↗
International guidelines for the selection of lung transplant candidates: 2006 update--a consensus report from the Pulmonary Scientific Council of the International Society for Heart and Lung Transplantation.
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Contraindications↗
Cadaveric donor selection and management.
While there is little doubt that proper donor selection is extremely important to achieve good outcomes from transplantation, there are only limited data regarding the current criteria utilized to select the "ideal donor". Importantly, there are not enough donor lungs available for all of those in need. Until an adequate supply of donor organs exists, lives will be lost on the transplant waiting list. While efforts have been made to increase donor awareness, additional transplants can be realized by improving donor utilization. This can be achieved by active participation of transplant teams in donor management and by utilizing "extended criteria" organs. Further studies are needed to assess the impact of using "extended criteria" donors, as this practice could result in increased posttransplant morbidity and mortality. This article summarizes the approach to identification of potential lung donors, optimal donor management, and the clinical importance of various donor factors upon recipient outcomes.
Cadaver↗
Impact of donor lung organisms on post-lung transplant pneumonia.
BACKGROUND: Fear of transmission of donor organisms that may result in recipient pneumonia has a negative impact on donor lung utilization. We reviewed our experience with routine donor bronchial aspiration and culture at the time of transplantation to study the impact of donor bronchial organisms on the development of recipient post-lung transplant pneumonia (PTP) and other outcomes. METHODS: We reviewed 80 consecutive single and bilateral lung transplants (SLTs and BLTs) from August 1998 to August 2001. Pediatric recipients and those not surviving >3 days were excluded. All donors met standard criteria for donor acceptance. All recipients received broad-spectrum antibiotics pending the results of final operating room cultures. PTP required clinical evidence (fever, leukocytosis and hypoxia), radiologic evidence (infiltrate), and culture confirmation during initial hospitalization or within 30 days. RESULTS: Sixty-four donors for 71 recipients (39 SLTs, 32 BLTs) comprised the study population. Organisms were grown from 57 (89%) donors and 46 were polymicrobial. A total of 149 organisms were cultured consisting of 21 different species, with Staphylococcus (n = 35) and Streptococcus (n = 33) being the most common. PTP was seen in 31 (41%) recipients, with Pseudomonas species (n = 13) the most prevalent. Of the 71 donor-recipient pairs, 2 had both donor and recipient with no growth and PTP. The donor organisms had a sensitivity of 0.75 with a low specificity of 0.04 and were negatively correlated with development of PTP. PTP was an independent predictor of overall mortality. CONCLUSIONS: The presence of donor organisms does not predict PTP. Therefore, donor acceptance criteria need to be re-examined.
Adult↗
Pluripotent allospecific CD8+ effector T cells traffic to lung in murine obliterative airway disease.
Long-term success in lung transplantation is limited by obliterative bronchiolitis, whereas T cell effector mechanisms in this process remain incompletely understood. Using the mouse heterotopic allogeneic airway transplant model, we studied T cell effector responses during obliterative airways disease (OAD). Allospecific CD8+ IFN-gamma+ T cells were detected in airway allografts, with significant coexpression of TNF-alpha and granzyme B. Therefore, using IFN-gamma as a surrogate marker, we assessed the distribution and kinetics of extragraft allo-specific T cells during OAD. Robust allospecific IFN-gamma was produced by draining the lymph nodes, spleen, and lung mononuclear cells from allograft, but not isograft recipients by Day 14, and significantly decreased by Day 28. Although the majority of allospecific T cells were CD8+, allospecific CD4+ T cells were also detected in these compartments, with each employing distinct allorecognition pathways. An influx of pluripotent CD8+ effector cells with a memory phenotype were detected in the lung during OAD similar to those seen in the allografts and secondary lymphoid tissue. Antibody depletion of CD8+ T cells markedly reduced airway lumen obliteration and fibrosis at Day 28. Together, these data demonstrate that allospecific CD8+ effector T cells play an important role in OAD and traffic to the lung after heterotopic airway transplant, suggesting that the lung is an important immunologic site, and perhaps a reservoir, for effector cells during the rejection process.
Animals↗
Mediastinal mass due to Aspergillus fumigatus after lung transplantation: a case report.
We report a rare case of mediastinal mass caused by Aspergillus fumigatus in a lung transplant recipient. The patient presented 9 months after bilateral lung transplantation for cystic fibrosis with intermittent fevers and new onset atrial fibrillation/flutter caused by a 7-cm mediastinal mass invading the left atrium. The mass was resected, and a prolonged course of voriconazole and caspofungin was given, which resulted in a complete clinical response. Despite long-term suppressive therapy with voriconazole, a relapse occurred 16 months after the initial diagnosis. This case highlights the challenges in the prevention and treatment of invasive aspergillosis in lung transplant recipients.
