Respir Med. 2025 Apr 22:108110. doi: 10.1016/j.rmed.2025.108110. Online ahead of print.

ABSTRACT

BACKGROUND: Chronic respiratory diseases are associated with significant disability and death. Pulmonary rehabilitation (PR) is recommended in the management of chronic respiratory diseases. There is limited population level data comparing PR utilization and completion among patients with chronic respiratory diseases.

METHODS: A retrospective, cross sectional analysis concerning PR use in adults residing in the U.S. with chronic obstructive pulmonary disease (COPD), interstitial lung disease (ILD), idiopathic pulmonary fibrosis (IPF), pulmonary hypertension, and bronchiectasis was conducted using the Merative™ MarketScan® Research Databases. PR use was identified using current procedural terminology (CPT) and healthcare common procedure coding system (HCPCS) codes. Demographics, comorbidities, oxygen use, medications, initiation and participation of PR by disease state were collected. Analysis involved chi-square tests and generalized estimating equations.

RESULTS: From 2014 to 2019, we identified 892,741 adults with chronic respiratory diseases and COPD was the most prevalent. PR initiation occurred in 2.3% and annual participation ranged from 1.5 % to 1.7 %. The IPF group had the largest proportion of patients that initiated PR compared to other groups. Completion of ≥ 8 sessions was greatest for the group with IPF (60.8 %), followed by non IPF ILD (56.2 %), bronchiectasis (55.3 %), pulmonary hypertension (55.1 %) and COPD (53.9 %). Completion of ≥ 8 sessions was significantly greater for the IPF group compared to the COPD group, (p <0.0001).

CONCLUSION: PR was underutilized among individuals with chronic respiratory disease, however the group with IPF demonstrated the greatest proportion of PR initiation and completion compared with other groups.

PMID:40273996 | DOI:10.1016/j.rmed.2025.108110

PLoS One. 2025 Apr 24;20(4):e0320242. doi: 10.1371/journal.pone.0320242. eCollection 2025.

ABSTRACT

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease with a fatal outcome, known for its rapid progression and unpredictable clinical course. However, the tools available for diagnosing and treating IPF are quite limited. This study aims to identify and screen potential biomarkers for IPF diagnosis, thereby providing new diagnostic approaches.

METHODS: We choosed datasets from the Gene Expression Omnibus (GEO) database, including samples from both IPF patients and healthy controls. For the training set, we combined two gene array datasets (GSE24206 and GSE10667) and utilized GSE32537 as the test set. We identified differentially expressed genes (DEGs) between IPF and normal tissues and determined IPF-related modules using Weighted Gene Co-expression Network Analysis (WGCNA). Subsequently, we employed two machine learning strategies to screen potential diagnostic biomarkers. Candidate biomarkers were quantitatively evaluated using Receiver Operating Characteristic (ROC) curves to identify key diagnostic genes, followed by the construction of a nomogram. Further validation of the expression of these genes through transcriptomic sequencing data from IPF and normal group animal models. Next, we conducted immune infiltration analysis, single-gene Gene Set Enrichment Analysis (GSEA), and targeted drug prediction. Finally, we created an artificial neural network model specifically for IPF.

RESULTS: We identified ASPN, COMP, and GPX8 as candidate biomarker genes for IPF, all of which exhibited Area Under the Curve (AUC) above 0.90. These genes were validated by RT-qPCR. Immune infiltration analysis revealed that specific immune cell types are closely related to IPF, suggesting that these immune cells may play a significant role in the pathogenesis of IPF.

CONCLUSION: ASPN, COMP, and GPX8 have been identified as potential diagnostic genes for IPF, and the most relevant immune cell types have been determined. Our research results propose potential biomarkers for diagnosing IPF and present new pathways for investigating its pathogenesis and devising novel therapeutic approaches.

PMID:40273141 | DOI:10.1371/journal.pone.0320242

Rheumatology (Oxford). 2025 Apr 24:keaf218. doi: 10.1093/rheumatology/keaf218. Online ahead of print.

ABSTRACT

OBJECTIVES: This randomized, placebo-controlled pilot trial evaluated the efficacy and safety of abatacept in patients with anti-synthetase syndrome-associated interstitial lung disease (ASyS-ILD).

