Dataset Information

Spirometrically significant acute rejection increases the risk for BOS and death after lung transplantation.

ABSTRACT: Acute rejection (AR) is a common complication following lung transplantation and is an established risk factor for bronchiolitis obliterans syndrome (BOS). AR clinical presentation varies considerably and is sometimes associated with an acute decrease in forced expiratory volume in 1 s (FEV1). We hypothesized that lung transplant recipients who experience such spirometrically significant AR (SSAR), as defined by a ?10% decline in FEV1 relative to the prior pulmonary function test, are subsequently at increased risk for BOS and worse overall survival. In a large single center cohort (n = 339), SSAR occurred in 79 subjects (23%) and significantly increased the risk for BOS (p < 0.0001, HR = 3.2, 95% CI 2.3-4.6) and death (p = 0.0001, HR = 2.3, 95% CI 1.5-3.5). These effects persisted after multivariate adjustment for pre-BOS AR and lymphocytic bronchiolitis burden. An analysis of the subset of patients who experienced severe SSAR (?20% decline in FEV1) resulted in even greater hazards for BOS and death. Thus, we demonstrate a novel physiological measure that allows discrimination of patients at increased risk for worse posttransplant outcomes. Further studies are needed to determine mechanisms of airflow impairment and whether aggressive clinical interventions could improve post-SSAR outcomes.

SUBMITTER: Davis WA

PROVIDER: S-EPMC3753790 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Spirometrically significant acute rejection increases the risk for BOS and death after lung transplantation.

Davis W A WA Finlen Copeland C A CA Todd J L JL Snyder L D LD Martissa J A JA Palmer S M SM

American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons 20111128 3

Acute rejection (AR) is a common complication following lung transplantation and is an established risk factor for bronchiolitis obliterans syndrome (BOS). AR clinical presentation varies considerably and is sometimes associated with an acute decrease in forced expiratory volume in 1 s (FEV1). We hypothesized that lung transplant recipients who experience such spirometrically significant AR (SSAR), as defined by a ≥10% decline in FEV1 relative to the prior pulmonary function test, are subsequent ...[more]

PMID: 22123337

Similar Datasets

Project description:Background & aimsAcute rejection is detrimental to most transplanted solid organs, but is considered to be less of a consequence for transplanted livers. We evaluated risk factors for and outcomes after biopsy-proven acute rejection (BPAR) based on an analysis of a more recent national sample of recipients of liver transplants from living and deceased donors.MethodsWe analyzed data from the Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL) from 2003 through 2014 as the exploratory cohort and the Scientific Registry of Transplant Recipients (SRTR) from 2005 through 2013 as the validation cohort. We examined factors associated with time to first BPAR using multivariable Cox regression or discrete-survival analysis. Competing risks methods were used to compare causes of death and graft failure between recipients of living and deceased donors.ResultsAt least 1 BPAR episode occurred in 239 of 890 recipients in A2ALL (26.9%) and 7066 of 45,423 recipients in SRTR (15.6%). In each database, risk of rejection was significantly lower when livers came from biologically related living donors (A2ALL hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.43-0.76; and SRTR HR, 0.78; 95% CI, 0.66-0.91) and higher in liver transplant recipients with primary biliary cirrhosis, of younger age, or with hepatitis C. In each database, BPAR was associated with significantly higher risks of graft failure and death. The risks were highest in the 12 month post-BPAR period in patients whose first episode occurred more than 1 year after liver transplantation: HRs for graft failure were 6.79 in A2ALL (95% CI, 2.64-17.45) and 4.41 in SRTR (95% CI, 3.71-5.23); HRs for death were 8.81 in A2ALL (95% CI, 3.37-23.04) and 3.94 in SRTR (95% CI, 3.22-4.83). In analyses of cause-specific mortality, associations were observed for liver-related (graft failure) causes of death but not for other causes.ConclusionsContrary to previous data, acute rejection after liver transplant is associated with significantly increased risk of graft failure, all-cause mortality, and graft failure-related death, regardless of primary liver disease etiology. Living donor liver transplantation from a biologically related donor is associated with decreased risk of rejection.

Project description:BackgroundAcute perivascular rejection (AR) is common in lung recipients and increases the risk for chronic lung allograft dysfunction (CLAD). Hyaluronan (HA), an extracellular matrix constituent, accumulates in experimental AR and can act as an innate immune agonist, breaking tolerance and potentiating alloimmunity. We previously demonstrated HA accumulates in CLAD after human-lung transplantation. We sought to determine if HA accumulates in the bronchoalveolar lavage fluid (BALF) concurrent with AR in lung recipients.MethodsThe cohort consisted of 126 first adult lung recipients at 5 transplant centers with a total of 373 BALF samples collected within the first posttransplant year. All samples were paired with a lung biopsy from the same bronchoscopy. BALF HA (ng/mL) was quantified by ELISA and log-transformed for analysis. Linear-mixed effect models, adjusted for potential confounders, were used to estimate the association between BALF HA concentration and the presence of AR on biopsy. The association between early posttransplant BALF HA levels and the development of CLAD was explored utilizing tertiles of maximum BALF HA level observed within the first 6 months of transplant.ResultsIn analyses adjusted for potential confounders, BALF HA concentration was significantly increased in association with AR (change in means on log-scale 0.31; 95% CI, 0.01-0.60; P = 0.044). When considered on the original scale (ng/mL), BALF HA concentrations were 1.36 times (36%) higher, on average, among samples with, versus without, AR. The cumulative incidence of CLAD was numerically higher in individuals in the highest tertiles of BALF HA level within the first 6 months after transplant, as compared with those in the lowest tertile; however, this difference was not statistically significant (P = 0.32).ConclusionsThese results demonstrate accumulation of HA in clinical AR and suggest a mechanism by which innate and adaptive immune activation might interact in the development of AR and CLAD.

Dataset Information

Spirometrically significant acute rejection increases the risk for BOS and death after lung transplantation.

Publications

Spirometrically significant acute rejection increases the risk for BOS and death after lung transplantation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets