Am J Physiol Cell Physiol. 2025 Mar 20. doi: 10.1152/ajpcell.00374.2024. Online ahead of print.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a progressive and degenerative interstitial lung disease characterized by complex etiology, unclear pathogenesis, and high mortality. Long non-coding RNAs (lncRNAs) have been identified as key regulators in modulating the initiation, maintenance, and progression of pulmonary fibrosis. However, the precise pathological mechanisms through which lncRNAs are involved in IPF remain limited and require further elucidation. A novel lncABCE1-5 was identified as significantly decreased by an ncRNA microarray analysis in our eight IPF lung samples compared with three donor tissues and validated by qRT-PCR analysis in clinical lung samples. To investigate the biological function of ABCE1-5, we performed loss-and gain-of-function experiments in vitro and in vivo. LncABCE1-5 silencing promoted A549 cell migration and A549 and BEAS-2B cell apoptosis, while enhancing the expression of proteins associated with extracellular matrix deposition, whereas overexpression of ABCE1-5 partially attenuated TGF-β-induced fibrogenesis. Forced ABCE1-5 expression by intratracheal injection of adeno-associated virus 6 (AAV6) revealing the anti-fibrotic effect of ABCE1-5 in BLM-treated mice. Mechanistically, RNA pull-down-mass spectrometry and RIP assay demonstrated that ABCE1-5 directly binds to keratin14 (krt14) sequences, potentially impeding its expression by perturbing mRNA stability. Furthermore, decreased ABCE1-5 levels can promote krt14 expression and enhance the phosphorylation of both mTOR and Akt; overexpression of ABCE1-5 in BLM mouse lung tissue significantly attenuated the elevated levels of p-mTOR and p-AKT. Knockdown of krt14 reversed the activation of mTOR signaling mediated by ABCE1-5 silencing. Collectively, the downregulation of ABCE1-5 mediated krt14 activation, thereby activating mTOR/AKT signaling, to facilitate pulmonary fibrosis progression in IPF.

PMID:40111939 | DOI:10.1152/ajpcell.00374.2024

Med Phys. 2025 Mar 20. doi: 10.1002/mp.17752. Online ahead of print.

ABSTRACT

BACKGROUND: Deep learning (DL)-based systems have not yet been broadly implemented in clinical practice, in part due to unknown robustness across multiple imaging protocols.

PURPOSE: To this end, we aim to evaluate the performance of several previously developed DL-based models, which were trained to distinguish idiopathic pulmonary fibrosis (IPF) from non-IPF among interstitial lung disease (ILD) patients, under standardized reference CT imaging protocols. In this study, we utilized CT scans from non-IPF ILD subjects, acquired using various imaging protocols, to assess the model performance.

METHODS: Three DL-based models, including one 2D and two 3D models, have been previously developed to classify ILD patients into IPF or non-IPF based on chest CT scans. These models were trained on CT image data from 389 IPF and 700 non-IPF ILD patients, retrospectively, obtained from five multicenter studies. For some patients, multiple CT scans were acquired (e.g., one at inhalation and one at exhalation) and/or reconstructed (e.g., thin slice and/or thick slice). Thus, for each patient, one CT image dataset was selected to be used in the construction of the classification model, so the parameters of that data set serve as the reference conditions. In one non-IPF ILD study, due to its specific study protocol, many patients had multiple CT image data sets that were acquired under both prone and supine positions and/or reconstructed under different imaging parameters. Therefore, to assess the robustness of the previously developed models under different (e.g., non-reference) imaging protocols, we identified 343 subjects from this study who had CT data from both the reference condition (used in model construction) and non-reference conditions (e.g., evaluation conditions), which we used in this model evaluation analysis. We reported the specificities from three model under the non-reference conditions. Generalized linear mixed effects model (GLMM) was utilized to identify the significant CT technical and clinical parameters that were associated with getting inconsistent diagnostic results between reference and evaluation conditions. Selected parameters include effective tube current-time product (known as "effective mAs"), reconstruction kernels, slice thickness, patient orientation (prone or supine), CT scanner model, and clinical diagnosis. Limitations include the retrospective nature of this study.

