Real-time and non-invasive acute lung rejection diagnosis using confocal LASER Endomicroscopy in lung transplant recipients: Results from the CELTICS study.

BACKGROUND AND OBJECTIVE: Traditionally, the diagnosis of acute rejection (AR) relies on invasive transbronchial biopsies (TBBs) to obtain histopathological samples. We aimed to evaluate the diagnostic yield of probe-based confocal laser endomicroscopy (pCLE) as a complementary and non-invasive tool for ACR screening, comparing its results with those obtained from TBBs. METHODS: Between January 2015 and April 2022, we conducted a retrospective study of all lung transplant recipients aged over 18 years at Toulouse University Hospital (France). All patients who underwent bronchoscopies with both TBBs and pCLE imaging were included. Two experienced interpreters (TV and MS) reviewed the pCLE images independently, blinded to all clinical information and pathology results. RESULTS: From 120 procedures in 85 patients, 34 abnormal histological samples were identified. Probe-based confocal laser endomicroscopy revealed significant associations between both alveolar (ALC) and perivascular (PVC) cellularities and abnormal histological samples (p<0.0001 and 0.003 respectively). Alveolar cellularity demonstrated a sensitivity (Se) of 85.3 %, specificity (Spe) of 43 %, positive predictive value (PPV) of 37.2 % and negative predictive value (NPV) of 88.1 %. For PVC, Se was 70.6 %, Spe 80.2 %, PPV 58.5 % and NPV 87.3 %. Intra-interpreter correlation (TV) was 88.3 % for the number of vessels (+/-1), 98.3 % for ALC and 90 % for PVC. Inter-interpreter correlation (TV and MS) was 80 % for vessels (+/-1), 97.5 % for ALC and 83.3 % for PVC. CONCLUSION: Our study demonstrates the feasibility of incorporating pCLE into clinical practice, demonstrating good diagnostic yield and reproducible outcomes in the screening of AR in lung transplant recipients.

[Bronchial thermoplasty for severe asthma]. / Place de thermoplastie bronchique dans la prise en charge de l'asthme sévère.

Bronchial thermoplasty has been developed over the past fifteen years and is the first endoscopic technique approved in the management of severe asthma. This procedure uses radiofrequency applied to the airway wall to target bronchial smooth muscle. Patients treated in randomized controlled trials have experienced significant decreases in the use of rescue medications, urgent care visits, and exacerbations rate. The lack of reliable predictive markers of response to this expensive, minimally-invasive technique currently makes it a last-line treatment option. We review the principles and supposed mechanisms of action of this treatment, the results from the main trials and clinical registry data and discuss the place of bronchial thermoplasty in the current management of severe asthma. We also discuss perspectives to better characterize the mechanisms of action and identify the responder phenotype, the main challenge of current studies.

Diagnostic of mediastinal lymphadenopathy in extrathoracic cancer: A place for EBUS-TBNA in real life practice?

INTRODUCTION: Mediastinal lymphadenopathy in patients with extrathoracic malignancy is common. To obtain tissue proof of metastatic spread, EBUS-TBNA is an alternative to mediastinoscopy or thoracoscopy, but there are limited data about its diagnostic performance. The aim of this study was to determine the diagnostic accuracy of EBUS-TBNA for the evaluation of mediastinal lymphadenopathy in patients with extrathoracic cancers. METHODS: We performed a multicenter retrospective study based on an online questionnaire to collect data from January 2011 to December 2012 in all patients with proven extrathoracic malignancy (current or past) and suspected mediastinal lymph node metastases who underwent EBUS-TBNA for diagnosis. RESULTS: Hundred and eighty-five patients were included. Extrathoracic malignancies observed were urological (43), breast (35), gastrointestinal (33), head and neck (30), melanoma (11), lymphoma (6), and others (27). EBUS-TBNA confirmed malignancy in 93 patients (50.3%): concordant metastases in 67 (36.2%); new lung cancer in 25 (13.5%); and 1 unidentified cancer. The diagnostic accuracy, sensitivity, specificity, negative predictive value, and positive predictive value were respectively 54.6%, 68.4%, 100%, 53.3%, and 100%. CONCLUSION: Mediastinoscopy remain the reference, but EBUS-TBNA may be considered as first line investigation in patients with suspected mediastinal lymph node metastases and extrathoracic malignancy. It prevented a surgical procedure in 50.3% of patients.

[Diagnostic flexible bronchoscopy. Recommendations of the Endoscopy Working Group of the French Society of Pulmonary Medicine]. / Les bonnes pratiques de la bronchoscopie souple diagnostique, en 2007.

