Biomedicines. 2024 Dec 19;12(12):2893. doi: 10.3390/biomedicines12122893.

ABSTRACT

Background/Objectives: A novel patient group with chronic pulmonary fibrosis is emerging post COVID-19. To identify patients at risk of developing post-COVID-19 lung fibrosis, we here aimed to identify systemic proteins that overlap with fibrotic markers identified in patients with idiopathic pulmonary fibrosis (IPF) and may predict COVID-19-induced lung fibrosis. Methods: Ninety-two proteins were measured in plasma samples from hospitalized patients with moderate and severe COVID-19 in Sweden, before the introduction of the vaccination program, as well as from healthy individuals. These measurements were conducted using proximity extension assay (PEA) technology with a panel including inflammatory and remodeling proteins. Histopathological alterations were evaluated in explanted lung tissue. Results: Connecting to IPF pathology, several proteins including decorin (DCN), tumor necrosis factor receptor superfamily member 12A (TNFRSF12A) and chemokine (C-X-C motif) ligand 13 (CXCL13) were elevated in COVID-19 patients compared to healthy subjects. Moreover, we found incrementing expression of monocyte chemotactic protein-3 (MCP-3) and hepatocyte growth factor (HGF) when comparing moderate to severe COVID-19. Conclusions: Both extracellular matrix- and inflammation-associated proteins were identified as overlapping with pulmonary fibrosis, where we found DCN, TNFRSF12A, CXCL13, CXCL9, MCP-3 and HGF to be of particular interest to follow up on for the prediction of disease severity.

PMID:39767799 | DOI:10.3390/biomedicines12122893

Biomolecules. 2024 Dec 15;14(12):1605. doi: 10.3390/biom14121605.

ABSTRACT

Histone deacetylases (HDACs) are enzymes that play an essential role in the onset and progression of cancer. As a consequence, a variety of HDAC inhibitors (HDACis) have been developed as potent anticancer agents, several of which have been approved by the FDA for cancer treatment. However, recent accumulated research results have suggested that HDACs are also involved in several other pathophysiological conditions, such as fibrotic, inflammatory, neurodegenerative, and autoimmune diseases. Very recently, the HDAC inhibitor givinostat has been approved by the FDA for an indication beyond cancer: the treatment of Duchenne muscular dystrophy. In recent years, more and more HDACis have been developed as tools to understand the role that HDACs play in various disorders and as a novel therapeutic approach to fight various diseases other than cancer. In the present perspective article, we discuss the development and study of HDACis as anti-fibrotic and anti-inflammatory agents, covering the period from 2020-2024. We envision that the discovery of selective inhibitors targeting specific HDAC isozymes will allow the elucidation of the role of HDACs in various pathological processes and will lead to the development of promising treatments for such diseases.

PMID:39766311 | DOI:10.3390/biom14121605

Antioxidants (Basel). 2024 Dec 2;13(12):1480. doi: 10.3390/antiox13121480.

ABSTRACT

The aging process significantly impacts lung physiology and is a major risk factor for chronic respiratory diseases, including chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), asthma, and non-IPF interstitial lung fibrosis. This narrative clinical review explores the molecular and biochemical hallmarks of aging, such as oxidative stress, telomere attrition, genomic instability, epigenetic modifications, proteostasis loss, and impaired macroautophagy, and their roles in lung senescence. Central to this process are senescent cells, which, through the senescence-associated secretory phenotype (SASP), contribute to chronic inflammation and tissue dysfunction. The review highlights parallels between lung aging and pathophysiological changes in respiratory diseases, emphasizing the role of cellular senescence in disease onset and progression. Despite promising research into modulating aging pathways with interventions like caloric restriction, mTOR inhibitors, and SIRT1 activators, clinical evidence for efficacy in reversing or preventing age-related lung diseases remains limited. Understanding the interplay between aging-related mechanisms and environmental factors, such as smoking and pollution, is critical for developing targeted therapies. This review underscores the need for future studies focusing on therapeutic strategies to mitigate aging's detrimental effects on lung health and improve outcomes for patients with chronic respiratory conditions.

