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

J Pharmacol Exp Ther. 2025 Apr 21;392(6):103588. doi: 10.1016/j.jpet.2025.103588. Online ahead of print.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is characterized by the pathological replacement of alveolar structures with thickened, inelastic fibrous tissue, which significantly hinders gas exchange in the lungs. Disulfiram (DSF), a Food and Drug Administration-approved drug for alcohol dependence, has shown potential in various diseases. This study investigates the effects of DSF on IPF and its mechanisms, focusing on the cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) pathway. Utilizing primary diseased human lung fibroblast-IPF cells and A549 cells induced with transforming growth factor-beta 1 to model epithelial-mesenchymal transition (EMT), we employed a battery of in vitro assays to assess cellular viability, migratory capacity, and the expression of fibrosis-related genes and proteins. To further substantiate our in vitro findings, a bleomycin-induced mouse model of IPF was treated with DSF, and subjected to a comprehensive evaluation of pulmonary function, histological examination, hydroxyproline assay, and western blot analysis to quantify the extent of fibrosis. DSF reduced cell viability and migration in fibrotic cell models. It increased COX-2 and PGE2 levels, regulated EMT, and extracellular matrix collagen deposition. In vivo, DSF improved pulmonary function and reduced EMT and extracellular matrix accumulation in mice. The COX-2/PGE2 axis was identified as a critical mediator of DSF's effects. DSF exhibits antifibrotic properties in IPF by modulating the COX-2/PGE2 signaling pathway. This study provides a novel therapeutic strategy for IPF and highlights the potential of repurposing DSF for clinical use in this context. SIGNIFICANCE STATEMENT: Disulfiram shows promise in treating idiopathic pulmonary fibrosis by targeting the cyclooxygenase-2/prostaglandin E2 pathway, offering a new therapeutic strategy and highlighting its potential for repurposing in this context.

PMID:40359874 | DOI:10.1016/j.jpet.2025.103588

Radiology. 2025 May;315(2):e241252. doi: 10.1148/radiol.241252.

ABSTRACT

Although idiopathic pulmonary fibrosis (IPF) is a type of idiopathic interstitial pneumonia (IIP), it is different from other IIPs. IPF also differs from interstitial lung disease (ILD) with known causes, including connective tissue disease, exposure, cysts and/or airspace filling disease, and sarcoidosis. More than 90% of IPFs demonstrate progressive disease. Non-IPF ILD has been classified as progressive pulmonary fibrosis on the basis of disease behavior (progressive disease that gets worse over time) as opposed to classification based on cause and/or morphologic characteristics. Progressive fibrosis predictors in ILD include demographic characteristics, underlying connective tissue disease, more extensive disease at CT, honeycombing and usual interstitial pneumonia (UIP) pattern at CT, and greater impairment of lung function. Hypersensitivity pneumonitis (HP), a type of ILD, is separated into fibrotic and nonfibrotic types. Extensive peribronchiolar metaplasia supports the diagnosis of fibrotic HP over UIP, as does predominantly peribronchiolar disease with relative subpleural sparing at CT. Interstitial lung abnormality (ILA) is incidentally identified at CT; thus, ILA is under radiologist purview. Subpleural fibrotic ILA is a prognostic imaging biomarker, predictive of worse prognosis. Photon-counting CT can provide high spatial resolutions of up to 125 μm (in-plane) and 200 μm (through-plane) for improved evaluation of abnormalities.

PMID:40358445 | DOI:10.1148/radiol.241252

Circ Res. 2025 May 13. doi: 10.1161/CIRCRESAHA.125.326173. Online ahead of print.

ABSTRACT

BACKGROUND: Pulmonary hypertension (PH) is a lethal disease characterized in part by progressive pulmonary arteriole (PA) remodeling. Excessive PA fibrosis and macrophage infiltration are often present in PH, but the potential associations are obscure. We investigated the link between interstitial macrophage (iMΦ) infiltration and PA fibrosis in PH and idiopathic pulmonary arterial hypertension.

