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Prognostic significance of early pulmonary function changes after onset of chronic lung allograft dysfunction.

ABSTRACT: BACKGROUND:Chronic lung allograft dysfunction (CLAD), including the phenotypes of bronchiolitis obliterans syndrome (BOS) and restrictive CLAD (R-CLAD), represents the leading cause of late death after lung transplantation. Little is known, however, regarding the natural history or prognostic significance of pulmonary function changes after the onset of these conditions. We examined changes in forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) over the first 18 months after CLAD. We also sought to determine whether lung function changes occurring early after CLAD impact longer term outcomes. METHODS:We performed a retrospective analysis of 216 bilateral lung recipients with CLAD, which included those with R-CLAD (n?=?65) or BOS (n?=?151). The course of FEV1 and FVC after CLAD was described. Cox proportional hazards models were used to evaluate the impact of a ?10% decline in FEV1 or FVC within the first 6 months of CLAD on graft loss after that time. RESULTS:Lung recipients with CLAD, whether BOS or R-CLAD, had the largest decreases in FEV1 and FVC within the first 6 months after onset. Moreover, a decline in FEV1 or FVC of ?10% within the first 6 months after CLAD was associated with a significantly increased hazard for graft loss after that time (hazard ratio [HR]?=?3.17, 95% confidence interval [CI] 1.56 to 6.42, p?=?0.001, and HR?=?2.80, 95% CI 1.66 to 4.70, p ? 0.001, respectively), an effect observed in both BOS and R-CLAD patients. CONCLUSIONS:Early physiologic changes after CLAD were independently associated with graft loss. This suggests lung function changes after CLAD, specifically a ?10% decline in FEV1 or FVC, could be a surrogate measure of graft survival.

SUBMITTER: Todd JL

PROVIDER: S-EPMC6371807 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Prognostic significance of early pulmonary function changes after onset of chronic lung allograft dysfunction.

Todd Jamie L JL Neely Megan L ML Finlen Copeland C A CA Frankel Courtney W CW Reynolds John M JM Palmer Scott M SM

The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation 20181031 2

<h4>Background</h4>Chronic lung allograft dysfunction (CLAD), including the phenotypes of bronchiolitis obliterans syndrome (BOS) and restrictive CLAD (R-CLAD), represents the leading cause of late death after lung transplantation. Little is known, however, regarding the natural history or prognostic significance of pulmonary function changes after the onset of these conditions. We examined changes in forced expiratory volume in 1 second (FEV<sub>1</sub>) and forced vital capacity (FVC) over the ...[more]

PMID: 30466803

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Project description:RationaleSince the pathogenesis of chronic lung allograft dysfunction (CLAD) remains poorly defined with no known effective therapies, the identification and study of key events which increase CLAD risk is a critical step towards improving outcomes. We hypothesized that bronchoalveolar lavage fluid (BALF) CXCR3 ligand concentrations would be augmented during organizing pneumonia (OP) and that episodes of OP with marked chemokine elevations would be associated with significantly higher CLAD risk.MethodsAll transbronchial biopsies (TBBX) from patients who received lung transplantation between 2000 to 2010 were reviewed. BALF concentrations of the CXCR3 ligands (CXCL9, CXCL10 and CXCL11) were compared between episodes of OP and "healthy" biopsies using linear mixed-effects models. The association between CXCR3 ligand concentrations during OP and CLAD risk was evaluated using proportional hazards models with time-dependent covariates.ResultsThere were 1894 bronchoscopies with TBBX evaluated from 441 lung transplant recipients with 169 (9%) episodes of OP and 907 (49%) non-OP histopathologic injuries. 62 (37%) episodes of OP were observed during routine surveillance bronchoscopy. Eight hundred thirty-eight (44%) TBBXs had no histopathology and were classified as "healthy" biopsies. There were marked elevations in BALF CXCR3 ligand concentrations during OP compared with "healthy" biopsies. In multivariable models adjusted for other injury patterns, OP did not significantly increase the risk of CLAD when BAL CXCR3 chemokine concentrations were not taken into account. However, OP with elevated CXCR3 ligands markedly increased CLAD risk in a dose-response manner. An episode of OP with CXCR3 concentrations greater than the 25th, 50th and 75th percentiles had HRs for CLAD of 1.5 (95% CI 1.0-2.3), 1.9 (95% CI 1.2-2.8) and 2.2 (95% CI 1.4-3.4), respectively.ConclusionsThis study identifies OP, a relatively uncommon histopathologic finding after lung transplantation, as a major risk factor for CLAD development when considered in the context of increased allograft expression of interferon-? inducible ELR- CXC chemokines. We further demonstrate for the first time, the prognostic importance of BALF CXCR3 ligand concentrations during OP on subsequent CLAD risk.

Dataset Information

Prognostic significance of early pulmonary function changes after onset of chronic lung allograft dysfunction.

Publications

Prognostic significance of early pulmonary function changes after onset of chronic lung allograft dysfunction.

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