Changes in fractional exhaled nitric oxide, forced expiratory volume in one second, and forced oscillation technique parameters over three years in adults with bronchial asthma managed under Yokohama Seibu Hospital's coordinated care system.

BACKGROUND: In western Yokohama, our hospital and primary care clinics manage adults with asthma via a coordinated care system. We investigated the changes in the fractional expired nitric oxide (FeNO), forced expiratory volume in 1 second (FEV1), and forced oscillation technique (FOT) parameters over 3 years in a cohort of patients in our collaborative system. METHODS: From 288 adults with well controlled asthma managed under the Yokohama Seibu Hospital coordinated care system between January 2009 and May 2018, we selected 99 subjects to undergo spirometry, FeNO and FOT testing over 3 years and analyzed the changes in these parameters. RESULTS: Of the 99 patients enrolled, 17 (17.2%) experienced at least one exacerbation (insufficiently controlled (IC)), whereas, 82 (82.8%) remained in well controlled during the 3-year study period. Of well-controlled patients, 54 patients (54.5%) met the criteria for clinical remission under treatment (CR); the remaining 28 patients did not meet the CR criteria (WC). There were no differences in FeNO, FEV1, or FOT parameters at baseline among the IC, WC, and CR groups. The levels of FEV1 decreased gradually, whereas the levels of FeNO decreased significantly over 3 years. The levels of percent predicted FEV1 (%FEV1) significantly increased. We also observed significant improvement in FOT parameters; reactance at 5 Hz (R5), resonant frequency (Fres), and integral of reactance up to the resonant frequency (AX). The CR group demonstrated significant relationships between the change in FeNO and the change in FEV1 and between the change in FEV1 and the change in FOT parameters. No significant correlations emerged in the IC or WC group. CONCLUSION: The decrease in FeNO and increase in %FEV1, we observed in all study participants suggest that the coordinated care system model benefits patients with asthma. Although it is difficult to predict at baseline which patients will experience an exacerbation, monitoring changes in FeNO and FEV1 is useful in managing patients with asthma. Furthermore, monitoring changes in R5, Fres, and AX via forced oscillation technique testing is useful for detecting airflow limitation.

[THE INFLUENCE OF SENSITIZATION TO ASPERGILLUS AND ALTERNARIA IN ADULT BRONCHIAL ASTHMATICS MANAGED VIA YOKOHAMA CITY SEIBU HOSPITAL'S COORDINATED-CARE SYSTEM].

BACKGROUND: The sensitizations to various fungal allergens influence to exacerbation of bronchial asthma. Aspergillus (Asp) and Alternaria (Alt) were one of important fungal allergens for asthma. AIM AND METHODS: To investigate the influence of sensitization to Asp or Alt in adult asthmatics managed via our asthma coordinated-care system, we recruited 119 patients (91 women) who were measured IgE for Asp (IgE-Asp) and IgE for Alt (IgE-Alt) at three times during two years,Results: In 119 patients, we detected positive IgE for Asp (IgE-Asp(+)) in 19 patients and positive IgE for Alt (IgE-Alt(+)) in 11 patients. 9 patients showed positive both of them. During two years, 7 patients became positive IgE-Asp and 3 cases became negative. And also, 3 cases became positive IgE-Alt and 3 cases became negative. At baseline, serum IgE, IgG4, and inhaled corticosteroid (ICS) dose of the group with IgE-Asp (+) or IgE-Alt (+), were significant higher than those of negative group. Among three groups, there was no significant change about other parameters at baseline, exacerbation frequency, or the change of parameters during two years. CONCLUSION: The sensitizations to Asp or Alt were present in 19 asthmatics (16%) managed via our coordinate-care system. During 2 years, there was not significant change at exacerbation frequency among three groups, but the levels of IgE, IgG4, or ICS dose were significantly higher at IgE-Asp (+) or IgE-Alt (+) group than negative group. In the asthma management, it was considered necessary to pay attention to the sensitization to Asp or Alt.

[THE RELATIONSHIP AMONG BRONCHIAL HYPERSENSITIVITY, BRONCHIAL HYPER REACTIVITY, AND BRONCHIAL HYPERRESPONSIVENESS IN ASTOGRAPH].

