Adult Lung Transplant Patients Research Articles

Serum Level of Immunosuppressants as a Marker of Effectiveness of Pharmaceutical Education in Solid Organ Transplantation

Solid organ transplantation promotes an increase in the quality of life of those with diseases that compromise the functioning of a specific organ, maximizing graft survival and reducing the need for retransplantation is essential. Post-transplant medication adherence is one of the factors that influence positive clinical outcomes, with this, the importance of pharmacotherapeutic follow-up at the hospital and outpatient level with the clinical pharmacist is addressed. Objectives: To verify the impact of pharmacotherapeutic guidance and follow-up on the compliance of serum levels of calcineurin inhibitors in lung and liver transplant patients. Methods: Descriptive and retrospective study with adult liver and lung transplant patients using calcineurin inhibitors, aged over 18 years, between 2018 and 2020. The variation index was calculated through the mean and standard deviation of serum levels collected during the index hospitalization, being used to assess the adequacy of serum levels in three different periods. Results: A total of 84 patients were transplanted, including 64 patients (45 liver transplants and 19 lung transplants). In a subgroup analysis, 42.22% of the liver patients and 47.37% of the lung transplant recipients did not have the same serum level in the first post-discharge consultation. After 1 year of transplantation and differentiated outpatient follow-ups, the target serum levels were reached in 63.16% and 77.78% of the studied populations, respectively. Conclusion: The importance of clinical action was demonstrated from the reflection obtained on the adequacy and conformity of serum levels of calcineurin inhibitors, not only at the hospital level but mainly on the pharmacotherapeutic follow-up carried out on an outpatient basis, in which we observed a more expressive value.

Eficacia de las intervenciones fisioterápicas sobre la musculatura respiratoria mediante técnicas de entrenamiento respiratorio en el postoperatorio de trasplantados pulmonares: una revisión sistemática

IntroductionRespiratory muscles are a limiter of exercise capacity in lung transplant patients. It is necessary to know the effectiveness of specific respiratory muscle training techniques carried out in the management of adult lung transplant patients in the postoperative period. Material and methodsA systematic review of clinical trials was carried out, which included adult lung transplant patients undergoing post-transplant respiratory training. A search was carried out in the databases PubMed/Medline, EMBASE, Scopus, Web of Science, Cochrane Library between January 2012 and September 2023, using the terms: “breathing exercise”, “respiratory muscle training”, “inspiratory muscle training”, “respiratory exercise”, “pulmonary rehabilitation”, “lung rehabilitation”; in combination with “lung transplantation”, “lung transplant”, “posttransplant lung”. No language limit. ResultsEleven trials were included with a total of 639 patients analyzed. Most training programs begin upon hospital discharge (more than one month post-transplant), few do so early (Intensive Care Unit). The duration varies from 1-12 months post-transplant. The interventions were based on aerobic training and peripheral muscle strength. Some of them included breathing exercises and chest expansions. The most used outcome variable was submaximal exercise capacity measured with the 6-minute walk test. ConclusionsTraining the respiratory muscles of the adult transplant patient favors the improvement of exercise capacity and quality of life. Aerobic training, as well as strength training of the rest of the peripheral muscles, contribute to the improvement of respiratory muscles.

Evaluation of host cellular responses to Epstein-Barr virus (EBV) in adult lung transplant patients with EBV-associated diseases.

Epstein-Barr virus (EBV)reactivation is commonly observed in lung transplant recipients (LTRs).However, cellular immune responses to EBV in adult LTRs have not been well described. We aimed to study CD4/CD8ratio, EBV-specificT cells polyfunctional responses and phenotypic changes in natural killer (NK)cells in adult LTRs presenting with EBV-associateddiseases. The CD4/CD8ratio was significantly decreased in LTRs with EBV DNAemia compared withLTRs without EBV DNAemia and healthy controls (HCs).Stimulation with EBV lytic antigen BZLF1 peptide pools induced significant individual and polyfunctional responses from CD8+ CD69+ T cells. Frequencies of CD8+ CD69+ T cells expressing CD107a were significantly higher in LTRs without EBV DNAemia than in LTRs with DNAemia. Frequencies of CD8+ CD69+ T cells concurrently expressing CD107a, IFN-γ,and TNF-αwere significantly greater in LTRs with and without EBV DNAemia than in HCs. Finally, BZLF1 induced significantly higher frequencies of CD8+ CD69+ T cells expressing CD107a and IFN-γin LTRs without EBV DNAemia when compared withEBNA3B. Frequency of more differentiated CD56dim CD16pos NK cells was significantly decreased in LTRs with EBV DNAemia and PTLD compared withHCs. In conclusion, we noted the presence of significant changes in circulating cellular immune responses to EBV in adult LTRs.

