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1.
Article in English | MEDLINE | ID: mdl-38199292

ABSTRACT

OBJECTIVE: Lung transplant for acute respiratory distress syndrome in patients supported with extracorporeal membrane oxygenation was rare before 2020, but was rapidly adopted to rescue patients with COVID-19 with lung failure. This study aims to compare the outcomes of patients who underwent lung transplant for COVID-associated acute respiratory distress syndrome and non-COVID acute respiratory distress syndrome, and to assess the impact of type and duration of extracorporeal membrane oxygenation support on survival. METHODS: Using the United Network for Organ Sharing database, we identified 311 patients with acute respiratory distress syndrome who underwent lung transplant from 2007 to 2022 and performed a retrospective analysis of the patients who required extracorporeal membrane oxygenation preoperatively, stratified by COVID-associated acute respiratory distress syndrome and non-COVID acute respiratory distress syndrome listing diagnoses. The primary outcome was 1-year survival. Secondary outcomes included the effect of type and duration of extracorporeal membrane oxygenation on survival. RESULTS: During the study period, 236 patients with acute respiratory distress syndrome and preoperative extracorporeal membrane oxygenation underwent lung transplant; 181 patients had a listing diagnosis of COVID-associated acute respiratory distress syndrome (77%), and 55 patients had a listing diagnosis of non-COVID acute respiratory distress syndrome (23%). Patients with COVID-associated acute respiratory distress syndrome were older, were more likely to be female, had higher body mass index, and spent longer on the waitlist (all P < .02) than patients with non-COVID acute respiratory distress syndrome. The 2 groups had similar 1-year survival (85.8% vs 81.1%, P = .2) with no differences in postoperative complications. Patients with COVID-associated acute respiratory distress syndrome required longer times on extracorporeal membrane oxygenation pretransplant (P = .02), but duration of extracorporeal membrane oxygenation support was not a predictor of 1-year survival (P = .2). CONCLUSIONS: Despite prolonged periods of pretransplant extracorporeal membrane oxygenation support, selected patients with acute respiratory distress syndrome can undergo lung transplant safely with acceptable short-term outcomes. Appropriate selection criteria and long-term implications require further analysis.

2.
J Heart Lung Transplant ; 43(4): 633-641, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38065239

ABSTRACT

BACKGROUND: Primary graft dysfunction (PGD) is the leading cause of early morbidity and mortality after lung transplantation. Accurate prediction of PGD risk could inform donor approaches and perioperative care planning. We sought to develop a clinically useful, generalizable PGD prediction model to aid in transplant decision-making. METHODS: We derived a predictive model in a prospective cohort study of subjects from 2012 to 2018, followed by a single-center external validation. We used regularized (lasso) logistic regression to evaluate the predictive ability of clinically available PGD predictors and developed a user interface for clinical application. Using decision curve analysis, we quantified the net benefit of the model across a range of PGD risk thresholds and assessed model calibration and discrimination. RESULTS: The PGD predictive model included distance from donor hospital to recipient transplant center, recipient age, predicted total lung capacity, lung allocation score (LAS), body mass index, pulmonary artery mean pressure, sex, and indication for transplant; donor age, sex, mechanism of death, and donor smoking status; and interaction terms for LAS and donor distance. The interface allows for real-time assessment of PGD risk for any donor/recipient combination. The model offers decision-making net benefit in the PGD risk range of 10% to 75% in the derivation centers and 2% to 10% in the validation cohort, a range incorporating the incidence in that cohort. CONCLUSION: We developed a clinically useful PGD predictive algorithm across a range of PGD risk thresholds to support transplant decision-making, posttransplant care, and enrich samples for PGD treatment trials.