RESULTS: For all three DL models, the overall specificity of the previously trained IPF diagnosis model decreased (p < 0.05 for two out of three models). GLMM further suggests that for at least one out of three models, mean effective mAs across the scan is the key factor that leads to the decrease in model predictive performance (p < 0.001); the difference of mean effective mAs between the reference and evaluation conditions (p = 0.03) and slice thickness (3 mm; p = 0.03) are flagged as significant factors for one out of three models; other factors are not statistically significant (p > 0.05).

CONCLUSION: Preliminary findings demonstrated the lack of robustness of IPF diagnosis model when the DL-based model is applied to CT series collected under different imaging protocols, which indicated that care should be taken as to the acquisition and reconstruction conditions used when developing and deploying DL models into clinical practice.

PMID:40111345 | DOI:10.1002/mp.17752

Aging Biol. 2024;2:e20240023. doi: 10.59368/agingbio.20240023. Epub 2024 Feb 13.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is an age-associated lung disease of unknown etiology that is characterized by exaggerated deposition of extracellular matrix (ECM), leading to distorted lung architecture, respiratory failure, and death. There are no truly effective treatment options for IPF, thus highlighting the importance of exploring new pathogenic mechanisms that underlie the development of fibrosis and of identifying new therapeutic targets. Insulin-like growth factors (IGFs) are known to be pro-fibrotic. However, the ubiquity and essentiality of IGF receptor signaling in normal physiology limit its potential as a direct therapeutic target. In a recent study, we found a highly significant correlation between expression of pregnancy-associated plasma protein (PAPP)-A in human IPF lung tissue and disease severity. PAPP-A is a unique metalloprotease that enhances local IGF action. In vitro studies support a role for proteolytically active PAPP-A in promoting a fibrotic phenotype in adult human lung fibroblasts. Here, we show that PAPP-A is preferentially expressed in mouse lung fibroblasts and that inhibition of PAPP-A in vivo through PAPP-A gene deletion or a specific neutralizing monoclonal antibody against PAPP-A markedly reduced the progression of bleomycin-induced lung fibrosis, as measured by significantly decreased ECM expression and improved lung histology. Surrogate markers of local IGF receptor activity in the lung were also significantly reduced, indicating indirect modulation of IGF signaling through PAPP-A. These results establish a role for PAPP-A in pulmonary fibrosis and point to PAPP-A as a selective and pharmacologically tractable target for IPF and possibly other fibrotic disorders.

PMID:40110162 | PMC:PMC11922547 | DOI:10.59368/agingbio.20240023

Front Pharmacol. 2025 Mar 5;16:1524505. doi: 10.3389/fphar.2025.1524505. eCollection 2025.

ABSTRACT

OBJECTIVE: This systematic review and meta-analysis aims to assess the efficacy of GBE in the treatment of IPF by evaluating its impact on total effective rate, blood gas analysis, pulmonary function tests, and markers of inflammation and fibrosis.

METHODS: We conducted a comprehensive search across seven databases, including PubMed, EMBASE, Web of Science, CNKI, Wanfang DATA, VIP, and CBM, without restrictions on publication date. Randomized controlled trials (RCTs) that investigated the effects of GBE on IPF patients were eligible for inclusion. Relevant literature was screened, and the data in the included studies were extracted for quality assessment according to the Risk of bias tool.

RESULTS: A total of 14 RCTs involving 1043 patients were included in the analysis. GBE significantly improved the total effective rate, arterial oxygen partial pressure, arterial oxygen saturation, forced vital capacity, forced expiratory volume in one second, maximum voluntary ventilation, and 6-min walk test compared to the control group. Additionally, there was a significant reduction in arterial carbon dioxide partial pressure, interleukin-4, hyaluronan, and laminin levels.

CONCLUSION: GBE may offer therapeutic benefits in IPF by improving respiratory function, modulating inflammation, and affecting fibrosis markers. These findings support the potential use of GBE as an adjunct therapy in IPF and suggest that further large-scale, multicenter trials are warranted to confirm its efficacy and safety.

PMID:40110130 | PMC:PMC11919911 | DOI:10.3389/fphar.2025.1524505

Clin Transplant. 2025 Mar;39(3):e70136. doi: 10.1111/ctr.70136.