Red Blood Cell Transfusion Prior to Lung Transplantation: Impact on Patient Outcomes.

There is an established association between red blood cell (RBC) transfusion and increased mortality and morbidity in cardiac surgery; however, there is little data demonstrating the influence of blood transfusion while awaiting lung transplantation. Therefore, our study compared the impact of pretransplant RBC transfusion on patient survival and post-transplantation adverse events. Adult lung transplant patient data were extracted retrospectively using the United Network for Organ Sharing thoracic database. Patients were stratified into two groups based on pretransplant transfusion status. In total, 28,217 patients were analyzed in our study (transfused: n = 1,415 and not transfused: n = 26,802). There was an increasing trend in pretransplant transfusion rates from 2006 to 2020. Transfused patients had a higher incidence of adverse events post-transplantation, including dialysis, stroke, and acute organ rejection before discharge. Multivariable survival analysis found an increased mortality risk in patients who required pretransplant transfusion(s) compared to those who did not have a transfusion (hazard ratio [HR]: 1.27; 95% confidence interval [CI]: 1.17-1.41; p < 0.001). There was no significant difference in bronchiolitis obliterans syndrome development between groups (HR: 0.92; 95% CI: 0.82-1.04; p = 0.185). To conclude, our study provides data to suggest that RBC transfusion(s) before lung transplantation are associated with increased patient morbidity and mortality, but have no association with chronic graft rejection development.

Early Change in Lower Limb Strength and Function in Lung Transplant Patients After Center-Based and Telerehabilitation.

The aim of this study was to examine the change and relationship among quadriceps torque (QT) and physical function in adult lung transplant (LTx) patients undergoing rehabilitation. A prospective study assessed 6-min walk test (6MWT) distance, QT, and Short Physical Performance Battery (SPPB) at the start of pre-habilitation and 10-12 wk post-LTx. Functional outcomes were examined for within-group differences for participants who completed center-based rehabilitation between September 2019 and March 2020 and participants who completed telerehabilitation ("telerehab") between March 2020 and June 2021 during COVID-19. Relationships between QT, SPPB, and 6MWT were examined pre- and post-LTx. A total of 49 LTx recipients were included (30 men, 61 [56-67] yr, 26 center-based rehab, and 23 telerehab). The 6MWT increased (median 75 m: 95% CI, 35 - 117, P < .0001), and the telerehab group showed an LTx decrease in QT (-9.6 Nm: 95% CI, -29 to -2.3, P = .02) and an increased gait speed (0.21 m/sec: 95% CI, 0.11 - 0.47, P < .0001). Pre-LTx QT showed a moderate correlation to pre-LTx SPPB ( r = 0.41, P = .004) and weak correlations to gait speed and 6MWT ( r ranging from 0.21 to 0.35, P < .05). Post-LTx QT showed moderate correlations to post-LTx SPPB ( r = 0.43, P = .002), gait speed ( r = 0.54, P < .001), five-time sit-to-stand ( r =-0.57, P < .0001), and 6MWT ( r = 0.62, P < .0001). Early post-LTx 6MWT and gait speed increased with no improvement in QT or other SPPB components. Correlations between QT and measures of exercise capacity and lower limb function were stronger post-LTx. Serial measurements may further inform functional trajectories and rehabilitation models.

Lung Transplant Outcomes in Adults in the United States: Retrospective Cohort Study Using Real-world Evidence from the SRTR.

