Multiple primary lung cancer: Updates and perspectives.

Management of multiple primary lung cancer (MPLC) remains challenging, partly due to its increasing incidence, especially with the significant rise in cases of multiple lung nodules caused by low-dose computed tomography screening. Moreover, the indefinite pathogenesis, diagnostic criteria, and treatment selection add to the complexity. In recent years, there have been continuous efforts to dissect the molecular characteristics of MPLC and explore new diagnostic approaches as well as treatment modalities, which will be reviewed here, with a focus on newly emerging evidence and future perspectives, hope to provide new insights into the management of MPLC and serve as inspiration for future research related to MPLC.

Differences between women and men in prolonged weaning.

BACKGROUND: In recent years, the importance of sex as a factor influencing medical care has received increasing attention in the field of intensive care medicine. The objective of this study was to examine the influence of sex in prolonged weaning. METHODS: A retrospective analysis of patients undergoing prolonged weaning at Thoraxklinik, University Hospital Heidelberg between 12/08 and 12/23 was conducted. Patients with neuromuscular diseases were excluded from the analyses. The risk factors for weaning failure in men and women were identified through stepwise cox-regression analyses. RESULTS: A total of 785 patients were included, of whom 313 (39.9%) were women. 77.9% of the women and 75.4% of the men were successfully weaned from invasive ventilation. In group comparisons and multivariable analyses, sex was not found to be a risk factor for weaning failure. Cox regression analyses were performed separately for both sexes on the outcome of weaning failure, adjusting for relevant covariates. The results indicated that age ≥ 65 years (HR 2.38, p < 0.001) and the duration of IMV before transfer to the weaning centre (HR 1.01/day, p < 0.001) were independent risk factors in men. In women, however, the duration of IMV before transfer (HR 1.01, p < 0.001), previous non-invasive ventilation (HR 2.9, p 0.005), the presence of critical illness polyneuropathy (HR 1.82; p = 0.040) and delirium (HR 2.50, p = 0.017) were identified as relevant risk factors. In contrast delirium was associated with a favourable weaning outcome in men (HR 0.38, p = 0.020) and nosocomial pneumonia as a reason for prolonged weaning in women (HR 0.43; p = 0.032). CONCLUSION: The analyses indicate that there are sex-based differences in the risk factors associated with weaning failure. Further studies, ideally prospective, should confirm these findings to assess whether sex is a factor that should be taken into account to improve weaning outcomes.

Role of multidrug-resistant bacteria in weaning from invasive mechanical ventilation.

BACKGROUND: Although multidrug-resistant bacteria (MDR) are common in patients undergoing prolonged weaning, there is little data on their impact on weaning and patient outcomes. METHODS: This is a retrospective analysis of consecutive patients who underwent prolonged weaning and were at a university weaning centre from January 2018 to December 2020. The influence of MDR colonisation and infection on weaning success (category 3a and 3b), successful prolonged weaning from invasive mechanical ventilation (IMV) with or without the need for non-invasive ventilation (NIV) compared with category 3c (weaning failure 3cI or death 3cII) was investigated. The pathogen groups considered were: multidrug-resistant gram-negative bacteria (MDRGN), methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus spp. (VRE). RESULTS: A total of 206 patients were studied, of whom 91 (44.2%) showed evidence of MDR bacteria (32% VRE, 1.5% MRSA and 16% MDRGN), with 25 patients also meeting the criteria for MDR infection. 70.9% of the 206 patients were successfully weaned from IMV, 8.7% died. In 72.2% of cases, nosocomial pneumonia and other infections were the main cause of death. Patients with evidence of MDR (infection and colonisation) had a higher incidence of weaning failure than those without evidence of MDR (48% vs. 34.8% vs. 21.7%). In multivariate analyses, MDR infection (OR 4.9, p = 0.004) was an independent risk factor for weaning failure, along with male sex (OR 2.3, p = 0.025), Charlson Comorbidity Index (OR 1.2, p = 0.027), pH (OR 2.7, p < 0.001) and duration of IMV before admission (OR 1.01, p < 0.001). In addition, MDR infection was the only independent risk factor for death (category 3cII), (OR 6.66, p = 0.007). CONCLUSION: Patients with MDR infection are significantly more likely to die during the weaning process. There is an urgent need to develop non-antibiotic approaches for the prevention and treatment of MDR infections as well as clinical research on antibiotic stewardship in prolonged weaning as well as in ICUs.

