[Graft-versus-host disease, a rare complication of lung transplantation]. / La maladie du greffon contre l'hôte, graft-versus-host disease, une complication exceptionnelle de la transplantation pulmonaire.

Graft-versus-host disease (GVHD) is a classic and frequent multisystemic complication of bone marrow allografts. It has also been reported after the transplantation of solid organs such as the liver or gut. Recent cases of GVHD have been reported after lung and heart-lung transplant. Skin, liver, gastrointestinal tract and bone marrow are the organ preferentially affected by GVHD. Corticosteroid is the first line treatment of GVHD. The prognosis reported in solid organ transplants is poor with infectious complications favoured by immunosuppressive therapy. In this article, we report a case of a patient with cystic fibrosis who presented a probable GVHD 18 months after a lung transplant and a literature review of similar cases.

[Indications of lung transplantation: Patients selection, timing of listing, and choice of procedure]. / Indications de la transplantation pulmonaire : sélection des candidats, critères d'inscription en liste d'attente, choix du type d'intervention.

Lung transplantation (LT) is now considered as an excellent treatment option for selected patients with end-stage pulmonary diseases, such as COPD, cystic fibrosis, idiopathic pulmonary fibrosis, and pulmonary arterial hypertension. The 2 goals of LT are to provide a survival benefit and to improve quality of life. The 3-step decision process leading to LT is discussed in this review. The first step is the selection of candidates, which requires a careful examination in order to check absolute and relative contraindications. The second step is the timing of listing for LT; it requires the knowledge of disease-specific prognostic factors available in international guidelines, and discussed in this paper. The third step is the choice of procedure: indications of heart-lung, single-lung, and bilateral-lung transplantation are described. In conclusion, this document provides guidelines to help pulmonologists in the referral and selection processes of candidates for transplantation in order to optimize the outcome of LT.

Legionellosis and lung abscesses: contribution of legionella quantitative real-time PCR to an adapted followup.

We report a case of severe Legionnaires' disease (LD) complicated by a lung abscess in an immunocompetent patient who required ECMO therapy and thoracic surgery. The results of repeated Legionella quantitative real-time PCR performed on both sera and respiratory samples correlated with the LD severity and the poor clinical outcome. Moreover, the PCR allowed for the detection of Legionella DNA in the lung abscess specimen, which was negative when cultured for Legionella. This case report provides a logical basis for further investigations to examine whether the Legionella quantitative PCR could improve the assessment of LD severity and constitute a prognostic marker.

[Bronchiolo-alveolar carcinoma and lung transplantation]. / Carcinome bronchioloalvéolaire et transplantation pulmonaire.

INTRODUCTION: Bronchiolo-alveolar carcinoma is a controversial indication for lung transplantation because of the risk of recurrence. We report three cases and propose some risk factors for recurrence. CASE REPORTS: Our study concerns three patients transplanted at the Louis-Pradel Hospital between 1991 and 2010. The first patient relapsed 86 months after transplantation, benefited from surgical treatment, then died of renal failure. A second patient died of infection, without recurrence, 72 months after transplantation. The third had an early recurrence at 7 months and died 27 months after transplantation. The risk factors for recurrence appear to be: clinically "aggressive" presentation and histological stromal pulmonary invasion by the carcinoma. CONCLUSION: Diffuse bronchiolo-alveolar carcinoma is a possible indication of lung transplantation. The risk of recurrence imposes some requirements: a precise histological diagnosis and a slow clinical course.

[Tracheotomy management in home mechanical ventilation]. / La gestion de la trachéotomie chez les patients adultes sous assistance ventilatoire à domicile.

INTRODUCTION: Despite a large increase in the use of long term non-invasive ventilation domiciliary ventilation via a tracheostomy remains necessary in certain cases of severe respiratory insufficiency. The object of this article is to describe the technical and human management required in domiciliary ventilation by tracheostomy. PERSPECTIVES: From the setting up of invasive ventilation in the home the choice of a tracheostomy tube to suit the patient and the management of the cuff by the patient or the family requires special attention by the prescribing physician. Currently humidification of the circuit is usually achieved by means of a hot water humidifier. Aspiration techniques, the changing and cleaning of the tracheostomy tube and the correct use of the speaking system need to be taught to the patient and the relatives. The main complications of domiciliary ventilation by tracheostomy are linked to the presence of the tube in the trachea and either mechanical (stenosis, granulomata, tracheal-oesophageal fistula) or infections. CONCLUSIONS: The prescribing physician should call on health care providers whose staff are trained in domiciliary ventilation by tracheostomy and include in his team nurses who can continue the education of the patient and relatives.

