Liver Involvement in Patients With PiZZ-Emphysema, Candidates for Lung Transplantation.

Information about the prevalence and nature of liver disorders in adults with alpha1-antitrypsin deficiency is scarce. At our center, systematic liver biopsy screening is part of the evaluation before lung transplantation (LT) in the emphysema patients with the PiZZ phenotype. Our aim was to report our experience with this prospective screening. Clinical, liver function, and imaging parameters as well as liver histology data were analyzed for 23 consecutive adult patients with PiZZ severe emphysema referred to our center for consideration of LT from 2006 to 2014. Overall 20 (87%) featured chronic liver disease characterized by a chronic inflammation and/or a significant portal fibrosis on histology. Two of the 23 patients (8.7%) had septal fibrosis according to the Metavir and Ishak scores and met our definition of severe chronic liver disease. They were both clinically asymptomatic with normal liver function tests. On abdominal ultrasonography, the liver appeared normal in one patient and with abnormal contours in the other. Our data indicate that in adults with PiZZ-related emphysema being evaluated for LT, most patients had some histologic involvement. The prevalence of severe liver dysfunction is <10%.

T Cells Promote Bronchial Epithelial Cell Secretion of Matrix Metalloproteinase-9 via a C-C Chemokine Receptor Type 2 Pathway: Implications for Chronic Lung Allograft Dysfunction.

Chronic lung allograft dysfunction (CLAD) is the major limitation of long-term survival after lung transplantation. CLAD manifests as bronchiolitis obliterans syndrome (BOS) or restrictive allograft syndrome (RAS). Alloimmune reactions and epithelial-to-mesenchymal transition have been suggested in BOS. However, little is known regarding the role of allogenicity in epithelial cell differentiation. Primary human bronchial epithelial cells (BECs) were treated with activated T cells in the presence or absence of transforming growth factor (TGF)-ß. The expression of epithelial and mesenchymal markers was investigated. The secretion of inflammatory cytokines and matrix metalloproteinase (MMP)-9 was measured in culture supernatants and in plasma from lung transplant recipients (LTRs): 49 stable, 29 with BOS, and 16 with RAS. We demonstrated that C-C motif chemokine 2 secreted by T cells supports TGF-ß-induced MMP-9 production by BECs after binding to C-C chemokine receptor type 2. Longitudinal investigation in LTRs revealed a rise in plasma MMP-9 before CLAD onset. Multivariate analysis showed that plasma MMP-9 was independently associated with BOS (odds ratio [OR] = 6.19, p = 0.002) or RAS (OR = 3.9, p = 0.024) and predicted the occurrence of CLAD 12 months before the functional diagnosis. Thus, immune cells support airway remodeling through the production of MMP-9. Plasma MMP-9 is a potential predictive biomarker of CLAD.

Role of HLA-G as a predictive marker of low risk of chronic rejection in lung transplant recipients: a clinical prospective study.

Human leukocyte antigen G (HLA-G) expression is thought to be associated with a tolerance state following solid organ transplantation. In a lung transplant (LTx) recipient cohort, we assessed (1) the role of HLA-G expression as a predictor of graft acceptance, and (2) the relationship between (i) graft and peripheral HLA-G expression, (ii) HLA-G expression and humoral immunity and (iii) HLA-G expression and lung microenvironment. We prospectively enrolled 63 LTx recipients (median follow-up 3.26 years [min: 0.44-max: 5.03]). At 3 and 12 months post-LTx, we analyzed graft HLA-G expression by immunohistochemistry, plasma soluble HLA-G (sHLA-G) level by enzyme-linked immunosorbent assay, bronchoalveolar lavage fluid (BALF) levels of cytokines involved in chronic lung allograft dysfunction (CLAD) and anti-HLA antibodies (Abs) in serum. In a time-dependent Cox model, lung HLA-G expression had a protective effect on CLAD occurrence (hazard ratio: 0.13 [0.03-0.58]; p = 0.008). The same results were found when computing 3-month and 1-year conditional freedom from CLAD (p = 0.03 and 0.04, respectively [log-rank test]). Presence of anti-HLA Abs was inversely associated with graft HLA-G expression (p = 0.02). Increased BALF level of transforming growth factor-ß was associated with high plasma sHLA-G level (p = 0.02). In conclusion, early graft HLA-G expression in LTx recipients with a stable condition was associated with graft acceptance in the long term.