These guidelines on flexible bronchoscopy depict important clues to be known and taken into account while practicing flexible bronchoscopy, in adult, except in emergency situations. This is a practical clarification. Safety conditions, complications, anesthesia, infectious risks, cleaning and disinfection are detailed from a review of the literature. Intensive care practice of bronchoscopy requires more attention due to higher risks patients and is discussed extensively. Standards and performances of the various sampling techniques complete this work. Indications for bronchoscopy, therapeutic and paediatric bronchoscopy are not covered in these guidelines.

[Use of endobronchial ultrasound in the management of cryptogenic haemoptysis]. / Apport de l'échoendoscopie radiaire dans la prise en charge de l'hémoptysie cryptogénique.

Currently about 50% of cases of haemoptysis are thought to be cryptogenic. Haemorrhage from the pulmonary arterial system is rare and usually due to aneurysms or pseudoaneurysms, the radiological diagnosis of which is often difficult. We report here the case of a patient admitted with a heavy haemoptysis in whom the thoracic CT scan did not reveal the diagnosis. Bronchoscopy with endobronchial ultrasound showed a vascular malformation of a branch of the pulmonary artery allowing a radiological embolisation. This case underlines the importance of bronchoscopy and the role of ultrasound in the diagnosis of haemoptysis, considered ideopathic, complicating vascular malformations.

Surfactant analysis during Pneumocystis carinii pneumonia in HIV-infected patients.

Pulmonary surfactant is altered in experimental Pneumocystis carinii pneumonia. Although P carinii is a major causative agent of pneumonia in immunocompromised patients, the pathophysiology of lung injury caused by this organism is poorly understood. Therefore, we studied bronchoalveolar lavage specimens obtained from 19 HIV-infected subjects with PCP compared with specimens from ten healthy control subjects. As iterative BAL was performed, 37 BAL specimens were analyzed for protein and phospholipid. The BAL samples were divided into two groups as follows: 22 BAL samples with the presence of P carinii and 15 BAL samples without P carinii. Compared to control subjects, HIV+ BAL presented a significant increase of PR and a decrease of total PL in both P carinii+ and P carinii- BAL, but in P carinii+ BAL, the fall of PL/PR ratio was significantly more pronounced compared to P carinii- (0.09 +/- 0.02 vs 0.19 +/- 0.04, p less than 0.02). The BAL performed during the recovery of PCP showed an improvement of initial biochemical abnormalities. Surfactant composition was also altered, with a phosphatidylcholine and phosphatidylglycerol drop and a sphingomyelin and lysophosphatidylcholine increase. The presence, even in P carinii- BAL, of less polar compounds of undetermined nature, was revealed. We concluded that in HIV+ patients, abnormalities of pulmonary surfactant were present before PCP, and that the development of PCP enhances these abnormalities. These surfactant alterations may contribute to the saprophyte-pathogen transformation of P carinii, but this hypothesis requires further investigation that is presently in progress.

[Intra-vascular lymphoma presenting with respiratory symptoms]. / Lymphome intravasculaire à présentation pulmonaire.

INTRODUCTION: Intra-vascular large cell lymphoma is a rare disease characterised by the proliferation of malignant cells within small blood vessels. CASE REPORT: We report a case of intra-vascular lymphoma presenting with unexplained dyspnoea, hypoxaemia and associated neurological symptom. The diagnosis was made by liver biopsy but the patient ultimately died. CONCLUSIONS: Earlier diagnosis with transbronchial biopsy might have improved the prognosis by allowing more prompt treatment.

[Disseminated aspergillosis with pulmonary and cardiac localization in an HIV-infected patient]. / Aspergillose disséminée avec localisations pulmonaires et cardiaques chez un sujet infecté par le VIH.

The authors report a case of invasive aspergillosis with pulmonary and cardiac involvement revealed by a pericarditis in a seropositive patient (VIH1). Clinical findings, differential diagnosis and outcome underly the issues encountered in the management of aspergillosis in AIDS patients. Indeed, the low prevalence of aspergillosis in AIDS and the insidious features of aspergillosis locations make the early diagnosis difficult. It is though essential for a favourable outcome under specific treatment. The risk factors, clinical characteristics and diagnostic procedures are mentioned as well as the various available treatments.

[Acquired right-to-left shunt with normal right heart pressure]. / Shunts intra-cardiaques droits-gauches acquis à pressions cardiaques droites normales.

