Potential Role of Computed Tomography Volumetry in Size Matching in Lung Transplantation.

BACKGROUND: Accumulated knowledge on the outcomes related to size mismatch in lung transplantation derives from predicted total lung capacity equations rather than individualized measurements of donors and recipients. The increasing availability of computed tomography (CT) makes it possible to measure the lung volumes of donors and recipients before transplantation. We hypothesize that CT-derived lung volumes predict a need for surgical graft reduction and primary graft dysfunction. METHODS: Donors from the local organ procurement organization and recipients from our hospital from 2012 to 2018 were included if their CT exams were available. The CT lung volumes and plethysmography total lung capacity were measured and compared with predicted total lung capacity using Bland Altman methods. We used logistic regression to predict the need for surgical graft reduction and ordinal logistic regression to stratify the risk for primary graft dysfunction. RESULTS: A total of 315 transplant candidates with 575 CT scans and 379 donors with 379 CT scans were included. The CT lung volumes closely approximated plethysmography lung volumes and differed from the predicted total lung capacity in transplant candidates. In donors, CT lung volumes systematically underestimated predicted total lung capacity. Ninety-four donors and recipients were matched and transplanted locally. Larger donor and smaller recipient lung volumes estimated by CT predicted a need for surgical graft reduction and were associated with higher primary graft dysfunction grade. CONCLUSION: The CT lung volumes predicted the need for surgical graft reduction and primary graft dysfunction grade. Adding CT-derived lung volumes to the donor-recipient matching process may improve recipients' outcomes.

Uncertainty analysis of chest X-ray lung height measurements and size matching for lung transplantation.

Background: Errors in measuring chest X-ray (CXR) lung heights could contribute to the occurrence of size-mismatched lung transplant procedures. Methods: We first used Bland-Altman analysis for repeated measures to evaluate contributors to measurement error of chest X-ray lung height. We then applied error propagation theory to assess the impact of measurement error on size matching for lung transplantation. Results: A total 387 chest X-rays from twenty-five donors and twenty-five recipients were measured by two raters. Individual standard deviation for lung height differences were independent of age, sex, donor vs. recipient, diagnostic group and race/ethnicity and all were pooled for analysis. Bias between raters was 0.27 cm (±0.03) and 0.22 cm (±0.06) for the right and left lung respectively. Within subject variability was the biggest contributor to error in measurement, 2.76 cm (±0.06) and 2.78 cm (±0.2) for the right and left lung height. A height difference of 4.4 cm or more (95% CI: ±4.2, ±4.6 cm) between the donor and the recipient right lung height has to be accepted to ensure matching for at least 95% of patients with the same true lung height. This difference decreases to ±1.1 cm (95% CI: ±0.9, ±1.3 cm) when the average from all available chest X-rays is used. The probability of matching a donor and a recipient decreases with increasing true lung height difference. Conclusions: Individual chest X-ray lung heights are imprecise for the purpose of size matching in lung transplantation. Averaging chest X-rays lung heights reduced uncertainty.

Lung protective ventilation based on donor size is associated with a lower risk of severe primary graft dysfunction after lung transplantation.

BACKGROUND: Mechanical ventilation immediately after lung transplantation may impact the development of primary graft dysfunction (PGD), particularly in cases of donor-recipient size mismatch as ventilation is typically based on recipient rather than donor size. METHODS: We conducted a retrospective cohort study of adult bilateral lung transplant recipients at our center between January 2010 and January 2017. We defined donor-based lung protective ventilation (dLPV) as 6 to 8 ml/kg of donor ideal body weight and plateau pressure <30 cm H2O. We calculated the donor-recipient predicted total lung capacity (pTLC) ratio and used logistic regression to examine relationships between pTLC ratio, dLPV and PGD grade 3 at 48 to 72 hours. We used Cox proportional hazards modelling to examine the relationship between pTLC ratio, dLPV and 1-year survival. RESULTS: The cohort included 373 recipients; 24 (6.4%) developed PGD grade 3 at 48 to 72 hours, and 213 (57.3%) received dLPV. Mean pTLC ratio was 1.04 ± 0.18. dLPV was associated with significantly lower risks of PGD grade 3 (OR = 0.44; 95% CI: 0.29-0.68, p < 0.001) and 1-year mortality (HR = 0.49; 95% CI: 0.29-0.8, p = 0.018). There was a significant association between pTLC ratio and the risk of PGD grade 3, but this was attenuated by the use of dLPV. CONCLUSIONS: dLPV is associated with decreased risk of PGD grade 3 at 48 to 72 hours and decreased 1-year mortality. Additionally, dLPV attenuates the association between pTLC and both PGD grade 3 and 1-year mortality. Donor-based ventilation strategies may help to mitigate the risk of PGD and other adverse outcomes associated with size mismatch after lung transplantation.

