Utility of bronchoalveolar lavage for COVID-19: a perspective from the Dragon consortium.

Diagnosing COVID-19 and treating its complications remains a challenge. This review reflects the perspective of some of the Dragon (IMI 2-call 21, #101005122) research consortium collaborators on the utility of bronchoalveolar lavage (BAL) in COVID-19. BAL has been proposed as a potentially useful diagnostic tool to increase COVID-19 diagnosis sensitivity. In both critically ill and non-critically ill COVID-19 patients, BAL has a relevant role in detecting other infections or supporting alternative diagnoses and can change management decisions in up to two-thirds of patients. BAL is used to guide steroid and immunosuppressive treatment and to narrow or discontinue antibiotic treatment, reducing the use of unnecessary broad antibiotics. Moreover, cellular analysis and novel multi-omics techniques on BAL are of critical importance for understanding the microenvironment and interaction between epithelial cells and immunity, revealing novel potential prognostic and therapeutic targets. The BAL technique has been described as safe for both patients and healthcare workers in more than a thousand procedures reported to date in the literature. Based on these preliminary studies, we recognize that BAL is a feasible procedure in COVID-19 known or suspected cases, useful to properly guide patient management, and has great potential for research.

Relaxation differences using EIS through bronchoscopy of healthy and pathological lung tissue.

The use of electrical impedance spectroscopy for lung tissue differentiation is an opportunity for the improvement of clinical diagnosis. The aim of this work is to distinguish among different lung tissue states by evaluating the differences among impedance spectrum parameters between two separate frequencies (15 kHz and 307 kHz) in the beta dispersion region. In previous studies we have used single frequency measurements for tissue differentiation. Differences (P < 0.05) are found between those tissues that undergo an increase in tissue density (neoplasm and fibrosis) and those tissues that lead to tissue destruction (emphysema). Electrical impedance spectroscopy shows its utility for lung tissue differentiation for diagnosis improvement among pathologies with different tissue structure. Further studies are necessary for the differentiation among those tissue states that are more similar to each other.Clinical Relevance- Expand the diagnostic tools currently available in bronchoscopy by using minimally-invasive bioimpedance measurements to differentiate between lung patterns.

Differentiation using minimally-invasive bioimpedance measurements of healthy and pathological lung tissue through bronchoscopy.

Purpose: To use minimally-invasive transcatheter electrical impedance spectroscopy measurements for tissue differentiation among healthy lung tissue and pathologic lung tissue from patients with different respiratory diseases (neoplasm, fibrosis, pneumonia and emphysema) to complement the diagnosis at real time during bronchoscopic procedures. Methods: Multi-frequency bioimpedance measurements were performed in 102 patients. The two most discriminative frequencies for impedance modulus (|Z|), phase angle (PA), resistance (R) and reactance (Xc) were selected based on the maximum mean pair-wise Euclidean distances between paired groups. One-way ANOVA for parametric variables and Kruskal-Wallis for non-parametric data tests have been performed with post-hoc tests. Discriminant analysis has also been performed to find a linear combination of features to separate among tissue groups. Results: We found statistically significant differences for all the parameters between: neoplasm and pneumonia (p < 0.05); neoplasm and healthy lung tissue (p < 0.001); neoplasm and emphysema (p < 0.001); fibrosis and healthy lung tissue (p ≤ 0.001) and pneumonia and healthy lung tissue (p < 0.01). For fibrosis and emphysema (p < 0.05) only in |Z|, R and Xc; and between pneumonia and emphysema (p < 0.05) only in |Z| and R. No statistically significant differences (p > 0.05) are found between neoplasm and fibrosis; fibrosis and pneumonia; and between healthy lung tissue and emphysema. Conclusion: The application of minimally-invasive electrical impedance spectroscopy measurements in lung tissue have proven to be useful for tissue differentiation between those pathologies that leads increased tissue and inflammatory cells and those ones that contain more air and destruction of alveolar septa, which could help clinicians to improve diagnosis.

Safety and Feasibility of Transbronchial Cryobiopsy in Mechanically Ventilated Patients

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Sarcoidosis following SARS-CoV-2 infection: Cause or consequence?

