Expert Rev Respir Med. 2025 Apr 27. doi: 10.1080/17476348.2025.2499651. Online ahead of print.

ABSTRACT

INTRODUCTION: Idiopathic pleuroparenchymal fibroelastosis (iPPFE) is a rare progressive interstitial lung disease characterized by upper-lobe fibrosis, severe restrictive impairment, and poor prognosis. Unlike idiopathic pulmonary fibrosis, in which acute exacerbations, chronic respiratory failure, and lung cancer are the major causes of death, iPPFE primarily leads to progressive respiratory failure, often complicated by malnutrition and recurrent pneumothorax. Despite growing recognition, its pathogenesis remains unclear and no effective treatments exist.

AREAS COVERED: This review summarizes the epidemiological, clinical, radiological, and pathological features of iPPFE, as well as diagnostic and prognostic advancements. Key prognostic factors include weight loss, reduced forced vital capacity, hypercapnia, and lower-lobe interstitial pneumonia. Serum biomarkers (e.g. latent transforming growth factor-beta binding protein-4) are being explored for early detection and prognostic purposes. Although antifibrotic agents show limited efficacy, supportive care - pulmonary rehabilitation, nutritional management, and pneumothorax prevention - remains essential. Research on the fibroelastotic pathways may inform the development of future therapies.

EXPERT OPINION: IPPFE remains a challenging disease. Therefore, early diagnosis and comprehensive management of this condition are crucial. Future research should refine prognostic models and explore novel therapeutic approaches for treating fibroelastosis. Lung transplantation may be an option for select patients. Further studies are required to optimize these outcomes.

PMID:40289399 | DOI:10.1080/17476348.2025.2499651

Diagn Pathol. 2025 Apr 26;20(1):53. doi: 10.1186/s13000-025-01654-x.

ABSTRACT

OBJECTIVE: This case report describes a patient with acute fibrinous and organising pneumonia (AFOP) presenting with mass-like imaging on chest computed tomography (CT), aiming to enhance clinical awareness of this rare disease.

CASE PRESENTATION: A 66-year-old man presented with cough, sputum, chest tightness and weight loss persisting for 1 month. Chest X-ray revealed a space-occupying lesion in the left lung. Further CT imaging demonstrated irregular soft tissue masses in both the upper and lower lobes of the left lung. Although the imaging findings suggested lung cancer, the final pathological diagnosis confirmed AFOP. The patient was treated with methylprednisolone, resulting in substantial improvement of the upper lobe lesion, whereas the lower lobe lesion showed minimal response. Following the addition of mycophenolate mofetil, the lower lobe lesion decreased substantially. Multiple lung biopsies confirmed the diagnosis of AFOP, with no evidence of a malignant tumour.

CONCLUSIONS: Acute fibrinous and organising pneumonia presents with non-specific imaging findings, and when manifesting as a mass-like lesion, it may be misdiagnosed as lung cancer. Pathological examination remains essential for diagnosis. Close monitoring of the clinical response is crucial during treatment, and the treatment plan should be tailored to individual patient needs.

PMID:40287744 | DOI:10.1186/s13000-025-01654-x

Sci Rep. 2025 Apr 26;15(1):14622. doi: 10.1038/s41598-025-98490-2.

ABSTRACT

Emerging evidence suggests that N6-methyladenosine (m6A) modification significantly influences lung injury, lung cancer, and immune responses. The current study explores the potential involvement of m6A modification in the development of IPF. This research analyzed the GSE93606 dataset of 20 non-IPF and 154 IPF patients, identifying 26 m6A regulators and developing predictive models with RF and SVM, assessed via ROC curves. A nomogram was created with selected m6A factors, including molecular subtyping, PCA for m6A features, immune cell analysis, DEG identification, and functional enrichment. In vitro experiments on MRC-5 cells used RT-qPCR and Western blotting, and virtual drug screening targeted the WTAP protein through molecular docking. Analysis revealed 26 differential m6A regulators in IPF patients, with 16 significant; IGFBP2 and YTHDF2 were overexpressed, while others decreased. RF and SVM models identified predictive m6A regulators, and a nomogram was developed using five factors to predict IPF incidence. Distinct m6A patterns showed changes in RNA levels of specific genes in the BLM-induced group, and five compounds targeting WTAP were identified. This research explored m6A factors' impact on IPF diagnosis and prognosis, identifying WTAP as a potential biomarker.