Subject(s)
Lung Transplantation , Primary Graft Dysfunction , Humans , Risk Factors , Risk Assessment , Primary Graft Dysfunction/diagnosis , Primary Graft Dysfunction/epidemiology , Prospective Studies , Retrospective Studies
3.
Am J Respir Crit Care Med ; 209(1): 91-100, 2024 Jan 01.
Article in English | MEDLINE | ID: mdl-37734031

ABSTRACT

Rationale: Primary graft dysfunction (PGD) is the leading cause of early morbidity and mortality after lung transplantation. Prior studies implicated proxy-defined donor smoking as a risk factor for PGD and mortality. Objectives: We aimed to more accurately assess the impact of donor smoke exposure on PGD and mortality using quantitative smoke exposure biomarkers. Methods: We performed a multicenter prospective cohort study of lung transplant recipients enrolled in the Lung Transplant Outcomes Group cohort between 2012 and 2018. PGD was defined as grade 3 at 48 or 72 hours after lung reperfusion. Donor smoking was defined using accepted thresholds of urinary biomarkers of nicotine exposure (cotinine) and tobacco-specific nitrosamine (4-[methylnitrosamino]-1-[3-pyridyl]-1-butanol [NNAL]) in addition to clinical history. The donor smoking-PGD association was assessed using logistic regression, and survival analysis was performed using inverse probability of exposure weighting according to smoking category. Measurements and Main Results: Active donor smoking prevalence varied by definition, with 34-43% based on urinary cotinine, 28% by urinary NNAL, and 37% by clinical documentation. The standardized risk of PGD associated with active donor smoking was higher across all definitions, with an absolute risk increase of 11.5% (95% confidence interval [CI], 3.8% to 19.2%) by urinary cotinine, 5.7% (95% CI, -3.4% to 14.9%) by urinary NNAL, and 6.5% (95% CI, -2.8% to 15.8%) defined clinically. Donor smoking was not associated with differential post-lung transplant survival using any definition. Conclusions: Donor smoking associates with a modest increase in PGD risk but not with increased recipient mortality. Use of lungs from smokers is likely safe and may increase lung donor availability. Clinical trial registered with www.clinicaltrials.gov (NCT00552357).


Subject(s)
Lung Transplantation , Primary Graft Dysfunction , Smoking , Tissue Donors , Humans , Biomarkers , Cotinine , Lung Transplantation/adverse effects , Primary Graft Dysfunction/epidemiology , Prospective Studies , Smoking/adverse effects
4.
J Heart Lung Transplant ; 42(10): 1455-1463, 2023 10.
Article in English | MEDLINE | ID: mdl-37290569

ABSTRACT

BACKGROUND: Lung transplant (LT) centers are increasingly evaluating patients with multiple risk factors for adverse outcomes. The effects of these stacked risks remains unclear. Our aim was to determine the relationship between the number of comorbidities and post-transplant outcomes. METHODS: We performed a retrospective cohort study using the National Inpatient Sample (NIS) and UNOS Starfile (USF). We applied a probabilistic matching algorithm using 7 variables (transplant: month, year, and type; recipient: age, sex, race, payer). We matched recipients in the USF to transplant patients in the NIS between 2016 and 2019. The Elixhauser methodology was used to identify comorbidities present on admission. We determined the associations between mortality, length of stay (LOS), total charges, and disposition with comorbidity numbers using penalized cubic splines, Kaplan-Meier, and linear and logistic regression methods. RESULTS: From 28,484,087 NIS admissions, we identified 1,821 LT recipients. Matches were exact in 76.8% of the cohort. While the remaining cohort had a probability match of ≥0.94. Penalized splines of Elixhauser comorbidity number identified 3 knots defining 3 groups of stacked risk: low (<3), medium (3-6), and high risk (>6). Inpatient mortality increased from low to medium to high-risk categories: (1.6%, 3.9%, and 7.0%; p < 0.001), as did LOS (16, 21, 29 days, p < 0.001), total charges ($553,057, $666,791, $821,641.5; p = 0.004) and discharge to a skilled nursing facility (15%, 20%, 31%; p < 0.001). CONCLUSIONS: Stacked risks adversely affect post-LT mortality, LOS, charges, and discharge disposition. Further study to understand the details of specific stacked risks is warranted.


Subject(s)
Hospitalization , Patient Discharge , Humans , Retrospective Studies , Length of Stay , Risk Factors
6.
Clin Chest Med ; 44(1): 105-119, 2023 03.
Article in English | MEDLINE | ID: mdl-36774158

ABSTRACT

Lung transplantation is often the only treatment option for patients with severe irreversible lung disease. Improvements in donor and recipient selection, organ allocation, surgical techniques, and immunosuppression have all contributed to better survival outcomes after lung transplantation. Nonetheless, lung transplant recipients still experience frequent complications, often necessitating treatment in an intensive care setting. In addition, the use of extracorporeal life support as a means of bridging critically ill patients to lung transplantation has become more widespread. This review focuses on the critical care aspects of lung transplantation, both before and after surgery.