ABSTRACT

BACKGROUND: Lung transplantation (LT) is a critical option for patients with advanced respiratory diseases, especially interstitial lung diseases (ILD). The GAP score (Gender, Age, Physiology) has shown prognostic value in idiopathic pulmonary fibrosis (IPF), but its utility in other progressive fibrotic diseases and LT candidates is less well-studied.

METHODS: This retrospective study included ILD patients evaluated as LT candidates between January 2017 and December 2023 at a single center. The GAP score was calculated for each patient, and patients were classified into GAP stages I, II, or III. Outcomes evaluated included LT waiting list inclusion, LT performed, death, and active follow-up without waiting list inclusion. The prognostic utility was analyzed using survival analysis, including Cox regression and Kaplan-Meier methods.

RESULTS: Of 413 ILD patients, 119 were included on the LT waiting list. GAP stage III was an independent predictor of transplant-free survival (HR = 2.720; p = 0.011). Patients in stage II showed a transplant-free survival of 51.3% at 2 years, while stage III had 49.2% survival at 1 year. GAP stages significantly predicted transplant outcomes and survival rates (p < 0.001).

CONCLUSION: The GAP score is a reliable prognostic tool for ILD patients being evaluated for LT, aiding in decision-making regarding referral and waiting list inclusion. It may serve as a useful marker for early referral and prioritization.

PMID:40109152 | DOI:10.1111/ctr.70136

Nature. 2025 Mar 19. doi: 10.1038/s41586-025-08727-3. Online ahead of print.

ABSTRACT

Fibrosis, the replacement of healthy tissue with collagen-rich matrix, can occur following injury in almost every organ1,2. Mouse lungs follow a stereotyped sequence of fibrogenesis-to-resolution after bleomycin injury3, and we reasoned that profiling post-injury histological stages could uncover pro-fibrotic versus anti-fibrotic features with functional value for human fibrosis. Here we quantified spatiotemporally resolved matrix transformations for integration with multi-omic data. First, we charted stepwise trajectories of matrix aberration versus resolution, derived from a high-dimensional set of histological fibre features, that denoted a reversible transition in uniform-to-disordered histological architecture. Single-cell sequencing along these trajectories identified temporally enriched 'ECM-secreting' (Csmd1-expressing) and 'pro-resolving' (Cd248-expressing) fibroblasts at the respective post-injury stages. Visium-based spatial analysis further suggested divergent matrix architectures and spatial-transcriptional neighbourhoods by fibroblast subtype, identifying distinct fibrotic versus non-fibrotic biomolecular milieu. Critically, pro-resolving fibroblast instillation helped to ameliorate fibrosis in vivo. Furthermore, the fibroblast neighbourhood-associated factors SERPINE2 and PI16 functionally modulated human lung fibrosis ex vivo. Spatial phenotyping of idiopathic pulmonary fibrosis at protein level additionally uncovered analogous fibroblast subtypes and neighbourhoods in human disease. Collectively, these findings establish an atlas of pro- and anti-fibrotic factors that underlie lung matrix architecture and implicate fibroblast-associated biological features in modulating fibrotic progression versus resolution.

PMID:40108456 | DOI:10.1038/s41586-025-08727-3

Eur Respir Rev. 2025 Mar 19;34(175):240147. doi: 10.1183/16000617.0147-2024. Print 2025 Jan.

ABSTRACT

Heat shock protein 90 (HSP 90) and its isoforms are a group of homodimeric proteins that regulate several cellular processes, such as the elimination of misfolded proteins, cell development and post-translational modifications of kinase proteins and receptors. Due to its involvement in extracellular matrix (ECM) remodelling, myofibroblast differentiation and apoptosis, HSP 90 has been investigated as a key player in the pathogenesis of lung fibrosis. Idiopathic pulmonary fibrosis (IPF) is the most common and deadly interstitial lung disease, due to the progressive distortion of lung parenchyma related to the overproduction and deposition of altered ECM, driven by transforming growth factor-β (TGF-β) dependent and independent pathways. The inhibition or induction of HSP 90 is associated with a reduced or increased expression of TGF-β receptors, respectively, suggesting a role for HSP 90 as a biomarker and therapeutic target in IPF. Experimental drugs such as geldanamycin and its derivatives 17-AAG (17-N-allylamino-17-demethoxygeldanamicin) and 17-DMAG (17-dimethylaminoethylamino-17-demethoxigeldanamycin), along with AUY-922, 1G6-D7, AT-13387, TAS-116 and myricetin, have been found to reduce lung fibrosis in both in vivo and in vitro models, supporting the role of this emerging target. This review aims to illustrate the structure and biological function of HSP 90 in the context of IPF pathobiology, as well as perspective application of this molecule as a biomarker and therapeutic target for IPF.

