Medicina (Kaunas). 2025 Jan 31;61(2):244. doi: 10.3390/medicina61020244.

ABSTRACT

Background and Objectives: Acute exacerbation of idiopathic pulmonary fibrosis (IPF-AE) often results in severe respiratory distress requiring treatment in the intensive care unit and has a high mortality rate. Identifying prognostic markers and assessing disease severity are crucial for clinicians to gain detailed insights. The mean platelet volume-to-platelet count ratio (MPR) is an inflammatory marker commonly used in malignancies. This study aimed to evaluate MPR and other factors affecting mortality in patients with IPF-AE who were monitored in the intensive care unit (ICU). Materials and Methods: This retrospective study was conducted on patients monitored in the ICU for IPF-AE between 2017 and 2023. Demographic characteristics, vital signs, laboratory and imaging findings, and administered treatments were reviewed. MPR was calculated by dividing the mean platelet volume by the platelet count. The primary endpoint was defined as 1-month in-hospital mortality. Results: A total of 59 patients monitored in the ICU for IPF-AE were included in the study. The mean age of the patients was 62.75 years, and 81.4% of the participants were male. During the 30-day follow-up period, 62.7% of the patients died. The need for invasive mechanical ventilation (IMV) was significantly associated with increased mortality (p < 0.001). The optimal cutoff value for MPR was determined to be 0.033, with a sensitivity of 83.7% and specificity of 63.64%, indicating its predictive value for mortality (AUC: 0.764; 95% CI: 0.635-0.864; p < 0.001). Conclusions: In this study, the need for IMV emerged as a critical parameter in predicting mortality in patients with IPF-AE. Additionally, the use of the MPR as a prognostic biomarker may offer a novel approach in the management of IPF patients. These findings could contribute to the development of strategies aimed at early intervention in IPF patients. Further studies with larger sample sizes are needed to validate these results. This study has demonstrated that MPR is a significant prognostic biomarker for predicting mortality in patients with IPF-AE who are managed in the intensive care unit. The potential use of MPR as a biomarker in clinical decision-making may provide new approaches to the management of IPF patients. Additionally, the need for IMV in IPF-AE emerges as a critical parameter for predicting mortality. These findings may contribute to the development of early intervention strategies for IPF patients. Further studies with larger cohorts are needed to validate these results.

PMID:40005361 | DOI:10.3390/medicina61020244

J Clin Med. 2025 Feb 17;14(4):1317. doi: 10.3390/jcm14041317.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a relatively common progressive fibrotic interstitial lung disease associated with significant morbidity and mortality. The available medications for IPF only slow down the disease process, with lung transplantation the only option for a cure. Non-pharmacological therapies are significant adjuncts that can improve symptom burden and quality of life with minimal or no side effects. Supplemental oxygen can improve exercise capacity and the sensation of dyspnea in a significant portion of patients with resting or exertional hypoxemia and has been supported by several professional societies. Pulmonary rehabilitation is a comprehensive program that includes education and therapeutic exercises to improve patient stamina and strength. It is one of the few interventions that have been shown to produce a meaningful increase in a patient's exercise capacity, but its wide adoption is limited by availability, especially in rural areas. Sleep optimization with supplemental oxygen and positive airway pressure therapy should actively be investigated for all patients diagnosed with IPF. Although gastroesophageal reflux control with non-pharmacological means is still controversial as an intervention to reduce the rate of lung function decline, it can help control reflux symptoms and improve cough intensity. IPF patients should be educated on the importance of balanced nutrition and the potential benefits of screening for lung transplantation. Palliative medicine can help with symptom control and should be considered for all patients regardless severity, but especially in those in the later stages of disease.

PMID:40004847 | DOI:10.3390/jcm14041317

J Clin Med. 2025 Feb 15;14(4):1300. doi: 10.3390/jcm14041300.

