Biomedical subjects
Publications and source records attributed to M Reynaud-Gaubert.
Ten years after right pneumonectomy for primary lung cancer, a 51 year old man developed a pulmonary artery stump thrombosis which produced microemboli in the remaining lung and, in turn, led to chronic pulmonary hypertension. This case strongly suggests that prolonged postoperative thromboembolic prophylaxis should be considered in patients undergoing right pneumonectomy.
OBJECTIVES: Diagnosis of interstitial lung diseases was recently improved by the use of diagnostic tools, such as high-resolution Computed Tomography, and by new insights in their pathogenesis and histology. This led the American Thoracic Society and the European Respiratory Society to propose a new classification of these diseases, in the aim to facilitate early diagnosis and specific care. CURRENT KNOWLEDGE AND KEY POINTS: Standard radiography gives the first suspicion of chronic diffuse infiltrative lung disease, and anamnesis and physical examination are essential steps of etiological diagnosis. High-Resolution computed tomography confirms the diagnosis of diffuse infiltrative lung disease. Longitudinal lung function tests are essential to assess the consequences of the lung disease. Lung biopsies are often, but not systematically, a useful tool. The 2000 classification consists of seven entities of idiopathic interstitial diseases which are defined on clinical, radiological and pathological criteria: idiopathic pulmonary fibrosis, non-specific interstitial pneumonia, cryptogenic organizing pneumonia, acute interstitial pneumonia, respiratory bronchiolitis associated interstitial lung disease, desquamative interstitial pneumonia and lymphoid interstitial pneumonia. The most frequent is Idiopathic Pulmonary Fibrosis, which has a poor prognosis. FUTURE PROSPECT AND PROJECTS: This new classification results from a multidisciplinary confrontation with chest physicians, radiologists and pathologists. A better characterization of anatomoclinical entities should lead to a better pronostic evaluation, more informative comparisons of published studies, and therefore to rational therapeutic approach.
CURRENT SITUATION: Pulmonary arterial hypertension (PAH) is a serious disease. Its prognostic is based on the functional status quantified by the NYHA class and the 6-min walking test, and the hemodynamic data. The algorithms of treatment are solely based on the hemodynamic data and the functional status. The main objective is to test whether basal concentrations of isoprostanes, Big endotheline 1, ADMA, high sensitivity CRP, NT-Pro-BNP and cardiac troponin T are a 3-year prognostic factor in PAH using a combined criterion: death from any cause and pulmonary or cardiopulmonary transplantation. MATERIALS AND METHODS: This is a multicenter, prospective, prognostic, single blinded study (plasma and urinary samples being blinded). The study started in november 2003, running for 2 years, with a 3 year follow-up for each patient. The main inclusion criterion is PAH. The data analysis will use a multivariable Cox model, taking into account the functional and hemodynamic parameters. EXPECTED RESULTS: This study will determine whether any of the biomarkers tested provides additional prognostic information in PAH in addition to the functional and hemodynamic parameters.
We evaluated the diaphragmatic function of seven patients with severe chronic respiratory failure before and after a bilateral lung transplantation (BLT), with follow-up at one year of pulmonary function tests, maximal inspiratory mouth pressure (MIP) and surface diaphragmatic electromyogram (Edi). The patients were asked to sustain target inspiratory pressures at -15, -30, and -50 cmH(2)O. We measured the endurance time (Tlim) to sustain inspiratory efforts and the power spectrum density function of Edi at each inspiratory maneuver. The Edi power spectra was analysed in terms of median frequency (MF), total power (TP) and energies in high-and low-frequency bands (EL and EH). Before BLT, a defect of the diaphragmatic function was evident: MIP was 62+/-7% of the predicted value and the Tlim measured at each inspiratory effort was very short ( 13+/-1 s, 10+/-1 s and 8+/-1 s at pressures of -15, -30, and -50 cmH(2)O, respectively). One month after BLT, the Tlim began to increase at all target inspiratory pressures and at 6 months MIP recovered to normal values. One month after BLT, there was a significant decrease in TP measured at the beginning of each inspiratory efforts and also an increase in the concomitant MF value. BLT markedly accentuated the maximal variations of TP, MF and low-frequency Edi energy. Some hypotheses are raised to explain this dramatic improvement in diaphragmatic function after BLT.