PMID:40107664 | DOI:10.1183/16000617.0147-2024

Eur Respir Rev. 2025 Mar 19;34(175):240238. doi: 10.1183/16000617.0238-2024. Print 2025 Jan.

ABSTRACT

BACKGROUND: Comorbidities can affect drug tolerability and health outcomes in patients with fibrotic interstitial lung disease. This systematic review and meta-analysis evaluated the types and prevalence of comorbidities amongst participants in pharmaceutical randomised controlled trials (RCTs) of idiopathic pulmonary fibrosis (IPF) and progressive pulmonary fibrosis (PPF).

METHODS: Ovid Medline, Embase and CENTRAL databases were searched to identify phase II and III pharmaceutical RCTs of IPF or PPF. Reporting of comorbidities was evaluated, with meta-analyses being performed for the prevalence of different conditions.

RESULTS: 34 articles were included, with 23 unique trials for IPF and one for PPF. A mean of 14 (range 1-44) comorbidities per study was reported in the IPF RCTs, with 11 being reported in the PPF RCT. Common comorbidities in the IPF RCT cohorts were systemic hypertension (pooled prevalence 45%, 95% CI 39-50%), hyperlipidaemia (38%, 95% CI 27-49%), gastro-oesophageal reflux disease (45%, 95% CI 36-54%), ischaemic heart disease (18%, 95% CI 13-42%) and diabetes mellitus (16%, 95% CI 13-20%). The PPF trial cohort had similar types and prevalence of comorbidities to those reported in the IPF trial cohorts.

CONCLUSIONS: Reporting of comorbidities varied across previous IPF RCTs, with limited data available for PPF. Prevalence of comorbidities reported in the IPF and PPF trial cohorts appear to be lower than those reported in prospective patient registries. There is a need for careful consideration of trial eligibility criteria with detailed reporting of comorbidities in future pharmaceutical RCTs to better understand the applicability of trial findings to real-world patients.

PMID:40107663 | DOI:10.1183/16000617.0238-2024

Respir Investig. 2025 Mar 18;63(3):394-398. doi: 10.1016/j.resinv.2025.03.006. Online ahead of print.

ABSTRACT

Both serum and bronchoalveolar lavage fluid levels of galectin-3 (Gal-3) are elevated in patients with idiopathic pulmonary fibrosis (IPF). Phase II study on inhaler with Gal-3 inhibitor for IPF has been ongoing. In this study, 30 treatment-naive patients of IPF were prospectively enrolled and their sera were stored before and after nintedanib treatment. Though Gal-3 levels tended to increase after nintedanib treatment, in some patients, Gal-3 levels decreased immediately after the treatment. Patients whose serum Gal-3 levels decreased 1 month after nintedanib treatment tended to experience a smaller annual decline in forced vital capacity (FVC) than patients with increased Gal-3 levels. Furthermore, the rate of change in Gal-3 levels 1 month after nintedanib treatment positively correlated with the rate of annual FVC decline, whereas that of other fibrotic markers did not correlate with the rate of annual FVC decline. This study suggested that a decline in serum Gal-3 levels immediately after nintedanib treatment may predict less progression of IPF treated with nintedanib.

PMID:40107223 | DOI:10.1016/j.resinv.2025.03.006

Respir Med Case Rep. 2025 Feb 27;54:102184. doi: 10.1016/j.rmcr.2025.102184. eCollection 2025.