ABSTRACT

Background: Patients with idiopathic pulmonary fibrosis (IPF) have a high prevalence of cardiovascular (CV) risk factors and an increased CV disease burden. The aim of this study was to investigate the prognostic role of the ascending aorta (AA) diameter in patients with mild-to-moderate IPF and to identify the main determinants of AA dilatation. Methods: All IPF patients without severe pulmonary hypertension who underwent a multi-instrumental evaluation, comprehensive of high-resolution computed tomography (HRCT) and transthoracic echocardiography (TTE), between September 2017 and November 2023, were retrospectively analyzed. The primary endpoint was the composite of "all-cause mortality or re-hospitalization for all causes", over a medium-term follow-up. The secondary endpoint was to evaluate the independent predictors of AA dilatation. Additionally, Bland-Altman analysis was used to assess the accuracy and precision of echocardiography-derived AA diameters compared with non-ECG gated HRCT measurements. Results: A total of 105 IPF patients and 102 age-, sex-, and CV risk factor-matched controls without IPF were evaluated retrospectively. Over a follow-up of 3.9 ± 1.9 yrs, 31 patients died and 47 were re-hospitalized. AA/height (HR 1.15, 95% CI 1.06-1.25, p < 0.001) was independently associated with the primary endpoint, whereas unindexed AA (HR 1.01, 95% CI 0.96-1.06, p = 0.83) and AA/BSA (HR 1.00, 95% CI 0.89-1.11, p = 0.39) were not. An AA/height > 20 mm/m showed 100% sensitivity and 63% specificity (AUC = 0.78) for predicting the primary endpoint. C-reactive protein (OR 1.87; 95% CI 1.21-2.89, p = 0.005) and left ventricular mass index (OR 1.13, 95% CI 1.04-1.24, p = 0.006) were independently associated with an AA/height > 20 mm/m in the whole study group. The Bland-Altman analysis revealed a bias of +2.51 mm (with the 95% limits of agreement ranging from -3.62 to 8.65 mm) for AA estimation, suggesting a general overestimation of the AA diameter by TTE in comparison to HRCT. Conclusions: AA dilatation is predictive of poor outcomes in IPF patients without advanced lung disease over a mid-term follow-up. The AA/height assessment may improve the prognostic risk stratification of IPF patients.

PMID:40004830 | DOI:10.3390/jcm14041300

J Clin Med. 2025 Feb 8;14(4):1093. doi: 10.3390/jcm14041093.

ABSTRACT

Interstitial lung diseases (ILDs) represent a heterogenous group of lung disorders marked by inflammation and/or fibrosis of the lung parenchyma, often leading to progressive shortness of breath and end-stage respiratory failure. In the U.S., ILDs affect approximately 650,000 individuals and cause approximately 25,000-30,000 deaths annually. Lung transplantation (LTx) offers definitive treatment for advanced ILD, with improved survival attributed to advancements in immunosuppression, organ preservation, surgical techniques, and postoperative care. However, disease recurrence in transplanted lungs remains a significant concern. Understanding the risk factors and mechanisms underlying recurrence is critical for refining recipient selection and improving outcomes. This review examines ILD recurrence post LTx and its implications for lung transplantation success.

PMID:40004625 | DOI:10.3390/jcm14041093

Diagnostics (Basel). 2025 Feb 16;15(4):474. doi: 10.3390/diagnostics15040474.

ABSTRACT

Hyperpolarized xenon-129 MRI (129XeMRI) has emerged as a powerful tool in the identification, evaluation, and assessment of disease endotyping and in response to interventions for a myriad of pulmonary diseases. Growing investigative efforts ranging from basic science to application in translational research have employed 129XeMRI in the evaluation of pulmonary conditions such as chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), asthma, and cystic fibrosis (CF). The novel feature of 129XeMRI is its ability to generate anatomic and physiologic readouts of the lung with resolution from the whole lung down to the lobar level. Additional advantages include being non-invasive and non-radioactive, and utilizing an inexpensive and ubiquitous noble gas as an inhalation contrast agent: xenon-129. In this review, we outline the clinical advances provided by 129XeMRI among common pulmonary diseases with high healthcare burdens in recent decades.