Midregional Proatrial Natriuretic Peptide (MRproANP) is associated with vertebral fractures and low bone density in patients with chronic obstructive pulmonary disease (COPD).

BACKGROUND: Patients with COPD are often affected by loss of bone mineral density (BMD) and osteoporotic fractures. Natriuretic peptides (NP) are known as cardiac markers, but have also been linked to fragility-associated fractures in the elderly. As their functions include regulation of fluid and mineral balance, they also might affect bone metabolism, particularly in systemic disorders such as COPD. RESEARCH QUESTION: We investigated the association between NP serum levels, vertebral fractures and BMD assessed by chest computed tomography (CT) in patients with COPD. METHODS: Participants of the COSYCONET cohort with CT scans were included. Mean vertebral bone density on CT (BMD-CT) as a risk factor for osteoporosis was assessed at the level of TH12 (AI-Rad Companion), and vertebral compression fractures were visually quantified by two readers. Their relationship with N-terminal pro-B-type natriuretic peptide (NT-proBNP), Mid-regional pro-atrial natriuretic peptide (MRproANP) and Midregional pro-adrenomedullin (MRproADM) was determined using group comparisons and multivariable analyses. RESULTS: Among 418 participants (58% male, median age 64 years, FEV1 59.6% predicted), vertebral fractures in TH12 were found in 76 patients (18.1%). Compared to patients without fractures, these had elevated serum levels (p ≤ 0.005) of MRproANP and MRproADM. Using optimal cut-off values in multiple logistic regression analyses, MRproANP levels ≥ 65 nmol/l (OR 2.34; p = 0.011) and age (p = 0.009) were the only significant predictors of fractures after adjustment for sex, BMI, smoking status, FEV1% predicted, SGRQ Activity score, daily physical activity, oral corticosteroids, the diagnosis of cardiac disease, and renal impairment. Correspondingly, MRproANP (p < 0.001), age (p = 0.055), SGRQ Activity score (p = 0.061) and active smoking (p = 0.025) were associated with TH12 vertebral density. INTERPRETATION: MRproANP was a marker for osteoporotic vertebral fractures in our COPD patients from the COSYCONET cohort. Its association with reduced vertebral BMD on CT and its known modulating effects on fluid and ion balance are suggestive of direct effects on bone mineralization. TRIAL REGISTRATION: ClinicalTrials.gov NCT01245933, Date of registration: 18 November 2010.

Risk factors for long-term invasive mechanical ventilation: a longitudinal study using German health claims data.

BACKGROUND: Long-term invasive mechanical ventilation (IMV) is a major burden for those affected and causes high costs for the health care system. Early risk assessment is a prerequisite for the best possible support of high-risk patients during the weaning process. We aimed to identify risk factors for long-term IMV within 96 h (h) after the onset of IMV. METHODS: The analysis was based on data from one of Germany's largest statutory health insurance funds; patients who received IMV ≥ 96 h and were admitted in January 2015 at the earliest and discharged in December 2017 at the latest were analysed. OPS and ICD codes of IMV patients were considered, including the 365 days before intubation and 30 days after discharge. Long-term IMV was defined as evidence of invasive home mechanical ventilation (HMV), IMV ≥ 500 h, or readmission with (re)prolonged ventilation. RESULTS: In the analysis of 7758 hospitalisations, criteria for long-term IMV were met in 38.3% of cases, of which 13.9% had evidence of HMV, 73.1% received IMV ≥ 500 h and/or 40.3% were re-hospitalised with IMV. Several independent risk factors were identified (p < 0.005 each), including pre-diagnoses such as pneumothorax (OR 2.10), acute pancreatitis (OR 2.64), eating disorders (OR 1.99) or rheumatic mitral valve disease (OR 1.89). Among ICU admissions, previous dependence on an aspirator or respirator (OR 5.13), and previous tracheostomy (OR 2.17) were particularly important, while neurosurgery (OR 2.61), early tracheostomy (OR 3.97) and treatment for severe respiratory failure such as positioning treatment (OR 2.31) and extracorporeal lung support (OR 1.80) were relevant procedures in the first 96 h after intubation. CONCLUSION: This comprehensive analysis of health claims has identified several risk factors for the risk of long-term ventilation. In addition to the known clinical risks, the information obtained may help to identify patients at risk at an early stage. Trial registration The PRiVENT study was retrospectively registered at ClinicalTrials.gov (NCT05260853). Registered at March 2, 2022.

