Real-time ultrasound-guided thoracentesis simulation using an optical see-through head-mounted display: a proof-of-concept study.

Aim: This study aimed to examine the feasibility and potential benefits of an optical see-through head-mounted display (OST-HMD) during real-time ultrasound-guided thoracentesis simulations. Material and methods: Six physicians performed a thoracentesis simulation using an OST-HMD and a wireless image transmission system. The time required, puncture needle visibility, pleural fluid collection success rate, and head movement during the procedure using a smart glass equipped with an inertial measurement unit were all recorded and compared with and without the HMD. Results: Study participants successfully extracted effusions in all procedures. The use of OST-HMD did not significantly affect the time of the procedure, but notably decreased the horizontal and vertical head movements during the procedure. Conclusions: The study demonstrated the feasibility of using an OST-HMD in a simulated real-time ultrasound-guided thoracentesis procedure and showed the potential of HMD in thoracentesis to improve ergonomics and accuracy. Further research is necessary to confirm these findings.

Optical Biopsies Using Probe-Based Confocal Laser Endomicroscopy for Autoimmune Pulmonary Alveolar Proteinosis.

INTRODUCTION: Increasing numbers of cases of mild asymptomatic pulmonary alveolar proteinosis (PAP) are being reported with the recent increase in chest computed tomography (CT). Bronchoscopic diagnosis of mild PAP is challenging because of the patchy distribution of lesions, which makes it difficult to obtain sufficient biopsy samples. Additionally, the pathological findings of mild PAP, particularly those that differ from severe PAP, have not been fully elucidated. This study aimed to clarify the pathological findings of mild PAP and the usefulness of optical biopsy using probe-based confocal laser endomicroscopy (pCLE). METHODS: We performed bronchoscopic optical biopsy using pCLE and tissue biopsy in 5 consecutive patients with PAP (three with mild PAP and two with severe PAP). We compared the pCLE images of mild PAP with those of severe PAP by integrating clinical findings, tissue pathology, and chest CT images. RESULTS: pCLE images of PAP showed giant cells with strong fluorescence, amorphous substances, and thin alveolar walls. Images of affected lesions in mild PAP were equivalent to those obtained in arbitrary lung lesions in severe cases. All 3 patients with mild PAP spontaneously improved or remained stable after ≥3 years of follow-up. Serum autoantibodies to granulocyte-macrophage colony-stimulating factor were detected in all 5 cases. CONCLUSION: Optical biopsy using pCLE can yield specific diagnostic findings, even in patients with mild PAP. pCLE images of affected areas in mild and severe PAP showed similar findings, indicating that the dysfunction level of pathogenic alveolar macrophages in affected areas is similar between both disease intensities.

Lethal ventricular arrhythmia due to entrectinib-induced Brugada syndrome: a case report and literature review.

Entrectinib, a multikinase inhibitor of ROS1 and tropomyosin receptor kinases, is recommended to treat ROS1-positive metastatic non-small cell lung cancer (NSCLC). In a previous study, entrectinib-related cardiotoxicity occurred in 2% of patients; however, lethal arrhythmias remain understudied. We encountered a case of fatal arrhythmia due to drug-induced Brugada syndrome caused by entrectinib. An 81-year-old Japanese male with lung adenocarcinoma harboring ROS1-fusion gene was treated with entrectinib. The patient developed lethal arrhythmias three days after drug initiation, including ventricular tachycardia with Brugada-like electrocardiogram changes. Echocardiography and coronary angiography revealed no evidence of acute coronary syndrome or myocarditis. Following the termination of entrectinib, the electrocardiogram abnormality improved within 12 days. Hence, paying special attention to and monitoring electrocardiogram changes is necessary. In addition, it is also necessary to consider early therapeutic interventions and discontinuation of the drug in cases of drug-induced Brugada syndrome.

Inhalation adherence for asthma and COPD improved during the COVID-19 pandemic: a questionnaire survey at a university hospital in Japan.

