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%.

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.

[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.

[Insisting on intravenous polyvalent immunoglobulin therapy in polymyositis in spite of the occurrence of sever hemolytic anemia]. / Poursuite du traitement d'une polymyosite par les immunoglobulines intraveineuses polyvalentes malgré la survenue d'une anémie hémolytique sévère.

A 23-year-old female with polymyositis received high dose intravenous immunoglobulin (IVIg) therapy. The patient suffered severe hemolytic anemia after receiving first course of IVIg infusion. This adverse reaction was likely due to allohemaglutinin A and B and from or high molecular weight IgG complexes contained in the preparation. Though this effect was observed, the treatment was repeated six times. A mild hemolysis occurred following each IVIg, with no clinical consequence. Involvement of the saturation of macrophagic receptors might explain this partial destruction of erythrocytes.

[Bronchiolitis with airflow obstruction in adults]. / Bronchiolites avec trouble ventilatoire obstructif de l'adulte.

PURPOSE: The purpose of this paper is twofold: to describe the clinical and anatomical characteristics of bronchiolitis associated with airflow obstruction in adults; to present through a clinical approach, a classification of the main aetiologies or pathological frames associated with that entity. KEY POINTS: The constrictive bronchiolitis type is the most frequently encountered. On clinical grounds, cough, crackles, and a progressive dyspnea develop usually within a few weeks. Radiological signs of bronchiolar abnormalities are best visualized on high resolution expiratory CT scan. The decrease in maximal airflows and oxygen tension is of limited amplitude and poorly reversible with bronchodilators. Diagnosis is easily performed when a causative event, or the clinical context, can be delineated: inhalation of toxic fumes, diffuse bronchiectasis, rheumatoid arthritis, lung or bone marrow transplantation. Delayed formation of bronchiectasis in the central airways is common. The treatment is not standardized; corticosteroids are usually prescribed as a first line therapy; the benefit of the addition of, or substitution with immunosuppressive drugs has not been adequately evaluated, but is, on the mean, of limited amplitude. PERSPECTIVES: Recent advances in the identification of inhaled agents toxic for the distal airways help in establishing appropriate measures of prevention. When the aetiology of the bronchiolitis cannot be suspected, extensive search of a causative agent should be performed, including microbial and mineral analysis of bronchoalveolar products. Negative results should lead to perform a surgical lung biopsy. The study of chronic rejection processes in animal models of lung transplantation, the identification of inhibitory factors of bronchiolar fibrogenesis, and the efficacy of some anti-cytokines on inflammatory processes could result in new therapeutic approaches.

Veno-occlusive disease of the liver after lung transplantation.

Veno-occlusive disease (VOD) of the liver is mainly described after chemo-irradiation conditioning regimens during haematopoietic stem cell transplantation (SCT) and has been sporadically reported after kidney and liver transplantation. In the latter cases, it is commonly attributed to azathioprine and/or tacrolimus. One case of tacrolimus-induced hepatic VOD developing after lung transplantation (LT) has been recently reported. Here we describe another case of VOD occurring after LT, but in which the causative role was played by azathioprine.

Exhaled NO may predict the decline in lung function in bronchiolitis obliterans syndrome.

Bronchiolitis obliterans syndrome (BOS) remains the leading cause of morbidity/mortality following lung transplantation. In recipients with BOS, markers predicting the decline in lung function are needed. The aim of this longitudinal study was to determine whether exhaled nitric oxide fraction (FeNO) measurements provide useful information for discriminating patients with unstable BOS from those with stable BOS. During a 14-month period, 145 FeNO measurements were performed in 50 lung transplant recipients. Among them, 16 recipients with BOS (32 FeNO measurements) were analysed. For each FeNO measurement, the patients were classified into three groups according to the decline in forced expiratory volume in one second (FEV1) within the following 6 months: 1) stable BOS free; 2) stable BOS (decline in FEV1 of <5%); and 3) unstable BOS (decline in FEV1 of > or =15%). The mean FeNO in patients with unstable BOS was significantly increased compared with that in stable BOS-free patients (18.4+/-5.7 versus 9.7+/-3.7 ppb) and that in patients with stable BOS (18.4+/-5.7 versus 9.7+/-3.3 ppb). The present findings suggest that, in patients with bronchiolitis obliterans syndrome, a raised exhaled nitric oxide fraction may predict the development of worrisome functional impairment during long-term follow-up.