Pulmonary fibrosis is a progressive and often fatal lung disorder whose clinical behavior is not fully explained by conventional injury-driven models. Fibrosis frequently progresses after the initiating insult has resolved, anti-inflammatory therapies have shown limited benefit in idiopathic pulmonary fibrosis, and current antifibrotic drugs slow but rarely reverse disease progression. Moreover, diverse conditions including idiopathic pulmonary fibrosis, post-ARDS or post-infectious fibrosis, radiation-induced injury, drug toxicity, and bronchopulmonary dysplasia arise from distinct causes yet may converge toward shared features of persistent fibrotic remodeling. Here we propose that pulmonary fibrosis represents a self-sustaining pathological tissue-repair state rather than a continuously injury-dependent process. Failure of alveolar epithelial regeneration produces persistent cellular senescence and chronic distress signaling that recruits reparative immune responses. These signals promote fibroblast survival and myofibroblast persistence, leading to extracellular matrix deposition and progressive tissue stiffening. Increased matrix stiffness further disrupts epithelial recovery through mechanotransduction pathways, creating a feedback loop linking epithelial dysfunction, immune mis-repair, stromal stabilization, and mechanical reinforcement. Within this framework, fibrosis persists because the lung behaves as a chronically unhealed wound. This model may help explain disease progression and heterogeneity and suggests that effective therapies must restore epithelial regeneration and disrupt system-level feedback rather than target single profibrotic pathways.
Tenosynovial giant cell tumor (TGCT) is a rare mesenchymal neoplasm arising from the synovium, tendon sheath, or bursa. Although the localized and diffuse forms of TGCT are typically considered benign, malignant TGCT characterized by marked histologic atypia and increased mitotic activity may exhibit aggressive clinical behavior. Pulmonary metastasis from malignant TGCT is rare and, in previously reported cases, pulmonary involvement has predominantly been described as parenchymal nodules or pleural lesions. In this article, we describe a rare case of endobronchial pulmonary metastasis occurring approximately 72 months after the initial diagnosis of malignant TGCT originating from the tendon sheath of the knee.
Microplastics (MPs) pollution represents a pressing global environmental challenge, with studies increasingly highlighting their associated health risks. Although MPs have been detected in human lung tissues, the majority of existing research has concentrated on their physicochemical characteristics, environmental distribution and pulmonary health risks. Consequently, our understanding of the specific biological targets and effective intervention strategies against these risks remains limited. To identify therapeutic targets, we screened for pulmonary differential metabolites between normal mice and mice exposed to airborne MPs, derived from dust fall of 10 cities in China. Proteomics results showed adenosine 5'-monophosphate-activated protein kinase (AMPK) signalling pathway was one of critical targets. Through molecular docking and molecular dynamics stimulation, honokiol (HNK) was selected as therapeutic drug to regulate AMPK. In vitro results demonstrated that HNK significantly ameliorated autophagy inhibition in RAW264.7 cell, and alleviated mitochondrial dysfunction in BEAS-2B cell. Drug mechanism research revealed that HNK activated autophagy via the AMPK/mammalian target of rapamycin (AMPK/mTOR) pathway, and promoted mitophagy through the AMPK/E3 ubiquitin protein ligase parkin (AMPK/Parkin) pathway, thereby restoring mitochondrial function. Further targeted energy metabolomics analysis illustrated that HNK regulated the guanosine triphosphate to guanosine diphosphate (GTP/GDP) ratio, adenosine triphosphate ‌(ATP) production, and nucleotide metabolism. These functions accelerated the restoration of autophagic flux, mitophagy reactivation and DNA repair. In conclusion, HNK effectively alleviates airborne MPs-induced autophagy inhibition, mitochondrial dysfunction and energy metabolism disorder via AMPK signalling, providing a promising intervention strategy for pulmonary injury caused by airborne MPs.
