Randomized, double-blind, controlled phase 1 trial of the candidate tuberculosis vaccine ChAdOx1-85A delivered by aerosol versus intramuscular route.

BACKGROUND: A BCG booster vaccination administered via the respiratory mucosa may establish protective immune responses at the primary site of Mycobacterium tuberculosis infection. The primary objective of this trial was to compare the safety and immunogenicity of inhaled versus intramuscular administered ChAdOx1-85A. METHODS: We conducted a single-centre, randomized, double-blind, controlled phase 1 study (Swiss National Clinical Trials Portal number SNCTP000002920). After a dose-escalation vaccination in nine BCG-vaccinated healthy adults, a dose of 1×1010 vp of ChAdOx1-85A was administered to twenty BCG-vaccinated adults that were randomly allocated (1:1) into two groups: aerosol ChAdOx1-85A with intramuscular saline placebo or intramuscular ChAdOx1-85A with aerosol saline placebo, using block randomisation. A control group of ten BCG-naïve adults received aerosol ChAdOx1-85A at the same dose. Primary outcomes were solicited and unsolicited adverse events (AEs) up to day 16 post-vaccination and Serious AEs (SAEs) up to 24 weeks; secondary outcomes were cell-mediated and humoral immune responses in blood and bronchoalveolar lavage (BAL) samples. FINDINGS: Both vaccination routes were well tolerated with no SAEs. Intramuscular ChAdOx1-85A was associated with more local AEs (mostly pain at injection site) than aerosol ChAdOx1-85A. Systemic AEs occurred in all groups, mainly fatigue and headaches, without differences between groups. Respiratory AEs were not different between BCG-vaccinated groups. Aerosol ChAdOx1-85A vaccination induced Ag85A BAL and systemic cellular immune responses with compartmentalization of the immune responses: aerosol ChAdOx1-85A induced stronger BAL cellular responses, particularly IFNγ/IL17+CD4+ T cells; intramuscular ChAdOx1-85A induced stronger systemic cellular and humoral responses. INTERPRETATION: Inhaled ChAdOx1-85A was well-tolerated and induced lung mucosal and systemic Ag85A-specific T cell responses. These data support further evaluation of aerosol ChAdOx1-85A and other viral vectors as a BCG-booster vaccination strategy. FUNDING: European Commission H2020 program (TBVAC2020 project, grant agreement 643381) via the Swiss State Secretariat for Education, Research and Innovation (SERI).

Allergic bronchopulmonary aspergillosis in a lung transplant recipient treated with mepolizumab.

Allergic bronchopulmonary aspergillosis (ABPA) is a complex hypersensitivity reaction to Aspergillus spp. ABPA diagnosis may be challenging due to its non-specific presentation. Standard ABPA treatment consists of systemic corticosteroids and antifungal agents. Mepolizumab, a monoclonal antibody against interleukin-5 seems to be a promising treatment for ABPA. Data about ABPA following lung transplantation (LuTx) are scarce. LuTx recipients are at higher risk for adverse effects of ABPA treatment compared to the general population. Here we present a case of a LuTx recipient who was successfully treated with mepolizumab for ABPA following LuTx. Prolonged administration of high dose prednisone was thus avoided. To our knowledge, this is the first case describing mepolizumab administration following LuTx. Mepolizumab seems particularly attractive as a corticosteroid-sparing agent or as an alternative option to antifungal treatments, because of its excellent safety profile and low risk of drug interactions.

Innovations to Improve Lung Isolation Training for Thoracic Anesthesia: A Narrative Review.

A double-lumen tube or bronchial blocker positioning using flexible bronchoscopy for lung isolation and one-lung ventilation requires specific technical competencies. Training to acquire and retain such skills remains a challenge in thoracic anesthesia. Recent technological and innovative developments in the field of simulation have opened up exciting new horizons and possibilities. In this narrative review, we examine the latest development of existing training modalities while investigating, in particular, the use of emergent techniques such as virtual reality bronchoscopy simulation, virtual airway endoscopy, or the preoperative 3D printing of airways. The goal of this article is, therefore, to summarize the role of existing and future applications of training models/simulators and virtual reality simulators for training flexible bronchoscopy and lung isolation for thoracic anesthesia.

[Lung cancer screening : towards the implementation of a pilot project in Switzerland]. / Dépistage du cancer pulmonaire : vers l'implémentation d'un projet pilote en Suisse.