Subject(s)
Lung Diseases , Lung Transplantation , Humans , Transplant Recipients , Lung Transplantation/methods , Lung , Lung Diseases/etiology , Critical Care
7.
J Heart Lung Transplant ; 41(12): 1839-1849, 2022 12.
Article in English | MEDLINE | ID: mdl-36216694

ABSTRACT

BACKGROUND: We sought to describe trends in extracorporeal membrane oxygenation (ECMO) use, and define the impact on PGD incidence and early mortality in lung transplantation. METHODS: Patients were enrolled from August 2011 to June 2018 at 10 transplant centers in the multi-center Lung Transplant Outcomes Group prospective cohort study. PGD was defined as Grade 3 at 48 or 72 hours, based on the 2016 PGD ISHLT guidelines. Logistic regression and survival models were used to contrast between group effects for event (i.e., PGD and Death) and time-to-event (i.e., death, extubation, discharge) outcomes respectively. Both modeling frameworks accommodate the inclusion of potential confounders. RESULTS: A total of 1,528 subjects were enrolled with a 25.7% incidence of PGD. Annual PGD incidence (14.3%-38.2%, p = .0002), median LAS (38.0-47.7 p = .009) and the use of ECMO salvage for PGD (5.7%-20.9%, p = .007) increased over the course of the study. PGD was associated with increased 1 year mortality (OR 1.7 [95% C.I. 1.2, 2.3], p = .0001). Bridging strategies were not associated with increased mortality compared to non-bridged patients (p = .66); however, salvage ECMO for PGD was significantly associated with increased mortality (OR 1.9 [1.3, 2.7], p = .0007). Restricted mean survival time comparison at 1-year demonstrated 84.1 days lost in venoarterial salvaged recipients with PGD when compared to those without PGD (ratio 1.3 [1.1, 1.5]) and 27.2 days for venovenous with PGD (ratio 1.1 [1.0, 1.4]). CONCLUSIONS: PGD incidence continues to rise in modern transplant practice paralleled by significant increases in recipient severity of illness. Bridging strategies have increased but did not affect PGD incidence or mortality. PGD remains highly associated with mortality and is increasingly treated with salvage ECMO.


Subject(s)
Lung Transplantation , Preimplantation Diagnosis , Primary Graft Dysfunction , Female , Pregnancy , Humans , Primary Graft Dysfunction/epidemiology , Incidence , Preimplantation Diagnosis/adverse effects , Prospective Studies , Retrospective Studies , Lung Transplantation/adverse effects
8.
J Heart Lung Transplant ; 41(10): 1511-1519, 2022 10.
Article in English | MEDLINE | ID: mdl-35864004

ABSTRACT

BACKGROUND: While cystic fibrosis transmembrane conductance regulator (CFTR) genotypes are associated with clinical outcomes in cystic fibrosis patients, it is unknown if genotype impacts lung transplant outcomes. We sought to compare lung transplant survival and time to bronchiolitis obliterans syndrome (BOS) between high-risk, low-risk, and not yet classified CFTR genotypes. METHODS: We used merged data from the Organ Procurement and Transplantation Network (2005-2017) and United States Cystic Fibrosis Foundation Patient Registry (2005-2016). Cox Proportional Hazards models compared graft failure after lung transplant and time to BOS among high-risk, low-risk, and not yet classified risk CFTR genotype classes. RESULTS: Among 1,830 cystic fibrosis lung transplant recipients, median survival for those with low-risk, high-risk, and not yet classified genotype was 9.83, 6.25, and 5.75 years, respectively. Adjusted Cox models showed recipients with a low-risk genotype had 39% lower risk of death or re-transplant compared to those with high-risk genotype (adjusted HR 0.61, 95% CI = 0.40, 0.91). A subset of 1,585 lung transplant recipients were included in the BOS subgroup analysis. Adjusted analyses showed no significant difference of developing BOS among high-risk, low-risk, or not yet classified genotypes. CONCLUSIONS: Lung transplant recipients with low-risk CFTR genotype have better survival after transplant compared to recipients with high-risk or not yet classified genotypes. Given these differences, future studies evaluating the mechanism by which CFTR genotype affects post-transplant survival could identify potential targets for intervention.


