Ther Adv Drug Saf. 2025 May 27;16:20420986251341645. doi: 10.1177/20420986251341645. eCollection 2025.

ABSTRACT

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, life-threatening lung disease with a global incidence of 0.09-1.30 per 10,000 individuals. Pirfenidone and nintedanib are the approved treatments for IPF.

OBJECTIVES: This study evaluated the real-world safety and tolerability profiles of pirfenidone and nintedanib in IPF patients treated at the Mediterranean Institute for Transplantation and Advanced Specialized Therapies (IRCCS ISMETT). A comparative analysis was conducted based on the number, types, and severity of adverse drug reactions (ADRs) and to identify potential predictors of treatment discontinuation or ADR onset based on patient characteristics.

DESIGN: A retrospective observational study was conducted on 531 IPF patients treated at IRCCS ISMETT with either pirfenidone or nintedanib.

METHODS: Eligible patients were selected based on the logged monthly dispensations provided by the pharmacy service for both therapies. Covariates were extracted from electronic medical records (age, sex, body mass index, smoking history, comorbidities, forced vital capacity (FVC) %, diffusing capacity of the lung for carbon monoxide (DLCO) %, 6-minute walk test (6-MWT), polytherapy, oxygen therapy, drug switch, etc.). ADRs were categorized by severity and follow-up status, and further classified according to the Medical Dictionary for Regulatory Activities, specifying the Preferred Terms and the related System Organ Classes. Chi-square or Fisher's exact test was used for categorical variables, and univariate and multiple logistic regression identified potential risk factors for ADR onset. Backward Stepwise logistic regression (BSLR) was used to determine independent variables associated with ADR occurrence.

RESULTS: The nintedanib group had more frequent ADRs related to gastrointestinal and hepatobiliary disorders, with nausea, diarrhea, anorexia, and weight loss as the most common. The pirfenidone group had more ADRs related to skin, nervous system, and vascular disorders, such as rash, nausea, dizziness, and blood pressure imbalances. Significant baseline differences between groups included age, smoking status, FVC (%), DLCO (%), and 6-MWT, with the nintedanib cohort showing worse baseline characteristics. A total of 450 ADRs were reported: 59.6% for nintedanib and 40.4% for pirfenidone. Independent variables that significantly increased the likelihood of experiencing ADR were drug change, treatment type, gender, and age.

CONCLUSION: Identifying ADR predictors is essential for personalizing treatment strategies. Both pirfenidone and nintedanib are crucial in managing IPF, highlighting the need for further research to optimize personalized therapies and patient outcomes.

PMID:40438276 | PMC:PMC12117236 | DOI:10.1177/20420986251341645

ERJ Open Res. 2025 May 27;11(3):00826-2024. doi: 10.1183/23120541.00826-2024. eCollection 2025 May.

ABSTRACT

INTRODUCTION: Up to 11% of patients are left with residual lung abnormalities following COVID-19 infection. It is unclear whether these changes resolve over time or progress to fibrosis. The airway microbiome is altered in interstitial lung disease, potentially contributing to pathogenesis and disease progression. We hypothesised that the airway microbiome in patients with post-COVID-19 residual lung abnormalities may be altered.

METHODS: The POST COVID-19 interstitial lung DiseasE (POSTCODE) study recruited subjects with post-COVID-19 residual lung abnormalities for bronchoscopy. 16S ribosomal RNA gene amplicon sequencing was performed on DNA extracted from bronchoalveolar lavage fluid and compared with that from patients with idiopathic pulmonary fibrosis, fibrotic hypersensitivity pneumonitis and control subjects.

RESULTS: 28 subjects with post-COVID-19 residual lung abnormalities were recruited an average of 11 months after infection. No significant associations were found between the lower airway microbiome or bacterial burden and disease severity or trajectory. There was no difference in bacterial burden between post-COVID-19 patients and interstitial lung disease or control subjects. Furthermore, no differences in microbial composition were observed between these patients and those with fibrotic hypersensitivity pneumonitis or controls. However, compared with idiopathic pulmonary fibrosis, there was an increased abundance of Streptococcus and higher α-diversity in subjects with post-COVID-19 residual lung abnormalities.

CONCLUSIONS: The microbiome and bacterial burden in the lower airways of subjects with post-COVID-19 residual lung abnormalities do not differ from those of controls. The microbiome differs from idiopathic pulmonary fibrosis. This, and the absence of associations between microbial features and disease severity or clinical outcomes, suggests that the microbiome is unlikely to contribute to residual lung abnormalities in patients recovering from COVID-19 infection.

