Aging (Albany NY). 2025 May 15;17. doi: 10.18632/aging.206250. Online ahead of print.

ABSTRACT

BACKGROUND: Both genetic and environmental factors can influence idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD) development. The gut microbiota plays crucial roles in maintaining tissue homeostasis. Dysregulation of the gut microbiota can result in disease. However, whether the alteration of the gut microbiota influences IPF and COPD remains unknown.

RESEARCH QUESTION: What is the causal relationship between IPF, COPD and the gut microbiota-related metabolic pathways? What are the potential intermediate mediators in this relationship?

STUDY DESIGN AND METHODS: Intersect the gut microbiota and its metabolic pathways associated with IPF and COPD. Utilizing summary data from GWAS in public databases, a two-sample Mendelian randomization (MR) analysis was conducted on the gut microbiota-related metabolic pathway, the aspartate superpathway, in relation to IPF and COPD. Furthermore, we employed a two-step MR to quantify the proportion of influence mediated by monocytes and cDCs on the aspartate superpathway in relation to IPF and COPD.

RESULTS: The MR analysis found that the aspartate superpathway decreased the risk of developing IPF and COPD. Monocytes and cDCs acted as intermediary substances, participating in this with influence proportions of 7.88% and 6.27%, respectively.

INTERPRETATION: There is a causal link between the gut microbiota-related metabolic pathway, the aspartate superpathway, and IPF and COPD, where the influence is partially mediated by monocytes and cDCs. In clinical practice, we increase the focus on gut microbiota-mediated immune cells in relation to IPF and COPD.

PMID:40378019 | DOI:10.18632/aging.206250

J Respir Biol Transl Med. 2025 Mar;2(1):10002. doi: 10.70322/jrbtm.2025.10002. Epub 2025 Mar 24.

ABSTRACT

Pulmonary arterial hypertension (PAH) is a progressive, lethal, and incurable disease of the pulmonary vasculature. A previous genome-wide association study (GWAS) with Affymetrix microarray analysis data exhibited elevated histidine triad nucleotide-binding protein 3 (HINT3) in the lung samples of PAH compared to control subjects (failed donors, FD) and the positive correlations of HINT3 with deubiquitinase USP11 and B-cell lymphoma 2 (BCL2). In this study, we aim to investigate the roles and interplay of USP11 and HINT3 in the apoptosis resistance of PAH. The levels of USP11 and HINT3 were increased in the lungs of idiopathic PAH (IPAH) patients and Hypoxia/Sugen-treated mice. USP11 and HINT3 interacted physically, as shown by co-immunoprecipitation (co-IP) assay in human pulmonary arterial endothelial cells (HPAECs). HINT3 was degraded by polyubiquitination, which was reversed by USP11. Furthermore, HINT3 interacted with the anti-apoptotic mediator, BCL2. Overexpression of USP11 increased BCL2 content, congruent to elevated lung tissue levels seen in IPAH patients and Hypoxia/Sugen-treated mice. Conversely, the knockdown of HINT3 function led to a depletion of BCL2. Thus, we conclude that USP11 stabilizes HINT3 activation, which contributes to endothelial apoptosis-resistance of pulmonary arterial endothelial cells in PAH. This can potentially be a novel therapeutic target for ubiquitination modulators for PAH.

PMID:40376595 | PMC:PMC12080269 | DOI:10.70322/jrbtm.2025.10002

Respir Res. 2025 May 15;26(1):185. doi: 10.1186/s12931-025-03227-4.

NO ABSTRACT

PMID:40375119 | DOI:10.1186/s12931-025-03227-4

Sci Rep. 2025 May 15;15(1):16969. doi: 10.1038/s41598-025-01459-4.