METHODS: Lung tissue samples from patients with idiopathic pulmonary arterial hypertension and experimental PH animals were obtained to analyze the extent of fibrosis and iMΦ infiltration in the different layers of PAs and their correlation with disease severity. Single-cell RNA sequencing, lineage tracing, histological analyses, iMΦ and PA smooth muscle cell coculture, and transgenic animal experiments were used to investigate the cell heterogeneity and origins and molecular mechanisms by which iMΦs promote PA fibrosis.

RESULTS: We found that increased collagen deposition and fibrosis in the PA media were most strongly related to the severity of PH, and medial iMΦ infiltration may be involved in these pathological processes. Single-cell transcriptomics revealed that MHCIIhiLYVE1loCCR2hi iMΦs were the major type of iMΦ that expanded upon Sugen-5416 and hypoxia plus normoxia stimulation and were responsible for PA medial fibrosis. Lineage tracing experiments suggested that these medial iMΦs were largely from recruited monocytes. Mechanistically, MHCIIhiLYVE1loCCR2hi iMΦs promoted the transition of PA smooth muscle cells to a fibroblast-like phenotype through the WNT11 (wingless member 11)/planar cell polarity (PCP) pathway. Wnt11 deletion in iMΦs from PH rats normalized the fibrotic PA smooth muscle cell phenotype and decreased PA medial fibrosis, thereby improving vascular compliance and protecting against PH. Moreover, myeloid-specific Ccr2 deficiency in PH-PAs inhibited the medial infiltration of MHCIIhiLYVE1loCCR2hi iMΦs, which also relieved PH.

CONCLUSIONS: This study demonstrates that the recruitment of MHCIIhiLYVE1loCCR2hi iMΦs leads to medial fibrosis in PH-PAs associated with PH severity and that inhibition of their pathogenicity or recruitment reverses PA medial fibrosis and PH.

PMID:40357547 | DOI:10.1161/CIRCRESAHA.125.326173

Front Pharmacol. 2025 Apr 28;16:1530697. doi: 10.3389/fphar.2025.1530697. eCollection 2025.

ABSTRACT

INTRODUCTION: To date, only two drugs, pirfenidone and nintedanib, are approved for the treatment of patients with idiopathic pulmonary fibrosis (IPF). In addition, very few studies have reported on the safety profile of either drug in large populations. This study aims to identify and compare adverse drug events (ADEs) associated with pirfenidone and nintedanib in real-world settings by analyzing data from the US Food and Drug Administration Adverse Event Reporting System (FAERS). In addition, we utilized data from the Japanese Adverse Drug Event Report (JADER) database for external validation.

METHODS: The ADE reports on both drugs from 2014 Q3 to 2024 Q2 in FAERS and from 2008 Q1 to 2024 Q1 in JADER were collected. After deduplication, Bayesian and non-Bayesian methods for disproportionality analysis, including Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multiple Gamma Poisson Shrinkers (MGPS), were used for signal detection. Additionally, time to onset (TTO) analysis were performed.

RESULTS: In total, 35,804 and 20,486 ADE reports were identified from the FAERS database for pirfenidone and nintedanib, respectively. At the system organ class (SOC) level, both drugs have a positive signal value for "gastrointestinal disorders," "respiratory, thoracic, and mediastinal disorders," and "metabolism and nutrition disorders." Other positive signals for pirfenidone include "general disorders and administration site conditions," and "skin and subcutaneous tissue disorders," while for nintedanib, they were "investigations," "infections and infestations," and "hepatobiliary disorders." Some positive signals were consistent with the drug labels, including nausea, decreased appetite, and weight decreased identified in pirfenidone, as well as diarrhea, decreased appetite, abdominal pain upper, and epistaxis identified in nintedanib. We also identified unexpected signals not listed on the drug label, such as decreased gastric pH, and pneumothorax for pirfenidone, and constipation, flatulence for nintedanib. The median onset time for ADEs was 146 days for pirfenidone and 45 days for nintedanib, respectively. Although the two antifibrotics differed in the proportion of periods in which the ADEs occurred, these ADEs were likely to continue even after a year of treatment. In the external validation of JADER, the number of reports for pirfenidone and nintedanib were 265, and 1,327, respectively. The disproportionality analysis at the SOC and preferred term (PT) levels supports the FAERS results.