The COVID-19 pandemic has been a worldwide medical challenge. Despite rapid advancements, many questions regarding SARS-CoV-2 interaction with other pathologies and long-term consequences remained unanswered. Sarcoidosis is a multi-systemic granulomatous disease that develops in genetically predisposed individuals following their exposure to an environmental trigger. We present the case of a patient who was diagnosed with sarcoidosis following a SARS-CoV-2 infection.

Bronchoalveolar Lavage Complements Transbronchial Cryobiopsy Diagnosis in Diffuse Interstitial Lung Diseases.

BACKGROUND: Bronchoalveolar lavage (BAL) is a technique classically used for the study of diffuse interstitial lung diseases (DILDs). Given the recent advances in the diagnosis of DILD by transbronchial cryobiopsy (TBCB), it is relevant to assess what BAL can contribute to TBCB. PATIENTS AND METHODS: This is a retrospective descriptive study that included patients with DILD who, between 2013 and 2017, underwent BAL and TBCB in the same bronchoscopy intervention. We evaluated the complementary information provided by BAL to TBCB that facilitated the diagnosis by a multidisciplinary committee. Epidemiological, clinical, and functional variables and high-resolution chest tomography findings were recorded, along with complications associated with the procedures. RESULTS: A total of 60 patients were included. TBCB, conditioned by the underlying radiologic pattern, provided diagnostic information in 75% of cases. BAL provided complementary information that supported the diagnosis and treatment in 22% of cases. Differential BAL findings were related to microbiology, cell count, and immunology. Regarding the safety of the procedure, 47% of the patients experienced complications, although none were serious. CONCLUSION: BAL findings contribute to TBCB findings in the diagnosis of DILDs, with no serious complications associated with their combined use.

Bronchial Thermoplasty Global Registry (BTGR): 2-year results.

OBJECTIVES: Bronchial thermoplasty (BT) is a device-based treatment for subjects ≥18 years with severe asthma not well controlled with inhaled corticosteroids and long-acting beta-agonists. The Bronchial Thermoplasty Global Registry (BTGR) collected real-world data on subjects undergoing this procedure. DESIGN: The BTGR is an all-comer, prospective, open-label, multicentre study enrolling adult subjects indicated for and treated with BT. SETTING: Eighteen centres in Spain, Italy, Germany, the UK, the Netherlands, the Czech Republic, South Africa and Australia PARTICIPANTS: One hundred fifty-seven subjects aged 18 years and older who were scheduled to undergo BT treatment for asthma. Subjects diagnosed with other medical conditions which, in the investigator's opinion, made them inappropriate for BT treatment were excluded. PRIMARY AND SECONDARY OUTCOME MEASURES: Baseline characteristics collected included demographics, Asthma Quality of Life Questionnaire (AQLQ), Asthma Control Test (ACT), medication usage, forced expiratory volume in one second and forced vital capacity, medical history, comorbidities and 12-month baseline recall data (severe exacerbations (SE) and healthcare utilisation). SE incidence and healthcare utilisation were summarised at 1 and 2 years post-BT. RESULTS: Subjects' baseline characteristics were representative of persons with severe asthma. A comparison of the proportion of subjects experiencing events during the 12 months prior to BT to the 2-year follow-up showed a reduction in SE (90.3% vs 56.1%, p<0.0001), emergency room visits (53.8% vs 25.5%, p<0.0001) and hospitalisations (42.9% vs 23.5 %, p=0.0019). Reductions in asthma maintenance medication dosage were also observed. AQLQ and ACT scores improved from 3.26 and 11.18 at baseline to 4.39 and 15.54 at 2 years, respectively (p<0.0001 for both AQLQ and ACT). CONCLUSIONS: The BTGR demonstrates sustained improvement in clinical outcomes and reduction in asthma medication usage 2 years after BT in a real-world population. This is consistent with results from other BT randomised controlled trials and registries and further supports improvement in asthma control after BT. TRIAL REGISTRATION NUMBER: NCT02104856.

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.

