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.

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.

European Respiratory Society guidelines on transbronchial lung cryobiopsy in the diagnosis of interstitial lung diseases.

BACKGROUND: In patients with interstitial lung diseases (ILD), histopathological input is often required to obtain a diagnosis. Surgical lung biopsy (SLB) is considered the reference standard, but many patients are clinically unfit to undergo this invasive procedure, and adverse events, length of hospitalisation and costs are considerable. This European Respiratory Society (ERS) guideline provides evidence-based clinical practice recommendations for the role of transbronchial lung cryobiopsy (TBLC) in obtaining tissue-based diagnosis in patients with undiagnosed ILD. METHODS: The ERS Task Force consisted of clinical experts in the field of ILD and/or TBLC and methodological experts. Four PICO (Patient, Intervention, Comparator, Outcomes) questions and two narrative questions were formulated. Systematic literature searches were performed in MEDLINE and Embase (up to June 2021). GRADE (Grading, Recommendation, Assessment, Development and Evaluation) methodology was applied. RESULTS: In patients with undiagnosed ILD and an indication to obtain histopathological data: 1) TBLC is suggested as a replacement test in patients considered eligible to undergo SLB, 2) TBLC is suggested in patients not considered eligible to undergo SLB, 3) SLB is suggested as an add-on test in patients with a non-informative TBLC, 4) no recommendation is made for or against a second TBLC in patients with a non-informative TBLC and 5) TBLC operators should undergo training, but no recommendation is made for the type of training required. CONCLUSIONS: TBLC provides important diagnostic information in patients with undiagnosed ILD. Diagnostic yield is lower compared to SLB, at reduced serious adverse events and length of hospitalisation. Certainty of the evidence is mostly "very low".

Respiratory Conditions Associated with Tracheobronchomegaly (Mounier-Kuhn Syndrome): A Study of Seventeen Cases.

BACKGROUND: Mounier-Kuhn syndrome (MKS) is a rare disorder characterized by enlargement of the trachea and main bronchi and associated with recurrent respiratory tract infections. OBJECTIVE: This multicenter, retrospective study was carried out to describe respiratory conditions associated with tracheobronchomegaly. METHODS: Nine institutions involved in the 'Groupe d'Endoscopie de Langue Française' (GELF) participated in this study. A standard form was used to record patient characteristics, treatments and follow-up from medical charts. RESULTS: Seventeen patients, 53% male, aged 58 ± 18 years at diagnosis were included. Recurrent infections revealed MKS in 88% of cases. Main comorbid conditions were diffuse bronchiectasis in 88% of patients and tracheobronchomalacia in 67% of cases. The exacerbation rate was 1.5 exacerbations/patient/year. The main non-respiratory morbid condition was gastroesophageal reflux disease in 29% of cases. Interventional bronchoscopy was performed in seven patients (41%), consisting of laser (n = 2) and tracheal stenting (n = 5). Complications related to stents were observed in 80% of cases with a mean stent duration of 8 months. Four deaths, including three due to respiratory causes, occurred during follow-up. CONCLUSIONS: This is the largest series of MKS reported in the literature, showing that bronchiectasis and tracheobronchomalacia are the main associated morbid conditions that constitute a challenge for treatment.

Enhancing antifungal treatment for chronic cavitary pulmonary aspergillosis through the addition of endobronchial valve therapy.

A 62-year-old male experienced anti-MDA5 dermatomyositis with lung involvement, treated with immunosuppressive therapy leading to chronic cavitary pulmonary aspergillosis in left upper lobe. Patient's history was complicated by complete left pneumothorax due to alveolar-pleural fistula occurring because of the rupture of the pulmonary cavitation. Left lung failed to re-expand despite a four-week period of pleural drainage. In addition to antifungal therapy, patient received endobronchial valve therapy in the anterior segmental bronchus of the left upper lobe leading to air leak cessation, left lung re expansion and aspergillosis cavitation closure.

Cell and cytokine analyses from bronchoalveolar lavage in non-critical COVID-19 pneumonia.