Safety and efficacy of a novel transbronchial radiofrequency ablation system for lung tumours: One year follow-up from the first multi-centre large-scale clinical trial (BRONC-RFII).

BACKGROUND AND OBJECTIVE: Radiofrequency ablation (RFA) is an emerging treatment of lung cancer, yet it is accompanied by certain safety concerns and operational limitations. This first multi-centre, large-scale clinical trial aimed to investigate the technical performance, efficacy and safety of an innovative transbronchial RFA system for lung tumours. METHODS: The study enrolled patients with malignant lung tumours who underwent transbronchial RFA using an automatic saline microperfusion system between January 2021 and December 2021 across 16 medical centres. The primary endpoint was the complete ablation rate. The performance and safety of the technique, along with the 1-year survival rates, were evaluated. RESULTS: This study included 126 patients (age range: 23-85 years) with 130 lung tumours (mean size: 18.77 × 14.15 mm) who had undergone 153 transbronchial RFA sessions, with a technique success rate of 99.35% and an average ablation zone size of 32.47 mm. At the 12-month follow-up, the complete ablation rate and intrapulmonary progression-free survival rates were 90.48% and 88.89%, respectively. The results of patients with ground-glass nodules (GGNs) were superior to those of the patients with solid nodules (12-month complete ablation rates: solid vs. pure GGN vs. mixed GGN: 82.14% vs. 100% vs. 96.08%, p = 0.007). No device defects were reported. Complications such as pneumothorax, haemoptysis, pleural effusion, pulmonary infection and pleural pain were observed in 3.97%, 6.35%, 8.73%, 11.11% and 10.32% of patients, respectively. Two subjects died during the follow-up period. CONCLUSION: Transbronchial RFA utilizing an automatic saline microperfusion system is a viable, safe and efficacious approach for the treatment for lung tumours, particularly for patients with GGNs.

Comparison between Endobronchial Ultrasound-Guided Transbronchial Node Biopsy and Transbronchial Needle Aspiration: A Meta-Analysis.

INTRODUCTION: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) can be limited by the inadequacy of intact tissues, especially in patients with lymphoma, sarcoidosis, and lymph node tuberculosis. A novel technique called transbronchial node biopsy (TBNB) by forceps or cryoprobe has been proposed and studied to improve specimen quality and diagnostic yield. We performed a systematic review of studies describing the safety and sensitivity of EBUS-TBNB versus EBUS-TBNA in diagnosing intrathoracic lymphadenopathy/masses. METHODS: We systematically searched MEDLINE, Embase, Cochrane, and China National Knowledge Infrastructure to identify studies focusing on the application of EBUS-TBNB for diagnosis of intrathoracic lymphadenopathy. The quality of each study was evaluated using the QUADAS-2 tool. Using inverse-variance (I-V) weighting, we performed a meta-analysis of diagnostic yield estimations. We also reviewed the complications related to the procedure. RESULTS: Thirteen studies were included in the final analysis. The meta-analysis yielded a pooled overall diagnostic yield of 77.80% (939/1,207) for EBUS-TBNA and 86.01% (834/958) for EBUS-TBNB, with an inverse-variance-weighted odds ratio of 3.13 (95% confidence interval [CI], 1.61-6.01; p = 0.0008) and I2 of 82%. The pooled diagnostic yield of EBUS-TBNB versus EBUS-TBNA for the diagnosis of malignancy (including primary lung cancer and extrapulmonary malignancy) was 84.53% (590/698) for EBUS-TBNA and 90.84% (476/524) for EBUS-TBNB, with an I-V-weighted OR of 2.33 (95% CI, 1.15-4.74; p = 0.02) and I2 of 64%. The pooled diagnostic yield of EBUS-TBNB versus EBUS-TBNA for the diagnosis of benignancy was 71.19% (252/354) for EBUS-TBNA and 86.62% (233/269) for EBUS-TBNB, with an I-V-weighted OR of 4.39 (95% CI, 2.00-9.65; p = 0.002) and I2 of 59%. The overall complications included bleeding (n = 11, 0.90%), pneumomediastinum (n = 6, 0.49%), pneumothorax (n = 6, 0.49%), pneumonia (n = 4, 0.33%), respiratory failure (n = 1, 0.08%), and haemoptysis (n = 1, 0.08%). The funnel plot analysis illustrated no major publication bias. CONCLUSIONS: EBUS-TBNB improves the overall diagnostic yield of sampling intrathoracic lymphadenopathy and mass lesions relative to EBUS-TBNA. The complication rate of EBUS-TBNB is higher than that of EBUS-TBNA but reportedly lower than that of surgical biopsies.