BACKGROUND: Bronchial hyperresponsiveness testing is useful for diagnosing and predicting the risk of bronchial asthma attacks. The Astograph is a tidal breathing method often used in as bronchial provocation testing in Japan. The minimum methachorine dose (Dmin) indicates bronchial sensitivity and is used mainly as an index of bronchial hyperresponsiveness. However, Dmin does not measured hyperresponsiveness, it cannot be compared directly with PC20 in standard methods using FEV1. METHODS: We investigated the relationship among sensitivity, reactivity, and hyperresponsiveness with the Astograph. We recruited 142 patients with confirmed or suspected bronchial asthma from outpatient clinic at St. Marianna University School of Medicine, Yokohama City Seibu Hospital. We calculated Dmin, SGrs/Grscont, PD35Grs, and PD15Grs compared them as bronchial hyperresponsiveness indices. RESULTS: Subjects had suspected asthma (n=103), or required assessment of asthma remission (n=39). There were significant relationships between logDmin and logPD35Grs (r=0.838, p<0.001), and between parameters and SGrs/Grscont (log PD35Grs r=-0.504, p<0.001, strong, logDmin: r=-0.191, p=0.023, weaker). Among subjects positive for hypersensitivity, (Dmin<10), 38 (36.5%) showed negative hyperresponsiveness (PD35Grs>25). PD15Grs was a strongly and significantly correlated with Dmin and PD35Grs. The ROC curve to detect PD35Grs<25, showed that the cutoff of PD15Grs was 10.7 (AUC 0.983, sensitivity 0.984, specificity 0.905). CONCLUSION: In Astograph, evaluation of bronchial hyperresponsiveness, we focused on relationship differences between sensitivity and reactivity, and hyperresponsiveness. We revealed the usefulness of the PD15Grs evaluation method.

Suitability of transbronchial brushing cytology specimens for next-generation sequencing in peripheral lung cancer.

Next-generation sequencing (NGS) enables the diagnosis of large numbers of gene aberrations during one examination, and precision medicine has been developed for patients with advanced non-small cell lung cancer (NSCLC). However, peripheral lung lesions account for the majority of advanced lung cancers, especially lung adenocarcinoma. In these cases, it is difficult to obtain tissue samples which contain sufficient tumor cells by transbronchial biopsy (TBB) with forceps. Even when the target lesions are quite small, bronchial brushing can obtain enough tumor cells by endobronchial ultrasonography using guide sheath (EBUS-GS). In this study, we investigate the suitability of bronchial brushing cytology specimens obtained by EBUS-GS-TBB to evaluate the correlation between the success rate of NGS and extracted DNA/RNA yields according to biopsy method. We prospectively collected 222 tumor samples obtained from patients with advanced lung cancer. All patients were enrolled in a prospective nationwide genomic screening project for lung cancer (LC-SCRUM-Japan/Asia). Genomic data were obtained from the clinico-genomic database of LC-SCRUM-Japan/Asia. The extraction yields of DNA/RNA from samples obtained by EBUS-GS-TBB were relatively low compared with tissue samples. The success rate of DNA sequencing for EBUS-GS-TBB was 97.9%, with no significant differences between biopsy methods. The success rate of RNA sequencing for EBUS-GS-TBB was 80.4%, which was relatively low compared with surgical biopsy samples (P = 0.069). However, some rare oncogenic driver aberrations were detected from these specimens. This study demonstrated that cytology samples obtained by transbronchial brushing with EBUS-GS-TBB were suitable for NGS analysis.

Correlation between Computed Tomographic Analysis and Pulmonary Function Measurements in Patients with Relapsing Polychondritis.