Transfusion-related acute lung injury after intravenous immunoglobulin treatment in a lung transplant recipient.

Three weeks after single-lung transplantation for pulmonary fibrosis, a patient with high serum levels of de novo donor-specific antibodies received high-dose intravenous immunoglobulin (IVIG) infusion (scheduled dose: 2 g/kg on 2 days) to prevent antibody-mediated rejection. Within the first hours after completion of infusions, he experienced acute lung injury involving the transplanted lung. Given the clinical evolution and the absence of an alternative diagnosis, transfusion-related acute lung injury (TRALI) was diagnosed. The IVIG administered on each day was from the same batch. At day 110, because of an increase in the serum titers of donor-specific antibodies, IVIG therapy was reintroduced but from a different batch, with excellent clinical tolerance. The lung injury was explored biologically, but no mechanism was revealed. Given the increasing use of IVIG in solid-organ recipients, clinicians should be aware of possible TRALI after IVIG infusion.

COVID-19 reinfection after pregnancy.

BACKGROUND: There have been reports of COVID-19 reinfections, but the immunological characterization of these cases is partial. We report a case of reinfection with SARS-CoV-2, where the first infection occurred in the course of late pregnancy. CASE PRESENTATION: On May 27, 2020, a 37-year-old woman gave birth at full term, 3 hours after full dilatation. She developed fever (38.3°C) after delivery. Mild biological anomalies compatible with COVID-19 were observed: lymphopenia, thrombocytopenia, elevated D-Dimers, CRP, and LDH. At 6-month follow-up, she reported having contracted COVID-19 with high fever, rhinorrhea, hand frostbites, cough, headache, dysgeusia and anosmia. CONCLUSIONS: We report a case of COVID-19 reinfection with a first mild infection during late pregnancy and a more aggressive second infection 5 months later.

[Updated indications and contraindications in 2022 for lung transplantation in France]. / Transplantation pulmonaire en France : actualisation des indications et contre-indications en 2022.

Lung transplantation (LTx) is the last-resort treatment for end-stage respiratory insufficiency, whatever its origin, and represents a steadily expanding field of endeavor. Major developments have been impelled over the years by painstaking efforts at LTx centers to improve donor and recipient selection, and multifaceted attempts have been made to meet the challenges raised by surgical management, perioperative care, and long-term medical complications. The number of procedures has increased, leading to improved post-LTx prognosis. One consequence of these multiple developments has been a pruning away of contraindications over time, which has, in some ways, complicated the patient selection process. With these considerations in mind, the Francophone Pulmonology Society (Société de Pneumology de Langue Française [SPLF]) has set up a task force to produce up-to-date working guidelines designed to assist pulmonologists in managing end-stage respiratory insufficiency, determining which patients may be eligible for LTx, and appropriately timing LTx-center referral. The task force has examined the most recent literature and evaluated the risk factors that continue to limit patient survival after LTx. Ideally, the objectives of LTx are to prolong life while improving quality of life. The guidelines developed by the task force apply to a limited resource and are consistent with the ethical principles described below.

Immunohistochemical study of HLA-G expression in lung transplant recipients.

