World Association for Bronchology and Interventional Pulmonology (WABIP) guidelines on airway stenting for malignant central airway obstruction.

Malignant Central Airway Obstruction (MCAO) encompasses significant and symptomatic narrowing of the central airways that can occur due to primary lung cancer or metastatic disease. Therapeutic bronchoscopy is associated with high technical success and symptomatic relief and includes a wide range of airway interventions including airway stents. Published literature suggests that stenting practices vary significantly across the world primarily due to lack of guidance. This document aims to address this knowledge gap by addressing relevant questions related to airway stenting in MCAO. An international group of 17 experts from 17 institutions across 11 countries with experience in using airway stenting for MCAO was convened as part of this guideline statement through the World Association for Bronchology and Interventional Pulmonology (WABIP). We performed a literature and internet search for reports addressing six clinically relevant questions. This guideline statement, consisting of recommendations addressing these six PICO questions, was formulated by a systematic and rigorous process involving the evaluation of published evidence, augmented with expert experience when necessary. Panel members participated in the development of the final recommendations using the modified Delphi technique.

Mapping IPF helps identify geographic regions at higher risk for disease development and potential triggers.

BACKGROUND AND OBJECTIVE: The relationship between IPF development and environmental factors has not been completely elucidated. Analysing geographic regions of idiopathic pulmonary fibrosis (IPF) cases could help identify those areas with higher aggregation and investigate potential triggers. We hypothesize that cross-analysing location of IPF cases and areas of consistently high air pollution concentration could lead to recognition of environmental risk factors for IPF development. METHODS: This retrospective study analysed epidemiological and clinical data from 503 patients registered in the Observatory IPF.cat from January 2017 to June 2019. Incident and prevalent IPF cases from the Catalan region of Spain were graphed based on their postal address. We generated maps of the most relevant air pollutant PM2.5 from the last 10 years using data from the CALIOPE air quality forecast system and observational data. RESULTS: In 2018, the prevalence of IPF differed across provinces; from 8.1 cases per 100 000 habitants in Barcelona to 2.0 cases per 100 000 in Girona. The ratio of IPF was higher in some areas. Mapping PM2.5 levels illustrated that certain areas with more industry, traffic and shipping maintained markedly higher PM2.5 concentrations. Most of these locations correlated with higher aggregation of IPF cases. Compared with other risk factors, PM2.5 exposure was the most frequent. CONCLUSION: In this retrospective study, prevalence of IPF is higher in areas of elevated PM2.5 concentration. Prospective studies with targeted pollution mapping need to be done in specific geographies to compile a broader profile of environmental factors involved in the development of pulmonary fibrosis.

Rapid effect of benralizumab in exacerbation of severe eosinophilic asthma associated with eosinophilic granulomatosis with polyangiitis.

BACKGROUND: Eosinophilic granulomatosis with polyangiitis (EGPA) is a disease that is associated with severe uncontrolled eosinophilic asthma. Eosinophils play an important pathogenic role in the development of both diseases. Benralizumab is an antieosinophilic monoclonal antibody that binds to the α subunit of the human interleukin 5 receptor that is expressed on the surface of the eosinophil and basophil. We present the first case of rapid improvement in symptoms and lung function during admission for exacerbation of a severe eosinophilic asthma associated with EGPA. CASE PRESENTATION: A 57-year-old man diagnosed with severe eosinophilic asthma associated to EGPA was admitted to the Pulmonology Department due to severe bronchospasm. At admission he presented 2300 eosinophils/µl. Despite intensive bronchodilator treatment, intravenous methylprednisolone at a dose of 80 mg/d, oxygen therapy, and budesonide nebulization, the patient continued to present daily episodes of bronchospasm. Ten days after admission, with blood eosinophil levels of 1700 cells/µl, benralizumab 30 mg sc was administered. That day, the Forced Expiratory Volume in the first second (FEV1) was 28% of the theoretical value (1150 ml). AT three days, FEV1 increased to 110 ml (31%). On the 9th day FEV1 was 51% (2100 ml). The blood eosinophil level on the 9th day was 0 cells/µl. CONCLUSIONS: The rapid improvement of FEV1 is in line with studies based on clinical trials that found improvement after two days in peak flow and one phase II study that showed rapid response in exacerbation of asthma in the emergency room. The antieosinophilic effect at 24 h and the effect in different tissues determine the rapid improvement and the potential advantage of benralizumab in the treatment of EGPA. This case suggests the usefulness of benralizumab in patients with EGPA and eosinophilic severe asthma who show bronchospasm refractory to conventional treatment during a hospitalization due to asthma exacerbation.