CONCLUSION: This study systematically investigates and compares the ADEs and their onset times at the SOC and specific PT levels for pirfenidone and nintedanib. Our results provide valuable pharmacological insights for the similarities and differences between the safety profiles of the two drugs and highlight the importance of monitoring and managing the toxicity profile associated with antifibrotic drugs.

PMID:40356972 | PMC:PMC12067420 | DOI:10.3389/fphar.2025.1530697

Orphanet J Rare Dis. 2025 May 12;20(1):226. doi: 10.1186/s13023-025-03758-5.

ABSTRACT

Hermansky-Pudlak Syndrome (HPS) type 1 (HPS-1) is an autosomal recessive disorder characterized by oculocutaneous albinism, platelet dysfunction, and pulmonary fibrosis (HPS-PF), the leading cause of mortality in these patients. HPS-PF manifests earlier than idiopathic pulmonary fibrosis, typically between 30 and 40 years of age. The etiology and drivers of HPS-PF progression remain poorly understood, and no FDA-approved therapies exist. Neutrophil extracellular traps (NETs) and neutrophil-derived mediators have emerged as key players in fibrosis, promoting lung injury, inflammation, and fibroblast activation. This study evaluates the role of neutrophil activation in age-related changes in patients with HPS-1, focusing on differences in inflammatory markers, neutrophil granules, and NETosis capacity. We observed significantly elevated levels of NETs, neutrophil granule proteins (NE, NGAL, LF), and inflammatory cytokines (IL-8, IL-6) in patients with HPS-1 older than 40 years compared to younger patients and healthy controls. Additionally, fibrosis-related markers (MMP-7 and MMP-8) were significantly higher in older patients. Elevated levels of anandamide (AEA), a circulating marker of HPS-PF, were positively associated with neutrophil granule markers in older patients, suggesting its association with fibrosis. Neutrophils from older patients also demonstrated increased NETosis capacity. These findings suggest that age-related neutrophil activation may contribute to an inflammatory environment that promotes fibrosis progression in HPS-1.

PMID:40355888 | DOI:10.1186/s13023-025-03758-5

BMJ Open. 2025 May 12;15(5):e094559. doi: 10.1136/bmjopen-2024-094559.

ABSTRACT

OBJECTIVES: Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease. Chest high-resolution CT (HRCT) is instrumental in IPF management, and the Quantitative Lung Fibrosis (QLF) score is a computer-assisted metric for quantifying lung disease using HRCT. This study aimed to assess the change in QLF score associated with a minimum clinically important difference (MCID) of IPF symptoms and physiological lung function, and also determine the MCID of QLF change associated with all-cause mortality to serve as an imaging biomarker to confirm disease progression and response to therapy.

DESIGN AND STUDY SETTING: We conducted post hoc analyses of prospective data from two IPF phase II studies of pamrevlumab, a fully human monoclonal antibody that binds to and inhibits connective tissue growth factor activity.

PARTICIPANTS: Overall, 152 patients with follow-up visits after week 24.

METHODS: We used the anchor-based Jaeschke's method to estimate the MCID of the QLF score that corresponded with the already established MCID of St. George's Respiratory Questionnaire (SGRQ) and percent-predicted forced vital capacity (ppFVC). We also conducted a Cox regression analysis to establish a sensitive and robust MCID of the QLF score in predicting all-cause mortality.