PMID:40002625 | DOI:10.3390/diagnostics15040474

Acta Pharmacol Sin. 2025 Feb 25. doi: 10.1038/s41401-025-01488-9. Online ahead of print.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a progressive lethal disease. Profibrotic fibroblast polarization during wound healing is one of the main causes of IPF, and the molecular mechanisms involved have yet to be fully determined. LIM domain-only protein 7 (LMO7), which acts as an E3 ubiquitin ligase, is highly expressed in the lung, brain and heart and plays important roles in embryonic development, cancer progression, inflammatory bowel disease and Dreifuss muscular dystrophy (EDMD). In this study, we investigated the role of LMO7 in pulmonary fibrosis. Bleomycin (BLM)-induced lung fibrosis was established in mice. For AAV-mediated gene therapy, AAV-Lmo7 shRNA (AAV-Lmo7 shRNA) was intratracheally administered 6 days before BLM injection. Through transcriptome analysis, we found that the expression of LMO7 was significantly upregulated in the fibroblasts of IPF patients and BLM-induced mice. Knockdown of LMO7 impaired the profibrotic phenotype of fibroblasts in BLM-treated mice and in primary lung fibroblasts stimulated with TGF-β in vitro. We observed that LMO7 binds to SMAD7, mediating its degradation by polyubiquitination of lysine 70 and increasing the stability of TGF-β receptor 1 (TGFβR1). Finally, intratracheal administration of adeno-associated virus (AAV)-mediated Lmo7 shRNA significantly ameliorated the progression of BLM-induced lung fibrosis. Our results suggest that LMO7 is a promising target for blocking profibrotic fibroblast polarization for the treatment of fibrotic lung disease. A model for the role of LMO7 in TGF-β/SMAD signaling during pulmonary fibrosis. During pulmonary fibrosis, ubiquitin E3 ligase LMO7 is up-regulated, and binds with. SMAD7. LMO7 mediates the ubiquitination of SMAD7 on Lysine 70, leading to its degradation, and further enhances the stability of transforming growth factor-beta receptor 1 (TGFβR1).

PMID:40000880 | DOI:10.1038/s41401-025-01488-9

Rheumatology (Oxford). 2025 Feb 25:keaf108. doi: 10.1093/rheumatology/keaf108. Online ahead of print.

ABSTRACT

OBJECTIVES: Antineutrophil cytoplasmic antibodies (ANCAs) are occasionally positive in patients with interstitial lung disease (ILD). The positivity rates of ANCAs in various types of ILD and the role of ANCAs in ILD are still unclear. The purpose of this study was to estimate the prevalence of ANCAs in Chinese people diagnosed with ILD (including idiopathic pulmonary fibrosis) and identify differences in clinical features, radiographic features, and survival between patients with ANCA-positive and ANCA-negative ILD.

METHODS: We retrospectively reviewed the data of 706 ILD patients with available ANCA results from March 2010 to October 2023 at the First Affiliated Hospital of Ningbo University. Patient demographics, symptoms, laboratory parameters, chest CT, and pulmonary function testing results were collected and analysed at each patient's initial diagnosis. The prevalence and associations of ANCAs with clinical characteristics and survival were evaluated.

RESULTS: ANCAs were positive in 158 of the 706 (22.4%) ILD patients. Compared with ANCA-negative ILD patients, ANCA-positive ILD patients tended to be older, had higher CRP and ESR levels, and had a significantly greater proportion of rheumatoid factor positivity. In total, 58.2% (92/158) of patients were ANCA-positive on average (41.6 ± 31.4) months after ILD diagnosis. Patients with ANCA-positive ILD had higher all-cause mortality than did those with ANCA-negative ILD (33.5% vs 25.0%, p = 0.033). The usual interstitial pneumonia (UIP) pattern (56.3%) was the most common chest HRCT pattern. The proportions of patients with honeycombing (p < 0.001) and oddly shaped cysts (p < 0.001) were significantly greater in the ANCA-positive ILD group than in the ANCA-negative ILD group. Acute exacerbation (AE) of ILD (HR 2.40, 95% CI 1.37-4.22, p = 0.002) was independently associated with shorter survival, and receiving glucocorticoids combined with immunosuppressants (HR 0.30, 95% CI 0.16-0.57, p < 0.001) was independently associated with longer survival in ANCA-positive ILD patients.