Autoimmune pulmonary alveolar proteinosis (APAP) is caused by impaired surfactant clearance due to neutralizing autoantibodies against granulocyte-macrophage colony-stimulating factor. Although whole-lung lavage and inhaled granulocyte-macrophage colony-stimulating factor therapy are established treatment options, pulmonary fibrosis is increasingly recognized as a clinically relevant complication in a subset of patients with APAP. However, the clinical behavior of APAP-associated fibrosing lung disease and the role of antifibrotic therapy remain unclear. A 54-year-old man with a 15-year history of APAP was referred to our institution. High-resolution computed tomography images obtained before referral showed slow progression of reticulation and traction bronchiectasis, suggesting fibrotic progression rather than recurrence of APAP. At presentation, forced vital capacity (FVC) was 3.31 L (80.0% predicted), and diffusion capacity for carbon monoxide (DLCO) was preserved. During 6 months of observation, FVC declined to 3.03 L (73.5% predicted), accompanied by worsening dry cough and exertional dyspnea. Nintedanib was initiated for a progressive fibrosing phenotype in the context of APAP. Thereafter, FVC remained relatively stable for 2 years, whereas DLCO declined during follow-up. APAP-associated fibrosing lung disease may present with a progressive fibrosing phenotype, but its diagnosis and management remain challenging. This case highlights the importance of distinguishing fibrotic progression from recurrence of intra-alveolar proteinosis.
Population-based analyses usually classify smoking status at survey enrollment, which combines people who quit before disease recognition with those who continued smoking through diagnosis and quit afterward. This study evaluated whether smoking cessation after a self-reported cardiopulmonary disease diagnosis was associated with subsequent all-cause and cause-specific mortality among adults reconstructed as smoking at diagnosis. This secondary analysis pooled ten cross-sectional National Health and Nutrition Examination Survey (NHANES) cycles from 1999-2000 through 2017-2018 and linked survey records to mortality follow-up through 2019. Adults aged ≥40 years with self-reported cardiovascular or chronic lung disease were included when self-reported smoking initiation, diagnosis, cessation, and current-smoking information permitted classification as smoking at diagnosis. Survey-weighted Cox models compared post-diagnostic quitters with persistent smokers. Models were unadjusted, demographic-adjusted, and fully adjusted for prespecified demographic, disease-history, smoking-history, and survey-cycle covariates. Among 2319 participants, 975 were post-diagnostic quitters, and 1344 were persistent smokers. During a median follow-up of 6.33 years, 999 all-cause, 272 heart-disease, and 244 cancer deaths occurred. In the fully adjusted model, post-diagnostic quitting was associated with lower heart-disease mortality (adjusted hazard ratio, AHR=0.59; 95% CI: 0.42-0.82; p=0.001). Associations with all-cause mortality (AHR=0.90; 95% CI: 0.74-1.09; p=0.276) and cancer mortality (AHR=0.72; 95% CI: 0.49-1.06; p=0.100) were not statistically significant. Findings for heart-disease mortality were consistent across landmark, overlap-weighted, smoking-burden-adjusted, disease-restricted, quit-age reconstruction, and leave-one-covariate-out analyses. Among adults retrospectively classified as smoking when cardiopulmonary disease was diagnosed, post-diagnostic cessation was associated with lower subsequent heart-disease mortality. The findings are observational and remain susceptible to survivor selection, reverse causation, recall and social-desirability bias, exposure changes after enrollment, mortality misclassification, and residual confounding.