PMID:40432814 | PMC:PMC12107383 | DOI:10.1183/23120541.00826-2024

Medicina (Kaunas). 2025 May 14;61(5):892. doi: 10.3390/medicina61050892.

ABSTRACT

Background: Interstitial lung disease (ILD) is characterized by pulmonary inflammation and fibrosis associated with persistent and refractory cough that significantly hinders quality of life. Conventional treatments for ILD-associated cough have shown limited efficacy, necessitating alternative therapeutic approaches. Gefapixant, a P2X3 receptor antagonist, can potentially alleviate chronic cough by inhibiting the ATP-mediated activation of sensory C-fibers, but its efficacy in ILD-associated cough remains unclear. This study observed the effects of gefapixant on ILD-associated refractory chronic cough. Methods: This prospective study enrolled patients with ILD-associated refractory chronic cough who received gefapixant at Sapporo Medical University Hospital between July 2022 and November 2023. Cough frequency, Leicester Cough Questionnaire (LCQ) score, cough severity visual analog scale (Cough VAS), and taste VAS were evaluated at baseline and at 2, 4, and 8 weeks after gefapixant administration. Results: Six patients completed the study. Their ILD subtypes included idiopathic pulmonary fibrosis (IPF), nonspecific interstitial pneumonia (NSIP), and connective tissue disease-associated ILDs (CTD-ILDs). After 8 weeks, the cough frequency decreased from 88.5 to 44.3 episodes per 30 min, LCQ scores increased from 8.3 to 13.6, and cough VAS scores decreased from 75.8 to 40.2. However, statistical significance was not reached due to high interindividual variability, with gefapixant being effective in some and ineffective in others. The most common adverse event was taste disorder, leading to discontinuation in one patient, but symptoms tended to lessen over the course of treatment. Conclusions: Gefapixant appears to be effective in reducing refractory cough related to ILD, although these results were not statistically significant because its effectivity widely varied across individuals. Further investigation is needed to identify patient subgroups with the greatest potential for treatment responsiveness.

PMID:40428850 | DOI:10.3390/medicina61050892

Diagnostics (Basel). 2025 May 16;15(10):1267. doi: 10.3390/diagnostics15101267.

ABSTRACT

Background/Objectives: Hypersensitivity pneumonitis (HP), a subtype of interstitial lung disease (ILD), is often misdiagnosed as idiopathic pulmonary fibrosis (IPF), particularly when the causative antigen cannot be identified. Typically resulting from chronic exposure to inhaled organic particles smaller than 5 microns, HP presents a diagnostic challenge. This report outlines a case of fibrotic HP initially misclassified as asthma. No triggering antigen was identified despite extensive investigation. The disease progressed despite corticosteroid, immunosuppressive, and antifibrotic therapy, ultimately leading to an advanced fibrotic stage and requiring lung transplantation. This clinical course is rare and infrequently reported, particularly in cases requiring lung transplantation without an identifiable causative antigen. Such progression is uncommon and underreported, especially in patients initially misclassified as having asthma. Methods: Medical records of 24 patients diagnosed with HP were reviewed. Only one case demonstrated progression to fibrotic HP; this case was selected for detailed analysis. Results: Clinical and functional deterioration occurred despite standard therapy. Given the advanced stage of fibrosis and treatment resistance, lung transplantation was deemed the next appropriate therapeutic option. Conclusions: HP remains underdiagnosed due to difficulties in identifying the causative antigen and overlapping features with other ILDs. Early and accurate differentiation from IPF is essential, particularly in progressive fibrotic forms unresponsive to conventional therapies.

PMID:40428260 | DOI:10.3390/diagnostics15101267

Biomedicines. 2025 Apr 30;13(5):1096. doi: 10.3390/biomedicines13051096.

ABSTRACT

In the original publication, there was a mistake in Figure 11 as published [...].

PMID:40427093 | DOI:10.3390/biomedicines13051096

Thorax. 2025 May 27:thorax-2024-222060. doi: 10.1136/thorax-2024-222060. Online ahead of print.

ABSTRACT

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive disease of lung parenchymal scarring that is triggered by repeated microinjury to a vulnerable alveolar epithelium. It is increasingly recognised that cellular ageing, whether physiological or accelerated due to telomere dysfunction, renders the epithelium less able to cope with injury and triggers changes in epithelial behaviour that ultimately lead to the development of disease.

