AMIA Jt Summits Transl Sci Proc. 2025 Jun 10;2025:607-613. eCollection 2025.

ABSTRACT

Although rare diseases (RD) are gaining priority in healthcare worldwide, developing research policies for studying them in public settings remains challenging due to the limited evidence available. Evidence generation is crucial for rare diseases, requiring systematic assessment of study quality across multiple sources. Given the scarcity of patients, literature and clinical trial data for orphan drugs, we developed RD-LIVES-a tool designed to automatically accelerate evidence collection from literature and clinical trials for systematic reviews and meta-analyses. This tool enhances our understanding of treatment outcomes, determines appropriate follow-up durations, and informs the required treatment impact size for new drugs. Using Idiopathic Pulmonary Fibrosis (IPF) as an example, we demonstrate how RD-LIVES automates evidence collection and element extraction. The results indicate that RD-LIVES plays a vital role in designing costly prospective trials and has the potential to increase the likelihood of successful trial outcomes.

PMID:40502246 | PMC:PMC12150729

AMIA Jt Summits Transl Sci Proc. 2025 Jun 10;2025:280-289. eCollection 2025.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a rare disease that is challenging to diagnose. Patients with IPF often spend years awaiting a diagnosis after the onset of initial respiratory symptoms, and only a small percentage receive antifibrotic treatment. In this study, we examine the associations between social determinants of health (SDoH) and two critical factors: time to IPF diagnosis following the onset of initial respiratory symptoms, and whether the patient receives antifibrotic treatment. To approximate individual SDoH characteristics, we extract demographic-specific averages from zip code-level data using the American Community Survey (via the U.S. Census Bureau API). Two classification models are constructed, including logistic regression and XGBoost classification. The results indicate that for time-to-diagnosis, the top three SDoH factors are education, gender, and insurance coverage. Patients with higher education levels and better insurance are more likely to receive a quicker diagnosis, with males having an advantage over females. For antifibrotic treatment, the top three SDoH factors are insurance, gender, and race. Patients with better insurance coverage are more likely to receive antifibrotic treatment, with males and White patients having an advantage over females and patients of other ethnicities. This research may help address disparities in the diagnosis and treatment of IPF related to socioeconomic status.

PMID:40502238 | PMC:PMC12150710

AMIA Jt Summits Transl Sci Proc. 2025 Jun 10;2025:290-299. eCollection 2025.

ABSTRACT

The Systematic reviews (SRs) for Idiopathic Pulmonary Fibrosis (IPF) play a crucial role in guiding evidence-based healthcare by synthesizing data across multiple studies. A key factor in ensuring the reliability and applicability of these reviews is the geographic diversity of the authors involved, as this can significantly influence the generalizability of findings. Traditional 2D maps used to visualize author locations often fall short in capturing the depth and regional disparities effectively, as overlapping points or dense clusters can obscure critical details, resulting in an incomplete view of geographic distribution. To address these limitations, this study introduces a novel approach that combines a 3D geographic map and a Temporal-Spatial Graph Attention Network (TS-GAT) to assess and visualize the geographic diversity of authors in SRs on IPF. The 3D visualization provides an enhanced, layered representation of author locations, revealing hidden regional disparities and biases. The TS-GAT captures both temporal and spatial relationships in the author collaboration network, allowing for deeper insights into the evolution of geographic representation over time. This integrated approach aims to uncover potential biases in global representation, offering a comprehensive understanding of the geographic spread and temporal trends in authorship within SRs, ultimately contributing to more balanced and inclusive evidence synthesis.

PMID:40502229 | PMC:PMC12150703

bioRxiv [Preprint]. 2025 Jun 8:2025.06.05.658120. doi: 10.1101/2025.06.05.658120.