Potential of Thermal Ablation Combined with Immunotherapy in Peripheral Lung Tumors: A Review and Prospect.

BACKGROUND: Lung tumors are prevalent malignancies associated with a high mortality rate, imposing significant medical and societal burdens. Although immunotherapy shows promise in improving survival, response rates are relatively modest. Thermal ablation can not only eliminate tumor cells directly but also enhance antitumor immunity response, thus manifesting a remarkable propensity to synergize with immunotherapy. SUMMARY: In this review, we provided a brief overview of the application of thermal ablation in peripheral lung tumors. We summarized the patient selection of thermal ablation. We highlighted the potential of thermal ablation to augment the antitumor immune response, offering a promising avenue for combined therapies. We summarized studies assessing the synergistic effects of thermal ablation and immunotherapy in preclinical and clinical settings. Lastly, we underscored the urgent issues that warrant in-depth exploration when applying thermal ablation and immunotherapy to lung tumor patients. KEY MESSAGES: This review emphasized the prospects of using thermal ablation combined with immunotherapy in patients with peripheral lung tumors. However, further research is needed to enhance and optimize this treatment strategy.

Transbronchial Cryobiopsy Using the Ultrathin 1.1-mm Cryoprobe with Ultrathin Bronchoscopy under Radial Endobronchial Ultrasound Guidance for Diagnosis of Peripheral Pulmonary Lesions.

INTRODUCTION: Today, the increasing number of incidentally detected peripheral pulmonary lesions (PPLs) within and outside lung cancer screening trials is a diagnostic challenge. This fact encourages further improvement of diagnostic procedures to increase the diagnostic yield of transbronchial biopsy, which has been shown to have a low complication rate. The purpose of this study was to evaluate the safety and feasibility of a new ultrathin 1.1 cryoprobe that can be placed through an ultrathin bronchoscope (UTB) using fluoroscopy and radial endobronchial ultrasonography (rEBUS) navigation for assessing PPLs. METHODS: Thirty-five patients with PPL less than 4 cm in diameter were prospectively enrolled to receive transbronchial cryobiopsies (TBCBs) using the ultrathin 1.1-mm cryoprobe. Navigation to the PPL was accomplished with the UTB. Under rEBUS and fluoroscopy guidance up to 4 cryobiopsies were obtained. The sample sizes of the biopsies were compared to a historic collective derived from a 1.9-mm cryoprobe and standard forceps. The feasibility and safety of the procedure, the cumulative and overall diagnostic yield, and the cryobiopsy sizes were evaluated. RESULTS: After detection with the rEBUS, TBCB was collected from 35 PPLs, establishing a diagnosis in 25 cases, corresponding to an overall diagnostic yield of 71.4%. There was no difference in diagnostic yield for PPL <20 mm or ≥20 mm. All cryobiopsies were representative with a mean tissue area of 11.9 ± 4.3 mm2, which was significantly larger compared to the historic collective (p = 0.003). Six mild and four moderate bleeding events and 1 case of pneumothorax were observed. CONCLUSIONS: Using the ultrathin 1.1-mm cryoprobe combined with an UTB for rEBUS-guided TBCB of PPL is feasible and safe. This diagnostic approach improves bronchoscopic techniques for diagnosing peripheral lung lesions and may contribute to improve diagnosis of lung cancer even in small PPL.

