Therapeutic bronchoscopy for malignant central airway obstructions caused by non-bronchogenic cancers: Results from the EpiGETIF registry.

BACKGROUND AND OBJECTIVE: Little is known about malignant central airway obstruction (MCAO) complicating the metastatic spread of non-bronchogenic solid cancers (NBC) and their bronchoscopic management. This study aimed to describe the epidemiology of this population and determine prognostic factors before therapeutic bronchoscopy (TB). METHODS: In this multicenter study using the EpiGETIF registry, we analysed patients treated with TB for MCAO caused by NBC between January 2019 and December 2022. RESULTS: From a database of 2389 patients, 436 patients (18%) with MCAO and NBC were identified. After excluding patients with direct local invasion, 214 patients (8.9%) were analysed. The main primaries involved were kidney (17.8%), colon (16.4%), sarcoma (15.4%), thyroid (8.9%) and head and neck (7.9%) cancers. Most patients (63.8%) had already received one or more lines of systemic treatment. Obstructions were purely intrinsic in 58.2%, extrinsic in 11.1% and mixed in 30.8%. Mechanical debulking was used in 73.4% of cases, combined with thermal techniques in 25.6% of cases. Airway stenting was required in 38.4% of patients. Median survival after TB was 11.2 months, influenced by histology (p = 0.002), performance status (p = 0.019), initial hypoxia (HR 1.45 [1.01-2.18]), prior oncologic treatment received (HR 1.82 [1.28-2.56], p < 0.001) and assessment of success at the end of the procedure (HR 0.66 [0.44-0.99], p < 0.001). Complications rate was 8.8%, mostly mild, with no procedure-related mortality. CONCLUSION: TB for MCAO caused by a NBC metastasis provides rapid improvement of symptoms and prolonged survival. Patients should be promptly referred by medical oncologists for bronchoscopic management based on the prognostic factors identified.

Therapeutic bronchoscopy for malignant central airway obstruction: Introduction to the EpiGETIF registry.

BACKGROUND AND OBJECTIVE: EpiGETIF is a web-based, multicentre clinical database created in 2019 aiming for prospective collection of data regarding therapeutic rigid bronchoscopy (TB) for malignant central airway obstruction (MCAO). METHODS: Patients were enrolled into the registry from January 2019 to November 2022. Data were prospectively entered through a web-interface, using standardized definitions for each item. The objective of this first extraction of data was to describe the population and the techniques used among the included centres to target, facilitate and encourage further studies in TB. RESULTS: Overall, 2118 patients from 36 centres were included. Patients were on average 63.7 years old, mostly male and smokers. Most patients had a WHO score ≤2 (70.2%) and 39.6% required preoperative oxygen support, including mechanical ventilation in 6.7%. 62.4% had an already known histologic diagnosis but only 46.3% had received any oncologic treatment. Most tumours were bronchogenic (60.6%), causing mainly intrinsic or mixed obstruction (43.3% and 41.5%, respectively). Mechanical debulking was the most frequent technique (67.3%), while laser (9.8%) and cryo-recanalization (2.7%) use depended on local expertise. Stenting was required in 54.7%, silicone being the main type of stent used (55.3%). 96.3% of procedure results were considered at least partially successful, resulting in a mean 4.1 points decrease on the Borg scale of dyspnoea. Complications were noted in 10.9%. CONCLUSION: This study exposes a high volume of TB that could represent a good source of future studies given the dismal amount of data about the effects of TB in certain populations and situations.

An International Survey of Practices in the Investigation and Endoscopic Treatment of Peripheral Pulmonary Lesions amongst Interventional Bronchoscopists.