ABSTRACT

Aberrant epithelial regeneration and immune remodeling are hallmarks of chronic lung diseases such as idiopathic pulmonary fibrosis (IPF), COPD, and post-viral syndromes. Yet how cellular context shapes these trajectories remains unresolved. We present a tunable, primary rat-derived lung organoid model that systematically varies immune, epithelial, and mesenchymal inputs to reveal how composition alone dictates epithelial plasticity and macrophage polarization. Across conditions, we observed the spontaneous emergence of disease-relevant transitional cell states, including Sox9+ stressed progenitors, RAS/AT0-like intermediates, and hillock-like cells, alongside distinct macrophage activation profiles. In mesenchyme-rich contexts, epithelial-immune-mesenchymal crosstalk appeared to reinforce inflammatory signaling and stabilize transitional persistence, while immune-dominant inputs favored ATI-like repair and squamous remodeling. Notably, hillock-like cells displayed context-specific polarization and expressed immune-regulatory genes, suggesting a role as epithelial orchestrators that help calibrate inflammatory response during regeneration. Connectomic analysis revealed that regenerative outcomes were associated with dynamic multicellular signaling networks that integrate stress sensing, immune coordination, and epithelial fate. This platform provides a tractable system for modeling context-specific repair and regenerative mechanisms and could inform therapeutic strategies aimed at redirecting epithelial fate in chronic lung disease.

PMID:40501591 | PMC:PMC12157698 | DOI:10.1101/2025.06.05.658120

Respir Res. 2025 Jun 11;26(1):213. doi: 10.1186/s12931-025-03180-2.

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a respiratory disease linked with deregulated immune responses, leading to hyperinflammation, acute respiratory distress syndrome, and pulmonary fibrosis, often with fatal outcomes. Neutrophils play a central role in COVID-19 pathogenesis, with elevated peripheral blood neutrophil counts correlating with disease severity. Despite extensive research, the molecular processes associated with neutrophil hyperactivation in COVID-19 remain elusive.

METHODS: To investigate the molecular signatures underlying neutrophil-driven pathology, we conducted transcriptome analysis in neutrophils isolated from the peripheral blood of COVID-19 patients versus healthy individuals. To evaluate the specificity of identified neutrophil signatures in COVID-19, we extended our transcriptomic analysis to neutrophils from patients with idiopathic pulmonary fibrosis (IPF), a non-infectious fibrotic lung disease. Additionally, immunofluorescence staining was performed on lung biopsy specimens from IPF patients to validate transcriptomic findings at the tissue level.

RESULTS: Our analysis revealed significant transcriptional changes in COVID-19 neutrophils, particularly in pathways involved in immune regulation, inflammation, and antiviral responses. Additionally, pathways associated with autophagy and chromatin remodeling were upregulated, while translation-related processes were suppressed, indicating an increased predisposition for neutrophil extracellular trap (NET) release. This neutrophil transcriptional signature in COVID-19 appears to be associated with the previously reported deregulation of the Activin/Follistatin system in the periphery. Notably, a comparative transcriptomic analysis with neutrophils isolated from IPF patients revealed the induction of substantially overlapping inflammatory processes, suggesting common deregulated responses in COVID-19 and IPF. Consistently, significant NET formation, a hallmark of COVID-19-related inflammation, was observed within lung biopsies from IPF patients.

CONCLUSION: By delineating both shared and disease-specific molecular pathways, our findings validate the critical role of neutrophils in COVID-19 and IPF pathophysiology, highlighting their involvement in balancing the inflammatory response across diverse lung diseases.

PMID:40500689 | DOI:10.1186/s12931-025-03180-2

Front Cell Infect Microbiol. 2025 May 27;15:1595500. doi: 10.3389/fcimb.2025.1595500. eCollection 2025.

ABSTRACT

INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease. However, the pathogeny of IPF is poorly understood, and therapeutic options are very limited. Periodontitis (PD) is a chronic inflammatory disease that leads to dysbiosis of both the oral microbiome and host immune responses. While previous studies have suggested a PD-IPF association, insights into the mechanisms remain limited.

METHODS: The PD mouse model was established by the ligation of molars and oral inoculation of subgingival plaques from PD patients and subsequently incorporated with a bleomycin-induced pulmonary fibrosis model. The effect of PD on pulmonary fibrosis was determined. Changes of immune cells were analysed using flow cytometry. Moreover, the microbiome changes of the lungs and oral cavity were assessed by 16S rRNA gene sequencing and fluorescence in situ hybridization. Finally, the effect and mechanism of the specific PD pathogen on pulmonary fibrosis were determined.

