Front Pharmacol. 2025 Feb 28;16:1486357. doi: 10.3389/fphar.2025.1486357. eCollection 2025.

ABSTRACT

BACKGROUND: Glycolysis plays a crucial role in fibrosis, but the specific genes involved in glycolysis in idiopathic pulmonary fibrosis (IPF) are not well understood.

METHODS: Three IPF gene expression datasets were obtained from the Gene Expression Omnibus (GEO), while glycolysis-related genes were retrieved from the Molecular Signatures Database (MsigDB). Differentially expressed glycolysis-related genes (DEGRGs) were identified using the "limma" R package. Diagnostic glycolysis-related genes (GRGs) were selected through least absolute shrinkage and selection operator (LASSO) regression regression and support vector machine-recursive feature elimination (SVM-RFE). A prognostic signature was developed using LASSO regression, and time-dependent receiver operating characteristic (ROC) curves were generated to evaluate predictive performance. Single-cell RNA sequencing (scRNA-seq) data were analyzed to examine GRG expression across various cell types. Immune infiltration analysis, Gene Set Enrichment Analysis (GSEA), and Gene Set Variation Analysis (GSVA) were performed to elucidate potential molecular mechanisms. A bleomycin (BLM)-induced pulmonary fibrosis mouse model was used for experimental validation via reverse transcription-quantitative polymerase chain reaction (RT-qPCR).

RESULTS: 14 GRGs (VCAN, MERTK, FBP2, TPBG, SDC1, AURKA, ARTN, PGP, PLOD2, PKLR, PFKM, DEPDC1, AGRN, CXCR4) were identified as diagnostic markers for IPF, with seven (ARTN, AURKA, DEPDC1, FBP2, MERTK, PFKM, SDC1) forming a prognostic model demonstrating predictive power (AUC: 0.831-0.793). scRNA-seq revealed cell-type-specific GRG expression, particularly in macrophages and fibroblasts. Immune infiltration analysis linked GRGs to imbalanced immune responses. Experimental validation in a bleomycin-induced fibrosis model confirmed the upregulation of GRGs (such as AURKA, CXCR4). Drug prediction identified inhibitors (such as Tozasertib for AURKA, Plerixafor for CXCR4) as potential therapeutic agents.

CONCLUSION: This study identifies GRGs as potential prognostic biomarkers for IPF and highlights their role in modulating immune responses within the fibrotic lung microenvironment. Notably, AURKA, MERTK, and CXCR4 were associated with pathways linked to fibrosis progression and represent potential therapeutic targets. Our findings provide insights into metabolic reprogramming in IPF and suggest that targeting glycolysis-related pathways may offer novel pharmacological strategies for antifibrotic therapy.

PMID:40093327 | PMC:PMC11906445 | DOI:10.3389/fphar.2025.1486357

Open Vet J. 2025 Jan;15(1):118-125. doi: 10.5455/OVJ.2024.v15.i1.11. Epub 2025 Jan 31.

ABSTRACT

BACKGROUND: Pulmonary fibrosis represents the most prevalent form of idiopathic interstitial pneumonia. The pathogenesis of pulmonary fibrosis using a bleomycin-induced mice model has indicated an imbalanced immune response such as an early massive inflammatory response, followed by fibrosis development. Therapy focused on restraining inflammation is one of the ways to inhibit fibrosis development. Elephantopus scaber ethanolic extract (ESEE) is known to have many beneficial compounds that were proven to possess anti-inflammatory activities, but its prospect in inhibiting pulmonary fibrosis development needs to be investigated.

AIM: This study aimed to evaluate the potency of ESEE treatment in inhibiting fibrosis development in the bleomycin-induced pulmonary fibrosis mice model.

METHODS: Healthy male BALB/c mice were divided into seven experimental groups (n = 8): healthy mice (N), vehicle mice (VC), pulmonary fibrosis mice (C-), pulmonary fibrosis received dexamethasone (C+), and pulmonary fibrosis mice received ESEE at a 0.0504 mg/kg body weight (BW) (D1), 0.1008 mg/kg BW (D2), and 0.2016 mg/kg BW (D3). Mice were given ESEE orally and intraperitoneal bleomycin injection daily for 14 days. Mice were then sacrificed on days 7 and 14 and spleens were isolated to determine the production of IL-10, TNF-α, and IFN-γ using flow cytometry.