Human leukocyte antigen-G (HLA-G), a nonclassical HLA class I protein, promotes immune tolerance of solid-organ allografts, yet its role in lung transplantation (LTx) is unknown. We examined the expression of HLA-G in lung allografts through immunohistochemistry by a cross-sectional study of 64 LTx recipients, classified into four groups (stable patients, acute rejection [AR], bronchiolitis obliterans syndrome [BOS] and symptomatic viral shedders). A marked expression of HLA-G in bronchial epithelial cells (BEC) was frequently observed in stable recipients (n = 18/35 [51%]), but not in patients with AR (n = 14) or with BOS (n = 8). HLA-G was also expressed by 4 of 7 symptomatic viral shedders. In addition, HLA-G-positive patients from the stable group (n = 35) experienced lower incidence of resistant AR and/or BOS during long-term follow-up, as compared with their HLA-G-negative counterparts. Finally, in vitro data showed that interferon-gamma, a cytokine present in lung allograft microenvironment, upregulated HLA-G mRNA and protein expression in primary cultured human BEC. We conclude that HLA-G expression in the bronchial epithelium of lung allograft is elevated in some LTx recipients in association with their functional stability, suggesting a potential role of HLA-G as a tolerance marker.

Severe axonal polyneuropathy after a FK506 overdosage in a lung transplant recipient.

FK506-induced polyneuropathies are rarely encountered. We report a case of axonal sensorimotor polyneuropathy in a lung transplant recipient that occurred during a FK506 overdosage. Onset was acute in the form of severe areflexic tetraparesis and resolution was observed after reduction of dosage. Because of increasing use of FK506 in solid organ transplantation, caution should be paid with FK506 dosage monitoring in cases of peripheral nervous system symptoms.

Preventive effect of inhaled nitric oxide and pentoxifylline on ischemia/reperfusion injury after lung transplantation.

BACKGROUND: The preventive effect of inhaled nitric oxide (NO) and pentoxifylline (PTX) administered during reperfusion has been demonstrated on experimental models of lung ischemia/reperfusion (I/R) injury but this strategy is not validated in clinical lung transplantation. The aim of this study was to assess retrospectively the protective effect of inhaled NO and PTX after lung transplantation. METHODS: Twenty-three consecutive patients who received inhaled NO (10 ppm) and PTX (NO-PTX group) at the time of reperfusion were compared retrospectively with (1) 23 consecutive patients transplanted just before the use of NO-PTX (control group 23); (2) 95 patients representing all the patients of the series who did not receive NO-PTX (control group 95), with respect to I/R injury related complications. In particular, the incidence of pulmonary reimplantation edema and early hemodynamic failure, the PaO2/FIO2 ratio as well as the duration of mechanical ventilation and the 2-month mortality rates were compared. RESULTS: Reimplantation edema was observed in 6/23 patients (26%) in the NO-PTX group vs. 13/23 patients (56%) in the control group 23 (P=0.035) and 48/95 patients (50%) in the control group 95 (P=0.035). The worst PaO2/FIO2 ratio during the first three postoperative days was 240-102 mmHg in the NO-PTX group vs. 162+/-88 mmHg (P=0.01) and 176+/-107 mmHg (P=0.01) in the control group 23 and the control group 95, respectively. The duration of mechanical ventilation was 2.1+/-2.4 days in the NO-PTX group vs. 7+/-9 days in the control group 23 (P=0.02) and 6+/-7 days in the control group 95 (P=0.01). The 2-month mortality rate was 4.3% in the NO-PTX group vs. 26% (P=0.04) and 21% (P=0.07) in the control group 23 and the control group 95, respectively. CONCLUSIONS: The marked decrease in the incidence of allograft dysfunction compared with two historical control groups suggests that PTX and inhaled NO given before and throughout reperfusion are protective against I/R injury in the setting of clinical transplantation.

Immediate and long-term results of bronchial artery embolization for life-threatening hemoptysis.