Minimally Invasive Real-Time Electrical Impedance Spectroscopy Diagnostic Tool for Lung Parenchyma Pathologies.

Electrical Impedance Spectroscopy has already demonstrated the ability to distinguish different tissues types, or tumors from normal tissue, or tissues displaying diverse degrees of pathology. When applying the technique, however, the necessity to make contact with the tissue often constitutes a practical limitation. Electrical Impedance Imaging (EIT), or in a broader sense, regional impedance assessment, struggle to assess different tissue conditions out of measurements from the surface of the body. But sensitivity is very small even for tissue a few centimeters under the skin, and in-vivo measurements are often not viable.The lung offer a third approximation by introducing a catheter though a bronchoscope, which is a routine clinical procedure. Measurements have been obtained by using 3 or 4-electrode techniques and allow us to distinguish, at least, fibrotic, emphysema or neoplastic regions from normal parenchyma. New instrumental developments, clinical measurements and preliminary results are presented and discussed.

Transbronchial biopsy results according to diffuse interstitial lung disease classification. Cryobiopsy versus forceps: MULTICRIO study.

BACKGROUND: In recent years, transbronchial cryobiopsy (TBCB) has come to be increasingly used in interventional pulmonology units as it obtains larger and better-quality samples than conventional transbronchial lung biopsy (TBLB) with forceps. No multicenter studies have been performed, however, that analyse and compare TBCB and TBLB safety and yield according to the interstitial lung disease (ILD) classification. OBJECTIVES: We compared the diagnostic yield and safety of TBCB with cryoprobe sampling versus conventional TBLB forceps sampling in the same patient. METHOD: Prospective multicenter clinical study of patients with ILD indicated for lung biopsy. Airway management with orotracheal tube, laryngeal mask and rigid bronchoscope was according to the protocol of each centre. All procedures were performed using fluoroscopy and an occlusion balloon. TBLB was followed by TBCB. Complications were recorded after both TBLB and TBCB. RESULTS: Included were 124 patients from 10 hospitals. Airway management was orotracheal intubation in 74% of cases. Diagnostic yield according to multidisciplinary committee results for TBCB was 47.6% and for TBLB was 19.4% (p<0.0001). Diagnostic yield was higher for TBCB compared to TBLB for two groups: idiopathic interstitial pneumonias (IIPs) and ILD of known cause or association (OR 2.5; 95% CI: 1.4-4.2 and OR 5.8; 95% CI: 2.3-14.3, respectively). Grade 3 (moderate) bleeding after TBCB occurred in 6.5% of patients compared to 0.8% after conventional TBLB. CONCLUSIONS: Diagnostic yield for TBCB was higher than for TBLB, especially for two disease groups: IIPs and ILD of known cause or association. The increased risk of bleeding associated with TBCB confirms the need for safe airway management and prophylactic occlusion-balloon use. TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT02464592.

Transbronchial cryobiopsy increases diagnostic confidence in interstitial lung disease: a prospective multicentre trial.

INTRODUCTION: The accurate diagnosis of individual interstitial lung diseases (ILD) is often challenging, but is a critical determinant of appropriate management. If a diagnosis cannot be made after multidisciplinary team discussion (MDTD), surgical lung biopsy is the current recommended tissue sampling technique according to the most recent guidelines. Transbronchial lung cryobiopsy (TBLC) has been proposed as an alternative to surgical lung biopsy. METHODS: This prospective, multicentre, international study analysed the impact of TBLC on the diagnostic assessment of 128 patients with suspected idiopathic interstitial pneumonia by a central MDTD board (two clinicians, two radiologists, two pathologists). The level of confidence for the first-choice diagnoses were evaluated in four steps, as follows: 1) clinicoradiological data alone; 2) addition of bronchoalveolar lavage (BAL) findings; 3) addition of TBLC interpretation; and 4) surgical lung biopsy findings (if available). We evaluated the contribution of TBLC to the formulation of a confident first-choice MDTD diagnosis. RESULTS: TBLC led to a significant increase in the percentage of cases with confident diagnoses or provisional diagnoses with high confidence (likelihood ≥70%) from 60.2% to 81.2%. In 32 out of 52 patients nondiagnostic after BAL, TBLC provided a diagnosis with a likelihood ≥70%. The percentage of confident diagnoses (likelihood ≥90%) increased from 22.7% after BAL to 53.9% after TBLC. Pneumothoraces occurred in 16.4% of patients, and moderate or severe bleeding in 15.7% of patients. No deaths were observed within 30 days. INTERPRETATION: TBLC increases diagnostic confidence in the majority of ILD patients with an uncertain noninvasive diagnosis, with manageable side-effects. These data support the integration of TBLC into the diagnostic algorithm for ILD.