BACKGROUND: Relapsing polychondritis (RP) is a rare systemic disease of unknown origin, with cartilaginous involvement in multiple organs. Airway involvement is the most important prognostic factor in RP. OBJECTIVES: Spirometric measurements and minimum tracheal cross-sectional area (mtCSA) have been reported as useful to assess the degree of airway stenosis. Because the length and severity of tracheal involvement in RP can vary, mtCSA might not provide enough information to assess tracheal abnormalities. We introduced tracheal volume (TrV) as a new method to evaluate correlations between chest computed tomography (CT) measurements and pulmonary function tests, including impulse oscillometry (IOS). METHOD: We analyzed chest CT images, spirometry, and IOS collected at our institution from April 2004 to March 2019. We calculated correlations between chest CT measurements using software (TrV, TrV/tracheal length [TrV/TL], and mtCSA) and pulmonary function parameters. RESULTS: Twenty-five of 73 clinically diagnosed patients with RP were included. Spirometric findings showed moderate airway obstruction. Peak flow (PEF) was strongly correlated with mtCSA, TrV, and TrV/TL (ρ = 0.74, p < 0.001). FEV1 was significantly correlated with mtCSA (ρ = 0.56, p = 0.004), TrV (ρ = 0.52, p = 0.007), and TrV/TL (ρ = 0.53, p = 0.006). Whereas respiratory resistance at 5 Hz (R5) and 20 Hz (R20) and resonant frequencies (RFs) were significantly correlated with TrV (ρ = -0.46, p = 0.021; ρ = -0.46, p = 0.046; and ρ = -0.42, p = 0.037, respectively), IOS parameters and mtCSA were not. CONCLUSIONS: In patients with RP, TrV and mtCSA were strongly correlated with spirometric measurements. Respiratory resistances assessed by IOS correlated only with TrV. This suggests TrV assessment reflects pulmonary function in patients with RP more appropriately than mtCSA.

Assessment of Extensive Airway Obstruction Using Point-by-Point Lateral Pressure Measurements during Bronchoscopy.

BACKGROUND: The positioning of the stent at the flow-limiting segment is crucial for patients with extensive airway obstruction to relieve dyspnea. However, CT and flow-volume curves cannot detect the area of maximal obstruction. OBJECTIVES: The aim of this study is to physiologically evaluate extensive airway obstruction during interventional bronchoscopy. METHODS: We prospectively measured point-by-point lateral airway pressure (Plat) at multiple points from the lower lobe bronchus to the upper trachea using a double-lumen catheter in 5 patients. The site of maximal obstruction was evaluated continuously to measure point-by-point Plat at multiple points when the airway catheter was withdrawn from the lower lobe bronchus to the upper trachea. RESULTS: Remarkable pressure differences occurred at the site of maximal obstruction assessed by point-by-point Plat measurements. After initial stenting in 1 case, migration of the maximal obstruction to a nonstented segment of the weakened airway was seen with extensive stenosis from the trachea to the bronchi. In the second case, in addition to radiological analysis, point-by-point Plat measurements could identify the location of the maximal obstruction which contributed to dyspnea. CONCLUSIONS: Point-by-point Plat measurement could be used to detect the site of maximal obstruction physiologically. Furthermore, Plat measurement could assess the need for additional procedures in real time in patients with extensive airway obstruction.

[A case of meningoencephalitis that developed during nivolumab use].

A 72-year-old woman developed a fever and consciousness disturbance after completing 8 courses of nivolumab for lung adenocarcinoma. A cerebrospinal fluid test showed an increased cell count, but bacterial culture, herpes simplex virus-polymerase chain reaction, acid-fast staining, and cytology were negative; serum paraneoplastic syndrome-related antibody was also negative. Serum and cerebrospinal fluid specimens were positive for anti-glutamate receptor (GluR) antibody, and fluid-attenuated inversion recovery images on head magnetic resonance imaging showed a high signal intensity at the right parietal lobe. The condition was determined to be immune-mediated encephalitis, and pulse steroid therapy was performed. The symptoms promptly improved after treatment. The patient in the present case was anti-GluR antibody-positive but was determined to have nivolumab-related encephalitis based on the clinical course. The use of immune checkpoint inhibitors has become widespread in recent years, although it can occasionally lead to encephalitis. We herein report our experience with immune checkpoint inhibitor-related encephalitis, which is seldom reported in Japan.

The Impact of EGFR Mutation Status and Brain Metastasis for Non-Small Cell Lung Cancer Treated with Ramucirumab plus Docetaxel.