RESULTS: The results revealed that a remarkable increase of TNF-α was found in the macrophage of pulmonary fibrosis mice model from day 7 to 14. An increase in IFN-γ production was also observed on day 7 and then decreased on day 14. The production of IL-10 was reduced in the fibrosis group at day 7 and continued to increase at day 14. Interestingly, ESEE treatment for 14 days could effectively reduce TNF-α and increase IFN-γ production. ESEE treatment could also maintain a stable production of IL-10 at each time point. ESEE at 0.1004 mg/kg BW (D2) showed the most effective activity in reducing pro-fibrotic cytokine than the dexamethasone group.

CONCLUSION: Ethanolic extract of ESEE has demonstrated its beneficial prospect in regulating pro-inflammatory and pro-fibrotic cytokine to inhibit fibrosis development.

PMID:40092211 | PMC:PMC11910286 | DOI:10.5455/OVJ.2024.v15.i1.11

J Transl Med. 2025 Mar 16;23(1):337. doi: 10.1186/s12967-025-06368-8.

ABSTRACT

OBJECTIVE: To identify potential therapeutic targets and evaluate the safety profiles for Idiopathic Pulmonary Fibrosis (IPF) using a comprehensive multi-omics approach.

METHOD: We integrated genomic and transcriptomic data to identify therapeutic targets for IPF. First, we conducted a transcriptome-wide association study (TWAS) using the Omnibus Transcriptome Test using Expression Reference Summary data (OTTERS) framework, combining plasma expression quantitative trait loci (eQTL) data with IPF Genome-Wide Association Studies (GWAS) summary statistics from the Global Biobank (discovery) and Finngen (duplication). We then applied Mendelian randomization (MR) to explore causal relationships. RNA-seq co-expression analysis (bulk, single-cell and spatial transcriptomics) was used to identify critical genes, followed by molecular docking to evaluate their druggability. Finally, phenome-wide MR (PheW-MR) using GWAS data from 679 diseases in the UK Biobank assessed the potential adverse effects of the identified genes.

RESULT: We identified 696 genes associated with IPF in the discovery dataset and 986 genes in the duplication dataset, with 126 overlapping genes through TWAS. MR analysis revealed 29 causal genes in the discovery dataset, with 13 linked to increased and 16 to decreased IPF risk. Summary data-based MR (SMR) confirmed six essential genes: ANO9, BRCA1, CCDC200, EZH1, FAM13A, and SFR1. Bulk RNA-seq showed FAM13A upregulation and SFR1 and EZH1 downregulation in IPF. Single-cell RNA-seq revealed gene expression changes across cell types. Molecular docking identified binding solid affinities for essential genes with respiratory drugs, and PheW-MR highlighted potential side effects.

CONCLUSION: We identified six key genes-ANO9, BRCA1, CCDC200, EZH1, FAM13A, and SFR1-as potential drug targets for IPF. Molecular docking revealed strong drug affinities, while PheW-MR analysis highlighted therapeutic potential and associated risks. These findings offer new insights for IPF treatment and further investigation of potential side effects.

PMID:40091050 | DOI:10.1186/s12967-025-06368-8

Contemp Clin Trials. 2025 Mar 14:107883. doi: 10.1016/j.cct.2025.107883. Online ahead of print.

ABSTRACT

BACKGROUND: Pulmonary fibrosis is a major complication of the Acute Respiratory Distress Syndrome (ARDS). Pirfenidone is an approved treatment for idiopathic pulmonary fibrosis. It may attenuate ARDS-related fibrosis and decrease the need for prolonged ventilation. Accordingly, we aimed to evaluate the effect of pirfenidone on ventilator-free days in patients with ARDS.

METHODS: In a multi-center, randomized, double-blind, placebo-controlled trial, we plan to randomly assign 130 adults invasively ventilated for ARDS to receive pirfenidone or placebo for up to 28 days. The primary outcome is days alive and ventilator free at 28 days. Secondary outcomes include ICU-free days, hospital free days all at 28 day, ICU mortality and hospital mortality. We will also assess fibroproliferative changes on high-resolution CT scans at ICU discharge and quality of life. Data analysis will be on an intention-to-treat basis.

DISCUSSION: The trial is ongoing and currently recruiting. It will be the first randomized controlled study to investigate whether, compared to placebo, pirfenidone reduces the number of days alive and ventilator-free in patients with ARDS. Its double-blind multicenter design will provide internal validity, minimal bias, and a degree of external validity. If our hypothesis is confirmed, this treatment would justify larger trials of this intervention.

TRIAL REGISTRATION: This trial was registered on ClinicalTrials.gov with the trial identification NCT05075161.