STUDY OBJECTIVES: Bronchial artery embolization (BAE) has been established as an effective technique in the emergency treatment of life-threatening hemoptysis, but few data concerning long-term results and complications of the procedure are available. The aim of this study was to analyze retrospectively the experience of BAE in our center with particular emphasis on medium-term and long-term results and on morbidity. SETTING: University hospital. PATIENTS: Fifty-six patients underwent bronchial arteriography from 1986 to 1996 in our center for the management of life-threatening hemoptysis. Of them, BAE was performed in 46 patients. Their mean age was 51 years (range, 19 to 89 years). The most frequent etiologies of hemoptysis were active or inactive tuberculosis, bronchiectasis, or idiopathic hemoptysis. RESULTS: BAE resulted in an immediate cessation of hemoptysis in 43 of the initial 56 patients (77%). During the first month after BAE, four patients who died from causes other than hemoptysis or who were referred to surgery were excluded from follow-up and in the 39 remaining patients, a complete cessation of hemoptysis was observed in 32 patients. A remission was noted in 28 of the 29 patients followed up between 30 and 90 days after BAE. Long-term control of bleeding was achieved in 25 of the initial 56 patients (45%) followed up beyond 3 months after BAE (median follow-up of 13 months; range, 3 to 76 months). Overall, complications of BAE consisted of two episodes of mediastinal hematoma and three episodes of neurologic damage, two of which improved without permanent sequelae. CONCLUSION: We conclude that BAE may result in long-term as well as immediate control of life-threatening hemoptysis but that complications are not unusual.

Prognosis of patients with advanced idiopathic pulmonary fibrosis requiring mechanical ventilation for acute respiratory failure.

STUDY OBJECTIVE: To evaluate the beneficial effect of mechanical ventilation (MV) in patients with idiopathic pulmonary fibrosis (IPF) who develop acute respiratory failure (ARF), with special emphasis on prognosis. DESIGN: Retrospective study. SETTING: Ten-bed respiratory ICU that is a part of a respiratory department actively involved in lung transplantation (LTx). PATIENTS: From 1991 to 1999, 23 patients (mean age, 52.9 years; range, 21 to 82 years) with IPF required MV for ARF. At admission to the ICU, 16 patients were potential candidates for LTx, with 5 patients already on the waiting list. MEASUREMENTS AND RESULTS: Survival and gas exchange under MV were assessed. The precipitating cause of ARF was also analyzed. With the exception of 1 patient who successfully received a single-lung transplant 6 h after initiation of MV, all the remaining 22 patients died while receiving MV (median survival, 3 days; range, 1 h to 60 days). The duration of MV correlated positively with baseline vital capacity (percent predicted) (R = 0.54; p = 0.01) and baseline total lung capacity (percent predicted) (R = 0.71; p < 0.001), and correlated negatively with baseline PaCO(2) (R = - 0.47; p = 0.03) and the duration of evolution of IPF (R = -0.50; p = 0.01). Duration of MV did not correlate with the duration of immunosuppressive therapy (R = - 0.24; p = 0.27) or duration of oxygen therapy (R = - 0.32; p = 0.14) prior to admission. The precipitating cause of ARF was most often not identified. CONCLUSIONS: Our data support the general belief that MV does not benefit IPF patients presenting with ARF. Initiation of MV in IPF patients is thus questionable and should, in our opinion, be restricted to patients in whom LTx can be performed within a few days after initiation of MV.

Morbidity and mortality related to the native lung in single lung transplantation for emphysema.

It has been advocated that a major drawback of single lung transplantation (SLT) is the risk of serious complications arising from the native lung. The morbidity and mortality related to the native lung in 46 patients who underwent SLT for pulmonary emphysema in Clichy from 1988 to 1997 were reviewed retrospectively. In particular, infectious complications and native lung hyperinflation were searched. Complications arising from the native lung are not unusual after SLT for subjects with emphysema, and it was concluded they are not responsible for a substantial mortality.

[Primary non-Hodgkin's lymphomas of the liver in human immunodeficiency virus infected patients. Three cases]. / Lymphomes non hodgkiniens primitifs du foie chez les malades infectés par le virus de l'immunodéficience humaine. Trois cas.

