橋本 直純

BACKGROUND: We compared the capabilities of quantitatively assessed paired inspiratory-expiratory area-detector computed tomography (ADCT) for pulmonary functional loss and disease severity evaluations between upright and supine ADCT in matched progressive pulmonary fibrosis (PPF) patients. MATERIALS AND METHODS: This retrospective cohort consisted of age-, sex-, and underlying disease-matched patients with PPF who underwent paired inspiratory-expiratory CT on upright ADCT (n = 40) and supine ADCT (n = 40), pulmonary function tests, and disease severity assessment. Based on CT data, the absolute values of the logarithm of the Jacobian determinant and warp-field magnitude of the whole lung and all lobes were calculated. Stepwise regression analyses were performed. RESULTS: On supine ADCT, both indices of the left lower lobe (LLL) were the first and only steps for pulmonary function test results and CT-assessed disease severity (absolute value of the logarithm of the Jacobian determinant: 0.139 ≤ r2 ≤ 0.175, 0.007 ≤ p ≤ 0.018; absolute value of the warp-field magnitude: 0.371 ≤ r2 ≤ 0.447, p < 0.001). However, on upright ADCT, both indices indicated that LLL was the first step and the right lower lobe was the second step for pulmonary function test results and CT-assessed disease severity (0.503 ≤ r2 ≤ 0.674, p < 0.001 or 0.000 < p ≤ 0.006 and 0.474 ≤ r2 ≤ 0.652, 0.002 ≤ p ≤ 0.045, respectively). CONCLUSION: Upright ADCT has equal to or better potential than supine ADCT for detecting pulmonary functional loss and evaluating disease severity when paired inspiratory-expiratory ADCT is applied in PPF patients. RELEVANCE STATEMENT: Upright ADCT has superior potential to supine ADCT for pulmonary functional loss and disease severity evaluations when paired inspiratory-expiratory ADCT is performed in patients with progressive pulmonary fibrosis (PPF). KEY POINTS: Matched progressive pulmonary fibrosis patients compared functional loss and disease severity evaluations between inspiratory-expiratory upright and supine area-detector CT. Clinical parameters demonstrated better correlations with upright than with supine inspiratory-expiratory area-detector CT. Warp-field magnitude showed better correlations with disease severities than the logarithm of the Jacobian determinant on each area-detector CT.

Introduction: Accurate diagnosis of peripheral pulmonary lesions is crucial in respiratory medicine. Radial endobronchial ultrasound (R-EBUS), navigation technologies, and ultrathin bronchoscopes have progressively enhanced distal airway access. Mixed reality (MR) offers a hands-free method for visualizing and manipulating CT-derived three-dimensional (3D) anatomy within the operator’s field of view. This retrospective study aimed to describe the technical feasibility and safety of intraprocedural MR-based holographic virtual bronchoscopy (VB) use. Methods: This study included patients who underwent bronchoscopy for peripheral pulmonary lesions using an MR-based 3D holographic VB system. CT datasets were converted into 3D polygon models and displayed on a HoloLens 2 headset. Operators/assistants intraprocedurally referenced and manipulated the hologram while advancing the bronchoscope. Procedural variables, R-EBUS findings, biopsy techniques, diagnostic yield, and complications were evaluated. Results: Eighteen patients were included. A direct bronchus sign was present in 12 lesions. The median bronchial generation that could be visualized on CT and 3D-VB was six, whereas bronchoscopy enabled advancement to a median of five generations. Radial EBUS demonstrated a within-lesion position in 13 cases. Biopsy techniques included forceps biopsy, cryobiopsy, and TBNA. The overall diagnostic yield was 72.2% (13/18), with malignant disease accounting for the majority of diagnoses. One patient developed mild pneumothorax, which resolved without drainage. Conclusion: MR-based holographic VB enabled real-time, hands-free 3D anatomical referencing without interrupting the procedure. Further prospective studies are warranted to assess procedural benefits and potential integration with other bronchoscopic modalities and devices.