ABSTRACT

Objective Idiopathic pulmonary fibrosis (IPF), which radiologically/pathologically manifests mainly as usual interstitial pneumonia (UIP), is easily confused with chronic hypersensitivity pneumonitis (CHP) and collagenous vascular disease in clinical settings, affecting the physician's diagnosis and treatment. Accurate identification of IPF from various diseases presenting as UIP is essential for effective diagnosis and therapy. Methods Gene expression data of CHP, IPF, and rheumatoid arthritis-UIP samples were downloaded from the GEO database, and specific biomarkers were identified to differentiate idiopathic UIP/IPF from secondary UIP. We compared gene expression of specific biomarkers between control, secondary UIP, and IPF groups. The mechanism of specific biomarkers in PF was explored by immunohistochemistry, quantitative polymerase chain reaction, immunofluorescence, and flow cytometry. Results We identified integrin alpha V (ITGAV) as a specific biomarker for distinguishing IPF from secondary UIP. We observed a gradual increase in ITGAV expression across the control, secondary UIP, and IPF groups. Animal studies indicated that the elevated expression of ITGAV in various immune cells, particularly in monocyte-derived macrophages, contributed to the development of PF. Conclusion ITGAV is a specific biomarker linked to the pathogenesis of IPF. The identification of ITGAV provides new perspectives for clinical diagnosis, mechanistic studies and new drug development in IPF.

PMID:40374686 | DOI:10.1038/s41598-025-01459-4

Cell Signal. 2025 May 13:111868. doi: 10.1016/j.cellsig.2025.111868. Online ahead of print.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disorder marked by deteriorating dyspnea and declining pulmonary function. Despite its rising prevalence and incidence, therapeutic options remain limited. PTEN-induced kinase 1 (PINK1), known for its role in PINK1/Parkin-dependent mitophagy, contributes to the pathogenesis of various lung diseases. In this study, we elucidate a previously unrecognized mechanism of PINK1, beyond its canonical mitophagy function, during pulmonary fibrosis. We established a bleomycin (BLM)-induced pulmonary fibrosis model in Pink1 knockout (Pink1-/-) mice and treated BEAS-2B cells with transforming growth factor-beta 1 (TGF-β1) to simulate the microenvironment of pulmonary fibrosis. A significant elevation in PINK1 expression was observed in vivo and in vitro systems. While PINK1/Parkin-dependent mitophagy was activated, mitophagy mediated by BCL2-interacting protein 3 (BNIP3) and FUN14 domain-containing 1 (FUNDC1) was suppressed. Further experiments in carbonyl cyanide m-chlorophenyl hydrazone (CCCP)-treated PINK1 knockout (KO) HEK293 cells and YFP-Parkin-expressing HeLa cells demonstrated that PINK1 deficiency enhanced BNIP3- and FUNDC1-mediated mitophagy, whereas PINK1 overexpression inhibited it. Moreover, dual BNIP3/FUNDC1 knockdown significantly reversed the anti-apoptotic effect of PINK1 KO. We conclude that PINK1 deficiency promotes the clearance of damaged mitochondria via BNIP3/FUNDC1 upregulation, preserving mitochondrial homeostasis, mitigating alveolar epithelial injury, and attenuating fibrosis. Thus, PINK1 may inhibit BNIP3- and FUNDC1-mediated mitophagy besides driving PINK1-dependent mitophagy during pulmonary fibrosis.

PMID:40373838 | DOI:10.1016/j.cellsig.2025.111868

Zentralbl Chir. 2025 May 15. doi: 10.1055/a-2563-3691. Online ahead of print.

ABSTRACT

Lung transplantation has evolved continuously since its first successful procedures in the 1960 s. The current guidelines from the International Society for Heart and Lung Transplantation (ISHLT) emphasise increasingly individualised patient assessment, which, in addition to the underlying lung disease, considers factors such as comorbidities, frailty, age, and social aspects. The expanded indications for lung transplantation are reflected in the refined risk assessment, which particularly includes patients with advanced chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), and pulmonary arterial hypertension (PAH). Furthermore, the criteria for patients with a history of cancer and those with infections such as HIV or multidrug-resistant organisms have been made more flexible, leading to a more inclusive transplantation policy. A key focus is on early transplant counselling, allowing patients the opportunity for transplantation before they develop acute exacerbations. These updated guidelines aim to maximise both the survival rates and the quality of life of transplant patients, through differentiated and risk-adjusted decision-making.

PMID:40373816 | DOI:10.1055/a-2563-3691

Sci Rep. 2025 May 14;15(1):16825. doi: 10.1038/s41598-025-99792-1.

