Endobronchial Biopsy Research Articles

Uncommon Presentation of Pulmonary Adenoid Cystic Carcinoma: A Case of Brain Metastasis in a Young Smoker

Abstract Introduction/Objective Pulmonary adenoid cystic carcinoma (PACC) is a rare entity, accounting for only 0.04-0.2% lung cancers, and mainly originating from the small salivary glands in the tracheobronchial tree. Due to slow-growing pattern and unspecific symptoms, the diagnosis is often delayed. While metastasis in PACC is uncommon, reports of brain metastasis are exceedingly rare. We present a case of PACC with metastasis to the brain in a young smoker. Methods/Case Report A 29-year-old female with history of smoking presented with headache, hypersomnia, episodes of vomiting and falling. Physical examination revealed multiple palpable nodes on the mid head, left temporal and right parietal area, left shoulder area were found. CT scan demonstrated complex cystic mass with a mural nodule within the left cerebellar hemisphere, with displacement of the cerebellar tonsils, as well as a 7.4 cm left infrahilar mass with heterogenous enhancement. Patient underwent craniotomy with tumor resection and left lower lobe endobronchial biopsy. Touch smear of the brain lesion showed clusters of hyperchromatic cells with myxoid like and hyalinized stroma. H&E stain showed cords of neoplastic cells embedded in a basophilic/myxoid stroma. Lung biopsy showed similar histological patterns. IHC stain showed the tumor cells were positive for epithelial and myoepithelial cells markers(CAM5.2, CK7, p63, Sox 10), retained INI1/BAF47 and BRG1 expression, negative for NUT and BCOR. Salivary Gland NGS Fusion Panel was performed and detected a MYBL1::NFIB [t(8;9)(8q13.1;9p23)] fusion alteration, which confirmed the diagnosis of adenoid cystic carcinoma. Considering no lesion was found in the patient’s head and neck, diagnosis of PACC was made. Results (if a Case Study enter NA) NA Conclusion PACC manifests three histologic subtypes: cribriform (most common), trabecular, and solid. In this case, brain and lung lesions exhibited similar patterns - nests of small, monomorphic cells within a myxoid-like and basophilic stroma background, consistent with trabecular pattern. Cytologically, densely packed cellular clusters were embedded in a myxoid like matrix. Distinguishing PACC from other salivary gland tumors is challenging. Immunostains for epithelial and myoepithelial cells, along with morphology, aid in diagnosis. The MYB::NFIB fusion helps differentiate from other lung salivary gland malignancies, but is found in a lower percentage of PACC cases (~40%) compared to other primary adnoid cystic carcinoma (~85%).

Deaths from asthma: a series of cases and their presentations, and the impact on local and global health

Abstract Introduction/Objective Asthma is a lung disease usually characterized by chronic inflammation that affects at least 300 million people globally at all life stages. Asthma is defined by respiratory symptoms such as coughing, wheezing, shortness of breath, and chest tightness with expiratory airflow limitation.The prevalence of asthma is increasing worldwide. Asthma is often under-diagnosed and under-treated, particularly in low- and middle-income countries. Severe disease can result in reduced quality of life or even premature death. Epidemiologic studies are being utilized to compare international incidences of asthma between populations so that etiologic mechanisms involved in the development of asthma can be discovered through research. Asthma prevalence studies require large numbers and high response rates amongst a random population to establish prevalence and severity with reasonable precision. Despite advances in treatments, guidelines, and preventable factors, deaths from asthma account for 250,000 premature deaths each year. Pathology has a key role in asthma identification through examination endobronchial biopsies and whole lung postmortem examination Methods/Case Report We present a series of asthma deaths with variable clinical presentations and histopathologic findings. The postmortem gross and histologic findings highlight the varying severities that asthma can have on the lungs. Knowledge of the clinical symptom presentations, identification of gross findings, appropriate sampling of lung tissue, identification of microscopic acute and chronic features help identify asthma related changes. Understanding common lifestyle, environmental, genetic, and medical care factors that serve as asthma triggers and their role in the onset or continuation of an acute exacerbation will allow for accurate determination of cause, contributing cause, and manner of death. This information, listed on the death certificate, is what helps correlate asthma prevalence with mortality allowing for appropriate allocation of funds for research, prevention and treatment. Results (if a Case Study enter NA) EP abstract Conclusion Outlined are the impacts that asthma can have on individuals, communities, and health systems globally but also ways to identify when death may be or is likely the result of asthma. While asthma cannot be cured, measuring the prevalence of disease and accurately determining asthma as the cause or contributing cause of death can help raise awareness and mitigate the consequences of severe disease.