[Outcome of adult patients with cystic fibrosis admitted to intensive care with respiratory failure: the role of non-invasive ventilation]. / Devenir des adultes mucoviscidosiques admis en réanimation pour décompensation respiratoire.

Recourse to mechanical ventilation may prove necessary in adult patients with cystic fibrosis who have reached the stage of severe respiratory insufficiency. We report the experience of an intensive care service using non-invasive ventilation (NIV) as the first step in the management of acute respiratory failure in these patients. The records of 16 patients with cystic fibrosis presenting with acute respiratory failure and treated with NIV were analysed retrospectively. The characteristics of the group were: mean age 26.9 +/- 9.5 years; mean FEV1 21.5 +/- 10.4% predicted; mean body mass index 16.8 +/- 2.1; mean Pa CO(2) on admission 66 +/- 15 mm Hg. The mean duration of NIV in the ICU was 10 +/- 7 days. Eight patients (50%) died after having been intubated on account of failure of NIV. The eight survivors were discharged home with long-term NIV (mean duration 235 +/- 158 days). Six of them have received a lung transplant. The mode of onset of respiratory failure was an important prognostic factor: a rapid onset (<7 days) was invariably associated with death, on the other hand a gradual deterioration (> 7 days) was noted in the eight patients able to leave the ICU. In conclusion NIV may be regarded as the treatment of choice in patients with cystic fibrosis admitted to ICU with respiratory failure. In the case of persistent hypercapnia after the acute episode long-term NIV may keep them stable while awaiting lung transplantation.

Constrictive bronchiolitis obliterans. Characterisation of fibrogenesis and lysyl oxidase expression patterns.

The process leading to irreversible fibrotic constriction of the bronchioles was studied in two cases of bronchiolitis obliterans (BO) after bone marrow transplantation. Because lysyl oxidase (LOX) is the main collagen cross-linking enzyme that might account for irreversible fibrosis, its expression was studied together with expression of extracellular matrix (ECM) proteins. Characteristic types of lesions could be distinguished on the basis of histological and immunohistological criteria. An inflammatory stage was characterised by infiltration restricted to the bronchioles by lymphocytes and dendritic cells. A fibro-inflammatory stage was characterised by the coexistence of a persistent immune cellular lesion pattern with further focal modelling of a sub-epithelial neo-synthesised connective matrix. LOX expression was observed at the tips of intra-luminal fibrotic protrusions, together with tenascin and cellular fibronectin. A fibrotic stage was characterised by dense ECM deposits spreading throughout the peri-bronchiolar connective tissue, resulting in bronchiole obliteration and final disappearance. In contrast to reversible cases of fibrosis, persistence of long-term LOX expression reflecting continuing fibrosing activity might account for the irreversible status of BO. Our two cases illustrated that, at inflammatory and fibro-inflammatory stages, BO may be stabilised by immunosuppressive treatment, while the persistence of LOX expression in the fibrotic stage might correspond to a disease that becomes irreversible and fatal.

Outcome of patients with idiopathic pulmonary fibrosis admitted to the ICU for respiratory failure.

STUDY OBJECTIVES: To analyze the outcome of acute respiratory failure (ARF) in patients with idiopathic pulmonary fibrosis (IPF), and to evaluate the benefits of invasive and noninvasive mechanical ventilation (MV). DESIGN: Retrospective study. SETTING: University hospital. PATIENTS: Fifteen consecutive patients with IPF referred to the ICU for ARF between January 1989 and June 1998. MEASUREMENTS AND RESULTS: Fifteen patients (mean +/- SD age, 64 +/- 10 years) were included. Eight patients had clinical, functional, and radiologic features of IPF, and the remaining seven patients also had biopsy specimen-proven IPF. The mean duration between diagnosis of IPF and admission to the ICU was 26.5 +/- 28 months. At the time of ICU admission, mean arterial blood gas levels were as follows: PaO(2)/fraction of inspired oxygen, 113 +/- 95; pH, 7.32 +/- 0.10; and PaCO(2), 55 +/- 21 mm Hg. All patients received MV; 12 patients required tracheal intubation, either at the time of ICU admission (n = 10) or after failure of noninvasive ventilation (NIV; n = 2); and 3 patients only received NIV. Three of the five patients receiving NIV died of respiratory failure. Eleven patients died in the ICU, either from hypoxemia (n = 8) or from septic shock (n = 3). Four patients were discharged alive from the ICU, and two of them died shortly thereafter. CONCLUSION: The outcome of patients with IPF referred to the ICU for ARF was very poor and not improved by MV. Without a clearly identified reversible cause of ARF, these patients should not benefit from admission to the ICU.