Patients with hepatocellular carcinoma (HCC) presenting with both portal vein tumor thrombus (PVTT) and pulmonary metastasis (PM) have a particularly poor prognosis and limited treatment options. Hepatic arterial infusion chemotherapy (HAIC)-based combination therapy has shown promising activity in advanced HCC, but evidence in this high-risk population remains limited. To evaluate the efficacy and safety of HAIC combined with lenvatinib and tislelizumab (HLP) in patients with HCC with concurrent PVTT and PM. Multicenter retrospective cohort study with propensity score matching (PSM). Treatment-naïve patients with HCC with concurrent PVTT and PM who received lenvatinib plus tislelizumab (LP), with or without HAIC, between June 2018 and June 2024 were included. PSM was performed to balance baseline characteristics between treatment groups. The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs). A total of 262 patients were enrolled, including 114 patients in the HLP group and 148 patients in the LP group. After 1:1 PSM, 96 matched pairs were analyzed. The HLP group achieved significantly longer median OS than the LP group (15.1 vs 7.0 months; hazard ratio (HR), 0.55; 95% confidence interval (CI), 0.40-0.76; p < 0.001) and longer median PFS (7.3 vs 3.7 months; HR, 0.77; 95% CI, 0.56-0.94; p = 0.033). The ORR (47.7% vs 19.8%; p < 0.001) and DCR (86.1% vs 49.0%; p < 0.001) were also significantly higher in the HLP group. Although both all-grade and grade 3/4 treatment-related AEs were more frequent in the HLP group, toxicities were manageable, and no grade 5 AEs were observed. In patients with HCC with concurrent PVTT and PM, HLP was associated with improved survival outcomes and tumor response compared with lenvatinib plus tislelizumab alone, with a manageable safety profile.
Single-inhaler triple therapy (SITT) combining an inhaled corticosteroid, long-acting β2-agonist, and long-acting muscarinic antagonist (ICS/LABA/LAMA) represents the current ceiling of inhaled pharmacotherapy for moderate-to-very-severe chronic obstructive pulmonary disease and severe uncontrolled asthma. Five device platforms are currently approved: two extrafine formulations delivering beclomethasone dipropionate/formoterol/glycopyrronium (the Modulite solution pressurised metered-dose inhaler [pMDI] and the NEXThaler breath-actuated dry powder inhaler [DPI]); the co-suspension pMDI Aerosphere platform (budesonide/glycopyrrolate/formoterol); the standard-particle Ellipta DPI (fluticasone furoate/umeclidinium/vilanterol); and the low-resistance, single-dose capsule-based DPI Breezhaler (mometasone furoate/indacaterol/glycopyrronium). Despite a shared pharmacological class, these systems differ in aerosol physics, particle engineering, intrapulmonary deposition patterns, and device-patient interaction. Furthermore, some of them are authorized only for COPD or asthma. This narrative review examines the technology and in vivo deposition evidence for each SITT platform, discusses real-world performance determinants (particle size, flow dependency, technique robustness), and proposes an expert-informed framework for patient-level device selection. Methodological limitations include reliance on in silico Functional Respiratory Imaging data when in vivo scintigraphy is unavailable, and inconsistent dose denominators across studies (emitted vs. metered dose). Cross-platform comparisons are limited by heterogeneous methodologies, and no SITT platform has demonstrated universal superiority. In platform-specific studies, NEXThaler shows relatively high lung deposition (∼55% of emitted dose) though flow-dependent; Aerosphere is robust to inhalation technique variations; Modulite provides extrafine, peripheral delivery; Ellipta and Breezhaler offer once-daily convenience with moderate deposition. Rational device selection requires structured assessment of patient inspiratory capacity, disease phenotype, coordination, and adherence. Head-to-head scintigraphy and prospective imaging-outcome studies represent major evidence gaps.