Lung cancer is responsible for one in five cancer-related deaths. Screening for lung cancer using low-dose chest CT (LDCT) is supported by several international studies targeting the at-risk population as part of an organised programme. Given the organisational challenges for the healthcare systems of the countries concerned, this involves setting up pilot screening projects. This requires close collaboration between the players involved, with a multidisciplinary approach structured around the participant, aiming to offer the expertise of the pulmonologist and the radiologist on the LDCT performed, interpreted with the help of artificial intelligence. Here we set out the elements needed to develop a screening programme, starting with the implementation of a pilot project.

Le cancer pulmonaire est responsable d'un décès lié au cancer sur cinq. Le dépistage du cancer pulmonaire par le scanner thoracique à faible dose (LDCT) est soutenu par plusieurs études internationales ciblant la population à risque dans le cadre d'un programme organisé. Vu les enjeux organisationnels pour le système de santé des pays concernés, cela passe par la mise en place de projets pilotes de dépistage. Cela requiert une collaboration étroite entre les différents acteurs, avec une approche multidisciplinaire structurée autour du participant visant à offrir l'expertise du pneumologue et du radiologue sur le LDCT effectué, interprété avec l'aide de l'intelligence artificielle. Nous exposons ici les éléments nécessaires à l'élaboration d'un programme de dépistage, en passant d'abord par la mise en place d'un projet pilote.

[Clinical approach to enlarged mediastinal and hilar lymph nodes other than the oncological causes]. / Adénomégalies médiastinohilaires - Approche clinique chez l'adulte immunocompétent hors contexte oncologique.

Widespread use of CT-scans leads to increased discovery of mediastinal and hilar lymph node enlargement, a frequent motive for consulting a pulmonologist. The persistence or progression of such lymphadenopathies outside of an oncological context is most often associated with an infectious process or inflammatory disorders. The history will also point to possible occupational or environmental exposure. The radiological characteristics specific to lymphadenopathies and any associated parenchymal lung damage will most often orient the diagnosis. Endobronchial ultrasound-guided techniques allow targeted and real-time sampling of the mediastinum and hilar lymph nodes, representing the first-line investigation before more invasive surgical procedures.

La découverte d'adénomégalies médiastinohilaires (AMH) est un motif fréquent de consultation en pneumologie. Utilisés à grande échelle, les CT-scans thoraciques en sont les principaux révélateurs. La persistance ou la progression d'AMH en dehors d'un contexte oncologique est le plus souvent d'origine infectieuse ou associée à un processus inflammatoire. L'anamnèse nous orientera vers une possible exposition à des facteurs environnementaux y compris en milieu professionnel. La plupart du temps, les caractéristiques radiologiques propres aux AMH ainsi qu'une éventuelle atteinte parenchymateuse pulmonaire associée pourront orienter le diagnostic. L'échoendoscopie bronchique permettant un échantillonnage ganglionnaire médiastinohilaire ciblé est l'examen de première intention avant des abords diagnostiques plus invasifs.

Endobronchial coil spring fiducial markers for CyberKnife® stereotactic body radiation therapy.

BACKGROUND AND OBJECTIVE: SBRT is an alternative treatment for early-stage inoperable lung cancer. Metallic FM allow to increase tumour tracking precision by CyberKnife®. Currently used techniques for FM placement have many limitations; transthoracic insertion has a high risk for pneumothorax, endovascular insertion requires expertise and dedicated angiography infrastructure and endobronchial linear-gold FM dislocate frequently. This is the first study to assess the safety and efficacy of cs-FM endobronchial insertion under fluoroscopy with or without R-EBUS assessment. METHODS: We retrospectively evaluated all consecutive patients undergoing endobronchial cs-FM placement for at least one PPL <25 mm between 10.2015 and 12.2019. TBB of the PPL were performed in case of a typical R-EBUS signal. PPL tracking accuracy by CyberKnife, complications, cs-FM migration rate and procedure duration were analysed. RESULTS: A total of 52 patients were treated during 55 procedures and 207 cs-FM were placed in 70 PPL. Tracking was successful for 65 of 70 (93%) PPL. R-EBUS was performed for 33 (47%) PPL and TBB for 9 (13%) PPL. Bronchospasm occurred once and any other complications were observed. Migration of cs-FM occurred in 16 of 207 (8%) cs-FM. Migration was more frequent when the target was in a previously irradiated area (P = 0.022). The median bronchoscopy duration was 31.5 min (n = 48 procedures). CONCLUSION: Bronchoscopic cs-FM placement is a rapid and safe procedure. It is associated with a low migration rate and allows precise SBRT delivery. Previous irradiation of the PPL was associated with a higher migration rate.

Bronchial anastomosis dehiscence and stenosis caused by donor-transmitted Mycoplasma hominis infection in a lung transplant recipient: Case report and literature review.