9183 Pituitary Metastasis Of Lung Adenocarcinoma Presenting As Anterior Pituitary Dysfunction

Abstract Disclosure: O. faour: None. M. Kinaan: None. S.K. Suryanarayanan: None. Introduction: The pituitary should not be overlooked as a site for metastasis and can be the first presentation of neoplastic disease in some patients. Most common presenting symptoms: headache, ophthalmoplegia, visual field defect and Arginine Vasopressin Deficiency (AVP-D). We present a case of pituitary metastasis of lung adenocarcinoma presenting as anterior Pituitary dysfunction that also showed partial AVP-D unmasked after starting steroids. Case Description: A 63-year-old male with history of tobacco use, COPD, and hypertension presented with syncope. He reported a 30lbs weight loss within prior 2 months, low energy, increased thirst, and polyuria. Physical exam was significant for cachexia, normal visual field on confrontation, and vital signs of BP 100/61, HR 83, and Weighing 180 lbs. Since he had syncope, Cortisol checked was undetectable and Free T4 was low, He was started on hydrocortisone and levothyroxine. CTA chest revealed a right hilar mass measuring 2.7 x 3 cm. Endobronchial biopsy was consistent with lung adenocarcinoma. MRI of pituitary gland revealed solid hypointense lesion with glandular thickening and diffuse heterogeneity involving most of the pituitary gland measuring up to 16 mm. No cavernous sinus invasion. Pituitary infundibulum showed diffuse thickening and enhancement of the pituitary stalk throughout with Intact posterior pituitary bright spot. Labs showed low LH, cortisol, ACTH, GH, TSH, and ADH. Initially, the patient was able to maintain a euvolemic status through increased water intake; however, he was later found to have partial central AVP-D when steroids were introduced. He responded to the use of Desmopressin, developed hyponatremia after 3 doses. He was started on a combination of carboplatin/pemetrexed/pembrolizumab but had no response and was transferred to palliative care/hospice and passed away within 7months after diagnosis.Discussion:Pituitary metastasis is rare and most commonly occurs in lung and breast cancers. Unfortunately, they are associated with poor prognosis. MRI findings of loss of posterior pituitary bright spot, thickening of the stalk, and dumbbell shape can be helpful in distinguishing between primary pituitary tumors and metastases. PET-FDG scan has limited value. Pituitary metastasis commonly presents with posterior pituitary dysfunction due to direct blood supply. Unmasking or worsening of AVP-D can happen with steroid replacement in patients requiring initiation or intensification of Desmopressin therapy. Treatment involves combination of surgery, radiation therapy, and systemic treatment for the primary cancer which can improve symptoms only but does not improve mortality. Presentation: 6/1/2024

Efficacy and safety of radial probe endobronchial ultrasound-guided biopsy for peripheral lung lesions in chronic obstructive pulmonary disease patients

Efficacy and safety of radial probe endobronchial ultrasound-guided biopsy for peripheral lung lesions in chronic obstructive pulmonary disease patients

Sensitization to Staphylococcus Enterotoxin: Relationship with Aspects of Disease Severity

Background/Objective: Sensitization to specific IgE Staphylococcus aureus enterotoxins (SEs) is associated with an increased risk for severe asthma development. Limited data exist regarding the association of seropositivity for specific IgE SEs and the different aspects of severe asthma. We aimed to determine whether the presence of SEs is associated with asthma-related parameters such as inflammatory cells in the airways, features of airway remodeling, and other variables relating to asthma assessment and severity. Methods: Fifty patients with severe asthma were recruited in the study. Demographics, comorbidities, asthma duration, and asthma medication were recorded by treating physicians. Specific IgE SE measurement, lung function, atopic status, asthma control test (ACT), sputum induction, bronchoscopy with BAL, and indices of airway remodeling were also assessed. Results: Twelve patients were positive to enterotoxin sensitization. Patients seropositive to specific IgE SEs significantly differed in regard to FEV1% pred and FEV1/FVC ratio compared to seronegative ones. Analyzing the inflammatory variables obtained from induced sputum, BAL, and endobronchial biopsies, the only significant difference was that of smooth muscle area (SMA), which was greater in specific IgE SE seropositive patients. The multivariate linear regression analysis showed two significant associations of specific IgE SE seropositivity. We found a negative with FEV1% pred with beta standardized coefficient 95%CI −0.054 (−0.083, −0.031), p < 0.001, and a positive with SMA with beta standardized coefficient 95%CI 0.054 (0.081, 0.037), p < 0.001. Conclusions: Seropositivity to specific IgE SEs in severe asthma is associated with more severe airflow limitation, obstruction, and upregulation in SMA, indicating a possible role in the remodeling process.