Cell and cytokine analyses from bronchoalveolar lavage (BAL) in non-critically ill patients with COVID-19 pneumonia are poorly described. This study focused on patients hospitalized in the non-intensive care unit for either suspected COVID-19 pneumonia or persistent respiratory symptoms following proven COVID-19 pneumonia. Overall, 54 patients who underwent BAL between April 2020 and February 2021 for suspected or follow-up of proven COVID-19 pneumonia were included. Based on SARS-CoV-2 polymerase chain reaction test results and clinical follow-up, three pulmonary disease groups were defined: non-COVID-19 (n = 20), acute COVID-19 (n = 13), and post-COVID-19 (n = 24) pneumonia patients. Cytological and cytokine analyses were performed on BAL fluid (IL-1ß, IL-6, IL-8, IL-10, TNF-α, IFN-γ, HGF, and TGF-ß), with investigators blinded to the patient groups. Lymphocytic alveolitis with plasmocytes was observed in acute COVID-19 pneumonia, returning to normal post-COVID-19. The highest cytokine levels were observed in COVID-19 patients, with significantly increased IFN-γ, IL-10, and HGF levels compared to non-COVID-19 patients, while significantly decreased IL-6, IL-8, IL-10, IFN-γ, TNF-α, and HGF levels were noted in post-COVID-19 patients. In COVID-19 patients, correlations between IL-10, TNF-α and IFN-γ concentrations were found. Lymphocytic alveolitis with plasmacytosis was found in non-critical COVID-19 pneumonia This alveolitis is associated with the presence of IL-6, IL-8, IL-10, TNF-α, IFN-γ and HGF. Alveolitis and cytokines levels decreased in post-COVID-19 pneumonia.

Artificial intelligence in thoracic surgery: past, present, perspective and limits.

Artificial intelligence (AI) technology is becoming prevalent in many areas of everyday life. The healthcare industry is concerned by it even though its widespread use is still limited. Thoracic surgeons should be aware of the new opportunities that could affect their daily practice, by direct use of AI technology or indirect use via related medical fields (radiology, pathology and respiratory medicine). The objective of this article is to review applications of AI related to thoracic surgery and discuss the limits of its application in the European Union. Key aspects of AI will be developed through clinical pathways, beginning with diagnostics for lung cancer, a prognostic-aided programme for decision making, then robotic surgery, and finishing with the limitations of AI, the legal and ethical issues relevant to medicine. It is important for physicians and surgeons to have a basic knowledge of AI to understand how it impacts healthcare, and to consider ways in which they may interact with this technology. Indeed, synergy across related medical specialties and synergistic relationships between machines and surgeons will likely accelerate the capabilities of AI in augmenting surgical care.

Treatment of chronic pulmonary aspergillosis by voriconazole in nonimmunocompromised patients.

BACKGROUND: There is no recognized medical treatment for chronic pulmonary aspergillosis (CPA) apart from surgery in patients with simple aspergilloma. To evaluate the efficacy of voriconazole in this setting, we conducted a retrospective multicenter study over a 3-year period. METHODS: For inclusion in the study, patients had to have received voriconazole for treatment of confirmed or probable CPA with a follow-up of at least 6 months. Clinical, radiologic, and mycologic data were collected at baseline, every 2 to 3 months, and at the end of treatment or at the date point. RESULTS: Twenty-four patients were included in the study, among which 9 patients presented with chronic cavitary pulmonary aspergillosis and 15 presented with chronic necrotizing pulmonary aspergillosis (CNPA). Voriconazole was given as a first-line treatment to 13 patients. The median duration of treatment and follow-up were 6.5 and 10 months, respectively. Three patients had to stop treatment with voriconazole because of toxicity. Symptoms and imagery findings were improved in 16 of 24 patients and 17 of 24 patients, respectively, at the end of follow-up. Mycology, which was positive at baseline in 21 of 23 patients, was negative in 18 of 19 patients at the end of follow-up; serologic test results were also negative in 6 of 19 evaluable patients, all of whom had CNPA. Improved radioclinical findings and mycologic eradication were observed at the end of follow-up in 11 of 19 patients (58%). Patients in whom the disease was controlled had a significantly longer median duration of treatment than patients in whom it was uncontrolled (9 vs 6 months, respectively; p = 0.04). CONCLUSION: Voriconazole provides effective treatment of CPA with an acceptable level of toxicity.

Needle aspiration as first-line management of primary spontaneous pneumothorax.

BACKGROUND: Initial management of primary spontaneous pneumothorax (PSP) remains a topic of debate. Recent guidelines recommend needle aspiration as the initial strategy for large PSP, but chest tube drainage is still widely used. METHODS: Over a six-year period, we used needle aspiration in all cases of large PSP at our center to assess this technique's efficacy in real-life clinical practice. Our prospective study in the pulmonary intensive care unit of a 680-bed university hospital included patients with a PSP greater than 20%, as estimated by the Light's index. Needle aspiration, performed after local anesthesia, used a plastic intravenous catheter. If it failed, we performed thoracic drainage. RESULTS: The study included 35 patients. The initial success rate of needle aspiration was 69% (n=24/35), the one-week success rate 63% (n=22/35), and the one-year rate 51% (n=18/35). Tolerance of needle aspiration was good except for transient vagal reaction in four patients. No risk factors (age, body mass index, delay before hospitalization, previous pneumothorax, or Light index at inclusion) predicted initial failure of needle aspiration. CONCLUSION: Our results confirmed that needle aspiration is an attractive therapeutic option for patients with large PSP: success was observed in approximately two thirds of cases.