Economic evaluation of the specialized donor care facility for thoracic organ donor management.

BACKGROUND: Over the last decade two alternative models of donor care have emerged in the United States: the conventional model, whereby donors are managed at the hospital where brain death occurs, and the specialized donor care facility (SDCF), in which brain dead donors are transferred to a SDCF for medical optimization and organ procurement. Despite increasing use of the SDCF model, its cost-effectiveness in comparison to the conventional model remains unknown. METHODS: We performed an economic evaluation of the SDCF and conventional model of donor care from the perspective of U.S. transplant centers over a 2-year study period. In this analysis, we utilized nationwide data from the Scientific Registry of Transplant Recipients and controlled for donor characteristics and patterns of organ sharing across the nation's organ procurement organizations (OPOs). Subgroup analysis was performed to determine the impact of the SDCF model on thoracic organ transplants. RESULTS: A total of 38,944 organ transplants were performed in the U.S. during the study period from 13,539 donors with an observed total organ cost of $1.36 billion. If every OPO assumed the cost and effectiveness of the SDCF model, a predicted 39,155 organ transplants (+211) would have been performed with a predicted total organ cost of $1.26 billion (-$100 million). Subgroup analysis of thoracic organs revealed that the SDCF model would lead to a predicted 156 additional transplants with a cost saving of $24.6 million. CONCLUSIONS: The U.S. SDCF model may be a less costly and more effective means of multi-organ donor management, particularly for thoracic organ donors, compared to the conventional hospital-based model.

Pseudomonas aeruginosa and acute rejection independently increase the risk of donor-specific antibodies after lung transplantation.

Factors contributing to donor-specific HLA antibody (DSA) development after lung transplantation have not been systematically evaluated. We hypothesized that the isolation of Pseudomonas aeruginosa in respiratory specimens would increase the risk of DSA development. Our objective was to determine the risk of DSA development associated with the isolation of Pseudomonas aeruginosa after lung transplantation. We conducted a single-center retrospective cohort study of primary lung transplant recipients and examined risk factors for DSA development using Cox regression models. Of 460 recipients, 205 (45%) developed DSA; the majority developed Class II DSA (n = 175, 85%), and 145 of 205 (71%) developed DSA to HLA-DQ alleles. Univariate time-dependent analyses revealed that isolation of Pseudomonas from respiratory specimens, acute cellular rejection, and lymphocytic bronchiolitis are associated with an increased risk of DSA development. In multivariable analyses, Pseudomonas isolation, acute cellular rejection, and lymphocytic bronchiolitis remained independent risk factors for DSA development. Additionally, there was a direct association between the number of positive Pseudomonas cultures and the risk of DSA development. Our findings suggest that pro-inflammatory events including acute cellular rejection, lymphocytic bronchiolitis, and Pseudomonas isolation after transplantation are associated with an increased risk of DSA development.

Rabbit antithymocyte globulin for the treatment of chronic lung allograft dysfunction.

BACKGROUND: Chronic lung allograft dysfunction (CLAD) is the leading cause of death beyond the first year after lung transplantation. Several treatments have been used to prevent the progression or reverse the effects of CLAD. Cytolytic therapy with rabbit antithymocyte globulin (rATG) has previously shown to be a potential option. However, the effect on patients with restrictive allograft syndrome (RAS) versus bronchiolitis obliterans syndrome (BOS) and the effect of cumulative dosing are unknown. METHODS: The charts of lung transplant patients treated with rATG at Barnes-Jewish Hospital from 2009 to 2016 were retrospectively reviewed. The primary outcome was response to rATG; patients were deemed responders if their FEV1 improved in the 6 months after rATG treatment. Safety endpoints included incidence of serum sickness, cytokine release syndrome, malignancy, and infectious complications. RESULTS: 108 patients were included in this study; 43 (40%) patients were responders who experienced an increase in FEV1 after rATG therapy. No predictors of response to rATG therapy were identified. Serum sickness occurred in 22% of patients, 15% experienced cytokine release syndrome, and 19% developed an infection after therapy. CONCLUSION: 40% of patients with CLAD have an improvement in lung function after treatment with rATG although the improvement was typically minimal.