ABSTRACT

An 81-year-old man with a history of interstitial lung disease attributed to idiopathic pulmonary fibrosis, severe aortic stenosis, and stable coronary artery disease was started on inhaled treprostinil for pulmonary hypertension associated with interstitial lung disease to optimize hemodynamics prior to the valve replacement procedure. However, two days after starting this treatment, the patient presented with an inferior-posterior ST elevation myocardial infarction. Urgent coronary angiography revealed a 95 % proximal right coronary artery stenosis, successfully treated with percutaneous coronary intervention and drug-eluting stent placement. This case raises a question of whether there could be a potential association between inhaled treprostinil initiation and acute myocardial infarction in patients with underlying coronary artery disease. With the documented stability of the patient's coronary artery disease prior to medication initiation, it is plausible to question whether treprostinil may have played a role in plaque destabilization.

PMID:40104432 | PMC:PMC11915154 | DOI:10.1016/j.rmcr.2025.102184

Nat Rev Drug Discov. 2025 Mar 18. doi: 10.1038/s41573-025-01158-9. Online ahead of print.

ABSTRACT

Fibrosis is a pathophysiological mechanism involved in chronic and progressive diseases that results in excessive tissue scarring. Diseases associated with fibrosis include metabolic dysfunction-associated steatohepatitis (MASH), inflammatory bowel diseases (IBDs), chronic kidney disease (CKD), idiopathic pulmonary fibrosis (IPF) and systemic sclerosis (SSc), which are collectively responsible for substantial morbidity and mortality. Although a few drugs with direct antifibrotic activity are approved for pulmonary fibrosis and considerable progress has been made in the understanding of mechanisms of fibrosis, translation of this knowledge into effective therapies continues to be limited and challenging. With the aim of assisting developers of novel antifibrotic drugs, this Review integrates viewpoints of biologists and physician-scientists on core pathways involved in fibrosis across organs, as well as on specific characteristics and approaches to assess therapeutic interventions for fibrotic diseases of the lung, gut, kidney, skin and liver. This discussion is used as a basis to propose strategies to improve the translation of potential antifibrotic therapies.

PMID:40102636 | DOI:10.1038/s41573-025-01158-9

Respir Investig. 2025 Mar 17;63(3):365-372. doi: 10.1016/j.resinv.2025.02.009. Online ahead of print.

ABSTRACT

BACKGROUND: Prognostic factors in patients with newly diagnosed idiopathic interstitial pneumonia (IIP) have rarely been analyzed using prospective data. This study investigated prognostic factors in patients with IIP.

METHODS: Central interstitial lung disease (ILD) experts established the diagnoses for fibrotic ILD. Prognostic factors using baseline data, including the pathological confidence level of usual interstitial pneumonia (UIP) assessed on a 0%-100% linear analog scale by high-resolution CT (HRCT), pulmonary function tests, and patient-reported outcomes were investigated.

RESULTS: Overall, 866 eligible patients were registered. Patients with unclassifiable idiopathic interstitial pneumonia (n = 272) survived longer than those with idiopathic pulmonary fibrosis (IPF) (n = 469) (hazard ratio [HR] = 0.67; [95% confidence interval [CI]: 0.47-0.95]; P = 0.022); however, IPF as IIPs classification was not a significant prognostic factor at diagnosis (P = 0.577). UIP pattern on HRCT, age, body mass index, forced vital capacity, diffusing capacity of the lungs for carbon monoxide, and St. George's Respiratory Questionnaire were risk factors for survival (P < 0.05). Patients with proposed progressive pulmonary fibrosis (PPF) had poorer prognoses than those without proposed PPF (HR = 5.63; [95% CI: 3.17-10.00]; P < 0.001). Patients with progressive fibrosing ILD (PF-ILD) had poorer prognoses than those without PF-ILD (HR = 7.85; [95% CI: 3.38-18.3]; P < 0.001).

CONCLUSIONS: A prospective registry of patients with newly diagnosed IIP provided evidence that the UIP pattern on HRCT by analog scale was a prognostic predictor. Proposed PPF and PF-ILD were valuable for discriminating prognosis. (JIPS Registry, ClinTrials.gov, NCT03041623).

