A deep learning-based model to estimate pulmonary function from chest x-rays: multi-institutional model development and validation study in Japan.

BACKGROUND: Chest x-ray is a basic, cost-effective, and widely available imaging method that is used for static assessments of organic diseases and anatomical abnormalities, but its ability to estimate dynamic measurements such as pulmonary function is unknown. We aimed to estimate two major pulmonary functions from chest x-rays. METHODS: In this retrospective model development and validation study, we trained, validated, and externally tested a deep learning-based artificial intelligence (AI) model to estimate forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) from chest x-rays. We included consecutively collected results of spirometry and any associated chest x-rays that had been obtained between July 1, 2003, and Dec 31, 2021, from five institutions in Japan (labelled institutions A-E). Eligible x-rays had been acquired within 14 days of spirometry and were labelled with the FVC and FEV1. X-rays from three institutions (A-C) were used for training, validation, and internal testing, with the testing dataset being independent of the training and validation datasets, and then x-rays from the two other institutions (D and E) were used for independent external testing. Performance for estimating FVC and FEV1 was evaluated by calculating the Pearson's correlation coefficient (r), intraclass correlation coefficient (ICC), mean square error (MSE), root mean square error (RMSE), and mean absolute error (MAE) compared with the results of spirometry. FINDINGS: We included 141 734 x-ray and spirometry pairs from 81 902 patients from the five institutions. The training, validation, and internal test datasets included 134 307 x-rays from 75 768 patients (37 718 [50%] female, 38 050 [50%] male; mean age 56 years [SD 18]), and the external test datasets included 2137 x-rays from 1861 patients (742 [40%] female, 1119 [60%] male; mean age 65 years [SD 17]) from institution D and 5290 x-rays from 4273 patients (1972 [46%] female, 2301 [54%] male; mean age 63 years [SD 17]) from institution E. External testing for FVC yielded r values of 0·91 (99% CI 0·90-0·92) for institution D and 0·90 (0·89-0·91) for institution E, ICC of 0·91 (99% CI 0·90-0·92) and 0·89 (0·88-0·90), MSE of 0·17 L2 (99% CI 0·15-0·19) and 0·17 L2 (0·16-0·19), RMSE of 0·41 L (99% CI 0·39-0·43) and 0·41 L (0·39-0·43), and MAE of 0·31 L (99% CI 0·29-0·32) and 0·31 L (0·30-0·32). External testing for FEV1 yielded r values of 0·91 (99% CI 0·90-0·92) for institution D and 0·91 (0·90-0·91) for institution E, ICC of 0·90 (99% CI 0·89-0·91) and 0·90 (0·90-0·91), MSE of 0·13 L2 (99% CI 0·12-0·15) and 0·11 L2 (0·10-0·12), RMSE of 0·37 L (99% CI 0·35-0·38) and 0·33 L (0·32-0·35), and MAE of 0·28 L (99% CI 0·27-0·29) and 0·25 L (0·25-0·26). INTERPRETATION: This deep learning model allowed estimation of FVC and FEV1 from chest x-rays, showing high agreement with spirometry. The model offers an alternative to spirometry for assessing pulmonary function, which is especially useful for patients who are unable to undergo spirometry, and might enhance the customisation of CT imaging protocols based on insights gained from chest x-rays, improving the diagnosis and management of lung diseases. Future studies should investigate the performance of this AI model in combination with clinical information to enable more appropriate and targeted use. FUNDING: None.

Combination of transbronchoscopic oxygen insufflation and a digital chest drainage system in endobronchial occlusion: a hybrid technique for localization of fistula in intractable pneumothorax.

BACKGROUND: The management of intractable secondary pneumothorax poses a considerable challenge as it is often not indicated for surgery owing to the presence of underlying disease and poor general condition. While endobronchial occlusion has been employed as a non-surgical treatment for intractable secondary pneumothorax, its effectiveness is limited by the difficulty of locating the bronchus leading to the fistula using conventional techniques. This report details a case treated with endobronchial occlusion where the combined use of transbronchoscopic oxygen insufflation and a digital chest drainage system enabled location of the bronchus responsible for a prolonged air leak, leading to the successful treatment of intractable secondary pneumothorax. CASE PRESENTATION: An 83-year-old male, previously diagnosed with chronic hypersensitivity pneumonitis and treated with long-term oxygen therapy and oral corticosteroid, was admitted due to a pneumothorax emergency. Owing to a prolonged air leak after thoracic drainage, the patient was deemed at risk of developing an intractable secondary pneumothorax. Due to his poor respiratory condition, endobronchial occlusion with silicone spigots was performed instead of surgery. The location of the bronchus leading to the fistula was unclear on CT imaging. When the bronchoscope was wedged into each subsegmental bronchus and low-flow oxygen was insufflated, a digital chest drainage system detected a significant increase of the air leak only in B5a and B5b, thus identifying the specific location of the bronchus leading to the fistula. With the occlusion of those bronchi using silicone spigots, the air leakage decreased from 200 mL/min to 20 mL/min, and the addition of an autologous blood patch enabled successful removal of the drainage tube. CONCLUSION: The combination of transbronchoscopic oxygen insufflation with a digital chest drainage system can enhance the therapeutic efficacy of endobronchial occlusion by addressing the problems encountered in conventional techniques, where the ability to identify the leaking bronchus is dependent on factors such as the amount of escaping air and the location of the fistula.