Intracardiac right-to-left shunting through a patent ovale foramen (POF) despite normal right-sided pressures is an uncommon cause of dyspnea with posture worsening in adults. We report herein 6 cases which sum up etiological circumstances, diagnostic workup and management of this syndrome. The main reported etiopathologic mechanism is consistent with a change in the internal configuration of the right atria leading to preferential blood flow from inferior vena cava through patent foramen ovale. The treatment lies on surgical closure of the septal defect, which can now be performed using a noninvasive percutaneous procedure.

[Respiratory function in heroin addicts with or without HIV infection. Study of 107 cases with a 6-month follow-up of 36 subjects]. / La fonction respiratoire chez l'héroïnomane avec et sans infection par le VIH. Etude de 107 cas avec un suivi à 6 mois chez 36 sujets.

Both intravenous drug addiction (IVDA) and HIV infection can involve respiratory system. So, we have studied pulmonary function in 107 heroin abusers during deprivation to clarify the extent of these two factors respectively. Two groups were separated: 50 subjects without HIV infection (HIV-) and 57 seropositive subjects (HIV+) in early stage of the disease (mean CD4 lymphocytes: 457 +/- 61/mm3). 36 subjects have been investigated 6 months later to evaluate the reversibility of possible observed abnormalities. Altered pulmonary function was encountered similarly in HIV+ and HIV-. DLco was abnormal in 40% of cases both in HIV+ (mean DLco: 63.4 +/- 1.1% of predicted values) and HIV- (mean DLco: 65.4 +/- 1.5% pred); obstructive lung disease was present in 18% of HIV- (FEV1/VC: 63.8 +/- 2.5) and 9% of HIV+ (FEV1/VC: 61 +/- 3.6); restrictive lung disease was found more frequently (16% vs 10%) in HIV+ (FEV1/VC: 81.2 +/- 2.1, TLC: 72.4 +/- 3.6% pred) than in HIV- (FEV1/VC: 84.2 +/- 1.6, TLC: 71.2 +/- 0.9% pred). These abnormalities were not associated with significant arterial blood gas modifications. As a whole, DLco tend to improve in the two groups and this significantly for HIV+ (p less than 0.03). But for individuals initial DLco alteration was persistent in 68% of cases suggesting slow improvement. In conclusion, in this study HIV+ and HIV- IVDA were not different concerning pulmonary function. In this risk group, DLco itself had a poor specificity and only it follow-up may be of interest for pulmonary opportunistic infection screening.

[Digital angiography. 1st evaluation of 1000 tests]. / Angiographie numérique. Premier bilan de 1 000 examens.

The authors report their experience of 1 000 examinations using digital subtraction angiography. The technique is particularly well suited to the study of the thoraco-abdominal aorta and its main branches. It is about 80% reliable for the exploration of cervico-encephalic vessels and somewhat less reliable for the vertebro-basilar territory. It is usually convenient for the study of the renal arteries: investigations for reno-vascular hypertension can now be carried out in one session beginning with angiography and ending with urography. Digital subtraction angiography is also very useful in the assessment of vascular surgery, whatever the area involved or the type of operation, and for the study of pulmonary vessels, notably when looking for pulmonary emboli. Digital subtraction arteriography is undoubtedly superior to conventional arteriography. Its impact remains to be determined, but is avoids the drawbacks of the venous route. Its present limitations are of a technical nature: the intensifying screen is too small so that the examination must proceed by segments, hence the need for repeated doses of contrast medium the dangers of which must be borne in mind when digital subtraction angiography is contemplated. On the other hand, this technique has obvious economical advantages: examinations can be performed in out-patients and substantial savings can be made on the number of films.

[Pulmonary artery hypertension in HIV seropositive drug addicts. Apropos of 10 cases]. / Hypertension artérielle pulmonaire chez le toxicomane VIH+. A propos de 10 cas.

Pulmonary hypertension (PH) is a classic complication associated with intravenous drug addiction. Various pathogenic mechanisms may be involved but HIV infection now appears to be the main etiologic factor. We report herein 10 case of PH occurred in HIV+ intravenous drug abusers. Each patient had several pathogenic factors: HIV infection, pills crushed and intravenously injected (6 cases), heavy and repeated consumption of amphetamines and cocaine (6 cases), cirrhosis with portal hypertension (2 cases), anticardiolipid antibodies (2 cases). The clinical findings were similar to those reported for PH in HIV seronegative patients; however, in 5 cases, opiates could have alleviated dyspnea, which became perceptible only at the time of drug withdrawal. Because drug addicts usually exhibit a weak support for medical prescriptions, long term therapy needing regular follow-up such as anticoagulation appears to be hazardous and even dangerous. The prognosis remains poor, since the progression of PH led to the death of one third patients within the year following the diagnosis.