PMID:39765809 | DOI:10.3390/antiox13121480

Xenobiotica. 2025 Jan 7:1-17. doi: 10.1080/00498254.2025.2450440. Online ahead of print.

ABSTRACT

Idiopathic Pulmonary Fibrosis (IPF) is a chronic respiratory disorder for which pirfenidone is the recommended first-line anti-fibrotic treatment. While pirfenidone has demonstrated efficacy in slowing the progression of IPF, its use is associated with several challenges and unresolved issues that impact patient outcomes. Pirfenidone administration can result in gastrointestinal side effects, photosensitivity reactions, and significant drug interactions, particularly in patients with hepatic impairment. For those who experience intolerable side effects, dose reductions or temporary discontinuations are frequently employed. However, there is limited data on the efficacy of reduced doses, creating uncertainty about the balance between tolerability and therapeutic benefit.The aim of this study is to evaluate the currently proposed dosage adjustments and to develop new dosage regimens tailored to the needs of patients. Simulations were conducted to explore pirfenidone pharmacokinetics under various challenging conditions, including dose titration, withdrawal, retitration, moderate and severe hepatic impairment, co-administration of moderate (e.g., omeprazole) and strong (e.g., smoking) inducers of the CYP1A2 enzyme, gastrointestinal adverse events, and photosensitivity reactions.Simulations led to specific recommendations for physicians regarding dosage regimens in each condition. The recommended dosage adjustments are designed to maintain concentrations within acceptable levels, ensuring both safe and effective treatment.

PMID:39764686 | DOI:10.1080/00498254.2025.2450440

Exp Biol Med (Maywood). 2024 Dec 23;249:10215. doi: 10.3389/ebm.2024.10215. eCollection 2024.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial lung disease with a poor prognosis. Its non-specific clinical symptoms make accurate prediction of disease progression challenging. This study aimed to develop molecular-level prognostic models to personalize treatment strategies for IPF patients. Using transcriptome sequencing and clinical data from 176 IPF patients, we developed a Random Survival Forest (RSF) model through machine learning and bioinformatics techniques. The model demonstrated superior predictive accuracy and clinical utility, as shown by the concordance index (C-index), the area under the operating characteristic curve (AUC), Brief scores, and decision curve analysis (DCA) curves. Additionally, a novel prognostic staging system was introduced to stratify IPF patients into distinct risk groups, enabling individualized predictions. The model's performance was validated using a bleomycin-induced pulmonary fibrosis mouse model. In conclusion, this study offers a new prognostic staging system and predictive tool for IPF, providing valuable insights for treatment and management.

PMID:39764456 | PMC:PMC11702306 | DOI:10.3389/ebm.2024.10215

J Imaging Inform Med. 2025 Jan 6. doi: 10.1007/s10278-024-01377-3. Online ahead of print.

ABSTRACT

A scoping review was conducted to investigate the role of radiological imaging, particularly high-resolution computed tomography (HRCT), and artificial intelligence (AI) in diagnosing and prognosticating idiopathic pulmonary fibrosis (IPF). Relevant studies from the PubMed database were selected based on predefined inclusion and exclusion criteria. Two reviewers assessed study quality and analyzed data, estimating heterogeneity and publication bias. The analysis primarily focused on deep learning approaches for feature extraction from HRCT images, aiming to enhance diagnostic accuracy and efficiency. Radiomics, utilizing quantitative features extracted from images, were computed using various tools to improve precision in analysis. Validation methods such as k-fold cross-validation were employed to assess model robustness and generalizability. Findings revealed that radiologic patterns in interstitial lung disease hold prognostic significance for patient survival. However, the additional prognostic value of quantitative assessment of fibrosis extent remains uncertain. IPF poses a substantial challenge in respiratory medicine, necessitating advanced diagnostic and prognostic tools. Radiomics emerges as a valuable asset, offering insights into disease characteristics and aiding in disease classification. It contributes to understanding underlying pathophysiological processes, facilitating more effective management of pulmonary disorders. Future research should focus on clarifying the additional prognostic value of quantitative assessment and further refining AI-based diagnostic and prognostic models for IPF.

PMID:39762544 | DOI:10.1007/s10278-024-01377-3

Tuberc Respir Dis (Seoul). 2025 Jan 6. doi: 10.4046/trd.2024.0168. Online ahead of print.

