Int J Mol Sci. 2024 Nov 28;25(23):12783. doi: 10.3390/ijms252312783.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a pulmonary disease characterized by excessive extracellular matrix protein deposition in the lung interstitium, subsequently causing respiratory failure. IPF still has a high medical unmet requirement due to the lack of effective treatments to inhibit disease progression. The etiology of IPF remains unclear, but mitochondrial dysfunction is considered to be associated with IPF development. Therefore, targeting mitochondrial abnormalities would be a promising strategy for treating IPF. Recently, exogenous mitochondrial transplantation has been beneficial for treating mitochondrial dysfunction. The current study aimed to examine the therapeutic effect of mitochondrial transplantation on IPF in vitro and in vivo. Mitochondria were isolated from human umbilical cord mesenchymal stem cells, referred to as PN-101. Human lung fibroblasts and human bronchial epithelial cells were exposed to transforming growth factor-β, followed by PN-101 treatment to determine the in vitro efficacy of mitochondrial transplantation. An IPF mouse model established by a single intratracheal instillation of bleomycin was utilized to determine the in vivo efficacy of the intravenously treated mitochondria. PN-101 attenuated mitochondrial damage, inhibited EMC production, and suppressed epithelial-to-mesenchymal transition in vitro. Additionally, intravenous PN-101 administration alleviated bleomycin-induced fibrotic processes in the IPF mouse model with a therapeutic context. Our data indicate that PN-101 is a novel and potential therapeutic agent for IPF.

PMID:39684495 | DOI:10.3390/ijms252312783

Cells. 2024 Dec 5;13(23):2005. doi: 10.3390/cells13232005.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is the most common interstitial lung disease with unknown etiology, characterized by chronic inflammation and tissue scarring. Although, Pirfenidone and Nintedanib slow the disease progression, no currently available drugs or therapeutic interventions address the underlying cause, highlighting the unmet medical need. A matricellular protein, Wnt-1-induced secreted protein 1 (WISP1), also referred to as CCN4 (cellular communication network factor 4), is a secreted multi-modular protein implicated in multi-organ fibrosis. Although the precise mechanism of WISP1-mediated fibrosis remains unclear, emerging evidence indicates that WISP1 is profibrotic in nature. While WISP1-targeting therapy is applied in the clinic for fibrosis, detailed interrogation of WISP1-mediated fibrogenic molecular and biological pathways is lacking. Here, for the first time, using NanoString® technology, we identified a novel WISP1-associated profibrotic gene signature and molecular pathways potentially involved in the initiation and progression of fibrosis in primary human dermal and lung fibroblasts from both healthy individuals and IPF patients. Our data demonstrate that WISP1 is upregulated in IPF-lung fibroblasts as compared to healthy control. Furthermore, our results confirm that WISP1 is downstream of the transforming growth factor-β (TGFβ), and it induces fibroblast cell proliferation. Additionally, WISP1 induced IL6 and CCL2 in fibroblasts. We also developed a novel, combined TGFβ and WISP1 in vitro system to demonstrate a role for WISP1 in the progression of fibrosis. Overall, our findings uncover not only similarities but also striking differences in the molecular profile of WISP1 in human fibroblasts, both during the initiation and progression phases, as well as in disease-specific context.

PMID:39682753 | DOI:10.3390/cells13232005

Respirology. 2024 Dec 16. doi: 10.1111/resp.14866. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: Acute exacerbation (AE) is often the fatal complication of idiopathic pulmonary fibrosis (IPF). Emerging evidence indicates that metabolic reprogramming and dysregulation of lipid metabolism are distinctive characteristics of IPF. However, the lipid metabolic mechanisms that underlie the pathophysiology of AE-IPF remain elusive.

METHODS: Serum samples for pilot study were collected from 34 Controls, 37 stable IPF (S-IPF) cases and 41 AE-IPF patients. UHPLC-MS/MS was utilized to investigate metabolic variations and identify lipid biomarkers in serum. ELISA, quantitative PCR and western blot were employed to validate the identified biomarkers.