Adult↗
The utility of cytopathology testing in lung transplant recipients.
BACKGROUND: Lung transplant recipients routinely undergo bronchoscopy, during which bronchoalveolar lavage (BAL) fluid and transbronchial biopsies are usually obtained. These specimens are typically sent for microbiology, histopathology and cytopathology testing. Cytopathology testing is expensive, and its diagnostic value is questionable. We hypothesized that cytopathology specimens have no additional diagnostic yield beyond that of microbiology and histopathology testing in the routine care of our lung transplant patients. METHODS: We reviewed all bronchoscopies performed on a cohort of patients who underwent lung transplantation between February 1999 and August 2002 at our institution. Demographic data, immunosuppressive therapy and the incidence of opportunistic infections in this cohort of 65 patients were reviewed. To ascertain the diagnostic value of cytopathology testing, microbiology and histopathology results from bronchoalveolar lavage and transbronchial biopsy tests were compared with cytopathology results. RESULTS: Three hundred sixty-six bronchoscopies were reviewed. Microbiologic and histopathology identified 51 cytomegalovirus-, 157 fungus- and 13 mycobacteria-positive specimens as well as respiratory syncitial virus, influenza A and B, enterovirus, actinomyces, Nocardia and mycoplasma. Cytopathology of BAL fluid identified only 3 cytomegalovirus- and 13 fungus-positive specimens. The only unique diagnoses made by cytopathology were 1 case of Aspergillus and 1 unidentifiable fungal element. CONCLUSIONS: We conclude that routine cytopathology testing has little additive diagnostic value in bronchoscopic specimens from lung transplant recipients. Cytopathology results did not alter patient management in any of our 366 cases. Centers should consider discontinuing routine use of cytopathology testing of BAL fluid for surveillance or clinically indicated bronchoscopy, because the yield of this expensive test is extremely low in the setting of lung transplantation.
Adolescent↗
Impact of secondary pulmonary hypertension on lung transplant outcome.
INTRODUCTION: Secondary pulmonary hypertension (SPH), defined as a mean pulmonary artery pressure (PAM) greater than 25 mm Hg, complicates end-stage lung diseases of varying etiology. Although previous studies have suggested that SPH does not adversely affect outcome, no study has assessed the impact of the degree of SPH. METHODS: A retrospective review of the lung transplant database was used to identify patients who underwent either single-lung (SLT) or bilateral lung transplantation (BLT) complicated by SPH. SPH patients were stratified into low SPH (PAM = 30-40 mm Hg) and high SPH (PAM > or = 40 mm Hg). Each group was further sub-categorized into SLT or BLT. Patients with a heart-lung transplant or primary pulmonary hypertension were excluded. Recipients without pulmonary hypertension transplanted over the same time were used as controls. Data are reported as controls vs low SPH vs high SPH. RESULTS: One hundred-four patients received lung transplants between August 1998 and March 2003. There were 45 patients (18 men and 27 women) with SPH. Of these, 28 patients had low SPH, and 17 patients had high SPH. Forty-two patients (18 men and 24 women) without PH were the controls. There were no significant differences between groups except pre-operative oxygen dependence (81% vs 100% vs 94%, respectively) and use of CPB (28.6% vs 57.1% vs 64.7%, respectively). PAO2-PaO2 gradients and PaO2/FIO2 ratios were significantly worse in the high SPH group (116.2 vs 132.9 vs 186.3; p < 0.006) and (277.8 vs 234.3 vs 214.4; p < 0.026) respectively. There was no statistical difference in length of mechanical ventilation or duration of intensive care unit stay between groups. PAMs were significantly different pre-operatively (22.2 +/- 0.8 vs 34.0 +/- 0.6 vs 47.8 +/- 2.0; p < 0.001) and post-operatively (20.9 +/- 1.1 vs 23.7 +/- 1.3 vs 24.8 +/- 2.1; p < 0.001). There were no operative deaths. There were 3 early deaths in the control group, 1 in the low SPH group, and 3 in the high SPH group, none were related to pulmonary hypertension. Actuarial survival at 12, 24, and 48 months was not significantly different among the groups nor between SLT or BLT with SPH. CONCLUSION: Although SPH increases the risk of reperfusion injury; survival is equivalent with mild or moderate pulmonary hypertension. Either SLT or BLT may be used in patients with SPH without compromising outcome. This has the added benefit of expanding the donor pool.
Adult↗
Thoracic organ transplantation in the United States, 1994-2003.