PMID:40101437 | DOI:10.1016/j.resinv.2025.02.009

J Clin Invest. 2025 Mar 18:e181775. doi: 10.1172/JCI181775. Online ahead of print.

ABSTRACT

Tissue regenerative responses involve complex interactions between resident structural and immune cells. Recent reports indicate that accumulation of senescent cells during injury repair contributes to pathological tissue fibrosis. Using tissue-based spatial transcriptomics and proteomics, we identified upregulation of the immune checkpoint protein, cytotoxic T-lymphocyte associated protein 4 (CTLA4) on CD8+ T cells adjacent to regions of active fibrogenesis in human idiopathic pulmonary fibrosis (IPF) and in a murine model of repetitive bleomycin lung injury model of persistent fibrosis. In humanized CTLA4 knock-in mice, treatment with ipilimumab, an FDA-approved drug that targets CTLA4, resulted in accelerated lung epithelial regeneration and diminished fibrosis from repetitive bleomycin injury. Ipilimumab treatment resulted in the expansion of Cd3e+ T cells, diminished accumulation of senescent cells, and robust expansion of type 2 alveolar epithelial cells, facultative progenitor cells of the alveolar epithelium. Ex-vivo activation of isolated CTLA4-expressing CD8+ cells from mice with established fibrosis resulted in enhanced cytolysis of senescent cells, suggesting that impaired immune-mediated clearance of these cells contribute to persistence of lung fibrosis in this murine model. Our studies support the concept that endogenous immune surveillance of senescent cells may be essential in promoting tissue regenerative responses that facilitate the resolution of fibrosis.

PMID:40100323 | DOI:10.1172/JCI181775

Sarcoidosis Vasc Diffuse Lung Dis. 2025 Mar 18;42(1):15604. doi: 10.36141/svdld.v42i1.15604.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease. Lung cancer (LC) is among the most crucial comorbidity factors in patients with IPF. IPF patients that are diagnosed with LC have a reduced mean survival time. Therapeutic strategies for LC in patients with IPF need to be adapted according to the individual treatment risk. Life-threatening acute exacerbation (AE) of IPF may occur in association with cancer treatment, thereby severely restricting the therapeutic options for IPF-associated LC. Because LC and anticancer treatments can worsen the prognosis of IPF, the prevention of LC is as critical as managing patients with IPF.

PMID:40100103 | DOI:10.36141/svdld.v42i1.15604

Cureus. 2025 Feb 15;17(2):e79036. doi: 10.7759/cureus.79036. eCollection 2025 Feb.

ABSTRACT

Erasmus syndrome (ES) is a rare condition characterized by the link between crystalline silica exposure, with or without silicosis, and systemic sclerosis (SSc). Although first noted over a century ago, its underlying mechanisms remain unclear. However, it is indistinguishable from idiopathic SSc in the general population. Its clinical presentation is heterogeneous, depending on the affected systems, with notable features, including skin fibrosis, microstomia, telangiectasia, Raynaud's phenomenon, arthralgia, and interstitial lung disease. Currently, there is no unified consensus on its treatment; however, organ-specific therapy is a reasonable approach. We report the case of a 43-year-old miner diagnosed with diffuse cutaneous SSc, where ES was diagnosed after an exhaustive history was taken, occupational exposure was characterized, differential diagnoses were excluded, and radiological and histopathological evidence of pulmonary silicosis was presented.

PMID:40099047 | PMC:PMC11912300 | DOI:10.7759/cureus.79036

BMC Med Genomics. 2025 Mar 17;18(1):54. doi: 10.1186/s12920-025-02110-x.

ABSTRACT

BACKGROUND: Post-Covid Pulmonary Fibrosis (PCPF) has emerged as a significant global issue associated with a poor quality of life and significant morbidity. Currently, our understanding of the molecular pathways of PCPF is limited. Hence, in this study, we performed whole transcriptome sequencing of the RNA isolated from the bronchoalveolar lavage (BAL) samples of PCPF and compared it with idiopathic pulmonary fibrosis (IPF) and non-ILD (Interstitial Lung Disease) control to understand the gene expression profile and associated pathways.