RESULTS: PD significantly aggravated pulmonary fibrosis in mice by increasing the infiltration of neutrophils and Th17 cells. Neutrophils and Th17 cells are critical in PD-induced aggravation of pulmonary fibrosis, and Th17 cells regulate neutrophils via IL-17A. The PD pathogen Porphyromonas gingivalis (Pg) was detected enriched in both the oral cavity and lungs. Pg was further determined to exacerbate pulmonary fibrosis by increasing the expansion of neutrophils and Th17 cells in mice.

CONCLUSION: PD aggravates pulmonary fibrosis in mice, which is likely induced by Pg-promoted infiltration of neutrophils and Th17 cells. Treatment targeting PD or Pg might be a promising strategy to clinically ameliorate IPF.

PMID:40496020 | PMC:PMC12149129 | DOI:10.3389/fcimb.2025.1595500

Tuberc Respir Dis (Seoul). 2025 Jun 10. doi: 10.4046/trd.2025.0056. Online ahead of print.

ABSTRACT

Antifibrotic drugs, available for the best part of the last decade in many parts of the world, has improved outcomes in patients with idiopathic pulmonary fibrosis and progressive pulmonary fibrosis. However, it is unclear whether patients suffering from these devastating conditions have timely and adequate access to antifibrotic therapy in the Asia Pacific region (APAC). In this mixed-methods narrative review of 12 APAC countries, integration of questionnaire-based insights of 31 regional clinical experts in interstitial lung disease (ILD) with publicly available pharmaco-economic information has been used to understand how country-specific challenges impact on antifibrotic accessibility. Overall, a broad range of approaches are utilised to provide antifibrotic treatment including centrally or state-determined drug budgets, pharmaceutical industry-subsidised initiatives, charitable support and self-paying (out-of-pocket) options. Impediments to antifibrotic access commonly arise from prohibitive drug pricing in relation to income, absence of universal coverage for pharmaceutical costs, lack of formal pharmaco-economic analysis or restrictions on the use of generic preparations. Unequal access to antifibrotic drugs is a vital unmet therapeutic need in the APAC region, one that is likely to be exacerbated by a rising fibrotic interstitial lung disease burden.

PMID:40494506 | DOI:10.4046/trd.2025.0056

Int Immunopharmacol. 2025 Jun 9;161:115017. doi: 10.1016/j.intimp.2025.115017. Online ahead of print.

ABSTRACT

BACKGROUND: NOTCH and autophagy significantly impact the pathogenesis of idiopathic pulmonary fibrosis (IPF); however, studies exploring their heterogeneity and potential correlation at the single-cell level are still lacking. Identifying the feature genes that are commonly regulated by both NOTCH and autophagy could significantly increase our understanding of IPF.

METHODS: We used single-cell RNA sequencing (scRNA-seq) to investigate the heterogeneity of NOTCH and autophagy activity across various cell types following IPF, with the aim of obtaining comprehensive biological insights into IPF. We utilized the AUCell, Ucell, singscore, ssGSEA, and AddModuleScore algorithms to identify common positively and negatively regulated NOTCH and autophagy activities at the IPF cellular level. Furthermore, we employed six machine learning algorithms, eXtreme Gradient Boosting, Boruta, random forest, least absolute shrinkage and selection operator, GBM, and SVM-RFE, to identify the optimal feature genes related to IPF at the BulkRNA-seq level. We further leveraged CellChat and pseudotime analysis to delve into the potential biological regulatory mechanisms of the characteristic genes.We further performed protein-level validation of key NOTCH and autophagy markers using Western blotting to confirm the consistency between transcriptomic predictions and pathway activation.

RESULTS: For the first time, at the cellular level, we showed that NOTCH and autophagy activities exhibit heterogeneity across different cell layers following IPF. However, their activities are remarkably consistent; they are highly active in macrophages, fibroblasts, monocytes, and lymphatic endothelial cells, whereas they display lower activity in NK, T, and plasma cells. These findings indicate a correlation between these two pathways in IPF. Consequently, we defined a set of genes that coregulate both pathways at the IPF level. Using various machine learning algorithms, we further identified key predictive genes for IPF, namely, IGFBP7, PPIC, and RUNX1.Western blot assays confirmed that the protein expression of NOTCH1, HEY1, HES1, Beclin1, and P62 followed the same activation trends inferred from transcriptomic analysis.

