Elise Cuquemelle

Diffuse alveolar hemorrhage in immunocompetent patients: Etiologies and prognosis revisited

BACKGROUND Diffuse alveolar hemorrhage (DAH) represents a diagnostic challenge of acute respiratory failure. Prompt identification of the underlying cause of DAH and initiation of appropriate treatment are required in order to prevent acute respiratory failure and irreversible loss of renal function. More than 100 causes of DAH have been reported. However, the relative frequency and the differential presentation of those causes have been poorly documented, as well as their respective prognosis. METHODS We retrospectively reviewed the charts of 112 consecutive patients hospitalized for DAH in a tertiary referral center over a 30-year period. RESULTS Twenty-four causes of DAH were classified into four etiologic groups: immune (n = 39), congestive heart failure (CHF; n = 33), miscellaneous (n = 26), and idiopathic DAH (n = 14). Based on this classification, clinical and laboratory features of DAH differed on hospital admission. Patients with immune DAH had more frequent pulmonary-renal syndrome (p < 0.001), extra-pulmonary symptoms (p < 0.01), and lower blood hemoglobin level than others (p < 0.001). Patients with CHF-related DAH were older and received more anticoagulant treatments than others (p < 0.05). Those with miscellaneous causes of DAH exhibited a shorter prodromal phase (p < 0.001) and had more frequent hemoptysis >200 mL (p < 0.05). Patients with idiopathic DAH had more bronchoalveolar lavage siderophages (p < 0.01). In-hospital mortality was 24.1%, ranging from 7.1% in patients with idiopathic DAH to 36.4% in those with CHF. CONCLUSIONS Arbitrary classification of DAH in four etiologic groups gives the opportunity to underline distinct presentations and outcomes of various causes of DAH.

Antibody-Mediated Rejection in Lung Transplantation: Clinical Outcomes and Donor-Specific Antibody Characteristics

In the context of lung transplant (LT), because of diagnostic difficulties, antibody‐mediated rejection (AMR) remains a matter of debate. We retrospectively analyzed an LT cohort at Foch Hospital to demonstrate the impact of AMR on LT prognosis. AMR diagnosis requires association of clinical symptoms, donor‐specific antibodies (DSAs), and C4d+ staining and/or histological patterns consistent with AMR. Prospective categorization split patients into four groups: (i) DSA positive, AMR positive (DSAposAMRpos); (ii) DSA positive, AMR negative (DSAposAMRneg); (iii) DSA limited, AMR negative (DSALim; equal to one specificity, with mean fluorescence intensity of 500–1000 once); and (iv) DSA negative, AMR negative (DSAneg). AMR treatment consisted of a combination of plasmapheresis, intravenous immunoglobulin and rituximab. Among 206 transplanted patients, 10.7% were DSAposAMRpos (n = 22), 40.3% were DSAposAMRneg (n = 84), 6% were DSALim (n = 13) and 43% were DSAneg (n = 88). Analysis of acute cellular rejection at month 12 showed higher cumulative numbers (mean plus or minus standard deviation) in the DSAposAMRpos group (2.1 ± 1.7) compared with DSAposAMRneg (1 ± 1.2), DSALim (0.75 ± 1), and DSAneg (0.7 ± 1.23) groups. Multivariate analysis demonstrated AMR as a risk factor for chronic lung allograft dysfunction (hazard ratio [HR] 8.7) and graft loss (HR 7.56) for DSAposAMRpos patients. Our results show a negative impact of AMR on LT clinical course and advocate for an early active diagnostic approach and evaluation of therapeutic strategies to improve prognosis.

Bedside Lung Ultrasound During Acute Chest Syndrome in Sickle Cell Disease.

AbstractLung ultrasound (LU) is increasingly used to assess pleural and lung disease in intensive care unit (ICU) and emergency unit at the bedside. We assessed the performance of bedside chest radiograph (CR) and LU during severe acute chest syndrome (ACS), using computed tomography (CT) as the reference standard.We prospectively explored 44 ACS episodes (in 41 patients) admitted to the medical ICU. Three imaging findings were evaluated (consolidation, ground-glass opacities, and pleural effusion). A score was used to quantify and compare loss of lung aeration with each technique and assess its association with outcome.A total number of 496, 507, and 519 lung regions could be assessed by CT scan, bedside CR, and bedside LU, respectively. Consolidations were the most common pattern and prevailed in lung bases (especially postero-inferior regions). The agreement with CT scan patterns was significantly higher for LU as compared to CR (&kgr; coefficients of 0.45 ± 0.03 vs 0.30 ± 0.03, P < 0.01 for the parenchyma, and 0.73 ± 0.08 vs 0.06 ± 0.09, P < 0.001 for pleural effusion). The Bland and Altman analysis showed a nonfixed bias of −1.0 (P = 0.12) between LU score and CT score whereas CR score underestimated CT score with a fixed bias of −5.8 (P < 0.001). The specificity for the detection of consolidated regions or pleural effusion (using CT scan as the reference standard) was high for LU and CR, whereas the sensitivity was high for LU but low for CR. As compared to others, ACS patients with an LU score above the median value of 11 had a larger volume of transfused and exsanguinated blood, greater oxygen requirements, more need for mechanical ventilation, and a longer ICU length of stay.LU outperformed CR for the diagnosis of consolidations and pleural effusion during ACS. Higher values of LU score identified patients at risk of worse outcome.