CONCLUSIONS: The prevalence of ANCAs in patients with ILD is not rare, and ANCA testing in ILD patients is necessary. Oddly shaped cysts with or without a UIP pattern may be a characteristic chest imaging manifestation of ANCA-positive ILDs. The frequency of AEs in ANCA-positive ILD patients is high, and more attention should be given to ANCA-positive ILD patients who have AEs.

PMID:39999033 | DOI:10.1093/rheumatology/keaf108

Lung. 2025 Feb 25;203(1):35. doi: 10.1007/s00408-025-00789-4.

ABSTRACT

PURPOSE: The natural history of IPF remains unpredictable despite antifibrotic treatment. In addition, some patients discontinue treatment due to the occurrence of adverse events. To date, no data exist on either the effect of long-term treatment or predictors of treatment response. In the present study, we aim to evaluate the functional trajectory of IPF patients treated with antifibrotics for at least three years and to establish predictors of treatment response.

METHODS: This multicenter study enrolled long-term survivors IPF patients provided they had stopped treatment for no longer than one month during at least three-year study period. Based on the absolute decline of FVC%predicted (pred.) observed during the 3-year treatment and normalized per year, patients were defined as progressors (≥ 5%) or non-progressors (< 5%).

RESULTS: We identify 172 IPF patients who completed three years of antifibrotic treatment with no interruption. The 27% of these IPF patients progressed despite complete adherence to treatment. Progressors were more likely to be non-smokers compared to non-progressors, with higher occurrence of diarrhea and with a more preserved lung function at diagnosis. FVC %pred. and liters at diagnosis, a greater FVC decline in the 1-st year of follow up, being non-smokers, and complaining of diarrhea over treatment are independent predictors of progression.

CONCLUSION: Almost one third of IPF patients adherent to three years of antifibrotics experience progression. A functional decline at first year of treatment despite preserved lung function at diagnosis, non-smoking status, and occurrence of diarrhea over treatment are independent predictors of disease progression.

PMID:39998625 | DOI:10.1007/s00408-025-00789-4

J Fungi (Basel). 2025 Jan 29;11(2):102. doi: 10.3390/jof11020102.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and interstitial disease with an unclear cause, believed to involve genetic, environmental, and molecular factors. Recent research suggested that Pneumocystis jirovecii (PJ) could contribute to disease exacerbations and severity. This article explores how PJ colonization might influence the pathogenesis of IPF. We performed a proteomic analysis to study the profile of control and IPF patients, with/without PJ. We recruited nine participants from the Virgen del Rocio University Hospital (Seville, Spain). iTRAQ and bioinformatics analyses were performed to identify differentially expressed proteins (DEPs), including a functional analysis of DEPs and of the protein-protein interaction networks built using the STRING database. We identified a total of 92 DEPs highlighting the protein vimentin when comparing groups. Functional differences were observed, with the glycolysis pathway highlighted in PJ-colonized IPF patients; as well as the pentose phosphate pathway and miR-133A in non-colonized IPF patients. We found 11 protein complexes, notably the JAK-STAT signaling complex in non-colonized IPF patients. To our knowledge, this is the first study that analyzed PJ colonization's effect on IPF patients. However, further research is needed, especially on the complex interactions with the AKT/GSK-3β/snail pathway that could explain some of our results.

PMID:39997396 | DOI:10.3390/jof11020102

Cells. 2025 Feb 10;14(4):251. doi: 10.3390/cells14040251.

ABSTRACT

Epigenetics regulates gene expression and thus cellular processes that underlie the pathogenesis of chronic lung diseases such as chronic obstructive pulmonary disease (COPD), asthma, and idiopathic pulmonary fibrosis (IPF). Environmental factors (e.g., air pollution, smoking, infections, poverty), but also conditions such as gastroesophageal reflux, induce epigenetic changes long before lung disease is diagnosed. Therefore, epigenetic signatures have the potential to serve as biomarkers that can be used to identify younger patients who are at risk for premature loss of lung function or diseases such as IPF. Epigenetic analyses also contribute to a better understanding of chronic lung disease. This can be used directly to improve therapies, as well as for the development of innovative drugs. Here, we highlight the role of epigenetics in the development and progression of chronic lung disease, with a focus on DNA methylation.