METHODS: Participants with active ASyS-ILD were randomized to receive abatacept (n = 9) or placebo (n = 11) for 24 weeks, followed by a 24-week open-label extension with abatacept for all participants. The primary end point was a change in % predicted forced vital capacity (%FVC) from baseline to week 24. Secondary endpoints included changes in the FVC (ml), % predicted diffusing capacity for carbon monoxide (%DLCO), shortness of breath questionnaire (SOBQ), and pulmonary disease activity on a visual analogue scale (VAS) at weeks 24 and 48. Pre-post baseline analysis of FVC and quantitative image analysis (QIA) of high-resolution computed tomographic scans were performed. Data was analyzed using a generalized linear mixed model. The study was not powered for primary or secondary endpoints.

RESULTS: At week 24, there was no significant difference in the primary end point of %FVC change between abatacept and placebo (between treatment difference of -0.35, 95%CI -6.91-6.21, p= 0.914) and in all secondary endpoints. However, by week 48, trends favoring abatacept in %FVC, FVC (ml), %DLCO, and SOBQ were observed without statistical significance. There was a significant improvement in pulmonary disease activity VAS and pre-post baseline slopes of %FVC and QIA scores in the abatacept arm. Abatacept was generally well tolerated.

CONCLUSION: Abatacept did not significantly improve %FVC at 24 weeks. However, trends at 48 weeks suggest potential benefits, supporting the need for a larger, long-term randomized controlled trial.

CLINICAL TRIAL REGISTRATION: clinicaltrials.gov; NCT03215927.

PMID:40272902 | DOI:10.1093/rheumatology/keaf218

Respir Res. 2025 Apr 23;26(1):157. doi: 10.1186/s12931-025-03237-2.

ABSTRACT

BACKGROUND: Interstitial lung disease (ILD), represented by idiopathic pulmonary fibrosis (IPF) and progressive pulmonary fibrosis (PPF), shows poor prognosis due to progressive fibrosis. Early therapeutic intervention is required to enhance the efficacy of antifibrotic drugs, highlighting the importance of early detection of ILD progression. Although candidate biomarkers for predicting ILD progression have been recently reported through omics analyses, clinically measurable biomarkers remain unestablished. This study aimed to identify clinically measurable biomarkers that could predict the degree of ILD progression.

METHODS: The serum levels of 13 candidate biomarkers were prospectively measured by chemiluminescent enzyme immunoassay and the utilities for predicting ILD progression were compared in the discovery cohort (total 252 patients). Moreover, we evaluated the utility of the identified biomarker in another independent cohort (154 patients with non-IPF-ILD) and examined the dynamics of the biomarker by immunoblotting and single-cell RNA sequencing (scRNA-seq) using samples of patients and a mouse model.

RESULTS: In the discovery cohort, C-C motif chemokine ligand (CCL)17 could reliably predict ILD progression, particularly in patients with ILD other than IPF, and showed significant associations with mortality (hazard ratio [HR] 3.70; 95% confidence interval [CI] 1.19-11.49; P = 0.015; cut-off value = 418 pg/mL). Consistently, in the validation cohort, the CCL17 high group showed significantly higher mortality (HR: 2.15; 95% CI 0.99-4.69; P = 0.049), and CCL17 was identified as an independent prognostic factor from corticosteroid or immunosuppressive agents use and ILD-gender-age-physiology index. Similar to the results of serum studies, CCL17 levels in the lungs of patients with PPF and model mice were higher than those in controls. They were positively correlated with CCL17 levels in the serum, suggesting that the increased serum CCL17 levels could reflect an increase in CCL17 levels in lung tissues. The scRNA-seq analysis of lung tissues from model mice suggested that the levels of CCL17 derived primarily from conventional dendritic cells and macrophages increased, especially during the profibrotic phase.

CONCLUSIONS: We identified serum CCL17 as a clinically measurable biomarker for predicting non-IPF-ILD progression. Serum CCL17 could enable the stratification of patients at risk of non-IPF-ILD progression, leading to appropriate early therapeutic intervention.

PMID:40269953 | DOI:10.1186/s12931-025-03237-2

Rev Mal Respir. 2025 Apr 22:S0761-8425(25)00168-8. doi: 10.1016/j.rmr.2025.04.002. Online ahead of print.

ABSTRACT

INTRODUCTION: Fibrosing interstitial lung diseases (ILD) are severe respiratory conditions that can lead to respiratory failure and death. Over the past decade, antifibrotic therapies have represented a significant therapeutic advancement and are now widely used.