RESULTS: QLF changes of 4.4% and 3.6% corresponded to the established MCID of a 5-point increase in SGRQ and a 3.4% reduction in ppFVC, respectively. QLF changes of 1% (HR=4.98, p=0.05), 2% (HR=4.04, p=0.041), 20 mL (HR=6.37, p=0.024) and 22 mL (HR=6.38, p=0.024) predicted mortality.

CONCLUSION: A conservative metric of 2% can be used as the MCID of QLF for predicting all-cause mortality. This may be considered in IPF trials in which the degree of structural fibrosis assessed via HRCT is an endpoint. The MCID of SGRQ and FVC corresponds with a greater amount of QLF and may reflect that a greater amount of change in fibrosis is required before there is functional change.

TRIAL REGISTRATION NUMBER: NCT01262001, NCT01890265.

PMID:40355288 | DOI:10.1136/bmjopen-2024-094559

Medicine (Baltimore). 2025 May 9;104(19):e42376. doi: 10.1097/MD.0000000000042376.

ABSTRACT

This study employed bioinformatics to investigate potential molecular markers associated with idiopathic pulmonary fibrosis (IPF) and examined their correlation with immune-infiltrating cells. Microarray data for IPF were retrieved from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) and module genes were identified through Limma analysis and weighted gene co-expression network analysis. Enrichment analysis and protein-protein interaction network development were performed on the DEGs. Machine learning algorithms, including least absolute shrinkage and selection operator regression, random forest, and extreme gradient boosting, were applied to identify potential key genes. The predictive accuracy was assessed through a nomogram and a receiver operating characteristic (ROC) curve. Additionally, the correlation between core genes and immune-infiltrating cells was assessed utilizing the CIBERSORT algorithm. An IPF model was established in a human fetal lung fibroblast 1 (HFL-1) through induction with transforming growth factor β1 (TGF-β1), and validation was conducted via reverse transcription-quantitative polymerase chain reaction. A sum of 1246 genes exhibited upregulation, whereas 879 genes were downregulated. Pathway enrichment analysis and functional annotation revealed that DEGs were predominantly involved in extracellular processes. Four key genes - cd19, cxcl13, fcrl5, and slamf7 - were identified. Furthermore, ROC analysis demonstrated high predictive accuracy for these 4 genes. Compared to healthy individuals, lung tissues from IPF patients exhibited an increased presence of plasma cells, CD4 memory-activated T cells, M0 macrophages, activated dendritic cells, resting NK cells, and M2 macrophage infiltration. The upregulation of cd19, cxcl13, fcrl5, and slamf7 in TGF-β1-treated HFL-1 cells was confirmed, aligning with the findings from the microarray data analysis. cd19, cxcl13, fcrl5, and slamf7 serve as diagnostic markers for IPF, providing fresh perspectives regarding the fundamental pathogenesis and molecular mechanisms associated with this condition.

PMID:40355204 | DOI:10.1097/MD.0000000000042376

J Ethnopharmacol. 2025 May 10:119934. doi: 10.1016/j.jep.2025.119934. Online ahead of print.

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal disease. Baihe Gujin decoction (BHGJ), a traditional Chinese medicine consisting of ten medicine food homology herbs, has shown therapeutic effects in various lung diseases; however, its efficacy in ameliorating IPF and the underlying mechanisms remain unclear.

AIM OF THE STUDY: This study aimed to evaluate the effects of BHGJ on IPF and investigate its potential mechanisms.

MATERIALS AND METHODS: We established a bleomycin (BLM)-induced IPF model and performed proteomic analysis. The therapeutic effects of BHGJ on IPF were assessed by measuring lung index, hydroxyproline (HYP) content, lung function parameters, and histopathological changes. Mechanistic insights were further explored using western blot and RT-qPCR analyses.

RESULTS: Our results demonstrated that BHGJ significantly alleviated BLM-induced IPF, improved lung function, reduced histopathological damage, and decreased collagen deposition. BHGF reduced apoptosis and inhibited EMT in TGF-β-induced A549 cells. Proteomic analysis revealed that its effects were associated with the modulation of the proline metabolism pathway.