ABSTRACT

The coexistence of chronic fibrosing idiopathic interstitial pneumonia (cf-IIP) and lung cancer (LC) in the same patient raises many doubts regarding patient prognosis and complicates decision-making in multidisciplinary thoracic committees. To provide new insights into the management and prognosis of patients with cf-IIP, we assessed the sociodemographic and clinical differences between patients with and without LC to evaluate their role in their mortality. Other factors were also studied. A longitudinal study was conducted from January 1, 2001, to December 31, 2020, in our hospital. All patients who attended the interstitial lung disease multidisciplinary unit and had a medical diagnosis of cf-IIP were included. The primary outcome was all-cause mortality. The independent variable was the presence of LC. Covariates: sociodemographic, clinical, and therapeutic variables. The mortality rate (MR) was expressed per 1000 patient-years with a 95% confidence interval (CI). Cox multiple regression analysis examined the influence of LC and other covariates on mortality. The results are expressed as hazard ratios (HRs) with CIs. A total of 313 patients with cf-IIP were included, with a follow-up of 1589.6 patient-years. There were 209 (66.8%) deaths. The MR was 131.5 (114.8-150.6), and 50% of patients died at 5.58 years from cf-IIP diagnosis. After adjusting for confounders, LC was associated with a significantly increased risk of mortality (HR 4.11; 2.50-6.77; p = 0.000), whereas antifibrotic treatment was the only factor that decreased the risk of mortality (HR 0.60; 0.43-0.84; p = 0.003). The prevalence of LC was 15.3%. The most common histopathological type was squamous cell carcinoma (39.6%). At diagnosis, 68.7% of LC cases were in stages III-IV. The most widely used treatment was chemotherapy and its combination (43.7%). Patients with cf-IIP who developed LC had a fourfold increased risk of mortality and shorter mean survival (2 years vs. 6 years) compared with those without LC. Therefore, we recommend LC screening in these patients.

PMID:40369244 | DOI:10.1038/s41598-025-99792-1

Acta Pharmacol Sin. 2025 May 14. doi: 10.1038/s41401-025-01558-y. Online ahead of print.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease characterized by complex aetiologies involving the accumulation of inflammatory cells, such as macrophages, in the alveoli. This process is driven by uncontrolled extracellular matrix (ECM) deposition and the development of fibrous connective tissues. Here, we observed that the mRNA expression of Ffar1, the gene encoding G protein-coupled receptor 40 (GPR40), is repressed, while Cd36 is increased in the bronchoalveolar lavage fluid (BALF), which is predominantly composed of alveolar macrophages, of IPF patients. Furthermore, the GPR40 protein was found to be largely adhered to macrophages and was pathologically downregulated in the lungs of bleomycin (BLM)-induced PF model mice (PF mice) compared with those of control mice. Specific knockdown of GPR40 in pulmonary macrophages by adeno-associated virus 9-F4/80-shGPR40 (AAV9-shGPR40) exacerbated the fibrotic phenotype in the PF mice, and activation of GPR40 by its determined agonist compound SC (1,3-dihydroxy-8-methoxy-9H-xanthen-9-one) effectively protected the PF mice from pathological exacerbation. Moreover, Ffar1 or Cd36 gene knockout mouse-based assays were performed to explore the mechanism underlying the regulation of GPR40 activation in pulmonary macrophages with compound SC as a probe. We found that compound SC mitigated pulmonary fibrosis progression by preventing M2 macrophage polarization from exerting profibrotic effects through the GPR40/PKD1/CD36 axis. Our results strongly support the therapeutic potential of targeting intrinsic GPR40 activation in pulmonary macrophages for IPF and highlight the potential of compound SC in treating this disease.