[Pulmonary and musculo-cutaneous thigh actinomycosis]. / Actinomycose pulmonaire et musculo-cutanée de la cuisse.

We report a case of actinomycosis presenting with both a thigh abscess and a pulmonary lesion. Diagnosis was obtained by biopsy of this abscess, showing sulfur granules and further identification of Actinomyces israelii together with Actinobacillus actinomycetemcomitans in culture. Furthermore. Actinomyces israelii was isolated from bronchial secretions.

[Lung complications of hematopoietic stem cell transplantation]. / Complications pulmonaires des greffes de cellules souches hématopoïétiques.

Bone marrow transplantation (BMT) is a potentially curative therapy in selected patients with hematologic disorders (acute leukemia, chronic myelogenous leukemia, lymphoma) or solid tumors (testicular or breast cancer). Pulmonary complications occur in 40 to 60% of patients receiving BMT, and are related to various mechanisms: chemotherapy-induced neutropenia, pulmonary toxicity of radiotherapy or chemotherapy, graft-versus-host disease. Bacterial or fungal pneumonia occurring during the initial period of neutropenia, and interstitial pneumonia (related to cytomegalovirus or of unknown origin) are the major respiratory complications of the first 100 days. Bacterial sinusitis and pulmonary infections, and obstructive airways disease related to bronchiolitis are the main late-onset respiratory disorders. No single risk factor can predict the development of these complications, which result from a sequence of events including infections, pulmonary injuries related to chemotherapy or radiotherapy, and inappropriate immunological reaction after transplantation. Antimicrobial prevention has been shown to reduce the mortality of these complications, but they still result in both important morbidity and mortality. They are the most frequent non relapse cause of death among long term surviving patients. Better understanding of their pathogenesis, and early recognition and treatment of respiratory complications of BMT should improve the efficacy of this therapy.

Post-transplant obstructive lung disease ("bronchiolitis obliterans"): a clinical comparative study of bone marrow and lung transplant patients.

Patients at a single pulmonary centre who developed obstructive lung disease after bone marrow transplantation (BMT) and lung transplantation (LT) were studied, in order to compare the clinical expression of post-transplant obstructive lung disease (PTOLD) (bronchiolitis obliterans) in these two conditions, which have so far been studied separately. Nine out of 179 patients surviving more than 100 days after BMT (5%) and 9 out of 44 patients surviving more than 100 days after LT (20%) developed post-transplant obstructive lung disease. This was defined by an irreversible airflow obstruction, as characterized by a forced expiratory volume in one second divided by forced vital capacity (FEV1/FVC) of less than 70%, and a FEV1 of less than 70% of predicted value. The mean interval between transplantation and the diagnosis of post-transplant obstructive lung disease was 262 days and 217 days for BMT and LT patients, respectively. In all cases, pulmonary symptoms consisted of dyspnoea and progressively productive cough. Bronchial dilatation on high-resolution computed tomography scans was the main imaging feature present in both groups of patients at the onset of post-transplant obstructive lung disease. The mean FEV1/FVC ratio was 51 and 54% for BMT and LT patients, respectively. All BMT and LT patients had normal transfer coefficient. Clinical chronic graft-versus-host disease was present in all BMT patients before or concurrent with the onset of post-transplant obstructive lung disease, and all LT patients had presented at least one episode of acute lung rejection.(ABSTRACT TRUNCATED AT 250 WORDS)

Bronchiectasis detected with thin-section CT as a predictor of chronic lung allograft rejection.