Antineutrophilic cytoplasmic antibodies glomerulonephritis (ANCA-GN) is the most common type of crescentic glomerulonephritis in the elderly. It is life-threatening, and early detection is key to facilitating complete remission with treatment. Albeit rare, more reports are implicating hydralazine use in the development of ANCA-associated vasculitis (AAV) and ANCA-GN. Classic treatment involves the use of corticosteroids with cyclophosphamide (+/- plasmapheresis) in ANCA-GN. However, a definite therapeutic approach and duration for drug-induced AAV has yet to be studied in clinical trials. In our case, we aim to provide another approach that would one day improve and structure therapy guidelines for drug-induced AAV. We present a 75-year-old female patient, with medical history of hypertension, atrial fibrillation status post ablation on anticoagulation, pulmonary hypertension, who came to the nephrology clinic with symptoms of fatigue, anorexia, nausea, weight loss, hemoptysis, and rise in serum creatinine to 2.39 mg/dL from baseline of 0.65 mg/dL, and by admission to the hospital in August 2024 was 4.6 mg/dL. Anti-MPO and anti-histone antibodies were positive; complement was normal. Renal biopsy confirmed pauci-immune necrotizing GN with crescents. Therapy included steroids, rituximab, cyclophosphamide, and plasmapheresis with clinical improvement and complete remission of extra-renal disease.
Anti-melanoma differentiation-associated gene 5 (anti-MDA5) antibody-positive dermatomyositis (DM) can manifest with a severe vasculopathic phenotype. We report a case of anti-MDA5 DM in a woman in her early 30s complicated by refractory cutaneous ulcers and pulmonary arterial hypertension (PAH). Despite the escalation of immunosuppressive therapy with glucocorticoids, tacrolimus, intravenous immunoglobulin, and cyclophosphamide, the cutaneous ulcers remained refractory. A progressive decline in diffusing capacity of the lung for carbon monoxide raised suspicion of PAH, which was subsequently confirmed by right heart catheterization. Consequently, combination therapy with mycophenolate mofetil (MMF) and rituximab (RTX) was initiated alongside bosentan. This regimen resulted in the prompt resolution of ulcers and improvement of PAH. Bosentan was discontinued, and azathioprine was initiated to maintain remission, allowing for a successful pregnancy and delivery of a healthy infant. This case suggests a potential role for an MMF- and RTX-containing combination regimen in refractory cutaneous ulcers and PAH associated with anti-MDA5 DM.
Graphene is increasingly produced and utilized in industrial applications, raising concerns regarding occupational exposure and associated health risks. While numerous toxicological studies have investigated the hazard potential of laboratory-produced graphene, relatively little is known about exposure to airborne graphene particles in actual workplace environments or the toxicity of samples collected in the workplace. In the present study, we combined occupational exposure assessment in a graphene production facility with in vitro toxicological evaluation of graphene samples produced by liquid-phase exfoliation of graphite versus particulate matter collected in the same production facility. Workplace air sampling was performed using stationary and personal samplers and particulate matter was collected for elemental carbon (EC) analysis, Raman microscopy-spectroscopy, and toxicological testing using human lung cell lines (A549 and BEAS-2B). Personal EC concentrations ranged from 3 to 484 μg/m3, with the highest exposure levels observed during graphite powder handling. Raman analysis confirmed the presence of graphene in the collected samples. Toxicological assessments showed that samples collected in the workplace did not elicit cytotoxic effects at the tested concentrations while dispersions of as-produced graphene evoked a dose-dependent loss of cell viability. Overall, this pilot study demonstrates the feasibility of combining occupational exposure measurements with toxicological testing of real-world samples and suggests that airborne materials collected during graphene production exhibit low hazard potential in human lung cells.