Body Composition after Endoscopic Lung Volume Reduction with Endobronchial Valves: A Prospective Study.

INTRODUCTION: Patients with chronic obstructive pulmonary disease (COPD) and emphysema experience malnutrition and pulmonary cachexia. Endoscopic lung volume reduction (ELVR) with endobronchial valves has not only improved lung function, exercise capacity, and quality of life but also influenced body weight. Only a few data are available on body composition changes after ELVR. METHODS: This single-center prospective study of patients with advanced COPD investigates body composition before and after endoscopic valve treatment using multifrequency bioelectrical impedance analysis (BIA). The following parameters were evaluated in addition to clinical data and routine tests: body weight, body mass index (BMI), basal metabolic rate, total body water, body fat, cell percentage, phase angle, intracellular water (ICW), extracellular water (ECW), extracellular mass (ECM), body cell mass (BCM), lean body mass (ECM + BCM), and fat-free mass index. RESULTS: A total of 23 patients (mean emphysema index 37.2 ± 7.5%, BMI 23.4 ± 4.3 kg/m2) experienced improvements in lung function and exercise capacity with ELVR. Complete lobar atelectasis was achieved in 39.1% of participants. A non-statistically significant increase in body weight and BMI was observed after ELVR (p = 0.111 and p = 0.102). BIA measurement revealed a worsening of phase angle, cell percentage and ECM/BCM and thus of body composition, but without statistical significance. This is mainly due to a statistically significant increase in ECM, ECW, and ICW (all p < 0.001). CONCLUSION: ELVR demonstrated no beneficial changes in body composition, although patients tend to gain weight. A larger cohort is warranted to confirm these findings.

Percutaneous Ultrasound-Guided Medication Injection: A Potential Technique for Subglottic Stenosis.

INTRODUCTION: Subglottic stenosis, manifested by granulation tissue hyperplasia, is challenging and requires multiple repeated treatments and stent maintenance at times. Corticosteroids prevent severe subglottic stenosis development owing to their antifibrotic and anti-inflammatory properties. Submucosal injection of glucocorticoids, a useful adjuvant therapeutic method, improves the mean interval between endoscopic procedures and reduces airway restenosis risks. CASE PRESENTATION: We report a rare case of a man with complex subglottic stenosis who underwent balloon dilatation combined with cryotherapy, stent placement, and adjuvant submucosal triamcinolone injection. The drug was injected efficiently and safely into the submucosal layer under percutaneous ultrasound guidance, and subglottic stenosis was well-controlled at a low cost. CONCLUSION: POCUS-guided medication injections may be a useful adjuvant medical therapy for subglottic stenosis.

A Novel Procedure for Endobronchial Ultrasound-Guided Transbronchial Mediastinal Cryobiopsy with a Puncture Dilation Catheter.

INTRODUCTION: Endobronchial ultrasound (EBUS)-guided transbronchial mediastinal cryobiopsy (TBMC) is increasingly used to diagnose mediastinal lymphadenopathy. Various methods have been used to create a tunnel between the airway wall and the lesions for this procedure, such as electrocautery and penetration with the sheath of the needle for EBUS-transbronchial fine needle aspiration. However, those methods are complex. CASE PRESENTATION: We developed a new technique called EBUS-TBMC via a tunnel, and we used it in four cases of mediastinal and/or hilar lymphadenopathy. We used a puncture dilation catheter to create a tunnel between the airway wall and the target lymph node. The cryoprobe was introduced to the target lymph node and cooled with liquid carbon dioxide for 5-9 s. The probe was subsequently pulled out with the samples to complete the EBUS-TBMC via a tunnel. A definite diagnosis was made based on pathological examination of the samples obtained in all four cases. After the procedure, none of the patients experienced moderate to severe bleeding, pneumothorax, pneumomediastinum, or other adverse events. CONCLUSION: EBUS-TBMC via a tunnel is a feasible and convenient procedure for the performance of TBMC. Further studies are required to evaluate the safety and efficacy of EBUS-TBMC via a tunnel.