Background.The Scientific Registry of Transplant Recipients was retrospectively analyzed to provide real-world evidence of the efficacy and safety of tacrolimus-based immunosuppressive regimens in adult lung transplant recipients in the United States.Methods.Adult recipients (N = 25 355; ≥18 y) of a primary deceased-donor lung transplant between January 1, 1999, and December 31, 2017, were followed for 3 y posttransplant based on immunosuppressive regimen at discharge: immediate-release tacrolimus (TAC) + mycophenolate mofetil (MMF), TAC + azathioprine (AZA), cyclosporine (CsA) + MMF, or CsA + AZA. The primary outcome was the composite endpoint of graft failure or death (all-cause) at 1 y posttransplant (calculated via a modified Kaplan–Meier method).Results.Discharge immunosuppressive regimens in lung transplant recipients changed over time, with a substantial increase in the use of TAC + MMF. TAC + MMF was the most common immunosuppressive regimen (received by 61.0% of individuals at discharge). The cumulative incidence of graft failure or death at 1 y posttransplant in adult lung transplant patients receiving TAC + MMF was 8.6% (95% confidence interval 8.1-9.1). Risk of graft failure or death was significantly higher in adults receiving CsA + MMF or CsA + AZA compared with TAC + MMF, with no significant difference seen between TAC + MMF and TAC + AZA. TAC + MMF had the highest continued use at 1 y posttransplant (72.0% versus 35.4%–51.5% for the other regimens). There was no increase in the rate of infection or malignancy in the TAC + MMF group.Conclusions.Real-world evidence from the most comprehensive database of transplant recipients in the United States supports the use of TAC in combination with MMF or AZA as maintenance immunosuppression in adult lung transplant recipients.

Comparison of endoscopic sinus surgery timing in lung transplant patients with cystic fibrosis

No studies have investigated when endoscopic sinus surgery (ESS) is best performed in lung transplant patients with cystic fibrosis (CF). We sought to examine the effects of ESS timing on pulmonary health in this population. A retrospective review of all adult lung transplant patients with CF who underwent ESS at our academic medical center over a near 25-year period was performed. Patients were split into two groups based on median time from lung transplantation to ESS. Twenty-three patients were included (12 ESS early and 11 ESS delayed). Outcomes included changes in pulmonary function tests (PFTs) from baseline, preoperative to postoperative measurements, the number and duration of hospitalizations for pulmonary exacerbations, and the number of antibiotic courses used specifically to treat pulmonary exacerbations during the 12 months before and after ESS. Baseline demographics, operative history, and pulmonary function characteristics were similar between groups. While the ESS early group saw significant improvement from preoperative percent-predicted FEV1 (ppFEV1 ) at 12months postoperatively (confidence interval [CI]: 0.729-11.452, p=0.030), there were no significant postoperative PFT changes for the ESS delayed group. Postoperative improvement in FEV1 and ppFEV1 at 12months was significantly higher for the ESS early group relative to the ESS delayed group (CI: 0.010-0.583, p=0.043; CI: 1.240-16.692, p=0.025; respectively). The ESS early group had a significant reduction in the need for total antibiotic courses compared with the ESS delayed group (ESS early median: -1, interquartile range [IQR]: -1.5 to -0.5vs. ESS delayed median: 0, IQR: 0 to 0; p=0.027). Earlier ESS interventions following lung transplantation may improve pulmonary function and attenuate pulmonary exacerbations in CF patients.

Chronic lung allograft dysfunction phenotype and prognosis by machine learning CT analysis.

Chronic lung allograft dysfunction (CLAD) is the principal cause of graft failure in lung transplant recipients and prognosis depends on CLAD phenotype. We used a machine learning computed tomography (CT) lung texture analysis tool at CLAD diagnosis for phenotyping and prognostication compared with radiologist scoring. This retrospective study included all adult first double lung transplant patients (January 2010-December 2015) with CLAD (censored December 2019) and inspiratory CT near CLAD diagnosis. The machine learning tool quantified ground-glass opacity, reticulation, hyperlucent lung and pulmonary vessel volume (PVV). Two radiologists scored for ground-glass opacity, reticulation, consolidation, pleural effusion, air trapping and bronchiectasis. Receiver operating characteristic curve analysis was used to evaluate the diagnostic performance of machine learning and radiologist for CLAD phenotype. Multivariable Cox proportional hazards regression analysis for allograft survival controlled for age, sex, native lung disease, cytomegalovirus serostatus and CLAD phenotype. 88 patients were included (57 bronchiolitis obliterans syndrome (BOS), 20 restrictive allograft syndrome (RAS)/mixed and 11 unclassified/undefined) with CT a median 9.5 days from CLAD onset. Radiologist and machine learning parameters phenotyped RAS/mixed with PVV as the strongest indicator (area under the curve (AUC) 0.85). Machine learning hyperlucent lung phenotyped BOS using only inspiratory CT (AUC 0.76). Radiologist and machine learning parameters predicted graft failure in the multivariable analysis, best with PVV (hazard ratio 1.23, 95% CI 1.05-1.44; p=0.01). Machine learning discriminated between CLAD phenotypes on CT. Both radiologist and machine learning scoring were associated with graft failure, independent of CLAD phenotype. PVV, unique to machine learning, was the strongest in phenotyping and prognostication.