OBJECTIVES: Currently, combination therapy of ramucirumab (RAM) + docetaxel (DOC) must play a more important role as a second-line treatment. Epithelial growth factor receptor (EGFR) mutation accounts for around 50% of oncogenic driver mutations in patients with advanced non-small cell lung cancer (NSCLC) in Asian subsets. The number of brain metastases (BM) is relatively higher in EGFR mutation-positive patients compared to EGFR wild-type patients. The objective of this study is to evaluate the efficacy of RAM + DOC focusing on EGFR mutation and BM. METHODS: We retrospectively reviewed consecutive advanced NSCLC patients who received combination therapy of RAM + DOC at three institutions. A total of 112 patients with NSCLC were enrolled for efficacy analyses. We evaluated the efficacy of RAM + DOC for EGFR-mutated NSCLC with endpoints including progression-free survival (PFS), time to treatment failure (TTF) and overall survival. RESULTS: Median PFS was 5.7 months for the EGFR mutant group compared with 3.6 months for the EGFR wild-type group (HR 0.53, 95% CI 0.32-0.87; p = 0.01). Median TTF was 5.1 months for the EGFR mutant group compared with 2.8 months for the EGFR wild-type group (HR 0.53, 95% CI 0.33-0.85; p = 0.007). Median PFS and TTF of the EGFR mutant group was significantly longer than median PFS and TTF of the EGFR wild-type group. The multivariate analysis identified EGFR mutation status as an independent favorable factor of PFS. In subset analyses of BM, median PFS of the EGFR mutant group (2.8 months) was significantly shorter than that of the EGFR wild-type group (5.1 months) (HR 7.27, 95% CI 1.78-29.68; p = 0.002). CONCLUSION: This study revealed that EGFR mutation status and BM might be predictive or prognostic factors for PFS.

Complicating effects of obstructive sleep apnea syndrome on the severity of adult asthma.

Introduction: Bronchial asthma (BA) and obstructive sleep apnea syndrome (OSAS) are common causes of respiratory disturbance. Many cases of patients with both conditions have been reported, and BA and OSAS may exacerbate each other, but information remains sparse.Methods:We retrospectively evaluated 60 patients under treatment for BA in our department between April 2016 and March 2018 who also underwent portable polysomnography (PSG) for suspected OSAS to assess potential association between PSG results and asthma treatment or respiratory function. BA was diagnosed and treated according to the Asthma Prevention and Management Guideline 2015.Results: We found that BA treatment intensity step was significantly higher for patients with BA who had concurrent moderate or severe OSAS (p = 0.0016). However, neither respiratory function, fraction of exhaled nitric oxide (FeNO), nor forced oscillation technique (FOT) differed significantly between patients with and without OSAS, and apnea hypopnea index was not significantly correlated with respiratory function, FeNO or FOT parameters.Conclusion:We conclude that even though BA patients with OSAS had good respiratory function, their BA was more severe than that of patients without OSAS, suggesting that OSAS may exacerbate BA. Background factors and asthma parameters were not predictive of PSG results, and patients with suspected OSAS should be evaluated proactively by using PSG.

A prospective observational study to assess PD-L1 expression in small biopsy samples for non-small-cell lung cancer.

BACKGROUND: Programmed cell death-1 (PD-1) immune checkpoint inhibitor antibody has proven to be effective in advanced non-small cell lung cancer (NSCLC) patients positive for programmed cell death-1 ligand-1 (PD-L1). However, there are currently no prospective studies evaluating PD-L1 expression for small biopsy samples. METHODS: To prospectively investigate the reliability of small samples for NSCLC, we included patients who underwent diagnostic biopsy by flexible bronchoscopy, computed tomography (CT) and ultra-sonography (US) guided core-needle to determine the PD-L1 expression status. In pathologically confirmed NSCLC, PD-L1 expression was evaluated using companion diagnostic PD-L1 immunohistochemistry. We evaluated: 1) tumor cell count and sample size, 2) tumor proportion score (TPS): <1, 1-49%, 50%≦, and 3) the concordance rate of TPS by biopsy and surgical samples. RESULTS: Of the 153 cases of PD-L1 expression, 110 were assessed using endobronchial ultrasonography guided transbronchial biopsy (EBUS-TBB) (thin bronchoscopy 84 cases; normal bronchoscopy 26 cases), 23 were endobronchial ultrasonography guided transbronchial needle aspiration (EBUS-TBNA), and 20 cases of CT or US-guided core-needle biopsy. Tumor cell count and sample size were significantly larger for normal bronchoscopy than thin bronchoscopy or EBUS-TBNA samples. Moreover, tumor cell counts for each subsequent biopsy decreased. In all cases, TPS distribution (undiagnosed, <1%, 1-49, 50%≦) was 2.6, 34.6, 31.4, 31.4%, respectively. TPS positive cases using thin bronchoscope was 55.9%, normal bronchoscope was 73.1% and EBUS-TBNA was 78.3%. In early stage adenocarcinoma, TPS was lower compared with advanced stages. Conversely, in squamous cell carcinoma, the rates of TPS were similar regardless of stage. The concordance rate of TPS by biopsy and surgical materials was 86.7%. CONCLUSION: Utilizing smaller samples for evaluation, the frequency of TPS was comparable to past clinical trials using larger samples. The differences in TPS were influenced by diagnostic tools, cancer histologic types and staging. The concordance of TPS between EBUS-TBB samples and surgical materials was high. TRIAL REGISTRATION: This study was performed at the Department of Respiratory Medicine at St. Marianna University School of Medicine Hospital, with ethics approval (#3590) and registered as a clinical trial ( UMIN000027030 ).

