Restrictive allograft syndrome post lung transplantation is characterized by pleuroparenchymal fibroelastosis (original) (raw)
We previously described restrictive allograft syndrome as a form of chronic lung allograft dysfunction, demonstrating restrictive pulmonary function decline. However, the histopathological correlates of restrictive allograft syndrome have yet to be satisfactorily described. We hypothesized that pulmonary pleuroparenchymal fibroelastosis, as has recently been described in bone marrow transplant recipients, may also be present in the lungs of patients with restrictive allograft syndrome. Retrospective review of 493 patients who underwent lung transplantation between 1 January 1996 and 30 June 2009, was conducted. Out of 47 patients with clinical features of restrictive allograft syndrome, 16 had wedge biopsy, re-transplant lung explant, or autopsy lung specimens available for review. All lungs showed varying degrees of pleural fibrosis. Fifteen of 16 showed parenchymal fibroelastosis, characterized by hypocellular collagen deposition with preservation and thickening of the underlying alveolar septal elastic network. The fibroelastosis was predominantly subpleural in distribution, with some cases also showing centrilobular and paraseptal distribution. A sharp demarcation was often seen between areas of fibroelastosis and unaffected lung parenchyma, with fibroblastic foci often present at this interface. Concurrent features of obliterative bronchiolitis were present in 14 cases. Another common finding was the presence of diffuse alveolar damage (13 cases), usually in specimens obtained o1 year after clinical onset of restrictive allograft syndrome. The single specimen in which fibroelastosis was not identified was obtained before the clinical onset of chronic lung allograft dysfunction, and showed features of diffuse alveolar damage. In conclusion, pleuroparenchymal fibroelastosis is a major histopathologic correlate of restrictive allograft syndrome, and was often found concurrently with diffuse alveolar damage. Our findings support a temporal sequence of diffuse alveolar damage followed by the development of pleuroparenchymal fibroelastosis in the histopathologic evolution of restrictive allograft syndrome.
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Internal Medicine, 2014
We herein report the case of a 31-year-old woman who presented with bilateral upper lobe volume loss and pleural irregularities with hilar retraction. She had undergone allogeneic bone marrow transplantation (BMT) for the treatment of acute lymphoblastic leukemia nine years earlier. A surgical lung biopsy showed pleural thickening and subpleural alveolar collapse and fibrosis, consistent with a diagnosis of pleuroparenchymal fibroelastosis (PPFE). Antecedent sicca syndrome and the absence of other causes of fibroelastosis suggested that these abnormalities were associated with chronic graft-versus-host disease (cGVHD). PPFE as a late, noninfectious complication is rare; however, the present case suggests a new class of BMT-related pulmonary complications associated with cGVHD.
Restrictive allograft syndrome (RAS): A novel form of chronic lung allograft dysfunction
The Journal of Heart and Lung Transplantation, 2011
BACKGROUND: Bronchiolitis obliterans syndrome (BOS) with small-airway pathology and obstructive pulmonary physiology may not be the only form of chronic lung allograft dysfunction (CLAD) after lung transplantation. Characteristics of a form of CLAD consisting of restrictive functional changes involving peripheral lung pathology were investigated. METHODS: Patients who received bilateral lung transplantation from 1996 to 2009 were retrospectively analyzed. Baseline pulmonary function was taken as the time of peak forced expiratory volume in 1 second (FEV 1). CLAD was defined as irreversible decline in FEV 1 Ͻ 80% baseline. The most accurate threshold to predict irreversible decline in total lung capacity and thus restrictive functional change was at 90% baseline. Restrictive allograft syndrome (RAS) was defined as CLAD meeting this threshold. BOS was defined as CLAD without RAS. To estimate the effect on survival, Cox proportional hazards models and Kaplan-Meier analyses were used. RESULTS: Among 468 patients, CLAD developed in 156; of those, 47 (30%) showed the RAS phenotype. Compared with the 109 BOS patients, RAS patients showed significant computed tomography findings of interstitial lung disease (p Ͻ 0.0001). Prevalence of RAS was approximately 25% to 35% of all CLAD over time. Patient survival of RAS was significantly worse than BOS after CLAD onset (median survival, 541 vs 1,421 days; p ϭ 0.0003). The RAS phenotype was the most significant risk factor of death among other variables after CLAD onset (hazard ratio, 1.60; confidential interval, 1.23-2.07). CONCLUSIONS: RAS is a novel form of CLAD that exhibits characteristics of peripheral lung fibrosis and significantly affects survival of lung transplant patients.
BJR|case reports, 2019
Pleuroparenchymal fibroelastosis (PPFE) is a very rare lung disease characterized by dense fibrous thickening of the visceral pleura and intra alveolar fibrosis containing prominent elastosis, with typical upper lobe predominance. PPFE usually shows progressive restrictive ventilatory impairment refractory to medical treatment; bilateral lung transplantation currently remains the only available therapeutic option. In this report we describe a case of suspected PPFE relapse after lung transplantation that, to our knowledge, has never been described in the medical literature. A 48-year-old male with Idiopathic Pleuroparenchymal Fibroelastosis (iPPFE) underwent a bilateral lung transplant in our Department. Eight months later, he presented with progressively worsening clinical condition, his respiratory state gradually deteriorated. HRCT again showed bilateral diffused parenchymal consolidations, with prevalence in the upper lobes and subpleural regions. A PPFE relapse was therefore su...
Clinical Transplantation
Rationale: Patients can change chronic lung allograft dysfunction (CLAD) phenotype, especially from BOS to mixed phenotype. Our aim was to further characterize these patients. Method: Mixed CLAD was defined as a restrictive physiology with persistent CT opacities, after initial bronchiolitis obliterans syndrome (BOS) diagnosis. The incidence, prognosis, pulmonary function, radiology, pathology and airway inflammation were compared between patients with restrictive allograft syndrome (RAS) and mixed CLAD. Result: 268 (44%) patients developed CLAD of which 47 (18%) were diagnosed with RAS 'ab initio', 215 (80%) with BOS and 6 (2%) an undefined phenotype. Twenty-five patients developed a mixed CLAD phenotype (24 BOS to mixed and 1 RAS to mixed). Survival after mixed phenotype diagnosis, was comparable (p=0.39) to RAS. More emphysema patients developed a mixed phenotype (p=0.020) compared to RAS ab initio, while mixed CLAD patients had a lower FEV 1 (p<0.0001) and FEV 1 /FVC (p=0.0002) at diagnosis compared to RAS ab initio. CT scans in patients with the mixed phenotype demonstrated apical predominance of the opacities (p=0.0034) with pleuro-parenchymal fibro-elastosis on histopathology. Conclusion: We further characterized patients with a mixed phenotype of CLAD. Although the survival after diagnosis was comparable to RAS ab initio patients, there was a difference in demography, pulmonary function, radiology and pathology.
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