Lung transplant recipient attitudes and beliefs on accepting an organ that is positive for hepatitis C virus.

Little is known about patient perceptions regarding HCV+ organ use in non-HCV-infected recipients. This study examined factors influencing the decision to accept HCV+ organs and the resulting impacts. Adult lung transplant (LT) patients or candidates who had consented to receive an HCV+ organ completed a survey including multiple choice, a five-point Likert scale, and free-text answers. A total of 67 LT recipients or candidates who had consented to receive HCV+ organs were enrolled, of which 21/67 (31%) received HCV+ lungs, 39 (58%) HCV- lungs, and seven (10%) were still waiting. Pre-transplant, 50/67 (75%) patients felt it was either "completely safe" or "very safe" to accept an HCV+ organ. Although 22/67 (33%) said they never or rarely took risks, they still made the decision to accept an HCV+ organ. Common reported reasons were desperation, perception of having "no choice," and increasing symptom severity. In the subset of patients that were transplanted with an HCV+ organ (n=21), only 12.5% reported second thoughts about accepting. Post-transplant, the majority (87.5%) never felt any anxiety about HCV and most (83%) reported no impact from HCV. Perception of treatment tolerability and ease was highly favorable. Use of HCV+ organs demonstrated minimal detrimental perceived impacts on lung transplant patients. Patients generally found the experience to be very positive.

A retrospective analysis of the safety and efficacy of apixaban use after lung transplant.

Direct acting oral anticoagulants (DOACs) have become the mainstay of treatment for patients requiring anticoagulation for atrial arrhythmias and venous thromboembolism (VTE) but safety and efficacy has not been established in lung transplantation. This is a retrospective review of 28 adult lung transplant patients who were prescribed apixaban for stroke prevention in atrial arrhythmias or treatment of VTE between October 15, 2015 and December 31, 2018. The primary outcome was a composite of efficacy and safety measured by recurrence or breakthrough of stroke or thromboembolism and bleeding events. Seven patients were treated for atrial arrhythmias and 21 treated for VTE. Fifteen patients received CYP3A4 or P-gp inhibitors at initiation of anticoagulation, and 4 of these patients received strong CYP3A4 inhibitors. During the follow-up period, one breakthrough DVT and one clinically relevant non-major bleed were observed. These data suggest that apixaban may be safe to use for lung transplant patients, and larger studies are warranted to assess long-term outcomes as well as safety and efficacy of alternative DOACs.

Effects of a Goal Directed Transfusion Protocol on Severe Primary Graft Dysfunction after Lung Transplantation

Transfusion during lung transplantation (LT) is linked to primary graft dysfunction (PGD) and worsened outcomes. Goal-directed protocols have improved outcomes in cardiac surgical populations and decreased transfusions in LT on cardiopulmonary bypass. We propose that the implementation of goal-directed transfusion protocol for LT would reduce the rate of transfusion and PGD grade 3 at 72hrs. We included adult LT patients performed on and off mechanical circulatory support (MCS) between March 1, 2017 and February 28, 2019. Patients undergoing multi-organ transplant, preoperative MCS, or who received preoperative transfusions were excluded. A ROTEM-guided transfusion algorithm was implemented February 28, 2018. Demographic and procedural characteristics of patients were compared pre- and post-protocol. The primary outcome was PGD grade 3 at 72hrs, as defined by 2016 ISHLT criteria. PGD was trended by month before and after implementation. Adherence was defined as the presence of intraoperative ROTEM results. 188 patients were included, and grouped by time period either into pre-protocol (N=101) or post-protocol (N=87). There were no statistically significant differences in procedural or demographic characteristics between groups (Table 1). While the PGD rate decreased from 27.7% (n=28) in the pre-period to 20.7% (n=18) in the post-period, this was a not statistically significant (p=0.26). Intraoperative protocol labs were sent in in 77% (n=67) of the post-protocol patients. PGD during the post-period was 25% in the non-adherent protocol cases and 19% in the protocol adherent cases (p=0.54). While we previously described a consistent reduction of median RBC units transfused post-protocol over 12 months, this protocol did not result in a consistently reduced severe PGD rate. Over 12 months, we observed a trend in reduced PGD rates after implementing our transfusion protocol. Teams should consider goal-directed transfusion protocols for LT.