RESULTS: There were 32 lipid metabolites and 5 lipid metabolism pathways enriched in all IPF patients compared to Controls. In AE-IPF versus S-IPF, 19 lipid metabolites and 12 pathways were identified, with 5-hydroxyeicosatetraenoic Acid (5-HETE) significantly elevated in AE-IPF. Both in internal and external validation cohorts, the serum levels of 5-HETE were significantly elevated in AE-IPF patients compared to S-IPF subjects. Consequently, the indicators related to 5-HETE in lipid metabolic pathway were significantly changed in AE-IPF patients compared with S-IPF cases in the lung tissues. The serum level of 5-HETE was significantly correlated with the disease severity (CT score and PaO2/FiO2 ratio) and survival time. Importantly, the receiver operating characteristic (ROC) curve, Kaplan-Meier analysis and Multivariate Cox regression analysis demonstrated that 5-HETE represents a promising lipid biomarker for the diagnosis and prognosis of AE-IPF.

CONCLUSION: Our study highlights lipid reprogramming as a novel therapeutic approach for IPF, and 5-HETE may be a potential biomarker of AE-IPF patients.

PMID:39681341 | DOI:10.1111/resp.14866

Curr Opin Allergy Clin Immunol. 2024 Dec 17. doi: 10.1097/ACI.0000000000001055. Online ahead of print.

ABSTRACT

PURPOSE OF REVIEW: To critically discuss the rationale for the use of drugs approved for idiopathic pulmonary fibrosis (IPF) to treat occupational interstitial lung diseases (OILDs).

RECENT FINDINGS: Although IPF and OILDs share several clinical, radiological and probably pathogenetic features, currently, OILDs do not have a standard of care. In recent years, our knowledge and understanding of ILDs has improved substantially. Recently, the progressive pulmonary fibrosis (PPF) phenotype, which refers to non-IPF fibrotic ILDs that progress despite appropriate treatment, has been defined. OILDs may also be progressive. Nintedanib, initially approved for treatment of IPF, is also approved in patients with PPF. On the other hand, pirfenidone is approved in IPF but not in PPF, due to the lack of robust evidence of efficacy in this patient subset.

SUMMARY: OILDs are a large and highly heterogeneous group of conditions without a proper standard of care. Nintedanib may slow functional decline and disease progression in progressive OILDs, and new clinical trials are ongoing.

PMID:39680372 | DOI:10.1097/ACI.0000000000001055

J Thorac Dis. 2024 Nov 30;16(11):7427-7445. doi: 10.21037/jtd-24-760. Epub 2024 Nov 14.

ABSTRACT

BACKGROUND: The prognosis for patients diagnosed with idiopathic pulmonary fibrosis (IPF) is exceedingly grim, and there are currently no pharmacological interventions available that effectively reduce mortality rates. Emerging evidence underscores the intimate connection between mitochondrial dysfunction and the onset and advancement of IPF. However, there remains a scarcity of prognostic models for assessing the risk associated with mitochondrial-related genes in IPF. This study aims to develop a comprehensive prognostic model for IPF that incorporates mitochondrial-related genes to enhance risk assessment and guide clinical decision-making.

METHODS: Two IPF-related microarray expression profiling datasets (GSE28042 and GSE70866) accompanied with survival data were acquired from the Gene Expression Omnibus (GEO) database. The "limma" R package was used to identify differentially expressed mitochondrial-related genes between normal samples and IPF samples. The prognostic model was constructed using univariate Cox regression, the least absolute shrinkage and selection operator (LASSO) Cox regression analyses, and multivariate Cox regression analysis. Multivariate independent prognostic analysis was conducted to ascertain whether the risk score could serve as an independent prognostic factor for predicting clinicopathological outcomes. A nomogram was employed to forecast the survival probability of IPF patients, providing valuable support for clinical decision-making processes. The CIBERSORT algorithm was utilized to examine discrepancies in immune cell infiltration within the model. The expression of genes screened from the prognostic model was validated in external data sets and western blot assays.