Propuesta multidisciplinar respecto al algoritmo diagnóstico de la fibrosis pulmonar idiopática: papel de la criobiopsia transbronquial / A Multidisciplinary Proposal for a Diagnostic Algorithm in Idiopathic Pulmonary Fibrosis: The Role of Transbronchial Cryobiopsy

El diagnóstico de la fibrosis pulmonar idiopática (FPI) es un proceso complejo que precisa la integración multidisciplinar de variables clínicas, radiológicas e histológicas. Cuando es preciso obtener muestras de parénquima pulmonar, la biopsia pulmonar quirúrgica ha sido el procedimiento recomendado por su rendimiento diagnóstico. Pero dada la morbimortalidad de esta técnica, se han explorado alternativas con menores riesgos. La más importante es la biopsia transbronquial con criosonda (criobiopsia transbronquial), que permite obtener tejido pulmonar con menor comorbilidad, con un rendimiento inferior a la biopsia quirúrgica pero superior a la biopsia transbronquial con pinza convencional. Por ello, en las recientes guías clínicas para el diagnóstico de la FPI se ha valorado esta opción, sin llegar a obtener una recomendación. En este artículo, resultado de un foro de discusión multidisciplinar, se pretende revisar la evidencia actual y hacer propuestas sobre el uso de la criobiopsia transbronquial para el diagnóstico de la FPI

The diagnosis of idiopathic pulmonary fibrosis (IPF) is a complex process that requires the multidisciplinary integration of clinical, radiological, and histological variables. Due to its diagnostic yield, surgical lung biopsy has been the recommended procedure for obtaining samples of lung parenchyma, when required. However, given the morbidity and mortality of this technique, alternative techniques which carry a lower risk have been explored. The most important of these is transbronchial cryobiopsy -transbronchial biopsy with a cryoprobe- which is useful for obtaining lung tissue with less comorbidity. Yield may be lower than surgical biopsy, but it is higher than with transbronchial biopsy with standard forceps. This option has been discussed in the recent clinical guidelines for the diagnosis of IPF, but the authors do not go so far as recommend it. The aim of this article, the result of a multidisciplinary discussion forum, is to review current evidence and make proposals for the use of transbronchial cryobiopsy in the diagnosis of IPF

A Multidisciplinary Proposal for a Diagnostic Algorithm in Idiopathic Pulmonary Fibrosis: The Role of Transbronchial Cryobiopsy. / Propuesta multidisciplinar respecto al algoritmo diagnóstico de la fibrosis pulmonar idiopática: papel de la criobiopsia transbronquial.

The diagnosis of idiopathic pulmonary fibrosis (IPF) is a complex process that requires the multidisciplinary integration of clinical, radiological, and histological variables. Due to its diagnostic yield, surgical lung biopsy has been the recommended procedure for obtaining samples of lung parenchyma, when required. However, given the morbidity and mortality of this technique, alternative techniques which carry a lower risk have been explored. The most important of these is transbronchial cryobiopsy -transbronchial biopsy with a cryoprobe- which is useful for obtaining lung tissue with less comorbidity. Yield may be lower than surgical biopsy, but it is higher than with transbronchial biopsy with standard forceps. This option has been discussed in the recent clinical guidelines for the diagnosis of IPF, but the authors do not go so far as recommend it. The aim of this article, the result of a multidisciplinary discussion forum, is to review current evidence and make proposals for the use of transbronchial cryobiopsy in the diagnosis of IPF.