Background: Good adherence to an inhaled medication protocol is necessary for the management of asthma and chronic obstructive pulmonary disease (COPD), and several interventions to improve adherence have been reported. However, the impact of patient life changes and psychological aspects on treatment motivation is obscure. Here, we investigated changes in inhaler adherence during the COVID-19 pandemic and how lifestyle and psychological changes affected it.Methods: Seven-hundred sixteen adult patients with asthma and COPD who had visited Nagoya University Hospital between 2015 and 2020 were selected. Among them, 311 patients had received instruction at a pharmacist-managed clinic (PMC). We distributed one-time cross-sectional questionnaires from January 12 to March 31, 2021. The questionnaire covered the status of hospital visits, inhalation adherence before and during the COVID-19 pandemic, lifestyles, medical conditions, and psychological stress. The Adherence Starts with Knowledge-12 (ASK-12) was used to assess adherence barriers.Results: Four-hundred thirty-three patients answered the questionnaire. Inhalation adherence was significantly improved in both diseases during the COVID-19 pandemic. The most common reason for improved adherence was fear of infection. Patients with improved adherence were more likely to believe that controller inhalers could prevent COVID-19 from becoming more severe. Improved adherence was more common in patients with asthma, those not receiving counseling at PMC, and those with poor baseline adherence.Conclusions: Inhalation adherence for asthma and COPD improved in the COVID-19 pandemic. The patients seemed to realize the necessity and benefits of the medication more strongly than before the pandemic, which motivated them to improve adherence.

Diagnostic value and safety of endobronchial ultrasonography with a guide sheath transbronchial biopsy for diagnosing peripheral pulmonary lesions in patients with interstitial lung disease.

Background: Radial endobronchial ultrasonography transbronchial biopsy with and without a guide sheath is a useful method for diagnosing peripheral pulmonary lesions (PPLs). However, the diagnostic yield and complications of radial endobronchial ultrasonography transbronchial biopsy for PPLs remains elusive in patients with interstitial lung disease (ILD). Methods: We retrospectively analysed 431 patients (69 with and 362 without ILD) who underwent radial endobronchial ultrasonography with a guide sheath transbronchial biopsy (EBUS-GS TBB) for PPLs from April 1, 2011, to March 31, 2020. We investigated the diagnostic yield and complications of the procedure for PPLs and compared them between patients with and without ILD. We also evaluated the factors contributing to successful diagnosis. Results: The diagnostic yield of radial endobronchial ultrasonography in patients with ILD was significantly lower than in those without ILD (62.3% vs. 75.4%, P=0.024). Multivariate analysis showed that the presence of ILD as background lung [odds ratio (OR) =0.517], probe position within the lesion (OR =4.654), and the presence of solid lesion (OR =1.946) significantly affected the diagnostic yield of PPLs. There was a significant difference in the rate of pneumothorax between the patients with ILD and those without ILD (4.3% vs. 0.6%, P=0.031). Conclusions: The presence of ILD as the background lung significantly affected the diagnostic yield of PPLs with radial EBUS-GS TBB. Regarding the complications, pneumothorax occurred more frequently in patients with ILD than in those without ILD.

A Diagnostic Predictive Model of Bronchoscopy with Radial Endobronchial Ultrasound for Peripheral Pulmonary Lesions.

BACKGROUND: Several factors have been reported to affect the diagnostic yield of bronchoscopy with radial endobronchial ultrasound (R-EBUS) for peripheral pulmonary lesions (PPLs). However, it is difficult to accurately predict the diagnostic potential of bronchoscopy for each PPL in advance. OBJECTIVES: Our objective was to establish a predictive model to evaluate the diagnostic yield before the procedure. METHOD: We retrospectively analysed consecutive patients who underwent diagnostic bronchoscopy with R-EBUS between April 2012 and October 2015. We assessed the factors that were predictive of successful bronchoscopic diagnosis of PPLs with R-EBUS using a multivariable logistic regression model. The accuracy of the predictive model was evaluated using the receiver operator characteristic area under the curve (ROC AUC). Internal validation was analysed using 10-fold stratified cross-validation. RESULTS: We analysed a total of 1,634 lesions; the median lesion size was 25.0 mm. Of these, 1,138 lesions (69.6%) were successfully diagnosed. In the predictive logistic model, significant factors affecting the diagnostic yield were lesion size, lesion structure, bronchus sign, and visible on chest X-ray. The predictive model consisted of seven factors: lesion size, lesion lobe, lesion location from the hilum, lesion structure, bronchus sign, visibility on chest X-ray, and background lung. The ROC AUC of the predictive model was 0.742 (95% confidence interval: 0.715-0.769). Internal validation using 10-fold stratified cross-validation revealed a mean ROC AUC of 0.734. CONCLUSIONS: The predictive model using the seven factors revealed a good performance in estimating the diagnostic yield.