STATE OF THE ART: Pirfenidone and nintedanib have been approved for the treatment of idiopathic pulmonary fibrosis (IPF), while only nintedanib has been approved for systemic sclerosis-related ILD and progressive pulmonary fibrosis (PPF). Both drugs help to reduce the decline in forced vital capacity (FVC) characterizing these three indications and to decrease mortality, acute exacerbations, and quality of life impairment in patients with IPF and PPF.

PERSPECTIVES: Tolerance to these treatments remains a major challenge, prompting evaluation of alternative administration routes, such as inhalation. Numerous ongoing clinical trials and encouraging results from phase 3 studies are expected to lead to the approval of new antifibrotic molecules.

CONCLUSIONS: Antifibrotic therapies have proven to be crucial in the management of IPF and PPF. Prescription should be a shared decision with the patient and may be considered at an early stage, even in elderly individuals, provided that dedicated support is avaialble.

PMID:40268574 | DOI:10.1016/j.rmr.2025.04.002

Eur Respir J. 2025 Apr 23:2402317. doi: 10.1183/13993003.02317-2024. Online ahead of print.

NO ABSTRACT

PMID:40268504 | DOI:10.1183/13993003.02317-2024

Br J Hosp Med (Lond). 2025 Apr 25;86(4):1-22. doi: 10.12968/hmed.2024.0934. Epub 2025 Apr 21.

ABSTRACT

Aims/Background Idiopathic pulmonary fibrosis (IPF) is associated with an increased mortality risk. However, the factors that contribute to this risk remain unknown. This study aimed to systematically review existing predictive models for IPF-related mortality and to evaluate prognostic factors associated with patient outcomes. Methods A comprehensive literature search was conducted on PubMed, Cochrane Library, Web of Science, and Embase for studies on IPF mortality risk prediction models published between 1 January 1984 and 15 November 2024. Two independent reviewers screened, extracted, and cross-checked the data. The risk of bias and model applicability were also evaluated. Results A total of 17 risk prediction models were identified. The area under the receiver operating characteristic (ROC) curve (AUC) ranged from 0.728 to 0.907, while the model validation results ranged from 0.750 to 0.920. The concordance index (C-index) of 10 studies was more than 0.7, indicating good predictive performance. This study encompassed a total of 17 risk prediction models incorporating between 3 and 8 combined prognostic variables, with the most frequently included predictors being forced vital capacity as a percentage of the predicted value (FVC%pred), carbon monoxide diffusion capacity as a percentage of the predicted value (DLCO%pred), gender, age, six-minute walk test (6MWT) results, and dyspnea severity. Conclusion Current IPF mortality risk prediction models remain in an exploratory phase, with a generally high risk of bias. Furthermore, the lack of external validation in some models limits their generalizability. Future research should focus on improving the applicability of the model to enhance clinical application.

PMID:40265534 | DOI:10.12968/hmed.2024.0934

J Mass Spectrom. 2025 May;60(5):e5138. doi: 10.1002/jms.5138.

ABSTRACT

Pulmonary fibrosis (PF) is a chronic and progressive lung disease with fatal consequences. The study of PF is challenging due to the complex mechanism involved, the need to understand the heterogeneity and spatial organization within lung tissues. In this study, we investigate the metabolic heterogeneity between two forms of lung fibrosis: idiopathic pulmonary fibrosis (IPF) and silicosis, using advanced spatially-resolved metabolomics techniques. Employing high-resolution mass spectrometry imaging, we spatially mapped and identified over 260 metabolites in lung tissue sections from mouse models of IPF and silicosis. Histological analysis confirmed fibrosis in both models, with distinct pathological features: alveolar destruction and collagen deposition in IPF, and nodule formation in silicosis. Metabolomic analysis revealed significant differences between IPF and silicosis in key metabolic pathways, including phospholipid metabolism, purine/pyrimidine metabolism, and the TCA cycle. Notably, phosphocholine was elevated in silicosis but reduced in IPF, while carnitine levels decreased in both conditions. Additionally, glycolytic activity was increased in both models, but TCA cycle intermediates showed opposing trends. These findings highlight the spatial metabolic heterogeneity of PF and suggest potential metabolic targets for therapeutic intervention. Further investigation into the regulatory mechanisms behind these metabolic shifts may open new avenues for fibrosis treatment.

PMID:40264277 | DOI:10.1002/jms.5138

Intern Med J. 2025 Apr 22. doi: 10.1111/imj.70051. Online ahead of print.