Pulmonary infection by Mycoplasma hominis (M hominis) in lung transplant (LTx) recipients is an uncommon yet potentially severe complication. Bronchial dehiscence in the context of M hominis infection has not been previously reported. In this report, we discuss a case of donor-derived M hominis infection in a LTx recipient with bilateral bronchial anastomoses dehiscence and stenosis. The infection was managed using a multidisciplinary approach: repeat surgical revision of the necrotic anastomosis; targeted antibiotic therapy with the combination of oral and inhaled fluoroquinolones, and oral doxycycline and continuous ventilatory support. Response to therapy was monitored through repeat bronchoscopy and serial quantitative PCR assays for M hominis in bronchoalveolar lavage and aspiration. The rare nature of M hominis infection after LTx, its difficult detection in conventional cultures and innate resistance to beta-lactams make diagnosis and timely treatment of this organism challenging. We recommend that transplant centers have a low threshold for screening for Mycoplasma infection, particularly in patients with unsatisfactory postoperative course and little response to broad-spectrum antimicrobial and antifungal coverage. Monitoring with PCR may help to adapt the duration of antibiotic therapy.

[Lung cancer screening in Switzerland†: Who†? How†? When†?] / Dépistage du cancer pulmonaire en Suisse†: Qui†? Comment†? Quand†?

Professional societies encourage the establishment of coordinated national screening programs for lung cancer by «â€…low-dose ¼ chest CT scans. The interdisciplinary Swiss Lung Cancer Screening Implementation Group (CH-LSIG) is exploring the feasibility of such a project. However, several questions still remain unanswered, namely the -financing of such a program, the ideal «â€…number-needed to screen ¼, the definition and follow-up of «â€…positive cases ¼, as well as the role of smoking cessation measures. The key points to discuss in the future with patients requesting screening are based on the «â€…shared -decision-making ¼ approach. Pilot projects guided by the CH-LSIG could help to identify the optimal strategy for establishing a national screening program based on the best available scientific evidence.

Les sociétés savantes encouragent le développement de programmes nationaux de dépistage du cancer pulmonaire par CT-scan thoracique low-dose. En Suisse, le groupe de travail ­interdisciplinaire Swiss Lung Cancer Screening Implementation Group (CH-LSIG) s'emploie à la mise en œuvre d'un tel projet. Néanmoins, de nombreuses questions demeurent encore ouvertes, portant sur le financement d'un tel programme, le Number ­Needed to Screen idéal, la définition des «â€…cas positifs ¼ et l'intégration optimale des mesures de sevrage tabagique. Le concept de décision médicale partagée servira de modèle pour répondre aux futurs patients demandeurs d'un examen de dépistage. Des projets pilotes guidés par le CH-LSIG pourraient permettre d'identifier la stratégie la plus performante afin d'implémenter un programme fondé sur les preuves.

[Computer instruments for the management of isolated pulmonary nodule. Detectability and prediction of malignancy]. / Outils informatiques pour la prise en charge du nodule pulmonaire isolé - Détectabilité et prédiction de malignité.

Lung cancer remains the most common cause of cancer deaths in the world, but its mortality can be significantly reduced by diagnosis and early detection. Computerized resources were developed to assist radiologists in their management of the large volume of thoracic images to be analyzed. Their objective is the detection of pulmonary nodules with high sensitivity and a low rate of false-positives and the ability to differentiate benign and malignant nodules. The volume of a pulmonary nodule and its volume doubling time are essential to nodule management. Computer aided detection or diagnosis (CAD) software are not currently used in clinically settings on a routine basis . Significant advances are expected due to the implementation of the artificial intelligence systems who will probably be integrated into the multidisciplinary management of any pulmonary nodule.

Le cancer du poumon reste la principale cause de décès par cancer dans le monde. Sa mortalité peut être significativement réduite par un diagnostic et un dépistage précoce. Des outils informatiques ont été développés afin d'aider les radiologues à gérer la quantité d'images thoraciques à analyser. Ils ont pour objectif la détection des nodules pulmonaires avec une haute sensibilité et un taux faible de faux positifs, mais aussi la différenciation des nodules bénins et malins. Le volume d'un nodule pulmonaire et le temps de doublement déterminent la suite de la prise en charge de ce nodule. Ces deux paramètres sont inclus dans la plupart des recommandations actuelles. Les logiciels de détection assistés par ordinateur (CAD) ne sont pas utilisés en routine clinique actuellement. Des avancées dans ce domaine sont attendues en utilisant l'intelligence artificielle, notamment dans le cadre de la prise de décision multidisciplinaire.

Ultrashort echo time imaging of the lungs under high-frequency noninvasive ventilation: A new approach to lung imaging.