BACKGROUND: Cisplatin-induced nephrotoxicity (CIN) is a major dose-limiting adverse event that can lead to both acute and chronic kidney injury. The formation of thiol-cisplatin conjugates within renal tubular cells has been implicated as a key mechanism underlying CIN. Flopropione is an inhibitor of cysteine conjugate β-lyase 1, an enzyme that catalyzes the formation of the thiol-cisplatin conjugate, which might prevent CIN. OBJECTIVE: We designed a clinical trial to evaluate the safety of flopropione in patients receiving cisplatin-based chemotherapy and explore its efficacy in preventing CIN. METHODS: This is a phase 1 and 2a, single-center, randomized, open-label trial conducted in patients undergoing cisplatin therapy. Participants are randomized in a 5:2 ratio per cohort to receive either flopropione or no treatment. On the day of cisplatin administration, the flopropione group receives oral flopropione twice daily (80 mg in cohort 1, 160 mg in cohort 2, and 240 mg in cohort 3). On the following day, all cohorts receive 3 doses of 80 mg of oral flopropione. A step-up dose escalation design is adopted, progressing from cohort 1 to 3 after confirming safety at each level. The primary end point is the safety of flopropione use in combination with cisplatin; the secondary end points include changes in the levels of urinary biomarkers of nephrotoxicity such as neutrophil gelatinase-associated lipocalin, liver-type fatty acid-binding protein, and kidney injury molecule-1. Blood and urine samples are collected within 48 hours before cisplatin administration and at 24 hours, 48 hours, and 1 week after its initiation for safety and efficacy assessments. RESULTS: The first participant was registered in July 2024. As of January 2026, participant registration is ongoing. The final participant will complete the study by March 2026. Publication of results is expected by March 2027. CONCLUSIONS: This study is expected to contribute to advances in preventive strategies for CIN by providing evidence that inhibition of cysteine conjugate β-lyase 1 by flopropione may attenuate CIN. TRIAL REGISTRATION: Japan Registry of Clinical Trials jRCTs041220021; https://jrct.mhlw.go.jp/en-latest-detail/jRCTs041220021. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/87907.

OBJECTIVES: Sivelestat sodium hydrate (SSH) may be effective in the early stage of acute respiratory distress syndrome (ARDS) before the neutrophil extracellular trap scaffold structure is complete. Therefore, patients with suppression of fibrinolysis (SF) before the secondary fibrinolytic process might benefit from SSH administration. The primary aim of this study was to determine the effect of the SF state and combination therapy on the effect of SSH administration. METHODS: We retrospectively reviewed the data of patients diagnosed with ARDS at Fujita Health University Hospital between July 2005 and December 2016. Patients with ARDS were stratified into the SF and hyperfibrinolysis (HF) groups. Using the fibrin degradation product (FDP)/D-dimer ratio, cut-off values were set as follows: FDP/D-dimer >2 for the HF group and FDP/D-dimer ≤2 for the SF group. The 28-day mortality was the primary endpoint. RESULTS: In total, 168 patients (71 in the HF group and 97 in the SF group) were included in the analysis. The mortality within 28 days was not different based on SSH administration in either group (HF group: p=0.956, SF group: p=0.957). In the SF group, the mortality rate within 28 days in SSH-treated patients who received antithrombotic drugs was significantly higher than that in patients who received SSH only (p<0.05). However, this finding was not present in the HF group (p=0.786). CONCLUSIONS: Concomitant use of SSH and antithrombotic drugs might worsen the treatment outcome of patients with ADRS in the SF state.

Bronchoscopic lung volume reduction (BLVR) with endobronchial valves is an established treatment for selected patients with advanced emphysema. A 74-year-old male patient with chronic obstructive pulmonary disease and severe dyspnea was scheduled to undergo BLVR targeting the right middle lobe bronchus based on high-resolution CT findings, which showed severe emphysematous changes with hyperinflation and fissure completeness of 98% in the right middle lobe. The physician conducted preoperative virtual reality (VR)-assisted planning using the patient's imaging data, enabling comprehensive visualisation of the bronchial tree, airway measurements, and procedural simulation. The Chartis system confirmed a 'no flow' pattern, supporting the absence of collateral ventilation. During the procedure, a size 5.5 valve was placed in the right B4/5 bronchus following VR and intraoperative assessments. The patient remained stable postoperatively without complications. VR enhanced procedural planning by improving airway assessment, optimising valve sizing, and reducing cognitive load, leading to increased efficiency and operator confidence. Further research is warranted to validate the utility of VR in bronchoscopic interventions.