CONCLUSIONS: In IPF, IGFBP7, PPIC, and RUNX1 might simultaneously upregulate NOTCH and autophagy activities in fibroblasts and lymphatic endothelial cells and further contribute to IPF progression.

PMID:40494203 | DOI:10.1016/j.intimp.2025.115017

Int Immunopharmacol. 2025 Jun 9;161:115003. doi: 10.1016/j.intimp.2025.115003. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease characterized by inflammation and fibrosis. Demethyleneberberine (DMB), a natural compound derived from traditional Chinese medicine, possesses both anti-inflammatory and antifibrotic properties. This study investigated the therapeutic potential of DMB in pulmonary fibrosis and elucidated its underlying mechanisms of action.

MATERIALS AND METHODS: Pulmonary fibrosis was induced in male C57BL/6 mice via intratracheal administration of bleomycin (BLM, 1.5 mg/kg). The mice were randomly assigned to four groups (n = 10 per group): control, BLM, BLM + DMB (5 mg/kg), and BLM + DMB (10 mg/kg). An in vitro model of pulmonary fibrosis was established by stimulating MLE-12 cells with transforming growth factor-β1 (TGF-β1, 5 ng/mL). Lung structural and functional changes were assessed using hematoxylin and eosin staining, lung-function testing, and micro-computed tomography. The relationship between NLRP3 and EMT during the process of DMB alleviating pulmonary fibrosis was further explored by inducing NLRP3 overexpression in vitro.

RESULTS: DMB treatment significantly alleviated histopathological alterations and reduced collagen deposition in lung tissues. It also inhibited activation of both the canonical and non-canonical NLRP3 inflammasomes. DMB reversed EMT-related marker expression in both in vivo and in vitro models. Notably, overexpression of NLRP3 in vitro partially abrogated the suppressive effect of DMB on the EMT.

CONCLUSION: DMB ameliorates pulmonary fibrosis by inhibiting NLRP3 inflammasome activation and suppressing the EMT. Inhibition of NLRP3 appears to play a critical role in mediating the antifibrotic effects of DMB. These findings imply that DMB may represent a promising therapeutic candidate for clinical management of IPF.

PMID:40494202 | DOI:10.1016/j.intimp.2025.115003

J Clin Invest. 2025 Jun 10:e188819. doi: 10.1172/JCI188819. Online ahead of print.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a fatal fibrotic lung disease characterized by impaired fibroblast clearance and excessive extracellular matrix (ECM) protein production. Wilms' Tumor 1 (WT1), a transcription factor, is selectively upregulated in IPF fibroblasts. However, the mechanisms by which WT1 contributes to fibroblast accumulation and ECM production remain unknown. Here, we investigated the heterogeneity of WT1-expressing mesenchymal cells using single-nucleus RNA sequencing of distal lung tissues from IPF patients and control donors. WT1 was selectively upregulated in a subset of IPF fibroblasts that co-expressed several pro-survival and ECM genes. The results of both loss-of-function and gain-of-function studies are consistent with a role for WT1 as a positive regulator of pro-survival genes to impair apoptotic clearance and promote ECM production. Fibroblast-specific overexpression of WT1 augmented fibroproliferation, myofibroblast accumulation, and ECM production during bleomycin-induced pulmonary fibrosis in young and aged mice. Together, these findings suggest that targeting WT1 is a promising strategy for attenuating fibroblast expansion and ECM production during fibrogenesis.

PMID:40493404 | DOI:10.1172/JCI188819

ERJ Open Res. 2025 Jun 9;11(3):00926-2024. doi: 10.1183/23120541.00926-2024. eCollection 2025 May.

ABSTRACT

BACKGROUND: This study aims to report real-life data on the characteristics and treatment patterns of patients with fibrosing interstitial lung disease (ILD; except idiopathic pulmonary fibrosis) across multiple specialised centres in Germany. Eligibility criteria included ILD affecting >10% of lung parenchyma on high-resolution computed tomography, a single breath diffusion capacity for carbon monoxide (D LCO) ≤80% predicted and active treatment of lung disease.