2669. Evaluation of Post-Operative Acute Kidney Injury with Piperacillin–Tazobactam Combined with Vancomycin for Lung Transplant Prophylaxis

BackgroundSeveral studies have identified that the addition of vancomycin (VAN) to piperacillin–tazobactam (PT) is associated with a higher incidence of nephrotoxicity when compared with other antibiotic regimens. Beginning in June 2017, our lung transplant antibiotic prophylaxis regimen was modified from PT monotherapy to VAN and PT.MethodsAll adult lung transplant patients between January 1, 2015 and November 10, 2018 were included. Patients were excluded if acute kidney injury (AKI) was present prior to transplant. Rates of AKI within 7 days of transplant were compared between those who received prophylaxis with PT and VAN vs. those receiving alternative regimens (AR). Patients receiving less than 1 dose of vancomycin or less than 3 doses PT (less than 24hours) were deemed to be in the alternative regimen group. AKI was defined as either an increase in serum creatinine (SCr) by ≥0.3 mg/dL within 48 hours or increase in SCr to ≥1.5 times baseline (within 7 days post-transplant). Secondary outcomes included duration of initial prophylactic antibiotic regimens, hospital length of stay (LOS), and all-cause inpatient mortality.ResultsEighty-six patients were included, 44 (51%) patients received PT/VAN. Baseline characteristics and results shown in Table 1. Of those receiving PT/VAN for prophylaxis, 24 (54%) developed AKI within 7 days of transplant while 15 (36%) of 42 patients receiving AR developed AKI (P = 0.08).ConclusionA larger proportion of patients that received PT/VAN for transplant antibiotic prophylaxis experienced AKI within 7 days. Although the difference did not reach statistical significance, a 19% higher incidence of AKI warrants need for further investigation. Disclosures All authors: No reported disclosures.

Lung clearance index in detection of post-transplant bronchiolitis obliterans syndrome.

BackgroundLong-term outcomes after lung transplantation are often limited by the development of obliterative bronchiolitis (OB), which is clinically defined using spirometry as bronchiolitis obliterans syndrome (BOS). Lung clearance index (LCI), derived from multiple breath washout (MBW) testing, is a global measure of ventilation heterogeneity that has previously been shown to be a more sensitive measure of obstructive small airway diseases than spirometry. We aimed to assess the feasibility of LCI in adult lung transplant patients and to compare LCI to BOS grade.Methods51 stable adult double-lung transplant recipients performed sulfur hexafluoride MBW in triplicate on a single occasion, using a closed-circuit Innocor device. BOS grades were derived from serial spirometry according to International Society for Heart and Lung Transplantation criteria and, where available, high-resolution computed tomography (HRCT) evidence of OB was recorded.ResultsLCI was successfully performed in 98% of patients. The within-visit coefficient of variation for repeat LCI measurements was 3.1%. Mean LCI increased significantly with BOS grades: no BOS (n=15), LCI 7.6; BOS-0p (n=16), LCI 8.3; BOS-1 (n=11), LCI 9.3; BOS-2–3 (n=9), LCI 13.2 (p<0.001). 27 patients had HRCT within 12 months. LCI in those with HRCT evidence of OB was higher than those without OB (11.1 versus 8.2, p=0.006). 47% patients displayed abnormal LCI (>7) despite a normal forced expiratory volume in 1 s (FEV1) (>80% of baseline).ConclusionsLCI measurement in lung transplant recipients is feasible and reproducible. LCI increased with increasing BOS grade. A significant proportion of this cohort had abnormal LCI with preserved FEV1, suggesting early subclinical small airway dysfunction, and supporting a role for MBW in the early identification of BOS.