Sputum examination is being increasingly used as a non-invasive method for the study of airway inflammation. However, the technical applications of sputum are still limited because of the small number of cells recovered. In attempt to extend applications of sputum examinations, we developed and standardised, the reverse transcriptase-polymerase chain reaction (RT-PCR), a sensitive and specific technique of detection of mRNA, in induced sputum samples. Total RNA were extracted from samples containing as few as 50 to 80,000 cells, using a phenol-chloroform extraction method. RT-PCR was successfully tested on beta-actin, interferon-gamma (IFN-gamma), interleukin-4 (IL-4) and tumour necrosis factor-beta (TGF-beta) genes. This protocol provides a simple technique to extract total RNA from a few number of induced sputum cells. It permits the semi-quantitatively study of cytokine gene expression in airways with simple means.
This study investigated interstitial pneumonia associated with amyopathic dermatomyositis, dermatomyositis and polymyositis, paying particular attention to muscular and/or cutaneous manifestations and their chronology relative to lung involvement. Patients included four males and 13 females, aged 51.7+/-10.8 yrs, who had surgical lung biopsy. Diagnoses included dermatomyositis (10 patients), polymyositis (four patients) and amyopathic dermatomyositis (three patients). Solitary respiratory manifestations preceded the onset of any skin or muscle disease in four cases (24%). Reticular and ground glass opacities were the most frequent computed tomography (CT) findings. Pathological review showed nonspecific interstitial pneumonia (eleven, 65%; cellular, two; cellular and fibrotic, five; fibrotic, four), usual interstitial pneumonia (two), organising pneumonia (two), lymphocytic interstitial pneumonia (one), and unclassifiable interstitial pneumonia (one). Nonspecific interstitial pneumonia was the most common histological pattern of interstitial pneumonia in patients with amyopathic dermatomyositis (three of three) and in patients with respiratory symptoms as the initial clinical manifestation of the connective tissue disease (three of four). Survival at 5 yrs was 50%. This study shows the clinician should remain alert to potential muscular or cutaneous manifestations whenever a pathological diagnosis of nonspecific interstitial pneumonia is made.
INTRODUCTION: The major obstacle to long-term survival after lung transplantation is chronic graft rejection (CR) which is defined histologically by obliterative bronchiolitis (OB). STATE OF THE ART: The causes of post-transplant OB are not fully understood, but there is evidence that this chronic process is influenced by both immunologically mediated injury directed against endothelial and specifically epithelial cells, and alloantigen-independent events, such as cytomegalovirus infection, ischaemic-reperfusion injury and biophysical alterations. The generation of an allogenic immune response seems to be the central event involved in the subsequent development of OB, and prior acute rejection is the strongest risk factor for CR. Whatever the role of each of the factors, injury to the bronchiolar structure is the primary event which triggers an invasion of various inflammatory cells and an increase in pro-inflammatory and chemotactic mediators within the bronchiolar wall. As the process evolves, an uncontrolled repair process, with sub-mucosal fibrous tissue proliferation leading to obstructive airway scarring involving mesenchymal cell and fibroblast replication, and connective-tissue deposition in response to profibrotic cytokines and growth factors released by local tissue. We review here the risk factors and the mechanisms, which are currently recognized in the development of OB. PERSPECTIVES AND CONCLUSIONS: A better understanding of the pathogenesis of CR by combining several techniques should allow detection of OB at a preclinical stage and may ultimately lead to novel preventive and therapeutic strategies for the condition.
Isolated absence of a pulmonary artery is an exceptional cause of massive hemoptysis. We report a 35-year-old woman with agenesis of the left pulmonary artery who presented with exsanguinating hemoptysis that prompted angiography with the aim to embolize the bleeding vessels selectively. The procedure could not be completed because of the presence of an anterior spinal artery branching from the aberrant systemic-to-pulmonary circulation. The patient successfully underwent an emergent pneumonectomy.
We report a case of acute accidental cyclosporine A intoxication in a lung transplant patient. The intoxication led to renal failure due to acute tubular necrosis, which was partially reversible. A review of the literature on the renal consequences of cyclosporine A intoxication is given.