PMID:40287490 | DOI:10.1038/s41598-025-98490-2

Molecules. 2025 Mar 21;30(7):1407. doi: 10.3390/molecules30071407.

ABSTRACT

Fennel waste is rich in compounds that may have beneficial effects on human health. For this reason, the most abundant metabolites in fennel were isolated as the following: quercetin-3-O-glucoside, quinic acid, 1,5-dicaffeoylquinic acid, kaempferol-3-O-glucuronide, and quercetin-3-O-glucuronide. After inducing inflammation in human bronchial epithelial cells by stimulating them with IL-1β, the cells were treated with the specialized Foeniculum vulgare metabolites at different concentrations to assess their anti-inflammatory effect. Eicosanoids, fatty acids, and sphingolipids were extracted from the cell medium and quantified by UPLC-ESI-QTRAP-MS/MS analysis. The anti-inflammatory activity of the metabolites isolated from fennel waste was demonstrated. They were able to alleviate the inflammatory state in human bronchial epithelium by modulating the metabolic expression of both pro- and anti-inflammatory eicosanoids, fatty acids, and sphingolipids. These findings suggest the potential use of fennel waste in the production of dietary supplements to alleviate the symptoms of chronic inflammatory diseases like asthma, chronic obstructive pulmonary disease (COPD), and idiopathic pulmonary fibrosis (IPF), where the continuous use of antiphlogistics may have significant side effects.

PMID:40286023 | DOI:10.3390/molecules30071407

Life (Basel). 2025 Mar 21;15(4):516. doi: 10.3390/life15040516.

ABSTRACT

There is increasing evidence supporting the use of morphofunctional assessment (MFA) as a tool for clinical characterization and decision-making in malnourished patients. MFA enables the diagnosis of malnutrition, sarcopenia, obesity, and cachexia, leading to a novel phenotype-based classification of nutritional disorders. Bioelectrical impedance analysis (BIVA), nutritional ultrasound® (NU) and computed tomography (CT) are included, along with functional tests like the Timed Up and Go test (TUG). Myoesteatosis, detectable via CT, can occur independently from nutritional phenotypes and has been identified as a significant mortality predictor in idiophatic pulmonary fibrosis (IPF). Our aim is to analyze the prevalence and overlap of nutritional phenotypes in IPF and evaluate the prognostic value of myoesteatosis. Our bicenter cross-sectional study included 82 IPF patients (84.1% male and with a medium age of 71.1 ± 7.35 years). MFA was performed using BIVA, NU, CT at the T12 level (CT-T12), the handgrip strength (HGS) test, and the TUG. CT-T12 BC parameters were analyzed using FocusedON® software, while statistical analyses were conducted with JAMOVI version 2.3.22. All four major nutritional phenotypes were represented in our cohort, with significant overlap. A total of 80.5% met the GLIM criteria for malnutrition, 14.6% had cachexia, 17% were sarcopenic, and 28% were obese. Of the obese patients, 70% were also malnourished, while 100% of sarcopenic obese patients (5.9% of total) had malnutrition. A total of 55% of sarcopenic patients with available CT also had myosteatosis, suggesting muscle quality deterioration as a potential driver of functional impairment. The presence of myosteatosis > 15% in T12-CT was an independent predictor of 12-month mortality (HR = 3.13; 95% CI: 1.01-9.70; p = 0.049), with survival rates of 78.1% vs. 96.6% in patients with vs. without myosteatosis, respectively. To conclude, this study underscores the relevance of MFA in the nutritional characterization of patients with IPF, demonstrating its potential to identify specific phenotypes associated with malnutrition, functional impairment, and the presence of myoesteatosis, thereby providing a valuable tool for clinical decision-making.

PMID:40283071 | DOI:10.3390/life15040516

Medicina (Kaunas). 2025 Mar 26;61(4):599. doi: 10.3390/medicina61040599.

