Nebulised liposomal amphotericin-B as maintenance therapy in allergic bronchopulmonary aspergillosis: a randomised, multicentre trial.

BACKGROUND: In allergic bronchopulmonary aspergillosis (ABPA), prolonged nebulised antifungal treatment may be a strategy for maintaining remission. METHODS: We performed a randomised, single-blind, clinical trial in 30 centres. Patients with controlled ABPA after 4-month attack treatment (corticosteroids and itraconazole) were randomly assigned to nebulised liposomal amphotericin-B or placebo for 6 months. The primary outcome was occurrence of a first severe clinical exacerbation within 24 months following randomisation. Secondary outcomes included the median time to first severe clinical exacerbation, number of severe clinical exacerbations per patient, ABPA-related biological parameters. RESULTS: Among 174 enrolled patients with ABPA from March 2015 through July 2017, 139 were controlled after 4-month attack treatment and were randomised. The primary outcome occurred in 33 (50.8%) out of 65 patients in the nebulised liposomal amphotericin-B group and 38 (51.3%) out of 74 in the placebo group (absolute difference -0.6%, 95% CI -16.8- +15.6%; OR 0.98, 95% CI 0.50-1.90; p=0.95). The median (interquartile range) time to first severe clinical exacerbation was longer in the liposomal amphotericin-B group: 337 days (168-476 days) versus 177 days (64-288 days). At the end of maintenance therapy, total immunoglobulin-E and Aspergillus precipitins were significantly decreased in the nebulised liposomal amphotericin-B group. CONCLUSIONS: In ABPA, maintenance therapy using nebulised liposomal amphotericin-B did not reduce the risk of severe clinical exacerbation. The presence of some positive secondary outcomes creates clinical equipoise for further research.

[Guidelines from the cancer (CC-AFU) and infection disease (CI-AFU) committees of the French Association of Urology for the management of adverse events and complications of BCG]. / Recommandations des Comités de cancérologie (CC-AFU) et d'infectiologie (CI-AFU) de l'Association française d'urologie pour la prise en charge effets indésirables et complications du BCG.

INTRODUCTION: Intravesical instillations of BCG are recommended for the treatment of high-risk non-muscle-invasive bladder cancer. However, their prolonged use remains limited by the associated potentially serious adverse effects or complications. The purpose of this article was to provide updated recommendations for the diagnosis and management of adverse events (AEs) or complications of intravesical BCG instillations. MATERIALS AND METHODS: Review of the literature in Medline (http://www.ncbi.nlm.nih.gov) and Embase (http://www.embase.com) using the following MeSH keywords or a combination of these keywords: "bladder," "BCG," "complication," "toxicity," "adverse events," "prevention," and "treatment". RESULTS: AEs or complications of BCG included genitourinary and systemic symptoms. The most common complications (cystitis, moderate fever) should be treated symptomatically and may require adjustment to allow patients to have the most complete BCG treatment possible. Serious complications are rare but must be identified promptly because of the life-threatening nature of the disease. Their management is based on the combination of anti-tuberculosis treatments, anti-inflammatory drugs and the definitive discontinuation of BCG. CONCLUSION: The management of BCG AEs requires early identification, rational and effective treatment if necessary, and discussion of the continuation of treatment for each situation.

Factors associated with delayed screening of contacts of tuberculosis cases in the Somme, France.

AIM: To analyze the factors associated with the time to initiating tuberculosis contact investigations in the Somme department, France. METHODS: All reported tuberculosis cases and all their contacts screened between 2007 and 2011 were retrospectively included. Univariate and multivariate analyses were conducted to determine the factors associated with a "system delay"≤1 month and a "contact delay"≤0 days. RESULTS: The mean time between the mandatory notification of a case of tuberculosis and the date set for the contact's screening (system delay) was 35.3 days and the average time between that date and when the contact was actually screened (contact delay) was 12.5 days. In multivariate analysis, a smear-positive sputum sample (OR: 3.68; 95% CI: 1.63-8.30) and a diagnosis at the university hospital (OR: 2.61; 95% CI: 1.14-5.96) were significantly associated with a system delay≤1 month. A smear-positive sputum sample (OR: 1.35; 95% CI: 1.08-1.69), male gender (OR: 1.21; 95% CI: 1.01-1.49), being born in a foreign country (OR: 1.31; 95% CI: 1.02-1.69), being a family member (OR: 1.37; 95% CI: 1.05-1.77), or being another type of close contact of the case (OR: 2.47; 95% CI: 1.81-3.36) were significantly associated with a contact delay≤0 days. CONCLUSION: System and contact delays were longer than recommended, and the factors associated with the lengthening of these delays need to be taken into account.