Chest computed tomography imaging improves potential lung donor assessment.

OBJECTIVE: Chest computed tomography (CT) imaging is being increasingly used for potential lung donor assessment. However, the efficacy of CT imaging in this setting remains unknown. We hypothesize that chest CT imaging independently affects the decision-making process in donor lung utilization. METHODS: We conducted a retrospective cohort study of all adult donation after brain death donors managed through our local organ procurement organization from June 2011 to November 2016. An experienced thoracic radiologist independently reviewed donor chest CT and chest x-ray images in a blinded, standardized manner to determine the presence of structural lung disease (eg, emphysema, interstitial lung disease [ILD]) and acute abnormalities (eg, traumatic lung injury [TLI]). Distinct models of lung utilization were fit to groups with initial partial pressure of oxygen (iPaO2) ≤300 mm Hg (suboptimal) and iPaO2 >300 mm Hg (optimal). RESULTS: The organ procurement organization managed 753 donors during the study period, with a lung utilization rate ([lung donors/all organ donors] × 100) of 36.5% (275 of 753). Four hundred forty-five (59.1%) donors received chest CT imaging, revealing emphysema (13.7%), ILD (2.5%), and TLI (7.2%). In univariate analysis, findings of TLI (odds ratio [OR], 2.23; 95% confidence interval [CI], 1.08-4.61) were positively associated with lung utilization, whereas findings of emphysema (OR, 0.18; CI, 0.08-0.40) were negatively associated with utilization. In multivariate analysis, CT findings of emphysema (OR, 0.21; CI 0.08-0.54) remained negatively associated with utilization. No potential donors with CT findings of ILD became lung donors. After controlling for chest x-ray findings, chest CT imaging findings of structural lung disease remained negatively associated with utilization (P = .0001). Lung utilization rate in the suboptimal and optimal iPaO2 populations was 35.1% and 41.4%, respectively, and CT findings of emphysema had a significant association with nonutilization in both groups. CONCLUSIONS: In the evaluation of potential lung donors, chest CT imaging findings of structural lung disease, such as emphysema and ILD, have a significant negative association with lung utilization. Our findings suggest that chest CT imaging might be an important adjunct to conventional lung donor assessment criteria.

Molecular assessment of rejection and injury in lung transplant biopsies.

BACKGROUND: Improved understanding of lung transplant disease states is essential because failure rates are high, often due to chronic lung allograft dysfunction. However, histologic assessment of lung transplant transbronchial biopsies (TBBs) is difficult and often uninterpretable even with 10 pieces. METHODS: We prospectively studied whether microarray assessment of single TBB pieces could identify disease states and reduce the amount of tissue required for diagnosis. By following strategies successful for heart transplants, we used expression of rejection-associated transcripts (annotated in kidney transplant biopsies) in unsupervised machine learning to identify disease states. RESULTS: All 242 single-piece TBBs produced reliable transcript measurements. Paired TBB pieces available from 12 patients showed significant similarity but also showed some sampling variance. Alveolar content, as estimated by surfactant transcript expression, was a source of sampling variance. To offset sampling variation, for analysis, we selected 152 single-piece TBBs with high surfactant transcripts. Unsupervised archetypal analysis identified 4 idealized phenotypes (archetypes) and scored biopsies for their similarity to each: normal; T-cell‒mediated rejection (TCMR; T-cell transcripts); antibody-mediated rejection (ABMR)-like (endothelial transcripts); and injury (macrophage transcripts). Molecular TCMR correlated with histologic TCMR. The relationship of molecular scores to histologic ABMR could not be assessed because of the paucity of ABMR in this population. CONCLUSIONS: Molecular assessment of single-piece TBBs can be used to classify lung transplant biopsies and correlated with rejection histology. Two or 3 pieces for each TBB will probably be needed to offset sampling variance.