Post-transplant lymphoproliferative disease is a complication of bone marrow and solid organ transplantation, mostly associated with Epstein-Barr virus infection and chronic immunosuppression. Even if spontaneous resolution after cessation of immunosuppressive therapy can be observed, the prognosis of this disorder is usually poor with a low response to specific treatment. We describe a case of B-cell lymphoma of the nasopharynx occurring 6 months after double-lung transplantation. In spite of its monoclonal nature, anti-CD 20 monoclonal antibody given in the presence of reduced immunosuppression resulted in a complete response. The patient also received "consolidation" radiation therapy to prevent the recurrence. The treatment was well tolerated with minimal side effects. The patient was asymptomatic and had a well functioning graft more than 1 year after therapy.
As defined by the International Society for Heart and Lung Transplantation, the diagnosis of posttransplant obliterative bronchiolitis (OB) is based on histopathologic features and/or spirometric staging criteria, using FEV(1) to determine the extent of disease. However, this last parameter reflects an advanced bronchiolar process. The present study investigated whether physiologic parameters reflecting smaller airways dysfunction on one hand, and neutrophils in bronchoalveolar lavage fluid (BALF) on the other hand, could be useful for the earlier detection of bronchiolitis obliterans syndrome (BOS). We analyzed data obtained both from 765 pulmonary function test results and from 467 BALF specimens from 45 patients who survived at least 1 yr after surgery (n = 47, including two retransplantations). Of the transplant procedures, 22 were associated with BOS and 25 were not. The mean delay from transplantation to the diagnosis of BOS was 578 d (range: 122 to 2,619 d). The threshold values of the following parameters were studied: decline in the forced expiratory flow rate at 25% to 75% of FVC (FEF(25-75)) to </= 70% of the predicted value and of baseline values, increase in the slope of the nitrogen washout curve (DeltaN(2)) > 3%, and alveolar neutrophilia >/= 20% of the total BALF cell count. Agreement on the diagnosis of BOS (using the decline in FEV(1)) was equally good for each of the four markers (kappa coefficient > 0.65, p < 10(-)(5)). In the OB group, mean delays after the threshold was reached for each of these parameters were 110 d (p = 0.09), 173 d (p = 0.03), 150 d (p = 0.003), and 131 d (p = 0.1), respectively, before the FEV(1) criteria were fulfilled. At the chosen threshold values, the decline in FEF(25-75), increase in DeltaN(2), and development of a substantial alveolar neutrophilia all occurred significantly before a decline in FEV(1) in posttransplant OB.
Lung transplantation (LT) became during the ten past years an important therapeutic option for cystic fibrosis adult patients with end-stage chronic lung disease. LT clearly improves both survival and long term quality of life. A rigorous selection of the candidates is of paramount importance to improve the results of LT because of the lack of shortage of organs. This selection requires a multidisciplinary assessment to refuse patients with absolute exclusion criteria or general medical conditions that impact negatively on short- and long-term outcome. One of the major difficulties is to determine the best time to refer patients to transplantation, arguing the comparison between the predicted survival time of the candidate, under optimal medical therapy, with or without LT. The selection period is also an active process to prepare the patients to the postoperative follow-up and includes a nutritional and rehabilitation program with an educational and psychological preparation. The aim of the present work is to gather the worldwide principles of the selection of the CF patients for LT, commonly used by the LT centers. These recommendations should provide the CF center practitioners with the main elements to prepare their patients to an LT project before a relentless end-stage clinical condition.
We report three cases of bronchial mucoepidermoid carcinoma (BMEC) of low-grade malignancy with a relafase-free follow up. BMEC are rare tumors. The microscopic findings distinguish low-grade tumors which occur in children and young adults and high-grade tumors concerning older patients; this grading is based on the study of the epidermoid component. If possible, conservative therapy is appropriate in low-grade tumors. The prognosis of high-grade tumors is poor.