Radiofrequency spectral analysis of EBUS for peripheral pulmonary lesions.

BACKGROUND AND OBJECTIVE: We previously reported that histogram-based quantitative evaluation for endobronchial ultrasonography (EBUS) B-mode images could differentiate between benign and malignant lesions. However, these images were generated from reconstructed raw radiofrequency (RF) signals and had some limitations. Currently, there are no reports on raw RF signal data to quantitatively differentiate ultrasound information for peripheral pulmonary lesions. METHODS: We prospectively hypothesized that RF spectral analysis from EBUS images could reveal sonographic features of peripheral pulmonary diseases. RF data were imported into a frequency spectral analysis software programme, comparing four parameters: mean frequency (MHz); slope; mid-band fit (dB); and y-intercept (dB), to differentiate between benign and malignant lesions. Furthermore, we compared subgroup analysis within benign and malignant lesions. RESULTS: RF data from EBUS images were obtained in 146 cases, of which, 106 lung cancers and 40 inflammatory diseases were present. Significant differences were observed for three parameters in benign and malignant lesions (mean frequency: P < 0.05, slope: P < 0.05, y-intercept: P < 0.01) with diagnostic accuracy of 61%, 57.5%, 63%, respectively. In subgroup analysis, the acute pneumonia group showed higher mean frequency, higher slope and lower y-intercept patterns compared to mycobacterial and fibrotic diseases (P < 0.05). In malignant lesions, small cell carcinoma showed higher mean frequency, higher slope and lower y-intercept pattern compared to other histopathological lung cancers (P < 0.01). CONCLUSION: RF analysis might be capable of demonstrating aspects of the lesion's pathological heterogeneity rather than precisely differentiating between benign and malignant lesions.

Pulmonary Perfusion Using Intrabronchial Capnography in Pulmonary Artery Stenosis.

Stenting at the flow-limiting segment can improve the ventilation-perfusion ratio in patients with central airway stenosis. However, there is no quantitative examination for assessing the perfusion status during interventional bronchoscopy. Intrabronchial capnography can estimate regional gas exchange by measuring carbon dioxide concentration. We herein report a case of bilateral bronchial stenosis where stenting was able to improve ventilation-perfusion ratio using intrabronchial capnography. A 44-year-old man was admitted to our institution with orthopnea. Chest computed tomography showed an extrinsic compression at the bilateral main bronchus and right pulmonary artery due to a mediastinal mass. After introduction of general anesthesia, arterial oxygen tension suddenly decreased in the supine position. After initial stenting, an increase was seen in ventilation at the right lung; however, a ventilation-perfusion mismatch occurred due to an increase in dead-space ventilation at the right pulmonary artery stenosis. Intrabronchial capnography was an effective modality to confirm the regional perfusion status during interventional bronchoscopy in real time.

Assessment of Bronchial Obstruction Using Lateral Pressure Measurement during Bronchoscopy.