Mask Continuous Positive Airway Pressure Increases Diaphragm Thickening Fraction in Healthy Subjects.

INTRODUCTION: The most widespread treatment for obstructive sleep apnoea and obesity hypoventilation syndrome is continuous positive airway pressure (CPAP). The addition of inspiratory support is a potential alternative. This is a physiological study to determine the effect of CPAP and inspiratory support pressure on respiratory effort measured by diaphragm thickening fraction (DTF) in healthy volunteers. METHODS: DTF was measured in spontaneously breathing, healthy volunteers during 4 phases: (I) without connection to a ventilator, (II) on a ventilator without any applied pressures, (III) with a CPAP of 5 cmH2O, and (IV) with an additional inspiratory support pressure of 5 cmH2O. RESULTS: Twenty-nine individuals agreed to participate. DTF was similar during the first two phases (32 ± 13% and 35 ± 22%). A considerable increase in DTF to 51 ± 21% was noted in phase III. The introduction of inspiratory support pressure during phase IV led to a reduction in DTF back to 36 ± 23% (p < 0.001). Tidal volume and minute ventilation were both slightly higher in phase IV compared to phase III. CONCLUSION: CPAP without inspiratory support pressure increases respiratory effort measured by DTF in healthy subjects. Further research is required to investigate this phenomenon in a clinical setting.

Advances in the Treatment of Pulmonary Nodules.

BACKGROUND: Early detection and accurate diagnosis of pulmonary nodules are crucial for improving patient outcomes. While surgical resection of malignant nodules is still the preferred treatment option, it may not be feasible for all patients. We aimed to discuss the advances in the treatment of pulmonary nodules, especially stereotactic body radiotherapy (SBRT) and interventional pulmonology technologies, and provide a range of recommendations based on our expertise and experience. SUMMARY: Interventional pulmonology is an increasingly important approach for the management of pulmonary nodules. While more studies are needed to fully evaluate its long-term outcomes and benefits, the available evidence suggests that this technique can provide a minimally invasive and effective alternative for treating small malignancies in selected patients. We conducted a systematic literature review in PubMed, designed a framework to include the advances in surgery, SBRT, and interventional pulmonology for the treatment of pulmonary nodules, and provided a range of recommendations based on our expertise and experience. KEY MESSAGES: As such, alternative therapeutic options such as SBRT and ablation are becoming increasingly important and viable. With recent advancements in bronchoscopy techniques, ablation via bronchoscopy has emerged as a promising option for treating pulmonary nodules. This study reviewed the advances of interventional pulmonology in the treatment of peripheral lung cancer patients that are not surgical candidates. We also discussed the challenges and limitations associated with ablation, such as the risk of complications and the potential for incomplete nodule eradication. These advancements hold great promise for improving the efficacy and safety of interventional pulmonology in treating pulmonary nodules.

Endobronchial Ultrasound-Based Support Vector Machine Model for Differentiating between Benign and Malignant Mediastinal and Hilar Lymph Nodes.

INTRODUCTION: The aim of the study was to establish an ultrasonographic radiomics machine learning model based on endobronchial ultrasound (EBUS) to assist in diagnosing benign and malignant mediastinal and hilar lymph nodes (LNs). METHODS: The clinical and ultrasonographic image data of 197 patients were retrospectively analyzed. The radiomics features extracted by EBUS-based radiomics were analyzed by the least absolute shrinkage and selection operator. Then, we used a support vector machine (SVM) algorithm to establish an EBUS-based radiomics model. A total of 205 lesions were randomly divided into training (n = 143) and validation (n = 62) groups. The diagnostic efficiency was evaluated by receiver operating characteristic (ROC) curve analysis. RESULTS: A total of 13 stable radiomics features with non-zero coefficients were selected. The SVM model exhibited promising performance in both groups. In the training group, the SVM model achieved an ROC area under the curve (AUC) of 0.892 (95% CI: 0.885-0.899), with an accuracy of 85.3%, sensitivity of 93.2%, and specificity of 79.8%. In the validation group, the SVM model had an ROC AUC of 0.906 (95% CI: 0.890-0.923), an accuracy of 74.2%, a sensitivity of 70.3%, and a specificity of 74.1%. CONCLUSION: The EBUS-based radiomics model can be used to differentiate mediastinal and hilar benign and malignant LNs. The SVM model demonstrated excellent potential as a diagnostic tool in clinical practice.