Does the guide sheath outperform the non-guide sheath method in endobronchial ultrasound-guided biopsy of peripheral pulmonary lesions?-a meta-analysis.

Endobronchial ultrasound (EBUS)-guided transbronchial biopsy with or without a guide sheath (EBUS-GS or EBUS-nGS) is commonly utilized for the diagnosis of peripheral pulmonary lesions (PPLs). The primary objective of this meta-analysis is to assess the diagnostic yield, surgical time, and safety of EBUS-GS and EBUS-nGS in patients presenting with PPLs, providing valuable insights for clinical decision-making. We conducted a systematic search of four databases (PubMed, Embase, Web of Science, Cochrane Library) up to January 2024. Two researchers independently screened the retrieved articles, extracted the data, assessed the quality of the studies, and conducted statistical analysis through Review Manager 5.4 and STATA 14.0. Subgroup analysis was used to explore potential sources of heterogeneity. Publication bias was assessed through funnel plot tests. Sensitivity analyses were also performed to evaluate the robustness of the combined results. The meta-analysis included data from nine studies comprising 2,898 patients. No publication bias was detected. There was no difference in the overall diagnostic rate of EBUS-GS and EBUS-nGS for PPLs [odds ratio (OR): 0.83, 95% confidence interval (CI): 0.64-1.08, Z-score (Z) =1.37, P=0.17]. Conversely, in cases utilizing a bronchoscope with an outer diameter of 3.0 mm (OR: 0.58, 95% CI: 0.40-0.84, Z=2.86, P=0.004), a 1.7-mm bronchoscope channel (OR: 0.70, 95% CI: 0.51-0.96, Z=2.21, P=0.03), or lesions ≤30 mm in size, or lesions situated in the lower lobe of the lung (OR: 0.59, 95% CI: 0.38-0.91, Z=2.36, P=0.02), the diagnostic rate was higher in the EBUS-nGS group. However, the EBUS-GS group demonstrated a tremendous advantage in terms of safety (OR: 0.64, 95% CI: 0.44-0.93, Z=2.33, P=0.02). EBUS-GS and EBUS-nGS showed no significant difference in the overall diagnostic rate for PPLs. When using a bronchoscope with an outer diameter of 3.0 mm or a channel diameter of 1.7 mm, or when lesions are ≤30 mm or located in the lower lobe of the lung, EBUS-nGS demonstrated a higher diagnostic rate, and EBUS-nGS demonstrated a higher diagnostic rate. However, EBUS-GS exhibited more tremendous advantages in terms of safety.

Abstract C172: Diversifying translational research models to address outcomes disparities in lung cancer

Abstract Introduction: Racial disparities in lung cancer remains a persistent and challenging problem, with African Americans experiencing the highest mortality of any race or ethnic group. Emerging evidence suggests that multiple biological factors affect the development and progression of lung cancer. Three-dimensional organoid culture models have become important instruments to use for biomarker analysis and drug sensitivity screening. Despite this strong rationale and potential, there is a lack of representative preclinical models from African American patients with lung cancer. Furthermore, there are no studies evaluating the ability to create organoids successfully using samples from different races. As such, our goal was to establish a diverse biobank of organoid models and determine the rate of successful development based on race and other factors. Methods: Patients with lung cancer from a large urban medical center were recruited to participate in the study from 2021 to 2024. Specimens were collected from surgical pulmonary resection or endobronchial biopsy. Each tissue specimen was divided into 3 pieces and allocated for genomic, transcriptomic and organoid development. Once collected, specimens allocated for organoid development were processed within 8 hours. Cells were isolated from tissues by mechanical and enzymatic dissociation and plated in Matrigel drops overlayed with optimized organoid media. Patient demographics, tumor characteristics and method of specimen collection were recorded. Results: A total of 29 patients consented to the study and had evaluable specimens collected. Mean age was 67 years. Fifty-five percent of patients (16/29) were female. White patients were 55 percent of cohort (16/29), while Black patients made up 45% (13/29). Approximately 62 (18/29) percent of patients were diagnosed with adenocarcinoma, followed by squamous cell carcinoma in 28 percent (8/29) of patients. Tumor stage was 55%, 28%, 3% and 14% for stages I, II, III and IV respectively. Overall, there was a successful organoid development rate of 69 percent (20/29). There was a strong trend toward higher success rates in Black patients compared to White patients (85% vs. 56%, p = 0.10). There were no significant differences in successful organoid development based on gender (p = 0.43), histology (p = 0.18) or tumor stage (p = 0.84). Conclusions: Establishment of a racially diverse set of organoid models will be an invaluable tool for biomarker discovery and for screening novel therapeutic agents. Black patients appear to have similar to improved propensity for successful organoid development. Future efforts should be focused on creating diverse biobanks to strengthen precision oncology efforts for Black patients, collectively helping to reduce racial outcomes disparities in patients with lung cancer. Citation Format: Amanda Pilling, Hollis Hutchings, Avi Cohen, Shirish Gadgeel, Ikenna Okereke. Diversifying translational research models to address outcomes disparities in lung cancer [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C172.