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Mycobacterium abscessus complex is a rapidly growing non-tuberculous mycobacterium(NTM) associated with difficult-to-treat pulmonary and extrapulmonary infections. Clinical management is complicated by intrinsic antimicrobial resistance, inducible macrolide resistance, and genomic heterogeneity. This study characterised five clinical pulmonary M. abscessus isolates from India using whole-genome sequencing (WGS)-based genomic, phylogenetic, and antimicrobial resistance analysis. Five clinical isolates recovered from pulmonary specimens were sequenced using the Illumina NovaSeq platform (Illumina, Inc., San Diego, California, United States) with paired-end 151 bp chemistry. Reads were quality filtered using fastp v1.0.1. Reference-guided alignment and consensus generation were performed using Burrows-Wheeler Aligner (BWA)-Maximal Exact Match (MEM) and SAMtools-based workflows. Genome annotation was conducted using Prokka v1.14.6, functional annotation using eggNOG-mapper, variant analysis using Genome Analysis Toolkit (GATK) HaplotypeCaller and SnpEff, and antimicrobial resistance gene detection using the Comprehensive Antibiotic Resistance Database (CARD). Phenotypic antimicrobial susceptibility findings and GenoType NTM-drug resistance (DR) Line Probe Assay Version 1.0 results (Bruker Corporation, Billerica, Massachusetts, United States) were used to support the interpretation of macrolide resistance-associated findings. The isolates generated 0.92-1.24 Gb of high-quality sequencing data, with Q30 values exceeding 95%. Genome coverage at ≥30× depth exceeded 91%, and average sequencing depth ranged from 44.16× to 149.59×. Annotation identified 4,457-4,751 coding sequences, 45-48 tRNA genes, three rRNA genes, and one tmRNA gene per isolate. Reference alignment ranged from 24.86% to 64.22%, supporting isolate-level genomic heterogeneity. MAB β-lactamase (blaMab) gene was detected in all isolates, while erm(41) was detected only in LIN. WGS-enabled isolate-level characterisation of pulmonary M. abscessus isolates from India demonstrated conserved genomic features with measurable heterogeneity. blaMab supports intrinsic β-lactam resistance, while erm(41) in LIN was consistent with an inducible macrolide resistance pattern supported by available phenotypic antimicrobial susceptibility testing.
The evaluation of diastolic function in patients with diabesity (i.e., combined obesity and type-2 diabetes mellitus) undergoing incretin-based therapy could facilitate its early detection and help prevent its progression to heart failure. In this small descriptive study, performed for exploratory and proof-of-concept purposes, a group of 15 diabesity cases with chest x-ray examinations (< 1 month) before and after ≥ 12 months of incretin-based therapy (absent ventricular/valvular dysfunction) were identified. Standard diabesity characteristics (Body Weight (kg), Body Mass Index (kg/m2), and Hemoglobin A1c) and AI-model diagnostic predictions of pulmonary venous hypertension (aka "pulmonary congestion") [None; Stage 1: vascular distention/redistribution but minimal interstitial edema; or Stage ≥ 2: vascular congestion with ≥ mild interstitial or alveolar edema] by validated AI-enabled chest x-ray staging, representing mean left atrial pressure in diastolic dysfunction, were evaluated pre- and post-therapy. According to weight-loss response to incretin therapy, cases clustered into equal-sized therapeutic categories as follows: (1) Significant Responders (9-30% decreases); (2) Insignificant Responders (0-2% decreases); and (3) Non-Responders (2-12% increases). Regarding hemoglobin A1c changes: (1) Significant Responders collectively decreased; (2) Insignificant Responders varied; and (3) Non-Responders were largely stable. Pre-therapy, all 15 cases demonstrated AI-enabled chest x-ray pulmonary venous hypertension staging evidence of diastolic dysfunction; post-therapy, 4 improved (especially the cases of greatest weight loss or hemoglobin A1c reduction), 5 were stable, and 6 worsened. Per therapeutic category, AI-enabled chest x-ray signs of functional response were: (1) Significant Responders (all demonstrating unequivocally decreased obesity and improved diabetes) collectively showed stable-decreased dysfunction; (2) Insignificant Responders (all demonstrating at most minimally decreased obesity, but stable-worsening diabetes in most) reflected stable-increased dysfunction in 60%; and (3) Non-Responders (all demonstrating increased obesity, but stable-improved diabetes) showed increased dysfunction in 80%. AI-enabled chest x-ray pulmonary venous hypertension staging potentially detects background subclinical diastolic dysfunction in diabesity and monitors its functional response to incretin-based therapy. The confirmation (or disproof), and assessments of durability and generalizability, of these preliminary results await a larger more definitive and controlled prospective study on the subject.
