Predictive value of chart-based frailty evaluation for lung transplant candidates.

Frailty, defined as a state of decreased physiologic reserve, has been correlated with poorer outcomes after hospitalization or surgery. Studies in lung transplant patients have associated frailty with an increased risk of post-transplant mortality; however, a unified approach is lacking. The identification of frail patients can help clinicians pre-emptively target modifiable risk factors and may facilitate risk stratification. The Frailty Risk Score (FRS) is a chart review-based approach based on eight symptoms and four laboratory biomarkers. We applied this method in a retrospective study to investigate its utility in predicting post-transplant lung outcomes. Eighty-four lung transplant recipients were evaluated, including 51 older (≥ 60) and 33 younger (< 60) patients. Median FRS score was 3.9, with 63 categorized as frail (75%) and 21 as non-frail (25%), using a previously published cut-off of ≥3 to define frailty. A high FRS was associated with readmission in the first year after transplantation and with the number of readmissions. There was also an association between FRS score and death (p = .047). FRS may be a viable tool in the assessment of lung transplant candidates. Frail patients may benefit from earlier referral and targeted therapy prior to transplant, as well as close post-transplant follow-up.

Changes in right heart haemodynamics and echocardiographic function in an advanced phenotype of pulmonary hypertension and right heart dysfunction associated with pulmonary fibrosis.

BACKGROUND: Pulmonary hypertension (PH)-targeted therapy in the setting of pulmonary fibrosis (PF) is controversial; the main clinical concern is worsening of systemic hypoxaemia. We sought to determine the effects of gentle initiation and chronic administration of parenteral treprostinil on right heart function in patients with PF associated with an advanced PH phenotype. METHODS: Open-label, prospective analysis of patients with PF-PH referred for lung transplantation (LT). Advanced PH was defined as mean pulmonary artery pressure (mPAP) ≥35 mm Hg. We compared haemodynamics, Doppler echocardiography (DE), oxygenation, dyspnoea and quality of life indices, and 6 min walk distance (6MWD) before and 12 weeks after parenteral treprostinil. RESULTS: 15 patients were recruited in the study. After therapy, there were significant improvements in right heart haemodynamics (right atrial pressure (9.5 ± 3.4 vs 6.0 ± 3.7); mPAP (47 ± 8 vs 38.9 ± 13.4); CI (2.3 ± 0.5 vs 2.7 ± 0.6); pulmonary vascular resistance (698 ± 278 vs 496 ± 229); transpulmonary gradient (34.7 ± 8.7 vs 28.5 ± 10.3); mvO2 (65 ± 7.2 vs 70.9 ± 7.4); and stroke volume index (29.2 ± 6.7 vs 33 ± 7.3)) and DE parameters reflecting right heart function (right ventricular (RV) end diastolic area (36.4 ± 5.2 vs 30.9 ± 8.2 cm(2)), left ventricular eccentricity index (1.7 ± 0.6 vs 1.3 ± 0.5), tricuspid annular planar systolic excursion (1.6 ± 0.5 vs 1.9 ± 0.2 cm)). These changes occurred without significant alteration in systemic oxygenation, heart rate, or mean systemic arterial pressure. In addition, improvements were seen in 6MWD (171 ± 93 vs 230 ± 114), 36-Item Short Form Health Survey Mental Component Summary aggregate (38 ± 11 vs 44.2 ± 10.7), University of California, San Diego Shortness of Breath Questionnaire (87 ± 17.1 vs 73.1 ± 21), and brain natriuretic peptide (558 ± 859 vs 228 ± 340). CONCLUSIONS: PH-targeted therapy may improve right heart haemodynamics and echocardiographic function without affecting systemic oxygen saturation in an advanced PH phenotype associated with RV dysfunction in the setting of PF.

Update on pathology of antibody-mediated rejection in the lung allograft.

PURPOSE OF REVIEW: The determination of antibody-mediated rejection (AMR) in the pulmonary allograft remains a diagnostic challenge. Herein, we review the pathologic findings from recent studies, including the International Society of Heart and Lung Transplantation (ISHLT) summary statement on pulmonary AMR and preliminary data from the Banff allograft pathology study on AMR in lung transplant patients. RECENT FINDINGS: Some pathologic findings, including acute lung injury and neutrophilic capillary infiltration, are likely to be associated with pulmonary AMR but do not appear to be specific pathologic markers. The ISHLT statement on pulmonary AMR lists numerous pathologic findings that may be associated with donor-specific antibodies (DSAs). Other recent studies, including the Banff study on pulmonary AMR, have found correlations between clinical AMR, defined in part by the presence of DSAs, and nonspecific acute lung injury and capillary neutrophils with or without C4d deposition. SUMMARY: At this time, the diagnosis of lung transplant AMR requires multidisciplinary coordination and is ultimately determined by the managing clinician. In the full clinical context, including knowledge of serologic data for the presence or absence of DSAs, pathologic interpretation may provide valuable information that can guide therapy and support the clinical diagnosis.