ABSTRACT

Usual Interstitial Pneumonia (UIP) is the most severe radiological/histological pattern of Interstitial Lung Disease (ILD). It is typical of Idiopathic Pulmonary Fibrosis (IPF), but is also frequently described in Autoimmune Rheumatic Diseases (ARDs), sharing with IPF common risk factors, genetic backgrounds, and in some cases, disease progression and prognosis. Following the results of the PANTHER study, immunosuppressive drugs are now not recommended for the treatment of IPF; however, their use for the treatment of UIP secondary to ARDs is still under debate. The aim of this review is to summarize existing knowledge on the clinical presentation of autoimmune UIP and its treatment with immunosuppressive drugs. We searched PubMed for English language clinical trials and studies on treatment of ARDs-ILD, looking for specific treatments of UIP-ARDs. The available clinical trials rarely stratify patients by ILD pattern, and clinical studies generally lack a comparison with a placebo group. In Systemic Sclerosis, UIP patients showed a non-significant trend of worsening under immunosuppression. On the contrary, in Interstitial Pneumonia with Autoimmune Features and, above all, Rheumatoid Arthritis, immunosuppressive treatment produced promising results in the management of UIP patients. In conclusion, the current evidence about the immunosuppressive treatment of UIP-ARDs is limited and conflicting. There is an urgent need to adequately assess this topic with specific clinical trials, as has already been performed for IPF. The possibility should be considered that different ARDs can respond differently to immunosuppression. Finally, a wider use of histological samples could produce valuable information from a diagnostic, therapeutic, and research point of view.

PMID:40282891 | DOI:10.3390/medicina61040599

AAPS PharmSciTech. 2025 Apr 25;26(5):113. doi: 10.1208/s12249-025-03112-9.

ABSTRACT

In this study, a quercetin-loaded liposome system modified with collagenase was developed to increase QU penetration in the ECM and improve IPF treatment. Quercetin-loaded long circulation liposome (QU-LP) and quercetin-loaded liposome modified with collagenase type I (QU-CLP) were prepared, followed by characterization of the encapsulation efficiency, particle size, morphology, and in vitro drug release. Their effect on the cytotoxicity of A549 cells was detected by the Cell Counting Kit-8, and the cellular uptake was investigated using cellular fluorescence imaging and flow cytometry. TGF-β1 induced A549 cell model was established to mimic pulmonary fibrosis to explore further the anti-pulmonary fibrosis effect of QU-CLP by CCK8 experiment. QU-CLP significantly improves the solubility and bioavailability of QU by encapsulating it in the internal cavity with a high encapsulation efficiency (EE%) of 92.86 ± 1.03%. Liposomes alleviate the influence of QU on normal A549 cell growth. Enhanced fluorescence intensity was observed in A549 cells treated with coumarin 6-labeled and collagenase-modified nanoliposomes (C6-CLP) after 4 h of incubation on the collagen matrix, confirming that collagenase-loaded liposomes could penetrate the collagen barrier and cells internalized more hydrophobic drug. The mean fluorescence intensity (MFI) of the C6-CLP group was 2.88 times that of the C6-labeled nanoliposomes (C6-LP). Moreover, QU-CLP significantly (**P < 0.01) inhibited the proliferation of A549 cells stimulated by TGF-β1. QU-CLP has excellent potential for delivering QU with enhanced bioavailability, high cellular uptake efficiency, and improved therapeutic efficacy in IPF.

PMID:40281247 | DOI:10.1208/s12249-025-03112-9

Lung. 2025 Apr 25;203(1):57. doi: 10.1007/s00408-025-00811-9.

ABSTRACT

PURPOSE: Combined lung-liver transplant (CLLT) is a complex yet life-saving procedure for patients with simultaneous end-stage lung and liver disease. Given the geographical allocation change to the lung allocation score (LAS) in 2017 and the recent SARS-CoV-2 outbreak in 2019, we aim to provide an updated analysis of the patient selection and outcomes of CLLTs.

METHODS: The UNOS registry was used to identify all patients who underwent CLLT between January 2014 and June 2023. To account for the changes made to LAS in 2017, baseline characteristics and outcomes were compared between era 1 (before 2017) and era 2 (after 2017). Risk factors for mortality were analyzed using the Cox regression hazard models. Recipient survival of up to 3 years was analyzed using the Kaplan-Meier method.

RESULTS: 117 CLLTs were performed (77.8% in era 2). Donor organs experienced significantly longer ischemic times (p = 0.039) and traveled longer distances (p = 0.025) in era 2. However, recipient (p = 0.79) and graft (p = 0.41) survival remained comparable at up to 3 years post-transplant between eras. CLLTs demonstrated similar long-term survival to isolated lung transplants (p = 0.73). Higher recipient LAS was associated with an increased mortality risk (HR 1.14, p = 0.034). Recipient diagnosis of idiopathic pulmonary fibrosis carried a 5.03-fold risk of mortality (p = 0.048) compared to those with cystic fibrosis.

