記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Long-term maintenance steroid therapy (MST) is often necessary for repeated relapses of chronic eosinophilic pneumonia (CEP). Because relapse does not indicate a worse prognosis, determining the optimal steroid dose to avoid overtreatment presents a clinical challenge. Our primary objective was to evaluate the optimal MST dose to prevent repeated relapses, and the secondary objectives included identifying serum eosinophil count at relapse and background factors of relapse. METHODS: A multicentre retrospective study was conducted on patients with steroid-treated CEP. Background characteristics were compared between the non-relapse and relapse groups. The optimal MST dose was determined based on dose at relapse and the final relapse prevention dose. Additionally, serum eosinophil count at relapse was assessed. RESULTS: A total of 79 patients were included, with 44 in the non-relapse group and 35 in the relapse group. The prednisolone doses required to achieve relapse-free rates of 50% (ED50) were 7.2 mg (95% CI, 4.6 to 23.6). The median serum eosinophil count at relapse was 1125 /µL (IQR, 735-2108). No clinically significant background factors were identified between the non-relapse and relapse groups. CONCLUSION: Our study demonstrated that a prednisolone dose of 7.2 mg achieved a 50% relapse-free rate in the relapse group. Based on these findings, we encourage clinicians to evaluate individual minimum effective steroid doses.

DOI： 10.1136/bmjresp-2024-002697

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Bortezomib (BTZ), a selective 26 S proteasome inhibitor, is clinically useful in treating multiple myeloma and mantle cell lymphoma. BTZ exerts its antitumor effect by suppressing nuclear factor-B in myeloma cells, promoting endothelial cell apoptosis, and inhibiting angiogenesis. Despite its success, pulmonary complications, such as capillary leak syndrome of the vascular hyperpermeability type, were reported prior to its approval. Although the incidence of these complications has decreased with the use of steroids, the underlying mechanism remains unclear. This study aims to investigate how BTZ influences endothelial cell permeability. METHODS: We examined the impact of BTZ on vascular endothelial cells, focusing on its effects on RhoA and RhoC proteins. Stress fiber formation, a known indicator of increased permeability, was assessed through the Rho/ROCK pathway. RESULTS: BTZ was found to elevate the protein levels of RhoA and RhoC in vascular endothelial cells, leading to stress fiber formation via the Rho/ROCK pathway. This process resulted in enhanced vascular permeability in a Rho-dependent manner. Furthermore, the stress fiber formation induced by BTZ had synergistic effects with the inflammatory mediator histamine. CONCLUSIONS: Our findings suggest that BTZ accumulates RhoA and RhoC proteins in endothelial cells, amplifying the inflammatory mediator-induced increase in the active GTP-bound state of Rho, thereby exaggerating vascular permeability during pulmonary inflammation. This study provides novel insights into the molecular mechanism underlying the pulmonary complications of BTZ, suggesting that BTZ may enhance inflammatory responses in pulmonary endothelial cells by increasing RhoA and RhoC protein levels.

DOI： 10.1186/s12890-024-03387-x

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

In pulmonary hypertension (PH) associated with chronic lung disease (CLD), identifying patients who would benefit from pulmonary vasodilators is a significant clinical challenge because the presence of PH is associated with poorer survival. This study evaluated the severity of pulmonary circulation impairment in patients with CLD-PH using pulmonary perfusion single-photon emission computed tomography/computed tomography (SPECT/CT). This single-center, observational study enrolled patients with CLD-PH who had a mean pulmonary arterial pressure (PAP) ≥ 25 mmHg, as confirmed by right heart catheterization. The primary outcome was to measure the percentage of pulmonary perfusion defect (%PPD), calculated by dividing the perfusion defect volume from perfusion SPECT images by the lung volume from CT scan images. The secondary outcome was to assess the correlation between %PPD and baseline characteristics. The median %PPD was 52.4% (interquartile range, 42.5%-72.3%) in 22 patients. In multivariate linear regression analysis, both forced vital capacity (β = 0.58, p = 0.008) and mean PAP (β = 0.68, p = 0.001) were significantly correlated with %PPD. In conclusion, significant correlation between mean PAP and %PPD in patients with CLD-PH was observed. This noninvasive assessment of %PPD may be useful for evaluating the severity of pulmonary circulation impairment in CLD-PH.

DOI： 10.1002/pul2.12423

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: Osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, is the standard treatment for patients with non-small cell lung cancer harboring EGFR mutations. Although the frequency of osimertinib-induced interstitial lung disease (osi-ILD) is high, the optimal cancer treatment after osi-ILD has not been established. This time, we focused on the safety and efficacy of gefitinib following osi-ILD. CASE PRESENTATION: We experienced six cases (five women and one man; median age: 74 years) in which gefitinib was administered after osi-ILD. All six cases had grade 2 or higher osi-ILD and required steroid treatment. The computed tomography imaging pattern of osi-ILD revealed organizing pneumonia in three cases, diffuse alveolar damage in two cases, and hypersensitivity pneumonia in one case. Eastern Cooperative Oncology Group performance status was 1 in four cases, 2 in one case, and 3 in one case. EGFR mutation status was exon 19 deletion in two cases and exon 21 L858R in four cases. Only one patient experienced recurrence of ILD after receiving gefitinib. The best response to gefitinib was partial response in two cases and stable disease in three cases; one case was not evaluable. The median progression-free survival after treatment with gefitinib was 190 days (95% confidence interval: 33-328). CONCLUSION: The treatment with gefitinib after the development of osi-ILD was safe and effective. Gefitinib may be a promising option for patients who recovered from severe osi-ILD.

DOI： 10.2147/OTT.S475836

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Sarcoidosis is a systemic granulomatous disease; however, the incidence of bone sarcoidosis is relatively rare. The short tubular bones of the hands and feet are most frequently affected, while the vertebrae and the pelvic bones are rarely involved. We hereby report a rare case of multiple bone sarcoidosis involving the vertebrae and pelvic bones, evaluated before and after steroid therapy using two different imaging modalities: bone scintigraphy and A 18F-fluorodeoxyglucose positron emission tomography combined with computed tomography (FDG-PET/CT). FDG-PET/CT is effective for detecting bone lesions; however, whole-body imaging is recommended to detect the short tubular bones of the hands and feet, which are most frequently affected.

DOI： 10.1016/j.rmcr.2024.102077

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