Association between Allosensitization and Waiting List Outcomes among Adult Lung Transplant Candidates in the United States.

Rationale: Allosensitization may be a barrier to lung transplant. Currently, consideration is not given to allosensitization when assigning priority on the lung transplant waiting list. Objectives: We aimed to examine the association between allosensitization and waiting list outcomes. Methods: We conducted a retrospective single-center cohort study of adults listed for lung transplant at our center between January 1, 2006, and December 31, 2016. We screened candidates for human leukocyte antigen antibodies before listing and examined the association between allosensitization and waiting list outcomes, including likelihood of transplant and death on the waiting list, using a competing risk model. Calculated panel-reactive antibody (CPRA) was used as a continuous measure of allosensitization. Results: Among 746 candidates who were listed for lung transplant during the study period, 263 (35%) were allosensitized, and 483 (65%) were not. In unadjusted analysis, allosensitized candidates had a decreased likelihood of transplant compared with nonallosensitized candidates (subhazard ratio [sHR], 0.71; 95% confidence interval [CI], 0.60-0.83; P < 0.001) and were more likely to die on the waiting list (sHR, 1.66; 95% CI, 1.08-2.58; P < 0.001). In multivariable modeling, increasing CPRA was associated with an increased risk of death and a decreased likelihood of transplant (sHR for death, 1.15 per 10% increase in CPRA; 95% CI, 1.07-1.22; P < 0.001; sHR for transplant, 0.89 per 10% increase in CPRA; 95% CI, 0.86-0.91; P < 0.001). Conclusions: Broad allosensitization was associated with longer waiting times, decreased likelihood of transplant, and increased risk of death among candidates on the waiting list for lung transplant. Consideration of allosensitization in organ allocation strategies might help mitigate this increased risk in highly allosensitized candidates.

Technical Considerations for Lung Transplantation in Kartagener's Syndrome.

Kartagener's syndrome is a rare genetic disorder of ciliated epithelial cells associated with recurrent respiratory tract infections, bronchiectasis, and situs inversus. In some patients, the accumulation of airway secretions and recurrent infections lead to end-stage lung disease, for which lung transplantation is the only effective treatment. Anatomical variations, such as dextrocardia and pulmonary situs inversus, make the procedure challenging, yet feasible with certain technical modifications and careful preparation of donor lungs. We report a case of bilateral lung transplantation without the use of cardiopulmonary bypass in a patient with Kartagener's syndrome while describing important technical details of the operation.

Bronchiolitis obliterans syndrome-free survival after lung transplantation: An International Society for Heart and Lung Transplantation Thoracic Transplant Registry analysis.

BACKGROUND: Lung transplant (LTx) recipients have low long-term survival and a high incidence of bronchiolitis obliterans syndrome (BOS). However, few long-term, multicenter, and precise estimates of BOS-free survival (a composite outcome of death or BOS) incidence exist. METHODS: This retrospective cohort study of primary LTx recipients (1994-2011) reported to the International Society of Heart and Lung Transplantation Thoracic Transplant Registry assessed outcomes through 2012. For the composite primary outcome of BOS-free survival, we used Kaplan-Meier survival and Cox proportional hazards regression, censoring for loss to follow-up, end of study, and re-LTx. Although standard Thoracic Transplant Registry analyses censor at the last consecutive annual complete BOS status report, our analyses allowed for partially missing BOS data. RESULTS: Due to BOS reporting standards, 99.1% of the cohort received LTx in North America. During 79,896 person-years of follow-up, single LTx (6,599 of 15,268 [43%]) and bilateral LTx (8,699 of 15,268 [57%]) recipients had a median BOS-free survival of 3.16 years (95% confidence interval [CI], 2.99-3.30 years) and 3.58 years (95% CI, 3.53-3.72 years), respectively. Almost 90% of the single and bilateral LTx recipients developed the composite outcome within 10 years of transplantation. Standard Registry analyses "overestimated" median BOS-free survival by 0.42 years and "underestimated" the median survival after BOS by about a half-year for both single and bilateral LTx (p < 0.05). CONCLUSIONS: Most LTx recipients die or develop BOS within 4 years, and very few remain alive and free from BOS at 10 years post-LTx. Less inclusive Thoracic Transplant Registry analytic methods tend to overestimate BOS-free survival. The Registry would benefit from improved international reporting of BOS and other chronic lung allograft dysfunction (CLAD) events.