ABSTRACT

Pulmonary fibrosis care, affecting both idiopathic pulmonary fibrosis and other forms of interstitial lung disease (ILD) characterised by fibrosis, has transformed with a range of innovations that affect the diagnosis, treatment and prognosis of this condition. Pharmacotherapeutic options have expanded, with increased indications for the application of effective antifibrotic therapy in non-IPF progressive pulmonary fibrosis as a solo treatment or combined with immunosuppression, emerging evidence for immunomodulatory therapy including biologic agents and greater access to clinical trials. The diagnostic approach to unclassifiable ILD now includes transbronchial lung cryobiopsy, a less invasive method to obtain histopathology with reduced morbidity and mortality compared to surgical lung biopsy. A multidisciplinary approach optimises the care of people with ILD and includes non-pharmacological management, addressing significant comorbidities, symptom care and advanced care planning. This review will summarise recent updates in pulmonary fibrosis management.

PMID:40260907 | DOI:10.1111/imj.70051

BMC Pulm Med. 2025 Apr 21;25(1):186. doi: 10.1186/s12890-025-03611-2.

ABSTRACT

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a deadly respiratory disease of older patients. IPF therapies (antifibrotics) are efficacious in slowing disease progression, but they are critically underutilized. Potential barriers to antifibrotic use are polypharmacy and potentially inappropriate medications (PIM). We examined the frequency of these factors for older patients with IPF.

METHODS: We retrospectively analyzed records of Veterans ≥ 65 years old in the Durham Veterans Affairs Health Care System who received a diagnosis of IPF and received care between 11 April 2023 and 9 September 2024. We analyzed medication profiles from the Corporate Data Warehouse including total medication counts, polypharmacy (≥ 5 medications), severe polypharmacy (> 15 medications), and prescription of a PIM in the anticholinergic, antidepressant, sedative, and antipsychotic classes using published geriatric guidelines (2023 Beers criteria, Screening Tool of Older People's Potentially Inappropriate Prescriptions [STOPP] version 3). Identified PIMs underwent protocolized review to categorize them further as likely appropriate or inappropriate.

RESULTS: We identified 367 Veterans ≥ 65 years old with a diagnosis of IPF diagnostic during our study period. Total medication count was high for older Veterans (mean 14.2, SD 7.0). Veterans commonly had polypharmacy (350/367, 95.4%), severe polypharmacy (161/367, 43.9%), and ≥ 1 PIM (97/367, 26.4%). After protocolized review, 5.7% (21/367) of older Veterans with IPF had a likely inappropriate medication without documentation of a failed preferred alternative.

CONCLUSION: For older Veterans with IPF, polypharmacy and PIM use were common and represent likely barriers to effective IPF pharmacotherapy initiation. Interventions that target these factors like deprescribing could improve antifibrotic use.

CLINICAL TRIAL NUMBER: Not applicable.

PMID:40259309 | DOI:10.1186/s12890-025-03611-2

Nat Commun. 2025 Apr 21;16(1):3748. doi: 10.1038/s41467-025-59093-7.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a severe lung disease occurring throughout the world; however, few clinical therapies are available for treating this disorder. Overactivated fibroblasts drive abnormal fibrosis accumulation to maintain dynamic balance between inflammation and extracellular matrix (ECM) stiffness. Given pulmonary cell can regenerate, the lung may possess self-repairing abilities if fibrosis is removed via clearance of overactivated fibroblasts. The aim of this study was to evaluate the therapeutic activity of transient antifibrotic chimeric antigen receptor (CAR) T cells (generated via a novelly-designed lipid nanoparticle-messenger RNA (LNP-mRNA) system) and explore the regeneration mechanisms of lung in a male mouse model of bleomycin-induced pulmonary fibrosis. Here we found that fibrosis-induced ECM stiffening impaired alveolar epithelial cell compensation. The proposed LNP-mRNA therapy eliminated overactivated fibroblasts to rescue pulmonary fibrosis. The restored ECM environment regulated the cellular profile. The elevated plasticity of AT2 and Pclaf+ cells increased AT1 cell population via polarization. Apoe+ macrophages and increased numbers of effector T cells were shown to reestablish pulmonary immunity. Hence, LNP-mRNA treatment for fibrosis can restore pulmonary structure and function to similar degrees to those of a healthy lung. This therapy is a potential treatment for IPF patients.