Predicting pulmonary embolism in patients infected with COVID-19 based on D-dimer levels and days between diagnosis of the infection and D-dimer determination.

Ruling out pulmonary embolism (PE) can be challenging in a situation of elevated D-dimer values such as in a case of COVID-19 infection. Our objective was to evaluate the difference in D-dimer values of subjects infected with COVID-19 in those with PE and those without and to analyze the predictive value of D-dimer for PE in these subjects based on the day of D-dimer determination. This was an observational, retrospective study, conducted at a tertiary hospital. All subjects with PCR-confirmed COVID-19 infection requiring hospital admission at our institution between the months of March and April 2020 were included in the study. We compared D-dimer levels in subjects who went on to develop a PE and those who did not. We then created a model to predict the subsequent development of a PE with the current D-dimer levels of the subject. D-dimer levels changed over time from COVID-19 diagnosis, but were always higher in subjects who went on to develop a PE. Regarding the predictive model created, the area under the curve of the ROC analyses of the cross-validation predictions was 0.72. The risk of pulmonary embolism for the same D-dimer levels varied depending on the number of days elapsed since COVID-19 diagnosis and D-dimer determination. To conclude, D-dimer levels were elevated in subjects with a COVID-19 infection, especially in those with PE. D-dimer levels increased during the first 10 days after the diagnosis of the infection and can be used to predict the risk of PE in COVID-19 subjects.

Bronchoscopist's perception of the quality of the single-use bronchoscope (Ambu aScope4™) in selected bronchoscopies: a multicenter study in 21 Spanish pulmonology services.

BACKGROUND: The disposable bronchoscope is an excellent alternative to face the problem of SARS-CoV-2 and other cross infections, but the bronchoscopist's perception of its quality has not been evaluated. METHODS: To evaluate the quality of the Ambu-aScope4 disposable bronchoscope, we carried out a cross-sectional study in 21 Spanish pulmonology services. We use a standardized questionnaire completed by the bronchoscopists at the end of each bronchoscopy. The variables were described with absolute and relative frequencies, measures of central tendency and dispersion depending on their nature. The existence of learning curves was evaluated by CUSUM analysis. RESULTS: The most frequent indications in 300 included bronchoscopies was bronchial aspiration in 69.3% and the median duration of these was 9.1 min. The route of entry was nasal in 47.2% and oral in 34.1%. The average score for ease of use, image, and aspiration quality was 80/100. All the planned techniques were performed in 94.9% and the bronchoscopist was satisfied in 96.6% of the bronchoscopies. They highlighted the portability and immediacy of the aScope4TM to start the procedure in 99.3%, the possibility of taking and storing images in 99.3%. The CUSUM analysis showed average scores > 70/100 from the first procedure and from the 9th procedure more than 80% of the scores exceeded the 80/100 score. CONCLUSIONS: The aScope4™ scored well for ease of use, imaging, and aspiration. We found a learning curve with excellent scores from the 9th procedure. Bronchoscopists highlighted its portability, immediacy of use and the possibility of taking and storing images.

Ultrathin Bronchoscopy with and without Virtual Bronchoscopic Navigation: Influence of Segmentation on Diagnostic Yield.