Integrating novel interventional techniques into pediatric pulmonology training.

To review the evolution of pediatric pulmonology interventions and propose strategies for advancing training in the field. I examined the historical development of pediatric pulmonology interventions and current training practices, including hands-on courses and fellowship programs. I reviewed a survey of US pediatric pulmonology centers to assess variability in procedural expertise. Historically, foreign body removal dominated pediatric pulmonology interventions. Advancements in technology have expanded the field to include techniques such as endobronchial and transbronchial biopsies, airway lumen restoration, and cryotherapy, enabling more accurate tissue sampling with larger specimens while maintaining safety. Hands-on courses, offered globally and at major conferences, provide opportunities for skill development, self-assessment, and networking. However, limited availability leads to high demand and long waiting lists. A survey of US pediatric pulmonology centers revealed significant variability in procedural expertise, highlighting the need for uniform training across institutions. To better integrate interventional techniques, I propose that pediatric pulmonology training could benefit from a structured, tiered approach: (1) expanding hands-on workshops and incorporating them into fellowship programs, (2) facilitating collaborations between centers of excellence to allow trainees to rotate through institutions with advanced expertise, and (3) developing an additional year of training for an "Advanced Pediatric Pulmonologist" certification. This approach aims to ensure proficiency in the latest interventional techniques, standardize care, and foster advancements across the field.

Assessment of needle-based confocal laser endomicroscopy (nCLE) as a tool for real-time diagnosis of non-small cell lung cancer.

The widespread deployment of screening programs has increased the number of suspected pulmonary nodules diagnosed. The main objective of this retrospective study was to evaluate the concordance between needle-based confocal laser endomicroscopy (nCLE) image patterns and pathology reports. In this retrospective study, we reviewed all cases of endobronchial navigational bronchoscopy (ENB) performed using the nCLE system as a guide for injecting a dye marker or for biopsy of a lung nodule. All surgeries were performed at the Thoracic Surgery Department, University Hospital Nancy, France, between June and October 2023. All navigation procedures were performed under general anesthesia by a senior resident supervised by a senior surgeon, and endobronchial positioning assistance was provided by using the nCLE probe. A total of 30 patients were included in this study. The median size of the suspicious lesions was 16 mm [interquartile range (IQR), 13 mm]. The average time the nCLE system was in contact with the lesion was 5 minutes (IQR, 5 minutes). In 22/30 patients, dark, enlarged pleomorphic cells were visualized, and for one patient, a mix of dark clusters and dark enlarged pleomorphic cells was visualized, leading to a diagnosis of cancer in 22/23 patients (95.6%). For five patients, dark clusters were visualized, resulting in a diagnosis of cancer in 100% of patients. Pathology was performed for 6/30 patients/21 (20%) by endobronchial biopsy and for 24 patients by surgical resection of the suspicious lesion (80%). By retrospectively analyzing the nCLE lung cancer criteria published by Wijmans et al. in 2019, we observed 95.6% and 100% positive diagnoses according to the images visualized during the assistance of positioning. We believe that this type of technology could be used in the future for endobronchial analysis of suspected lesions and eventually for replacing frozen section analysis. However, the diagnostic value of this system needs to be confirmed, particularly for benign lesions.