The benefit of programmed cell death protein-1 (PD-1)/programmed cell death protein ligand-1 (PD-L1) inhibitors remains unclear in non-small cell lung cancer (NSCLC) patients with poor performance status (PS). In the current multi-centre retrospective cohort study, advanced or recurrent NSCLC patients treated with PD-1/PD-L1 inhibitors were enrolled. Of the 219 patients enrolled, 44 had PS 2-4. The objective response rate (ORR) of patients with PS 2-4 in 1st line was 33%. Among 1st line group, median progression-free survival (PFS) in patients with PS 2 was significantly longer compared to that in patients with PS 3-4 (15.3 months vs. 0.9 months, P = 0.039, Log-rank test). Among previously treated patients, the ORR of patients with PS 2-4 was only 4%, and PFS and overall survival was poor even in patients with PS 2. PD-1/PD-L1 inhibitors can be an option for PS 2 NSCLC patients in 1st line setting.

OBJECTIVE: Peripheral helper T (Tph) cells, together with plasma cells, are the major pathogenic lymphocytes in the synovium in rheumatoid arthritis (RA). However, whether these cells are involved in RA-associated lung and/or airway disease is unknown. METHODS: Tph cells in sputum were analyzed by flow cytometry and compared with those in synovial fluid and synovial tissue. Forty RA subjects for whom induced sputum could be collected were analyzed along with sputum Tph cells and several clinical parameters; RA severity was assessed using the Disease Activity Score for 28 joints (DAS28). Lung and airway disease was assessed by chest computed tomography (CT), pulmonary function test, the chronic obstructive pulmonary disease (COPD) Assessment Test (CAT), and sputum culture. Tph cells in the lung of RA subjects were analyzed using lung resection samples in a separate cohort. RESULTS: Tph cells were observed in the sputum, as well as the lung, synovial fluid, and synovial tissue of RA patients. Sputum Tph cells were increased in patients with airway disease. Among these patients, Tph cells were more frequent in those with high DAS28, high serum immunoglobulin G (IgG), and high sputum IgG. However, there was no association between Tph cells and the severity of airway disease as assessed by chest CT findings, lung function, CAT, and sputum culture. CONCLUSIONS: Tph cells were increased in the airways as well as in the synovium in patients with RA. Airway Tph cells were associated with severity of RA but not with the severity of airway disease. Airway Tph cells may represent a novel target for disease management and treatment.

Epithelioid hemangioendothelioma (EHE) with pleural involvement presents significant diagnostic challenges, particularly in terms of differentiating it from malignant pleural effusion caused by other types of cancer, such as lung carcinoma. While most cases of EHE follow an indolent course, some can deteriorate rapidly, particularly those with serosal involvement such as pleural metastasis. In this report, we describe a case in which semi-rigid thoracoscopic cryobiopsy under local anesthesia yielded adequate specimens safely for diagnosis of pleural dissemination of EHE. The patient was a 46-year-old woman who had been diagnosed with multifocal EHE affecting the liver and both lungs a decade earlier. After radiofrequency ablation for the hepatic lesions and 2 years of chemotherapy, she was monitored without specific treatment for approximately 8 years with no significant tumor progression. She presented to our department following a rapid increase in left-sided pleural effusion over the previous month. Based on the clinical course and imaging findings, the diagnosis was initially difficult. However, thoracoscopic cryobiopsy provided definitive confirmation of pleural EHE.

BACKGROUND: The increasing prevalence of lung cancer in the elderly population necessitates a closer evaluation of diagnostic and therapeutic approaches. This study aimed to compare the safety and diagnostic efficacy of transbronchial lung cryobiopsy (TBLC) between patients ≥ 80 years and younger patients. METHODS: A retrospective review was conducted of 96 patients diagnosed with peripheral lung cancer who underwent TBLC between April 2021 and October 2023. The patients were categorized into two groups: the elderly group (age ≥ 80 years, n = 20) and younger group (age < 80 years; n = 76). Data regarding the biopsy yield, complications, and feasibility of molecular analyses were collected and analyzed. RESULTS: The diagnostic yield of TBLC was comparable between the elderly and younger groups (95% vs. 89.5%, p = 0.679). Biomarker testing, including programmed death-ligand 1 expression and genetic mutations, were feasible in all cases diagnosed with cancer using TBLC samples. No significant differences were observed in major complications such as pneumothorax or bleeding. CONCLUSIONS: TBLC was found to be a safe and effective diagnostic tool for peripheral lung cancer in elderly patients and provided adequate samples for molecular testing. Since the complication rates did not significantly differ between the two age groups, age alone should not be considered a contraindication for the procedure.