A single-center experience of 1500 lung transplant patients.

OBJECTIVE: Over the past 30 years, lung transplantation has emerged as the definitive treatment for end-stage lung disease. In 2005, the lung allocation score (LAS) was introduced to allocate organs according to disease severity. The number of transplants performed annually in the United States continues to increase as centers have become more comfortable expanding donor and recipient criteria and have become more facile with the perioperative and long-term management of these patients. We report a single-center experience with lung transplants, looking at patients before and after the introduction of LAS. METHODS: We retrospectively reviewed 1500 adult lung transplants at a single center performed between 1988 and 2016. Patients were separated into 2 groups, before and after the introduction of LAS: group 1 (April 1988 to April 2005; 792 patients) and group 2 (May 2005 to September 2016; 708 patients). RESULTS: Differences in demographic data were noted over these periods, reflecting changes in allocation of organs. Group 1 patient average age was 48 ± 13 years, and 404 subjects (51%) were male. Disease processes included emphysema (52%; 412), cystic fibrosis (18.2%; 144), pulmonary fibrosis (16.1%; 128) and pulmonary vascular disease (7.2%; 57). Double lung transplant (77.7%; 615) was performed more frequently than single lung transplant (22.3%; 177). Group 2 average age was 50 ± 14 years, and 430 subjects (59%) were male. Disease processes included pulmonary fibrosis (46%; 335), emphysema (25.8%; 188), cystic fibrosis (17.7%; 127) and pulmonary vascular disease (1.6%; 11). Double lung transplant (96.2%; 681) was performed more frequently than single lung transplant (3.8%; 27). Overall incidence of grade 3 primary graft dysfunction (PGD) in group 1 was significantly lower at 22.1% (175) than in group 2 at 31.6% (230) (P < .001). Nonetheless, overall hospital mortality was not statistically different between the 2 groups (4.4% vs 3.5%; P < .4). Most notably, survival at 1 year was statistically different at 646 (81.6%) for group 1 and 665 (91.4%) for group 2 (P < .02). CONCLUSIONS: Patient demographics over the study period have changed with an increased number of fibrotic patients transplanted. In addition, more aggressive strategies with donor/recipient selection appear to have resulted in a higher incidence of primary graft dysfunction. This does not, however, appear to affect patient survival on index hospitalization or at 1 year. In fact, we have observed a significant improvement in survival at 1 year in the more recent era. This observation suggests that continued expansion of possible donors and recipients, coupled with a more sophisticated understanding of primary graft dysfunction and long-term chronic rejection, can lead to increased transplant volume and prolonged survival.

Impact of Delayed Chest Closure on Surgical Site Infection After Lung Transplantation.

BACKGROUND: Delayed chest closure is an increasingly used approach in the management of bleeding and hemodynamic instability after lung transplantation. We sought to evaluate the impact of delayed chest closure on surgical site infection. METHODS: We performed a single-center retrospective cohort study and included adult patients who received a lung transplant at our center between January 1, 2010, and July 31, 2014. We defined surgical site infection as a thoracotomy incision wound or pleural space infection. Follow-up was complete through 6 months after transplantation. We used logistic regression models to examine the impact of delayed chest closure on surgical site infection and to identify other potential risk factors. RESULTS: During the study period, 67 of the 232 transplant procedures (29%) required delayed chest closure, and surgical site infection developed in 22 recipients (9%). Among the patients with surgical site infection, 18 experienced a wound infection, and 8 experienced a pleural space infection; 4 experienced concomitant wound and pleural space infection. Among the 67 who underwent delayed chest closure, 13 patients (19%) experienced a surgical site infection compared with 9 of the 165 patients (5%) who underwent primary closure (p = 0.001). In multivariate analysis, delayed chest closure was an independent risk factor for surgical site infection. CONCLUSIONS: Although delayed chest closure may have an important role in the immediate management of recipients of a lung transplant, it is an independent risk factor for surgical site infection, and this is associated with increased morbidity.