Epidermal growth factor receptor mutation-positive advanced lung adenocarcinoma presenting with acute respiratory failure diagnosed by thin bronchoscope through transnasal route under high-concentration oxygen mask.

A 59-year-old woman complained of continuous dyspnea. Computed tomography revealed multiple pulmonary nodules, mildly small enlarged mediastinal lymph nodes and a nodule in the liver segment 8. Her dyspnea worsened with respiratory failure 4 days after presentation. Liver biopsy was not possible as she could not hold her breath; thus, we performed bronchoscopy. For biopsy, the pulmonary nodules with a positive bronchus sign were preferred over the mildly small enlarged mediastinal lymph nodes. Bronchoscopy under non-invasive positive pressure ventilation (NPPV) or high-flow nasal cannula (HFNC) was impossible because of the lack of equipment. Therefore, we biopsied via thin bronchoscope through nasal cavity under a high-concentration oxygen mask. Pathological findings revealed epidermal growth factor receptor mutation-positive lung adenocarcinoma. For patients with respiratory failure who cannot undergo bronchoscopy under NPPV or HFNC, thin bronchoscopy through the nasal cavity under a high-concentration oxygen mask may be clinically useful to prevent hypoxaemia during the procedure.

Prevention of droplet dispersal with 'e-mask': A new daily use endoscopic mask during bronchoscopy.

BACKGROUND AND OBJECTIVE: Bronchoscopy is an airborne particle-generating procedure. However, few methods for safe bronchoscopy have been developed. To reduce airborne particles during bronchoscopy, we created an 'e-mask', which is a simple, disposable mask for patients. Our objective was to evaluate the e-mask's protective ability against airborne particles and to assess respiratory adverse events and complications. METHODS: Patients with stage 2-4 chronic obstructive pulmonary disease were excluded. We performed visualization and quantifying experiments on airborne particles with and without the e-mask. We prospectively evaluated whether wearing the e-mask during bronchoscopy was associated with the incidence of patients requiring >5 L/min oxygen to maintain >90% oxygen saturation, and patients with >45 mm Hg end-tidal carbon dioxide (EtCO2 ) elevation, in addition to complications, compared to historical controls. RESULTS: In the visualization experiment, more than ten thousand times of airborne particles were generated without the e-mask than with the e-mask. The volume of airborne particles was significantly reduced with the e-mask, compared to that without the e-mask (p = 0.011). Multivariate logistic regression analysis revealed that wearing the e-mask had no significant effect on the incidence of patients requiring >5 L/min oxygen to maintain >90% oxygen saturation, (p = 0.959); however, wearing the e-mask was a significant factor in >45 mm Hg EtCO2 elevation (p = 0.026). No significant differences in complications were observed between the e-mask and control groups (5.8% vs. 2.5%, p = 0.395). CONCLUSION: Wearing the e-mask during bronchoscopy significantly reduced the generation of airborne particles during bronchoscopy without increasing complications.

Virtual Bronchoscopy-Guided Transbronchial Biopsy Simulation Using a Head-Mounted Display: A New Style of Flexible Bronchoscopy.