Factors associated with time to mandatory tuberculosis notification in the Somme department, France.

BACKGROUND: The associated factors contributing to a delay in mandatory tuberculosis notification in the Somme department, France, are not yet known. The objective of this study was to analyze these factors. METHODS: All reported cases of tuberculosis between 2007 and 2011 were retrospectively included. Univariate and multivariate analyses were conducted to investigate the factors associated with a short time to notification, i.e., ≤48h. RESULTS: Between 2007 and 2011, a total of 175 cases of tuberculosis were reported to the Somme Regional Health Agency. Of the 145 (83.8%) cases of tuberculosis with at least one pulmonary location, 57.7% had a positive sputum smear. The mean time between the diagnosis of tuberculosis and mandatory notification was 6.1 days. It was 2.6 days for tuberculosis cases with a positive sputum smear versus 8.3 days for cases with a negative sputum smear; 2.0 days for severe cases and 6.3 days for simpler forms. In multivariate analysis, only a positive sputum smear was significantly associated with a short time to mandatory notification (OR 2.44; 95%CI 1.18-5.00; P=0.02). CONCLUSION: The time to mandatory notification is longer than recommended. Better collaboration between the parties involved in tuberculosis control and their continuing medical education could reduce this delay in the Somme department.

Cardiovascular and Venous Thromboembolic Events After Hospital Discharge for COVID-19: A Prospective Single Center Study.

Coronavirus disease 2019 (COVID-19) is associated with an increase in venous thrombotic and cardiovascular (CV) events has been reported during hospitalization. No systematic ultrasound follow-up to evaluate sequelae was ever that took place carried out prospectively associated with the evaluation of CV morbidity-mortality at 3 months post-discharge. Consecutive patients hospitalized for COVID-19 in the Amiens-Picardie University Hospital between 1st February and 31st August 2020 were included. The primary objective was the thrombosis incidence at 3 months after hospital discharge. Thrombosis was defined as either venous thromboembolism (VTE) or a CV event (CVE: myocardial infarction (MI), stroke or peripheral arterial disease). A secondary objective was to determine the risk factors for thrombotic events. We included 498 patients (279 men; 56%) of median age 66 (55-76) years. The primary composite outcome occurred in 27 patients (5.4%); 19 patients (3.8%) presented a CVE (stroke, n = 5; MI, n = 9; and peripheral arterial disease, n = 5). Two patients (0.8%) presented VTE. Six patients (1.2%) died. In multivariate analysis, a previous CVE was associated with thrombosis (OR 3.11; 95% CI 1.17-8.24). COVID-19 was significantly associated with thrombotic events post hospital discharge. Special attention should be given to CVE in the follow-up of patients with a previous thrombotic event.

Clinical standards for diagnosis, treatment and prevention of post-COVID-19 lung disease.

BACKGROUND: The aim of these clinical standards is to provide guidance on 'best practice' care for the diagnosis, treatment and prevention of post-COVID-19 lung disease.METHODS: A panel of international experts representing scientific societies, associations and groups active in post-COVID-19 lung disease was identified; 45 completed a Delphi process. A 5-point Likert scale indicated level of agreement with the draft standards. The final version was approved by consensus (with 100% agreement).RESULTS: Four clinical standards were agreed for patients with a previous history of COVID-19: Standard 1, Patients with sequelae not explained by an alternative diagnosis should be evaluated for possible post-COVID-19 lung disease; Standard 2, Patients with lung function impairment, reduced exercise tolerance, reduced quality of life (QoL) or other relevant signs or ongoing symptoms ≥4 weeks after the onset of first symptoms should be evaluated for treatment and pulmonary rehabilitation (PR); Standard 3, The PR programme should be based on feasibility, effectiveness and cost-effectiveness criteria, organised according to local health services and tailored to an individual patient's needs; and Standard 4, Each patient undergoing and completing PR should be evaluated to determine its effectiveness and have access to a counselling/health education session.CONCLUSION: This is the first consensus-based set of clinical standards for the diagnosis, treatment and prevention of post-COVID-19 lung disease. Our aim is to improve patient care and QoL by guiding clinicians, programme managers and public health officers in planning and implementing a PR programme to manage post-COVID-19 lung disease.