CONCLUSION: In the post-2017 LAS change era, CLLTs are increasingly performed with comparable outcomes to isolated lung transplants. A careful, multidisciplinary approach to patient selection and management remains paramount to optimizing outcomes for this rare patient population.

PMID:40281222 | DOI:10.1007/s00408-025-00811-9

Sci Rep. 2025 Apr 25;15(1):14448. doi: 10.1038/s41598-025-97037-9.

ABSTRACT

To investigate the molecular mechanisms underlying idiopathic pulmonary fibrosis (IPF), we analyzed the GSE173355 and GSE173356 datasets obtained from the NCBI-GEO database. We identified differentially expressed genes (DEGs) and differentially methylated sites. Functional enrichment analysis was conducted for both DEGs and differentially methylated sites. Functional enrichment analysis was performed for both DEGs and differentially methylated sites, alongside an examination of immune-related scores, proportions, and GSVA enrichment scores of immune cells in IPF versus control samples. An integrated gene-methylation association analysis revealed 8 genes with expression levels negatively influenced by methylation. The Rap1 pathway, Focal adhesion, and Axon guidance were significantly enriched among both DEGs and differentially methylated sites. Immune-related scores were notably lower in the IPF group compared to the control group, with marked differences in immune cell proportions and GSVA enrichment scores. Screening of DEGs identified 361 differentially expressed immune-related genes (IRGs). Protein-protein interaction (PPI) network analysis using the STRING database and Cytoscape software unveiled 10 key genes and 3 core subnetworks. RT-qPCR validation in bleomycin-induced IPF mouse model and A549 EMT model confirmed the reliability of most findings. These results provide new insights into IPF pathogenesis and potential therapeutic strategies, necessitating further functional validation.

PMID:40280949 | DOI:10.1038/s41598-025-97037-9

Free Radic Biol Med. 2025 Apr 23:S0891-5849(25)00244-8. doi: 10.1016/j.freeradbiomed.2025.04.034. Online ahead of print.

ABSTRACT

Mitochondrial oxidative damage-mediated dysfunction is implicated in pulmonary pathogenesis, yet the molecular mechanisms linking redox imbalance to pulmonary fibrosis remain elusive. In this study, we demonstrate that DNA methyltransferase 3A (DNMT3A) drives fibroblast activation and pulmonary fibrosis by epigenetically repressing superoxide dismutase 2 (SOD2), a critical antioxidant enzyme. Using fibroblast-specific DNMT3A-deficient mice and bleomycin-induced pulmonary fibrosis models, we observed that DNMT3A ablation significantly attenuated mitochondrial oxidant overproduction, restored mitochondrial membrane potential (MMP), and reduced fibrotic progression. Mechanistically, DNMT3A directly bound to the SOD2 promoter, inducing hypermethylation and transcriptional silencing, which exacerbated oxidative stress and fibroblast proliferation. Conversely, AAV6-mediated SOD2 overexpression or DNMT3A knockdown rescued SOD2 expression, suppressed mitochondrial oxidative burden, and ameliorated fibrosis. Clinically, idiopathic pulmonary fibrosis (IPF) patient tissues exhibited elevated DNMT3A levels, diminished SOD2 expression, and marked mitochondrial dysfunction, corroborating our experimental findings. These results unveil a novel DNMT3A/SOD2 axis as an epigenetic regulator of mitochondrial redox dysregulation-driven fibrosis, providing a potential therapeutic avenue for targeting oxidative damage in pulmonary fibrotic disorders.

PMID:40280315 | DOI:10.1016/j.freeradbiomed.2025.04.034

Biochem Pharmacol. 2025 Apr 23:116959. doi: 10.1016/j.bcp.2025.116959. Online ahead of print.