Using OPTN/SRTR data, this article reviews the state of thoracic organ transplantation in 2003 and the previous decade. Time spent on the heart waiting list has increased significantly over the last decade. The percentage of patients awaiting heart transplantation for >2 years increased from 23% in 1994 to 49% by 2003. However, there has been a general decline in heart waiting list death rates over the decade. In 2003, the lung transplant waiting list reached a record high of 3,836 registrants, up slightly from 2002 and more than threefold since 1994. One-year patient survival for those receiving lungs in 2002 was 82%, a statistically significant improvement from 2001 (78%). The number of patients awaiting a heart-lung transplant, declining since 1998, reached 189 in 2003. Adjusted patient survival for heart-lung recipients is consistently worse than the corresponding rate for isolated lung recipients, primarily due to worse outcomes for heart-lung recipients with congenital heart disease. A new lung allocation system, approved in June 2004, derives from the survival benefit of transplantation with consideration of urgency based on waiting list survival, instead of being based solely on waiting time. A goal of the policy is to minimize deaths on the waiting list.
Female↗
Cadaveric donor selection and management.
The current availability of lung donors is far exceeded by the number of potential transplant recipients who are waiting for an organ. This disparity results in significant morbidity and mortality for those on the waiting list. Although it is desirable to increase overall consent rates for organ donation, doing so requires an intervention to affect societal response. In contrast, increased procurement of organs from marginal donors and improved donor management may be realized through increased study and practice changes within the transplant community. Transplantation of organs from marginal or extended-criteria donors may result in some increase in complications or mortality, but this possibility must be weighed against the morbidity and risk of death risk faced by individuals on the waiting list. The effects of this trade-off are currently being studied in kidney transplantation, and perhaps in the near future lung transplantation may benefit from a similar analysis. Until that time, the limited data regarding criteria for donor acceptability must be incorporated into practice to maximize the overall benefits of lung transplantation.
Adult↗
The course of neurofibromatosis type 1 on immunosuppression after lung transplantation: report of 2 cases.
We describe 2 patients with neurofibromatosis type 1 (NF1) who underwent lung transplantation. Case 1 reports a patient with NF1 with no complications 5 years after bilateral lung transplantation. Case 2 details a patient with NF1 diagnosed with both post-transplant lymphoproliferative disorder (PTLD) and massive intra-abdominal sarcoma consistent with a malignant nerve sheath tumor 9 months after lung transplantation. There was no clinical evidence of sarcoma preceding or immediately following lung transplant as demonstrated by a normal abdominal sonogram 3 months post-transplantation. Although an increased risk for cancer has been documented in NF1, the rapid malignant degeneration of a neurofibroma following transplantation raises concern about immunosuppression and transplantation candidacy among individuals with NF1.
Abdominal Neoplasms↗
Surrogate markers and risk factors for chronic lung allograft dysfunction.
Obliterative bronchiolitis (OB) is the histologic correlate of chronic allograft dysfunction in pulmonary transplantation. The histologic diagnosis of OB is challenging, therefore a physiologic definition, bronchiolitis obliterans syndrome (BOS) based on pulmonary function tests has been used as a surrogate marker for OB for the last decade. BOS has proven to be the best available surrogate marker for OB and is predictive of the ultimate endpoints of graft and patient survival. Multiple other clinical markers have been reported and proposed as alternates for or complements to BOS grade, but all need further evaluation and validation in large, prospective clinical trials. Lastly, given the early occurrence and high incidence of chronic allograft dysfunction, the easily measurable endpoint of BOS grade, and our lack of understanding of ways to prevent or alter the course of BOS, lung transplant recipients represent an ideal population for clinical trials targeting prevention and treatment of chronic allograft dysfunction.
Adult↗
Transmission of glioblastoma multiforme following bilateral lung transplantation from an affected donor: case study and review of the literature.
Donor-acquired solid organ malignancy is a rare complication of organ transplantation. We report a case of a patient who received bilateral lung transplants for pulmonary fibrosis from a donor with known glioblastoma multiforme (GBM). The lungs, heart, liver, and kidneys were harvested after a lethal intracranial bleed and accepted for transplantation by four centers. An enlarged hilar lymph node sampled at the time of transplant was found to contain GBM. Four months later, the patient developed diffuse interstitial pulmonary infiltrates with mediastinal lymphadenopathy. Lung biopsy confirmed metastatic GBM. The patient died 2 weeks after the diagnosis was established. The patient receiving the donor liver also developed GBM. We present a case study, review of the literature, and suggested interventions to minimize the risk of transmission.