[SARS-CoV-2 infection: Available data on 15th April 2021]. / Infection à SARS-CoV-2 : connaissances au 15 avril 2021.

INTRODUCTION: Since January 2020, when the first cases of SARS-CoV-2 infection were diagnosed in France, pulmonologists have been at the heart of the crisis and should be responsible for the management of acute COVID-19 (and any possible sequelae) BACKGROUND: Many drugs have been evaluated or are currently under evaluation as possible specific treatment for SARS-CoV-2. Nevertheless, as of April 15, 2021, the only recommended treatment in current practice is the "standard of care", i.e. the symptomatic management of infection with SARS-CoV-2. This review presents the state of knowledge on COVID-19 in the acute phase (virological, immunological, epidemiological and therapeutic data) available on 15th April, 2021. OUTLOOK: A large number of clinical trials are currently ongoing. It is important to propose to patients the opportunity to participate in clinical trials and to structure the research in order to complete the studies. CONCLUSION: Current management is based on oxygen therapy, thromboprophylaxis and in some cases corticosteroids. No antiviral therapy is currently recommended. These data are constantly evolving.

[Guide for management of patients with possible respiratory sequelae after a SARS-CoV-2 pneumonia. Support proposals developed by the French-speaking Respiratory Medicine Society. Version of 10 November 2020]. / Guide de prise en charge des séquelles respiratoires post infection à SARS-CoV-2. Propositions de prise en charge élaborées par la Société de Pneumologie de Langue Française. Version du 10 novembre 2020.

The French-speaking Respiratory Medicine Society (SPLF) proposes a guide for the management of possible respiratory sequelae in patients who have presented with SARS-CoV-2 pneumonia (COVID-19). The proposals are based on known data from previous epidemics, preliminary published data on post COVID-19 follow-up and on expert opinion. The proposals were developed by a group of experts and then submitted, using the Delphi method, to a panel of 22 pulmonologists. Seventeen proposals were validated ranging from additional examinations after the minimum assessment proposed in the SPLF monitoring guide, to inhaled or systemic corticosteroid therapy and antifibrotic agents. These proposals may evolve over time as knowledge accumulates. This guide emphasizes the importance of multidisciplinary discussion.

Correlation between the Epworth Sleepiness Scale and the Maintenance of Wakefulness Test in Obstructive Sleep Apnea Patients Treated with Positive Airway Pressure.

BACKGROUND: The Epworth sleepiness scale (ESS) is often used to evaluate the impact of treatment in patients with obstructive sleep apnea hypopnea syndrome (OSA). We aimed to evaluate the correlation between ESS and the Maintenance of Wakefulness Test (MWT) in a population of OSA patients treated with positive airway pressure (PAP). METHODS: We retrospectively included all patients during a 2-year period who were diagnosed with OSA in our sleep clinic and required PAP therapy. ESS was evaluated at baseline and after PAP therapy for all patients, and all had a concomitant MWT. Correlation between final ESS, change in ESS, and MWT were evaluated using Spearman's correlation. Given that MWT is considered as the gold standard, the diagnostic performance of ESS was evaluated against MWT. RESULTS: Hundred thirty-four OSA patients were included. At the time of MWT, 89.6% of the patients were compliant (PAP use ≥4hours/night), and only 9 (6.7%) had persistent sleepiness despite PAP treatment (mean sleep latency at MWT<19.4min). Moderate correlation was observed between final ESS and MWT (Spearman's correlation coefficient=-0.42), but no correlation was found between change in ESS and MWT. Diagnostic performance was as follows for final ESS: sensitivity=55.6%, specificity=84.8%, PPV=20.8%, and NPV=96.4%. CONCLUSIONS: ESS was moderately correlated with MWT in a population of OSA patients compliant with PAP therapy. In this population, ESS showed poor diagnostic performance in identifying patients with persistent excessive daytime sleepiness. CLINICALTRIALS. GOV IDENTIFIER: NCT03629834.