BACKGROUND: Bronchoscopy is a safe technique for diagnosing peripheral pulmonary lesions (PPLs), and virtual bronchoscopic navigation (VBN) helps guide the bronchoscope to PPLs. OBJECTIVES: We aimed to compare the diagnostic yield of VBN-guided and unguided ultrathin bronchoscopy (UTB) and explore clinical and technical factors associated with better results. We developed a diagnostic algorithm for deciding whether to use VBN to reach PPLs or choose an alternative diagnostic approach. METHODS: We compared diagnostic yield between VBN-UTB (prospective cases) and unguided UTB (historical controls) and analyzed the VBN-UTB subgroup to identify clinical and technical variables that could predict the success of VBN-UTB. RESULTS: Fifty-five cases and 110 controls were included. The overall diagnostic yield did not differ between the VBN-guided and unguided arms (47 and 40%, respectively; p = 0.354). Although the yield was slightly higher for PPLs ≤20 mm in the VBN-UTB arm, the difference was not significant (p = 0.069). No other clinical characteristics were associated with a higher yield in a subgroup analysis, but an 85% diagnostic yield was observed when segmentation was optimal and the PPL was endobronchial (vs. 30% when segmentation was suboptimal and 20% when segmentation was optimal but the PPL was extrabronchial). CONCLUSIONS: VBN-guided UTB is not superior to unguided UTB. A greater impact of VBN-guided over unguided UTB is highly dependent on both segmentation quality and an endobronchial location of the PPL. Segmentation quality should be considered before starting a procedure, when an alternative technique that may improve yield can be chosen, saving time and resources.

Simple and robust speckle detection method for fire and heat detection in harsh environments.

Standard laser-based fire detection systems are often based on measuring the variation of optical signal amplitude. However, mechanical noise interference and loss from dust and steam can obscure the detection signal, resulting in faulty results or the inability to detect a potential fire. The presented fire detection technology will allow the detection of fire in harsh and dusty areas, which are prone to fires, where current systems show limited performance or are unable to operate. It is not the amount of light or its wavelength that is used for detecting fire, but how the refractive index randomly fluctuates due to heat convection from the fire. In practical terms, this means that light obstruction from ambient dust particles will not be a problem as long as a small fraction of the light is detected and that fires without visible flames can still be detected. The standalone laser system consists of a Linux-based Red Pitaya system, a cheap 650 nm laser diode, and a positive-intrinsic-negative photo-detector. Laser light propagates through the monitored area and reflects off a retroreflector generating a speckle pattern. Every 3 s, time traces and frequency noise spectra are measured, and eight descriptors are deduced to identify a potential fire. Both laboratory and factory acceptance tests have been performed with success.

Objective Endoscopic Measurements of Central Airway Stenosis: A Pilot Study.

BACKGROUND: Endoscopic estimation of the degree of stenosis in central airway obstruction is subjective and highly variable. OBJECTIVE: To determine the benefits of using SENSA (System for Endoscopic Stenosis Assessment), an image-based computational software, for obtaining objective stenosis index (SI) measurements among a group of expert bronchoscopists and general pulmonologists. METHODS: A total of 7 expert bronchoscopists and 7 general pulmonologists were enrolled to validate SENSA usage. The SI obtained by the physicians and by SENSA were compared with a reference SI to set their precision in SI computation. We used SENSA to efficiently obtain this reference SI in 11 selected cases of benign stenosis. A Web platform with three user-friendly microtasks was designed to gather the data. The users had to visually estimate the SI from videos with and without contours of the normal and the obstructed area provided by SENSA. The users were able to modify the SENSA contours to define the reference SI using morphometric bronchoscopy. RESULTS: Visual SI estimation accuracy was associated with neither bronchoscopic experience (p = 0.71) nor the contours of the normal and the obstructed area provided by the system (p = 0.13). The precision of the SI by SENSA was 97.7% (95% CI: 92.4-103.7), which is significantly better than the precision of the SI by visual estimation (p < 0.001), with an improvement by at least 15%. CONCLUSION: SENSA provides objective SI measurements with a precision of up to 99.5%, which can be calculated from any bronchoscope using an affordable scalable interface. Providing normal and obstructed contours on bronchoscopic videos does not improve physicians' visual estimation of the SI.

Positive Airway Pressure to Enhance Computed Tomography Imaging for Airway Segmentation for Virtual Bronchoscopic Navigation.