ABSTRACT

Idiopathic Pulmonary Fibrosis (IPF) is a disease that includes inflammation and scarring of the lung tissues. Cyclin-dependent kinase 8 (CDK8) is a target of interest due to its role in inflammatory pathways. CDK8 can also modulate the TGF-β/Smad signaling associated with IPF. Herein, a structure-based virtual screening (SBVS) campaign led to the identification of three CDK8 inhibitors. Testing of candidate inhibitors in protein and cellular assays confirmed CDK8 inhibition, with the most potent inhibitor producing an IC50 value of 398.8 nM. Computational analysis identified pharmacological interactions that lead to CDK8 inhibition. No significant cytotoxicity was observed when the inhibitor was treated in vitro. Further results showed that the inhibitor can disrupt proteins associated with the epithelial-mesenchymal transition (EMT) and reduce cell migration. Additionally, the inhibitor can disrupt the TGF- β1/Smad signaling axis in the nucleus, potentially impacting the transcription of IPF related protein expression, when treated in cells at 5 µM. Comparisons to structures of known CDK8 inhibitors showed the identified inhibitor to be structurally novel. When tested against a panel of kinases at 1 µM, the most potent inhibitor demonstrated a favorable CDK8 selectivity profile. The identification of the CDK8 inhibitors in this study can be used in future drug design studies and as CDK8 probes to explore alternative therapeutics for IPF.

PMID:40280247 | DOI:10.1016/j.bcp.2025.116959

Cell Biol Toxicol. 2025 Apr 25;41(1):73. doi: 10.1007/s10565-025-10031-9.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF), characterized by fibroblast activation and collagen deposition, is a progressive lung disease that lacks effective interventions. Ubiquitin-specific peptidase 10 (USP10) acts as a multifunctional player in inflammatory response and progression of cancers, the effect on pulmonary fibrosis is unknown. Here, we demonstrated downregulated expression of USP10 in fibrotic lung tissues of IPF patients. In the current study, lung tissues were collected at the end of weeks 1, 2, or 3 post bleomycin (BLM)-intratracheal delivery. Consistently, USP10 expression levels were reduced after BLM challenge in a time-dependent manner. Mice treated with lentivirus overexpressing USP10 exhibited mitigative lung injury and reduced collagen deposition. USP10 overexpression enhanced autophagy in BLM-treated mouse lungs. Interestingly, the protective effect of USP10 was attenuated as the pulmonary autophagy flux was blocked by autophagy inhibitor 3-methyladenine (3-MA). Primary human and mouse lung fibroblasts were treated with pro-fibrotic TGF-β1 to verify the role of USP10 in vitro. Mechanically, the deubiquitinating enzyme USP10 interacted with Sirtuin 6 (Sirt6) and inhibited its degradation. Furthermore, USP10 overexpression inhibited the activation of Sirt6-mediated AKT/mTOR pathway in both lung tissues and fibroblasts. Our findings suggest that USP10 might attenuate pulmonary fibrosis through the promotion of Sirt6/AKT/mTOR-mediated autophagy. These data prioritize USP10 as a therapeutic target for treating IPF.

PMID:40278953 | DOI:10.1007/s10565-025-10031-9

Infect Dis Rep. 2025 Apr 3;17(2):28. doi: 10.3390/idr17020028.

ABSTRACT

BACKGROUND: Interstitial lung diseases (ILDs) are a heterogeneous group of conditions that can cause fibrosis of the lung interstitium, resulting in respiratory failure and death. Patients with an ILD, particularly idiopathic pulmonary fibrosis (IPF) or connective tissue disease-associated ILDs (CTD-ILDs), are prone to develop chronic pulmonary infections such as tuberculosis (TB) and non-tuberculous mycobacterial pulmonary disease (NTM-PD).

METHODS: This case series examines the management of three ILD patients with a usual interstitial pneumonia (UIP) pattern and concomitant NTM-PD or TB at National Institute for Infectious Diseases "Lazzaro Spallanzani" in Rome, Italy, over three years (2019-2022).

RESULTS AND CONCLUSIONS: Multi-disciplinary discussion (MDD) was crucial to define the therapeutic approach due to the increased risk of side effects and drug interactions. Our work underscored how a comprehensive diagnostic evaluation, enriched by MDD, is useful for optimizing the management and reducing drug-related adverse effects and interactions in ILD patients with cavitary lesions.

PMID:40277955 | DOI:10.3390/idr17020028

Adv Respir Med. 2025 Mar 28;93(2):6. doi: 10.3390/arm93020006.