OBJECTIVE: The purpose of this study was to evaluate the risk of lung cancer surgery, following induction chemo and/or radiotherapy. METHODS: This retrospective study included 69 patients treated from January 1990 to January 1998 for a primary lung cancer in whom surgery had been performed after induction treatment. Surgery had not been considered initially for the following reasons: N2 disease (IIIA; n = 25), temporary functional impairment (2 stages IB and 2 stages IIIA [N2]; n = 4); doubtful resectability (stage IIIB [T4]; n = 40). The medical regimen resulted in combined radio-chemotherapy in 43 patients who received 2 to 4 cycles of chemotherapy (average = 2.9 +/- 0.8 cycles) and 43 +/- 8 Gy (20 to 60 Gy), or chemotherapy alone in 26 patients (3 +/- 0.7 cycles). RESULTS: Exploratory thoracotomy was performed in 4 patients (6%). The in-hospital mortality was 9% (n = 6) from respiratory origin in all cases. There were 4 reoperations (6%): 3 for bronchial fistula and 1 for bleeding. Thirty five patients (51%) required blood transfusion (4.5 +/- 3.8 cell packs). The incidence of early and delayed bronchial fistula after pneumonectomy was 15%. Thirteen patients had a postoperative pneumonia (19%). CONCLUSION: Surgery for lung cancer after induction chemo and/or radiotherapy is associated with an increased risk. While the mortality seems "acceptable", the morbidity rate however is high.
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INTRODUCTION: Lung cancer is the first cause of cancer mortality in male patients in France. Treatment varies depending on the histological type and the disease extent at diagnosis. CURRENT KNOWLEDGE AND KEY POINTS: Videothoracoscopic staging appears to be an accurate method to assess the stage of lung cancer to guide rational management as it allows for 1) an accurate tissue diagnosis when standard methods failed, 2) the identification of a parietal or mediastinal invasion when suspected by CT-scan findings, 3) lymph node sampling of sites that are poorly or not reachable with mediastinoscopy, 4) the diagnosis of pleural or pericardial metastases in patients with effusion or indeterminate nodules, and finally 5) the conclusive answer to the diagnostic dilemma caused by the presence of a contralateral pulmonary nodule in patients with a potentially curable tumor. FUTURE PROSPECTS AND PROJECTS: Video-assisted thoracoscopy thus appears to have a complementary role in intrathoracic lung cancer staging when conventional methods are equivocal. Its main side-advantage is the opportunity to proceed without delay to the surgical treatment, when appropriate, in the same operative settings, or to perform in the same session various procedures, i.e., talc poudrage and pericardial window, to palliate adverse symptoms occurring in some of those patients. Obviously, equally efficient and less invasive approaches should have been considered previously. To date, however, videothoracoscopic evaluation of tumor resectability is not achievable. Finally, one may suppose that positron emission tomography will probably reduce the role of those invasive surgical procedures in a near future.
Multiple pulmonary arteriovenous malformations (PAVM) constitute an uncommon cause of respiratory disability. They may lead to severe hypoxaemia via right-to-left shunts and are sources of substantial mortality and morbidity. Conservative surgical resection has been proposed as the treatment of choice. More recently, percutaneous balloon or coil embolization of the feeding vessels offered an efficacious and safe alternative therapy for patients whose fistulas are too numerous to excise. This study reports an unusual case of respiratory disability in a patient with multiple and microscopic pulmonary arteriovenous malformations who failed to respond to embolotherapy and who received a double lung transplantation with good initial outcome.
Respiratory disease is the major cause of morbidity and mortality in cystic fibrosis. Cystic fibrosis was long treated in the pediatric setting, but improved survival has led to the implication of adult pneumology in therapeutic management. Since the gene causing cystic fibrosis has been clone, our knowledge of the pathophysiology of the disease has literally exploded, particularly concerning the deleterious consequences of defective expression and distribution of CFTR (cystic fibrosis transmembrane conductance regulator) protein in chronic lung inflammation and infection. This knowledge has led to an optimization of existing therapeutic strategies and to the formulation of hypotheses for the development of new pharmaceutical reagents, allowing an assessment of disease outcome not only in terms of survival but also in terms of quality of life. Early in vivo clinical trials have been encouraging although the efficacy of gene transfer and expression remain modest and the optimal vector remains to be determined. Different potential pharmacological approaches are being studied in order to correct for defective CFTR function at different levels of gene mutation, and to modulate the disorder in transepithelial ionic transfer. One could expect in the near future to see combinations of complementary genotype-specific drugs used for the treatment of cystic fibrosis after patient genotyping to categorize the type of mutation.