PMID:39996724 | DOI:10.3390/cells14040251

J Labelled Comp Radiopharm. 2025 Jan-Feb;68(1-2):e4133. doi: 10.1002/jlcr.4133.

ABSTRACT

(R)-2-(4-(5-Chloropyrimidin-2-yl)piperidin-1-yl)-4-((1-(hydroxymethyl)cyclobutyl)amino)-6,7-dihydrothieno[3,2-d]pyrimidine 5-oxide (BI 1015550, 1) is a potent and selective inhibitor of phosphodiesterase type 4 (PDE4) being developed for the treatment of idiopathic pulmonary fibrosis (IPF) and progressive pulmonary fibrosis (PPF). We report the synthesis of this drug candidate labelled with carbon 14 and deuterium. The carbon 14 synthesis was completed in three radioactive steps in 27% overall yield, with a specific activity of 52 mCi/mmol (1.92 GBq/mmol), radiochemical purity, and enantiomeric excess higher than 99%. The deuterium labelled compound was prepared in seven steps in 67% overall yield and with isotopic enrichment, chemical purity, and enantiomeric excess higher than 99%.

PMID:39995220 | DOI:10.1002/jlcr.4133

Nat Biotechnol. 2025 Feb 24. doi: 10.1038/s41587-025-02569-0. Online ahead of print.

ABSTRACT

Human lungs contain unique cell populations in distal respiratory airways or terminal and respiratory bronchioles (RA/TRBs) that accumulate in persons with lung injury and idiopathic pulmonary fibrosis (IPF), a lethal lung disease. As these populations are absent in rodents, deeper understanding requires a human in vitro model. Here we convert human pluripotent stem cells (hPS cells) into expandable spheres, called induced respiratory airway progenitors (iRAPs), consisting of ~98% RA/TRB-associated cell types. One hPS cell can give rise to 1010 iRAP cells. We differentiate iRAPs through a stage consistent with transitional type 2 alveolar epithelial (AT2) cells into a population corresponding to mature AT1 cells with 95% purity. iRAPs with deletion of Heřmanský-Pudlák Syndrome 1 (HPS1), which causes pulmonary fibrosis in humans, replicate the aberrant differentiation and recruitment of profibrotic fibroblasts observed in IPF, indicating that intrinsic dysfunction of RA/TRB-associated alveolar progenitors contributes to HPS1-related IPF. iRAPs may provide a system suitable for IPF drug discovery and validation.

PMID:39994483 | DOI:10.1038/s41587-025-02569-0

Sci Rep. 2025 Feb 24;15(1):6670. doi: 10.1038/s41598-025-91060-6.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is characterised by progressive worsening of lung function. In some cases, IPF is accompanied by air-trapping and emphysema. This study aimed to evaluate air trapping quantified with RV/TLC in patients with IPF. This retrospective study included 122 patients diagnosed with IPF in South Korea between January 2011 and December 2020. Air trapping was defined as RV/TLC ≥ 0.40. Increased RV/TLC was found in 34.4% of all patients. The RV/TLC negatively correlated with lung function (forced expiratory volume in 1 s and functional vital capacity [FVC]) and showed consistent results after 1 year of follow-up. After propensity score matching, FVC and diffusion capacity between the groups showed no statistical difference. No difference in lung function decline was found between the increased and not increased RV/TLC groups. Regarding univariable analysis, the patients in the increased RV/TLC group had a lower risk of all-cause mortality (hazard ratio 1.753, P = 0.034). Using multivariable analysis, age, pirfenidone treatment, and FVC were significant factors for survival but not increased RV/TLC. Increased RV/TLC was related to emphysema and demonstrated a negative relationship with lung function. Although increased RV/TLC might relate to poor clinical outcome, it was not independent prognostic factor for IPF.

PMID:39994366 | DOI:10.1038/s41598-025-91060-6

Front Immunol. 2025 Feb 7;16:1458341. doi: 10.3389/fimmu.2025.1458341. eCollection 2025.