METHODS: BAL samples from PCPF (n = 3), IPF (n = 3), and non-ILD Control (n = 3) (individuals with apparent healthy lung without interstitial lung disease) groups were obtained and RNA were isolated for whole transcriptomic sequencing. Differentially Expressed Genes (DEGs) were determined followed by functional enrichment analysis and qPCR validation.

RESULTS: A panel of differentially expressed genes were identified in bronchoalveolar lavage fluid cells (BALF) of PCPF as compare to control and IPF. Our analysis revealed dysregulated pathways associated with cell cycle regulation, immune responses, and neuroinflammatory processes. Real-time validation further supported these findings. The PPI network and module analysis shed light on potential biomarkers and underscore the complex interplay of molecular mechanisms in PCPF. The comparison of PCPF and IPF identified a significant downregulation of pathways that were more prominent in IPF.

CONCLUSION: This investigation provides crucial insights into the molecular mechanism of PCPF and also outlines avenues for prospective research and the development of therapeutic approaches.

PMID:40098116 | DOI:10.1186/s12920-025-02110-x

J Clin Med. 2025 Mar 3;14(5):1693. doi: 10.3390/jcm14051693.

ABSTRACT

Background: Patients suffering from idiopathic pulmonary fibrosis (IPF) may experience acute exacerbation (AE-IPF), which frequently results in acute respiratory failure (ARF) requiring hospitalization. Objective: This study aims to determine if survival has improved over the last decade in patients hospitalized for ARF consequent to AE-IPF, in view of the progress recently made in pharmacological and supportive treatment strategies. Methods: This was an observational retrospective single-center study. The data of 14 patients admitted to an Intermediate Respiratory Care Unit (IRCU) between 1 January 2004 and 31 December 2013 (group A) were compared with those of 26 patients admitted between 1 January 2014 and 31 December 2023 (group B). This study's primary endpoint was survival following IRCU admission. Results: Survival time was significantly longer in the second group of patients compared to the first one [median survival time: 134 (31-257) vs. 25.5 (20-50) days; p < 0.001]. Group B patients also had a lower IRCU mortality rate (6/26 vs. 10/14; p = 0.003) and a significantly shorter stay in the IRCU [6 (1-60) vs. 14 (1-43) days; p = 0.039]. Conclusions: Innovative pharmacologic treatments and supportive therapeutic strategies are able to prolong survival and reduce the risk of in-hospital mortality in patients with AE-IPF hospitalized for ARF.

PMID:40095670 | DOI:10.3390/jcm14051693

J Epidemiol Glob Health. 2025 Mar 17;15(1):44. doi: 10.1007/s44197-025-00377-y.

ABSTRACT

BACKGROUND: Advances in the understanding of idiopathic pulmonary fibrosis (IPF) and international cooperation have led to the publication and subsequent updates of international practice guidelines. The impact of these guidelines, especially significant updates occurring after 2011, on IPF epidemiology and clinical practices remains relatively unexplored.

METHODS: This retrospective nationwide population-based study utilized the Whole-Population Datafiles (WPD) of Taiwan's National Health Insurance Research Database that contained basic demographics, complete claim data, and causes of death for all insured persons. We refined the code-based definition to identify IPF cases from the WPD between 2011 and 2019. Independent validation confirmed the high accuracy of this definition. We analyzed the annual standardized rates of IPF incidence, prevalence, overall and IPF-specific all-cause mortality. Additionally, we examined trends in the prescription of selected medications and the proportions of patients with respiratory failure receiving invasive (IMV) and non-invasive (NIV) mechanical ventilation.

RESULTS: We included 4359 incident cases of IPF. From 2011 to 2019, the annual standardized incidence rates increased from 1.66 (95% confidence interval [CI], 1.36-1.97) to 11.35 (95% CI, 10.65-12.04) per 100,000 standard population, and the annual standardized prevalence rates increased from 1.98 (95% CI, 1.65-2.31) to 27.25 (95% CI, 26.17-28.33) per 100,000 standard population. The standardized IPF-specific all-cause mortality and respiratory failure rates remained stable. Male and older patients received IPF diagnoses more frequently, and experienced higher mortality rates, compared to their female and younger counterparts. Most deaths were attributed to respiratory causes, without significant seasonal variation. Changing trends in the management of IPF mirrored with the evolving guideline recommendations, and showed diminishing roles of immunosuppressants, growing usage of antifibrotics, and NIV usage surpassing IMV.