RESULTS: We developed a prognostic model for mitochondrial-related risks, incorporating ARMCX2 and ACOT11, and subsequently validated its predictive efficacy in the validation set. The IPF samples were stratified into high-risk and low-risk groups based on the median of the risk score. According to Kaplan-Meier curve analysis, the high-risk group exhibited inferior outcomes compared to the low-risk group. The time-dependent receiver operating characteristic (ROC) analysis demonstrated the accurate prognostic capability of the risk model for IPF. A nomogram, accompanied by calibration curves, was presented to predict 1-, 2-, and 3-year survival in IPF patients. The risk model we employed not only unveiled significant disparities in functional enrichment between the high-risk and low-risk groups, but also demonstrated a robust correlation with the infiltration of specific immune cells.

CONCLUSIONS: In this study, the mitochondrial-related prognostic model incorporating ARMCX2 and ACOT11 demonstrates potential clinical utility for informing decision-making in IPF patients and offers valuable insights for future therapeutic interventions.

PMID:39678889 | PMC:PMC11635208 | DOI:10.21037/jtd-24-760

Adv Sci (Weinh). 2024 Dec 15:e2406751. doi: 10.1002/advs.202406751. Online ahead of print.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a lethal disease with substantial unmet medical needs. While aberrant epithelial remodeling is a key factor in IPF progression, the molecular mechanisms behind this process remain elusive. Harnessing a 3D patient-derived organoid model and multi-omics approach, the first inventory of the connection between metabolic alteration, chromatin accessibility, and transcriptional regulation in IPF aberrant epithelial remodeling is provided. This remodeling is characterized by an increase in chromatin accessibility, particularly at JUNB motif-enriched promoter regions proximal to transcription start sites of metabolic and pro-fibrotic genes. Mechanistically, JUNB undergoes O-linked β-N-acetylglucosamine modification (O-GlcNAcylation), a critical step in modulating pro-fibrotic responses to chronic injury. This modification is pivotal in fostering the emergence of aberrant epithelial basal cells in the alveolar niche, a proposed driver of IPF pathology. Specific deletion of O-GlcNAcylation sites on JUNB attenuates the metaplastic differentiation of basal cells, thereby aiding in the restoration of the alveolar lineage. Together, the findings reveal a novel link between metabolic dysregulation and cell fate regulation at the chromatin level in fibrosis, mediated by the O-GlcNAc-JUNB axis, suggesting avenues for the development of new therapeutic strategies in IPF.

PMID:39676507 | DOI:10.1002/advs.202406751

Lab Invest. 2024 Dec 13:102210. doi: 10.1016/j.labinv.2024.102210. Online ahead of print.

ABSTRACT

Interstitial lung disease (ILD), characterized by inflammation and fibrosis, often suffers from low diagnostic accuracy and consistency. Traditional H&E staining primarily reveals cellular inflammation with limited detail on fibrosis. To address these issues, we introduce a pioneering label-free quantitative multiphoton fiber histology (MPFH) technique that delineates the intricate characteristics of collagen and elastin fibers for ILDs diagnosis. We acquired co-located multiphoton and H&E-stained images from a single tissue slice. Multiphoton imaging was performed on the deparaffinized section to obtain fibrotic tissue information, followed by H&E staining to capture cellular information. This approach was tested in a blinded diagnostic trial among 7 pathologists involving 14 relatively normal lung patients and 31 ILD patients (11 idiopathic pulmonary fibrosis (IPF) / usual interstitial pneumonia (UIP), 14 nonspecific interstitial pneumonia (NSIP), and 6 pleuroparenchymal fibroelastosis (PPFE)). A customized algorithm extracted quantitative fiber indicators from multiphoton images. These indicators, combined with clinical and radiological features, were used to develop an automatic multi-class ILDs classifier. Using MPFH, we can acquire high-quality, co-localized images of collagen fibers, elastin fibers, and cells. We found that the type, distribution, and degree of fibrotic proliferation can effectively distinguish between different subtypes. The blind study showed MPFH enhanced diagnostic consistency (kappa values from 0.56 to 0.72) and accuracy (from 73.0% to 82.5%, p=0.0090). The combination of quantitative fiber indicators effectively distinguished between different tissues, with areas under the receiver operating characteristic curves exceeding 0.92. The automatic classifier achieved 93.8% accuracy, closely paralleling the 92.2% accuracy of expert pathologists. The outcomes of our research underscore the transformative potential of MPFH in the field of f-ILD diagnostics. By integrating quantitative analysis of fiber characteristics with advanced machine learning algorithms, MPFH facilitates the automatic and accurate identification of various fibrotic disease subtypes, showcasing a significant leap forward in precision diagnostics.

