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1.
Nutritional Risk Index: A Predictive Metric for Mortality After Lung Transplant.
Bigelow, B, Toci, G, Etchill, E, Krishnan, A, Merlo, C, Bush, EL
The Annals of thoracic surgery. 2021;(1):214-220
Abstract
BACKGROUND Malnourishment is associated with poor outcomes after lung transplantation. Validated screening tools for patients awaiting lung transplants are needed. We assessed the association of the Nutritional Risk Index (NRI) with outcomes after lung transplantation. METHODS We categorized adult patients (aged more than 18 years) undergoing incident lung transplantation in the Scientific Registry of Transplant Recipients between 2005 and 2018 (n = 13,392) according to NRI categories of malnutrition: none, 100 or greater; mild, 97.5 to 100 or less; moderate, 83.5 to 97.5 or less; and severe, less than 83.5. We used Cox models to characterize the association of NRI categories with all-cause mortality within 5 years, graft failure within 1 year, and length of stay. In a subset of patients (n = 11,634), we used logistic regression to assess the association of NRI with airway dehiscence, reintubation, and chest tube placement. RESULTS Of the 13,392 lung transplant recipients (mean age 55 years; 58.6% male) in the study, the most common indication for transplant was idiopathic pulmonary fibrosis (36.2%), followed by chronic obstructive pulmonary disease (27.3%), and cystic fibrosis (12.6%). Based on the NRI, 54.4% were non-malnourished, 12.4% mildly, 25.9% moderately, and 7.2% severely malnourished. Five-year mortality was higher among patients with severe malnutrition (44.6%) compared with patients who were non-malnourished (38.9%). Severe malnourishment remained significantly associated with higher mortality risk, with adjustment for covariates (hazard ratio 1.47; 95% confidence interval, 1.26 to 1.58). The length of stay was significantly longer among patients with severe malnutrition (median 15 days) compared with non-malnourished recipients (median 18 days). This difference persisted after adjustment for covariates (severe malnutrition hazard ratio 0.85; 95% confidence interval, 0.79 to 0.91). CONCLUSIONS The NRI before transplant is an independent predictor of postoperative mortality and morbidity among lung transplant patients.
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2.
Cystic fibrosis foundation consensus statements for the care of cystic fibrosis lung transplant recipients.
Shah, P, Lowery, E, Chaparro, C, Visner, G, Hempstead, SE, Abraham, J, Bhakta, Z, Carroll, M, Christon, L, Danziger-Isakov, L, et al
The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation. 2021;(7):539-556
Abstract
Cystic fibrosis (CF) is the indication for transplantation in approximately 15% of recipients worldwide, and Cystic Fibrosis Lung Transplant Recipients (CFLTRs) have excellent long-term outcomes. Yet, CFLTRs have unique comorbidities that require specialized care. The objective of this document is to provide recommendations to CF and lung transplant clinicians for the management of perioperative and underlying comorbidities of CFLTRs and the impact of transplantation on these comorbidities. The Cystic Fibrosis Foundation (CFF) organized a multidisciplinary committee to develop CF Lung Transplant Clinical Care Recommendations. Three workgroups were formed to develop focused questions. Following a literature search, consensus recommendations were developed by the committee members based on literature review, committee experience and iterative revisions, and in response to public comment. The committee formulated 32 recommendation statements in the topics related to infectious disease, endocrine, gastroenterology, pharmacology, mental health and family planning. Broadly, the committee recommends close coordination of care between the lung transplant team, the cystic fibrosis care center, and specialists in other disciplines with experience in the care of CF and lung transplant recipients. These consensus statements will help lung transplant providers care for CFLTRs in order to improve post-transplant outcomes in this population.
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3.
Impact of a Mobile Health Intervention on Long-term Nonadherence After Lung Transplantation: Follow-up After a Randomized Controlled Trial.