[Guide for follow-up of patients with SARS-CoV-2 pneumonia. Management proposals developed by the French-language Respiratory Medicine Society. Version of 10 May 2020]. / Guide pour le suivi respiratoire des patients ayant présenté une pneumonie à SARS-CoV-2. Propositions de prise en charge élaborées par la Société de pneumologie de langue française. Version du 10 mai 2020.

The French-language Respiratory Medicine Society (SPLF) proposes a guide for the follow-up of patients who have presented with SARS-CoV-2 pneumonia. The proposals are based on known data from previous epidemics, on acute lesions observed in SARS-CoV-2 patients and on expert opinion. This guide proposes a follow-up based on three categories of patients: (1) patients managed outside hospital for possible or proven SARS-CoV-2 infection, referred by their physician for persistent dyspnoea; (2) patients hospitalized for SARS-CoV-2 pneumonia in a medical unit; (3) patients hospitalized for SARS-CoV-2 pneumonia in an intensive care unit. The subsequent follow-up will have to be adapted to the initial assessment. This guide emphasises the possibility of others causes of dyspnoea (cardiac, thromboembolic, hyperventilation syndrome…). These proposals may evolve over time as more knowledge becomes available.

Mycobacterium xenopi pulmonary infections: a multicentric retrospective study of 136 cases in north-east France.

BACKGROUND: Owing to its low incidence, the management of Mycobacterium xenopi pulmonary infections is not clearly defined. A multicentre retrospective study was performed to describe the features of the disease and to evaluate its prognosis. METHODS: All patients with M xenopi satisfying the 1997 ATS/IDSA criteria from 13 hospitals in north-east France (1983-2003) were included in the study. Clinical, radiological and bacteriological characteristics and data on the management and outcome were collected. RESULTS: 136 patients were included in the analysis, only 12 of whom presented with no co-morbidity. Three types of the disease were identified: (1) a classical cavitary form in patients with pre-existing pulmonary disease (n = 39, 31%); (2) a solitary nodular form in immunocompetent patients (n = 41, 33%) and (3) an acute infiltrate form in immunosuppressed patients (n = 45, 36%). 56 patients did not receive any treatment; the other 80 patients received first-line treatment containing rifamycin (87.5%), ethambutol (75%), isoniazid (66.2%), clarithromycin (30%) or fluoroquinolones (21%). After a follow-up of 36 months, 80 patients (69.1%) had died; the median survival was 16 months (range 10-22). Two independent prognostic factors were found: the acute infiltrate form was associated with a bad prognosis (hazard ratio 2.6, p = 0.001) and rifamycin-containing regimens provided protection (hazard ratio 0.325, p = 0.006). Clarithromycin-containing regimens did not improve the prognosis. CONCLUSIONS: In contrast to recent guidelines, this study showed three different types of the disease (cavitary, nodular or diffuse infiltrate forms) with a different prognosis. In order to improve survival, all patients with M xenopi infection should be treated with a rifamycin-containing regimen. The usefulness of clarithromycin remains to be evaluated.

Multidisciplinary advisory teams to manage multidrug-resistant tuberculosis: the example of the French Consilium.