INTRODUCTION: The investigation of peripheral pulmonary lesions (PPLs) can be challenging. Several bronchoscopic modalities have been developed to reach and biopsy PPL but the level of adoption of these techniques by interventional pulmonologists (IPs) is unknown. This international survey was conducted to describe current practices in PPL investigation among IP. METHODS: This survey was sent to all members of the World Association for Bronchology and Interventional Pulmonology, Canadian Thoracic Society Procedures Assembly, AABIP, and the Groupe d'Endoscopie Thoracique et Interventionnel Francophone. The survey was composed of 48 questions and three clinical cases to establish a portrait of modalities used to investigate and treat PPL by IP around the world. RESULTS: Three hundred and twelve IP responded to the survey. Most of them practice in Europe (n = 122), North America (n = 97), and Asia (n = 49). Half of responders perform more than 100 endoscopic procedures for PPL annually. General anesthesia and conscious sedation are used in similar proportions (53% and 47%, respectively). Rapid on site evaluation (ROSE) is used when sampling PPL by 42%. Radial EBUS (69%), fluoroscopy (55%), and electromagnetic navigation (27%) are the most widely used techniques. Most IP combine techniques (89%). Robotic bronchoscopy (15%) and cone-beam CT (8%) are almost exclusively used in the USA where, respectively, 60% and 37% of respondents reported using these modalities. Ten percent of IP currently had access to endoscopic treatment modalities for PPL. However, half of the remaining IP plan to acquire an endoscopic treatment modality in the next 2 years. CONCLUSION: Available techniques and practices worldwide vary significantly regarding PPL investigation and treatment.

The risk of road traffic crashes for occupational drivers: A responsibility study with comparison to the general population.

BACKGROUND: Road accidents are the leading type of work-related fatalities, but the impact of work-related travel on overall traffic safety has been scarcely studied. OBJECTIVE: The main objective of the present study was to assess drivers' relative road accident risk between work-related and personal journeys. METHODS: A responsible/non-responsible case-control study was performed on a sample of 7,051 road accidents in France from the VOIESUR project. Logistic regression determined odds-ratios according to work-related versus personal travel, and identified risk factors for responsibility, specific to each of the two sub-groups. RESULTS: Drivers traveling on duty or commuting home were significantly less often responsible for accidents than drivers on personal journeys: OR = 0.75 [0.63; 0.89] and 0.65 [0.53; 0.80] respectively. Responsibility was significantly more frequent in commuting to versus from work: OR = 1.38 [1.06; 1.78]. Among on-duty drivers, professional passenger-transport drivers had the lowest risk of responsibility (OR = 0.25 [0.11; 0.58]), while those on temporary or work/study contracts and professional light goods vehicle drivers had the highest risk (OR = 11.64 [2.15; 62.94] and OR = 29.83 [5.19; 171.38] respectively). When driving under the influence of alcohol, risk of responsibility was higher in commuting home than in personal journeys. CONCLUSION: On-duty drivers showed lower risk of responsibility for an accident than other drivers. However, on-duty drivers on temporary or work/study contracts, who are usually not subject to specific regulations, showed higher risk, and should be the subject of particular attention regarding occupational risk prevention.

Role of bronchoscopy for respiratory involvement in granulomatosis with polyangiitis and microscopic polyangiitis.

Objectives: This study describes data from bronchoscopy performed at the diagnosis of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Methods: We conducted a retrospective study between 2004 and 2019 in patients aged >18 years with a diagnosis of microscopic polyangiitis (MPA) or granulomatosis with polyangiitis (GPA) who underwent bronchoscopy at onset of the disease. We collected bronchoalveolar lavage (BAL) and histological findings obtained during bronchoscopy. Results: 274 patients with AAV were identified. Among 92 bronchoscopies, 62 were performed at diagnosis, and 58 procedures were finally analysed. Cough was more frequent in patients with MPA than GPA (p=0.02). The presence of endobronchial lesions (24.1%) was found to be significantly associated with GPA (p<0.0001) and proteinase 3-ANCA (p=0.01). The most frequent endobronchial lesions were inflammation and hyperaemia of the bronchial mucosa (50%), followed by stenoses (28%), ulcerations (21%) and mass-like granulomatosis (7%). The diagnostic yield of bronchial biopsies was useful for visible lesions (66.6% versus 0%; p=0.006). On BAL, diffuse alveolar haemorrhage (DAH) was detected in 31 (53.4%) patients and was more frequent in MPA patients (70.4% versus 38.7%; p=0.016). In 16.1% of DAH cases, BAL confirmed the diagnosis despite the absence of clinical or biological arguments. The incidence of microbial infections on BAL (38%) was similar between MPA and GPA (p=0.54). Conclusion: Bronchoscopy is an informative procedure at the onset of AAV disease in patients with respiratory manifestations. Endobronchial lesions are more frequently found in GPA and should be biopsied. BAL can be used to confirm DAH or diagnose superadded infection.