Geramita, EM, DeVito Dabbs, AJ, DiMartini, AF, Pilewski, JM, Switzer, GE, Posluszny, DM, Myaskovsky, L, Dew, MA
Transplantation. 2020;(3):640-651
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Abstract
BACKGROUND In a randomized controlled trial, lung transplant recipients (LTRs) using a mobile health intervention, Pocket Personal Assistant for Tracking Health (Pocket PATH), showed better adherence to the medical regimen than LTRs receiving usual care during the first year posttransplant. We examined whether these effects were maintained beyond the end of the trial and evaluated other potential risk factors for long-term nonadherence. METHODS Adherence in 8 areas was evaluated at follow-up in separate LTR and family caregiver (collateral) assessments. Pocket PATH and usual care groups' nonadherence rates were compared; multivariable regression analyses then examined and controlled for other patient characteristics' associations with nonadherence. RESULTS One hundred five LTRs (75% of survivors) were assessed (M = 3.9 years posttransplant, SD = 0.8). Nonadherence rates in the past month were 23%-81% for self-care and lifestyle requirements (diet, exercise, blood pressure monitoring, spirometry), 13%-23% for immunosuppressants and other medications, and 4% for tobacco use, with 31% clinic appointment nonadherence in the past year. In multivariable analysis, the Pocket PATH group showed lower risk of nonadherence to lifestyle requirements (diet/exercise) than the usual care group (P < 0.05). Younger age and factors during the first year posttransplant (acute graft rejection, chronically elevated anxiety, less time rehospitalized, nonadherence at the final randomized controlled trial assessment) were each associated with nonadherence in at least 1 area at follow-up (P < 0.05). CONCLUSIONS Pocket PATH did not have sustained impact on most areas of the regimen, although we identified other risk factors for long-term nonadherence. Future work should explore strategies to facilitate sustained effects of mobile health interventions.
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4.
Montelukast in chronic lung allograft dysfunction after lung transplantation.
Vos, R, Eynde, RV, Ruttens, D, Verleden, SE, Vanaudenaerde, BM, Dupont, LJ, Yserbyt, J, Verbeken, EK, Neyrinck, AP, Van Raemdonck, DE, et al
The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation. 2019;(5):516-527
Abstract
BACKGROUND Chronic lung allograft dysfunction (CLAD) is a major cause of post‒lung transplant mortality, with limited medical treatment options. In this study we assessed the association of montelukast treatment with pulmonary function and outcome in lung transplant recipients with progressive CLAD. METHODS We performed a retrospective study of all lung transplant recipients transplanted between July 1991 and December 2016 at our center and who were treated for at least 3 months with montelukast for progressive CLAD, despite at least 3 months of prior azithromycin therapy. Main outcome parameters included evolution of pulmonary function and progression-free and overall survival. RESULTS A total of 153 patients with CLAD (115 with bronchiolitis obliterans syndrome and 38 with restrictive allograft syndrome) were included, of whom 46% had a forced expiratory volume in 1 second (FEV1) measure of between 66% and 80%, 31% an FEV1 between 51% and 65%, and 23% an FEV1 ≤50% of best post-operative FEV1 at start of montelukast. Montelukast was associated with attenuation in rate of FEV1 decline after 3 and 6 months, respectively (both p < 0.0001). Patients in whom FEV1 improved or stabilized after 3 months of montelukast (81%) had significantly better progression-free (p < 0.0001) and overall (p = 0.0002) survival after CLAD onset, as compared to those with further decline of FEV1 (hazard ratio [HR] 2.816, 95% confidence interval [CI] 1.450 to 5.467, p = 0.0022 for overall survival after CLAD onset in risk-adjusted multivariate analysis). CONCLUSIONS Montelukast was associated with a significant attenuation in rate of FEV1 decline in a substantial proportion of patients with established CLAD, which correlated with better outcome. Further study is required regarding use of montelkast.
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Pulmonary hypertension is not a risk factor for grade 3 primary graft dysfunction after lung transplantation.
Cottini, SR, Brandi, G, Pagnamenta, A, Weder, W, Schuepbach, RA, Béchir, M, Huber, LC, Benden, C
Clinical transplantation. 2018;(5):e13251
Abstract
Grade 3 primary graft dysfunction (PGD3) represents the most important risk factor for patient mortality during the first year after lung transplantation (LTX). We investigated whether pretransplant pulmonary hypertension (PH) is a risk factor for the development of PGD3. This retrospective, single-center cohort study included 96 candidates undergoing right heart catheterization (RHC) prior to being listed for LTX between March 2000 and October 2015. Based on their mean pulmonary artery pressure (mPAP) levels, the patients were classified into 3 groups: (1) <25 mm Hg, (2) 25-34 mm Hg and (3) ≥35 mm Hg. Forty-seven patients were classified in group 1, 31 in group 2, and 18 in group 3. Fifteen recipients (16%, 95%-CI 8-23) developed PGD3. In the univariate analysis, the diagnosis of interstitial lung disease (ILD) compared to COPD (OR: 7.06, P = .005), blood transfusion >1000 mL during surgery (OR: 5.25, P = .005), the need for intra-operative cardio-pulmonary bypass (CPB) or extra-corporeal membrane oxygenation (ECMO) (OR: 4, P = .027), mPAP (OR 1.06, P = .007) and serum high density lipoprotein-cholesterol (HDL-C) (OR 0.09, P = .005) were associated with PGD3. In the multivariable logistic regression analysis, only HDL-C (OR 0.10, P = .016) was associated with PGD3 based on our single-center cohort data analysis.