CONCLUSIONS: Our findings reflected the longitudinal impact of the recently evolving guideline recommendations on IPF epidemiology and real-world management.

PMID:40095261 | DOI:10.1007/s44197-025-00377-y

J Clin Med. 2025 Feb 24;14(5):1496. doi: 10.3390/jcm14051496.

ABSTRACT

Telomeropathies, or telomere biology disorders (TBDs), are syndromes that can cause a number of medical conditions, including interstitial lung disease (ILD), bone marrow failure, liver fibrosis, and other diseases. They occur due to genetic mutations to the telomerase complex enzymes that result in premature shortening of telomeres, the caps on the ends of cellular DNA that protect chromosome length during cell division, leading to early cell senescence and death. Idiopathic pulmonary fibrosis (IPF) is the most common manifestation of the telomere biology disorders, although it has been described in other interstitial lung diseases as well, such as rheumatoid arthritis-associated ILD and chronic hypersensitivity pneumonitis. Telomere-related mutations can be inherited or can occur sporadically. Identifying these patients and offering genetic counseling is important because telomerapathies have been associated with poorer outcomes including death, lung transplantation, hospitalization, and FVC decline. Additionally, treatment with immunosuppressants has been shown to be associated with worse outcomes. Currently, there is no specific treatment for TBD except to transplant the organ that is failing, although there are a number of promising treatment strategies currently under investigation. Shortened telomere length is routinely discovered in patients undergoing lung transplantation for IPF. Testing to detect early TBD in patients with suggestive signs or symptoms can allow for more comprehensive treatment and multidisciplinary care pre- and post-transplant. Patients with TBD undergoing lung transplantation have been reported to have both pulmonary and extrapulmonary complications at a higher frequency than other lung transplant recipients, such as graft-specific complications, increased infections, and complications related to immunosuppressive therapy.

PMID:40095034 | DOI:10.3390/jcm14051496

J Inflamm Res. 2025 Mar 11;18:3449-3468. doi: 10.2147/JIR.S497734. eCollection 2025.

ABSTRACT

BACKGROUND: Rheumatoid arthritis (RA) and idiopathic pulmonary fibrosis (IPF) share a common pathogenic mechanism, but the underlying mechanisms remain ambiguous. Our study aims at exploring the genetic-level pathogenic mechanism of these two diseases.

METHODS: We carried out bioinformatics analysis on the GSE55235 and GSE213001 datasets. Machine learning was employed to identify candidate genes, which were further verified using the GSE92592 and GSE89408 datasets, as well as quantitative real-time PCR (qRT-PCR). The expression levels of TOP2A in RA and IPF in vitro models were confirmed using Western blotting and qRT-PCR. Furthermore, we explored the influence of TOP2A on the occurrence and development of RA and IPF by using the selective inhibitor PluriSIn #2 in an in vitro model. Finally, an in vivo model of RA and IPF was constructed to assess TOP2A expression levels via immunohistochemistry.

RESULTS: Our bioinformatics analysis suggests a potential intersection in the pathogenic mechanisms of RA and IPF. We have identified 7 candidate genes: CXCL13, TOP2A, MMP13, MMP1, LY9, TENM4, and SEMA3E. Our findings reveal that the expression level of TOP2A is significantly elevated in both in vivo and in vitro models of RA and IPF. Additionally, our research indicates that PluriSIn #2 can effectively restrain inflammatory factors, extracellular matrix deposition, migration, invasion, the expression and nuclear uptake of p-smad2/3 protein in RA and IPF in vitro models.

CONCLUSION: There is a certain correlation between RA and IPF at the genetic level, and the molecular mechanisms of their pathogenesis overlap, which might be the reason for the progression of RA. Among the candidate genes we identified, TOP2A may influence the occurrence and development of RA and IPF through the TGF-β/Smad signal pathway. This could be beneficial to the study of the pathogenesis and treatment of RA and IPF.

PMID:40093950 | PMC:PMC11910056 | DOI:10.2147/JIR.S497734