Impact of pharmacological and non-pharmacological interventions on mortality in chronic obstructive pulmonary disease (COPD) patients.

PURPOSE: This review aimed to summarise evidence about the impact of pharmacological and non-pharmacological interventions on survival in COPD patients. METHODS: We performed a narrative literature review on the effect of pharmacological and non-pharmacological interventions on survival in COPD patients. RESULTS: Inhaled therapies are central to reduce symptoms in COPD. In particular, inhaled steroids seem to have the greatest effect on mortality. Despite the anti-inflammatory effects attributed to statins, their benefit in COPD has been shown only in cases of combined cardiovascular diseases. The use of beta-blockers in COPD has not been associated with increased COPD-related mortality and a beneficial effect on all-cause mortality has even been shown in COPD patients with cardiovascular diseases. Influenza and pneumococcal vaccination reduced the occurrence of exacerbations and mortality due to COPD. In addition, long-term oxygen therapy (LTOT) (≥15h/day) in COPD patients with severe hypoxemia had a positive effect on survival. Regarding non-pharmacological interventions, it has been demonstrated that smoking cessation, treatment compliance and nutritional supplementation for underweight patients also have a positive effect on survival. Non-invasive ventilation results were dependent on patient PaCO2 levels. In patients with advanced COPD, further prospective studies are needed to know the effect of bronchoscopic lung volume reduction and lung transplant on COPD survival. Regarding lung transplant, a survival benefit in patients with a pre-transplant BODE score of ≥7 has been shown in retrospective studies. CONCLUSION: Most of the studies did not evaluate survival as the main criteria and further long-term studies on the global management of COPD are required.

Guidelines for the management of chronic cough in adults. Endorsed by the French speaking society of respiratory diseases (Société de Pneumologie de Langue Française, SPLF), the Société Française d'Oto-Rhino-Laryngologie et de Chirurgie de la Face et du Cou (SFORL), the Société Française de Phoniatrie et de Laryngologie (SFPL), the Société Nationale Française de Gastro-entérologie (SNFGE).

Patients with chronic cough experience a high alteration of quality of life. Moreover, chronic cough is a complex entity with numerous etiologies and treatments. In order to help clinicians involved in the management of patients with chronic cough, guidelines on chronic cough have been established by a group of French experts. These guidelines address the definitions of chronic cough and the initial management of patients with chronic cough. We present herein second-line tests that might be considered in patients with cough persistence despite initial management. Experts also propose a definition of unexplained or refractory chronic cough (URCC) in order to better identify patients whose cough persists despite optimal management. Finally, these guidelines address the pharmacological and non-pharmacological interventions useful in URCC. Thus, amitryptilline, pregabalin, gabapentin or morphine combined with speech and/or physical therapy are a mainstay of treatment strategies in URCC. Other treatment options, such as P2 × 3 antagonists, are being developed.

A third vaccine dose equalises the levels of effectiveness and immunogenicity of heterologous or homologous COVID-19 vaccine regimens, Lyon, France, December 2021 to March 2022.