PMID:39675724 | DOI:10.1016/j.labinv.2024.102210

Adv Med Sci. 2024 Dec 13:S1896-1126(24)00064-6. doi: 10.1016/j.advms.2024.12.001. Online ahead of print.

ABSTRACT

PURPOSE: Interstitial lung disease (ILD) damages the lungs and can be caused by environmental exposures and collagen-vascular diseases. The systemic immune-inflammation index (SII) is investigated to diagnose and manage ILDs in different etiological diseases. The study aims to examine the usefulness of SII in diagnosing specific ILDs like Sjogren's syndrome (SjS)-ILD, interstitial pneumonia with autoimmune features (IPAF), and idiopathic pulmonary fibrosis (IPF).

MATERIALS AND METHODS: In this cross-sectional study, we included 109 patients with IPAF, IPF, and SjS-ILD. Demographic characteristics, symptoms, lung patterns, autoantibodies, and SII were assessed. Morphologic, serologic, and clinical factors determined the classification of IPAF. Student's t-test, Mann-Whitney U test, Pearson-Spearman's method, and receiver operating characteristic (ROC) curves were used to analyze data.

RESULTS: Male patients were more common in IPF and IPAF, while SjS-ILD had mostly female patients. Raynaud's phenomenon and dry mouth/eyes were more common in SjS-ILD compared to IPF and IPAF. The groups had significant differences in patterns, antinuclear antibody positivity, and SII levels. SII levels differed significantly between IPAF, SjS-ILD, and IPF patients, and were correlated with CRP in IPAF and SjS-ILD. The cut-off value of the SII between IPAF and IPF in patients with ILD was 576.1 with 76.0% sensitivity and 76.0% specificity.

CONCLUSIONS: Evaluation of SII provides valuable information for understanding and identifying different disease groups with ILDs.

PMID:39675699 | DOI:10.1016/j.advms.2024.12.001

Int J Pharm. 2024 Dec 12:125074. doi: 10.1016/j.ijpharm.2024.125074. Online ahead of print.

ABSTRACT

Pirfenidone (PFD) is one of the first-line drugs for treating idiopathic pulmonary fibrosis, while directly delivering PFD to lung showed better efficiency. However, PFD is a non-glass former and easily precipitates into larger-sized crystals that are undesirable for pulmonary delivery. Hence, the fabrication of PFD particles with pulmonary delivery efficiency remains challenging. Herein, a series of particles were prepared by spray freeze drying a PFD and leucine mixed solution. The sub-ambient behavior of the mixed solution was evaluated via a differential scanning calorimeter. The effects of the PFD/leucine mass ratio and freezing temperature on the particle morphology, size, crystal polymorphism, molecular structure and in vitro aerosol performance were investigated. Shortening the lifetime of the droplet and adding proper amounts of leucine are the keys to decreasing the PFD crystal size and improving its dispersity. The optimal sample is SF-80D-P95L5-2, with high FPF and eFPF values of ∼ 65.97 % and ∼ 27.86 %, and owing to its high drug loading (95 %), the FPD and eFPD are extremely high at ∼ 6.27 mg and ∼ 2.65 mg, respectively, equivalent to ∼ 6.27 mg and ∼ 2.65 mg PFD deposited in the lungs and alveoli, respectively, when 10 mg dry powder is inhaled. This work provides a potential strategy for tuning the precipitation behavior of PFD microcrystals with high pulmonary drug delivery efficiency.

