閉塞性細気管支炎

BACKGROUND: Organizing pneumonia (OP) is a rare interstitial lung disease that may occur secondary to drug exposure. Although OP has been described during rituximab treatment, the association with ocrelizumab remains elusive, with evidence limited to a few recent cases. We aimed to characterize ocrelizumab-related OP in the context of the existing literature. METHODS: Clinical, radiological, laboratory, therapeutic, and outcome data were retrospectively collected from multiple sclerosis (MS) patients with ocrelizumab-associated OP at our center and descriptively compared with 17 cases identified through a literature review. RESULTS: Among 626 ocrelizumab-treated MS patients, five cases of OP were observed (0.8%) (3 females, median age=54 years, range=27-64). OP developed after a mean treatment exposure of 5.1 years (standard deviation (SD=2.9) and a mean interval of 10.8 weeks (SD=10.4) following the last infusion. Clinical presentation was characterized by persistent antibiotic-refractory fever, sometimes accompanied by nonproductive cough. Chest CT consistently showed patchy ground-glass opacities and consolidations. All patients received prednisone 0.5-1 mg/kg/day for a median duration of 30 days (range=15-60), followed by gradual tapering. Despite initial clinical response, respiratory relapses and residual radiological lung abnormalities were observed in four patients during a median follow-up of 29 months (range=4-47). Ocrelizumab was discontinued in all patients. Only one patient initiated ozanimod two years after OP onset. DISCUSSION: Our findings support the emerging evidence of ocrelizumab-related OP and show substantial consistency with previously reported cases. Further studies are needed to clarify the potential role of CD20+ lymphocyte depletion in OP pathogenesis.

BACKGROUND: Bronchiolitis obliterans syndrome (BOS) is a devastating complication of allogeneic hematopoietic stem cell transplantation (HSCT) characterized by onset of obstructive lung disease. Oscillometry is a novel pulmonary function assessment technology which superimposes pressure waves on normal tidal breathing, and the alterations in flow and pressure caused by the external waves are measured. Oscillometry assesses physiological parameters that provide insight into respiratory mechanics. We hypothesized that oscillometry may allow for detection of small airway disease to diagnose BOS, especially in children unable to perform spirometry. METHODS: We conducted a cross-sectional study to characterize oscillometry findings in patients with BOS compared to a control cohort of HSCT patients without BOS. PFT testing were performed on all patients at the time of oscillometry testing. RESULTS: Thirty-six patients post HSCT were approached, 18 with BOS and 18 controls. These two groups were similar in demographic parameters. BOS patients had significantly abnormal spirometry values. Oscillometry results demonstrated significant differences between the two cohorts in X5, AX, R5, R5-19 and (R5-19)/R5. There were significant differences between BOS and transplant control groups when assessing the association between oscillometry parameter and spirometry parameters. CONCLUSION: In our cohort oscillometry revealed significant differences between the BOS and non- BOS cohort. Resistance at R5 Hz and the difference between R5-R19 Hz, which characterizes peripheral lung resistance, were both abnormally increased when compared with non- BOS subjects. In addition, reactance parameters, X5 and AX, which correlate with lung stiffness demonstrated significant differences between the BOS and non- BOS cohorts. Our data reveal a strong correlation between oscillometric and spirometric abnormalities in patients with established BOS originally identified by standard spirometry testing. In addition, oscillometry suggests localization of increased resistance in the lung periphery supporting our hypothesis that oscillometry might be complementary to spirometry, and enhance our ability to diagnose BOS. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04098445.

OBJECTIVE: We aimed to characterize the inflammatory and complication profiles of patients with retroperitoneal unicentric Castleman disease (UCD), compare the clinical features of UCD with an MCD-like inflammatory state (UCD-MIS) and non-MIS cases, and describe treatment patterns and follow-up outcomes. MATERIALS AND METHODS: We retrospectively analyzed 75 patients with retroperitoneal UCD treated at our institution between 2000 and 2025, focusing on inflammatory phenotypes, severe complications, surgical extent, and follow-up outcomes. RESULTS: UCD-MIS was identified in 20 patients (26.7%). Paraneoplastic pemphigus (PNP) occurred in 9 patients (12.0%), bronchiolitis obliterans (BO) in 8 (10.7%), and amyloid A (AA) amyloidosis in 2 (2.7%). Patients with UCD-MIS more frequently had PNP (35.0% vs. 3.6%; FDR-adjusted P = 0.004) and BO (25.0% vs. 5.5%; FDR-adjusted P = 0.042) than those without MIS. For treatment, 61 patients underwent surgery, including 57 complete resections. During a median follow-up of 60.8 months (range, 6.1-266.2 months), two deaths occurred. Both patients had PNP and met the criteria for UCD-MIS, and one also had BO. Neither patient had undergone surgical excision of the UCD lesion. The small number of deaths precluded between-group survival comparisons. CONCLUSION: Comprehensive screening for complications is essential in retroperitoneal UCD, and complete surgical excision remains the cornerstone of therapy when technically feasible.

Chronic lung allograft dysfunction (CLAD) is the leading cause of late morbidity and mortality after lung transplantation. Bronchiolitis obliterans syndrome (BOS), a major CLAD phenotype, is characterized by obliterative bronchiolitis (OB). While microvascular perturbations are described in BOS, their cellular and molecular characteristics remain unclear. Intact human CLAD lungs (n=3) underwent hierarchical phase-contrast tomography (HiP-CT) for three-dimensional vascular mapping. In OB-affected airways vs. controls (n=4 each), endothelial subtypes were characterized by multiplex immunofluorescence imaging, interactome changes quantified with CellChat and GeoMx spatial transcriptomics performed on CD31+ regions. HiP-CT revealed hypertrophic vessels infiltrating obliterated airways and forming web-like microvascular networks, absent in controls. Immunofluorescent imaging showed increased PLVAP+/VWA1+ systemic venous and PDPN+ lymphatic cells in OB lesions. Cell-cell interaction analysis showed that PLVAP+/VWA1+ systemic venous cells exhibited increased incoming and outgoing interaction strength, primarily directed toward other endothelial cells and fibroblasts, characterized by inflammatory and fibrotic signalling. Spatial transcriptomics demonstrated upregulation of inflammatory/matrix-remodelling genes and downregulation of homeostatic regulators in BOS endothelial cells. BOS lungs display altered vascular architecture and endothelial composition, with gene expression shifts consistent with pro-inflammatory and fibrogenic processes in CD31+ regions. These findings suggest a potential involvement of vascular remodelling in CLAD pathophysiology.