BackgroundTo cope with the persistence of the COVID-19 epidemic and the decrease in antibody levels following vaccination, a third dose of vaccine has been recommended in the general population. However, several vaccine regimens had been used initially for the primary vaccination course, and the heterologous Vaxzevria/Comirnaty regimen had shown better efficacy and immunogenicity than the homologous Comirnaty/Comirnaty regimen.AimWe wanted to determine if this benefit was retained after a third dose of an mRNA vaccine.MethodsWe combined an observational epidemiological study of SARS-CoV-2 infections among vaccinated healthcare workers at the University Hospital of Lyon, France, with a prospective cohort study to analyse immunological parameters before and after the third mRNA vaccine dose.ResultsFollowing the second vaccine dose, heterologous vaccination regimens were more protective against infection than homologous regimens (adjusted hazard ratio (HR) = 1.88; 95% confidence interval (CI): 1.18-3.00; p = 0.008), but this was no longer the case after the third dose (adjusted HR = 0.86; 95% CI: 0.72-1.02; p = 0.082). Receptor-binding domain-specific IgG levels and serum neutralisation capacity against different SARS-CoV-2 variants were higher after the third dose than after the second dose in the homologous regimen group, but not in the heterologous group.ConclusionThe advantage conferred by heterologous vaccination was lost after the third dose in terms of both protection and immunogenicity. Immunological measurements 1 month after vaccination suggest that heterologous vaccination induces maximal immunity after the second dose, whereas the third dose is required to reach the same level in individuals with a homologous regimen.

Broadening the scope for three-dimensional printed airway stents.

The ideal airway stent is still not available. Indications for 3D stents currently are limited to rare cases. Therefore, further research is required to investigate whether personalised airway stents will perform better than conventional stents. https://bit.ly/3GLjPa4.

Impact of bronchoscopic lung volume reduction with endobronchial valves on dynamic hyperinflation: Results from the PIERCE study.

BACKGROUND AND OBJECTIVE: Dynamic hyperinflation (DH) is a major marker of exertional dyspnoea in severe emphysema. We hypothesized that bronchoscopic lung volume reduction (BLVR) using endobronchial valves (EBVs) decreases DH. METHODS: In this prospective bi-centre study from both Toulouse and Limoges Hospitals, we assessed DH during an incremental cycle ergometry before and 3 months after EBVs treatment. The primary objective was to observe the change in inspiratory capacity (IC) at isotime. Target lobe volume reduction (TLVR) and changes in residual volume (RV), forced expiratory volume in one-second (FEV1 ), mMRC, 6 minutes walking distance (6MWD), BODE and other dynamic measures like tele-expiratory volume (EELV) were also analysed. RESULTS: Thirty-nine patients were included, of whom thirty-eight presented DH. IC and EELV at isotime significantly improved (+214 mL, p = 0.004; -713 mL, p Ë‚ 0.001, respectively). Mean changes were +177 mL for FEV1 (+19%, p < 0.001), -600 mL for RV (p < 0.0001), +33 m for 6MWD (p < 0.0001), respectively. Patients who responded on RV (>430 mL decrease) and FEV1 (>12% gain) had better improvements compared to non-responders (+368 mL vs. +2 mL; +398 mL vs. -40 mL IC isotime, respectively). On the opposite, in patients who responded on DH (>200 mL IC isotime increase), changes in TLV (-1216 mL vs. -576 mL), FEV1 (+261 mL vs. +101 mL), FVC (+496 mL vs. +128 mL) and RV (-805 mL vs. -418 mL) were greater compared to non-responders. CONCLUSIONS: DH decreases after EBVs treatment, and this improvement is correlated with static changes.

A 3D-engineered silicone stent to treat a refractory bronchopleural fistula.

A novel 3D-engineered silicone stent was successfully used to treat a refractory bronchopleural fistula of the right lower lobe in a patient with an open-window thoracostomy who complained of severe dysphonia and recurrent infections https://bit.ly/3GrKs2p.

Productive HIV-1 infection of tissue macrophages by fusion with infected CD4+ T cells.