Anticoagulation Strategies in the Perioperative Period for Lung Transplant: 4-Factor Prothrombin Complex Concentrate for Warfarin Reversal

Purpose Transfusion during lung transplantation (LT) is associated with worsened outcomes. When recipients require anticoagulation at listing, they are at increased risk of bleeding during LT if the drug effects are not rapidly reversed. Four-factor prothrombin complex concentrate (4-F PCC) is recently available for rapid warfarin reversal. Here we describe clinical outcomes in waitlisted recipients who were anticoagulated on warfarin and reversed with 4-F PCC at the time of LT. Methods The electronic medical records of all adult LT patients between 2/2014-8/2018 were queried. 4-F PCC became available in 2014, and routinely used for warfarin reversal in 2017. When indicated, patients were anticoagulated with warfarin at listing. During LT, 4-F PCC was administered immediately upon arrival to the OR and prior to incision, per recommended dose. We report 72-hour transfusion requirements, as well as short and long-term clinical outcomes. Results 451 LT patients’ records were queried; of those, 4 patients received full dose 4-F PCC for warfarin reversal, for off pump LT. We describe clinical characteristics of the recipient, the surgery, relevant medications administered, and outcomes in Table 1. 72-hr transfusion requirements ranged from 0 to 2 RBCs, with cryoprecipitate and platelets ranging from 0 to 2 U. FFP use varied tremendously because 1 patient required plasmapheresis perioperatively. Patient 2 had a deep vein thrombosis after 30 days during the index hospitalization. All patients were discharged home and have survived to date. Conclusion When warfarin is utilized as a therapeutic anticoagulation strategy at listing for lung transplant, 4F-PCC safely and effectively reverses its effects.

Outcomes of endoscopic sinus surgery in adult lung transplant patients with cystic fibrosis.

Cystic Fibrosis (CF) is the most common autosomal recessive disease in Caucasian population. Due to its pathological mechanism, chronic rhino sinusitis (CRS) associated or not with nasal polyposis usually occurs in adults and affects close to one-half of all CF patients. The goal of our work was to evaluate the impact of Endoscopic Sinus Surgery (ESS) in the quality of life (QoL) of the CF patients and demonstrate an improvement of the functional outcomes in the patients underwent the surgical procedure rather than in the not treated ones, particulary in lung transplant patients. We studied 54 adult patients affected by CF. Lund-Kennedy, Lund-Mackay scores, and SNOT-22 were analysed.14 had lung transplant and 9 had both lung tranplant and ESS procedures. 22 (40.7%) out of 54 CF patients underwent ESS. This group presented more likely complaints consistent with CRS. Lund-Kennedy and Lund-Mackay scores appeared higher in the ESS group: 10 (range of 6-12) and 15 (range of 12-20), respectively. SNOT-22 showed median values for non-ESS and ESS group of 20 (range of 3-68) and 40 (range of 10-73), respectively. ESS represents the best option to improve clinical QoL of CF patients who do not response to conventional medical therapy, with a stabilization of respiratory function after transplantation.

Everolimus Use for Intolerance or Failure of Baseline Immunosuppression in Adult Heart and Lung Transplantation.

BackgroundEverolimus can be utilized after heart or lung transplantation to reduce calcineurin inhibitor associated nephrotoxicity, due to cell cycle inhibitor adverse effects, and as adjunct therapy for rejection, cardiac allograft vasculopathy, and bronchiolitis obliterans syndrome.Material/MethodsA single-center, retrospective cohort study was conducted including 51 adult heart transplant patients (n=32) and lung transplant patients (n=19) started on everolimus due to immunosuppressive therapy intolerance or failure, between 2010 and 2017. Everolimus indication, response, efficacy, and tolerability were assessed.ResultsEverolimus was most commonly initiated due to leukopenia/neutropenia (n=17, 33%) or renal dysfunction (n=13, 25%). Leukopenia/neutropenia resolved in 76% of patients (13 out of 17 patients). Renal function (GFR) increased 7.4 mL/min from baseline to 3 months after everolimus initiation (P=0.011). The most common adverse effects were edema (n=23, 45%) and hyperlipidemia (n=25, 49%). A high discontinuation rate was observed (n=21, 41%), mostly from edema.ConclusionsEverolimus might be beneficial in heart and lung transplant patients with leukopenia or neutropenia and lead to modest, short-term renal function improvement. Patient selection is crucial because adverse effects frequently lead to everolimus discontinuation.

Medical image of the week: Plastic bronchitis in an adult lung transplant patient

Medical image of the week: Plastic bronchitis in an adult lung transplant patient

Shedding light on an unknown reality in solid organ transplant patients' self-management: A contextual inquiry study.