PMID:39674382 | DOI:10.1016/j.ijpharm.2024.125074

Int J Biochem Cell Biol. 2024 Dec 11:106728. doi: 10.1016/j.biocel.2024.106728. Online ahead of print.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a severe lung disease affecting around 5 million people globally, with a median survival of 3-4 years. Characterized by excessive scarring of lung tissue, IPF results from the accumulation of myofibroblasts that deposit extracellular matrix (ECM), causing fibrosis. Current treatments, pirfenidone and nintedanib, slow the disease but do not stop its progression. IPF pathogenesis involves repeated alveolar injury, leading to pro-fibrotic mediators like TGFβ1, which trigger fibroblast-to-myofibroblast transitions and ECM deposition. Recent research suggests that transient receptor potential (TRP) channels, such as TRPV4, TRPC6, and TRPA1, play a key role in regulating calcium signalling and mechanical stress, crucial in myofibroblast activation. Targeting TRP channels may disrupt fibrosis and offer new therapeutic strategies. Preclinical studies indicate that inhibiting TRP channels could reduce fibrosis, warranting further trials to explore their efficacy and safety in treating IPF and related fibrotic conditions.

PMID:39672503 | DOI:10.1016/j.biocel.2024.106728

Respir Investig. 2024 Dec 12;63(1):102-108. doi: 10.1016/j.resinv.2024.11.017. Online ahead of print.

ABSTRACT

BACKGROUND: The prognosis of acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is extremely poor. However, recent clinical reports suggest that direct hemoperfusion with polymyxin B-immobilized fiber column (PMX) treatment may have beneficial effects in patients with AE-IPF. The aim of this multicenter prospective study was to investigate the effectiveness and safety of PMX treatment in AE-IPF.

METHODS: We conducted a prospective study of patients with AE-IPF treated by PMX at two institutions in Japan. Each patient received 2-3 sessions of PMX treatment with a target duration of 6-24 h. The primary endpoint was the survival rate at day 28 after the PMX treatment.

RESULTS: The survival rate of the patients on day 28 after PMX treatment was 65% [95% confidence interval (CI): 40.3-81.5%]. The lower limit of 95% CI in the study was higher than the survival rate of 40%, which was the upper limit of the survival rate in AE-IPF receiving conventional treatments, as reported previously. The survival rate of the patients 12 weeks after PMX was 50% (95% CI: 27.1-69.2%). The changes in the difference between alveolar and arterial oxygen tension and the partial pressure of arterial oxygen/fraction of inspired oxygen improved as the number of PMX sessions increased, and significant improvements were observed at the end of the second PMX session. The safety of PMX was clinically acceptable.

CONCLUSIONS: This prospective multicenter study suggests that PMX treatment is safe for patients with AE-IPF and may improve their oxygenation and prognosis.

PMID:39672072 | DOI:10.1016/j.resinv.2024.11.017

Medicina (B Aires). 2024;84(6):1286.

NO ABSTRACT

PMID:39666430

Oncogene. 2024 Dec 11. doi: 10.1038/s41388-024-03236-5. Online ahead of print.

ABSTRACT

Lung cancer is a fatal complication of idiopathic pulmonary fibrosis (IPF) with a poor prognosis. Current treatments are insufficient in improving the prognosis of lung cancer patients with comorbid idiopathic pulmonary fibrosis (IPF-LC). Senescent fibroblasts, as stromal cells in the tumor microenvironment, influence tumor progression via exosomes. With evidence that fibroblast senescence is an important mechanism of IPF, we investigated the impact of senescent IPF lung fibroblast (diseased human lung fibroblasts, DHLF)-derived exosomes on non-small cell lung cancer (NSCLC). We found DHLF expressed significant senescence markers, and promoted NSCLC proliferation, invasion, and epithelial-mesenchymal transition. Specifically, senescent DHLF showed strong secretion of exosomes, and these exosomes enhanced the proliferation and colony-forming ability of cancer cells. Proteomic analysis showed DHLF-derived exosomes exhibited upregulated senescence-associated secretory phenotype (SASP) factors, notably MMP1, which activates the surface receptor PAR1. Knocking down MMP1 or using PAR1 inhibitors reduced the tumor-promoting effects of DHLF-derived exosomes in vivo and in vitro. Mechanistically, MMP1 acted by activating the PI3K-AKT-mTOR pathway. In conclusion, our results suggest that exosomal MMP1 derived from senescent IPF fibroblasts promotes NSCLC proliferation and colony formation by targeting PAR1 and activating the PI3K-AKT-mTOR pathway. These findings provide a novel therapeutic approach for patients with IPF-LC.