PMID:40090666 | DOI:10.1016/j.cct.2025.107883

SLAS Discov. 2025 Mar 14:100226. doi: 10.1016/j.slasd.2025.100226. Online ahead of print.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive age-related lung disease with an average survival of 3-5 years post-diagnosis if left untreated. It is characterized by lung fibrosis, inflammation, and destruction of lung architecture, leading to worsening respiratory symptoms and physiological impairment, ultimately culminating in progressive respiratory failure. The development of novel therapeutics for the treatment of IPF represents a significant unmet medical need. Fibroblast to myofibroblast transition (FMT) in response to fibrogenic mediators such as transforming growth factor beta 1 (TGF-β1) has been identified as a key cellular phenotype driving the formation of myofibroblasts and lung fibrosis in IPF. Establishing a robust and high-throughput in vitro human FMT assay is crucial for uncovering new disease targets and for efficiently screening compounds for the advancement of novel therapeutics aimed at targeting myofibroblast activity. However, creating a robust FMT assay suitable for high-throughput drug screening has proven challenging due to the requisite level of automation. In this study, we focus on evaluating different automation approaches for liquid exchange and compound dosing in the human FMT assay. A semi-automated assay, capable of screening a large number of compounds that inhibit TGF-β1-induced FMT in both Normal Human Lung Fibroblasts (NHLF) and IPF-patient derived Disease Human Lung Fibroblasts (IPF-DHLF), has been successfully developed and optimized. We demonstrate that the optimized FMT assay using liquid handling automation exhibits great assay reproducibility, shows good assay translation using human lung fibroblasts from normal healthy versus IPF-patients, and demonstrates acceptable human primary donor variability. This allows for the standardization of comparisons of compound anti-fibrotic potency across IPF projects.

PMID:40090552 | DOI:10.1016/j.slasd.2025.100226

Semin Arthritis Rheum. 2025 Mar 15;72:152708. doi: 10.1016/j.semarthrit.2025.152708. Online ahead of print.

ABSTRACT

OBJECTIVE: Genome-wide association studies (GWAS) facilitate construction of polygenic risk scores (PRSs) for rheumatoid arthritis (RA) and idiopathic pulmonary fibrosis (IPF). We investigated associations of RA and IPF PRSs with RA and high-resolution chest computed tomography (HRCT) parenchymal lung abnormalities.

METHODS: Participants in COPDGene, a prospective multicenter cohort of current/former smokers, had chest HRCT at study enrollment. Using genome-wide genotyping, RA and IPF PRSs were constructed using GWAS summary statistics. HRCT imaging underwent visual inspection for interstitial lung abnormalities (ILA) and quantitative CT (QCT) analysis using a machine-learning algorithm that quantified percentage of normal lung, interstitial abnormalities, and emphysema. RA was identified through self-report and DMARD use. We investigated associations of RA and IPF PRSs with RA, ILA, and QCT features using multivariable logistic and linear regression.

RESULTS: We analyzed 9,230 COPDGene participants (mean age 59.6 years, 46.4 % female, 67.2 % non-Hispanic White, 32.8 % Black/African American). In non-Hispanic White participants, RA PRS was associated with RA diagnosis (OR 1.32 per unit, 95 %CI 1.18-1.49) but not ILA or QCT features. Among non-Hispanic White participants, IPF PRS was associated with ILA (OR 1.88 per unit, 95 %CI 1.52-2.32) and quantitative interstitial abnormalities (adjusted β=+0.50 % per unit, p = 7.3 × 10-8) but not RA. There were no statistically significant associations among Black/African American participants.

CONCLUSIONS: RA and IPF PRSs were associated with their intended phenotypes among non-Hispanic White participants but performed poorly among Black/African American participants. PRS may have future application to risk stratify for RA diagnosis among patients with ILD or for ILD among patients with RA.

PMID:40090204 | DOI:10.1016/j.semarthrit.2025.152708

Phytomedicine. 2025 Mar 8;140:156628. doi: 10.1016/j.phymed.2025.156628. Online ahead of print.

ABSTRACT

BACKGROUND: The Active Ingredient Composition of Jinshui Huanxian Formula (ECC-JHF) consists of five active ingredients: icariin, isoliquiritigenin, nobiletin, peimine, and paeoniflorin, which demonstrate notable therapeutic effects on pulmonary fibrosis.

PURPOSE: Inhibition of glycolysis has been demonstrated to be effective in treating experimental idiopathic pulmonary fibrosis (IPF). This research seeks to explore the impact of aerobic glycolysis on the mitigation of pulmonary fibrosis through ECC-JHF.