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The timing and extent of acute physiotherapy involvement following lung transplantation: An observational study.
Tarrant, BJ, Holland, A, Le Maitre, C, Robinson, R, Corbett, M, Bondarenko, J, Button, B, Thompson, B, Snell, G
Physiotherapy research international : the journal for researchers and clinicians in physical therapy. 2018;(3):e1710
Abstract
BACKGROUND AND PURPOSE Physiotherapy "standard care" for the acute post lung transplant recipient has not yet been documented. We aimed to analyse how soon patients commence exercise and how much time is dedicated to this during physiotherapy sessions acutely post lung transplantation. METHODS Prospective observational study of bilateral sequential and single lung transplant recipients for any indication, ≥18 years. Participants were observed during 6 physiotherapy sessions: 3 initial and 3 prior to acute inpatient discharge. Duration and content of each session was recorded, consisting of physical exercise and non-exercise tasks. RESULTS Thirty participants, 20 male, median age 58.5 (interquartile range 54.5-65.0) were observed over 173 sessions. Chronic obstructive pulmonary disease was the most common transplant indication (n = 12, 40%). Bilateral lung transplant was performed in 90% (n = 27) of participants. First time to mobilise was 2 (2-3) days. Participants received 14 (12.8-23.8) sessions over 18 (17-31) days. The mean duration of physiotherapy in the initial phase was 107.8 (standard deviation 21.8) min, with 22.9 (7.5) min spent exercising. In the final phase, exercise time increased to 28.1 (11.4) min out of 84.1 (24.6) min. Assessment was the most common non-exercise component, at 26.6 (7.9) and 22.1 (12.5) min across the three initial and final sessions. IMPLICATIONS FOR PHYSIOTHERAPY PRACTICE Lung transplant recipients spent 21-34% of observed sessions performing physical exercise beginning 48 hr following surgery. Remaining physiotherapist time was spent on assessment, respiratory interventions, education, and patient-specific duties. The use of physiotherapy assistants, structured, progressive exercise programs, and continued workplace innovation may enable a higher percentage of physiotherapist supervised physical exercise in the future.
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High-dose vitamin D after lung transplantation: A randomized trial.
Vos, R, Ruttens, D, Verleden, SE, Vandermeulen, E, Bellon, H, Van Herck, A, Sacreas, A, Heigl, T, Schaevers, V, Van Raemdonck, DE, et al
The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation. 2017;(8):897-905
Abstract
BACKGROUND Vitamin D may have innate immunomodulatory functions with potentially beneficial therapeutic effects in lung transplant recipients. METHODS This was a single-center, double blind, randomized, placebo-controlled, prevention trial of once-monthly oral vitamin D (cholecalciferol; 100,000 IU, n = 44) vs placebo (n = 43) during 2 years in adult lung transplant recipients enrolled from October 2010 to August 2013. Primary outcome was prevalence of chronic lung allograft dysfunction (CLAD) 3 years after transplantation. Secondary outcomes included overall survival, prevalence of acute rejection, lymphocytic bronchiolitis and infection, lung function, pulmonary and systemic inflammation, and bone mineral density. RESULTS All included patients underwent bilateral lung transplantation and were mostly middle-aged men with prior smoking-related emphysema. Levels of 25-hydroxy vitamin D after 1 year (p < .001) and 2 years (p < .001) were significantly higher in the vitamin D group compared with the placebo group. No difference was observed for CLAD prevalence (p = 0.7) or CLAD-free survival between both groups (p = 0.7). Secondary outcomes were overall comparable between both groups (all p > 0.05). CONCLUSIONS Once-monthly oral vitamin D supplementation after lung transplantation fails to demonstrate a significant difference in CLAD prevalence, innate immunomodulatory, or a beneficial clinical effect compared with placebo.
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First case of atypical takotsubo cardiomyopathy in a bilateral lung-transplanted patient due to acute respiratory failure.
Ghadri, JR, Bataisou, RD, Diekmann, J, Lüscher, TF, Templin, C
European heart journal. Acute cardiovascular care. 2015;(5):482-5
Abstract
Takotsubo cardiomyopathy which is characterised by a transient left ventricular wall motion abnormality was first described in 1990. The disease is still not well known, and as such it is suggested that an emotional trigger is mandatory in this disease. We present the case of a 51-year old female patient seven years after bilateral lung transplantation, who developed acute respiratory distress syndrome and subsequently suffered from atypical takotsubo cardiomyopathy with transient severe reduction of ejection fraction and haemodynamic instability needing acute intensive care treatment. Acute respiratory failure has emerged as an important physical trigger factor in takotsubo cardiomyopathy. Little is known about the association of hypoxia and takotsubo cardiomyopathy which can elicit a life-threatening condition requiring acute intensive care. Therefore, experimental studies are needed to investigate the role of hypoxia in takotsubo cardiomyopathy.