PMID:39663393 | DOI:10.1038/s41388-024-03236-5

Life Sci. 2024 Dec 9:123302. doi: 10.1016/j.lfs.2024.123302. Online ahead of print.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease characterized by irreversible lung scarring with a poor prognosis. Emerging evidence has revealed that IPF is an aging-related disease, and the development of cellular senescence plays a pivotal role in persistent remodeling and fibrotic scarring, acting as a key mechanism in the pathophysiology of IPF. Exploring therapeutic strategies for modulating cellular senescence can provide crucial insights into unraveling IPF processes. Here, we have identified Nitazoxanide (NTZ), an FDA-approved antiprotozoal agent, has specific effects on inhibiting cellular senescence development. In the bleomycin and D-galactose-induced senescence model, NTZ effectively inhibits senescence associated-β-gal staining and preserves cell proliferation ability. We also found that NTZ effectively impedes senescence progression in the bleomycin-induced pulmonary fibrosis model, while mitigating the release of senescence-associated secretory phenotype and alleviating pulmonary fibrosis. The anti-senescence effect of NTZ is mechanistically dependent on the preservation of nuclear SIRT1 expression. We observed that PI3K induces a WIPI1-mediated nucleophagic degradation of SIRT1, while NTZ effectively inhibits PI3K and suppresses WIPI1 expression, thereby maintaining SIRT1 expression in the nucleus and exerting its anti-senescence function. Collectively, our research has shown that NTZ can inhibit PI3K in senescence progression, leading to the inhibition of WIPI1-mediated SIRT1 nucleophagic degradation. As a result, NTZ alleviates fibrosis by inhibiting senescence development.

PMID:39662775 | DOI:10.1016/j.lfs.2024.123302

Semin Thorac Cardiovasc Surg. 2024 Dec 9:S1043-0679(24)00103-5. doi: 10.1053/j.semtcvs.2024.10.003. Online ahead of print.

ABSTRACT

OBJECTIVE: The American Association for Thoracic Surgery (AATS) Clinical Practice Standards Committee (CPSC) previously published important considerations in determining who is at high risk for complications or mortality after lobectomy. Sublobar resection, stereotactic ablative radiotherapy, or image-guided thermal ablation is typically considered when the risks associated with lobectomy are high. The current objective was to evaluate important lung-nodule-related factors to consider during treatment selection for high-risk patients with stage I non-small cell lung cancer (NSCLC).

METHODS: The AATS CPSC assembled an expert panel. The expert panel generated an a priori list of lung-nodule-related factors to consider in treatment selection and graded the relative importance of each factor on a scale of 1-10 in an anonymous survey after systematic review of the literature.

RESULTS: The expert panel survey identified several lung-nodule-related factors to consider in treatment selection. The panel ranked tumor location (peripheral vs central, mean score 8.4), tumor size (mean score 8.1), proximity to bronchovascular and critical structures (mean score 7.8), and the presence of interstitial lung disease/idiopathic pulmonary fibrosis (mean score 7.8) as the most important factors to consider.

CONCLUSIONS: This article summarizes the lung-nodule-related factors to consider when deciding between sublobar resection, stereotactic ablative radiotherapy, and image-guided thermal ablation during treatment selection for high-risk patients with stage I NSCLC. When possible, obtaining a biopsy is very important prior to non-surgical treatments. The choice of which modality is optimal in high-risk patients with stage I NSCLC is complex. A multi-disciplinary review of patient and tumor characteristics is essential for achieving an optimal decision.

PMID:39662535 | DOI:10.1053/j.semtcvs.2024.10.003

J Innate Immun. 2024 Dec 11:1-14. doi: 10.1159/000543083. Online ahead of print.

ABSTRACT

BACKGROUND: Interstitial lung diseases (ILD) are poorly understood disorders characterised by diffuse damage to the lung parenchyma, with inflammation and fibrosis. Some manifest a progressive fibrotic phenotype with high fatality and limited treatment options, such as idiopathic pulmonary fibrosis (IPF).