SETTING: The World Health Organization (WHO) recommends that multidrug-resistant tuberculosis (MDR-TB) treatment should be managed in collaboration with multidisciplinary advisory committees (consilia). A formal national Consilium has been established in France since 2005 to provide a centralised advisory service for clinicians managing MDR-TB and extensively drug-resistant (XDR-TB) cases.OBJECTIVE: Review the activity of the French TB Consilium since its establishment.DESIGN: Retrospective description and analysis of the activity of the French TB Consilium.RESULTS: Between 2005 and 2016, 786 TB cases or contacts of TB cases were presented at the French TB Consilium, including respectively 42% and 79% of all the MDR-TB and XDR-TB cases notified in France during this period. Treatment regimens including bedaquiline and/or delamanid were recommended for 42% of the cases presented at the French TB Consilium since 2009. Patients were more likely to be presented at the French TB Consilium if they were born in the WHO Europe Region, had XDR-TB, were diagnosed in the Paris region, or had resistance to additional drugs than those defining XDR-TB.CONCLUSION: The French TB Consilium helped supervise appropriate management of MDR/XDR-TB cases and facilitated implementation of new drugs for MDR/XDR-TB treatment.

[Endobronchial ultrasound with transbronchial needle aspiration: Evaluation of clinical practice]. / Échobronchoscopie avec ponction transbronchique à l'aiguille : évaluation des pratiques.

INTRODUCTION: Endobronchial ultrasound with transbronchial needle aspiration (EBUS-TBNA) has undergone a large increase in France since 2007. The aim is to study the evolution of the indications for EBUS-TBNA in our region during the period 2008-2013. MATERIAL AND METHODS: We conducted a retrospective observational study including all the patients who underwent an EBUS-TBNA procedure in Picardie from 2008 to 2013. The respective proportion for each indication was noted. RESULTS: During the study period, 1036 EBUS-TBNA procedures were performed with a continuous increase in number (86 in 2008 versus 275 in 2013). We observed an increase in the proportion of procedures performed for a suspected diagnosis of sarcoidosis (OR=1.31; IC 95% [1.09-1.58]; P=0.005) and for the simultaneous diagnosis and staging of lung cancer (OR=1.12; IC 95% [1.02-1.24]; P=0.022). For the diagnosis of sarcoidosis, we observed an improvement in the diagnostic yield between the periods [2008-2010] and [2011-2013] (42.9% versus 72.5%). CONCLUSION: A continuous increase in the number of EBUS-TBNA procedures was observed during the period 2008-2013. It was associated with a modification in practice with an increased proportion of procedures performed for the diagnosis of sarcoidosis.

[Risks associated with the use of non-steroidal anti-inflammatory drugs during pneumonia]. / Risques associés à la prise d'anti-inflammatoires non stéroïdiens au cours de la pneumonie.

INTRODUCTION: Outpatient treatment of community-acquired pneumonia (CAP) patients with non-steroidal anti-inflammatory drugs (NSAIDs) is frequent, although this is not based on clinical recommendations and there is no scientific evidence supporting better symptom relief in comparison to acetaminophen. STATE OF THE ART: Experimental data suggest that NSAIDs alter the intrinsic functions of neutrophils, limit their locoregional recruitment, alter bacterial clearance and delay the resolution of inflammatory processes during acute bacterial pulmonary challenge. In hospitalized children and adults with CAP, observational data suggest a strong and independent association between the outpatient exposure to NSAIDs and the occurrence of pleuropulmonary complications (pleural empyema, excavation, and abscess). In the only study taking into account possible protopathic bias, the association still persists. Other markers of morbidity have been described, including delay in hospital management, prolonged antibiotic therapy, and higher transfer rate to an intensive care unit. PERSPECTIVES: Data describing the role of self-medication and the biological mechanisms involved are needed. CONCLUSIONS: Intake of NSAIDs during outpatient treatment of CAP is probably the second modifiable factor of morbidity after inadequate antibiotic therapy. In light of existing data in children and adults, health authorities should urgently reassess the risk-benefit ratio of NSAIDS in CAP.

[Management of severe hemoptysis: experience in a specialized center]. / Prise en charge des hémoptysies graves: expérience d'un centre spécialisé

Bronchiectasis, cancer and tuberculosis account for the majority of haemoptysis requiring intensive care unit admission. Bedside evaluation (volume and bronchoscopic active bleeding) is safe to screen patients for arteriography and bronchial artery embolisation (BAE). First-line interventional arteriography should be favour over surgery in patients with non traumatic life-threatening hemoptysis. Surgery must be reserved in cases of failure or recurrence of bleeding after BAE.