ABSTRACT

Idiopathic nonspecific interstitial pneumonia (iNSIP) is recognized as a distinct entity among various types of idiopathic interstitial pneumonias (IIP). It is identified histologically by the nonspecific interstitial pneumonia (NSIP) pattern. A diagnosis of iNSIP is feasible once secondary causes or underlying diseases are ruled out. Usually presenting with respiratory symptoms such as shortness of breath and cough, iNSIP has a subacute or chronic course. It predominantly affects females aged 50 to 60 years who are non-smokers. Key imaging findings on chest high-resolution computed tomography (HRCT) include bilateral reticular opacities in lower lungs, traction bronchiectasis, reduced lung volumes and, ground-glass opacities. Abnormalities are typically diffuse across both lungs with subpleural distributions. Treatment often involves systemic steroids, either alone or in combination with other immunosuppressants, although evidence supporting effectiveness of these treatments is limited. Prognosis is generally more favorable for iNSIP than for idiopathic pulmonary fibrosis (IPF), with many studies reporting a 5-year survival rate above 70%. Antifibrotic agents should be considered in a condition, , termed progressive pulmonary fibrosis (PPF), where pulmonary fibrosis progressively worsens.

PMID:39761948 | DOI:10.4046/trd.2024.0168

Front Cell Infect Microbiol. 2024 Dec 20;14:1479801. doi: 10.3389/fcimb.2024.1479801. eCollection 2024.

ABSTRACT

Interstitial lung disease (ILD) is characterized by chronic inflammation and scarring of the lungs, of which idiopathic pulmonary fibrosis (IPF) is the most devastating pathologic form. Idiopathic pulmonary fibrosis pathogenesis leads to loss of lung function and eventual death in 50% of patients, making it the leading cause of ILD-associated mortality worldwide. Persistent and subclinical microbial infections are implicated in the acute exacerbation of chronic lung diseases. However, while epidemiological studies have highlighted pollutants, gastric aspirate, and microbial infections as major causes for the progression and exacerbation of IPF, the role of persistent microbial infections in the pathogenesis of IPF remains unclear. In this review, we have focused on the role of persistent microbial infections, including viral, bacterial, and fungal infections, and their mechanisms of action in the pathogenesis of IPF. In particular, the mechanisms and pathogenesis of the Gram-negative bacteria Non-typeable Haemophilus influenzae (NTHi) in ILDs are discussed, along with growing evidence of its role in IPF, given its unique ability to establish persistent intracellular infections by leveraging its non-capsulated nature to evade host defenses. While antibiotic treatments are presumably beneficial to target the extracellular, interstitial, and systemic burden of pathogens, their effects are significantly reduced in combating pathogens that reside in the intracellular compartments. The review also includes recent clinical trials, which center on combinatorial treatments involving antimicrobials and immunosuppressants, along with antifibrotic drugs that help mitigate disease progression in IPF patients. Finally, future directions focus on mRNA-based therapeutics, given their demonstrated effectiveness across a wide range of clinical applications and feasibility in targeting intracellular pathogens.

PMID:39760094 | PMC:PMC11695292 | DOI:10.3389/fcimb.2024.1479801

Turk J Biol. 2024 Oct 23;48(6):379-389. doi: 10.55730/1300-0152.2713. eCollection 2024.

ABSTRACT

BACKGROUND/AIM: No specific pharmacological treatment regimen for idiopathic pulmonary fibrosis (IPF) exists. Therefore, new antiinflammatory therapeutic strategies are needed. Cannabinoids (CBs), known for their inflammation-modulating and antifibrotic effects, may be potential medication candidates for treating IPF. We aim to evaluate the inflammation-modulating and antifibrotic effects of CB receptor (CBR) agonists and antagonists in lipopolysaccharide-stimulated normal human lung fibroblast, epithelial cells, IPF fibroblast cells, and monocytes.