SUMMARY: The degree to which inflammation plays a role in fibrosis progression is unknown. However, wound healing and fibrosis are intricate processes influenced by various inflammatory factors. Extracellular nucleosides and nucleotides, including adenosine triphosphate (ATP), activate pro-inflammatory responses of innate immunity and are widely implicated in tissue fibrosis across different organs. The pro-inflammatory effects of extracellular nucleotides occur via P1 and P2 purinergic receptors, expressed across the lung and immune system, and have been implicated in various pulmonary diseases including pulmonary fibrosis. This review amalgamates available data on the complex role of P1 and P2 purinergic receptor signalling in pulmonary fibrosis and discusses perspectives for novel treatments.

KEY MESSAGES: Purinergic signalling plays a complex and pivotal role in pulmonary fibrosis, warranting further study. The intricate interplay between P1 and P2 receptor pathways necessitates a comprehensive approach to understand their collective impact. While evidence from preclinical models is promising, human studies are essential for further understanding in pulmonary fibrosis. Advances in receptor-specific agonists and antagonists provide novel avenues for research and may ultimately lead to new therapies for patients.

PMID:39662078 | DOI:10.1159/000543083

J Bras Pneumol. 2024 Dec 6;50(5):e20240058. doi: 10.36416/1806-3756/e20240058. eCollection 2024.

ABSTRACT

OBJECTIVE: The frequency of obstructive sleep apnea (OSA) in patients with idiopathic pulmonary fibrosis (IPF) is high. The clinical course of non-IPF interstitial lung disease (ILD) can be similar to that of IPF. We sought to assess the frequency and predictors of OSA in patients with non-IPF fibrotic ILD, as well as the impact of positive airway pressure (PAP) therapy on the quality of life of such patients.

METHODS: This was a prospective study in which non-IPF fibrotic ILD patients underwent a home sleep apnea test. The patients with and without OSA were compared, and a multivariate logistic regression model was used to identify independent predictors of OSA. At 3 months after initiation of PAP therapy, we evaluated the participating patients for respiratory events, nocturnal hypoxemia, and changes in quality of life.

RESULTS: Of a total of 50 patients, 50% were male, and 76% were diagnosed with OSA. The mean age was 67.8 ± 8.3 years. The patients with OSA had significantly lower TLC (p = 0.033) and awake SpO2 (p = 0.023) than did those without OSA. In the multivariate logistic regression model, SpO2 (OR = 0.46; p = 0.016) and TLC (OR = 0.95; p = 0.026) remained significantly associated with OSA risk. A total of 12 patients received PAP therapy. At 3 months after initiation of PAP therapy, 91.7% were well controlled, Epworth Sleepiness Scale scores decreased significantly (p = 0.006), and emotional well-being tended to improve (p = 0.068). PAP therapy corrected nocturnal hypoxemia in all patients.

CONCLUSIONS: We found a high frequency of OSA in patients with non-IPF fibrotic ILD. A low TLC was an independent predictor of a higher risk of OSA. PAP therapy can correct nocturnal hypoxemia. There should be a low threshold for suspicion of OSA and initiation of PAP therapy in patients with non-IPF fibrotic ILD.

PMID:39661832 | DOI:10.36416/1806-3756/e20240058

Asian J Pharm Sci. 2024 Aug;19(4):100944. doi: 10.1016/j.ajps.2024.100944. Epub 2024 Jul 14.

ABSTRACT

Mesenchymal stem cells (MSCs) have emerged as promising candidates for idiopathic pulmonary fibrosis (IPF) therapy. Increasing the MSC survival rate and deepening the understanding of the behavior of transplanted MSCs are of great significance for improving the efficacy of MSC-based IPF treatment. Therefore, dual-functional Au-based nanoparticles (Au@PEG@PEI@TAT NPs, AuPPT) were fabricated by sequential modification of cationic polymer polyetherimide (PEI), polyethylene glycol (PEG), and transactivator of transcription (TAT) penetration peptide on AuNPs, to co-deliver retinoic acid (RA) and microRNA (miRNA) for simultaneously enhancing MSC survive and real-time imaging tracking of MSCs during IPF treatment. AuPPT NPs, with good drug loading and cellular uptake abilities, could efficiently deliver miRNA and RA to protect MSCs from reactive oxygen species and reduce their expression of apoptosis executive protein Caspase 3, thus prolonging the survival time of MSC after transplantation. In the meantime, the intracellular accumulation of AuPPT NPs enhanced the computed tomography imaging contrast of transplanted MSCs, allowing them to be visually tracked in vivo. This study establishes an Au-based dual-functional platform for drug delivery and cell imaging tracking, which provides a new strategy for MSC-related IPF therapy.