Intravascular large B-cell lymphoma (IVLBCL) is a rare extranodal neoplasm in which malignant B cells proliferate predominantly within small blood vessels. Because lymphadenopathy, mass lesions, circulating malignant cells, and specific radiological findings may be absent, IVLBCL can closely mimic other medical conditions, resulting in delayed diagnosis. This case is notable for a prolonged culture-negative sepsis-like presentation with persistent unexplained hypoxemia due to predominant pulmonary microvascular involvement, further obscured by lupus-like autoimmune features and subsequent COVID-19 infection. An older woman in her early 70s presented with fever, lethargy, weight loss, back pain, hypotension, raised inflammatory markers, cytopenia, markedly elevated lactate dehydrogenase (LDH), and progressive hypoxemia. She was initially treated for presumed sepsis, but repeated microbiological investigations and serial imaging did not identify an infectious source, and clinical improvement was not sustained. A transient malar rash and a positive antinuclear antibody raised concern for a lupus-like autoimmune disease; however, testing for anti-double-stranded DNA and extractable nuclear antigen was negative, and the broader autoimmune workup did not support systemic lupus erythematosus as the unifying diagnosis. Subsequent severe acute respiratory syndrome coronavirus 2 infection further complicated the interpretation of hypoxemia and deterioration. Despite antimicrobial therapy, corticosteroids, antiviral treatment, and supportive care, she developed progressive multiorgan failure and died approximately six weeks after admission. Postmortem examination revealed widespread multiorgan IVLBCL involving the lungs, heart, kidneys, liver, spleen, and multiple additional extranodal sites. Pulmonary capillary involvement provided a clinicopathological explanation for persistent unexplained hypoxemia. This case demonstrates how IVLBCL may remain concealed when several plausible diagnoses coexist. Persistent culture-negative fever, constitutional decline, cytopenia, high LDH, nondiagnostic imaging, treatment nonresponse, and unexplained hypoxemia should prompt consideration of IVLBCL and early tissue-based investigation.
Digital health technologies offer a promising approach to strengthening self-management capacity among patients with chronic obstructive pulmonary disease (COPD), yet clinical application is hampered by poor adherence, low sustained engagement, and limited self-management ability. Although previous studies have identified general self-management challenges in COPD, few have systematically investigated patients' preferences for digital tools or translated these insights into actionable design principles. This hinders the user-centred development and effective deployment of digital interventions for this population. This study aimed to explore the self‑management challenges and preferences for mobile health (mHealth) among COPD patients, with the ultimate goal of translating these findings into design principles for a persuasive self‑management application. We conducted in-depth personal interviews with 15 patients with COPD and five healthcare professionals to explore the challenges of self-management and preferences for mHealth. Data were analyzed using thematic analysis. Subsequently, a structured expert consultation was held to translate the findings into key principles for a persuasive self-management application. Five themes regarding barriers to effective self-management were identified: (1) negative emotional experience, (2) poor health literacy, (3) insufficient family support, (4) inadequate professional health care, and (5) economic burden. Patients expressed four key preferences for digital health technologies: (1) simplicity, (2) personalized decision support, (3) self-report, (4) early warning of deterioration. Furthermore, the panel discussion distilled these findings into eight essential key principles: motivation, simplicity, credibility, guidance, personalization, self-report, warning, and continuity. This study provides new insights into user-centered mHealth tools for COPD self-management. We derived core design principles from patients' demands to inform targeted digital interventions. These principles require validation in female, higher-literacy and multi-center samples before wide application. Future work will complete the remaining CeHRes Roadmap stages of design, operationalization and evaluation to refine this framework. What is Already Known about this Topic? Many patients with chronic obstructive pulmonary disease hope to use mobile applications to manage their respiratory conditions and daily health. Properly designed mobile applications can assist patients in better self-care. Nevertheless, there are still very few development standards formulated according to the actual daily needs of patients with COPD, which makes it difficult for developers to create self-management applications that are both user-friendly and clinically effective. What this Paper Adds? We collected feedback from patients with chronic obstructive pulmonary disease and medical staff through one-on-one interviews, and also gathered professional advice from an interdisciplinary expert panel. Based on these inputs, we identified practical approaches to support routine health management and developed eight actionable design guidelines for creating user-friendly mobile health tools. The Implications of this Paper Our results help medical teams better grasp what people with COPD actually want from mobile health self-management tools. Clinicians and app developers can build mobile health apps that match COPD users’ real needs and preferences. This work offers clear practical guidance to create health tools that center on the person living with COPD.