[Pulmonary hypertension in patient with beta-thalassemia major]. / Hypertension artérielle pulmonaire chez un patient porteur d'une bêta-thalassémie majeure.

We report a case of pulmonary hypertension (PH) in a 35-year old patient with beta-thalassemia major; he had commenced blood transfusions after the age of 4 years and had been splenectomised at the age of 6 years. PH clinical presentation was not uncommon. Hemodynamic study revealed precapillary PH with high cardiac output; vasodilators agents led to significant pulmonary responsiveness. In beta-thalassemia, whereas congestive heart failure is common and due to cardiac hemosiderin deposition, PH appears to be non rare but its etiopathogenic mechanism remain unclear and probably non univoqual. Hypoxemia as well as hemodynamic changes related to chronic anemia including increased pulmonary flow might play an important role. Management should include blood transfusions to correct anemia, the indication and the choice of vasodilator agents need to be evaluated.

[Pulmonary embolism in patients using estrogen-progestagen contraceptives]. / Embolies pulmonaires sous contraception estro-progestative.

OBJECTIVES: The risk of thromboembolism in patients taking estrogen-progestagen oral contraceptive drugs has apparently increased since the introduction of third-generation progestagens (desogestrel, gestodene). We examined the clinical features, risk factors and outcome of pulmonary embolism in this context. PATIENTS AND METHODS: We reviewed 11 cases of thromboembolism in patients on oral contraception and hospitalized in emergency situations in 1995 and 1996 for pulmonary embolism in order to determine the gravity of the thromboembolic event, risk factors and type of drug used. RESULTS: Early clinical signs had preceded the onset of embolism by 2 to 164 days. PaO2 was below 70 mmHg in 4 patients. Diagnosis was achieved with pulmonary scintigraphy (11 cases), spiral CT (3 cases) and angiopneumography (2 cases). Duplex Doppler visualized the phlebitis in 7 patients. Given heparin (with fibrinolysis in 3 cases) then anti-vitamin K, and after withdrawal of the oral contraceptive, outcome was favorable in all cases. There were no recurrences. The nature of the oral contraceptive varied. Five patients were taking third-generation progestagens. In two cases, embolism had occurred following a change from a second-generation to a third-generation progestagen. Family history of phlebitis and/or abnormal laboratory findings were observed in 6 patients: resistance to activated protein C (2 patients), protein C deficiency (2 patients), anticardiolipin (2 patients) and low-titre antinuclear antibodies (2 patients). CONCLUSION: Pulmonary embolism in patients on oral contraceptives persists despite changes in the hormone content of the drugs. Diagnosis is often delayed. Family history of thrombosis or biological risk factors are often found.

[Cardiac tolerance of a beta 2-sympathomimetic spray in 37 asthmatic adults monitored by Holter recording]. / Tolérance cardiaque d'un bêta 2-sympathomimétique en spray chez 37 adultes asthmatiques suivis par enregistrement Holter.

Thirty-seven asthmatic adults (27 women, 10 men), aged 28 to 70 yrs (mean 50. yrs), in a stable condition, were studied to assess the cardiac tolerance of B2SM sprays. These patients had no cardiac arrhythmia (checked by echocardiography), no hypertension and no hyperthyroidism. Two thirds had severe asthma, and 16 suffered from chronic asthma. After their condition was stabilized, they continued their previous treatment, consisting of theophylline (34 cases), moderate corticotherapy (19 cases), atropine spray (14 cases). Holter monitoring was performed before and 3 days after the institution of treatment by Fenoterol spray at 1,600 micrograms per day in 4 doses at fixed times. Gasometry was tested immediately before and during the protocol. Before B2SM treatment, 26 patients had a normal Holter, 11 had an abnormal first recording (4 important atrial ectopic beats (EBs), 5 ventricular EBs, 1 associating the two), 1 patient had an episode of ventricular tachycardia (VT). With Fenoterol, we observed (with no clinical manifestation) the aggravation of 1 pre-existing atrial EBs and 2 ventricular EBs. Two patients had a short episode of tachycardia but the role of Fenoterol was uncertain: one case was an elderly hypoxaemic patient and in the second a high theophylline level (20 mg/l) was found. The arrhythmogenic property peculiar to B2SM in spray form seems low at the dose we used. However in this study and in certain circumstances, such as hypoxemia, metabolic acidosis, or theophylline overload, the use B2SM may have contributed, together with other factors, to induce disquieting infraclinical cardiac dysrhythmia. We stress that this short-term study involved stable asthmatic patients under surveillance in hospital conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

[An unusual mediastinal mass]. / Une masse médiastinale atypique.