MATERIALS AND METHODS: We detected CBRs in normal human lung fibroblasts (LL24) and IPF fibroblast cells (LL29), epithelial cells (A549) and monocytes (THP-1) by flow cytometry. We determined TGF-β1, IL-8, and TNF-α inflammatory cytokines in the LL24, LL29, A549, and THP-1 cell culture supernatants on days 1 and 5 by ELISA. We evaluated the cell viability in LL24, LL29, and A549 cells on days 1, 3, and 5 spectrophotometrically and detected collagen Type I (ColI) production in the LL24 and LL29 cell culture supernatants on days 1, 3, and 5 by ELISA.

RESULTS: LL24, LL29, A549, and THP-1 cells exhibited CB1 (CB1R) and CB2 (CB2R) receptors. CB1R and CB2R agonists WIN55,212-2 and JWH015 inhibited fibroblastic and epithelial cell proliferation on day 5. TGF-β1 and TNF-α release increased, while IL-8 release decreased in LL24, LL29, A549, and THP-1 cells in response to the administration of WIN55,212-2 and JWH015 at a 10-2 mM concentration. CB1R and CB2R antagonists AM251 and AM630 did not block agonistic responses, suggesting a nonclassical CBR-mediated pathway. CB2R agonist JWH015 decreased ColI expression in IPF lung fibroblasts LL29 on day 3.

CONCLUSION: These results suggest that CB signaling regulates the progression of pulmonary inflammation and fibrosis via CBR activation. This may offer a potential pharmacological tool for developing antifibrosis therapies.

PMID:39758842 | PMC:PMC11698192 | DOI:10.55730/1300-0152.2713

Health Qual Life Outcomes. 2025 Jan 5;23(1):3. doi: 10.1186/s12955-024-02326-y.

ABSTRACT

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is associated with high mortality, heavy economic burden, limited treatment options and poor prognosis, and seriously affects the health-related quality of life (HRQoL) and life expectancy of patients. This systematic review and meta-analysis of HRQoL and health state utility value (HSUV) in IPF patients and the instruments used in this assessment aimed to provide information sources and data support for the future research on IPF HRQoL and HSUV.

METHODS: We searched the PubMed, EMBASE, Web of Science and Cochrane Library databases for studies reporting the HRQoL or HSUV of IPF patients, with the retrieval time from the establishment of each database to April 2024. After two researchers independently screened the literature, extracted the data, and evaluated the risk of bias in the included studies, pooled analysis was performed on the measurement tools adopted in more than two studies. Subgroup analysis was employed to explore the source of heterogeneity, and sensitivity analysis was used to assess the robustness of the results. Funnel-plot directed evaluation combined with Egger's test quantitative evaluation was conducted to detect publication bias.

RESULTS: Sixty-nine studies were ultimately included, covering eighteen measurement tools. The literature quality was generally excellent. The St. George's Respiratory Questionnaire (SGRQ), EuroQoL Five Dimensions Questionnaire (EQ-5D), Short Form-36 (SF-36) and the King's Brief Interstitial Lung Disease (KBILD) were the most common instruments, among which the EQ-5D included the HSUV and the visual analog scale (VAS). The results of the meta-analysis revealed that the pooled SGRQ total score was 45.28 (95% confidence interval [CI] 41.10-49.47), the mean EQ-5D utility score was 0.75 (95% CI: 0.72-0.79), the total EQ-5D VAS score was 66.88 (95% CI: 63.75-70.01), and the pooled SF-36 physical component summary (PCS) and mental component summary (MCS) score were 36.70 (95% CI: 32.98-40.41) and 48.99 (95% CI: 47.44-50.55), respectively. The total KBILD score was 58.31 (95% CI: 55.43-61.19), the IPF specific version of the SGRQ (SGRQ-I) was 40.38 (95% CI: 28.81-51.96) and the Leicester Cough Questionnaire (LCQ) score was 16.09 (95% CI: 15.45-16.74). The pooled result of the University of California San Diego Shortness of Breath Questionnaire (USCD-SOBQ) was 45.05 (95% CI: 41.56-48.55). The results of other instruments, such as the tool to assess quality of life in IPF (ATAQ-IPF), the World Health Organization Quality of Life assessment 100 (WHOQoL-100) and the 12-item short-form health survey (SF-12) were similar to those of the above measurement tools. Regretfully, subgroup analyses did not identify the source of heterogeneity, but sensitivity analyses demonstrated robustness of our results. Except for the SGRQ total, our results showed little possibility of publication bias.