Falsely Elevated Plasma Creatinine Due to an Immunoglobulin M Paraprotein.

The most common method for measuring plasma creatinine is based on its reaction with picric acid. However, enzymatic methods are becoming more popular due to improved specificity. We present a case of falsely elevated plasma creatinine values obtained by an enzymatic method that turned out to be due to a monoclonal immunoglobulin M (IgM) paraprotein. A 63-year-old woman evaluated for lung transplantation had falsely increased plasma creatinine levels (1.54-1.71mg/dL; corresponding to estimated glomerular filtration rates of 32-36 mL/min/1.73m2) as measured by the Roche Creatinine plus enzymatic assay when compared with the picric acid-based procedure and several other enzymatic methods, which gave plasma creatinine values of 0.7 to 0.8mg/dL. Serum protein electrophoresis revealed an IgM κ light chain paraprotein. Removal of high-molecular-weight (>30kDa) proteins by ultrafiltration reduced the patient's plasma creatinine level by the Roche enzymatic method to 0.7mg/dL. Addition of the patient's immunoglobulin fraction to plasma from other patients with normal plasma creatinine levels resulted in values that were increased by 0.58 to 0.62mg/dL. Furthermore, removal of non-IgM immunoglobulins with protein G-coupled beads did not eliminate the interference from the patient's plasma. Taken together, these studies demonstrate that falsely elevated plasma creatinine values by the Roche enzymatic method can be due to an IgM paraprotein.

Hyperammonemia Syndrome After Lung Transplantation: A Single Center Experience.

BACKGROUND: Hyperammonemia is a rare, often fatal complication after transplantation. The etiology is unknown, but recognition and rapid treatment may help to improve the survival of this unusual syndrome. We present the largest case series to date of hyperammonemia after lung transplantation (LTx) and discuss a treatment protocol that has been developed at our institution. METHODS: We conducted a retrospective cohort series of patients who underwent LTx between January 1, 2000, and December 31, 2013. Patients who developed hyperammonemia syndrome in the posttransplantation period, which was defined as symptoms of encephalopathy and plasma ammonia level exceeding 200 µmol/L on at least 1 occasion, were included. Data including demographics, antimicrobial and immunosuppression regimens, ammonia levels and other pertinent laboratory data, treatments administered, and outcomes were recorded. RESULTS: Eight of 807 lung transplant recipients developed hyperammonemia syndrome postoperatively during this time period. Median time to onset was 9.0 days, and median peak ammonia level was 370 µmol/L. All 8 patients were treated with hemodialysis, 7 of 8 patients were treated with bowel decontamination, and 5 of 8 patients were treated with nitrogen scavenging agents. Six of the 8 patients died. CONCLUSIONS: The incidence of hyperammonemia syndrome in LTx patients was approximately 1%. Future research is needed to determine the efficacy of treatment, including hemodialysis, bowel decontamination, antibiotics, and the use of nitrogen scavenging agents in lung recipients with hyperammonemia.

The impact of pre-transplant allosensitization on outcomes after lung transplantation.

BACKGROUND: Allosensitization can be a significant barrier to transplantation for some patients, and previous studies suggested that pre-transplant allosensitization was associated with worse outcomes after lung transplantation. However, human leukocyte antigen (HLA) antibody testing has evolved significantly over the past 10 years, and current assays are highly sensitive and specific. METHODS: We examined the impact of pre-transplant allosensitization on post-transplant outcomes in the era of solid-phase multiplex HLA antibody detection assays in this retrospective, single-center study of 304 adult transplant recipients between January 1, 2006, and December 31, 2012. We accepted donor organs for allosensitized patients if a virtual crossmatch was compatible with all previously identified antibodies. RESULTS: In univariate and multivariate Cox proportional hazards models, pre-transplant allosensitization, the calculated panel reactive antibody, and the number of pre-transplant HLA antibodies were not associated with the development of acute cellular rejection, lymphocytic bronchiolitis, donor-specific HLA antibodies, chronic lung allograft dysfunction, or graft failure. CONCLUSIONS: Pre-transplant allosensitization does not adversely affect outcomes after lung transplantation when the potentially reactive HLAs are avoided in the donor by a virtual crossmatch with the recipient.