Diagnostic efficacy of endobronchial ultrasound-guided transbronchoscopic lung biopsy for identifying tuberculous nodules

BackgroundMicrobiological diagnosis of pulmonary tuberculosis (PTB) is hampered by a low pathogen burden, low compliance and unreliable sputum sampling. Although endobronchial ultrasound-guided transbronchoscopic lung biopsy (EBUS-TBLB) has been found to be useful for the assessment of intrapulmonary nodules in adults, few data are available for the clinical diagnosis of pulmonary tuberculosis. Here, we evaluated EBUS-TBLB as a diagnostic procedure in adult patients with radiologically suspected intrapulmonary tuberculous nodules.MethodsThis was a retrospective analysis of patients admitted with pulmonary nodules between January 2022 and January 2023 at Hangzhou Red Cross Hospital. All patients underwent EBUS-TBLB, and lung biopsy samples were obtained during hospitalization. All samples were tested for Mycobacterium tuberculosis using acid‒fast smears, Bactec MGIT 960, Xpert MTB/RIF, next-generation sequencing (NGS), and DNA (TB‒DNA) and RNA (TB‒RNA). The concordance between different diagnostic methods and clinical diagnosis was analysed via kappa concordance analysis. The diagnostic efficacy of different diagnostic methods for PTB was analysed via ROC curve.ResultsA total of 107 patients were included in this study. Among them, 86 patients were diagnosed by EBUS-TBLB, and the overall diagnostic rate was 80.37%. In addition, 102 enrolled patients had benign lesions, and only 5 were diagnosed with lung tumours. Univariate analysis revealed that the diagnostic rate of EBUS-TBLB in pulmonary nodules was related to the location of the probe. The consistency analysis and ROC curve analysis revealed that NGS had the highest concordance with the clinical diagnosis results (agreement = 78.50%, κ = 0.558) and had the highest diagnostic efficacy for PTB (AUC = 0.778). In addition, Xpert MTB/RIF + NGS had the highest concordance with the clinical diagnosis results (agreement = 84.11%, κ = 0.667) and had the highest efficacy in the diagnosis of PTB (AUC = 0.826).ConclusionEBUS-TBLB is a sensitive and safe method for the diagnosis of pathological pulmonary nodules. Xpert MTB/RIF combined with NGS had the highest diagnostic efficacy and can be used in the initial diagnosis of PTB.

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

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. 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. 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. 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.

Influence of climatic changes on respiratory health in a teaching herd of outdoor-housed horses

Horses maintained outdoors may experience a lower-allergenic environment compared to their stabled counterparts. This study hypothesizes that climatic changes in southern Brazil can influence respiratory status. To test this hypothesis, we evaluated the lower airways of 17 horses from a teaching herd in southern Brazil, maintained outdoors, during winter, spring, and summer. Except for one mare with a history of severe asthma, all horses were considered healthy and underwent a physical examination. Airway endoscopic evaluation included scoring for tracheal mucus (0−5) and bronchial septum thickness (1−5). Bronchoalveolar lavage fluid (BALF) was collected at three time points, while bronchial septum biopsies were performed during spring and summer for airway epithelial investigation. Data analysis involved repeated measures ANOVA and Wilcoxon tests (p < 0.05). Tracheal mucus score and septal thickness did not differ across investigation periods. In BALF cytology, the mean percentage of neutrophils was higher in spring than summer (7.9 ± 13.4 % vs. 4.5 ± 11.7 %, P = 0.037), and eosinophil count was higher in winter than spring (0.64 ± 1.29 % vs. 0.03 ± 0.13 %, P = 0.034) and summer (0.64 ± 1.29 % vs. 0.14 ± 0.60 %, P = 0.023). Histopathological observations showed no differences between time points, and no correlations were observed with BALF analyses (P > 0.05). This study demonstrates that, even in an outdoor environment, horses' airways exhibit cytological modifications associated with different seasons, indicating a need for deeper investigation; endobronchial biopsy did not contribute to the clinical diagnosis.

Central Lung Cancer Location Along with Bronchoscopic Correlation- A Retrospective Cross-Sectional Study