CONCLUSIONS: HRQoL in IPF patients is generally poor, and all domains are severely affected. With the aggravation of disease, HRQoL and HSUV shows a relatively downward trend, and income level is also an important factor affecting HRQoL and HSUV. At present, the published studies on IPF HRQoL and HSUV have applied many measurement tools with high interstudy heterogeneity, and future research on the optimal disease measurement tools should be strengthened. Our study provides high-quality comprehensive evidence for IPF HRQoL and HSUV, which can be used to guide clinical and economic evaluation in the future.

PMID:39757157 | DOI:10.1186/s12955-024-02326-y

Zhonghua Jie He He Hu Xi Za Zhi. 2025 Jan 12;48(1):66-71. doi: 10.3760/cma.j.cn112147-20241007-00580.

ABSTRACT

The notable advances on interstitial lung disease (ILD) published in Chinese and international authoritative journals from October 2023 to September 2024 were systematically reviewed in this annual review. Advances on pathogenesis, diagnosis, treatment, global and/or Chinese comments and guidelines of idiopathic pulmonary fibrosis, connective tissue disease-associated ILD and sarcoidosis were reviewed in detail in our paper.

PMID:39757099 | DOI:10.3760/cma.j.cn112147-20241007-00580

Biol Pharm Bull. 2024;47(12):2165-2172. doi: 10.1248/bpb.b24-00534.

ABSTRACT

Idiopathic pulmonary fibrosis (PF) is an irreversible and chronic inflammatory condition with limited therapeutic options and a high mortality rate. We aimed to determine the possible role and mechanisms of wogonin (WGN) on PF. A rat model of PF was established with intratracheally administrated with bleomycin (BLM), followed by intravenously injecting with WGN and weekly body weight measurements for four weeks. Hematoxylin-eosin (H&E) and Masson's trichrome staining were implemented for histopathological analysis. In addition, the levels of fibrotic proteins and indicators of the mitogen-activated protein kinase (MAPK) pathway were assessed with Western blot. RT-quantitative (q)PCR experiment was conducted to investigate the fibrotic proteins' mRNA expression. Ultimately, the concentrations of glutathione peroxidase (GSH-PX), malonaldehyde (MDA), and superoxide dismutase (SOD) were ascertained with appropriate kits. The results showed that WGN administration significantly reversed BLM-induced body weight reduction, alleviated pathological fibrosis, and reduced the Ashcroft score and the lung wet-to-dry weight ratio. Additionally, WGN suppressed the rise of fibrotic protein levels in BLM-treated rat's lung tissues. Furthermore, WGN attenuated BLM-stimulated oxidative stress, as evidenced by the increased GSH-PX and SOD levels and decreased MDA levels in vivo. Finally, wogonin supplements significantly lowered the extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 MAPK phosphorylation levels in the BLM-treated rat's lung tissues. In conclusion, our study proved that PF induced by BLM administration can be mitigated by WGN treatment via suppressing the MAPK pathway, indicating that WGN is a candidate therapeutic agent for managing PF.

PMID:39756931 | DOI:10.1248/bpb.b24-00534

Respir Med. 2025 Jan 2:107939. doi: 10.1016/j.rmed.2025.107939. Online ahead of print.

ABSTRACT

INTRODUCTION: Ca2+ signaling in fibroblasts would be one of the important mediators of lung fibrosis. This study investigated the relationship between calcium channel blocker usage and the risk of developing interstitial lung disease and idiopathic pulmonary fibrosis.

MATERIAL AND METHODS: This cohort study used data from the Korean National Health Screening Cohort spanned from January 1, 2004, to December 31, 2015. The study included 394,142 participants. CCB usage, as a time-dependent variable assessed every two years, was categorized by medication status (ever-users and never-users) and further divided into five groups based on cumulative defined daily dose: <182.5, 182.5-365.0, 365.0-547.5, and ≥547.5. Incidence rates of ILD and IPF among CCB users compared to never-users, analyzed using time-dependent Cox regression models.