ABSTRACT

Background: Acute exacerbation (AE) of idiopathic pulmonary fibrosis (IPF) is one of the most challenging events in the disease course due to the high mortality despite treatment. The role of corticosteroid treatment in AE-IPF has never been defined, even though it is used in current clinical practice. We performed a meta-analysis to determine the effects of steroid treatment on the acute exacerbation outcomes in idiopathic pulmonary fibrosis (IPF). Objectives: To evaluate the impact of steroids on mortality in patients affected by an acute exacerbation of IPF. Methods: This meta-analysis was performed in accordance with the PRISMA statement. A systemic literature search was conducted through Google Scholar, Scopus, WoS, PubMed, and JSTOR. Manuscripts from January 2014 to September 2024 were included in the analysis. Articles were included on whether participants had an acute exacerbation of IPF. Regarding the intervention performed, we evaluated the studies in which patients underwent treatment with corticosteroids. As outcomes, studies were included if they analyzed the overall mortality. Results: A total of 2156 records were initially identified. Nineteen studies (3277 patients) were ultimately included in the final analysis, comparing 1552 patients who received steroids to 1725 patients without steroids. Steroid treatment poses a higher risk, as suggested by the summary measures (RR of 1.78; CI 1.29-2.76, p = 0.00001). Conclusions: This meta-analysis investigated the debated role of corticosteroid treatment during acute exacerbation of idiopathic pulmonary fibrosis. Overall, steroid therapy is associated with increased risk. Clinicians should carefully weigh the risks and benefits of corticosteroid therapy in acute exacerbation of IPF.

PMID:40277510 | DOI:10.3390/arm93020006

J Comput Aided Mol Des. 2025 Apr 25;39(1):19. doi: 10.1007/s10822-025-00596-2.

ABSTRACT

Ubiquitin-specific proteases (USPs) are crucial regulators of protein degradation pathways, influencing diverse cellular processes and disease mechanisms. Among them, USP30 plays a pivotal role in mitochondrial quality control and has been implicated in idiopathic pulmonary fibrosis (IPF), a chronic lung disease for which current therapies merely slow disease progression. The high flexibility of USP30's catalytic site, coupled with its dependence on covalent interaction with the catalytic cysteine presents significant challenges in discovering suitable small molecule inhibitors. In this study, we identified three non-covalent small molecule inhibitors for USP30 using molecular modeling, X-ray crystallography, and virtual screening. These findings offer valuable insights and novel chemical starting points for further medicinal chemistry optimization.

PMID:40274689 | DOI:10.1007/s10822-025-00596-2

J Ethnopharmacol. 2025 Apr 22:119866. doi: 10.1016/j.jep.2025.119866. Online ahead of print.

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Saengmaek-san (SMS) is a herbal prescription comprising Liriope platyphylla, Panax ginseng, and Schisandra chinensis. In traditional Korean medicine (TKM), SMS has been used to treat a condition known as the dual deficiency of qi and yin in the lungs, a syndrome characterized by the depletion of vitality and body fluids, often resulting from heat exhaustion. SMS has primarily been used to promote fluid production, alleviate dry cough, and relieve progressive dyspnea.

AIM OF THE STUDY: The current study was planned to explore the efficacy and underlying mechanisms of SMS in managing idiopathic pulmonary fibrosis.

MATERIALS AND METHODS: In mice with bleomycin-induced pulmonary fibrosis, the SMS water extract was administered at doses of 50, 150, and 450 mg/kg twice daily for 14 days. The extent of pulmonary fibrosis was assessed using the Ashcroft scale in stained lung tissues. The levels of transforming growth factor-β, α-smooth muscle actin (α-SMA), and collagen accumulation were also evaluated. Bronchoalveolar lavage fluid (BALF) was collected to measure the total cell counts, white blood cell ratios, and cytokine levels (IL-6 and IL-10).

RESULTS: We observed statistically significant and potential anti-fibrotic effects in the SMS 450 mg/kg treatment group in terms of preventing body weight loss, decreasing Ashcroft scale, and reducing macrophage and granulocyte counts in BALF, as well as reducing α-SMA and collagen production. Additionally, an increase was observed in the levels of anti-inflammatory cytokine IL-10.

CONCLUSIONS: SMS demonstrated potential as a therapeutic candidate for idiopathic pulmonary fibrosis by exerting anti-inflammatory effects and reducing collagen deposition.

PMID:40274032 | DOI:10.1016/j.jep.2025.119866

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