Subject(s)
Bronchiolitis Obliterans , Cystic Fibrosis , Lung Transplantation , Bronchiolitis Obliterans/genetics , Cystic Fibrosis/genetics , Cystic Fibrosis/surgery , Cystic Fibrosis Transmembrane Conductance Regulator/genetics , Genotype , Humans , Lung Transplantation/adverse effects , Retrospective Studies , United States/epidemiology
10.
Clin Transplant ; 35(11): e14447, 2021 11.
Article in English | MEDLINE | ID: mdl-34365656

ABSTRACT

It is unknown whether some donor specific antibodies (DSA) can be crossed at the time of lung transplant without desensitization or augmented induction immunosuppression. This study assessed whether crossing low-level pre-transplant DSA (defined as mean fluorescence intensity [MFI] 1000-6000) without augmented immunosuppression is associated with worse retransplant-free or chronic lung allograft dysfunction (CLAD)-free survival. Of the 458 included recipients, low-level pre-transplant DSA was crossed in 39 (8.6%) patients. The median follow-up time was 2.2 years. There were 15 (38.5%) patients with Class I DSA and 24 (61.5%) with Class II DSA. There was no difference in adjusted overall retransplant-free survival between recipients where pre-transplant DSA was and was not crossed (HR: .98 [95% CI = .49-1.99], P = .96). There was also no difference in CLAD-free survival (HR: .71 [95% CI = .38-1.33], P = .28). There was no difference in Grade 3 PGD at 72 h (OR: 1.13 [95% CI = .52-2.48], P = .75) or definite or probable AMR (HR: 2.22 [95% CI = .64-7.61], P = .21). Lung transplantation in the presence of low-level DSA without planned augmented immunosuppression is not associated with worse overall or CLAD-free survival among recipients with intermediate-term follow-up.


Subject(s)
Isoantibodies , Lung Transplantation , Graft Rejection/etiology , Graft Survival , HLA Antigens , Histocompatibility Testing , Humans , Immunosuppression Therapy , Retrospective Studies , Tissue Donors
11.
Curr Opin Organ Transplant ; 26(3): 321-327, 2021 06 01.
Article in English | MEDLINE | ID: mdl-33938469

ABSTRACT

PURPOSE OF REVIEW: Primary graft dysfunction (PGD) is a devastating complication in the acute postoperative lung transplant period, associated with high short-term mortality and chronic rejection. We review its definition, pathophysiology, risk factors, prevention, treatment strategies, and future research directions. RECENT FINDINGS: New analyses suggest donation after circulatory death and donation after brain death donors have similar PGD rates, whereas donors >55 years are not associated with increased PGD risk. Recipient pretransplant diastolic dysfunction and overweight or obese recipients with predominant abdominal subcutaneous adipose tissue have increased PGD risk. Newly identified recipient biomarkers and donor and recipient genes increase PGD risk, but their clinical utility remains unclear. Mixed data still exists regarding cold ischemic time and PGD risk, and increased PGD risk with cardiopulmonary bypass remains confounded by transfusions. Portable ex vivo lung perfusion (EVLP) may prevent PGD, but its use is limited to a handful of centers. Although updates to current PGD treatment are lacking, future therapies are promising with targeted therapy and the use of EVLP to pharmacologically recondition donor lungs. SUMMARY: There is significant progress in defining PGD and identifying its several risk factors, but effective prevention and treatment strategies are needed.


Subject(s)
Lung Transplantation , Primary Graft Dysfunction , Extracorporeal Circulation , Humans , Lung , Lung Transplantation/adverse effects , Primary Graft Dysfunction/etiology , Primary Graft Dysfunction/prevention & control , Risk Factors , Tissue Donors
13.
J Thorac Dis ; 13(11): 6618-6627, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34992840