Comparison of the specimen quality of endobronchial ultrasound-guided intranodal forceps biopsy using standard-sized forceps versus mini forceps for lung cancer: A prospective study.

BACKGROUND AND OBJECTIVE: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a diagnostic procedure with adequate performance; however, its ability to provide specimens of sufficient quality and quantity for treatment decision-making in advanced-stage lung cancer may be limited, primarily due to blood contamination. The use of a 0.96-mm miniforceps biopsy (MFB) permits true histological sampling, but the resulting small specimens are unsuitable for the intended applications. Therefore, we introduced a 1.9-mm standard-sized forceps biopsy (SFB) and compared its utility to that of MFB. METHODS: We prospectively enrolled patients from three institutions who presented with hilar/mediastinal lymphadenopathy and suspected advanced-stage lung cancer, or those who were already diagnosed but required additional tissue specimens for biomarker analysis. Each patient underwent MFB followed by SFB three or four times through the tract created by TBNA using a 22-gauge needle on the same lymph node (LN). Two pathologists assessed the quality and size of each specimen using a virtual slide system, and diagnostic performance was compared between the MFB and SFB groups. RESULTS: Among the 60 enrolled patients, 70.0% were diagnosed with adenocarcinoma. The most frequently targeted sites were the lower paratracheal LNs, followed by the interlobar LNs. The diagnostic yields of TBNA, MFB and SFB were 91.7%, 93.3% and 96.7%, respectively. The sampling rate of high-quality specimens was significantly higher in the SFB group. Moreover, the mean specimen size for SFB was three times larger than for MFB. CONCLUSION: SFB is useful for obtaining sufficient qualitative and quantitative specimens.

A Case of Successful Removal of a Foreign Body Located in the Peripheral Airway Using Flexible Bronchoscopy with Virtual Bronchoscopy Navigation.

A case in which a foreign body located in the peripheral airway of the lung was removed by flexible bronchoscopy using a virtual bronchoscopy navigation (VBN) system has been reported. The patient was a 60-year-old man. Chest radiography revealed an incidental foreign body in the left lower lung. Chest computed tomography with 1.0-mm slices was used to create a VBN system and confirm the foreign body in left B9biiαy, which was removed by flexible bronchoscopy. Thus, peripheral foreign bodies can be safely removed using flexible bronchoscopy by creating a VBN system in advance.

Clinical significance of KL-6 in immune-checkpoint inhibitor treatment for non-small cell lung cancer.

PURPOSE: Krebs von den Lungen-6 (KL-6) functions as a tumor marker, as well as a diagnostic tool for interstitial pneumonia (IP). However, the significance of KL-6 in the immune-checkpoint inhibitor (ICI) treatment of non-small cell lung cancer (NSCLC), especially in patients without IP, is unknown. METHODS: This multicenter, retrospective study, which included patients with advanced NSCLC who received ICI therapy, analyzed the association between serum KL-6 values and ICI efficacy and the association between serum KL-6 values and ICI-induced interstitial lung disease (ILD) occurrence, focusing primarily on patients without IP. RESULTS: In total, 322 patients had available KL-6 values before ICI therapy. Among 202 patients without IP who received ICI monotherapy, the high-KL-6 group (≥ 500 U/mL) showed significantly shorter progression-free survival (PFS) and overall survival (OS) than the low-KL-6 group (< 500 U/mL) (median: 2.1 vs. 3.6 months, p = 0.048; median: 9.2 vs. 14.5 months, p = 0.035). There was no significant difference in response rate between the KL-6 high and low groups (19% vs. 29%, p = 0.14). In the multivariate analysis, high KL-6 was a significant predictor of poor PFS (hazard ratio [HR], 1.52; 95% confidence interval [CI] 1.10-2.11, p = 0.012) and OS (HR, 1.51; 95% CI 1.07 - 2.13, p = 0.019) for patients treated with ICI monotherapy. There was no significant difference in the occurrence rate of ILD between the high KL-6 and low KL-6 groups in patients with (20% vs. 15%, p = 1.00) or without IP (12% vs. 12%, p = 1.00). CONCLUSION: In ICI monotherapy for NSCLC without IP, elevated serum KL-6 levels were associated with poorer outcomes.