CONCLUSIONS: BHGJ effectively attenuated IPF progression via regulating proline metabolism, providing a potential therapeutic strategy for pulmonary fibrosis.

PMID:40354839 | DOI:10.1016/j.jep.2025.119934

BMC Pulm Med. 2025 May 10;25(1):229. doi: 10.1186/s12890-025-03703-z.

ABSTRACT

BACKGROUND: The role of chronic inflammation in non-idiopathic pulmonary fibrosis fibrotic interstitial lung disease (non-IPF f-ILD) remains unclear, with varied responses to anti-inflammatory or immunosuppressive therapy. A reliable predictor for guiding treatment response may enhance clinical decision-making and minimize adverse treatment effects. We hypothesized that elevated C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) may be associated with improved treatment response.

METHODS: Our retrospective cohort study compared treatment response to anti-inflammatory therapy in patients with non-IPF f-ILD stratified by baseline CRP and ESR levels. Treatment response was defined as: (1) relative increase in percent predicted forced vital capacity (FVC%) ≥ 5% in 6 months or ≥ 10% in 12 months; or (2) no change or any increase in FVC% if FVC% decline was noted prior to treatment. Logistic regression was used to delineate outcome predictors with FVC% change over time assessed with linear mixed effects models.

RESULTS: Of 832 non-IPF f-ILD patients screened, 167 received anti-inflammatory therapy and baseline inflammatory marker testing stratified into high vs. low-to-normal groups (104 vs. 63, respectively). Median age was 64 years, and 57% were diagnosed with a systemic autoimmune rheumatic disease (SARD). Treatment response was greater in those with elevated inflammatory markers (56% vs. 35%; OR 2.45 [1.243-4.828] P = 0.010) even after adjustment for a priori covariables. SARD diagnosis was associated with treatment response (OR 2.90 [1.45-5.81] P = 0.003), independent of inflammatory marker level. A positive FVC% slope was observed in treated patients with initially elevated inflammatory markers (P = 0.003).

CONCLUSION: Patients with non-IPF f-ILD and elevated inflammatory markers appear to be more responsive to anti-inflammatory therapy with slower FVC decline over time. These findings suggest baseline serum ESR and CRP may be feasible and reliable predictors of treatment response in certain subgroups.

PMID:40348969 | DOI:10.1186/s12890-025-03703-z

Int J Cancer. 2025 May 9. doi: 10.1002/ijc.35471. Online ahead of print.

ABSTRACT

Tumor-associated fibrosis contributes to an immunosuppressive microenvironment that hinders effective anti-tumor immune responses. This study investigates the potential of IOA-289, a novel autotaxin (ATX) inhibitor, which blocks lysophosphatidate (LPA) production and signaling, in modulating fibrosis in breast tumors. Bioinformatic analysis of human breast tumors revealed a strong correlation between levels of LPA1,-4 receptors and extracellular matrix (ECM) genes. Interaction of ECM molecules and integrin β1/CD44 between myofibroblasts and other cell types had the highest contribution to cell-cell communication. We showed that LPA induced α-smooth muscle actin mRNA in mouse mammary fibroblasts and increased expressions of collagen type-I α1 chain (COL1A1) and lamininγ1. IOA-289 decreased the expressions of COL1A1, fibronectin-1, and transforming growth factor β1 (TGFβ1) in E0771 breast tumors in mice. Masson's trichrome staining revealed a marked decrease in collagen deposition within breast tumors of IOA-289-treated mice. Decreased tumor fibrosis aligns with previous findings that IOA-289 enhanced the infiltration of CD8+ cytotoxic T cells and decreased fibrotic factors including leukemia inhibitory factor and transforming growth factor-beta1 in tumors. We also demonstrated that E0771 cells express negligible ATX and LPA receptors. Therefore, ATX inhibition did not affect cancer cells directly in our model. These results underscore the potential of ATX inhibitors in reprogramming the tumor microenvironment to favor anti-tumor immunity and attenuate fibrosis. ATX inhibitors are in clinical trials for treating idiopathic pulmonary fibrosis and pancreatic cancer. Our results support the development of ATX inhibitors as a strategy for improving the treatment of breast cancer and other diseases involving fibrosis.