MicroRNA-144 dysregulates the transforming growth factor-ß signaling cascade and contributes to the development of bronchiolitis obliterans syndrome after human lung transplantation.

BACKGROUND: Bronchiolitis obliterans syndrome (BOS), chronic lung allograft rejection, remains an impediment for the function of the transplanted organ. In this study, we defined the role of the microRNA (miRNA) miR-144 in fibroproliferation leading to BOS. METHODS: Biopsy specimens were obtained from 20 lung transplant recipients with BOS((+)) and 19 without BOS((-)). Expression of miR-144 and its target, transforming growth factor-ß (TGF-ß)-induced factor homeobox 1(TGIF1), were analyzed by real-time polymerase chain reaction and Western blot. Overexpression of miR-144 and luciferase reporter genes were performed to elucidate miRNA-target interactions. The function of miR-144 was evaluated by transfecting fibroblasts and determining the response to TGF-ß by analyzing Sma- and Mad-related family (Smads), fibroblast growth factor, TGF-ß, and vascular endothelial growth factor. Smooth muscle actin-α-positive stress fibers and F-actin filaments in lung fibroblasts were analyzed by immunofluorescence. RESULTS: Analysis of miR-144 in the biopsy specimens demonstrated 4.1 ± 0.8-fold increases in BOS(+) compared with BOS(-) patients, with a significant reduction in TGIF1 (3.6 ± 1.2-fold), a corepressor of Smads. In vitro transfection confirmed that over-expression of miR-144 results in a reduction in TGIF1 and an increase in SMAD2, SMAD4, fibroblast growth factor-6, TGF-ß, and vascular endothelial growth factor. Increasing miR-144 by transfecting, increased smooth muscle actin-α and fibronectin, and knockdown of miR-144 diminished fibrogenesis in MRC-5 fibroblasts. CONCLUSIONS: miR-144 is a critical regulator of the TGF-ß signaling cascade and is over-expressed in lungs with BOS. Therefore, miR-144 is a potential target toward preventing fibrosis leading to BOS after lung transplant.

Cadaveric nerve allotransplantation in the treatment of persistent thoracic neuralgia.

When relief from neuralgia cannot be achieved with traditional methods, neurectomy may be considered to abate the stimulus, and primary opposition of the terminal nerve ending is recommended to prevent neuroma. Nerve repair with autograft is limited by autologous nerves available for large nerve defects. Cadaveric allografts provide an unlimited graft source without donor-site morbidities, but are rapidly rejected unless appropriate immunosuppression is achieved. An optimal treatment method for nerve allograft transplantation would minimize rejection while simultaneously permitting nerve regeneration. This report details a novel experience of nerve allograft transplantation using cadaveric nerve grafts to desensitize persistent postoperative thoracic neuralgia.

Lung transplant or bust: patients' recommendations for ideal lung transplant education.

CONTEXT: Effective lung transplant education helps ensure informed decision making by patients and better transplant outcomes. OBJECTIVE: To understand the educational needs and experiences of lung transplant patients. DESIGN: Mixed-method study employing focus groups and patient surveys. SETTING: Barnes-Jewish Hospital in St Louis, Missouri. PATIENTS: 50 adult lung transplant patients: 23 pretransplant and 27 posttransplant. MAIN OUTCOME MEASURES: Patients' interest in receiving specific transplant information, the stage in the transplant process during which they wanted to receive the education, and the preferred format for presenting the information. RESULTS: Patients most wanted information about how to sustain their transplant (72%), when to contact their coordinator immediately (56%), transplant benefits (56%), immunosuppressants (54%), and possible out-of-pocket expenses (52%). Patients also wanted comprehensive information early in the transplant process and a review of a subset of topics immediately before transplant (time between getting the call that a potential donor has been found and getting the transplant). Patients reported that they would use Internet resources (74%) and converse with transplant professionals (68%) and recipients (62%) most often. DISCUSSION: Lung transplant patients are focused on learning how to get a transplant and ensuring its success afterwards. A comprehensive overview of the evaluation, surgery, and recovery process at evaluation onset with a review of content about medications, pain management, and transplant recovery repeated immediately before surgery is ideal.