RATIONALE: Virtual bronchoscopic navigation (VBN) guidance to peripheral pulmonary lesions is often limited by insufficient segmentation of the peripheral airways. OBJECTIVES: To test the effect of applying positive airway pressure (PAP) during CT acquisition to improve segmentation, particularly at end-expiration. METHODS: CT acquisitions in inspiration and expiration with 4 PAP protocols were recorded prospectively and compared to baseline inspiratory acquisitions in 20 patients. The 4 protocols explored differences between devices (flow vs. turbine), exposures (within seconds vs. 15-min) and pressure levels (10 vs. 14 cmH2O). Segmentation quality was evaluated with the number of airways and number of endpoints reached. A generalized mixed-effects model explored the estimated effect of each protocol. MEASUREMENTS AND MAIN RESULTS: Patient characteristics and lung function did not significantly differ between protocols. Compared to baseline inspiratory acquisitions, expiratory acquisitions after 15 min of 14 cmH2O PAP segmented 1.63-fold more airways (95% CI 1.07-2.48; p = 0.018) and reached 1.34-fold more endpoints (95% CI 1.08-1.66; p = 0.004). Inspiratory acquisitions performed immediately under 10 cmH2O PAP reached 1.20-fold (95% CI 1.09-1.33; p < 0.001) more endpoints; after 15 min the increase was 1.14-fold (95% CI 1.05-1.24; p < 0.001). CONCLUSIONS: CT acquisitions with PAP segment more airways and reach more endpoints than baseline inspiratory acquisitions. The improvement is particularly evident at end-expiration after 15 min of 14 cmH2O PAP. Further studies must confirm that the improvement increases diagnostic yield when using VBN to evaluate peripheral pulmonary lesions.

Current Practice of Airway Stenting in the Adult Population in Europe: A Survey of the European Association of Bronchology and Interventional Pulmonology (EABIP).

BACKGROUND: Airway stenting (AS) commenced in Europe circa 1987 with the first placement of a dedicated silicone airway stent. Subsequently, over the last 3 decades, AS was spread throughout Europe, using different insertion techniques and different types of stents. OBJECTIVES: This study is an international survey conducted by the European Association of Bronchology and Interventional Pulmonology (EABIP) focusing on AS practice within 26 European countries. METHODS: A questionnaire was sent to all EABIP National Delegates in February 2015. National delegates were responsible for obtaining precise and objective data regarding the current AS practice in their country. The deadline for data collection was February 2016. RESULTS: France, Germany, and the UK are the 3 leading countries in terms of number of centres performing AS. These 3 nations represent the highest ranked nations within Europe in terms of gross national income. Overall, pulmonologists perform AS exclusively in 5 countries and predominately in 12. AS is performed almost exclusively in public hospitals. AS performed under general anaesthesia is the rule for the majority of institutions, and local anaesthesia is an alternative in 9 countries. Rigid bronchoscopy techniques are predominant in 20 countries. Amongst commercially available stents, both Dumon and Ultraflex are by far the most commonly deployed. Finally, 11 countries reported that AS is an economically viable activity, while 10 claimed that it is not. CONCLUSION: This EABIP survey demonstrates that there is significant heterogeneity in AS practice within Europe. Therapeutic bronchoscopy training and economic issues/reimbursement for procedures are likely to be the primary reasons explaining these findings.

Colchicine Treatment for Tracheobronchial Amyloidosis.

Tracheobronchial amyloidosis is an infrequent disease characterized by the deposition of proteinaceous material in the tracheobronchial tree. The disease generally has a high morbidity and variable mortality in the years following diagnosis. There is no consensus on the optimal treatment. We report a case of a 63-year-old woman who presented with a diffuse tracheobronchial amyloidosis associated with laryngeal involvement, which required a percutaneous tracheostomy due to high-grade subglottic stenosis, with no evidence of systemic amyloidosis. After treatment exclusively with colchicine, she had a complete resolution of the stenotic area, with a very good response from the tracheobronchial amyloidosis disease, with only minor yellow plaques persisting. The patient has remained asymptomatic in the next 4 years of follow-up, with no evidence of endoscopic progression. This is the first documented case of this kind of response of tracheobronchial amyloidosis to colchicine treatment alone. A review of the available literature is presented.

Combined Bronchial Artery Embolization and Endobronchial Resection for Bronchial Carcinoid: A Safety and Feasibility Pilot Study.