Lung Transplant Outcomes in Systemic Sclerosis with Significant Esophageal Dysfunction. A Comprehensive Single-Center Experience.

RATIONALE: Consideration of lung transplantation in patients with systemic sclerosis (SSc) remains guarded, often due to the concern for esophageal dysfunction and the associated potential for allograft injury and suboptimal post-lung transplantation outcomes. OBJECTIVES: The purpose of this study was to systematically report our single-center experience regarding lung transplantation in the setting of SSc, with a particular focus on esophageal dysfunction. METHODS: We retrospectively reviewed all lung transplants at our center from January 1, 2000 through August 31, 2012 (n = 562), comparing the SSc group (n = 35) to the following lung transplant diagnostic subsets: all non-SSc (n = 527), non-SSc diffuse fibrotic lung disease (n = 264), and a non-SSc matched group (n = 109). We evaluated post-lung transplant outcomes, including survival, primary graft dysfunction, acute rejection, bronchiolitis obliterans syndrome, and microbiology of respiratory isolates. In addition, we defined severe esophageal dysfunction using esophageal manometry and esophageal morphometry criteria on the basis of chest computed tomography images. For patients with SSc referred for lung transplant but subsequently denied (n = 36), we queried the reason(s) for denial with respect to the concern for esophageal dysfunction. MEASUREMENTS AND MAIN RESULTS: The 1-, 3-, and 5-year post-lung transplant survival for SSc was 94, 77, and 70%, respectively, and similar to the other groups. The remaining post-lung transplant outcomes evaluated were also similar between SSc and the other groups. Approximately 60% of the SSc group had severe esophageal dysfunction. Pre-lung transplant chest computed tomography imaging demonstrated significantly abnormal esophageal morphometry for SSc when compared with the matched group. Importantly, esophageal dysfunction was the sole reason for lung transplant denial in a single case. CONCLUSIONS: Relative to other lung transplant indications, our SSc group experienced comparable survival, primary graft dysfunction, acute rejection, bronchiolitis obliterans syndrome, and microbiology of respiratory isolates, despite the high prevalence of severe esophageal dysfunction. Esophageal dysfunction rarely precluded active listing for lung transplantation.

Pathologic findings in lung allografts with anti-HLA antibodies.

BACKGROUND: Despite data indicating a positive correlation between donor-specific anti-HLA antibodies (DSAs) and early development of bronchiolitis obliterans syndrome (BOS) in lung allografts, the role of an antibody-mediated process in acute and chronic lung allograft rejection has not been elucidated. In this study we evaluated pathologic features of transplant lung biopsies in patients with and without DSAs. METHODS: Forty-one lung transplant biopsies from 41 patients at our institution were included in our study. The biopsy H&E slides were reviewed in a blinded fashion, and scored for presence of microvascular inflammation, acute rejection, bronchiolar inflammation and acute lung injury, as well as diffuse alveolar damage (DAD). Microvascular inflammation was graded by the presence of capillary neutrophils on a scale of 0 to 4(+). For immunohistochemical analysis, the pattern and intensity of staining for C4d and C3d deposition were evaluated in airways and alveolar capillaries. RESULTS: Histopathology suspicious for antibody-mediated rejection (AMR)-defined as≥2(+) neutrophilic infiltration and/or DAD-were more common in DSA-positive cases than controls (11 of 16 vs 6 of 25, p<0.01). Evidence of allograft dysfunction was significantly more common among patients with both DSA and suspicious histopathology compared with controls (5 of 10 vs 3 of 25, p = 0.03). The combination of DSAs and histopathology suspicious for AMR was associated with both BOS (p = 0.002) and mortality (p = 0.03). Immunohistochemistry for C3d and C4d showed no correlation with each other, DSAs or histopathology. CONCLUSIONS: Grade 2(+) neutrophilic infiltration is the histopathologic finding most closely related to DSAs with graft dysfunction and development of BOS in lung transplant recipients and may be a marker for AMR.

Treprostinil to reverse pulmonary hypertension associated with idiopathic pulmonary fibrosis as a bridge to single-lung transplantation.

The available therapies and prognosis of idiopathic pulmonary fibrosis remain relatively poor, and concurrent pulmonary hypertension further increases the risk of death and complications after lung transplantation. Limited data exist for the treatment of pulmonary hypertension associated with idiopathic pulmonary fibrosis. We describe a case where intravenous treprostinil was used to bridge an elderly patient with idiopathic pulmonary fibrosis with severe pulmonary hypertension to successful single-lung transplantation.