ABSTRACT

Many advances in lung transplant have occurred over the last few decades in the understanding of primary graft dysfunction (PGD) though effective prevention and treatment remain elusive. This review will cover prior understanding of PGD, recent findings, and directions for future research. A consensus statement updating the definition of PGD in 2016 highlights the growing complexity of lung transplant perioperative care taking into account the increasing use of high flow oxygen delivery and pulmonary vasodilators in the current era. PGD, particularly more severe grades, is associated with worse short- and long-term outcomes after transplant such as chronic lung allograft dysfunction. Growing experience have helped identify recipient, donor, and intraoperative risk factors for PGD. Understanding the pathophysiology of PGD has advanced with increasing knowledge of the role of innate immune response, humoral cell immunity, and epithelial cell injury. Supportive care post-transplant with technological advances in extracorporeal membranous oxygenation (ECMO) remain the mainstay of treatment for severe PGD. Future directions include the evolving utility of ex vivo lung perfusion (EVLP) both in PGD research and potential pre-transplant treatment applications. PGD remains an important outcome in lung transplant and the future holds a lot of potential for improvement in understanding its pathophysiology as well as development of preventative therapies and treatment.

14.
J Cyst Fibros ; 20(3): 506-510, 2021 05.
Article in English | MEDLINE | ID: mdl-32736949

ABSTRACT

Individuals with cystic fibrosis (CF) have an increased risk for gallbladder abnormalities and biliary tract disease, but the reported incidence of these manifestations of CF varies widely in the literature. With the approval of elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA), increasing numbers of CF patients have been initiated on highly effective cystic fibrosis transmembrane regulator (CFTR) modulator therapy. While elevations in hepatic panel are known potential side effects of CFTR modulators, there have been no published cases of biliary disease or acute cholecystitis attributed to these medications. In this case series, we describe seven patients at two adult CF centers with biliary colic shortly after initiation with ELX/TEZ/IVA, six of whom required cholecystectomy.


Subject(s)
Biliary Tract Diseases/chemically induced , Biliary Tract Diseases/surgery , Chloride Channel Agonists/adverse effects , Cholecystectomy , Cystic Fibrosis/drug therapy , Adult , Aminophenols/adverse effects , Benzodioxoles/adverse effects , Drug Combinations , Female , Humans , Indoles/adverse effects , Male , Pyrazoles/adverse effects , Pyridines/adverse effects , Pyrrolidines/adverse effects , Quinolones/adverse effects
15.
Ann Transl Med ; 8(6): 415, 2020 Mar.
Article in English | MEDLINE | ID: mdl-32355859

ABSTRACT

Viral infections are associated with significant morbidity and mortality in lung transplant recipients. Importantly, several viral infections have been associated with the development of chronic lung allograft dysfunction (CLAD). Community-acquired respiratory viruses (CARV) such as influenza and respiratory syncytial virus (RSV), are frequently associated with acute and chronic rejection. Cytomegalovirus (CMV) remains a significant burden in regards to morbidity and mortality in lung transplant recipients. Epstein-Barr virus (EBV) is mostly involved with the development of post-transplant lymphoproliferative disorder (PTLD), a lymphoid proliferation that occurs in the setting of immunosuppression. On the other hand, the development of direct acting antivirals for hepatitis C virus (HCV) is changing the use of HCV-positive organs in transplantation. In this article we will focus on reviewing common viral infections that have a significant impact on lung transplant recipients looking at epidemiology, prevention and potential treatment.