The occurrence of primary non Hodgkin's lymphoma of the liver has rarely been reported in patients with the human immunodeficiency virus infection. We report 3 cases in these patients, presenting with a single liver tumor in 2 cases and multiple tumors in one case. Diagnosis was made by guided-biopsy. Histologically, there was B diffuse large cell lymphoma in 2 cases, and immunoblastic lymphoma in one case. In one case, RNA of Epstein-Barr virus was found in the nucleus of tumor cells by in situ hybridization. No extrahepatic localization was found in any of the 3 cases. One patient died one week after diagnosis, but the 2 other patients were treated by chemotherapy and were still alive 6 and 30 months later. In patients infected by human immunodeficiency virus, primary non Hodgkin's lymphoma should be investigated in case of liver tumor in order to provide early treatment.

[Spontaneous splenic rupture: report of three new cases and review of the literature]. / Ruptures non traumatiques de la rate: trois nouveaux cas et revue de la littérature.

This study reports 3 new cases of spontaneous (or atraumatic) splenic rupture of the spleen, including two with massive hemoperitoneum and one with a secondary rupture of splenic infarct, and reviews the literature about this rare disease. These spontaneous ruptures are rare and potentially fatal. They result from infectious diseases (mainly mononucleosis and and paludism) and hematological diseases (mainly malignant hemopathies) in more than 50% of cases. Mortality is close to 20%, and includes some deaths occurring before diagnosis was established and postoperatives deaths, which can result from delayed management and bad general condition of the patients. Splenectomy is usually mandatory. Non-surgical treatment can be indicated only in young and stable patients.

[Impact of Chlamydia pneumoniae infections on asthma]. / Impact des infections à Chlamydia pneumoniae sur la maladie asthmatique.

VIRUSES AND BACTERIA: The fact that the airways are exposed to a large number of infectious agents could explain the frequency of respiratory infections and their causal effect in bronchial inflammation. Viruses are most often the causal agent, but the frequency of bacterial infections make them potential candidates in certain respiratory diseases. Chlamydia are particularly important due to their capacity to provoke immune dysfunction and chronic inflammation. EFFECT ON ASTHMA: It is not surprising to find biological evidence of Chlamydia pneumoniae infection in a large number of subjects who experience major degradation of their asthma because asthmatic subjects are particularly susceptible to respiratory infections and Chlamydia pneumoniae is a frequent cause of such infections. PATHOGENIC EFFECT: Finding Chlamydia pneumoniae as the causal agent in asthma is however much more surprising, with a much different consequence. There are however many epidemiological and clinical findings and case observations (Chlamydia pneumoniae asthma associations, prolonged favorable course in certain obstructive bronchial diseases after a short antibiotic regimen) as well as provocative pathophysiological data favoring this particular form of "infectious asthma". FURTHER INFORMATION: Large-scale studies with rigorous methodology remain to be performed. The would be needed to determine the exact relationship between Chlamydia pneumoniae infections and certain types of asthma, particularly when wheezing occurs after a respiratory infection and when chronic obstruction develops. The could also determine the role of anti-Chlamydia pneumoniae antibiotics in case of obstructive respiratory failure and also determine their efficacy on long-term outcome.

[Selection criteria of candidates for lung transplantation]. / Critères de sélection des candidats à la transplantation pulmonaire.

Amongst the elements which contributed to the success of the early lung transplants at the beginning of the 1980's we feel that the careful selection of candidates probably played a predominant role. If some of the selection criteria initially described remain somewhat intangible, others have either been eased or have been invalidated. The experience acquired over the last 15 years has enabled to precise the optimal moment to include patients on the waiting list and to refine the choice for the type of surgical procedure according to the underlying disease. This article aims to review the different selection criteria for candidates for transplantation and stresses those which have recently undergone change.