Tris(1-chloro-iso-propyl) phosphate (TCIPP) emerged as the predominant organophosphorus flame retardants (OPFRs) in both dust and air environments. This study investigated its respiratory toxicity using mouse inhalation model. Molecular docking and dynamics simulations revealed that TCIPP could binds to glutathione peroxidase 4 (GPX4) with an affinity of -5.3098 kcal/mol, stabilizing the protein conformation. Inhalation TCIPP exposure (34 μg/m3 for 1 h) significantly reduced GPX4 expression and GSH levels in lung tissue. Histopathological examination indicated severe pulmonary injury, including inflammatory cell infiltration, alveolar wall thickening and apoptosis after TCIPP inhalation. Besides, DHE staining revealed that the ROS level increased by 94.7% in the lung after TCIPP exposure. Meanwhile, the results revealed a 50.7% increase in lung iron content (Fe2+), along with elevated ferroptosis markers (p53, Transferrin Receptor 1 (TFR1)) and reduced FTH1 levels following TCIPP inhalation. These effects were counteracted by the ferroptosis inhibitor Fer‑1 (0.8 mg/kg), which also attenuated pathological damage, ROS accumulation, and NLRP3‑mediated pyroptosis. Concurrently, electron microscopy analysis demonstrated mitochondrial cristae membrane disruption and shrinkage, accompanied by dysregulated expression of mitochondrial dynamics regulators (down‑regulated Mfn1/2 and up‑regulated Drp1), all of which were reversed by Fer‑1. Collectively, the results indicate that TCIPP inhalation induces GPX4‑dependent ferroptosis, promoting inflammatory responses and mitochondrial imbalance, ultimately driving respiratory toxicity. Ferroptosis thus represents a potential therapeutic target for organophosphorus flame retardant‑associated lung injury, which may aid in biomarker discovery for related pulmonary diseases.
To explore the feasibility and preliminary behavior of the Computer-Aided Lung Informatics for Pathology Evaluation and Rating (CALIPER) tool in detecting radiologic differences in lung parenchyma of lung transplant recipients undergoing extracorporeal photopheresis (ECP) for chronic lung allograft dysfunction (CLAD). We performed a retrospective case review on a series of adult lung transplant recipients at Mayo Clinic who had a baseline CT following transplant, underwent ECP for CLAD, and had follow-up CT imaging. Our primary outcome was temporal change in lung parenchymal morphology exemplars assessed by CALIPER. Secondary outcomes included changes in distribution of vascular-related structures, calculated lung volumes, and spirometric indices. Data was analyzed using a linear mixed effects model. Of 91 eligible recipients with CLAD, 15 were treated with ECP. Following ECP we observed an increase in normal lung tissue (p = 0.038) and a decrease in interstitial lung abnormalities (p = 0.003). There was no significant difference in hyperlucent areas, distribution of pulmonary vascular-related structures, or calculated lung volumes. There was a slight increase in FVC (p < 0.001) after initiation of ECP, but no significant change in FEV1. Initiation of ECP was associated with favorable parenchymal changes as calculated by CALIPER in this sample of patients.