Implementing an Evidence-Based COPD Hospital Discharge Protocol: A Narrative Review and Expert Recommendations.

Discharge bundles, comprising evidence-based practices to be implemented prior to discharge, aim to optimise patient outcomes. They have been recommended to address high readmission rates in patients who have been hospitalised for an exacerbation of chronic obstructive pulmonary disease (COPD). Hospital readmission is associated with increased morbidity and healthcare resource utilisation, contributing substantially to the economic burden of COPD. Previous studies suggest that COPD discharge bundles may result in fewer hospital readmissions, lower risk of mortality and improvement of patient quality of life. However, evidence for their effectiveness is inconsistent, likely owing to variable content and implementation of these bundles. To ensure consistent provision of high-quality care for patients hospitalised with an exacerbation of COPD and reduce readmission rates following discharge, we propose a comprehensive discharge protocol, and provide evidence highlighting the importance of each element of the protocol. We then review care bundles used in COPD and other disease areas to understand how they affect patient outcomes, the barriers to implementing these bundles and what strategies have been used in other disease areas to overcome these barriers. We identified four evidence-based care bundle items for review prior to a patient's discharge from hospital, including (1) smoking cessation and assessment of environmental exposures, (2) treatment optimisation, (3) pulmonary rehabilitation, and (4) continuity of care. Resource constraints, lack of staff engagement and knowledge, and complexity of the COPD population were some of the key barriers inhibiting effective bundle implementation. These barriers can be addressed by applying learnings on successful bundle implementation from other disease areas, such as healthcare practitioner education and audit and feedback. By utilising the relevant implementation strategies, discharge bundles can be more (cost-)effectively delivered to improve patient outcomes, reduce readmission rates and ensure continuity of care for patients who have been discharged from hospital following a COPD exacerbation.

Diagnostic Utility and Safety of Non-Intubated Cryobiopsy Technique Using a Novel Ultrathin Cryoprobe in Addition to Conventional Biopsy Techniques for Peripheral Pulmonary Lesions.

BACKGROUND: Transbronchial cryobiopsy enables high-quality sample collection around the probe tip. Meanwhile, existing cryoprobes have less flexibility and a higher risk of bleeding. The ultrathin cryoprobe with a 1.1-mm diameter addresses these problems and allows specimens to be directly retrieved through the working channel of a thin bronchoscope. OBJECTIVE: This study evaluated the diagnostic utility and safety of non-intubated cryobiopsy using an ultrathin cryoprobe added to conventional biopsy for diagnosing peripheral pulmonary lesions (PPLs). METHODS: The data of patients who underwent conventional biopsy followed by non-intubated cryobiopsy to retrieve specimens through the thin bronchoscope's working channel for diagnosing PPLs at Osaka Metropolitan University Hospital from July 2021 to June 2022 were retrospectively collected. They were analyzed to evaluate the diagnostic utility and safety of adding non-intubated cryobiopsy to conventional biopsy for PPLs. The characteristics of PPLs that obtain additional diagnostic benefits from cryobiopsy over conventional biopsy were also investigated. RESULTS: The analysis included 113 patients. The diagnostic yields of conventional biopsy and non-intubated cryobiopsy were 70.8% and 82.3%, respectively (p = 0.009). The total diagnostic yield was 85.8%, higher than conventional biopsy alone (p < 0.001). Although one moderate bleeding occurred, no severe complications developed. The additional diagnostic benefits of non-intubated cryobiopsy over conventional biopsy were demonstrated when the radial endobronchial ultrasound (R-EBUS) showed "adjacent to" (60.3% vs. 82.8%, p = 0.017). CONCLUSIONS: Non-intubated cryobiopsy using an ultrathin cryoprobe has high diagnostic utility and safety for diagnosing PPLs, with additional diagnostic benefits over conventional biopsy depending on the R-EBUS image.

Characterization of Severe Uncontrolled Asthma in Japan: Analysis of Baseline Data from the PROSPECT Study.