METHODS: As of the interim analysis cut-off, 655 patients (mean±sd age 65.9±11.7 years, 54.5% male) were included. The most common ILD subtypes were fibrosing hypersensitivity pneumonitis (31.2%), fibrosing ILD (22.0%), rheumatoid arthritis and connective tissue disease ILDs (13.0%) and unclassifiable fibrosing ILD (13.0%).

RESULTS: Lung function metrics included total lung capacity at 68.3±17.6% predicted, forced vital capacity at 69.8±19.8% predicted, forced expiratory volume in 1 s at 73.7±19.5% predicted and D LCO at 33.8±15.6% predicted. Current treatments included oral steroids (62.6%), antifibrotic therapy (50.7%), azathioprine (14.4%), methotrexate (10.2%) and mycophenolate mofetil (11.1%). Patients on antifibrotic therapy were typically older at diagnosis and registry inclusion, more often male, had more comorbidities, a lower 6-min walk distance and reduced lung function metrics compared with those not on antifibrotic therapy. Notably, 27.3% of the patients on antifibrotic therapy did not meet progression criteria (INBUILD), whereas 40.1% of patients not receiving antifibrotic therapy did meet those criteria.

CONCLUSION: The patient characteristics observed align with those observed in randomised controlled trials and other noninterventional studies. Patients on antifibrotic therapy generally had more severe disease profiles.

PMID:40491463 | PMC:PMC12147108 | DOI:10.1183/23120541.00926-2024

OMICS. 2025 Jun 10. doi: 10.1089/omi.2025.0066. Online ahead of print.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) and pulmonary hypertension (PH) are two chronic conditions that can coexist occasionally, resulting in high morbidity and mortality. Despite their clinical association, the underlying genetic mechanisms and therapeutic targets that might link these two chronic disorders remain poorly understood. The present study used in silico analyses and machine learning to uncover genetic features and potential therapeutic targets shared by IPF and PH. Differentially expressed genes (DEGs) were identified using RNA sequencing data from the Gene Expression Omnibus, which revealed a total of 13 common DEGs between IPF and PH. Importantly, among the identified genes, TFF3 was significantly upregulated in both diseases. TFF3 is targeted by aminoglutethimide as identified through the Drug Gene Interaction Database, and with an interaction score of 3.26. Using the Protein Contact Atlas, PROCHECK, PROSA, and ProtParam tools, the structural model of TFF3 was validated. Finally, molecular docking analysis demonstrated a binding affinity score of -6.1 kcal/mol between TFF3 and aminoglutethimide, indicating a stable and potentially effective interaction between aminoglutethimide and the target protein. Aminoglutethimide displayed favorable ADMET properties as well. In conclusion, this in silico study reports (1) potential overlapping molecular links between IPF and PH, and (2) in silico potential of aminoglutethimide and TFF3 in drug repurposing for therapeutic interventions targeting both IPF and PH. These findings also challenge the traditional paradigm of pharmaceutical innovation that has long relied on the "one drug, one disease" premise, and highlight the potentials of "one drug, polydisease" paradigm of drug discovery and development.

PMID:40491360 | DOI:10.1089/omi.2025.0066

Zhonghua Jie He He Hu Xi Za Zhi. 2025 Jun 12;48(6):592-593. doi: 10.3760/cma.j.cn112147-20241202-00713.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a disease of unknown etiology characterized by chronic progressive fibrosing interstitial lung disease. In 2017, the INBUILD study introduced the concept of progressive fibrosing interstitial lung disease (PF-ILD) and confirmed the efficacy of nintedanib for its treatment. In 2022, the ATS/ERS/JRS/ALAT guidelines established the concept of progressive pulmonary fibrosis (PPF) along with a standardized diagnostic criterion for non-IPF forms of progressive fibrosing interstitial lung disease. PPF serves as a collective term for chronic progressive fibrosing interstitial lung diseases that exclude IPF, with disease progression similar to that of IPF and a poor prognosis. Although some scholars propose that PPF can replace the preceding concept of PF-ILD, the author contends that PPF cannot substitute for PF-ILD, and the term "PF-ILD" should remain in use. The integration of IPF and PPF can be considered equivalent to PF-ILD and can be succinctly expressed as: PF-ILD=IPF+PPF.

PMID:40491154 | DOI:10.3760/cma.j.cn112147-20241202-00713

Zhonghua Jie He He Hu Xi Za Zhi. 2025 Jun 12;48(6):589-591. doi: 10.3760/cma.j.cn112147-20241218-00745.