METHODS: A pulmonary fibrosis mouse model was generated through the administration of bleomycin (Bleomycin). The degree of pulmonary fibrosis was analyzed through hematoxylin and eosin (H&E) staining as well as Masson's trichrome staining. Western Blot (WB), Immunofluorescence (IF), and real-time quantitative PCR (Q-PCR) assay for fibroblast activation markers and glycolysis-related genes in lung tissues. The Lactic Acid (LA) Content Assay Kit was employed to quantify lactate concentrations in lung tissues and fibroblast cultures. Immunoprecipitation (IP) was applied to detect lactylated modified protein levels, and mass spectrometry (MS) was used to analyze lactate substrate profiles in fibroblasts. WB was employed to detect the lactate modification level of histone H3K18 (H3K18la). The targets of ECC-JHF were analyzed using network pharmacology, while molecular docking and cellular enthusiasm transfer analysis (CETSA) examined the binding of ECC-JHF to SRC. The influence of ECC-JHF on SRC activation was assessed using WB. SRC small interfering RNA (siSRC) was designed and transfected into L929 cells to validate the function of SRC in the inhibition of fibroblast activation by ECC-JHF.

RESULTS: In BLM-induced pulmonary fibrosis mice, ECC-JHF significantly reduced alveolar inflammation and collagen deposition. In lung tissues and fibroblasts, ECC-JHF notably inhibited the expression of HK2, lactate levels, and lactylated modifying proteins. IP-MS and WB analyses showed that ECC-JHF significantly reduced H3K18la levels. Network pharmacology analysis, molecular docking and CETSA results indicated that SRC serves as a key target for ECC-JHF. siSRC effectively mitigated the impact of ECC-JHF on the expression of HK2, levels of H3K18la, and the activation of fibroblasts.

CONCLUSION: ECC-JHF may improve pulmonary fibrosis by inhibiting SRC activation, blocking HK2-mediated lactate production, down-regulating H3K18la levels, and inhibiting fibroblast activation. Our results serve as a significant reference for the advancement of ECC-JHF and the exploration of IPF.

PMID:40090047 | DOI:10.1016/j.phymed.2025.156628

Expert Rev Pharmacoecon Outcomes Res. 2025 Mar 16. doi: 10.1080/14737167.2025.2480718. Online ahead of print.

ABSTRACT

INTRODUCTION: Objective: To systematically review studies on the cost-effectiveness of pirfenidone compared to nintedanib in patients with idiopathic pulmonary fibrosis (IPF).

METHODS: Data sources: PubMed, EMBASE, Scopus, and Web of Science. Inclusion criteria: Full economic evaluations comparing pirfenidone versus nintedanib in IPF patients. Assessment: Quality of Health Economic Studies (QHES) tool for study quality.

RESULTS: Nine studies met the inclusion criteria with QHES scores of 0.91 or higher. The incremental cost-effectiveness ratios (ICERs) ranged from $66,434 to $1,668,321 per quality-adjusted life year (QALY) in the United States. Nintedanib was found to be cost-effective in five studies.

CONCLUSIONS: Nine studies met the inclusion criteria with QHES scores of 0.91 or higher. The incremental cost-effectiveness ratios (ICERs) ranged from $66,434 to $1,668,321 per quality-adjusted life year (QALY) in the United States. Nintedanib was found to be cost-effective in five studies.Nintedanib appears to be a more cost-effective treatment for IPF compared to pirfenidone. Further research is needed, particularly in low- and middle-income countries, considering healthcare system perspectives and varied willingness-to-pay thresholds.

PMID:40089935 | DOI:10.1080/14737167.2025.2480718

BMC Health Serv Res. 2025 Mar 15;25(1):385. doi: 10.1186/s12913-025-12506-1.

ABSTRACT

OBJECTIVES: Novel non-invasive machine learning algorithms may improve accuracy and reduce the need for biopsy when diagnosing idiopathic pulmonary fibrosis (IPF). We conducted a cost-effectiveness analysis of diagnostic strategies for IPF.

METHODS: We developed a decision analytic model to evaluate diagnostic strategies for IPF in the United States. To assess the full spectrum of costs and benefits, we compared four interventions: a machine learning diagnostic algorithm, a genomic classifier, a biopsy-all strategy, and a treat-all strategy. The analysis was conducted from the health sector perspective with a lifetime horizon. The primary outcome measures were costs, Quality-Adjusted Life-Years (QALYs) gained, and Incremental Cost-Effectiveness Ratios (ICERs) based on the average of 10,000 probabilistic runs of the model.