[Relationships between COPD and nontuberculous mycobacteria pulmonary infections]. / Relations entre la BPCO et les infections à mycobactéries non tuberculeuses.

Nontuberculous mycobacteria (NTM) pulmonary infections are increasingly frequent in pneumological practice. The diagnosis is based on an association of clinical, microbiological and radiological criteria. Some risk factors for NTM disease have been described, including chronic respiratory diseases, but without specific focus on chronic obstructive pulmonary disease (COPD). COPD patients have more risk to be infected by NTM than patients with the main other chronic respiratory diseases (except cystic fibrosis) (odds ratio [OR] at 15.7 in a case-control study). This NTM pulmonary infection is associated with a greater decline in forced expiratory volume in one second (FEV1) and an increased exacerbation rate. Inhaled corticosteroids (ICS) increase the risk of COPD patients developing an NTM infection (OR at 16.9), especially if ICS are still used at the time of diagnosis. Chronic macrolide treatment could possibly select resistant NTM strains and so could make the treatment clearly more difficult as macrolides are the cornerstone NTM treatment. NTM infections in patients with COPD are probably underestimated and should be kept in mind, particularly when patients have frequent exacerbations and display accelerated respiratory function decline, before implementing ICS or macrolides.

[Mediastinitis after endobronchial ultrasound-guided transbronchial needle aspiration]. / Médiastinite secondaire à une ponction transbronchique échoguidée à l'aiguille : étiologie et prise en charge.

INTRODUCTION: Endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive procedure used for the diagnosis of mediastinal and hilar lymphadenopathy. OBSERVATION: We describe a case of mediastinitis appearing 15 days after an EBUS-TBNA procedure in a 79 years old male patient. The mediastinitis was treated surgically by thoracotomy with a wide excision of infected tissue requiring transplantation of a serratus anterior muscle flap pedicled on a branch of the thoracodorsal artery. It was coupled with broad spectrum antibiotics. This medico-surgical management led to a favorable outcome. Microbiological analysis of the mediastinal collections revealed two pathogens: Streptococcus constellatus (a germ present in the normal flora of the oral cavity) and Mycobacterium tuberculosis. A standard first line quadruple antituberculous drug regimen was subsequently given to the patient. CONCLUSION: This episode of Streptococcus constellatus mediastinitis was a complication of the EBUS-TBNA procedure. The operating channel of the bronchoscope had probably been contaminated when aspirating the oral cavity secretions with subsequent needle contamination and a direct bacterial inoculation during the transbronchial mediastinal puncture. The severity of such a complication justifies a medical consultation in cases of fever or chest pain following an EBUS-TBNA procedure.

[Pulmonary infection with Mycobacterium malmoense. Difficulties in diagnosis and treatment]. / Infection pulmonaire à Mycobacterium malmoense. Difficultés diagnostiques et de thérapeutiques.

INTRODUCTION: Pulmonary infection due to Mycobacterium malmoense can be difficult to diagnose. These difficulties can be responsible for a delay in the implementation of optimal treatment. Moreover, the treatment is not standardized. OBSERVATION: We report the case of a 56-year-old patient who developed a Mycobacterium malmoense pulmonary infection whose diagnosis was delayed due to initial suspicion of pulmonary Mycobacterium tuberculosis infection. Once the diagnosis was confirmed, the patient was treated empirically with rifampicin, ethambutol, and clarithromycin for 12 months after culture conversion, giving a total of 15 months. The clinical and radiological outcomes were favorable. DISCUSSION: This clinical case highlights the difficulties of diagnosing pulmonary atypical mycobacterial infection according to the American Thoracic Society criteria, particularly Mycobacterium malmoense, a non-tuberculous mycobacterium (NTM) quite uncommon in France. Currently, there are new diagnostic techniques such as GenoType Mycobacteria Direct®. The second issue is the poorly standardized treatment of this NTM and many others, that are based on the recommendations of the British Thoracic Society. A national register has been set up by the MycoMed network, based essentially on the work of microbiologists but this register is unfortunately not exhaustive. CONCLUSION: A more systematic reporting strategy could allow cohort studies and therefore provide us with data on the most efficient drugs in the treatment of the rarest NTM infections.