PMID:40258811 | DOI:10.1038/s41467-025-59093-7

Am J Physiol Lung Cell Mol Physiol. 2025 Apr 21. doi: 10.1152/ajplung.00039.2025. Online ahead of print.

ABSTRACT

Type 2 inflammation and epithelial-to-mesenchymal transitions (EMTs) play critical roles in airway repair after damage from allergens or parasites. The matricellular protein periostin (POSTN) has increased expression in inflammatory conditions and has been implicated in fibrosis and EMT, suggesting a role in airway repair. This study investigates the role of periostin in airway epithelial and lung fibroblast wound repair using an in vitro wound model. Our results demonstrate that the type 2 cytokine IL-13 induces periostin secretion from primary human airway epithelial basal cells. Periostin knockdown in human airway epithelial cells (HAEs) and human lung fibroblasts (HLFs) impairs wound closure, indicating that periostin is required for airway repair. In a coculture model of HAE and HLFs, fibroblast-secreted POSTN is required for airway epithelial wound repair, suggesting that periostin is involved in paracrine signaling between the two cell types. These findings highlight periostin's critical function in epithelial and fibroblast-mediated wound repair, suggesting its potential as a therapeutic target for diseases characterized by aberrant wound healing and fibrosis, such as asthma and idiopathic pulmonary fibrosis.

PMID:40257107 | DOI:10.1152/ajplung.00039.2025

Breathe (Sheff). 2025 Apr 17;21(2):240260. doi: 10.1183/20734735.0260-2024. eCollection 2025 Apr.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease with limited treatment options. Despite the approval of pirfenidone and nintedanib that slow disease progression, IPF remains a disease with poor survival. Promising therapeutic candidates were tested as potential treatments for IPF and while some drugs were successful in phase II clinical trials, their successful transition to positive phase III was unfortunately disappointing. This highlights the "regression to the truth" concept in drug development, whereby positive phase II trial results may simply be a statistical anomaly rather than the result of true efficacy. We examine three pivotal trials of novel IPF therapies, zinpentraxin alfa, ziritaxestat and pamrevlumab, that failed in late-stage clinical development. These failures underscore common pitfalls in IPF drug development, including inadequate phase II sample sizes, reliance on surrogate endpoints like forced vital capacity, and challenges integrating background antifibrotic therapies. Moving forward, innovative approaches like adaptive trial designs, Bayesian statistics and composite endpoints could improve trial robustness. Moreover, platform trials may accelerate drug development by testing multiple therapies simultaneously. Negative trials are not failures but opportunities for learning. By recognising and addressing these challenges, while also embracing novel trial methodologies, we can enhance drug development and improve IPF outcomes.

PMID:40255293 | PMC:PMC12004256 | DOI:10.1183/20734735.0260-2024

Breathe (Sheff). 2025 Apr 17;21(2):240176. doi: 10.1183/20734735.0176-2024. eCollection 2025 Apr.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and fatal interstitial fibrosing disease and, despite some well-known risk factors, its cause is still unknown. Cough is experienced by most patients and is commonly chronic and refractory, having a significant impact on quality of life. Its aetiology is complex, combining factors related to interstitial lung disease (ILD) such as an increased sensitivity of cough-sensitive nerves, structural lung changes and inflammation, genetic factors, several comorbidities and medication-adverse effects. Despite the therapeutic advancements in IPF over the past decade with the introduction of antifibrotic drugs that slow disease progression, effective treatment options for cough in IPF remain unavailable. Cough management often relies on empirical approaches based on studies involving chronic cough patients of unspecified causes and ILD physicians' personal experiences. Different classes of medications have been tried over time and, more recently, the focus has turned to neuromodulators and opioids, but several studies have shown suboptimal efficacy in cough. On the other hand, these drugs are associated with significant physical, psychological and economic burdens. However, the future brings us hope to the extent that most current ongoing clinical trials are using new molecules and some have demonstrated promising antitussive effects. This review aims to provide a practical guide to understanding and managing cough in IPF patients, presenting pharmacological and non-pharmacological approaches over time, as well as those treatments that are currently being investigated in clinical settings.

PMID:40255292 | PMC:PMC12004257 | DOI:10.1183/20734735.0176-2024

Breathe (Sheff). 2025 Apr 17;21(2):240167. doi: 10.1183/20734735.0167-2024. eCollection 2025 Apr.