RESULTS: Compared to a biopsy-all strategy the machine learning algorithm and genomic classifer reduced diagnostic-related costs by $14,876 and $3,884, respectively. Use of the machine learning algorithm consistently reduced diagnostic costs. When including downstream treatment costs and benefits of anti-fibrotic treatment, the machine learning algorithm had an ICER of $331,069 per QALY gained compared to the biopsy-all strategy. The genomic classifier had a higher ICER of $390,043 per QALY gained, while the treat-all strategy had the highest ICER of $3,245,403 per QALY gained. Results were sensitive to changes in various input parameters including IPF treatment costs, sensitivity and specificity of novel screening tools, and the rate of additional diagnostics following inconclusive results. High treatment costs were found to drive overall cost regardless of the diagnostic method. As treatment costs lowered, the supplemental diagnostic tools became increasingly cost-effective.

CONCLUSIONS: Novel tools for diagnosing IPF reduced diagnostic costs, while overall incremental cost-effectiveness ratios were high due to treatment costs. New IPF diagnosis approaches may become more favourable with lower-cost treatments for IPF.

PMID:40089758 | DOI:10.1186/s12913-025-12506-1

Toxicol Appl Pharmacol. 2025 Mar 13:117285. doi: 10.1016/j.taap.2025.117285. Online ahead of print.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF), a progressive interstitial lung disease of unknown etiology, remains a therapeutic challenge with limited treatment options. This study investigates the therapeutic potential and molecular mechanisms of Tryptanthrin, a bioactive indole quinazoline alkaloid derived from Isatis tinctoria L., in pulmonary fibrosis. In a bleomycin-induced murine IPF model, Tryptanthrin administration (5 and 10 mg/kg/day for 28 days) significantly improved pulmonary function parameters and attenuated histological evidence of fibrosis. Mechanistic analysis revealed dual pathway modulation: Tryptanthrin suppressed MAPK/NF-κB signaling through inhibition of phosphorylation events, subsequently reducing pulmonary levels of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6). Concurrently, it attenuated TGF-β1/Smad pathway activation by decreasing TGF-β1 expression and Smad2/3 phosphorylation, thereby downregulating fibrotic markers including COL1A1, α-smooth muscle actin (α-SMA), and fibronectin in lung tissues. Complementary in vitro studies using Lipopolysaccharide (LPS) or TGF-β1-stimulated NIH3T3 fibroblasts confirmed these anti-inflammatory and anti-fibrotic effects through analogous pathway inhibition. Our findings demonstrate that Tryptanthrin exerts therapeutic effects against pulmonary fibrosis via coordinated modulation of both inflammatory (MAPK/NF-κB) and fibrotic (TGF-β1/Smad) signaling cascades, suggesting its potential as a novel multi-target therapeutic agent for IPF management.

PMID:40089192 | DOI:10.1016/j.taap.2025.117285

BMC Pulm Med. 2025 Mar 14;25(1):118. doi: 10.1186/s12890-025-03572-6.

ABSTRACT

OBJECTIVE: Respiratory muscle dysfunction in patients with idiopathic pulmonary fibrosis (IPF) is a big challenge for treatment and rehabilitation. To quantitatively assess diaphragm and chest wall dysfunction using dynamic Magnetic Resonance Imaging (Dyn-MRI) in patients with IPF.

METHODS: Ninety-six patients with IPF and 50 gender- and age-matched controls were prospectively included and underwent D-MRI with a dynamic fast spoiled gradient-recalled echo sequence. Respiratory muscles function were assessed with thoracic anterior-posterior (AP), left-right (LR), cranial-caudal (CC) metrics. Moreover, lung area ratios, height (DH), and area (DA) of diaphragm curvature between end-inspiration and end-expiration during both quiet and deep breathing.

RESULTS: During quiet breathing, the functional metrics of the diaphragm and chest wall were comparable between IPF patients and controls. However, during deep breathing, IPF patients exhibited significantly reduced ratios of AP, CC, and lung area compared to controls. Moreover, the median ratios of DH and DA were higher in IPF patients than in controls (DH: 0.96 vs. 0.81, p < 0.001; DA: 1.00 vs. 0.90, p < 0.001). Furthermore, the ratios of AP, CC, and lung area during deep breathing were found to correlate with pulmonary function, total lung volume, and 6-minute walk distance.

CONCLUSION: D-MRI demonstrated dysfunction in the diaphragm and chest wall among IPF patients, with respiratory muscle dysfunction showing a correlation with the severity of disease.