PMID:40369224 | DOI:10.1038/s41401-025-01558-y

Sci Rep. 2025 May 14;15(1):16801. doi: 10.1038/s41598-025-01759-9.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease. Recent evidence suggests that the pathogenesis of IPF may involve abnormalities in mitochondrial energy metabolism. This study aimed to identify mitochondrial energy metabolism related differentially expressed genes (MEMRDEGs) and to elucidate their potential mechanistic involvement in IPF. We employed a multistep bioinformatics approach, including data extraction from the Gene Expression Omnibus database, removal of batch effects, and normalization and differential gene expression analyses. We then conducted Gene Ontology, Kyoto Encyclopedia of Genes and Genomes enrichment, and gene set enrichment analyses. A protein-protein interaction network was constructed from the STRING database, and hub genes were identified. Receiver operating characteristic curve analysis was performed to evaluate immune infiltration. Our integrated analysis of IPF datasets identified 25 MEMRDEGs. Nine hub genes emerged as central to mitochondrial energy metabolism in IPF. COX5A, EHHADH, and SDHB are potential biomarkers for diagnosing IPF with high accuracy. Single-sample gene set enrichment analysis revealed significant differences in the abundances of specertainfic immune cell types between IPF samples and controls. In conclusion, COX5A, EHHADH, and SDHB are potential biomarkers for the high-accuracy diagnosis of IPF. These findings pave the way for further investigations into the molecular mechanisms underlying IPF.

PMID:40369105 | DOI:10.1038/s41598-025-01759-9

Intern Med. 2025;64(10):1552-1562. doi: 10.2169/internalmedicine.4493-24. Epub 2025 May 15.

ABSTRACT

Nintedanib inhibits disease progression in patients with idiopathic pulmonary fibrosis (IPF) and dramatically improves the lung function in patients known to be super-responders (SRs). However, there are no reports on quantitative high-resolution computed tomography (HRCT), and the HRCT imaging characteristics of SRs remain unknown. We herein present the case of a 66-year-old man with IPF who was a SR to nintedanib treatment, which showed a marked improvement compared to other patients with IPF upon quantitative HRCT evaluation using the artificial intelligence (AI) software 3D Slicer. This study is worth reporting because a quantitative HRCT assessment using AI may be necessary to understand the SR characteristics.

PMID:40368830 | DOI:10.2169/internalmedicine.4493-24

Intern Med. 2025 May 15. doi: 10.2169/internalmedicine.5575-25. Online ahead of print.

NO ABSTRACT

PMID:40368795 | DOI:10.2169/internalmedicine.5575-25

Intern Med. 2025 May 15. doi: 10.2169/internalmedicine.5447-25. Online ahead of print.

ABSTRACT

Objectives To analyze the influence of age of the onset on myositis organ damage and to identify the factors influencing myositis organ damage, as clinical manifestations of myopathies differ by the age of onset and the background of patients. Methods Factors influencing organ damage [SLICC/ACR Damage Index (SDI)] were identified using the Japanese multicenter myositis registry (MYKO, n=220). Factors influencing organ damage were identified using a multivariate analysis. SDI was compared among juvenile-onset (<20 years old), adolescent-onset (20-64 years), and elderly-onset (>64 years) groups. Results There was a correlation between the age at onset and the SDI score (Spearman's rank correlation coefficient ρ=0.28). Elderly patients exhibited more widespread organ damage, including neuropsychiatric, renal, pulmonary, cardiovascular, peripheral vascular, gastrointestinal, skin, and diabetes, whereas juvenile-onset patients exhibited musculoskeletal damage. Adolescent-onset patients had the lowest incidence of ocular and malignant damage. A regression analysis revealed that an older onset age (coefficient, β=0.03), longer disease duration (β=0.05), and total dose of glucocorticoid (β=3.35x10-5) influenced SDI. After adjusting for disease duration, the influences of anti-MDA5 [hazard ratio (95% confidence interval), 4.47 (2.17-9.21)] on pulmonary fibrosis and a history of steroid pulse [2.16 (1.16-4.05)] on muscle atrophy or weakness were shown. Conclusions There were associations between the age of onset and autoantibodies with myositis organ damage. Musculoskeletal damage was greater in patients with a juvenile onset. An older age of onset is associated with severe organ damage. These findings highlight the importance of considering the age of onset and autoantibodies for assessing the prognosis and developing treatment plans for myopathies.

PMID:40368794 | DOI:10.2169/internalmedicine.5447-25

Breathe (Sheff). 2025 May 13;21(2):240261. doi: 10.1183/20734735.0261-2024. eCollection 2025 Apr.