ABSTRACT

Interstitial lung disease (ILD) is a heterogeneous chronic form of lung disease. The pathogenesis of ILD is poorly understood and a common form of ILD, idiopathic pulmonary fibrosis (IPF) is associated with poor prognosis. There is evidence for substantial dysregulated immune responses in ILD. The microbiome is a key regulator of the immune response, and the lung microbiome correlates with alveolar immunity and clinical outcomes in ILD. Most observational lung microbiome studies have been conducted in patients with IPF. A consistent observation in these studies is that the bacterial burden of the lung is elevated in patients with IPF and predicts mortality. However, our understanding of the mechanism is incomplete and our understanding of the role of the lung microbiome in other forms of ILD is limited. The microbiomes of the oropharynx and gut may have implications for the lung microbiome and pulmonary immunity in ILD but require substantial further research. Here, we discuss the studies supporting a role for the lung microbiome in the pathogenesis of IPF, and briefly describe the putative role of the oral-lung axis and the gut-lung axis in ILD.

PMID:40255291 | PMC:PMC12004254 | DOI:10.1183/20734735.0167-2024

Stem Cell Res Ther. 2025 Apr 20;16(1):194. doi: 10.1186/s13287-025-04313-6.

ABSTRACT

BACKGROUND: Idiopathic pulmonary fibrosis is a progressive lung disorder, presenting clinically with symptoms such as shortness of breath and hypoxemia. Despite its severe prognosis and limited treatment options, the pathogenesis of idiopathic pulmonary fibrosis remains poorly understood. This study aims to investigate the therapeutic potential of mesenchymal stromal cells in treating idiopathic pulmonary fibrosis, focusing on their ability to modulate regulatory T cells through the low tumor necrosis factor superfamily member 4 (TNFSF4) pathway. The goal is to identify mesenchymal stromal cells subtypes with optimal immunomodulatory effects to enhance regulatory T cells functions and ameliorate fibrosis.

METHODS: We identified the immune characteristics of idiopathic pulmonary fibrosis by mining and analyzing multiple public datasets and detecting regulatory T cells in the blood and lung tissues of idiopathic pulmonary fibrosis patients. An extensive examination followed, including assessing the impact of mesenchymal stromal cells on regulatory T cells proportions in peripheral blood and lung tissue, and exploring the specific role of TNFSF4 expression in regulatory T cells modulation. Whole-genome sequencing and cluster analysis were used to identify mesenchymal stromal cells subtypes with low TNFSF4 expression.

RESULTS: Mesenchymal stromal cells characterized by TNFSF4 expression (TNFSF4low-MSCs) demonstrated enhanced ability to regulate regulatory T cells subpopulations and exhibited pronounced anti-fibrotic effects in the bleomycin-induced idiopathic pulmonary fibrosis mouse model. These mesenchymal stromal cells increased regulatory T cells proportions, reduced lung fibrosis, and improved survival rates. TNFSF4-tumor necrosis factor receptor superfamily member 4 (TNFRSF4) signaling was identified as a critical pathway influencing regulatory T cells generation and function.

CONCLUSIONS: Our findings underscore the pivotal role of TNFSF4 in mesenchymal stromal cells mediated regulatory T cells modulation and highlight the therapeutic potential of selecting mesenchymal stromal cells subtypes based on their TNFSF4 expression for treating idiopathic pulmonary fibrosis. This approach may offer a novel avenue for the development of targeted therapies aimed at modulating immune responses and ameliorating fibrosis in idiopathic pulmonary fibrosis.

TRIAL REGISTRATION: Our study involved collecting 10 mL of peripheral blood from idiopathic pulmonary fibrosis patients, and the Medical Ethics Committee of Nanjing Drum Tower Hospital approved our study protocol with the approval number 2023-675-01.

PMID:40254578 | DOI:10.1186/s13287-025-04313-6

J Ethnopharmacol. 2025 Apr 19:119763. doi: 10.1016/j.jep.2025.119763. Online ahead of print.

NO ABSTRACT

PMID:40254530 | DOI:10.1016/j.jep.2025.119763

Respir Investig. 2025 Apr 17;63(4):481-487. doi: 10.1016/j.resinv.2025.04.008. Online ahead of print.

ABSTRACT

BACKGROUND: The Japanese government operates a medical subsidy system for intractable diseases, including idiopathic pulmonary fibrosis (IPF). Registering with this system requires filling out a clinical survey form, which encompasses multiple survey items regarding the patient's disease and functional status. In this study, we retrospectively analyzed the forms of new applicants with IPF in 2019 to evaluate the clinical and functional characteristics.