Endobronchial Valves in Treatment of Persistent Air Leak: European Case-Series Study and Best Practice Recommendations - From an Expert Panel.

INTRODUCTION: Persistent air leak (PAL) is associated with prolonged hospitalization, high morbidity and increased treatment costs. Conservative treatment consists of observation, chest tube drainage, and pleurodesis. Guidelines recommend surgical evaluation if air leak does not respond after 3-5 days. One-way endobronchial valves (EBV) have been proposed as a treatment option for patients with PAL in which surgical treatment is not feasible, high risk or has failed. We aimed to provide a comprehensive overview of reported EBV use for PAL and issue best practice recommendations based on multicenter experience. METHODS: We conducted a retrospective observational case-series study at four different European academic hospitals and provided best practice recommendations based on our experience. A systematic literature review was performed to summarize the current knowledge on EBV in PAL. RESULTS: We enrolled 66 patients, male (66.7%), median age 59.5 years. The most common underlying lung disease was chronic obstructive pulmonary disease (39.4%) and lung cancer (33.3%). The median time between pneumothorax and valve placement was 24.5 days (interquartile range: 14.0-54.3). Air leak resolved in 40/66 patients (60.6%) within 30 days after EBV treatment. Concerning safety outcome, no procedure-related mortality was reported and complication rate was low (6.1%). Five patients (7.6%) died in the first 30 days after intervention. CONCLUSION: EBV placement is a treatment option in patients with PAL. In this multicenter case-series of high-risk patients not eligible for lung surgery, we show that EBV placement resulted in air leak resolution in 6 out of 10 patients with a low complication rate. Considering the minimally invasive nature of EBV to treat PAL as opposed to surgery, further research should investigate if EBV treatment should be expanded in low to intermediate risk PAL patients.

Lung Tensioning Device Coil Treatment in Patients with Severe Emphysema: A Prospective Safety and Feasibility Trial (EFFORT).

INTRODUCTION: Currently, there is a lack of bronchoscopic lung volume reduction options that do not depend on fissure integrity. Endobronchial coils have been extensively studied to address this need but exhibited variable patient response and have been discontinued. Lung tension device (LTD) coils represent the next-generation coil treatment. This study aimed to evaluate safety, feasibility, and efficacy of LTD-coil treatment. METHODS: Patients with advanced emphysema and hyperinflation were enrolled at two European sites. LTD-coils (Free Flow Medical, Fremont, CA, USA) were implanted in the two most destructed lobes, as determined by quantitative CT analysis, in two separate procedures. The primary endpoint was 3-month follow-up after the last treatment. RESULTS: Fourteen patients (50% male, median age 64 years, FEV1 23%predicted, RV 249%predicted) received LTD-coil treatment: 12 received bilateral and 2 unilateral treatment. Six serious respiratory adverse events occurred within the initial 3 months posttreatment, including one device-associated death. Treatment significantly reduced in- and expiratory volume of the treated lobes (-410 [-710, -340], p = 0.004 and -650 [-730, -190] mL, p < 0.001, respectively) and improved quality of life (SGRQ total score -4.6 [-21.0, -2.6], p < 0.001). However, at a group level, no significant improvements in pulmonary function or 6-min walk distance were observed. Responder rates ranged from 18% to 54% for the different endpoints. CONCLUSION: This first-in-human study shows that the new LTD-coil procedure is feasible with a safety profile comparable to the previous coil treatment. While the treatment effectively reduced lobar volume and modestly improved quality of life up to 3 months' follow-up, at a group level it did not significantly enhance pulmonary function or exercise capacity.

Radiation Principles, Protection, and Reporting for Interventional Pulmonology: A World Association of Bronchology and Interventional Pulmonology White Paper.