TRIAL REGISTRATION: This article presents a prospective observational study that does not include the outcomes of any healthcare interventions on human participants. The study was registered on September 11, 2018, under the registration number NCT03666234.

PMID:40087606 | DOI:10.1186/s12890-025-03572-6

Am J Hosp Palliat Care. 2025 Mar 14:10499091251325566. doi: 10.1177/10499091251325566. Online ahead of print.

ABSTRACT

BackgroundDyspnea is a prevalent and distressing symptom in interstitial lung diseases with significant effects on patients' quality of life and associated with poorer prognosis. Guidelines recommend a multidimensional dyspnea assessment tool. We developed a validated 9-item scale, the Edmonton Dyspnea Inventory (EDI), in which dyspnea severity is rated across different settings including at rest, during activities of daily living, and self-reported exercise and crises. The standardized, multidimensional tool captures dyspnea intensity for specific contexts, which clinicians can use to manage dyspnea more individually and effectively. Early studies support the feasibility to use the EDI in outpatient settings. The purpose of this study was to explore perceptions of the EDI by community health care professionals.MethodsWe conducted a qualitative study using an inductive approach and open coding for content analysis. Email invitations were sent to community health care professionals and informed consent obtained from the twelve participants. Two focus groups and one key informant interview were conducted. Themes were extracted from transcripts and field note analyses.ResultsFour main themes described their dyspnea assessment with the EDI: the EDI is a meaningful clinical assessment tool; they explicitly engage and educate patients to effectively use the EDI; they use the EDI to personalize and evaluate dyspnea management; and the EDI is valuable for communication and interprofessional collaboration.ConclusionCommunity health care professionals perceived the EDI as valuable to assess dyspnea and personalize management. They recommended it be used in clinical practice and healthcare education for interprofessional dyspnea management for ILD patients.

PMID:40085021 | DOI:10.1177/10499091251325566

J Rehabil Med Clin Commun. 2025 Mar 6;8:40698. doi: 10.2340/jrm-cc.v8.40698. eCollection 2025.

ABSTRACT

OBJECTIVE: To evaluate the benefits of inpatient rehabilitation for a patient with post-COVID-19 pulmonary fibrosis and to provide guidance for rehabilitation professionals, as many conventional therapeutic interventions are not tolerated and are poorly defined.

DESIGN: A case report.

SUBJECTS/PATIENTS: A 72-year-old man with a COVID-19-related idiopathic pulmonary fibrosis exacerbation.

RESULTS: The patient was admitted to inpatient rehabilitation with hypoxia and poor endurance for functional activities. Rehabilitation activities were focused on providing patient/family education, energy conservation, low level activities to build strength, problem solving for mobility, and discharge planning within safe medical parameters. Rehabilitation therapies were graded to meet the patient's physiologic needs and focused on patient and family training. The patient made limited functional gains and continued to have high oxygen needs but achieved his goal of returning home.

CONCLUSION: Patients with COVID-19-related idiopathic pulmonary fibrosis exacerbations can be treated in acute rehabilitation effectively. With more patients developing post-COVID-19 pulmonary fibrosis, appropriate rehabilitation strategies are important for safe discharge planning. Prioritizing patient/family education may allow these more medically fragile patients to return home.

PMID:40083891 | PMC:PMC11905151 | DOI:10.2340/jrm-cc.v8.40698

Ther Adv Respir Dis. 2025 Jan-Dec;19:17534666251326743. doi: 10.1177/17534666251326743. Epub 2025 Mar 14.

ABSTRACT

BACKGROUND: Pulmonary fibrosis is a severe, progressive form of interstitial lung disease associated with increased morbidity and mortality. Pulmonary hypertension often accompanies severe pulmonary fibrosis and is also associated with worse outcomes. Antifibrotic therapy and pulmonary vasodilator therapy have demonstrated clinical benefits in pulmonary fibrosis and pulmonary hypertension, respectively. However, the benefit of combined antifibrotic and pulmonary vasodilator therapy in patients with both pulmonary fibrosis and pulmonary hypertension is less established.

OBJECTIVES: We aimed to determine the effectiveness of a combination pulmonary vasodilator and antifibrotic therapy with regard to transplant-free survival and six-minute walk distance improvement in patients with pulmonary fibrosis and pulmonary hypertension.

DESIGN: This was a retrospective cohort study of patients with pulmonary fibrosis (idiopathic pulmonary fibrosis, combined pulmonary fibrosis and emphysema, and other fibrotic interstitial lung disease) and pulmonary hypertension diagnosed via right heart catheterization. Patients received antifibrotic therapy with or without pulmonary vasodilator therapy.