METHODS: The following patient data were collected: sex, age, smoking status, history of surgical lung biopsy, disease severity (using Japanese severity classification [JSC]), serum biomarkers, findings on chest high-resolution computed tomography (HRCT), functional status, symptoms, and treatment.

RESULTS: Of the 4796 patients reviewed (76.1 % males; mean age = 73.4 ± 8.1 years), 23.6 % had a mild disease (JSC stages I-II) and 76.4 % had a severe disease (stages III-IV). The HRCT of most patients revealed honeycombing, traction bronchiectasis and/or bronchiolectasis, reticular shadows, and subpleural shadows. The positivity rates for elevated serum levels of Krebs von Lungen-6 (KL-6) and surfactant protein-D (SP-D) were 92.6 % and 89.3 %, respectively. As the severity increased, the biomarker positivity rate increased. Approximately half of the patients with milder diseases experienced transportation challenges, and 30 % complained of pain and/or discomfort and anxiety and/or depression.

CONCLUSIONS: In approximately 90 % of patients, serum KL-6 and SP-D levels increased and the positive rate increased as the disease severity increased. Even patients with mild diseases experience challenges in transportation as well as pain, discomfort, anxiety, or depression.

PMID:40250140 | DOI:10.1016/j.resinv.2025.04.008

Front Immunol. 2025 Mar 31;16:1549277. doi: 10.3389/fimmu.2025.1549277. eCollection 2025.

ABSTRACT

Idiopathic Pulmonary Fibrosis (IPF) is a chronic, progressive lung disease characterized by abnormal epithelial repair, persistent inflammation, and excessive extracellular matrix deposition, leading to irreversible scarring and respiratory failure. Central to its pathogenesis is the dysregulation of the PI3K/Akt signaling pathway, which drives fibroblast activation, epithelial-mesenchymal transition, apoptosis resistance, and cellular senescence. Senescent cells contribute to fibrosis through the secretion of pro-inflammatory and profibrotic factors in the senescence-associated secretory phenotype (SASP). Current antifibrotic therapies, Nintedanib and Pirfenidone, only slow disease progression and are limited by side effects, highlighting the need for novel treatments. This review focuses on the role of PI3K/Akt signaling in IPF pathogenesis, its intersection with inflammation and fibrosis, and emerging therapeutic approaches targeting molecules along this pathway.

PMID:40248697 | PMC:PMC12004373 | DOI:10.3389/fimmu.2025.1549277

ERJ Open Res. 2025 Apr 14;11(2):00978-2024. doi: 10.1183/23120541.00978-2024. eCollection 2025 Mar.

ABSTRACT

BACKGROUND: A shared genetic component between coronavirus disease 2019 (COVID-19) and idiopathic pulmonary fibrosis (IPF) has been described based on analyses of individual risk variants. Here we used a whole-genome polygenic risk score (PRS) approach to further evaluate age- and sex-stratified genetic overlap between IPF and severe COVID-19 to give insight into shared biological mechanisms that might both inform therapeutic strategies for both diseases.

METHODS: We used results from the largest genome-wide association study of clinically defined IPF risk (4125 cases/20 464 controls) and individual-level data from the SCOURGE European study of COVID-19 (5968 cases/9056 controls). We calculated IPF PRSs and assessed their association with COVID-19 severity, stratified by age and sex. We performed replication in an independent dataset of Latin-American patients (1625 cases/1887 controls). Enrichment and pathway-specific PRS analyses were performed to study biological pathways associated with COVID-19 severity.

RESULTS: IPF PRSs were significantly associated with COVID-19 hospitalisation and severe illness in Europeans and replicated in a Latin-American cohort. The strongest association was found in <60 years patients, especially among younger males (p=6.39×10-5). Pathway-specific PRSs analyses supported a link to cadherin and integrin signalling pathways.

CONCLUSIONS: The study indicates age and sex-dependent genome-wide genetic overlap between IPF and severe COVID-19 and highlights specific shared biological mechanisms underlying both conditions. This could also imply that individuals with a high IPF genetic risk are at an overall increased risk of developing lung sequelae resulting from severe COVID-19.

PMID:40247961 | PMC:PMC12004260 | DOI:10.1183/23120541.00978-2024