PMID:40345856 | DOI:10.1002/ijc.35471

J Heart Lung Transplant. 2025 May 7:S1053-2498(25)01961-8. doi: 10.1016/j.healun.2025.04.022. Online ahead of print.

ABSTRACT

As we have previously shown, Idiopathic pulmonary fibrosis lung transplant recipients (IPF-LTRs) with short-telomere length (STL) are prone to develop significant cytopenias and poor tolerance to cell cycle inhibitors, specifically Mycophenolate mofetil (MMF), post-transplant. We investigated the use of Belatacept as an alternative immunosuppressive agent in a prospective, open-label cohort of 9 ST-IPF-LTRs at our institution. These patients were either challenged with MMF (majority) or immediately started on Belatacept post-transplant with the goal to bridge to Everolimus, an mTOR inhibitor that is commonly used post-transplant. We describe outcomes in the first-year post-transplant including the incidence of Acute Cellular Rejection (ACR), Epstein-Barr Virus (EBV) viremia, and one case of Post-Transplant Lymphoproliferative Disorder (PTLD) at 13 months. The use of Belatacept post-lung transplant may be an acceptable short-term alternative therapy to cell cycle inhibitors in ST-IPF-LTRs with cytopenias but may lead to higher risk of EBV viremia and PTLD when Belatacept is used long-term in these patients.

PMID:40345564 | DOI:10.1016/j.healun.2025.04.022

Prim Care Companion CNS Disord. 2025 May 1;27(2):24cr03883. doi: 10.4088/PCC.24cr03883.

NO ABSTRACT

PMID:40344540 | DOI:10.4088/PCC.24cr03883

J Appl Toxicol. 2025 Jun;45(6):948-963. doi: 10.1002/jat.4758. Epub 2025 Jan 30.

ABSTRACT

4,4'-Diaminodiphenylmethane (DAPM) is an aromatic amine used in the industrial synthesis of polyurethane. In rats, acute DAPM exposure induces biliary epithelial cell injury in the liver, but subchronic exposure promotes a female-specific pulmonary arterial hypertension (PAH). PAH in humans is four times more prevalent in women than men. To shed light on mechanisms explaining the female selectivity of PAH in humans, we examined molecular pathways underlying DAPM-induced PAH in female rats. Intersections between DAPM-mediated hepatic injury and DAPM-induced PAH were also interrogated. Intact compared to ovariectomized female rats were gavaged once weekly for 12 weeks with DAPM or vehicle. Morphometric analysis in lung sections was used to quantify PAH pathology. mRNA from liver were assessed for DAPM-induced alterations in genes associated with aryl hydrocarbon receptor, estrogen response, and endothelin-1 signaling. mRNA from pulmonary arteries were subjected to transcript profiling, and pathways associated with differentially expressed genes were mapped. First, DAPM-induced PAH was exacerbated by ovariectomy. Although DAPM-mediated liver injury per se was not correlated with its induction of PAH, increases in levels of the potent vasoconstrictor endothelin-1 were exacerbated by ovariectomy and were correlated with increased expression of Edn1 in the liver. In pulmonary arteries, transcript profiling revealed that DAPM and ovariectomy interacted to dysregulate estrogen receptor, VEGF, PI3K/AKT, endothelin-1, glucocorticoid receptor, IL-17A, and idiopathic pulmonary fibrosis signaling. One of the most dysregulated genes associated with both DAPM and estrogen status was Serpine1.

PMID:40344275 | DOI:10.1002/jat.4758