Renin-angiotensin-aldosterone system (RAAS) inhibitors, including angiotensin-converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs), are commonly prescribed antihypertensive medications with proposed antifibrotic and bone-protective effects. Their impact on outcomes following total shoulder arthroplasty (TSA) remains unclear. This study evaluates the association between perioperative RAAS inhibitor exposure and postoperative outcomes after TSA. A retrospective cohort study using the TriNetX network identified patients undergoing primary shoulder arthroplasty (2005-2025), stratified by ACEi or ARB use. One-to-one propensity score matching was performed. Outcomes included 90-day medical complications and 1-year mechanical complications and revision. Post-matching, 27,938 patients per cohort (ARB vs. control) and 30,602 per cohort (ACEi vs. control) were included. Neither ARB nor ACEi use reduced rates of manipulation under anesthesia or capsular release at one year. Both cohorts had higher 90-day rates of emergency department visits, readmission, myocardial infarction, and acute renal failure. ACEi use was additionally associated with pulmonary embolism, deep-vein thrombosis, transfusion, and sepsis. At one year, both cohorts showed higher rates of periprosthetic joint infection, aseptic loosening, and revision. Dislocation risk was increased with ACEi use only. Perioperative RAAS inhibitor use was not associated lower rates of antifibrotic procedures following TSA. Instead, RAAS inhibitor use was associated with higher rates of several perioperative medical complications and longer-term surgical events, including infection and revision. ACE inhibitor exposure demonstrated a broader complication profile compared with ARB exposure. However, because patients receiving RAAS inhibitors often have greater comorbidity burden, these findings should be interpreted as associative rather than causal. Retrospective Cohort Study.
The current state of respiratory physical therapy for adult pneumonia in Japan is insufficiently characterized. This study aimed to elucidate the current practices of respiratory physical therapy in Japan, including its implementation specifics, clinical frameworks, and medical reimbursement, with the aim of optimization respiratory physical therapy for adult pneumonia. A cross-sectional questionnaire survey comprising 21 questions was administered to members of the Japanese Society of Respiratory Physical Therapy. The survey items encompassed basic institutional information, existence of protocols, timing of rehabilitation prescriptions, clinical and educational systems for respiratory physical therapy (such as training systems), and content of respiratory physical therapy. The timing of rehabilitation prescriptions for adult pneumonia "varies depending on clinical decision-making by attending physicians" in 35.4% of institutions, and only 8.3% of facilities had established rehabilitation protocols. Furthermore, the most pressing issue concerning respiratory physical therapy for adult pneumonia was identified as "the lack of guidelines for respiratory physical therapy (pulmonary rehabilitation) for pneumonia," with 92 institutions citing this as the most significant problem. The practice of respiratory physical therapy for adult pneumonia in Japan varies across institutions, with a lack of reference materials, including clinical practice guidelines, potentially contributing to this variability. These findings highlight the need for further research and the development of optimized clinical guidance.
Patients with chronic obstructive pulmonary disease (COPD) and type 2 diabetes mellitus (T2DM) are at increased risk of sepsis, yet the comparative infection-related outcomes of newer antihyperglycemic agents remain unclear. We evaluated the associations of glucagon-like peptide-1 receptor agonists (GLP-1RAs) versus sodium-glucose cotransporter 2 inhibitors (SGLT2is) with infection outcomes in this population. In this retrospective cohort study using the TriNetX global federated database, individuals aged 40-100 years with coexisting COPD and T2DM who initiated a GLP-1RA or SGLT2i between 2021 and 2024 were identified. A new-user, active-comparator design with 1:1 propensity score matching was applied. Sepsis was the primary outcome; all-cause mortality and components of the primary outcome were secondary. Cox proportional hazards models estimated hazard ratios (HRs) with 95% confidence intervals (CIs). After matching, 45,491 pairs were included. Compared with SGLT2is, GLP-1RAs showed lower risks of sepsis (adjusted HR, 0.832; 95% CI, 0.781-0.887), all-cause mortality (0.642; 0.598-0.689), and severe sepsis (0.841; 0.774-0.914). In patients with COPD and T2DM, GLP-1RAs were associated with significantly lower risks of sepsis and all-cause mortality compared with SGLT2is.