16.
Respir Res ; 21(1): 68, 2020 Mar 12.
Article in English | MEDLINE | ID: mdl-32164673

ABSTRACT

Compelling data have linked disease progression in patients with idiopathic pulmonary fibrosis (IPF) with lung dysbiosis and the resulting dysregulated local and systemic immune response. Moreover, prior therapeutic trials have suggested improved outcomes in these patients treated with either sulfamethoxazole/ trimethoprim or doxycycline. These trials have been limited by methodological concerns. This trial addresses the primary hypothesis that long-term treatment with antimicrobial therapy increases the time-to-event endpoint of respiratory hospitalization or all-cause mortality compared to usual care treatment in patients with IPF. We invoke numerous innovative features to achieve this goal, including: 1) utilizing a pragmatic randomized trial design; 2) collecting targeted biological samples to allow future exploration of 'personalized' therapy; and 3) developing a strong partnership between the NHLBI, a broad range of investigators, industry, and philanthropic organizations. The trial will randomize approximately 500 individuals in a 1:1 ratio to either antimicrobial therapy or usual care. The site principal investigator will declare their preferred initial antimicrobial treatment strategy (trimethoprim 160 mg/ sulfamethoxazole 800 mg twice a day plus folic acid 5 mg daily or doxycycline 100 mg once daily if body weight is < 50 kg or 100 mg twice daily if ≥50 kg) for the participant prior to randomization. Participants randomized to antimicrobial therapy will receive a voucher to help cover the additional prescription drug costs. Additionally, those participants will have 4-5 scheduled blood draws over the initial 24 months of therapy for safety monitoring. Blood sampling for DNA sequencing and genome wide transcriptomics will be collected before therapy. Blood sampling for transcriptomics and oral and fecal swabs for determination of the microbiome communities will be collected before and after study completion. As a pragmatic study, participants in both treatment arms will have limited in-person visits with the enrolling clinical center. Visits are limited to assessments of lung function and other clinical parameters at time points prior to randomization and at months 12, 24, and 36. All participants will be followed until the study completion for the assessment of clinical endpoints related to hospitalization and mortality events. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02759120.


Subject(s)
Anti-Infective Agents/therapeutic use , Idiopathic Pulmonary Fibrosis/drug therapy , Multicenter Studies as Topic/methods , Pragmatic Clinical Trials as Topic/methods , Randomized Controlled Trials as Topic/methods , Research Design , Humans , Idiopathic Pulmonary Fibrosis/diagnosis , Treatment Outcome
17.
PLoS One ; 13(10): e0205065, 2018.
Article in English | MEDLINE | ID: mdl-30286195

ABSTRACT

Studies demonstrate that Tropheryma whipplei (T. whipplei) is present in the lungs of healthy individuals without acute respiratory symptoms or acute respiratory infection and is more common in the lungs of HIV-infected individuals and in smokers. The impact of T. whipplei colonization in the lung on local inflammation and pulmonary dysfunction in HIV-infected individuals is currently unknown. In this study, we performed specific polymerase chain reaction (PCR) and sequencing for T. whipplei in bronchoalveolar lavage (BAL) and induced sputum (IS) samples in 76 HIV-infected participants from three clinical sites. Pulmonary function and proinflammatory cytokine and chemokine levels in BAL were measured. Frequency of T. whipplei in either BAL or IS was 43.4%. The sensitivity and specificity of IS compared to BAL for detection of T. whipplei was 92.3% and 84.2%, respectively, and isolates of T. whipplei in the BAL and IS in the same subject shared genetic identity. Pulmonary function measures were not associated with T. whipplei colonization, and proinflammatory cytokine and chemokine levels in BAL and plasma as well as percentages of inflammatory cells in BAL and IS were not higher in colonized individuals. Overall, these results indicate that T. whipplei colonization in the lung is common, but may not be associated with decreased pulmonary function or inflammation in HIV-infected individuals.


Subject(s)
Actinomycetales Infections/complications , HIV Infections/complications , Inflammation/complications , Lung/physiopathology , Tropheryma , Actinomycetales Infections/epidemiology , Actinomycetales Infections/physiopathology , Biomarkers/metabolism , Bronchoalveolar Lavage , Chemokines/metabolism , Coinfection/epidemiology , Coinfection/physiopathology , Cytokines/metabolism , Female , HIV Infections/epidemiology , HIV Infections/physiopathology , Humans , Inflammation/epidemiology , Inflammation/physiopathology , Lung/microbiology , Lung Diseases/complications , Lung Diseases/epidemiology , Lung Diseases/physiopathology , Male , Middle Aged , Respiratory Function Tests , Sputum/microbiology , Tropheryma/genetics
18.
J Heart Lung Transplant ; 37(12): 1443-1447, 2018 12.
Article in English | MEDLINE | ID: mdl-30228085