PURPOSE: To evaluate bronchiectasis detected with thin-section computed tomography (CT) as a potential early finding of chronic lung allograft rejection. MATERIALS AND METHODS: Forty patients were studied at least 6 months after transplantation. Follow-up CT scans were obtained 6-48 months after transplantation and were retrospectively reviewed for evidence and anatomic extent of bronchiectasis. Irreversible dysfunction of the lung transplant, called the bronchiolitis obliterans syndrome (BOS), was staged according to pulmonary function testing. Pathologic proof of bronchiolitis obliterans was obtained. RESULTS: BOS occurred in 14 (35%) of the 40 patients. When considering bronchiectasis preceding BOS, bronchiectasis was a predictor of chronic rejection with a sensitivity of 14%, a specificity of 77%, a positive predictive value of 25%, and a negative predictive value of 63%. Bronchiectasis appeared concomitantly with BOS in eight (67%) of 12 patients. CONCLUSION: The diagnosis of chronic rejection relies on the degree of impairment of pulmonary function. When the diagnosis is only suspected on the basis of minimal impairment, CT can aid in the diagnosis of rejection by depicting early pulmonary changes.

[Cutaneous Kaposi's sarcoma with pulmonary carcinomatous lymphangitis in patient with heart transplantation]. / Sarcome de Kaposi cutané avec lymphangite carcinomateuse pulmonaire chez un transplanté cardiaque.

The great strides in organ transplantation have been accompanied by some specific pathologies, notably, neoplasia, including Kaposi's sarcoma which occupies the third place in frequency after cutaneous tumours and malignant lymphomas. We report a case of cutaneous Kaposi's sarcoma developing some six months after a cardiac transplant. The modulation of immuno-suppression and treatment with Alpha interferon allowed an initial stabilisation of the cutaneous lesions. However, there were secondary developments of the lesions and, 21 months after the initial presentation, the patient developed a diffuse infiltrating pneumonia leading to death. The autopsy revealed lymphangitis carcinomatosis of Kaposi's sarcoma type. This observation underlines the therapeutic difficulties seen in Kaposi's sarcoma after organ transplantation when there is no alternative to allow a significant reduction or cessation of immuno-suppression.

[Anatomoclinical diversity of bronchiolitis obliterans after lung transplantation. Anatomical study of 16 cases among 64 transplantations]. / Diversité anatomo-clinique des bronchiolites oblitérantes après transplantation pulmonaire. Etude anatomique de 16 cas sur 64 transplantations.

The aim of this study was to define the presence, histological types and extent of bronchiolitis obliterans (BO) after lung transplantation and to discuss the place of bronchiolitis obliterans in the progressive obstructive ventilatory disorder observed in some patients and considered to correspond to "chronic lung rejection". The histological lesions were studied in 16 subjects surviving for more than one month after lung transplantation or heart-lung transplantation: 12 autopsies, 3 surgical biopsies and one lung explanted for retransplantation. Thirteen subjects presented lesions of bronchiolitis obliterans: 5 cases of granulomatous BO, 6 cases of proliferative BO, one acute necrotising BO and one tuberculous granulomatous BO. Three of these patients presented an obstructive ventilatory disorder: one death on the 213rd day (acute necrotising BO), one retransplantation on the 672nd day (granulomatous BO), one death 53 days after surgical biopsy on the 247th day (proliferative BO). Two patients undergoing surgical biopsies with lesions of proliferative BO are still alive (cases 15 and 16) and do not present any signs of obstructive ventilatory disorder. This study suggests the existence of various histological types of BO in transplanted lungs, which is not exclusively of immunopathological origin, that infections and various inhalations also play a role and that alterations of pulmonary structures other than bronchioles are also involved in the pathogenesis of the obstructive ventilatory disorder (functional destruction of the transplant), corresponding to "chronic lung rejection".

In vitro HIV-1 entry and replication in Langerhans cells may clarify the HIV-1 genome detection by PCR in epidermis of seropositive patients.