ABSTRACT

This review summarises some of the key features of interstitial lung diseases (ILDs) from a translational science point of view and brings insights into potential therapeutic options. Genetic predisposition and environmental factors like smoking, pollution and infections significantly impact the onset, progression and treatment response in ILDs, highlighting the need for personalised management. Fibroblasts are central to ILD pathology, influencing the tissue microenvironment, immune cell interactions and extracellular matrix (ECM) production, making them critical therapeutic targets. Monocyte-derived M2 macrophages drive fibrosis in idiopathic pulmonary fibrosis by secreting cytokines and remodelling the ECM. Understanding macrophage subtypes and their dynamics offers new therapeutic possibilities. Chronic type 2 immunity contributes to fibrosis, emphasising the need to enhance protective markers in order to even out the balance shift of pathological immune responses in ILD treatments. Serum biomarkers like Krebs von den Lungen-6 (KL-6), surfactant protein (SFTP) D, matrix metalloproteinase-7 (MMP-7), and C-C motif chemokine ligand (CCL)-18 are valuable for diagnosing and predicting ILD progression, although more research is needed for clinical application. Animal models, especially bleomycin-based models, offer insights into ILD pathology, but challenges like lung hyperinflation highlight the need for careful model selection and translational research to bridge preclinical and clinical findings.

PMID:40365095 | PMC:PMC12070197 | DOI:10.1183/20734735.0261-2024

Breathe (Sheff). 2025 May 13;21(2):240169. doi: 10.1183/20734735.0169-2024. eCollection 2025 Apr.

ABSTRACT

Interstitial lung diseases (ILDs) are now the most common indication for lung transplant internationally. Given that many lung transplant candidates with idiopathic pulmonary fibrosis are older, referral to a pulmonary rehabilitation programme is important to help mitigate the adverse outcomes associated with frailty. Despite this increase many patients with ILD who would potentially benefit from lung transplant are either not referred or referred too late. Particularly relevant in ILD which may have prominent extra-pulmonary manifestations is a multidisciplinary assessment of comorbidities which may impact on post lung transplant outcomes. Particular challenges in lung transplant for ILD are increasing age, comorbidities, donor lung sizing and the risk-benefit balance of single versus bilateral lung transplant. Evidence is continuing to evolve for lung transplant in rarer ILDs, including surfactant protein associated ILD and TERT mutations. Unfortunately, the number of potential lung transplant recipients exceeds available donor organs and some patients will die without transplant. Palliative care is an important aspect of managing patients on an active lung transplant list to help optimise physical and psychological symptoms associated with uncertainty on an active lung transplant list.

PMID:40365094 | PMC:PMC12070198 | DOI:10.1183/20734735.0169-2024

J Clin Med. 2025 Apr 30;14(9):3118. doi: 10.3390/jcm14093118.

ABSTRACT

Background: The global health burden of chronic respiratory diseases, such as chronic obstructive pulmonary disease (COPD), asthma, idiopathic pulmonary fibrosis (IPF), and acute respiratory distress syndrome (ARDS) affects billions of people and is associated with high levels of healthcare expenditure. Conventional therapies (bronchodilators and corticosteroids) provide symptomatic benefit but take no effect on disease progression, demonstrating the need to develop new therapies. Emerging therapies treat the underlying mechanisms of these chronic diseases, which provide symptomatic relief and benefit the underlying disease. Methods: This review assesses the evolution of therapeutic interventions for chronic lung diseases from a series of established inhaled combination therapies to biologics, gene therapy, and even AI-based stratification of therapies for patients. In addressing these issues, we review the mechanisms of action, evidence of efficacy, and clinical trial evidence, while discussing access issues affecting the implementation of these therapies and ethical issues in relation to their use. Results: The review highlights recent developments in treatment approaches, such as gene therapies aimed at cystic fibrosis mutations, advanced drug delivery pathways for more accurate targeting, and stem cell-based therapies designed to replace damaged lung tissue. These developments have the potential to improve outcomes for chronic lung diseases, but the challenges, including a lack of access, adequate patient selection, and long-term safety, need to be addressed. Conclusions: New therapies offer tremendous potential, but their transition from laboratory to clinic still face numerous barriers including access, regulation, and a need for personalized therapy approaches. The review indicates that future research should develop strategies to reduce barriers to access, improve distribution, and improve clinical guidelines to successfully implement these new therapies.