BACKGROUND: There is growing evidence to support bronchoscopic resection of well-circumscribed typical carcinoids. However, massive bleeding and risk of recurrence can potentially complicate this approach. OBJECTIVES: The aim of this study was to assess the safety and feasibility of endobronchial resection of carcinoids preceded by bronchial artery embolization. METHODS: Five patients with centrally located typical carcinoids were recruited, 4 with a curative intent and 1 for palliation of a carcinoid with mediastinal invasion. All patients underwent selective embolization of the feeding bronchial artery 24-48 h prior to endobronchial resection, which was performed with a rigid bronchoscope and neodymium:yttrium-aluminium-perovskite laser. RESULTS: Minimal bleeding was noted during tumour resection. After a median (range) follow-up of 20 (14-48) months, only the case with segmental extension of the tumour had local recurrence, which was treated successfully using cryotherapy (with negative endobronchial biopsies since), and no cases of metastatic spread occurred. One patient, in whom the histopathological diagnosis was changed from typical to atypical carcinoid following resection, went on to have a surgical bilobectomy 3 months later. Extensive fibrosis was noted at the site of original tumour resection with no evidence of residual disease. CONCLUSIONS: Bronchial artery embolization prior to endobronchial resection of centrally located carcinoids is feasible and safe. The reduction in bleeding may facilitate and simplify the procedure. The possible application of this combined therapy to the management of atypical carcinoids warrants the design of a larger prospective clinical trial.

Radiomics and Clinical Data for the Diagnosis of Incidental Pulmonary Nodules and Lung Cancer Screening: Radiolung Integrative Predictive Model.

INTRODUCTION: Early diagnosis of lung cancer (LC) is crucial to improve survival rates. Radiomics models hold promise for enhancing LC diagnosis. This study assesses the impact of integrating a clinical and a radiomic model based on deep learning to predict the malignancy of pulmonary nodules (PN). METHODOLOGY: Prospective cross-sectional study of 97 PNs from 93 patients. Clinical data included epidemiological risk factors and pulmonary function tests. The region of interest of each chest CT containing the PN was analysed. The radiomic model employed a pre-trained convolutional network to extract visual features. From these features, 500 with a positive standard deviation were chosen as inputs for an optimised neural network. The clinical model was estimated by a logistic regression model using clinical data. The malignancy probability from the clinical model was used as the best estimate of the pre-test probability of disease to update the malignancy probability of the radiomic model using a nomogram for Bayes' theorem. RESULTS: The radiomic model had a positive predictive value (PPV) of 86%, an accuracy of 79% and an AUC of 0.67. The clinical model identified DLCO, obstruction index and smoking status as the most consistent clinical predictors associated with outcome. Integrating the clinical features into the deep-learning radiomic model achieves a PPV of 94%, an accuracy of 76% and an AUC of 0.80. CONCLUSIONS: Incorporating clinical data into a deep-learning radiomic model improved PN malignancy assessment, boosting predictive performance. This study supports the potential of combined image-based and clinical features to improve LC diagnosis.

Clinical characteristics of complete responders versus non-complete responders to omalizumab, benralizumab and mepolizumab in patients with severe asthma: a long-term retrospective analysis.

BACKGROUND: Some patients with severe asthma may benefit from treatment with biologics, but evidence has been mostly collected from randomized controlled trials (RCTs), in which patients' characteristics are different from those encountered in asthma patients in the real-world setting. The aim of this study was to describe the clinical features of complete responders versus non-complete responders to long-term treatment with biologics in patients with severe asthma attended in routine daily practice. METHODS: Data of a cohort of 90 patients with severe asthma who were treated with biologics (omalizumab, benralizumab, and mepolizumab) for at least 12 months and were followed up to March 2022. Data recorded included clinical characteristics and effectiveness of treatment (exacerbation, Asthma Control Test [ACT] score, lung function, use of maintenance oral corticosteroids [mOCS]), FeNO, and blood eosinophils at baseline, at 12 months, and at the end of follow-up. Complete response is considered if, in addition to not presenting exacerbations or the use of mOCS, the ACT score was >20 and, the FEV1 >80% predicted. RESULTS: An improvement in all asthma control parameters was observed after 12 months of treatment and a mean follow-up of 55 months. After 12 months of treatment 27.2% of patients met the criteria of complete response and this percentage even increased to 35.3% at the end of follow-up. Long-term complete response was associated to better lung function with mepolizumab and omalizumab treatment and to less previous exacerbations in the benralizumab group. The main cause of not achieving a complete response was the persistence of an airflow obstructive pattern. CONCLUSIONS: This study shows that omalizumab, benralizumab, and mepolizumab improved the clinical outcomes of patients with severe asthma in a clinic environment with similar effect sizes to RCTs in the long term follow-up. Airflow obstruction, however, was a predictor of a non-complete response to biologics.