Being dendritic antigen-presenting cells in skin and mucous membrane, Langerhans cells (LC) occur in areas at risk for inoculation by human immunodeficiency virus (HIV), and the question whether LC act as a target, reservoir, or vector for transmission of HIV has given rise to much controversy. To address this question, we first analyzed the epidermal compartment of skin from patients seropositive for HIV DNA. Second, we tested the susceptibility of each cell type normally found in this compartment to in vitro infection by HIV-1. A non-denatured DNA was obtained from epidermal sheets after a thermochemical treatment of biopsies (0.5 M ethylenediaminetetraacetic acid (EDTA), pH 7.5 at 60 degrees C for 90 seconds). Optimization of amplification of viral genome was performed with three primer pairs derived from gag, env, and pol sequences. Polymerase chain reaction (PCR) products were analyzed by Southern blot. Viral genome was found in five of 11 HIV-seropositive patients. To control the permissivity of epidermal cell population for HIV, cells isolated from the epidermal sheet of normal skin by trypsinization were co-cultured with HIV-1-carrying promonocytic cells (U937) and observed by electron microscopy. After 3-6 h of co-culture, numerous virions were either tightly bound or apparently engaged in the process of internalization through receptor-mediated endocytosis. At day 4 of co-culture, some infected LC appeared to release mature viral particles through bud formation. The in vitro HIV-1 entry and replication in LC may confirm the presence of the HIV-1 genome by PCR in epidermis of seropositive patients. The consequences of the permissivity of LC for HIV on the antigen-presenting function remain to be determined.

[Bronchiolitis obliterans with severe obstructive ventilation disorder after a bone marrow transplant. Study of 7 cases]. / Bronchiolite oblitérante avec trouble ventilatoire obstructif sévère après allogreffe de moelle osseuse. Etude de 7 cas.

In 40 to 60% of bone marrow grafts there are pulmonary complications of which the most frequent is the occurrence of an interstitial pneumonia. We report 7 cases here of a more rare complication, that of bronchiolitis obliterans (BO). Between December 1979 and November 1989, 7 patients (3.4% of our cases of GMO) have developed over several months a chronic obstructive respiratory failure (a mean VEMS of 43% of the theoretical value) in the year following the transplantation (mean delay 190 days). 6 patients presented with cutaneous, digestive or hepatic signs of chronic graft v host illness (GVH) whereas the prevalence of this complication in the population studied was 17%. Treatment combining bronchodilators and immunosuppressants was only successful in 2 cases and the outcome was fatal in the 5 other cases as a result of respiratory failure (mean delay 208 days between the appearance of respiratory symptoms and death). The pathogenesis of BO after GMO remains poorly understood. It may rest on an immune process during the course of which the BO would be the result of a chronic pulmonary GVH. Another hypothesis is that the state of the immunosuppression in these patients would favour the appearance of a bronchiolitis of an infectious origin, particularly viral. The prognosis of BO after GMO is very poor and in the absence of specific effective treatment the therapeutic strategy remains essentially that of prevention by the early detection of respiratory anomalies.

[Subpleural air cysts. A complication of barotrauma during mechanical ventilation]. / Les kystes aériens sous-pleuraux. Une complication barotraumatique de la ventilation mécanique.

The presence of air in the interstitial pulmonary tissues is shown as interstitial emphysema and is often the first sign of barotrauma. It results from hyper-pressure in the airways occurring for the greater part of the time on some underlying pulmonary pathology. This extra alveolar air may diffuse into the interstitium and collect under the visceral pleura, appearing on radiographs as air cysts from 3 to 10 centimeters in diameter. We described 7 cases of air cysts occurring in adults on mechanical ventilation. The lesions seem to us to represent a radiological entity and evidence of barotrauma due to mechanical ventilation and possessing its own potential outcome, namely rupture leading to pneumothorax, infection, persistence, or disappearance. The early occurrence in its history of a particular disease should be noted, enabling one to minimise the factors contributing to the barotrauma.

[Pleuro-pulmonary suppurations]. / Suppurations pleuro-pulmonaires.

Lung abscess and empyema are rare in healthy people. They usually occur when such predisposing factors as alcoholism, diabetes mellitus, immunodepression, neurological disorders, previous chest surgery and bronchial stenosis are present. Evacuation of pus and antibiotic therapy form the basis of treatment. Anaerobic bacteria are the most common causative agents, and they are particularly suspected in patients with putrid sputum or pleural fluid. The penicillin-metronidazole combination is used in these anaerobic infections. In every case, a careful search for the responsible organism has to be made in order to choose the best antibiotic.