ABSTRACT

BACKGROUND: Patients with greater adiposity before lung transplantation are at an increased risk for worse post-transplant outcomes. Few studies have addressed whether pre-transplant weight loss mitigates this risk. In this study we examined the association between pre-transplant weight loss and post-transplant clinical outcomes. METHODS: We conducted a retrospective cohort study of patients who received a lung transplant at the Duke University Hospital from May 1, 2005 to April 30, 2015. The sample included adult transplant recipients with restrictive, obstructive, and vascular diseases. Cox proportional hazards models were used to examine mortality and chronic lung allograft dysfunction (CLAD)-free survival, and negative binomial regression analyses were used to examine length of stay (LOS). Weight loss was assessed from change in body mass index (BMI). RESULTS: The cohort consisted of 810 patients. Initially, 403 (50%) were overweight and 109 (13%) were obese by BMI criteria. Greater pre-transplant weight loss was associated with dose-response improvements in survival (hazard ratio [HR] 0.83 [0.72 to 0.97], p = 0.018), with modest (0% to 3%, HR 0.91), moderate (7% to 10%, HR 0.83), and high (>15%, HR 0.71) levels of weight loss conferring longer survival, independent of initial weight (p = 0.533 for interaction). Weight loss was also associated with improved CLAD-free survival (HR 0.84 [0.71 to 0.99], p = 0.034) and shorter LOS (b = ‒0.17, p < 0.001). CONCLUSIONS: Weight loss before transplantation was associated with improved short- and long-term clinical outcomes, independent of initial weight. Survival improved proportionally to percentage of weight lost. The mechanisms by which weight loss improve clinical outcomes warrant further exploration.


Subject(s)
Lung Transplantation , Postoperative Complications/etiology , Primary Graft Dysfunction/etiology , Respiratory Insufficiency/etiology , Weight Loss , Adult , Aged , Body Mass Index , Cohort Studies , Female , Humans , Length of Stay/statistics & numerical data , Male , Middle Aged , Postoperative Complications/mortality , Preoperative Period , Primary Graft Dysfunction/mortality , Proportional Hazards Models , Respiratory Insufficiency/mortality , Retrospective Studies , Survival Analysis
19.
Psychosom Med ; 80(4): 403-409, 2018 05.
Article in English | MEDLINE | ID: mdl-29533326

ABSTRACT

OBJECTIVE: Depressive symptoms are common among lung transplant recipients and have been associated with worse clinical outcomes. However, few studies have examined the association between depressive symptoms assessed at multiple time points or behavioral mechanisms by which posttransplant depressive symptoms may confer greater clinical risk. We therefore examined the associations between depressive symptoms, exercise capacity, chronic lung allograft dysfunction (CLAD), and mortality prospectively in a large sample of lung transplant recipients. METHODS: Between July 2009 and February 2016, 251 lung transplant recipients were assessed before transplantation and again approximately 3 weeks and 3 months after transplant. Depressive symptoms were assessed using the Centers for Epidemiologic Studies of Depression scale. Functional exercise capacity was assessed using the 6-minute walk test. Cox proportional hazards models were used to examine the associations between depressive symptoms, exercise capacity, CLAD, and mortality. RESULTS: During a median (range) follow-up of 4.5 (0.1 to 6.3) years, 53 participants (21%) died. Greater depressive symptoms (hazard ratio [HR] = 1.39 [95% CI = 1.05 to 1.84], p = .021) and poorer exercise capacity (HR = 0.58 [95% CI = 0.38 to 0.90], p = .021) assessed 3 months after transplant were both independently associated with mortality. Although greater depressive symptoms were associated with lower exercise capacity (ß = -0.14, p = .039), exercise capacity did not mediate the association between depressive symptoms and mortality. In secondary analyses, depressive symptoms were independently predictive of CLAD (HR = 1.29 [95% CI = 1.01 to 1.65], p = .045) and the composite outcome of CLAD and mortality in a clustered event model (HR = 1.30 [1.09 to 1.56], p = .005). CONCLUSIONS: Depressive symptoms are associated with mortality and CLAD after lung transplantation, independent of exercise capacity.


Subject(s)
Depression , Lung Diseases , Lung Transplantation , Outcome Assessment, Health Care , Physical Fitness/physiology , Adult , Aged , Allografts , Depression/complications , Depression/epidemiology , Depression/physiopathology , Female , Follow-Up Studies , Humans , Lung Diseases/etiology , Lung Diseases/mortality , Lung Diseases/physiopathology , Lung Diseases/surgery , Lung Transplantation/adverse effects , Lung Transplantation/mortality , Lung Transplantation/psychology , Male , Middle Aged , Outcome Assessment, Health Care/statistics & numerical data
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