RESULTS: The incidence rates were 27.7 per 100,000 person-years for ILD and 15.0 per 100,000 person-years for IPF among never-users, compared to 19.5 per 100,000 person-years for ILD and 13.9 per 100,000 person-years for IPF among ever-users. The adjusted hazard ratios (aHRs) were 0.68 [95% confidence interval (CI), 0.55-0.83] for ILD and 0.69 (95% CI, 0.54-0.88) for IPF. Increasing categories of CCB usage were significantly associated with a lower risk of ILD [aHRs: 1.23 (95% CI, 0.97-1.56), 1.20 (0.85-1.71), 0.49 (0.30-0.81), and 0.27(0.19-0.39)] and IPF [aHRs: 1.21 (95% confidence interval, 0.89-1.64), 1.45 (0.96-2.20), 0.83 (0.52-1.33), and 0.25 (0.16-0.38)], compared to never-users.

CONCLUSIONS: This study found that individuals using CCBs had a significantly lower risk of interstitial lung disease and idiopathic pulmonary fibrosis compared to never-users in a dose-response manner.

PMID:39755283 | DOI:10.1016/j.rmed.2025.107939

Sci Rep. 2025 Jan 3;15(1):610. doi: 10.1038/s41598-024-84820-3.

ABSTRACT

Interstitial lung disease (ILD) is known to be a major complication of systemic sclerosis (SSc) and a leading cause of death in SSc patients. As the most common type of ILD, the pathogenesis of idiopathic pulmonary fibrosis (IPF) has not been fully elucidated. In this study, weighted correlation network analysis (WGCNA), protein‒protein interaction, Kaplan-Meier curve, univariate Cox analysis and machine learning methods were used on datasets from the Gene Expression Omnibus database. CCL2 was identified as a common characteristic gene of IPF and SSc. The genes associated with CCL2 expression in both diseases were enriched mainly in chemokine-related pathways and lipid metabolism-related pathways according to Gene Set Enrichment Analysis. Single-cell RNA sequencing (sc-RNAseq) revealed a significant difference in CCL2 expression in alveolar epithelial type 1/2 cells, mast cells, ciliated cells, club cells, fibroblasts, M1/M2 macrophages, monocytes and plasma cells between IPF patients and healthy donors. Statistical analyses revealed that CCL2 was negatively correlated with lung function in IPF patients and decreased after mycophenolate mofetil (MMF) treatment in SSc patients. Finally, we identified CCL2 as a common biomarker from IPF and SSc, revealing the common mechanism of these two diseases and providing clues for the study of the treatment and mechanism of these two diseases.

PMID:39753882 | DOI:10.1038/s41598-024-84820-3

EBioMedicine. 2025 Jan 2;112:105538. doi: 10.1016/j.ebiom.2024.105538. Online ahead of print.

ABSTRACT

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a fibrosing interstitial pneumonia with restrictive ventilation. Recently, the structural and functional defects of small airways have received attention in the early pathogenesis of IPF. This study aimed to elucidate the characteristics of small airway epithelial dysfunction in patients with IPF and explore novel therapeutic interventions to impede IPF progression by targeting the dysfunctional small airways.

METHODS: Airway trees spanning the proximal-distal axis were harvested from control lungs and explanted lungs with end-stage IPF undergoing transplant. Qualified basal cells (BCs, p63/Krt5/ITGA6/NGFR) were expanded, and their cellular functions, feasibility, safety and efficacy for transplantation therapy in IPF were validated with experiments in vitro and mouse model. Single-cell RNA-sequencing was employed to elucidate the underlying mechanisms governing the BCs based therapy. Based upon these evidences, three patients with advanced IPF and small airway dysfunction received autologous-BCs transplantation. Post-transplantation assessments included lung function, exercise capacity and high resolution computed tomography (HRCT) scans were analyzed to quantify the clinical benefits conferred by the BCs transplantation.

FINDINGS: An overall landscape of senescent phenotype in airway epithelial cells and airway stem/progenitor cells along the proximal-distal axis of the airway tree in IPF were outlined. In contrast to the cells situated in distal airways, BCs located in small bronchi in IPF displayed a non-senescent phenotype, with comparable proliferative, differentiative capabilities, and similar transcriptomic profiles to normal controls. In a mouse model of pulmonary fibrosis, BCs exhibited promising protective efficacy and safety for transplantation therapy. Autologous BCs transplantation in three advanced IPF patients with small airway dysfunction yielded significant clinical improvements in pulmonary function, particularly evidence in lung volume and small airway function.