METHODS: Patients who received combination antifibrotic therapy and pulmonary vasodilator therapy were compared to those prescribed antifibrotic therapy alone. Transplant-free survival and change in six-minute walk distance were compared between the two groups. Multivariable Cox regression was performed to determine predictors of transplant-free survival.

RESULTS: Patients who received antifibrotic and pulmonary vasodilator therapy had significantly improved transplant-free survival (log rank p = 0.001). Treatment with antifibrotic and pulmonary vasodilator therapy was significantly and independently associated with reduced risk of death or lung transplantation (HR 0.24, 95% CI 0.06-0.93, p = 0.04). These patients had worse pulmonary hemodynamics than those receiving antifibrotic therapy alone.

CONCLUSION: We found a potential survival benefit when pulmonary vasodilator therapy was given in combination with antifibrotic therapy in patients with pulmonary fibrosis and pulmonary hypertension. This may be reflective of a pulmonary vascular phenotype among those with pulmonary fibrosis and pulmonary hypertension. Further trials are needed to better elucidate which patients benefit from combination therapy.

PMID:40083194 | DOI:10.1177/17534666251326743

Thorax. 2025 Mar 13:thorax-2024-221537. doi: 10.1136/thorax-2024-221537. Online ahead of print.

ABSTRACT

BACKGROUND: The diagnosis of interstitial lung disease (ILD) can pose a challenge as the pulmonary function test (PFT) is only minimally affected at the onset. To improve early diagnosis, this study aims to explore the potential of artificial intelligence (AI) software in assisting pulmonologists with PFT interpretation for ILD diagnosis. The software provides an automated description of PFT and disease probabilities computed from an AI model.

STUDY METHODS: In study phase 1, a cohort of 60 patients, 30 of whom had ILD, were retrospectively diagnosed by 25 pulmonologists (8 junior physicians and 17 experienced pneumologists) by evaluating a PFT (body plethysmography and diffusion capacity) and a short medical history. The experts screened the cohort twice, without and with the aid of AI (ArtiQ.PFT, V.1.4.0, ArtiQ, BE) software and provided a primary diagnosis and up to three differential diagnoses for each case. In study phase 2, 19 pulmonologists repeated the protocol after using ArtiQ.PFT for 4-6 months.

RESULTS: Overall, AI increased the diagnostic accuracy for various lung diseases from 41.8% to 62.3% in study phase 1. Focusing on ILD, AI improved the detection of lung fibrosis as the primary diagnosis from 42.8% without AI to 72.1% with AI (p<0.0001). Phase 2 yielded a similar outcome: using AI increased ILD diagnosis based on primary diagnosis (53.2% to 75.1%; p<0.0001). ILD detections without AI support significantly increased between phase 1 and phase 2 (p=0.028) but not with AI (p=0.24).

INTERPRETATION: This study shows that AI-based decision support on PFT interpretation improves accurate and early ILD diagnosis.

PMID:40081903 | DOI:10.1136/thorax-2024-221537

Tuberc Respir Dis (Seoul). 2025 Mar 13. doi: 10.4046/trd.2024.0181. Online ahead of print.

ABSTRACT

Rare forms of interstitial lung diseases (ILDs) present with unique clinical features and require different treatment strategies. Respiratory bronchiolitis-associated ILD mainly affects smokers, showing ground-glass opacities on chest computed tomography (CT) scans and pigmented macrophages in the bronchoalveolar lavage fluid. Smoking cessation is essential for treatment, with corticosteroids used for severe cases. Desquamative interstitial pneumonia, also related to smoking, is characterized by exertional dyspnea, dry cough, restrictive lung function, and ground-glass opacities on high-resolution CT. Lymphoid interstitial pneumonia involves lymphocytic proliferation and is associated with autoimmune diseases or infections, treated with corticosteroids. Acute interstitial pneumonia resembles acute respiratory distress syndrome but occurs without a clear cause and is managed with supportive care. Idiopathic pleuroparenchymal fibroelastosis results in fibrosis in the upper lobes, primarily in nonsmokers, and is diagnosed through clinical and imaging findings, with no effective treatment to improve survival. Each condition has distinct pathological features, clinical presentations, and treatment approaches, along with variable prognoses.

PMID:40081337 | DOI:10.4046/trd.2024.0181

Respir Investig. 2025 Mar 12;63(3):334-341. doi: 10.1016/j.resinv.2025.03.005. Online ahead of print.