INTRODUCTION: Primary mediastinal tumors are rare diseases including a broad spectrum of pathologies ranging from the well-known, such as lymphoma, thymoma or germ-line tumors to some very unusual presentations. CASE REPORT: We describe a solitary mediastinal mass compressing the bronchial and vascular system in a patient suffering from chronic dyspnea. Diagnosis, obtained by means of a CT-guided biopsy, was a melanoma without any sign of a primary cutaneous lesion which harbored the BRAF V600E mutation. CONCLUSIONS: An exclusive mediastinal presentation of a malignant melanoma is exceptional and, in the context of BRAF mutation needs to be considered and diagnosed given the potential therapeutic impact.

[An analysis of treatment delays of thoracic cancers: a prospective study]. / Analyse des délais de prise en charge des cancers thoraciques: étude prospective.

INTRODUCTION: Lung cancer is the main cause of cancer death in France. The diagnosis is often late and the delay between the onset of symptoms and management is considered an aggravating factor. MATERIAL AND METHODS: Our prospective study collected the dates of the start of management of 139 consecutive patients receiving first line treatment for thoracic cancer in our hospital between November 2008 and May 2009. The aim of this study was to evaluate the delays in medical or surgical treatments in patients with thoracic cancer and to determine the cause of these delays. RESULTS: The median delay between the first abnormal chest X-ray and treatment was 9.6 weeks. The delays were significantly shorter in the late stages and in small cell cancer (P=0.001). There was a tendency for shorter delays in women and for longer delays in older patients. CONCLUSION: Evaluation of the delays in treatment, particularly in the early stages, is part of the quality control of management of these diseases.

[Incidence and characteristics of bronchial colonisation in patient with lung cancer: a retrospective study of 388 cases]. / Incidence et caractéristiques des colonisations des voies respiratoires lors du diagnostic de cancer bronchique: étude rétrospective de 388 cas.

INTRODUCTION: Bronchial colonisation is frequently reported in patients with lung cancer. These colonisations could influence patient therapeutic management and prognosis. The aim of our study is refine incidence and nature of bronchial colonisations in patients presenting with lung cancer. METHODS: Three hundred and eighty-eight patients with lung cancer underwent a flexible bronchoscopy at the time of diagnosis. Among them, 216 patients had a bacteriological, mycobacteriological and fungal investigation. Type and frequency of these colonisations were analyzed. RESULTS: Potential pathogens were found in 39.8% of samples, including mainly 39.8% of Gram-negative bacilli (Haemophilus influenzae, Enterobacter sp., Escherichia coli). In addition, we found 0.9% of mycobacteria and 13.9% of Candida albicans. Among these 216 patients where microbiological analysis was performed, patient features and tumor stage were not significantly correlated to microbial colonisation. CONCLUSIONS: Colonisation of airways is frequently reported when a lung cancer is diagnosed. Our data suggest that bronchial colonisation should be prospectively collected due to its potential interest in the management of lung cancer patients.

The Idefix enhancer-blocking insulator also harbors barrier activity.

Chromatin insulators are cis-regulatory sequences participating in the regulation of gene expression. Their presence within the genome is associated with two main functions. One of them is an enhancer-blocking function that blocks enhancer-promoter communication when the insulator is located in between. The second is a boundary or barrier function that insulates independent units of transcription. This latter is observed when two insulators flanking a gene and its regulatory sequences block the regulatory influences of surrounding chromatin. Some years ago, we reported the presence of an insulator within the retrotransposon Idefix from Drosophila melanogaster. This insulator displays an enhancer-blocking activity toward an enhancer located within a second retrotransposon called ZAM. Here, we show that this insulator is not specific to the ZAM enhancer but has the capacity to interfere in the communication established between a broad range of cis-regulatory enhancer and a promoter. Furthermore, we show that, if it is placed on both sides of a transgene, this insulator acts as a barrier able to isolate the transgene from its repressive or enhancing environment. Thus, the Idefix insulator carries both an enhancer-blocking and a barrier activity. According to these properties, the Idefix insulator might prove to be a useful tool to isolate artificial transgenes from positive or negative influences from their integration sites.