Purpose: Treatment patterns and patient characteristics are not well elucidated among Japanese patients with severe uncontrolled asthma who currently have various treatment options, including biologics. We analyzed baseline characteristics of patients who did/did not initiate biologic treatment in PROSPECT, a 24-month observational study. Patients and Methods: Patients with severe uncontrolled asthma were prospectively enrolled at 34 sites in Japan from December 2019 to September 2021. The enrolled population was divided based on initiation/non-initiation of biologic treatment within 12 weeks after enrollment. Patient demographics, clinical characteristics, biomarker levels, and asthma-related treatment were assessed at enrollment. Results: Of 289 patients meeting the enrollment criteria, 127 patients initiated biologic treatment (BIO group: omalizumab, n = 16; mepolizumab, n = 10; benralizumab, n = 41; and dupilumab, n = 60) and 162 patients did not (non-BIO group). The proportion of patients with ≥2 asthma exacerbations was higher in the BIO group than the non-BIO group (65.0% vs 47.5%). Patients receiving omalizumab had the highest frequency of allergic rhinitis (87.5% vs other BIOs: 40.0%-53.3%). Patients receiving benralizumab and dupilumab had the highest incidence of nasal polyps (benralizumab: 19.5%, dupilumab: 23.3%, other BIOs: 0.0%). The proportion of patients with blood eosinophils ≥300 cells/µL was higher with benralizumab (75.6%) than other BIOs (26.7%-42.9%). Conclusion: This analysis of baseline data from the PROSPECT study is the first to clarify the characteristics of Japanese patients with severe uncontrolled asthma. BIOs were not necessarily prescribed to patients in whom they were indicated; however, for patients who received them, selection appeared to be made appropriately based on asthma phenotypes.

Influence of Smoking History on the Effectiveness of Immune-checkpoint Inhibitor Therapy for Non-small Cell Lung Cancer: Analysis of Real-world Data.

BACKGROUND/AIM: There is no real-world data in an Asian population to investigate the difference between the outcome of immune-checkpoint inhibitor (ICI) monotherapy and combination therapy for non-small cell lung cancer (NSCLC) based on smoking status. In this study, we investigated the correlation between smoking status and the efficacy of ICI therapy for NSCLC patients. PATIENTS AND METHODS: This multicentre retrospective study enrolled patients with recurrent or metastatic NSCLC who were treated using ICI therapy between December 2015 and July 2020. We analysed the objective response rate (ORR) of patients who received ICI monotherapy or combination therapy, based on smoking status using Fisher's exact test, and progression-free survival (PFS) and overall survival (OS) based on smoking status using the Kaplan-Meier method, the log-rank test, and Cox proportional hazards model. RESULTS: A total of 487 patients were included in the study. In the ICI monotherapy group, non-smokers showed significantly lower ORR and shorter PFS and OS than smokers (10% vs. 26%, p=0.002; median: 1.8 vs. 3.8 months, p<0.001; median: 8.0 vs. 15.4 months, p=0.026). In the ICI combination therapy group, non-smokers showed significantly longer OS than smokers (median: not reached vs. 26.3 months, p=0.045), and there was no significant difference in ORR and PFS between non-smokers and smokers (63% vs. 51%, p=0.43; median: 10.2 vs. 9.2 months, p=0.81). In the multivariate analysis of patients who received ICI combination therapy, the "non-smoker" status was not significantly associated with PFS [hazard ratio (HR)=1.31; 95% confidence interval (CI)=0.70-2.45, p=0.40] and OS (HR=0.40; 95% CI=0.14-1.13, p=0.083). CONCLUSION: Non-smokers showed worse outcomes than smokers with ICI monotherapy, but not with ICI combination therapy.

Distinct contributions of muscle mass and strength stratified by nutritional status to physical activity in patients with chronic obstructive pulmonary disease.

BACKGROUND: Physical activity is one of the most important prognostic factors for patients with chronic obstructive pulmonary disease (COPD). Physical activity correlates significantly with skeletal muscle mass and strength. Pulmonary rehabilitation has been conducted to improve physical activity, but its effectiveness has been inconsistent. Nutritional status is also related to physical activity in patients with COPD. The relationships between skeletal muscle mass, strength, and nutritional status evaluated using the Mini Nutritional Assessment Short Form (MNA-SF) were investigated. How nutritional status alters the relationships between physical activity, exercise capacity, skeletal muscle mass, and strength was also investigated. METHODS: This retrospective, cross-sectional study enrolled 81 outpatients with COPD. In all patients, physical activity, exercise capacity, body composition assessment, and MNA-SF were assessed. The relationships between physical activity, exercise capacity, skeletal muscle mass, and strength were examined according to the MNA-SF. RESULTS: The MNA-SF high group had significantly higher skeletal muscle mass than the MNA-SF low group when skeletal muscle strength was the covariate. In the MNA-SF low group, physical activity positively correlated with skeletal muscle mass. In the MNA-SF high group, physical activity positively correlated with skeletal muscle strength. CONCLUSIONS: This study showed that the nutritional status of patients with COPD alters the relationship between physical activity and skeletal muscle mass or strength. Optimizing rehabilitation with nutrition interventions according to nutritional status might improve physical activity in patients with COPD.