Macrophages are essential for HIV-1 pathogenesis and represent major viral reservoirs. Therefore, it is critical to understand macrophage infection, especially in tissue macrophages, which are widely infected in vivo, but poorly permissive to cell-free infection. Although cell-to-cell transmission of HIV-1 is a determinant mode of macrophage infection in vivo, how HIV-1 transfers toward macrophages remains elusive. Here, we demonstrate that fusion of infected CD4+ T lymphocytes with human macrophages leads to their efficient and productive infection. Importantly, several tissue macrophage populations undergo this heterotypic cell fusion, including synovial, placental, lung alveolar, and tonsil macrophages. We also find that this mode of infection is modulated by the macrophage polarization state. This fusion process engages a specific short-lived adhesion structure and is controlled by the CD81 tetraspanin, which activates RhoA/ROCK-dependent actomyosin contractility in macrophages. Our study provides important insights into the mechanisms underlying infection of tissue-resident macrophages, and establishment of persistent cellular reservoirs in patients.

Prior SARS-CoV-2 infection enhances and reshapes spike protein-specific memory induced by vaccination.

The diversity of vaccination modalities and infection history are both variables that have an impact on the immune memory of individuals vaccinated against SARS-CoV-2. To gain more accurate knowledge of how these parameters imprint on immune memory, we conducted a long-term follow-up of SARS-CoV-2 spike protein-specific immune memory in unvaccinated and vaccinated COVID-19 convalescent individuals as well as in infection-naïve vaccinated individuals. Here, we report that individuals from the convalescent vaccinated (hybrid immunity) group have the highest concentrations of spike protein-specific antibodies at 6 months after vaccination. As compared with infection-naïve vaccinated individuals, they also display increased frequencies of an atypical mucosa-targeted memory B cell subset. These individuals also exhibited enhanced TH1 polarization of their SARS-CoV-2 spike protein-specific follicular T helper cell pool. Together, our data suggest that prior SARS-CoV-2 infection increases the titers of SARS-CoV-2 spike protein-specific antibody responses elicited by subsequent vaccination and induces modifications in the composition of the spike protein-specific memory B cell pool that are compatible with enhanced functional protection at mucosal sites.

Endobronchial valves: 1st Multicenter retrospective study on the 2-step approach.

BACKGROUND: Although the endobronchial valves (EBV) were successfully developed as treatment for severe emphysema, its main complication, pneumothorax, remained an important concern. OBJECTIVE: To assess whether the placement of Zephyr© endobronchial valves throughout 2 procedures instead of 1 minor the frequency of pneumothorax without lowering the benefits of such treatment. METHODS: This retrospective study was conducted in 15 pulmonology department in France. All the patients met the inclusion criteria of the recommendation set by the expert panel on the Endoscopic Lung Volume Reduction (ELVR) updated in 2019. As recommended, all the scan were analyzed with the StratX© (PulmonX Corporation, Redwood city, CA) protocol, and completed by a Chartis© (PulmonX Corporation, Redwood city, CA) in case of questionable fissure. During the first procedure, all but the most proximal sub-segment of the targeted lobe were occluded. One month after, EBV were placed in the bronchus of the last subsegment. All patients were evaluated before and 3 months after the second procedure. RESULTS: Between March 2019 and December 2020, 96 patients received EBV treatment. 12 patients (12.5%) presented a pneumothorax (3 after the 1st step and 9 after the 2nd procedure). Beside pneumothorax, the main adverse event was exacerbation (10.4%) and pneumonia (4.1%). No death were reported. Significant improvement were found for FEV1 (14.6 ± 25.3%), RV (- 0.69 ± 2.1 L), 6MWT (34.8 ± 45.9 m), BODE Score (-1.41 ± 1.41pts), and mMRC scale (-0.85 ± 0.7pts). These results are compared not only to the results previously published using the usual approach but also to our previous publication evaluating the 2-step approach. Some patients presented authentic segmental atelectasis despite infralobar treatment. CONCLUSION: Placing EBV during 2 procedures instead of one led to a significant decrease of post treatment pneumothoraces without increasing the rate of other complications. It does not seem to alter the benefits of such therapy for severe emphysema. These results must be confirmed by launching a multicenter, prospective, randomized, controlled study to compare the frequency of pneumothorax and the efficacy of this new approach with the usual one-time procedure.