PMID:40364149 | DOI:10.3390/jcm14093118

J Clin Med. 2025 Apr 29;14(9):3068. doi: 10.3390/jcm14093068.

ABSTRACT

Background/Objectives: The usefulness of presepsin, which is released from macrophages, in acute exacerbation of interstitial lung diseases (AE-ILDs) is unknown. We aimed to investigate the utility of monitoring presepsin with other AE-ILD markers before and after steroid pulse therapy in AE-ILDs. Methods: This pilot single-center retrospective observational study involved 16 patients with AE-ILDs, including the AE of idiopathic pulmonary fibrosis and idiopathic nonspecific interstitial pneumonia and rapidly progressive connective tissue disease-associated ILD. Patients who survived 90 days were assigned to the survival group (n = 9). The remaining patients were classified in the non-survivor group (n = 7). To evaluate the therapeutic efficacy of steroid pulse therapy, specific serum markers were selected-presepsin, as a novel AE-ILD marker, and surfactant protein D, C-reactive protein, and lactate dehydrogenase (LDH), as classical AE-ILD markers. Results: Thirteen out of sixteen patients with AE-ILDs showed high presepsin levels (presepsin ≥ 470 pg/mL) before steroid pulse therapy. The post-/pre-presepsin ratio and the post-/pre-LDH ratio, calculated by dividing the presepsin and LDH levels after therapy by the levels before therapy, respectively, showed a positive correlation (r = 0.579, p = 0.021). As a result of this correlation, the post-/pre-presepsin-LDH index was created, obtained from the "post-/pre-presepsin ratio" multiplied by the "post-/pre-LDH ratio". In a receiver operating characteristic curve analysis for non-survival, the post-/pre-presepsin-LDH index showed good discrimination as a prognostic marker for a poor outcome (AUC: 0.873, 95% confidence interval: 0.655-0.999). Conclusions: Tracking presepsin and LDH simultaneously may be useful for determining treatment response to steroid pulse therapy in the clinical management of AE-ILDs.

PMID:40364100 | DOI:10.3390/jcm14093068

Diagnostics (Basel). 2025 Apr 29;15(9):1139. doi: 10.3390/diagnostics15091139.

ABSTRACT

Background: Chronic cough is a common symptom in patients with interstitial lung diseases (ILDs), which significantly affects health-related quality of life (HRQoL). The prevalence of chronic cough varies from 30% to almost 90% in different ILDs, with the highest rate in patients with idiopathic pulmonary fibrosis. However, the pathophysiology of cough in ILDs remains poorly understood, with multiple proposed mechanisms contributing to its development. This knowledge gap complicates both clinical assessment and treatment, as current therapeutic strategies target general cough mechanisms rather than ILD-specific pathways. This review synthesizes existing data to clarify distinct cough mechanisms across ILD subtypes and identify opportunities for more targeted therapeutic strategies in this challenging patient population. Moreover, cough can be a clinical marker of disease severity and a predictor of ILD progression and transplant-free survival. Effective cough-specific therapeutic options that consider potential mechanisms, comorbidities, and individual effects on HRQoL are needed for cough associated with ILD. Therefore, the aim of this review was to analyze the prevalence, the impact on HRQoL, the pathophysiology, and the management of chronic cough in ILDs. Methods: We performed a comprehensive search in PubMed, MEDLINE, Embase, and the Cochrane Library. This review included randomized clinical trials, observational studies, systematic reviews, and meta-analyses in adults with chronic cough comparing ILD types. The following were excluded: commentaries, letters, case reports and case series, conference abstracts, and studies and publications lacking cough-specific outcomes. Results: Several approaches to reduce cough frequency and severity were described: antifibrotic agents, neuromodulators, opiates, inhaled local anesthetics, oxygen, speech therapy, and anti-reflux therapy. Some therapeutic approaches, such as oral corticosteroids and thalidomide, can cause significant side effects. Novel agents, such as P2X3 receptor antagonists, which are in phase III trials (COUGH-1/2), show promising results for refractory cough and may benefit ILD-related cough. Conclusions: Thus, a comprehensive assessment of cough is required for effective cough treatment in patients with ILDs considering possible mechanisms and individual impact on QoL.