Pulmonary fibrosis in antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis: a series of 49 patients and review of the literature.

Pulmonary fibrosis (PF) is an uncommon manifestation observed in patients with antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV), particularly microscopic polyangiitis (MPA). While patients with PF associated with AAV seem to have a worse prognosis, these patients have been described only in case reports or small retrospective case series. In this retrospective multicenter study, we report the main features and long-term outcomes of patients with PF associated with AAV, fulfilling the American College of Rheumatology criteria and/or Chapel Hill definitions. Forty-nine patients (30 men [61%]; median age at diagnosis of AAV, 68 [interquartile range, 58-73] years) with PF associated with AAV were identified. Forty (81.6%) patients had MPA and 9 (18.4%) had granulomatosis with polyangiitis. The diagnosis of PF preceded the onset of vasculitis in 22 (45%) patients. Usual interstitial pneumonia was the main radiologic pattern (n = 18, 43%). ANCA were mostly of antimyeloperoxidase specificity (88%). All patients were treated with glucocorticoids as induction therapy, combined with cyclophosphamide (CYC) (n = 36, 73.5%) or rituximab (RTX) (n = 1, 2%). Factors associated with mortality included occurrence of chronic respiratory insufficiency (hazard ratio [HR], 7.44; 95% confidence interval [CI], 1.6-34.5; p = 0.003), induction therapy with glucocorticoids alone (HR, 2.94; CI, 1.05-8.33; p = 0.04), and initial weigh loss (HR, 2.83; CI, 1.05-7.65; p = 0.041). The 3-year survival rate in patients treated with glucocorticoids alone or combined with an immunosuppressant (CYC or RTX) as induction therapy was 64% (95% CI, 41-99) and 94% (95% CI, 86-100), respectively (p = 0.03). After a median follow-up of 48 months [interquartile range, 14-88 mo], 18 (37%) patients died, including 11 related to respiratory insufficiency. PF is a rare manifestation of AAV with a very poor prognosis. Induction therapy with CYC might improve the outcome.

Functional analysis of DNA gyrase mutant enzymes carrying mutations at position 88 in the A subunit found in clinical strains of Mycobacterium tuberculosis resistant to fluoroquinolones.

We investigated the enzymatic efficiency and inhibition by quinolones of Mycobacterium tuberculosis DNA gyrases carrying the previously described GyrA G88C mutation and the novel GyrA G88A mutation harbored by two multidrug-resistant clinical strains and reproduced by site-directed mutagenesis. Fluoroquinolone MICs and 50% inhibitory concentrations for both mutants were 2- to 43-fold higher than for the wild type, demonstrating that these mutations confer fluoroquinolone resistance in M. tuberculosis.

Functional results of unilateral lung volume reduction surgery in alpha1-antitrypsin deficient patients.

Lung volume reduction surgery (LVRS) has been shown to improve lung function and exercise tolerance in patients with severe emphysema. Some predictors of poor outcome have been described but the role of alpha1-antitrypsin (alpha1-AT) deficiency is still not well known. The aim of this study was to analyze the results of unilateral LVRS in our center according to the alpha1-AT status. The results of LVRS in 17 deficient patients and 35 nondeficient patients were analyzed at 3-6 months and 1 year after surgery. Compared with baseline, a significant improvement of FEV1, partial pressure in arterial blood (PaO2), dyspnea score and walking distance was observed in the two groups at 3-6 months after surgery and the studied parameters remained significantly improved at 1 year in the nondeficient group. By contrast, PaO2 and walking distance returned towards baseline in the deficient group at 1 year whereas improvement of FEV1 and dyspnea score was persistent. Mean values of FEV, at baseline, 3-6 months, and 1 year were 22 +/- 6%, 29 +/- 11%, and 26 +/- 9% and 28 +/- 12%, 38 +/- 17%, and 40 +/- 17% predicted in the deficient group and in the non-deficient group, respectively. In conclusion, the functional benefit is short-lasting in alpha1-AT deficient patients after unilateral LVRS.