ABSTRACT

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a degenerative respiratory condition characterized by significant mortality rates and a scarcity of available treatment alternatives. Cuproptosis, a novel form of copper-induced cell death, has garnered attention for its potential implications. The study aimed to explore the diagnostic value of cuproptosis-related hub genes in patients with IPF. Additionally, multiple bioinformatics analyses were employed to identify immune-related biomarkers associated with the diagnosis of IPF, offering valuable insights for future treatment strategies.

METHODS: Four microarray datasets were selected from the Gene Expression Omnibus (GEO) collection for screening. Differentially expressed genes (DEGs) associated with IPF were analyzed. Additionally, weighted gene coexpression network analysis (WGCNA) was employed to identify the DEGs most associated with IPF. Ultimately, we analyzed five cuproptosis-related hub genes and assessed their diagnostic value for IPF in both the training and validation sets. Additionally, four immune-related hub genes were screened using a protein-protein interaction (PPI) network and evaluated through the receiver operating characteristic (ROC) curve. Lastly, single-cell RNA-seq was employed to further investigate differential gene distribution.

RESULTS: We identified a total of 92 DEGs. Bioinformatics analysis highlighted five cuproptosis-related genes as candidate biomarkers, including three upregulated genes (CFH, STEAP1, and HDC) and two downregulated genes (NUDT16 and FMO5). The diagnostic accuracy of these five genes in the cohort was confirmed to be reliable. Additionally, we identified four immune-related hub genes that demonstrated strong diagnostic performance for IPF, with CXCL12 showing an AUROC of 0.90. We also examined the relationship between these four genes and immune cells. CXCL12 was significantly negatively associated with neutrophils, while CXCR2 was associated exclusively with neutrophils, consistent with our single-cell sequencing results. CTSG showed a primarily positive association with follicular helper T, and SPP1 was most strongly associated with macrophages. Finally, our single-cell sequencing data revealed that in patients with IPF, CXCL12 was highly expressed in the endothelial cell subset (ECs), while SPP1 exhibited high expression in multiple cellular populations. The expression of the CTSG showed statistically significant differences in monocyte macrophages.

CONCLUSION: The research methodically depicted the intricate interplay among five cuproptosis-related genes, four immune-related hub genes, and IPF, offering new ideas for diagnosing and treating patients with IPF.

PMID:39991151 | PMC:PMC11842377 | DOI:10.3389/fimmu.2025.1458341

Theranostics. 2025 Jan 13;15(6):2092-2103. doi: 10.7150/thno.106367. eCollection 2025.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a progressive disease characterized by an excessive collagen deposition ultimately leading to tissue stiffening and functional decline. Beyond IPF, other progressive pulmonary fibrosis are often associated with connective tissue diseases and may develop in ∼18-32% of patients. Therapeutic options are limited to nintedanib and pirfenidone which are only able to reduce fibrosis progression without curing it. The current lack of biomarker to accurately assess and predict disease progression and therapy efficacy for IPF remains a major clinical concern. Methods: In our study, collagen deposition was monitored in bleomycin-induced lung fibrosis in mice by in vivo molecular imaging using a collagen-targeted radiopharmaceutical, [68Ga]Ga-NODAGA-collagelin. Fibrosis progression was also monitored using computed tomography, the gold standard technique to detect lung fibrosis in patients. Results: We demonstrated that the bleomycin-induced increase in collagen lung content can be accurately quantified by [68Ga]Ga-NODAGA-collagelin PET imaging in correlation with disease stage and severity. The lung uptake of [68Ga]Ga-NODAGA-collagelin was mainly found in fibrotic areas of lungs in bleomycin-receiving mice. Most interestingly, [68Ga]Ga-NODAGA-collagelin PET imaging allowed the in vivo non-invasive monitoring of nintedanib efficacy as well as the anti-fibrotic effect of the JAK inhibitor, tofacitinib. Conclusion: Thus, collagen-targeted PET imaging appears as a promising non-invasive tool for staging, monitoring and prediction of disease progression and therapy efficacy towards personalized medicine in IPF.