ABSTRACT

Interstitial lung diseases (ILD) comprise a group of diseases with varied etiologies and trajectories. Some terminologies in ILD could be easily misapplied in clinical practice if just interpreted literally, which significantly hamper diagnostic accuracy and scientific reproducibility. Therefore, correct understanding and appropriate usage of these terminologies are helpful to harmonize clinical practice and research methodologies. This article will elaborate on five noun concepts that are easily misused in the diagnosis and treatment of ILD, including interstitial lung abnormality (ILA), post-coronavirus interstitial lung disease (PC-ILD), progressive pulmonary fibrosis (PPF), hypersensitivity pneumonitis (HP) and unclassifiable interstitial lung disease (uILD).

PMID:40491153 | DOI:10.3760/cma.j.cn112147-20241218-00745

Int J Rheum Dis. 2025 Jun;28(6):e70320. doi: 10.1111/1756-185X.70320.

ABSTRACT

BACKGROUND: Analyzing longitudinal real-world data with nonuniform study-time intervals is challenging. This study aimed to identify subgroups in heterogeneous clinical courses of idiopathic inflammatory myopathies-associated interstitial lung disease (IIM-ILD) using a growth rate model and to assess their prognostic significance.

METHODS: In this retrospective cohort study, 243 chest high-resolution computed tomography (HRCT) scans from 80 patients with IIM-ILD were analyzed using a computer-aided quantification system to estimate quantitative lung fibrosis (QLF) scores. Longitudinal patterns were identified through a growth-rate model, and a landmark survival analysis was performed using the last HRCT date as an anchor.

RESULTS: Using the growth-rate model, we identified five different patterns in the serial QLF scores: progressive (n = 19), improving (n = 20), convex (n = 10), others (mostly concave, n = 22), and stable (n = 9). When the group with the progressive pattern was divided into the rapid progression and slow progression by the median progression rate (g = 1.029%/month), the rapid progressive group was significantly associated with mortality (Hazard ratio 15.926, 95% confidence interval 1.079-548.324, p = 0.043), compared to the reference group. However, the intensity of immunosuppression or QLF scores at landmark time were not associated with mortality.

CONCLUSION: Combined volumetric measurement of lung fibrosis and application of growth-rate model had the potential to identify subgroups in analyzing complex, dynamic real-world data of IIMs-ILD. This approach may help extrapolate the future course and provide useful information about prognosis in patients with ILD.

PMID:40488961 | DOI:10.1111/1756-185X.70320

Acta Pharm Sin B. 2025 May;15(5):2301-2322. doi: 10.1016/j.apsb.2025.03.023. Epub 2025 Mar 13.

ABSTRACT

Alternative splicing (AS) serves as a fundamental regulatory mechanism in gene expression, contributing to proteomic diversity by generating an array of mRNA isoforms from precursor mRNA via distinct splice site combinations. In light of the limited therapeutic options currently available, the exploration of AS as a target for drug development is of paramount importance. This review offers an exhaustive analysis of the biological functions and underlying molecular mechanisms associated with various AS-induced splice variants, RNA-binding proteins, and cis-elements, highlighting their significance as clinical biomarkers. We place particular emphasis on the current therapeutic applications of AS in an array of lung diseases, including but not limited to lung cancer, cystic fibrosis, silicosis, acute respiratory distress syndrome, pneumonia, asthma, chronic obstructive pulmonary diseases, pulmonary arterial hypertension, and idiopathic pulmonary fibrosis. The review delves into the role of AS events in the diagnosis and treatment of lung diseases, focusing on the regulatory influence of splicing factors and RNA-binding proteins, while also enumerating the mutated components implicated in AS misregulation. Consequently, a comprehensive understanding of the intricate mechanisms governing these splicing events could potentially offer novel avenues for the development of splicing-targeted therapeutics and diagnostic tools for the prevention and treatment of lung diseases.

PMID:40487667 | PMC:PMC12145001 | DOI:10.1016/j.apsb.2025.03.023

Thorax. 2025 Jun 8:thorax-2024-222149. doi: 10.1136/thorax-2024-222149. Online ahead of print.