Background: Lung cancer is currently the leading cause of death from neoplastic diseases worldwide. During the preceding decades, it was the most commonly occurring malignant disease, both in terms of impact and mortality. Fiberoptic bronchoscopy is the most important diagnostic tool for lung cancer. Early tissue diagnosis and proper staging remains the key to the management of the lung cancer patient. Endobronchial forceps biopsy has high diagnostic yield from the visible lesions. The aim of the study was to evaluate diagnostic yield of endobronchial biopsy. Methods: A Cross Sectional Retrospective study of all patients with provisional diagnosis of lung cancer based on computed tomography (CT) scan of chest undergoing fiberoptic bronchoscopy was done at Department of Respiratory Medicine, Ibn Sina Diagnostic &amp; Consultation Center, Chattogram, Bangladesh from July 2022 to June 2023. All fiberoptic bronchoscopy was done in endoscopy suite under local anesthesia. Patients were explained about the procedure thoroughly. Endobronchial biopsy was the main procedure performed. Results: A total of 120 patients underwent bronchoscopy for suspected lung cancer. The mean age of the patients was 58 years with range of 18 to 75 years. Among them 93 (77.5%) were male and 27 (22.5%) were female. Majority of the patients, 108 (90%) were smoker with a mean pack year of 42. The lesion was present more in right side (N=65) than the left side (N=55). Majority of the lesion was present in lobar bronchus followed by main bronchus. Bronchoscopy was normal in 10 patients (8.3%). 12 patients had lesion in multiple locations. The diagnostic yield of endobronchial biopsy was 75%. The diagnostic yield for central tumor was 81.6% which was statistically significant (p&lt;0.001) compared to peripheral tumor and extrinsic compression. Conclusion: Endobronchial biopsy provides good diagnostic yield especially in central tumors. Fiberoptic bronchoscopy is a safe procedure.

The role for endobronchial biopsy in the era of endobronchial ultrasound guided transbronchial needle aspiration for the diagnosis of sarcoidosis: a single center experience.

Endobronchial biopsy (EBBX) has been reported to increase diagnostic yield for pulmonary sarcoidosis. The purpose of this study is to investigate the diagnostic yield for EBBX following endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA). We identified a cohort of patients in the University of Minnesota Sarcoidosis Registry who had EBBx and EBUS-TBNA as part of workup for abnormal chest imaging. Data regarding demographics, biopsy approach and technique were recorded. Our cohort included 37 patients (53.24±9.5, Male, 22±0.57; 3.8% were African American). In these patients who had EBBX, EBUS-TBNA was performed in 100% of patients and TBBX was performed in 2 patients (5%). EBBX was positive in 9 patients (24%) and EBUS-TBNA was positive in 34 patients (92%). TBBX was diagnostic in one of two patients. EBBX was the only diagnostic tissue in 3 of the 37 patients (8%). Conclusion: The diagnostic yield of EBBX is lower than previously reported, with only 8% of EBBXs demonstrating granulomatous inflammation. However, instrumentation used for obtaining EBBX as well as the presence of visible lesions does influence the diagnostic yield. Studies with adequate power are needed before implementing changes in clinical practice. When performed alongside EBUS-TBNA, EBBX did not significantly add to the diagnostic yield in sarcoidosis unless visible lesions were observed.

Increased Muc5AC and Decreased Ciliated Cells in Severe Asthma Partially Restored by Inhibition of IL-4Rα Receptor.

The role of IL-13 on the airway epithelium in severe asthma leading to airway remodeling remains poorly understood. To study IL-13 induced airway remodeling on goblet cells and cilia in the airway epithelium in severe asthma and the impact of an anti-IL4Rα antibody, dupilumab, in vitro. Quantitative CT (qCT) lungs and endobronchial biopsies and brushings were obtained in 51 participants (22 severe, 11 non-severe asthma and 18 healthy participants) in the Severe Asthma Research Program (SARPIII) and measured for mucin and cilia related proteins. Epithelial cells were differentiated in air-liquid interphase (ALI) with IL-13 +/-dupilumab and assessed for mucin, cilia, cilia beat frequency (CBF) and epithelial integrity (transepithelial electrical resistance, TEER). Increased Muc5AC (Δ+263.2±92.7 lums/EpiArea) and decreased ciliated cells (Δ-0.07±0.03 Foxj1+cells/EpiArea) were observed in biopsies from severe asthma when compared to healthy (p<0.01 and p=0.047 respectively). RNAseq of epithelial cell brushes confirmed a Muc5AC increase with a decrease in a 5-gene cilia-related mean in severe asthma compared to healthy (all p<0.05). IL-13 (5 ng/mL) differentiated ALI cultures of healthy and asthmatic (severe and non-severe participants) increased Muc5AC, decreased cilia (α-acytl-tubulin) in healthy (Δ+6.5±1.5%, Δ-14.1±2.7%; all p<0.001 respectively) and asthma (Δ+4.4±2.5%, Δ-13.1±2.7%; p=0.084, p<0.001 respectively); decreased epithelial integrity (TEER) in healthy (-140.9±21.3 [ohms], p<0.001) while decreasing CBF in asthma (Δ-4.4±1.7 [Hz], p<0.01). When dupilumab was added to ALI with IL-13, there was no significant decrease in Mu5AC but there was restoration of cilia in healthy and asthma participants (absolute increase of 67.5% and 32.5% cilia, all p<0.05 respectively) while CBF increased (Δ+3.6±1.1 [Hz], p<0.001) and TEER decreased (only in asthma Δ-37.8±16.2 [ohms] p<0.05). IL-13 drives features of airway remodeling in severe asthma which are partially reversed by inhibiting IL-4Rα receptor in vitro.