BACKGROUND: Although ultrashort echo time (UTE) sequences allow excellent assessment of lung parenchyma, image quality remains lower than that of computed tomography (CT). PURPOSE: To investigate a high-frequency noninvasive ventilation (HF-NIV) technique allowing a stabilized inspiration and to compare image quality with current dedicated MR sequences. STUDY TYPE: Prospective. POPULATION: Ten healthy volunteers. FIELD STRENGTH/SEQUENCE: 3D radial UTE sequence at 1.5T. ASSESSMENT: UTE-HF-NIV sequence was compared with UTE-free-breathing (UTE-FB), reconstructed at end expiration (UTE-Exp) and average (UTE-Avg), and breath-hold VIBE sequences. The distance from lung apex to the dome of the right hemidiaphragm was measured. Visual assessment of the visibility and sharpness of normal anatomical structures was carried out. Dedicated software also quantitatively evaluated vessel-lung and right lung-liver interface sharpness. Apparent signal ratio (Sr) and contrast ratios (Cr) were quantitatively evaluated. STATISTICAL TESTS: Wilcoxon signed rank test for visual scores, paired t-test for continuous variables, significance at P < 0.05. RESULTS: The distance between apex and the right hemidiaphragmatic dome was significantly larger (P < 0.001) with UTE-HF-NIV compared with UTE-FB and VIBE acquisitions. Vessel and airway visibility had identical median visual scores with all UTE methods. Median visual scores for sharpness of vessels and airways were significantly higher (P < 0.001) with HF-NIV (vessels = 3; airways = 2) than in UTE-FB (vessels = 2; airways = 1) and VIBE (vessels = 1; airways = 1). Software-based vessel sharpness evaluation resulted in larger values in 8/10 volunteers with UTE-HF-NIV (67.3 ± 9.8) compared with UTE-Avg (62.3 ± 12.6) but the average difference was not significant (P = 0.28). The sharpness of the lung-liver interface was significantly higher (P < 0.001) with HF-NIV (17.3 ± 5.3) compared with UTE-Avg (14.1 ± 3.9). Significantly higher values (P < 0.01) of Sr and Cr were observed with UTE-HF-NIV compared with UTE-FB and VIBE. DATA CONCLUSION: HF-NIV allowing acquisition at full inspiration significantly improves image quality for lung imaging. This could offer the option to alternate some follow-up CT studies by using this technique. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;50:1789-1797.

[Lung and pleural space ultrasonography for pulmonologist]. / L'échographie pleuro-pulmonaire pour le pneumologue.

In the past twenty years ultrasound has been the subject of renewed interest in lung exploration in the broad sense. The necessity of accessing a means of rapid exploration at the bed of the patient in a critical situation has led to the development of a pleuro-pulmonary ultrasound semiology to make it a diagnostic tool of choice which exceeds the strict framework intensive care units and emergency services. With the diagnosis of thoracic tumors or the exploration of interstitial syndromes, it tends to integrate more into the daily practice of the pulmonologist. This article is a review of the possibilities offered by ultrasound in the field with its advantages and limitations.

Depuis une vingtaine d'années, l'échographie fait l'objet d'un regain d'intérêt pour l'exploration pulmonaire au sens large. La nécessité d'accéder à un moyen d'exploration rapide au lit du malade en situation critique a mené au développement d'une sémiologie échographique pleuro-pulmonaire jusqu'à en faire un outil diagnostique de choix dont l'utilisation dépasse désormais le cadre strict des unités de soins intensifs et des services d'urgence. Avec le diagnostic des tumeurs thoraciques ou encore l'exploration des syndromes interstitiels, elle tend à s'intégrer davantage dans la pratique quotidienne du pneumologue. Cet article est une revue des possibilités qu'offre l'échographie dans ce domaine avec ses avantages et ses limites.

A 3-step therapeutic strategy for severe alveolar proteinosis.

Pulmonary alveolar proteinosis (PAP) is characterized by accumulation of lipoproteinaceous material in the terminal airways. Whole lung lavage (WLL) remains the gold standard treatment but may be particularly challenging in cases of severe hypoxemia. We present a 3-step strategy that was used in a patient with PAP-associated refractory hypoxemia and that combined venovenous extracorporeal membrane oxygenation (vvECMO), double-lumen orotracheal intubation, and bilateral multisegmental sequential lavage (MSL). The procedure was well tolerated and permitted weaning from the ventilator.

Complications of valve lung volume reduction in a case of previous pleurodesis.

Lung volume reduction with valves is increasingly used to treat selected patients with severe emphysema. The indications for this procedure have been previously described; however, its contraindications have not yet been conclusively established. This case highlights the potentially severe complications of endobronchial one-way valve placement in the setting of a previous pleurodesis.