ABSTRACT

BACKGROUND: Prior work suggests different interstitial lung diseases (ILDs) that share the radiological usual interstitial pneumonia (UIP) pattern have an overall worse prognosis. However, epidemiological data with longitudinal sampling and replication remains lacking.

METHODS: Data was used from the Pulmonary Fibrosis Foundation Patient Registry (PFF-PR) (n=932) and a meta-cohort of ILD research studies (n=1579). Linear mixed-effects models and Cox proportional hazard models were used to determine forced vital capacity (FVC) slopes and 5-year transplant-free survival, respectively, by ILD diagnosis and UIP radiological pattern. Secondarily, we examined FVC and survival by diagnosis and radiological fibrosis quantified by data-driven texture analysis (DTA) in the PFF-PR. Models were adjusted for age, sex, smoking and antifibrotic and immunosuppression medication use.

RESULTS: The proportions of idiopathic pulmonary fibrosis (IPF), fibrotic hypersensitivity pneumonitis (FHP) and connective tissue disease (CTD)-ILD were the following for PFF-PR (70%, 11%, 19%) and meta-cohort (21%, 32%, 47%). In the PFF-PR, CTD-ILD with UIP CT pattern was associated with slower FVC decline (-34.4 mL/year) compared with IPF (-158.4 mL/year) and longer transplant-free survival (HR 0.50, 95% CI 0.29 to 0.85). This was replicated in the meta cohort for FVC (-53.1 vs -185.9 mL/year, p<0.0001) and survival (HR 0.38, 95% CI 0.27 to 0.53). A similar pattern was seen using DTA to objectively categorise patients into higher and lower radiological fibrosis. Between IPF and FHP-UIP, FVC decline was not significantly different in the PFF-PR (-203.4 vs -158.4 mL/year, p=0.58) and meta-cohort (-124.0 vs -185.9 mL/year, p=0.25).

CONCLUSIONS: Even in the presence of a UIP CT pattern, there may still be differences in lung function over time and survival, particularly for CTD-ILD.

PMID:40484639 | DOI:10.1136/thorax-2024-222149

Chest. 2025 Jun 6:S0012-3692(25)00687-7. doi: 10.1016/j.chest.2025.05.036. Online ahead of print.

ABSTRACT

BACKGROUND: Identifying biomarkers is vital for interstitial lung disease (ILD) management and prognostication. While anti-Ro52 antibodies are frequently detected in autoimmune diseases, their significance in ILD remains unclear.

RESEARCH QUESTION: What is the prognostic significance of anti-Ro52 positivity in patients with ILD?

STUDY DESIGN AND METHODS: This retrospective cohort study used an ILD registry of patients seen at an academic tertiary hospital's ILD clinic between 2015 and 2024. All patients diagnosed with ILD and tested for anti-Ro52 antibody status were divided into anti-Ro52 positive (Anti-Ro52+) and negative (Anti-Ro52-) groups. The primary outcome was ILD progression or all-cause death. ILD progression was defined as any of the following: hospitalization due to ILD; absolute decline in forced vital capacity percent of predicted value ≥10% from baseline; or lung transplantation. Kaplan-Meier method and Cox proportional hazards regression model were used for survival analysis.

RESULTS: Of 1,026 patients tested for the anti-Ro52 antibody (median age: 70 years; 52% male), 154 (15%) were Anti-Ro52+. Underlying ILD subtypes were as follows: interstitial pneumonia with autoimmune features (IPAF) (n = 489, 48%), connective tissue disease-ILD (n = 132, 13%), idiopathic pulmonary fibrosis (n = 103, 10%), hypersensitivity pneumonitis (n = 61, 6%), and other idiopathic ILD (n = 241, 24%). The Anti-Ro52+ group was younger (median age 67 vs. 70 years), was more likely to have CTD (28% vs. 10%) and more frequently had a copositive myositis-specific antibody (29% vs. 16%). After a median follow-up of 25.6 months, anti-Ro52+ subjects had a higher risk of ILD progression or death (hazard ratio 2.10; 95% CI, 1.61-2.73; P<0.001) and had a higher risk of lung transplant or death (hazard ratio 1.61; 95% CI, 1.11-2.35; P=0.014) on multivariable analysis.