Background/need. The increases in reference images and information during bronchoscopy using virtual bronchoscopic navigation (VBN) and fluoroscopy has potentially created the need for support using a head-mounted display (HMD) because bronchoscopists feel difficulty to see displays that are at a distance from them and turn their head and body in various directions. Methodology and device description. The binocular see-through Moverio BT-35E Smart Glasses can be connected via a high-definition multimedia interface and have a 720p high-definition display. We developed a system that converts fluoroscopic (live and reference), VBN, and bronchoscopic image signals through a converter and references them using the Moverio BT-35E. Preliminary results. We performed a virtual bronchoscopy-guided transbronchial biopsy simulation using the system. Four experienced pulmonologists performed a simulated bronchoscopy of 5 cases each with the Moverio BT-35E glasses, using bronchoscopy training model. For all procedures, the bronchoscope was advanced successfully into the target bronchus according to the VBN image. None of the operators reported eye or body fatigue during or after the procedure. Current status. This small-scale simulation study suggests the feasibility of using a HMD during bronchoscopy. For clinical use, it is necessary to evaluate the safety and usefulness of the system in larger clinical trials in the future.

Guide sheath versus non-guide sheath method for endobronchial ultrasound-guided biopsy of peripheral pulmonary lesions: a multicentre randomised trial.

BACKGROUND: Guide sheaths (GSs) have been widely used during radial probe endobronchial ultrasound-guided transbronchial biopsy (rEBUS-TBB) of peripheral pulmonary lesions. However, it remains unknown whether a GS enhances the diagnostic yield. We compared the diagnostic yields of small peripheral pulmonary lesions between rEBUS-TBB with and without a GS. METHODS: In eight institutions, patients with peripheral pulmonary lesions ≤30 mm in diameter were enrolled and randomised to undergo rEBUS-TBB with a GS (GS group) or without a GS (non-GS group) using a 4.0-mm thin bronchoscope, virtual bronchoscopic navigation and fluoroscopy. The primary end-point was the diagnostic yield of the histology specimens. RESULTS: A total of 605 patients were enrolled; ultimately, data on 596 (300 in the GS group and 296 in the non-GS group) with peripheral pulmonary lesions having a longest median diameter of 19.6 mm were analysed. The diagnostic yield of histological specimens from the GS group was significantly higher than that from the non-GS group (55.3% versus 46.6%; p=0.033). Interactions were evident between the diagnostic yields, procedures, lobar locations (upper lobe versus other regions; p=0.003) and lesion texture (solid versus part-solid nodules; p=0.072). CONCLUSIONS: The diagnostic yield for small peripheral pulmonary lesions afforded by rEBUS-TBB using a GS was higher than that without a GS.

A Pilot Study of Transbronchial Biopsy Using Endobronchial Ultrasonography with a Guide Sheath in the Diagnosis of Peripheral Pulmonary Lesions in Patients with Interstitial Lung Disease.

The occurrence of interstitial lung disease (ILD) with peripheral pulmonary lesions (PPLs) is closely linked to the development of lung cancer. Yet, the best diagnostic approach for identifying PPLs in patients with ILD remains elusive. This study retrospectively investigated the application of transbronchial biopsy (TBB) using endobronchial ultrasonography with a guide sheath (EBUS-GS) to the effective and safe diagnosis of PPLs when compared with conventional TBB. The study sample included a consecutive series of 19 patients with ILD who underwent conventional TBB or TBB using EBUS-GS at Tosei General Hospital between 1 April 2013 and 31 October 2015. The two techniques were compared based on diagnostic yield and associated complications. The diagnostic yield of EBUS-GS TBB was significantly higher than that of conventional TBB (p = 0.009), especially for small lesions (≤20 mm), lesions located in the lower lobes, lesions with a positive bronchus sign, and lesions visible by chest radiography (p = 0.010, p = 0.022, p = 0.006, and p = 0.002, respectively). There were no significant differences in complication rates. Therefore, EBUS-GS is an effective alternative for the diagnosis of PPLs in patients with ILD, without additional complications.

Endobronchial Ultrasonography with a Guide Sheath Transbronchial Biopsy for Diagnosing Peripheral Pulmonary Lesions within or near Fibrotic Lesions in Patients with Interstitial Lung Disease.