PMID:39990206 | PMC:PMC11840721 | DOI:10.7150/thno.106367

Toxicol Rep. 2025 Jan 31;14:101941. doi: 10.1016/j.toxrep.2025.101941. eCollection 2025 Jun.

ABSTRACT

Silicosis is an occupational fibrotic lung disease caused by exposure to respirable crystalline silica dust particles produced during industrial activities. Other crystalline silica-induced pulmonary disorders include a predisposition to mycobacterial infections, obstructive airway diseases, idiopathic pulmonary fibrosis, and lung cancer. This review paper discusses the burden of silicosis and associated co-morbidities in developed as well as developing countries globally using the published data of various government agencies, related organizations, and epidemiological findings. Moreover, it sheds light on diverse mechanisms of silicosis, outlining molecular events and peculiar alterations in lung parenchyma leading to this occupational lung disease. Evaluation of pathophysiological mechanisms could aid in the identification of novel target molecules and treatments; to date, there is no curative treatment for silicosis. In recent periods, a lot of attention has been focused on the development and fabrication of suitable nanocarriers for improved and sustained drug delivery in the pulmonary system. Nanoparticle-based therapeutic modality has been evaluated in in-vitro and ex-vivo silicosis models for prolongation of drug activity and improved therapeutic outcomes. The preclinical findings open the doors to clinical trials for operational and regenerative nanoformulations, which eventually create a positive change in medical practice. The following review summarizes various therapeutic approaches available and in the pipe line for silicosis and also stresses the preventive practices for effectively combating this occupational hazard.

PMID:39989982 | PMC:PMC11847043 | DOI:10.1016/j.toxrep.2025.101941

Expert Opin Ther Targets. 2025 Feb 22. doi: 10.1080/14728222.2025.2471579. Online ahead of print.

ABSTRACT

INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease with a dismal prognosis. While the standard-of-care (SOC) drugs approved for IPF represent a significant advancement in antifibrotic therapies, they primarily slow disease progression and have limited overall efficacy and many side effects. Consequently, IPF remains a condition with high unmet medical and pharmacological needs.

AREAS COVERED: A wide variety of molecules and mechanisms have been implicated in the pathogenesis of IPF, many of which have been targeted in clinical trials. In this review, we discuss the latest therapeutic targets that affect extracellular matrix (ECM) homeostasis and the activation of lung fibroblasts, with a specific focus on ECM invasion.

EXPERT OPINION: A promising new approach involves targeting ECM invasion by fibroblasts, a process that parallels cancer cell behavior. Several cancer drugs are now being tested in IPF for their ability to inhibit ECM invasion, offering significant potential for future treatments. The delivery of these therapies by inhalation is a promising development, as it may enhance local effectiveness and minimize systemic side effects, thereby improving patient safety and treatment efficacy.

PMID:39985559 | DOI:10.1080/14728222.2025.2471579

Compr Physiol. 2025 Feb;15(1):e70004. doi: 10.1002/cph4.70004.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a chronic respiratory disease characterized by progressive scarring of the lung parenchyma. While two drugs have been approved by the US Food and Drug Administration (FDA) for IPF, median survival remains limited at 3 years, and the discovery of novel therapeutic targets is urgently needed. Recent studies indicate that immune cells play a critical role in regulating fibrosis. In this Mini Review, we discuss the recent literature focused on cells of the myeloid lineage that serve as key agents of pathologic interorgan communication in fibrosis. These cells are recruited from the bone marrow and have been found to be key drivers of the fibrotic process in the lung.

PMID:39980172 | DOI:10.1002/cph4.70004

Mol Med. 2025 Feb 20;31(1):70. doi: 10.1186/s10020-025-01128-2.

ABSTRACT

BACKGROUND: Lack of understanding of interstitial lung disease (ILD) associated with systemic sclerosis (SSc) and rheumatoid arthritis (RA) hinders the early and accurate identification of these devastating diseases. Current clinical tools limitations highlight the need to complement them with accessible and non-invasive methods. Accordingly, we focused on identifying useful matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) as new biomarkers with clinical value in the diagnosis and prognosis of RA-ILD+ and SSc-ILD+.