INTERPRETATION: Anti-Ro52 seropositive ILD is associated with significantly worse progression-free and transplant-free survival and may inform disease prognostication and monitoring.

PMID:40484372 | DOI:10.1016/j.chest.2025.05.036

Respir Med Res. 2025 May 8;88:101175. doi: 10.1016/j.resmer.2025.101175. Online ahead of print.

ABSTRACT

INTRODUCTION: Data about interstitial lung diseases (ILDs) epidemiology in the Afro-Caribbean population is lacking. Differences in incidence and prevalence compared to European populations have already been reported. The main objective of this study was to estimate ILD incidence in Guadeloupe overall and by etiology. The secondary objective was to determine the clinical, demographic, and environmental characteristics of patients with ILD.

MATERIALS AND METHODS: We conducted a descriptive epidemiological study to estimate the incidence and prevalence of ILD in Guadeloupe between 2013 and 2019 and assess its etiological distribution.

RESULTS: A total of 235 ILD cases in Guadeloupe were included. The incidence of ILD was 6.87 cases per 100,000 population per year, and the prevalence was 32.22 cases per 100,000 population. ILDs associated with connective tissue diseases accounted for 34 % of cases, with an incidence of 2.12 per 100,000 population. Sarcoidosis represented 31 % of cases, with an incidence of 1.72 per 100,000 population. Idiopathic ILDs made up 21 % of cases, with an incidence of 1.72 per 100,000 population. In this cohort, 25 % of patients were smokers, and 29 % of those with idiopathic pulmonary fibrosis (IPF) were farmers or agricultural workers.

CONCLUSION: We report the first study on ILD epidemiology in a native Afro-Caribbean population. Incidence and prevalence figures are lower than those previously reported in European populations. The main etiologies were connective tissue diseases, sarcoidosis, and idiopathic ILD.

PMID:40483743 | DOI:10.1016/j.resmer.2025.101175

Hereditas. 2025 Jun 7;162(1):98. doi: 10.1186/s41065-025-00464-x.

ABSTRACT

BACKGROUND: This study aims to identify and investigate biomarkers associated with mitochondrial-related genes (MRGs) and programmed cell death-related genes (PCDRGs) that concurrently influence the progression of idiopathic pulmonary fibrosis (IPF) and to explore the underlying biological mechanisms involved.

METHODS: The GSE28042 and GSE27957 datasets, comprising 1,136 MRGs and 1,548 PCDRGs, were utilized in this study. Differentially expressed genes (DEGs) between the IPF and control groups were initially identified through differential expression analysis. Subsequently, key module genes closely associated with IPF samples were selected using Weighted Gene Co-expression Network Analysis (WGCNA). Intersection genes 1 and 2 were then identified by overlapping DEGs with key module genes, MRGs, and PCDRGs. Candidate genes were further selected through Spearman correlation analysis involving intersection genes 1 and 2. Additionally, biomarkers were identified, and a risk model was developed using Cox regression analysis, proportional hazards (PH) assumption testing, and machine learning methods. Patients with IPF were stratified into high- and low-risk cohorts. Finally, functional enrichment analysis, immune infiltration analysis, regulatory network construction, and reverse transcription quantitative PCR (RT-qPCR) were conducted separately to validate the findings.

RESULTS: CD28 and PF4 were identified as biomarkers, and a risk model was established. The distinct risk cohorts exhibited differences in pathways related to hemostasis, prion diseases, and other biological processes. A significant positive correlation with was observed between CD28 and native CD4 T cells, while PF4 showed a negative correlation with activated NK cells. Based on these two biomarkers, 30 miRNAs and 532 lncRNAs were predicted, resulting in the construction of a lncRNA-miRNA-biomarker network. Additionally, 11 chemicals associated with these biomarkers were identified. RT-qPCR analysis further confirmed that expression levels of CD28 and PF4 were significantly reduced in IPF samples (P < 0.05).

CONCLUSION: The results of this study suggested that the biomarkers CD28 and PF4 might play a potential role in the pathogenesis of IPF and might have an impact on the prognosis of the disease. These findings might offer valuable insights for future treatment strategies and prognostic evaluation for patients with IPF.

PMID:40483519 | DOI:10.1186/s41065-025-00464-x