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Three-year results of an investigator-driven multicenter, international, randomized open-label de novo trial to prevent BOS after lung transplantation.
Glanville, AR, Aboyoun, C, Klepetko, W, Reichenspurner, H, Treede, H, Verschuuren, EA, Boehler, A, Benden, C, Hopkins, P, Corris, PA, et al
The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation. 2015;(1):16-25
Abstract
BACKGROUND Chronic lung allograft dysfunction (CLAD), predominantly manifest as bronchiolitis obliterans syndrome (BOS), is the primary cause of morbidity and death after lung transplantation. We assessed the efficacy and safety of 2 de novo immunosuppression protocols to prevent BOS. METHODS This was a multicenter, prospective, international, randomized (1:1) open-label superiority study of de novo enteric-coated mycophenolate sodium (MPS) vs delayed-onset everolimus (RAD), both arms in combination with cyclosporine (CsA) monitored by 2-hour post-dose (C2) levels, and corticosteroids. Target C2 levels were lower in the RAD group because RAD is known to potentiate CsA nephrotoxicity. Cytolytic induction therapy was not used. Patients were stratified at entry for cystic fibrosis. Confirmation of anastomotic healing was required for randomization. Primary efficacy was freedom from BOS Grade 1 on intention-to-treat (ITT) analysis. Secondary efficacy parameters were patient and graft survival and severity of rejection. Treatment failure was defined by graft loss, patient death, drug cessation, or need for other therapy. RESULTS The 3-year freedom from BOS Grade 1 was 70% for MPS (n = 80) vs 71% for RAD (n = 84; p = 0.95 by log-rank) in ITT but was lower in the RAD arm of the per-protocol population (p = 0.03). The 3-year survival was 84% (MPS) vs 76% (RAD; p = 0.19 by log-rank). Thirteen patients switched from MPS vs 31 from RAD (p < 0.01). Days on MPS were greater than days on RAD (p < 0.01). Rejection events proven by biopsy specimen were more common on MPS (p = 0.02), as were leucopenia (p < 0.01), diarrhea (p < 0.01), and cytomegalovirus infection (p = 0.04). Venous thromboembolism was more frequent on RAD (p = 0.02). Creatinine at 3 years was 160 ± 112 μmol/1iter in MPS patients vs 152 ± 98 μmol/1iter in RAD patients (p = 0.67). CONCLUSIONS This 3-year ITT analysis found no significant difference between arms but was underpowered to accept the null hypothesis that RAD and MPS have equivalent efficacy in preventing BOS or death after lung transplantation.
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10.
Rehabilitation in Patients before and after Lung Transplantation.
Langer, D
Respiration; international review of thoracic diseases. 2015;(5):353-62
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Abstract
Lung transplantation is an established treatment for patients with end-stage lung disease. It has been observed that despite near-normal lung function, exercise intolerance and reductions in quality of life (QOL) often persist up to years after transplantation. Several modifiable pre- and posttransplant factors are known to contribute to these persisting impairments. Physiological changes associated with severe and chronic lung disease, limb muscle dysfunction, inactivity/deconditioning, and nutritional depletion can affect exercise capacity and physical functioning in candidates for lung transplantation. After transplantation, extended hospital and intensive care unit stay, prolonged sedentary time, persisting inactivity, immunosuppressant medications and episodes of organ rejection may all impact lung recipients' recovery. Available evidence will be reviewed and content will be proposed (both evidence and experience based) for rehabilitation interventions prior to transplantation, during hospitalization after transplantation, and in both the immediate (≤12 months after hospital discharge) and long-term (>12 months after hospital discharge) posttransplant phase. Outpatient rehabilitation programs including supervised exercise training have been shown to be effective in improving limb muscle dysfunction, exercise capacity, and QOL both before and after transplantation if offered appropriately. Unmet research needs included the absence of sufficiently powered randomized controlled trials measuring the effects of rehabilitation interventions on crucial long-term outcomes such as sustained improvements in QOL, participation in daily activity, survival, incidence of morbidities and cost-effectiveness. Remotely monitored (telehealth) home-based exercise or pedometer-based walking interventions might be interesting alternatives to supervised outpatient rehabilitation interventions in the long-term posttransplant phase and warrant further investigation.