Adult↗
Maintenance azithromycin therapy for bronchiolitis obliterans syndrome: results of a pilot study.
Bronchiolitis obliterans syndrome remains the leading cause of morbidity and mortality in the pulmonary transplant population. Previous studies show that macrolide antibiotics may be efficacious in the treatment of panbronchiolitis and cystic fibrosis. In the latter, azithromycin decreases the number of respiratory exacerbations, improves FEV1, and improves quality of life. We hypothesized that oral azithromycin therapy may improve lung function in patients with bronchiolitis obliterans syndrome. To test this hypothesis, we conducted an open-label pilot trial using maintenance azithromycin therapy in six lung transplant recipients (250 mg orally three times per week for a mean of 13.7 weeks). In this study, five of these six individuals demonstrated significant improvement in pulmonary function, as assessed by FEV1, as compared with their baseline values at the start of azithromycin therapy. The mean increase in the percentage of predicted FEV1 values in these individuals was 17.1% (p </= 0.05). In addition, the absolute FEV1 increased by 0.50 L (range -0.18 to 1.36 L). These data suggest a potential role for maintenance macrolide therapy in the treatment of bronchiolitis obliterans syndrome in lung transplant recipients.
Administration, Oral↗
An outbreak of Pseudomonas aeruginosa infections associated with flexible bronchoscopes.
BACKGROUND: Endoscopes, including bronchoscopes, are the medical devices most frequently associated with outbreaks of nosocomial infections. We investigated an outbreak of Pseudomonas aeruginosa infections after bronchoscopic procedures. METHODS: Microbiologic results were reviewed to determine the rates of recovery of P. aeruginosa from bronchoalveolar-lavage specimens. Environmental samples from endoscopes and the endoscopy suite were cultured. Medical records were reviewed to identify infections in the 14 days after a bronchoscopy. RESULTS: The rate of recovery of P. aeruginosa from bronchoalveolar-lavage specimens obtained with use of endoscopy-suite bronchoscopes increased from 10.4 percent at base line to 31.0 percent during the outbreak (relative risk, 2.97; 95 percent confidence interval, 2.28 to 3.90). Cultures of samples from three bronchoscopes grew P. aeruginosa, whereas cultures of samples from the environment, instrument-cleaning machines, and gastrointestinal endoscopes did not. The three bronchoscopes had been part of a nationwide recall. A total of 414 patients underwent bronchoscopy during the outbreak, and there were 48 respiratory tract and bloodstream infections among 39 of these patients (9.4 percent). In 32 infections (66.7 percent), P. aeruginosa was confirmed as a potentially causative organism. Exposure to a potentially contaminated bronchoscope may have had a role in the death of three patients. The rate of recovery of P. aeruginosa returned to base line after the instruments were removed from service. CONCLUSIONS: This large outbreak of P. aeruginosa infections related to bronchoscopy was apparently caused by a loose biopsy-port cap in the bronchoscopes. Instrument safety and surveillance methods for bronchoscopy must be improved, and better recall procedures are needed for medical devices.
Academic Medical Centers↗
Pulmonary resection following lung transplantation.
BACKGROUND: The morbidity of lung transplantation is higher than other solid organ transplants. Little is known about the outcomes of patients who require pulmonary resection following lung transplantation. We reviewed our experience to evaluate and discern any variables affecting outcome of pulmonary resections performed following lung transplantation. METHODS: A retrospective review of the lung transplant database was performed. Data are presented as mean +/- standard error (median). RESULTS: A total of 136 lung transplants (80 single lung transplants [SLT], 55 bilateral lung transplants [BLT], and 3 heart-lung transplants [HLT]) were performed from August 1995 to February 2002. Twelve pulmonary resections, 7 lobectomies, and 5 wedge resections were performed on 11 patients. The indication for lobectomy was infection in 5 of 7 lobectomies (3 fungal, 2 bacterial), mass in 1 of 7, and infarction in 1 of 7. The indication for wedge resection was native lung hyperinflation in 4 of 5 wedge resections and mass in 1 of 5. The native lung was resected in 3 of 7 lobectomies and 4 of 5 wedge resections. An allograft lobectomy was performed following 1 SLT and 3 BLT and a wedge resection was performed after 1 SLT. The mean time to pulmonary resection was 12.4 +/- 3.9 (9.1) months. Survival postresection was 17.2 +/- 5.8 (8.3) months and 5 of 11 patients are still alive. There were no bronchial stump leaks following lobectomy. CONCLUSIONS: Major pulmonary resections can safely be performed following lung transplant. We recommend early intervention to optimize outcomes.
Adult↗