The use and availability of diverse advanced X-ray based imaging and guidance systems in the field of interventional pulmonology are rapidly growing. This popularity links inextricably to an increase in ionizing radiation use. Knowing ionizing radiation is hazardous, knowledge and competent use of X-ray imaging and guidance systems are important. The globally implemented As Low As Reasonably Achievable (ALARA) principle demands careful attention to minimize radiation exposure while achieving the precise goals of the intervention and imaging therein. To allow careful and targeted weighing of risk against reward while using X-ray based equipment, proper background knowledge of physics as well as imaging system aspects are needed. This white paper summarizes the principles of ionizing radiation which are crucial to enhance awareness and interpretation of dosimetric quantities. Consecutively, a consensus on standards for reporting radiation exposure in interventional pulmonology procedures is indicated to facilitate comparisons between different systems, approaches and results. Last but not least, it provides a list of practical measures, considerations and tips to optimize procedural imaging as well as reduce radiation dose to patients and staff.

The Diagnostic Efficiency and Safety of Transbronchial Lung Cryobiopsy Using 1.1-mm Cryoprobe in Diagnosing Interstitial Lung Disease.

INTRODUCTION: Transbronchial lung cryobiopsy (TBLC) is increasingly used to diagnose interstitial lung disease (ILD). The 1.1-mm cryoprobe has recently been available in clinical practice. The diagnostic yield and safety of TBLC using a 1.1-mm cryoprobe need to be confirmed. METHODS: A prospective, randomized controlled trial was conducted in patients with suspected ILD and randomly assigned to 1.1-mm and 1.9-mm cryoprobe groups. The primary outcome was the diagnostic yield of multidisciplinary discussion. Secondary outcomes were sample quality and incidence of complications. The tension and stress effects during TBLC onto the target lobe caused by 1.1-mm and 1.9-mm cryoprobes were also evaluated using finite element analysis. RESULTS: A total of 224 patients were enrolled. No significant differences were observed in the diagnostic yield (80.4% vs. 79.5%, p = 0.845) and sample quality scores (5.73 ± 0.64 vs. 5.66 ± 0.77; p = 0.324) between the 1.9-mm cryoprobe group and 1.1-mm cryoprobe group. The average surface areas of samples in 1.1-mm cryoprobe group were smaller, while no difference in sample weights was observed. A decreased incidence of moderate bleeding was found in the 1.1-mm cryoprobe group (17.0% vs. 6.2%, p = 0.027), while there was no difference in the incidence of the pneumothorax, there was a trend to higher rate of pneumothorax in 1.1-mm group. In finite element analysis, the 1.1-mm cryoprobe required the largest tension and produced the largest stress. CONCLUSION: Compared with a 1.9-mm cryoprobe, there was no difference in specimen quality or diagnostic rate but smaller sample size with a 1.1-mm cryoprobe. There was a decreased risk of moderate bleeding, but a trend towards increased risk for pneumothorax with 1.1-mm cryoprobe. TRAIL REGISTRATION: Clinicaltrials.gov identifier NCT04047667; registered August 4, 2019.

Correlation of diaphragm thickening fraction and oesophageal pressure swing in non-invasive ventilation of healthy subjects.

INTRODUCTION: The diaphragm thickening fraction (DTF) may be a valuable tool for estimating respiratory effort in non-invasive ventilation. The primary aim of this physiological study is the investigation of the correlation of DTF with oesophageal pressure swings (ΔPoes). A secondary aim is to assess the discriminatory capacity of the index tests for different exercise loads. METHODS: Healthy volunteers underwent spontaneous breathing and non-invasive ventilation with a sequence of different respirator settings. The first sequence was carried out at rest. The same sequence was repeated twice, with additional ergometry of 25 and 50 Watts, respectively. DTF and ΔPoes were measured during each ventilation configuration. RESULTS: 23 individuals agreed to participate. DTF was moderately correlated with ΔPoes (repeated measures correlation ρ = 0.410, p < 0.001). Both ΔPoes and DTF increased consistently with exercise loading in every ventilation configuration, however ΔPoes showed greater discriminatory capacity. CONCLUSION: DTF was moderately correlated with ΔPoes and could discriminate reasonably between exercise loads in a small cohort of non-invasively ventilated healthy subjects. While it may not accurately reflect the absolute respiratory effort, DTF might help titrating individual non-invasive respiratory support. Further investigations are needed to test this hypothesis. TRIAL REGISTRATION: This study was not prospectively registered.