BACKGROUND: In patients with bronchial obstruction estimating the location of the maximal obstruction is crucial for guiding interventional bronchoscopy. However, flow-volume curves cannot discriminate between the right and left lungs. OBJECTIVES: The aim of this study was to physiologically evaluate bronchial obstruction during interventional bronchoscopy. METHODS: We prospectively measured lateral airway pressure (Plat) at either side of the obstruction using a double-lumen catheter (pressure-pressure [P-P] curve) simultaneously to assess the degree of bronchial obstruction in 22 patients. The shape of the P-P curve was assessed to confirm the site of maximal obstruction. RESULTS: In the experimental study, Plat was uniform between both bronchi in the normal model. For the unilateral and bilateral obstruction models, a phase shift was only seen for the more obstructed side. In healthy subjects, the angle of the P-P curve was close to 45° and linear in shape. In patients with bronchial obstruction, the angle was much smaller but approached 45° after the bronchoscopic procedure. The degree of bronchial obstruction was significantly correlated with the angle of the P-P curve (r = -0.51, p < 0.01). Dyspnea significantly increased when the airway lumen was obstructed by more than 60% (p < 0.0001), and when the P-P curve appeared loop-shaped (p < 0.01). CONCLUSIONS: The shape of the P-P curve could be used to detect the site of maximal obstruction for the optimal positioning of the stent and assess the need for additional procedures in real time in patients with bronchial obstruction.

Regional Lung Sound Asynchrony in Chronic Obstructive Pulmonary Disease Patients.

BACKGROUND: Regional lung sound distribution in chronic obstructive pulmonary disease (COPD) is reported to be asynchronous. Mathematical analyses using vibration response imaging (VRI), such as left and right lung asynchrony (gap index; GI) and regional lung asynchrony (asynchrony score; AS), are useful measures to evaluate lung sound asynchrony. OBJECTIVES: The aim of this study was to investigate the association of lung sound asynchrony with pulmonary functions and emphysematous lesions in COPD patients. METHODS: VRI recordings and pulmonary function tests were performed in 46 stable male COPD patients and in 40 healthy male smokers. Lung sound asynchrony was evaluated using GI, AS of the left and right lung (AS L-R), and AS of the upper and lower lung (AS U-L). In 38 patients, computed tomography taken within 6 months was available and analyzed. RESULTS: AS L-R and AS U-L were significantly higher in COPD patients than in healthy smokers, with no significant difference in GI. There were no significant correlations with either AS and pulmonary functions, excluding a negative correlation between AS U-L and diffusion capacity. Although there were no significant correlations between both AS and severity of emphysema, significant positive correlations were observed between heterogeneity of emphysematous lesions and AS L-R (ρ = 0.38, p < 0.05) or AS U-L (ρ = 0.51, p < 0.005). CONCLUSIONS: Regional lung sounds are distributed more asynchronously in COPD patients than in healthy smokers, which correlates with the heterogeneous distribution of emphysematous lesions.

[Bronchoscopic treatments for COPD].

Several non-surgical and minimally invasive bronchoscopic interventions, such as bronchoscopic lung volume reduction (BLVR) techniques, have been developed to treat patients with severe chronic obstructive pulmonary disease (COPD). BLVR has been studied for treatment in severe COPD patients with emphysema. BLVR with one-way endobronchial valves is reported to be effective for patients with a heterogeneous emphysema distribution and without inter-lobar collateral ventilation. For the patients with collateral ventilation, and for the patients with homogeneous emphysema, BLVR with lung volume reduction coil has shown promising results. Targeted lung denervation(TLD) is a novel bronchoscopic intervention based on ablation of parasympathetic nerves surrounding the main bronchi. TLD seems to be effective for COPD with chronic bronchitis phenotype. This review gives a general overview of BLVR with one-way valve and lung volume reduction coil, and TLD.

Histogram-based quantitative evaluation of endobronchial ultrasonography images of peripheral pulmonary lesion.

BACKGROUND: Endobronchial ultrasonography using a guide sheath (EBUS-GS) is an increasingly common bronchoscopic technique, but currently, no methods have been established to quantitatively evaluate EBUS images of peripheral pulmonary lesions. OBJECTIVES: The purpose of this study was to evaluate whether histogram data collected from EBUS-GS images can contribute to the diagnosis of lung cancer. METHODS: Histogram-based analyses focusing on the brightness of EBUS images were retrospectively conducted: 60 patients (38 lung cancer; 22 inflammatory diseases), with clear EBUS images were included. For each patient, a 400-pixel region of interest was selected, typically located at a 3- to 5-mm radius from the probe, from recorded EBUS images during bronchoscopy. Histogram height, width, height/width ratio, standard deviation, kurtosis and skewness were investigated as diagnostic indicators. RESULTS: Median histogram height, width, height/width ratio and standard deviation were significantly different between lung cancer and benign lesions (all p < 0.01). With a cutoff value for standard deviation of 10.5, lung cancer could be diagnosed with an accuracy of 81.7%. Other characteristics investigated were inferior when compared to histogram standard deviation. CONCLUSIONS: Histogram standard deviation appears to be the most useful characteristic for diagnosing lung cancer using EBUS images.