The amount of hyaluronic acid and airway remodelling increase with the severity of inflammation in neutrophilic equine asthma

BackgroundEquine asthma (EA) is a chronic lower airway inflammation that leads to structural and functional changes. Hyaluronic acid (HA) has crucial functions in the extracellular matrix homeostasis and inflammatory mediator activity. HA concentration in the lungs increases in several human airway diseases. However, its associations with naturally occurring EA and airway remodelling have not been previously studied. Our aim was to investigate the association of equine neutrophilic airway inflammation (NAI) severity, airway remodelling, and HA concentration in horses with naturally occurring EA. We hypothesised that HA concentration and airway remodelling would increase with the severity of NAI. HA concentrations of bronchoalveolar lavage fluid supernatant (SUP) and plasma of 27 neutrophilic EA horses, and 28 control horses were measured. Additionally, remodelling and HA staining intensity were assessed from endobronchial biopsies from 10 moderate NAI horses, 5 severe NAI horses, and 15 control horses.ResultsThe HA concentration in SUP was higher in EA horses compared to controls (p = 0.007). Plasma HA concentrations were not different between the groups. In the endobronchial biopsies, moderate NAI horses showed epithelial hyperplasia and inflammatory cell infiltrate, while severe NAI horses also showed fibrosis and desquamation of the epithelium. The degree of remodelling was higher in severe NAI compared to moderate NAI (p = 0.048) and controls (p = 0.016). Intense HA staining was observed in bronchial cell membranes, basement membranes, and connective tissue without significant differences between the groups.ConclusionThe release of HA to the airway lumen increases in naturally occurring neutrophilic EA without clear changes in its tissue distribution, and significant airway remodelling only develops in severe NAI.

Distinguishing Bronchial Carcinoid from Benign Bronchocele using 68Ga-DOTATOC PET/CT Imaging.

Bronchial carcinoids are low-grade neuroendocrine tumors with slow growth rates and the potential to spread to nearby lymph nodes. Here we present a challenging case of bronchial carcinoid visualized alongside an adjacent benign bronchocele. Chest computed tomography (CT) identified the endobronchial mass with unclear morphological and diagnostic insights. A differential diagnosis of several benign and malignant etiologies was made. Subsequently, an endobronchial biopsy confirmed lung carcinoid. For better evaluation, a 68Ga-labeled 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid-d-Phe1-Tyr3-octreotide (68Ga-DOTATOC) positron emission tomography/CT scan was performed. The scan revealed a locally confined endobronchial mass with intense 68Ga-DOTATOC expression. Adjacent benign bronchocele was visualized with insignificant 68Ga-DOTATOC expression. Histopathological examination of the resected upper lobe confirmed these findings. This case highlights the importance of somatostatin receptor imaging in accurately identifying the extent of carcinoid tumors in the primary, nodal, and metastatic domains.

A Multiscale Connected UNet for the Segmentation of Lung Cancer Cells in Pathology Sections Stained Using Rapid On-Site Cytopathological Evaluation

Lung cancer is an increasingly serious health problem worldwide, and early detection and diagnosis are crucial for successful treatment. With the development of artificial intelligence and the growth of data volume, machine learning techniques can play a significant role in improving the accuracy of early detection in lung cancer.This study proposes a deep learning-based segmentation algorithm for rapid on-site cytopathological evaluation (ROSE) to enhance the diagnostic efficiency of endobronchial ultrasoundguided transbronchial needle aspiration biopsy (EBUS-TBNA) during surgery. By utilizing the CUNet3+ network model, cell clusters, including cancer cell clusters, can be accurately segmented in ROSE-stained pathological sections. The model demonstrated high accuracy, with an F1-score of 0.9604, recall of 0.9609, precision of 0.9654, and accuracy of 0.9834 on the internal testing dataset. It also achieved an AUC of 0.9972 for cancer identification. The proposed algorithm provides time savings for on-site diagnosis, improves EBUS-TBNA efficiency, and outperforms classical segmentation algorithms in accurately identifying lung cancer cell clusters in ROSE-stained images. It effectively reduces over-segmentation, decreases network parameters, and enhances computational efficiency, making it suitable for real-time patient evaluation during surgical procedures.