In patients with interstitial lung disease (ILD), the most frequent locations of lung cancer are within or near fibrotic lesions. However, the diagnostic yield for peripheral pulmonary lesions (PPLs) within or near fibrotic lesions using endobronchial ultrasonography with a guide sheath transbronchial biopsy (EBUS-GS TBB) may be unsatisfactory compared to that for PPLs distant from fibrotic lesions because of the difficulty in reaching the lesions. Our objectives were to evaluate the yield for PPLs using EBUS-GS TBB according to the proximity of PPLs to fibrotic lesions and to determine factors affecting the yield for PPLs. We retrospectively investigated 323 consecutive lesions using EBUS-GS TBB between 1 November 2014 and 31 December 2016. We identified PPLs with ILD in such lesions. PPLs with ILD were divided into PPLs within or near fibrotic lesions which met the criterion of PPLs, and of fibrotic lesions overlapping each other (PPLs-FL) and those distant from fibrotic lesions, which met the criterion of PPLs and the area of fibrotic lesion not overlapping each other (PPLs-NFL). Of the 323 lesions, 55 were included (31 PPLs-FL and 24 PPLs-NFL). The diagnostic yield for PPLs-FL was significantly lower than for PPLs-NFL (45.2% vs. 83.3%, p = 0.004). Multivariate analysis revealed that PPLs-NFL (odds ratio (OR) = 7.509) and a probe position within the lesion (OR = 4.172) were significant factors affecting diagnostic yield. Lesion's positional relation to fibrotic lesions and the probe position were important factors affecting the successful diagnosis via EBUS-GS TBB in these patients.

The Value of Additional Conventional Transbronchial Biopsy in the Negative Results of Rapid On-site Evaluation During Endobronchial Ultrasound With Guide Sheath to Diagnose Small Peripheral Lung Cancer.

Objective: The accuracy of rapid on-site evaluation (ROSE) during endobronchial ultrasonography with guide sheath (EBUS-GS) was reported to be approximately 90% for diagnosing small peripheral pulmonary lesions (PPLs). When ROSE during EBUS-GS for diagnosing small peripheral lung cancer is carried out and does not include malignant cells in a position whereby the probe was located within or adjacent to the lesion, the best technique for overcoming the lower diagnostic yield remains unknown. This study aimed to evaluate factors affecting positive results of ROSE during EBUS-GS in such a probe position. Moreover, when the results of ROSE were consistently negative, we evaluated the effectiveness of conventional transbronchial biopsy (TBB) in addition to EBUS-GS alone. Methods: We performed a retrospective analysis of consecutive patients who underwent EBUS-GS combined with ROSE for diagnosing small peripheral lung cancer (≤30 mm). We classified the results of ROSE into two groups based on the presence of malignant cells: the ROSE positive group (included malignant cells) and the ROSE negative group (did not include malignant cells). The significant predictors of positive ROSE results during EBUS-GS were analyzed using multivariate logistic regression analyses. Results: We identified 67 lesions (43 lesions in the ROSE positive group and 24 lesions in the ROSE negative group, respectively). Multivariate logistic analysis revealed that the significant factor affecting positive ROSE results was lesion size (>15 mm) (OR = 9.901). The diagnostic yield of additional conventional TBB to EBUS-GS was significantly higher than that of EBUS-GS alone (75.0% vs 33.3%, P = .041). Conclusion: The positive results of ROSE during EBUS-GS were significantly influenced by lesion size (>15 mm). When the results of ROSE during EBUS-GS were consistently negative in a position whereby the probe was located within or adjacent to the lesion, additional conventional TBB was effective to improve the diagnostic yield compared with EBUS-GS alone.

Unusual presentation of recurrent follicular lymphoma as diffuse granular shadow.

A 75-year-old man was diagnosed with advanced follicular lymphoma because of enlarged cervical lymph nodes. He received chemotherapy and was in complete remission for four years. However, after four years, he developed diffuse lymphadenopathy in the abdominal and iliac area suspected to be recurrent follicular lymphoma. At the time, he was asymptomatic and did not have any accompanying lung lesions. Due to his asymptomatic state, careful monitoring was chosen. Later, he developed diffuse granular shadow in the lung fields. A definite diagnosis was difficult to achieve without histological findings. Therefore, transbronchial lung biopsy of the lesions was performed. The pathology and immunohistochemistry of the lesions revealed recurrent follicular lymphoma. Although the frequency of recurrent follicular lymphoma presenting with diffuse granular shadow is uncommon, recurrent malignant lymphoma should be considered as a differential diagnosis in case with a history of malignant lymphoma.