INTERPRETATION: Epithelia of small bronchi in IPF contain functional and expandable basal stem cells, which exert therapeutic benefits via bronchoscopic implantation. Our findings offer a potential for IPF treatment by targeting small airways.

FUNDING: National Natural Science Foundation of China (82430001, 81930001, and 81900059), Shanghai Shenkang Hospital Development Center (SHDC2020CR3063B), Department of Science and Technology of Shandong Province (2024HWYQ-058).

PMID:39753035 | DOI:10.1016/j.ebiom.2024.105538

Lung. 2025 Jan 3;203(1):16. doi: 10.1007/s00408-024-00758-3.

ABSTRACT

PURPOSE: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrotic lung disorder characterized by dry cough, fatigue, and exacerbated dyspnea. The prognosis of IPF is notably unfavorable, becoming extremely poor when the disease advances acutely. Effective therapeutic intervention is essential to mitigate disease progression; hence, early diagnosis and treatment are paramount. When high-resolution computed tomography (HRCT) reveals usual interstitial pneumonia (UIP), a diagnosis of IPF can be established. However, when HRCT fails to conclusively confirm IPF, the diagnostic pathway becomes intricate and necessitates a multidisciplinary approach involving clinicians, radiologists, and pathologists. Consequently, the objective of this study was to investigate new diagnostic approaches through bronchoalveolar lavage (BAL) analysis.

METHODS: BAL is a commonly utilized diagnostic tool for interstitial lung diseases. We review the application of bronchoalveolar lavage (BALF) in idiopathic pulmonary fibrotic disease, emphasizing that the cellular and solute composition of the lower respiratory tract offers valuable insights.

RESULTS: This review delineates the advancements in diagnosing IPF cases that remain indeterminate via HRCT, leveraging BALF analysis. In contrast to surgical lung biopsy, BAL is minimally invasive and offers potential diagnostic utility through the identification of specific BALF biomarkers.

CONCLUSION: Augment the clinical diagnostic armamentarium for IPF, particularly in scenarios where HRCT findings are inconclusive.

PMID:39751999 | DOI:10.1007/s00408-024-00758-3

Eur J Hum Genet. 2025 Jan 2. doi: 10.1038/s41431-024-01772-y. Online ahead of print.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a progressive, late-onset disease marked by lung scarring and irreversible loss of lung function. Genetic factors significantly contribute to both familial and sporadic cases, yet there are scarce evidence-based studies highlighting the benefits of integrating genetics into the management of IPF patients. In this study, we performed whole-exome sequencing and telomere length (TL) measurements on IPF patients and their relatives. We then identified rare deleterious variants using three virtual gene panels encompassing IPF or TL genes with varying levels of evidence supporting their potential relationship with the disease. We identified 10 candidate variants in well-established disease genes, and these results were validated using two automatic prioritization tools (Exomiser and Franklin). Pathogenic variants were found in two telomere-related genes (RTEL1 and NAF1), and both were associated with severe TL shortening. Our results suggest that this tiered virtual panel strategy is sufficiently robust and serves as a viable solution in clinical practice. It generates valuable genetic data which can be interpreted and validated with the expertise of a multidisciplinary team.

PMID:39748130 | DOI:10.1038/s41431-024-01772-y

Sci Rep. 2025 Jan 2;15(1):143. doi: 10.1038/s41598-024-83787-5.