Expression of glucocorticoid receptor and HDACs in airway smooth muscle cells is associated with response to steroids in COPD

BackgroundSteroid insensitivity in Chronic Obstructive Pulmonary Disease (COPD) presents a problem for controlling the chronic inflammation of the airways. The glucocorticoid receptor (GR) mediates the intracellular signaling of inhaled corticosteroids (ICS) by interacting with transcription factors and histone deacetylases (HDACs). The aim of this study was to assess if COPD patients’ response to ICS in vivo, may be associated with the expression of GR, the complex of GR with transcription factors, and the expression of various HDACs in vitro.MethodsPrimary airway smooth muscle cells (ASMC) were established from endobronchial biopsies obtained from patients with asthma (n = 10), patients with COPD (n = 10) and subjects that underwent diagnostic bronchoscopy without pathological findings and served as controls (n = 6). ASMC were also established from 18 COPD patients, 10 responders and 8 non-responders to ICS, who participated in the HISTORIC study, an investigator-initiated and driven clinical trial that proved the hypothesis that COPD patients with high ASMC in their endobronchial biopsies respond better to ICS than patients with low ASMC. Expression of GR and its isoforms GRα and GRβ and HDACs was investigated in primary ASMC in the absence or in the presence of dexamethasone (10− 8M) by western blotting. The complex formation of GR with transcription factors was assessed by co-immunoprecipitation.ResultsExpression of GR and its isoform GRα but not GRβ was significantly reduced in ASMC from COPD patients as compared to controls. There were no significant differences in the expression of GR, GRα and GRβ between responders and non-responders to ICS. However, treatment with dexamethasone upregulated the expression of total GR (p = 0.004) and GRα (p = 0.005) after 30 min in responders but not in non-responders. Τhe formation of the complex GR-c-Jun was increased 60 min after treatment with dexamethasone only in responders who exhibited significantly lower expression of HDAC3 (p = 0.005) and HDAC5 (p < 0.0001) as compared to non-responders.ConclusionsThese data suggest that ASMC from COPD patients who do not respond to treatment with ICS, are characterized by reduced GR-c-Jun complex formation and increased expression of HDAC3 and HDAC5.Trial registrationISRCTN11017699 (Registration date: 15/11/2016).

ALL THE ROADS LEAD TO THE MYSTERIOUS DISEASE

Abstract A 58–year–old man with familiarity for sudden cardiac death was accepted to the hospital for dyspnea. Two years before he underwent cardiac angiography which showed a significative lesion of the descending artery which was treated with the placement of a drug eluting stent. For the appearance of an atrio–ventricular block 2:1, a permanent pacemaker was implanted. A transthoracic echocardiogram demonstrated: mildly dilated left ventricle with a reduced global systolic function (calculated ejection fraction was of 25%). Computed tomography with intravenous contrast of the chest showed upper, mid and lower multifocal nodularity with irregular margins with predominantly peri –bronchial distribution. The patient underwent bronchoscopy with endotracheal ultrasound and multiple transbronchial biopsies. Bronchoalveolar lavage (BAL) was negative for fungi infections, bacteria (including Mycobacterium Complex), and malignant cells. Endobronchial biopsies revealed non–necrotizing, well–formed granulomas embedded in dense hyaline sclerosis. Also the ratio of CD4+/CD8+ cells was within limits. FDG PET–TC scan showed: multiple enhancing areas in the lungs and lymph nodes probably of an inflammatory nature and therefore compatible with pulmonary sarcoidosis. A high dosage cortisone therapy was started, the patient was transferred to undergo endomyocardial biopsy, subsequently tested positive for multisystemic disease. Sarcoidosis is a rare disease with extremely heterogeneous clinical presentations. Actually, it is characterized by non–necrotizing granulomas, aggregates of epithelial cells, macrophages, multinucleated giant cells and CD4+ T lymphocytes, which infiltrate different tissues. When symptomatic, cardiac sarcoidosis includes conduction abnormalities, arrhythmias and ventricle dilation with hearth failure. Rhythm disorders, which rang from first to third degree, are the most common manifestation together with atrial fibrillation and ventricular tachyarrhythmias which can be explained with reentrant mechanisms from the granulomatous scar. Both atria–ventricular blocks and history of ventricular tachycardia elevate the risk for sudden cardiac death, which may be the first and unique manifestation of the disease. If myocardial involvement is extensive, cardiac sarcoidosis can present with hearth failure.