High Emergency Lung Transplantation: dramatic decrease of waiting list death rate without relevant higher post-transplant mortality

Many candidates for lung transplantation (LT) die on the waiting list, raising the question of graft availability and strategy for organ allocation. We report the experience of the new organ allocation program, “High Emergency Lung Transplantation” (HELT), since its implementation in our center in 2007. Retrospective analysis of 201 lung transplant patients, of whom 37 received HELT from 1st July 2007 to 31th May 2012. HELT candidates had a higher impairment grade on respiratory status and higher Lung Allocation Score (LAS). HELT patients had increased incidence of perioperative complications (e.g., perioperative bleeding) and extracorporeal circulatory assistance (75% vs. 36.6%, P = 0.0005). No significant difference was observed between HELT and non‐HELT patients in mechanical ventilation duration (15.5 days vs. 11 days, P = 0.27), intensive care unit length of stay (15 days vs. 10 days, P = 0.22) or survival rate at 12 (81% vs. 80%), and 24 months post‐LT (72.9% vs. 75.0%). Lastly, mortality on the waiting list was spectacularly reduced from 19% to 2% when compared to the non‐HELT 2004–2007 group. Despite a more severe clinical status of patients on the waiting list, HELT provided similar results to conventional LT. These results were associated with a dramatic reduction in the mortality rate of patients on the waiting list.

Characteristics of Donor-Specific Antibodies Associated With Antibody-Mediated Rejection in Lung Transplantation

Although donor-specific anti-human leukocyte antigen (HLA) antibodies (DSAs) are frequently found in recipients after lung transplantation (LT), the characteristics of DSA which influence antibody-mediated rejection (AMR) in LT are not fully defined. We retrospectively analyzed 206 consecutive LT patients of our center (2010–2013). DSAs were detected by using luminex single antigen beads assay and mean fluorescence intensity was assessed. Within the study population, 105 patients had positive DSA. Patients with and without AMR (AMRPos, n = 22, and AMRNeg, n = 83, respectively) were compared. AMRPos patients had significantly greater frequencies of anti-HLA DQ DSA (DQ DSA) than AMRNeg patients (95 vs 58%, respectively, p < 0.0001). Compared to AMRNeg patients, AMRPos patients had higher DQ DSA sum MFI [7,332 (2,067–10,213) vs 681 (0–1,887), p < 0.0001]. DQ DSA when associated with AMR, had more frequent graft loss and chronic lung allograft dysfunction (CLAD). These data suggest (i) that DSA characteristics clearly differ between AMRPos and AMRNeg patients and (ii) the deleterious impact of DQ DSA on clinical outcome.

193 Isolated lung transplantation (LT) for cystic fibrosis patients with portal hypertension (PHT)

Objectives PHT is the main manifestation of liver disease in adults CF patients. The risk of hepatic decompensation after isolated LT is unknown. The model for end-stage liver disease (MELD) score is not relevant for the indication to combined lungs-liver transplantation. We presented the postoperative outcome of isolated lung transplantation in CF patients with asymptomatic PHT. Methods From 2008 to 2014, 14 isolated LT (over 299) were proceeded over CF patients with PHT. Results All Patients had asymptomatic liver disease before LT but all had PHT on the CT scan: splenomegaly (14–19 cm) in 10 patients, portosystemic collaterals in 8, all had portal vein dilatation >14 (diameter 17±2.3 mm). The liver stiffness measurement (LMS) was elevated 18±8 kPa when in our adult CF center median LSM was 5.9 kPa in 241 CF patients. Thirteen patients had normal liver and renal function. Gastroesophageal varices were absents in 10 screened patients. After LT, 4 patients required ECMO, 6 developed easy to treat ascites associated with transient renal insufficiency (4) or intestinal complications (2). One developed transient ascitis 7 months after LT associated with sepsis and renal dysfunction. Hepatocellular function remain normal in all patients. Every patient is still alive (mean time 42±22 months). Conclusion Carefully selected CF patients with end-stage lung disease and portal hypertension can tolerate isolated lung transplantation. The non-invasive evaluation of the severity of PHT has to be evaluated. Prospective multicentric study is need to clearly define the indications of combined lung–liver transplantation.