Risk factors for pulmonary infection after diagnostic bronchoscopy in patients with lung cancer.

Pulmonary infection is a relatively rare but serious complication of flexible bronchoscopy. The aim of this study was to identify the risk factors for pulmonary infectious complications after diagnostic bronchoscopy in patients with lung cancer. We retrospectively analyzed the medical records of 636 patients who underwent bronchoscopic biopsy for lung cancer diagnosis between April 2011 and March 2016. We compared patients' characteristics, chest computed tomography and bronchoscopic findings, undertaken procedures, and final diagnoses between patients who developed the complication and those who did not. Pulmonary infection after the diagnostic bronchoscopy occurred in 19 patients (3.0%) and included pneumonia in 16 patients and lung abscess in 3. Patients with larger lesions, presence of endobronchial lesions, histology of small cell lung cancer, and advanced disease stage tended to develop pulmonary infectious complications more often. Our multivariate analysis revealed that a larger lesion size and the presence of endobronchial lesions were independently associated with post-bronchoscopy pulmonary infection. Although we found no mortality associated with the infections, two patients were left with significant performance status deterioration after the pulmonary infection and received no anticancer treatment. In conclusion, endobronchial lesions and a larger lesion size are independent risk factors for the incidence of infections following bronchoscopic biopsy in patients with lung cancer.

Endobronchial ultrasound-guided transbronchial needle aspiration under non-invasive positive pressure for the diagnosis of lung metastasis due to renal cell carcinoma in a patient with respiratory failure.

A 65-year-old man with chronic respiratory failure caused by chronic obstructive pulmonary disease, had a pulmonary nodule adjacent to the inlet of right B1 and B3. The patient had undergone a surgery for right renal cell carcinoma and colon cancer 6 years prior. We attempted endobronchial ultrasound-guided transbronchial needle aspiration under non-invasive positive pressure ventilation for diagnosis, with rapid on-site cytology, which was performed without complications. The histological findings revealed lung metastasis involving renal cell carcinoma. Endobronchial ultrasound-guided transbronchial needle aspiration under non-invasive positive pressure ventilation is useful for diagnosing lesions that require access up to the segmental bronchus in patients with respiratory failure.

Diagnostic contribution of cytological examination to endobronchial ultrasound-guided transbronchial biopsy for lung malignancies.

Although endobronchial ultrasound guided transbronchial biopsy (TBB) with a guide sheath (EBUS-GS) is widely used for diagnosis of peripheral pulmonary lesions, the diagnostic contribution of cytology (bronchial brushing, bronchial washing and biopsy forceps rinse) has not been established. To determine the diagnostic contribution of cytological examination to EBUS-GS-TBB, we reviewed medical records of patients with lung malignancies who had undergone TBB with EBUS-GS (EBUS-GS group, n=187) or TBB without EBUS-GS (conventional TBB [CTBB] group, n=197) at Nagoya University Hospital. Although the mean size of target lesions was significantly larger in the CTBB group than the EBUS-GS group, the total diagnostic rate was equivalent between two groups (EBUS-GS: 73.3%, CTBB: 66.0%). In the EBUS-GS group, cytological procedures increased the diagnostic rate by 9.1% (17/137), compared with only 4.1% (8/130) in the CTBB group. Sensitivity of cytology among biopsy-negative patients was significantly higher in EBUS-GS group than CTBB group (P=0.022). Furthermore, in the EBUS-GS group, among 17 patients whose malignant diagnoses could only be established cytologically, bronchial brushing contributed to the malignant diagnosis in 64.7% (11/17). These data may suggest that cytological examination, especially bronchial brushing, may be an important diagnostic contributor in EBUS-GS-TBB.