METHODS: Peripheral blood was collected from patients with RA-ILD+ (n = 49) and SSc-ILD+ (n = 38); as well as with RA-ILD- (n = 25), SSc-ILD- (n = 20) and idiopathic pulmonary fibrosis (IPF) (n = 39). MMP-1, MMP-2, MMP-3, MMP-7, MMP-9, MMP-10, MMP-12, TIMP-1, and TIMP-2 serum levels were measured using xMAP Technology.

RESULTS: Concerning early connective tissue disease (CTD)-ILD+ diagnosis, increased MMP-7, MMP-9, MMP-10, and MMP-12 levels were found in RA-ILD+ and SSc-ILD+ patients in relation to RA-ILD- and SSc-ILD- patients, respectively. RA-ILD+ patients showed higher MMP-2 levels and lower TIMP-1 levels than RA-ILD- patients. Interestingly, a reliable utility for identifying ILD in CTD was confirmed for the MMP-2, MMP-7, MMP-9, MMP-10, MMP-12, and TIMP-1 combination in RA and MMP-7, MMP-9, MMP-10, and MMP-12 combinatorial signature in SSc. Regarding accurate CTD-ILD+ diagnosis, RA-ILD+ and SSc-ILD+ patients showed lower MMP-7 and MMP-10 levels than IPF patients. Lower MMP-9 and TIMP-1 levels and higher MMP-3 levels were found in RA-ILD+ compared to IPF. Remarkably, effectively better differentiation between CTD-ILD+ and IPF was confirmed for a 5-biomarker signature consisting of MMP-3, MMP-7, MMP-9, MMP-10, and TIMP-1 in RA as well as for the MMP-7 and MMP-10 combination in SSc. Finally, in RA-ILD+ patients, higher MMP-10 levels were associated with worse pulmonary function, increased MMP-2 levels were related to the treatment with conventional synthetic disease-modifying anti-rheumatic drugs, and decreased TIMP-1 levels were linked with positivity rheumatoid factor status.

CONCLUSIONS: MMPs and TIMPs form combinatorial biomarker signatures with clinical value for non-invasive, early, and accurate diagnosis of RA-ILD+ and SSc-ILD+, constituting promising screening tools in clinical practice.

PMID:39979794 | DOI:10.1186/s10020-025-01128-2

Eur Respir J. 2025 Feb 20:2401114. doi: 10.1183/13993003.01114-2024. Online ahead of print.

ABSTRACT

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is characterized by significant, but poorly understood immune and antibody responses. This study examines the spatial transcriptomes and microenvironmental niches of antibody-producing plasma cells and tertiary lymphoid structures (TLS) in IPF lungs, and the molecular pathways influencing antibody accumulation and pulmonary fibrosis.

METHODS: Explant lung tissues from IPF patients and control normal lungs were used for spatial transcriptome assays and validating RNA-scope and immunofluorescence assays. Fibroblasts derived from IPF and control lungs were examined for their capability to attract plasma cells. Neutralizing antibodies were administered to investigate molecules affecting pulmonary plasma cell accumulation and fibrosis in bleomycin-treated mice.

RESULTS: Human IPF lungs exhibited a remarkably widespread distribution of plasma cells and local antibodies in the fibrotic regions, disseminating from plasma cell-generating TLS. Novel mural cells wrapped the vessels in TLS regions, expressing CCR7 ligands that attracted T cells into TLS to promote plasma cell generation. Distinct IPF-associated fibroblasts further secreted CXCL12, providing an extramedullary niche to foster the dissemination and accumulation of plasma cells in the fibrotic regions. Neutralization of CCR7 ligands or CXCL12 reduced plasma cell and local antibody accumulation in the lungs of bleomycin-treated mice, leading to reduced TGFβ concentrations and alleviated pulmonary fibrosis.

CONCLUSIONS: Plasma cells and local antibodies are widely distributed in the fibrotic regions of IPF lungs. Distinct subsets of IPF-associated mural cells and fibroblasts promote pathological plasma cell and antibody accumulation. These findings have potential implications for strategies aimed at targeting immune and antibody responses to combat IPF.

PMID:39978854 | DOI:10.1183/13993003.01114-2024