ABSTRACT

The study investigates the prognostic value of [18F]fluorodeoxyglucose (FDG) PET/CT in patients with idiopathic pulmonary fibrosis (IPF). A total of 346 IPF patients who underwent FDG PET/CT between 2007 and 2020 were analyzed. Pulmonary FDG uptake [target to background ratio (TBR)] was binarized by optimal cut-off value based on survival analysis. The PET-modified GAP (Gender, Age, lung Physiology) score-based staging system included a category for FDG uptake, and its prognostic prediction was compared with the conventional GAP score. Survival analyses were conducted for progression-free, overall, and disease-specific survival. The low FDG uptake group showed a significantly better prognosis than the high uptake group, with cut-off values of 7.26 (p < 0.001), 7.15 (p = 0.04), and 9.23 (p = 0.01) for progression-free, overall, and disease-specific survival, respectively. The PET-modified GAP score-based staging system differentiated better than the conventional GAP system, particularly between stages I and II in overall survival (p = 0.001 vs. p = 0.08). For disease-specific survival, the PET-modified model showed better performance than the original GAP model (p = 0.06 vs. p = 0.33), though neither was statistically significant. Pulmonary FDG uptake in PET/CT is a reliable biomarker for predicting the prognosis of IPF patients and enhances the conventional GAP staging system's predictive value for patient survival.

PMID:39747497 | DOI:10.1038/s41598-024-83787-5

Clin Exp Pharmacol Physiol. 2025 Feb;52(2):e70017. doi: 10.1111/1440-1681.70017.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a lethal lung disease characterised by irreversible lung structure and function. Phillygenin (PHI) is a lignan extracted from Forsythiae fructus with the activities of anti-inflammatory and antioxidant. This study aimed to explore the protective effect of PHI on IPF. The mouse model of IPF was established by bleomycin (BLM), and then treated with PHI. After 15 days of administration, the lung index was calculated. H&E staining, Masson staining and immunohistochemical methods were used to detect the effect of PHI on pulmonary fibrosis. MDA and SOD were tested to evaluate the effect of PHI on lung tissue oxidative stress. Western blot was used to detect the effect of PHI on the expressions of α-SMA, p-smad2, TGF- β1, Nrf2, HO-1 and NQO-1. Network pharmacology was used to identify the key signalling pathways for PHI to improve IPF, and Western blot was used to validate the result. The results showed that PHI prevented mice from BLM-induced IPF, manifested by reducing lung index, improving lung tissue pathological damage, inhibiting collagen deposition and expression of fibrosis markers including α-SMA, collagen1, p-smad2 and TGF-β1. PHI inhibited oxidative stress by upregulating the expressions of Nrf2, HO-1 and NQO-1. Network pharmacology revealed that PI3K-Akt-mTOR signalling pathway was the underlying target of PHI for IPF. Molecular docking indicated strong binding of PHI with PIK3CA, AKT1 and RELA. Western blot validated that PHI downregulated the PI3K-Akt-mTOR signalling pathway and stimulated autophagy. This study indicated that PHI prevented BLM-induced pulmonary fibrosis by inhibiting PI3K-Akt-mTOR signalling pathway.

PMID:39746665 | DOI:10.1111/1440-1681.70017

Int Immunopharmacol. 2025 Jan 1;147:113979. doi: 10.1016/j.intimp.2024.113979. Online ahead of print.

ABSTRACT

This review explores the progressive domain of network pharmacology and its potential to revolutionize therapeutic approaches for Interstitial Lung Diseases (ILDs), a collective term encompassing Interstitial Pneumonia, Pneumoconiosis, Connective Tissue Disease-related ILDs, and Sarcoidosis. The exploration focuses on the profound legacy of traditional medicines, particularly Ayurveda and Traditional Chinese Medicines (TCM), and their largely unexplored capacity in ILD treatment. These ancient healing systems, characterized by their holistic methodologies and multifaceted treatment modalities, offer a promising foundation for discovering innovative therapeutic strategies. Moreover, the review underscores the amalgamation of artificial intelligence (AI) and machine learning (ML) methodologies with bioinformatics, creating a computational synergy capable of deciphering the intricate biological networks associated with ILDs. Network pharmacology has tailored the hypothesis from the conventional "one target, one drug" towards a "network target, multi-component therapeutics" approach. The fusion of traditional literature and computational technology can unveil novel drugs, targets, and pathways, augmenting effective therapies and diminishing adverse effects related to current medications. In conclusion, this review provides a comprehensive exposition of how Network Pharmacology tools can leverage the insights of Ayurveda and TCM to craft efficacious therapeutic solutions for ILDs. It sets the stage for future investigations in this captivating interdisciplinary domain, validating the use of traditional medicines worldwide.

PMID:39746273 | DOI:10.1016/j.intimp.2024.113979