Treatment with anti-IgE and anti-IL-5 biologics significantly improved clinical outcomes in severe asthma patients.The rate of complete responders of 27.2% at 12 months even increased to 35.3% at the end of a mean follow-up of 55 months.The persistence of an airflow obstructive pattern was the main cause of the failure to achieve complete response.

Measurement of IFN-γ and IL-2 for the assessment of the cellular immunity against SARS-CoV-2.

The study of specific T-cell responses against SARS-CoV-2 is important for understanding long-term immunity and infection management. The aim of this study was to assess the dual IFN-γ and IL-2 detection, using a SARS-CoV-2 specific fluorescence ELISPOT, in patients undergoing acute disease, during convalescence, and after vaccination. We also evaluated humoral response and compared with T-cells with the aim of correlating both types of responses, and increase the number of specific response detection. Blood samples were drawn from acute COVID-19 patients and convalescent individuals classified according to disease severity; and from unvaccinated and vaccinated uninfected individuals. IgGs against Spike and nucleocapsid, IgMs against nucleocapsid, and neutralizing antibodies were also analyzed. Our results show that IFN-γ in combination with IL-2 increases response detection in acute and convalescent individuals (p = 0.023). In addition, IFN-γ detection can be a useful biomarker for monitoring severe acute patients, as our results indicate that those individuals with a poor outcome have lower levels of this cytokine. In some cases, the lack of cellular immunity is compensated by antibodies, confirming the role of both types of immune responses in infection, and confirming that their dual detection can increase the number of specific response detections. In summary, IFN-γ/IL-2 dual detection is promising for characterizing and assessing the immunization status, and helping in the patient management.

Evaluation of Light's criteria in cytologically proved malignant pleural effusions.

BACKGROUND: Malignant pleural effusions are usually described as exudates. However, several studies have determined a high incidence of cytologically proved malignant effusions in transudates. The study aims to determine the compliance of cytologically proved malignant pleural effusions with Light's Criteria and to assess when it is necessary to perform more studies in transudates. METHODS: We have retrospectively reviewed all the cytologically positive effusions at our institution over six years. Biochemical characteristics were recorded, and Light's criteria were determined for each effusion. We analyzed the effusions' compliance with the criteria and determined whether its primary tumor or the presence of cirrhosis, acute kidney injury or congestive heart failure could interfere in the criteria being met. RESULTS: Overall, 224 patients presented malignant pleural effusions with biochemical pleural fluid analysis. Two (0.9%) were transudative effusions and two hundred and twenty-two (99.1%) were exudative effusions. Lung carcinoma, breast carcinoma and ovarian carcinoma were the most frequent primary tumors. One hundred and two (45.94%) patients met three Light criteria, 77 (34.68%) patients met two criteria and 43 (19.36%) met one criterion. Both patients with transudative malignant pleural effusions presented concomitant malignant ascites. CONCLUSIONS: Malignant transudative pleural effusions were 0.9% of our patients. We found no relation between transudative malignant effusions and the presence of cirrhosis, acute kidney injury or congestive heart failure, or the type of tumor. We found no difference between the tumor type and the distribution of Light's criteria met.

Impact of the COVID-19 pandemic on diagnosis of respiratory diseases in the Northern Metropolitan Area in Barcelona (Spain).

OBJECTIVE: The COVID-19 pandemic has had a great effect on the management of chronic diseases, by limiting the access to primary care and to diagnostic procedures, causing a decline in the incidence of most diseases. Our aim was to analyze the impact of the pandemic on primary care new diagnoses of respiratory diseases. METHODS: Observational retrospective study performed to describe the effect of COVID-19 pandemic on the incidence of respiratory diseases according to primary care codification. Incidence rate ratio between pre-pandemic and pandemic period was calculated. RESULTS: We found a decrease in the incidence of respiratory conditions (IRR 0.65) during the pandemic period. When we compared the different groups of diseases according to ICD-10, we found a significant decrease in the number of new cases during the pandemic period, except in the case of pulmonary tuberculosis, abscesses or necrosis of the lungs and other respiratory complications (J95). Instead, we found increases in flu and pneumonia (IRR 2.17) and respiratory interstitial diseases (IRR 1.41). CONCLUSION: There has been a decrease in new diagnosis of most respiratory diseases during the COVID-19 pandemic.