Traditional quantitative and qualitative research methods inadequately capture the complexity of patients' daily self-management. Contextual inquiry methodology, using home visits, allows a more in-depth understanding of how patients integrate immunosuppressive medication intake, physical activity, and healthy eating in their daily lives, and which difficulties they experience when doing so. This mixed-method study comprised 2 home visits in 19 purposively selected adult heart, lung, liver, and kidney transplant patients, asking them to demonstrate how they implement the aforementioned health behaviors. Meanwhile, conversations were audio-taped and photographs were taken. Audio-visual materials were coded using directed content analysis. Difficulties and supportive strategies were identified via inductive thematic analysis. We learned that few patients understood what "sufficiently active" means. Physical discomforts and poor motivation created variation across activity levels observed. Health benefits of dietary guidelines were insufficiently understood, and their implementation into everyday life considered difficult. Many underestimated the strictness of immunosuppressive medication intake, and instructions on handling late doses were unclear. Interruptions in routine and busyness contributed to nonadherence. We also learned that professionals often recommend supportive strategies, which patients not always like or need. This contextual inquiry study revealed unique insights, providing a basis for patient-tailored self-management interventions.

Therapy options for chronic lung allograft dysfunction–bronchiolitis obliterans syndrome following first-line immunosuppressive strategies: A systematic review

Long-term success of lung transplantation is limited by the development of chronic lung allograft dysfunction (CLAD), of which bronchiolitis obliterans syndrome (BOS) is the most common form. This systematic review sought to identify the current evidence base for CLAD-BOS therapies after initial immunosuppressive treatment strategies. The MEDLINE, Embase, and Cochrane Library databases from inception to May 3, 2016, were searched using keywords relating to CLAD-BOS, study designs, and treatments of interest, including extracorporeal photopheresis (ECP), aerosolized cyclosporine, total lymphoid irradiation (TLI), alemtuzumab, and montelukast. Titles, abstracts, and full texts were screened by 2 independent reviewers to identify studies of CLAD-BOS second-line therapy in adult lung transplant patients. Quality was assessed according to the Downs and Black checklist. Of the 936 individual citations identified, 47 reports of 40 studies met inclusion criteria, including 17 full publications, 11 recent (2015-2016), and 12 older (pre-2015) congress proceedings. Most of the full publications and recent abstracts investigated ECP (n = 11), TLI (n = 5), alemtuzumab (n = 4), and montelukast (n = 2). Most studies were uncontrolled and retrospective. Compared with standard therapy alone, improved lung function and survival was reported for ECP in 2 studies without randomization, with lower-quality evidence for improved lung function for TLI, montelukast, and aerosolized cyclosporine. Because most identified studies were of retrospective and uncontrolled design, comparison of treatment effects was limited. Available evidence suggests stabilized lung function after ECP in combination with established immunosuppressive regimens in late-line CLAD-BOS treatment, with fewer data for TLI, montelukast, and aerosolized cyclosporine.

Risk Factors for De Novo Malignancy Following Lung Transplantation.

Risk factors for non-skin cancer de novo malignancy (DNM) after lung transplantation have yet to be identified. We queried the United Network for Organ Sharing database for all adult lung transplant patients between 1989 and 2012. Standardized incidence ratios (SIRs) were computed by comparing the data to Surveillance, Epidemiology, and End Results Program data after excluding skin squamous/basal cell carcinomas. We identified 18 093 adult lung transplant patients; median follow-up time was 1086 days (interquartile range 436-2070). DNMs occurred in 1306 patients, with incidences of 1.4%, 4.6%, and 7.9% at 1, 3, and 5 years, respectively. The overall cancer incidence was elevated compared with that of the general US population (SIR 3.26, 95% confidence interval [CI]: 2.95-3.60). The most common cancer types were lung cancer (26.2% of all malignancies, SIR 6.49, 95% CI: 5.04-8.45) and lymphoproliferative disease (20.0%, SIR 14.14, 95% CI: 9.45-22.04). Predictors of DNM following lung transplantation were age (hazard ratio [HR] 1.03, 95% CI: 1.02-1.05, p < 0.001), male gender (HR 1.20, 95% CI: 1.02-1.42, p = 0.03), disease etiology (not cystic fibrosis, idiopathic pulmonary fibrosis or interstitial lung disease, HR 0.59, 95% CI 0.37-0.97, p = 0.04) and single-lung transplantation (HR 1.64, 95% CI: 1.34-2.01, p < 0.001). Significant interactions between donor or recipient smoking and single-lung transplantation were noted. On multivariable survival analysis, DNMs were associated with an increased risk of mortality (HR 1.44, 95% CI: 1.10-1.88, p = 0.009).