A Quantitative Computed Tomography Analysis of Fissure Integrity and Emphysema Destruction in Japanese Patients with Severe Chronic Obstructive Pulmonary Disease.

Objective Bronchoscopic lung volume reduction (BLVR) using a one-way endobronchial valve (EBV) can provide clinically meaningful benefits to chronic obstructive pulmonary disease (COPD) patients. Although the Japanese Pharmaceuticals and Medical Devices Agency approved EBVs in November 2022, information regarding the number of Japanese patients with severe COPD eligible for BLVR treatment is still lacking. We therefore screened computed tomography (CT) images of patients with severe COPD using a quantitative CT (QCT) analysis to estimate the proportion of candidates eligible for BLVR treatment with an EBV. Methods CT scans of COPD patients with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages 3 and 4 were retrospectively analyzed using QCT to evaluate fissure integrity and tissue destruction. The difference in volume-weighted percentage was measured using the density scores of the target lobe and ipsilateral non-target lobe at -910 Hounsfield units. The target lobe was defined as the most affected lobe, with an emphysema destruction score of >50% for each patient. Results High-resolution CT scans of 32 patients (GOLD 3=19, GOLD 4=13) were analyzed. The target lobe could not be identified in 1 patient, whereas the target lobes for 8 patients were not surrounded by fissures with ≥80% completeness. Conversely, in 13 patients, the target lobes were surrounded by fissures with >95% completeness. The remaining 10 patients had fissure completeness between 80% and 95% at the target lobes and were considered candidates for collateral ventilation assessment. Conclusion A QCT analysis showed that 23 of 32 patients with severe COPD could be considered for a thorough examination of BLVR treatment with EBV.

Efficacy of combined transbronchial lung cryobiopsy and conventional forceps biopsy for lung malignancies: a prospective cohort study.

There are few prospective reports of transbronchial lung cryobiopsy (TBLC) for malignant tumors in combination with forceps biopsy. We investigated the clinical parameters in which TBLC is superior to forceps biopsy. This is a prospective cohort study to analyse the efficacy of TBLC for suspected malignancy. TBLC was performed after brushing cytology and forceps biopsy, and the diagnostic yield for TBLC, brushing cytology, and forceps biopsy were examined. Adverse events were defined as those requiring additional procedures. Next-generation sequencing (NGS) analysis was performed in each case of non-small cell lung cancer. Of the 100 patients, malignancy was confirmed in 94 cases. The diagnostic yield for TBLC/forceps biopsy/brushing cytology was 86/81/82% respectively, while the diagnostic yield for all procedures combined was 94%. There was no significant difference in the diagnostic yield between TBLC and forceps biopsy. When comparing the biopsy site, the diagnostic yield for TBLC at the lower lobe was significantly higher than forceps biopsy (P < 0.01). Endobronchial ultrasonography imaging using a guide-sheath did not significantly differ in the diagnostic yield of TBLC. The success rate of NGS for TBLC specimens was 100% (26 cases). Adverse events included two cases of severe bleeding. TBLC of peripheral lesions may improve the diagnostic yield when combined with forceps biopsy and brushing cytology. The diagnostic yield of TBLC was higher at the lower lobes. Furthermore, TBLC provided sufficient specimen quality for NGS.

EML4-ALK Gene Mutation Detected with New NGS Lung Cancer Panel CDx Using Sputum Cytology in a Case of Advanced NSCLC.

The detection of driver gene mutations has become essential for lung cancer; however, insufficient sample sizes make gene panel tests difficult to use. We previously reported that the lung cancer compact panel TM (LCCP) could detect EGFR and MET gene mutations with sputum cytology. To date, the detection of gene mutation using RNA from sputum samples is considered practically difficult. We report a case in which the EML4-ALK fusion gene was successfully detected from a sputum sample using the LCCP that was just released in Japan as a new next-generation sequencing lung cancer panel, CDx.