ABSTRACT

BACKGROUND: The 6-min walk test (6MWT) is frequently used in pulmonary fibrosis (PF) research. It evaluates an individual's sub-maximal exercise performance by measuring the distance they walk and their vital signs across 6 min. In research studies, the 6-min walk distance (6MWD) is often used as a surrogate marker for disease progression. The aim of this study was to systematically assess the association between 6MWT parameters and mortality in PF.

METHODS: MEDLINE, EMBASE, CINAHL, and CENTRAL databases were searched for studies reporting mortality and 6MWD in patients with PF. Study quality was assessed using a modified Newcastle-Ottawa Scale. Studies were included if they reported associations between the 6MWT in pulmonary fibrosis and mortality. Results were presented as a narrative synthesis.

RESULTS: 2312 studies were identified, 22 studies met the pre-defined inclusion criteria, comprising 5940 Idiopathic PF patients. Baseline 6MWD was found to be loosely associated with mortality (Ranges: univariate HR 0.89-4.72, multivariate HR 0.96-2.65), while a decrease in 6MWD across 24-weeks was correlated with a higher risk of mortality (Ranges: univariate HR 2.25-4.81, multivariate HR 1.72-4.3).

DISCUSSION: This review found that a low baseline 6MWD, and a 6-month decrease in 6MWD were strongly correlated with increased mortality in Idiopathic PF patients. As the 6MWT is a safe, easy-to-conduct test, it is appropriate for use as a marker of patient prognosis, in both clinical and research settings.

OPEN SCIENCE FRAMEWORK PROTOCOL REGISTRATION: DOI 10.17605/OSF.IO/3D7BV.

PMID:40081204 | DOI:10.1016/j.resinv.2025.03.005

Funct Integr Genomics. 2025 Mar 13;25(1):62. doi: 10.1007/s10142-025-01571-8.

NO ABSTRACT

PMID:40080215 | DOI:10.1007/s10142-025-01571-8

Radiol Cardiothorac Imaging. 2025 Apr;7(2):e240382. doi: 10.1148/ryct.240382.

ABSTRACT

Pleuroparenchymal fibroelastosis (PPFE) is an interstitial lung disease (ILD) characterized at CT by upper lobe-predominant pleural thickening and subpleural fibrosis and histologically by visceral pleural fibrosis and subpleural fibroelastosis. Although initially classified as a rare idiopathic interstitial pneumonia, many cases are related to known risk factors, particularly hematopoietic stem cell and lung transplant, or observed in association with other ILDs. This review summarizes the diagnostic criteria for PPFE and illustrates the CT and histologic manifestations, aiming to familiarize the radiologist with the range of findings suggestive of the diagnosis. Keywords: Conventional Radiography, CT, Pulmonary, Thorax, Lung, Pleura, Complications, Transplantation, Fibrosis © RSNA, 2025.

PMID:40079759 | DOI:10.1148/ryct.240382

Int J Mol Sci. 2025 Mar 5;26(5):2327. doi: 10.3390/ijms26052327.

ABSTRACT

Filtration bleb (FB) fibrosis represents the primary risk factor for glaucoma filtration surgery (GFS) failure. We reviewed the most recent literature on post-GFS fibrosis in humans, focusing on novel molecular pathways and antifibrotic treatments. Three main literature searches were conducted. First, we performed a narrative review of two models of extra-ocular fibrosis, idiopathic pulmonary fibrosis and skin fibrosis, to improve the comprehension of ocular fibrosis. Second, we conducted a systematic review of failed FB features in the PubMed, Embase, and Cochrane Library databases. Selected studies were screened based on the functional state and morphological features of FB. Third, we carried out a narrative review of novel potential antifibrotic molecules. In the systematic review, 11 studies met the criteria for analysis. Immunohistochemistry and genomics deemed SPARC and transglutaminases to be important for tissue remodeling and attributed pivotal roles to TGFβ and M2c macrophages in promoting FB fibrosis. Four major mechanisms were identified in the FB failure process: inflammation, fibroblast proliferation and myofibroblast conversion, vascularization, and tissue remodeling. On this basis, an updated model of FB fibrosis was described. Among the pharmacological options, particular attention was given to nintedanib, pirfenidone, and rapamycin, which are used in skin and pulmonary fibrosis, since their promising effects are demonstrated in experimental models of FB fibrosis. Based on the most recent literature, modern patho-physiological models of FB fibrosis should consider TGFβ and M2c macrophages as pivotal players and favorite targets for therapy, while research on antifibrotic strategies should clinically investigate medications utilized in the management of extra-ocular fibrosis.

PMID:40076946 | DOI:10.3390/ijms26052327