PMID:39660166 | PMC:PMC11630633 | DOI:10.1016/j.ajps.2024.100944

Sarcoidosis Vasc Diffuse Lung Dis. 2024 Dec 10;41(4):e2024051. doi: 10.36141/svdld.v41i4.15198.

ABSTRACT

BACKGROUND: Interstitial lung diseases have high mortality associated with hospitalization for decompensation. There are doubts about the factors involved in the progression of fibrosis, for example the role played by acute exacerbations. With this work, the authors intend to analyze whether there are predictive parameters of mortality related to exacerbations.

METHODS: A retrospective study was carried out of patients admitted to the Pulmonology department of Coimbra University Hospital Center for exacerbation of fibrosing lung disease between January 2019 and December 2020. These were classified as: idiopathic pulmonary fibrosis (IPF), fibrosing hypersensivity pneumonitis (FHP) and other fibrosing lung diseases. Statistical analysis was performed using SPSS 26.0 considering statistically significant p<0.05 values.

RESULTS: The results show that IPF is associated with longer hospital stay in relation to fibrosing HP and other fibrosing lung diseases mean of 20.93 days (95% CI: 14.69-27.18) vs 11.8 days (95% CI: 1.05-17.22, p=0.023) vs 12.23 days (95% CI 2.06-15.34, p=0.007), respectively. Regarding mortality, there was no difference between IPF, PH and other fibrosing diseases (p=0.631).

CONCLUSION: This study demonstrated that IPF, compared to PH and other fibrosing diseases, is associated with longer hospital stays, probably due to its progressive course despite the institution of corticosteroid therapy. As shown in previous studies, it was concluded that there is no difference in terms of mortality between IPF exacerbations and other forms of fibrosing lung disease.

PMID:39655596 | DOI:10.36141/svdld.v41i4.15198

Sarcoidosis Vasc Diffuse Lung Dis. 2024 Dec 10;41(4):e2024050. doi: 10.36141/svdld.v41i4.15675.

ABSTRACT

BACKGROUND AND AIM: Lung cancer is one of the significant comorbidities seen in patients with Idiopathic Pulmonary Fibrosis (IPF). However, there is limited data on non-IPF Pulmonary Fibrosis (PF) patients with lung cancer (LC). The present study aims to compare the characteristics and survival outcomes of patients diagnosed with LC in IPF and non-IPF PF.

METHODS: The multicenter data records of IPF and non-IPF PF patients diagnosed with lung cancer between 2010- 2022 were analyzed in this descriptive, cross-sectional, and retrospective study.

RESULTS: Of the 251 patients involved in this study [164 IPF-LC, 87 non-IPF PF-LC], 89.6% were male, the mean age was 69±7.9 years and the smoking rate was 85.7%. Honeycomb pattern was more frequently observed in IPF-LC patients [62.8%,37.9%p<0.001], whereas ground-glass opacity [33.5%,59.8%p<0.001] and emphysema [37.8%,59.8%p<0.001] were more frequently seen in non-IPF PF-LC patients. The most commonly seen histological type was squamous cell carcinoma [42.7%,33.9%], followed by adenocarcinoma [28.2%; 32.2%]. [46.4%;47.2%] and their 5-year mortality rates were high [64.6%, 63.2%]. The median survival for both groups was 2±0.22 years [median 95% CI (1.55-2.44)]. The shortest survival time was observed in non-IPF PF-LC subgroup with unclassified PF [1±0.253 years median 95% CI (0.50-1.49) (p=0.030)].

CONCLUSIONS: The majority of IPF and non-IPF PF LC patients were male, elderly, and had a high smoking rate. Squamous cell carcinoma was the most frequently seen histological type and they had short survival periods and high mortality rates. The survival period of unclassified non-IPF PF-LC patients was found to be the shortest.

PMID:39655590 | DOI:10.36141/svdld.v41i4.15675