PMID:40361957 | DOI:10.3390/diagnostics15091139

Cancers (Basel). 2025 Apr 29;17(9):1504. doi: 10.3390/cancers17091504.

ABSTRACT

BACKGROUND/OBJECTIVES: Molecular imaging, especially PET, has advanced significantly, shifting from metabolic radiotracers like 2-deoxy-2-[18F]fluoro-D-glucose [18F]FDG to target-specific probes. Among these, αvβ6-integrin has emerged as a promising target in cancer and non-cancer diseases. This review focuses on the radiochemical properties and initial clinical applications of the [68Ga]Ga-Trivehexin PET probe.

METHODS: The literature review on [68Ga]Ga-Trivehexin systematically evaluated both preclinical and clinical studies, with particular emphasis on its radiochemical characteristics and preliminary clinical applications, while highlighting advancements, associated challenges, and the potential for future developments in the field.

RESULTS: This study highlights the significant advancements achieved with [68Ga]Ga-Trivehexin in the field of molecular imaging. The optimized multimeric system has substantially enhanced the radiotracer's pharmacokinetic properties, binding affinity, and selectivity for αvβ6 integrin, demonstrating up to an 18-fold improvement compared to previous monomeric tracers. The synthesis protocol has been refined to achieve high radiochemical purity (>95%), essential for safe clinical use. Preliminary clinical applications, particularly in head and neck cancer (HNC) and pancreatic ductal adenocarcinoma (PDAC), have shown promising results, with high detection rates and improved differential diagnosis compared to [18F]FDG. Furthermore, [68Ga]Ga-Trivehexin PET/CT has shown potential in non-oncological conditions, such as idiopathic pulmonary fibrosis (IPF) and primary hyperthyroidism, suggesting broader clinical applicability.

CONCLUSIONS: [68Ga]Ga-Trivehexin is a promising PET probe for imaging αvβ6-integrin in cancers and non-oncological diseases like idiopathic pulmonary fibrosis (IPF) and primary hyperparathyroidism (PHP).

PMID:40361431 | DOI:10.3390/cancers17091504

Korean J Intern Med. 2025 May;40(3):458-467. doi: 10.3904/kjim.2024.244. Epub 2025 Apr 30.

ABSTRACT

BACKGROUND/AIMS: Patients with acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) typically have a poor prognosis; however, no effective treatment is available. In recent years, several retrospective studies have suggested the clinical benefits of direct hemoperfusion with a polymyxin B-immobilized fiber column (PMX-DHP) in patients with AE-IPF. Herein, we aimed to investigate the efficacy and safety of PMX-DHP treatment in patients with AE-IPF.

METHODS: Patients diagnosed with AE-IPF (n = 10) with a partial pressure of oxygen to fraction of inspiratory oxygen ratio (P/F ratio) > 100 were prospectively enrolled at a single center. PMX-DHP was performed twice for 6 hours (at 24-h intervals) at a flow rate of 80-100 mL/min, and steroid pulse therapy was concurrently administered (500 mg of methylprednisolone for 3 d).

RESULTS: The mean patient age was 67 years, and 80.0% were male. During the follow-up (median, 42.5 d; interquartile range, 16.0-174.0 d), seven (70.0%) patients died (including two who underwent transplantation); the in-hospital mortality rate was 70%, while the 30- and 90-day mortality rates were 50.0% and 70.0%, respectively. After 48 hours of PMX-DHP treatment, the P/F ratio improved (mean, 160.0 vs. 229.0; p = 0.054) and C-reactive protein level decreased (mean, 8.3 mg/dL vs. 3.5 mg/dL; p = 0.012). During hospitalization, no PMX-DHP-associated adverse events were observed.

CONCLUSION: Our results suggest that PMX-DHP treatment may be useful at improving oxygenation and reducing inflammation in patients with AE-IPF with acceptable safety profiles, however without affecting their prognosis.

PMID:40360222 | DOI:10.3904/kjim.2024.244

Korean J Intern Med. 2025 May;40(3):345-346. doi: 10.3904/kjim.2025.111. Epub 2025 Apr 30.

NO ABSTRACT

PMID:40360217 | DOI:10.3904/kjim.2025.111