AIMS: This review aims to highlight how, with increasing age, the alveolar epithelium becomes vulnerable to exogenous insults. We discuss the downstream consequences of alveolar epithelial dysfunction on epithelial phenotype, alveolar repair and pro-pathogenic interactions with other alveolar niche-resident cell types which drive IPF pathogenesis.

NARRATIVE: We highlight how a wide array of cellular mechanisms that maintain cellular homeostasis become dysfunctional with ageing. Waning replicative capacity, genomic stability, mitochondrial function, proteostasis and metabolic function all contribute to a phenotype of vulnerability to 'second hits'. We discuss how in IPF the alveolar epithelium becomes dysfunctional, highlighting changes in repair capacity and fundamental cellular phenotype and how interactions between abnormal epithelium and other alveolar niche-resident cell types perpetuate disease.

CONCLUSIONS: The ageing epithelium is a vulnerable epithelium which, with the cumulative effects of environmental exposures, fundamentally changes its behaviour towards stalled differentiation, failed repair and profibrotic signalling. Further dissection of aberrant epithelial behaviour, and its impact on other alveolar cell types, will allow identification of novel therapeutic targets aimed at earlier pathogenic events.

PMID:40425299 | DOI:10.1136/thorax-2024-222060

Thorax. 2025 May 27:thorax-2025-223227. doi: 10.1136/thorax-2025-223227. Online ahead of print.

NO ABSTRACT

PMID:40425298 | DOI:10.1136/thorax-2025-223227

Toxicol Appl Pharmacol. 2025 May 25:117412. doi: 10.1016/j.taap.2025.117412. Online ahead of print.

ABSTRACT

PURPOSE: There is a need to generate new treatments against pulmonary diseases such as idiopathic fibrosis and asthma. N-acetylcysteine (NAC) has multiple clinical applications, but its unstable nature and route of administration limits its effectiveness. New pulmonary delivery strategies, such as liposomes made of lung surfactant lipids, could overcome NAC's limitations. This work aims to evaluate the efficacy of NAC combined with liposomes as a treatment for asthma and in preventing fibrotic development.

METHODS: Unilamellar vesicles were obtained through the dehydration-rehydration method followed by multiple membrane extrusion and characterized by Dynamic Light Scattering and Transmission electron microscopy. Lung fibrosis was induced by bleomycin administration, and liposomal formulation of NAC (LipoNAC) was evaluated as a preventive treatment. LipoNAC formulation was also evaluated in a therapeutic regimen for asthma using the classic ovalbumin model. For both models, the administration of the treatment was via the intranasal route.

RESULTS: NAC treatments (free NAC and LipoNAC) improved lung histopathology and decreased collagen deposition when tested in the lung fibrosis model. Only LipoNAC decreased serum levels of lactate dehydrogenase, myeloperoxidase activity in lung fluid and lung TGF-β. Although both treatments decreased Th2 cytokine and histopathological inflammation in the asthma model, only LipoNAC treatment significantly decreased mucus in asthmatic mice.

CONCLUSIONS: These results indicate that surfactant liposomal delivery of NAC potentiates its anti-inflammatory, mucolytic, and antioxidant activity, rendering it a promising therapy for respiratory diseases.

PMID:40425069 | DOI:10.1016/j.taap.2025.117412

Biochim Biophys Acta Mol Basis Dis. 2025 May 26;1871(7):167924. doi: 10.1016/j.bbadis.2025.167924. Online ahead of print.

NO ABSTRACT

PMID:40424856 | DOI:10.1016/j.bbadis.2025.167924

Radiology. 2025 May;315(2):e243651. doi: 10.1148/radiol.243651.

ABSTRACT

Background Limited evidence exists on the prevalence and outcomes of interstitial lung abnormalities (ILAs) in lung cancer screening populations, particularly Asian populations. Purpose To investigate the prevalence of ILAs and the association of ILAs with lung cancer, idiopathic pulmonary fibrosis (IPF), and mortality outcomes in an Asian population. Materials and Methods In this nationwide, population-based retrospective study, baseline screenings from the Korean National Lung Cancer Screening Program performed between August 2019 and December 2020 were analyzed. ILAs were identified from CT structured reports based on program radiologists' visual assessment, and ILA prevalence was analyzed across age groups. Incidence rate ratios were calculated for lung cancer incidence, IPF, and all-cause mortality comparing individuals with ILAs versus individuals without ILAs, and multivariable Cox regression analyses were performed to examine associations between ILAs and these outcomes. Results Among 125 600 individuals (mean age, 62 years ± 5.3 [SD]; 123 331 men), ILA prevalence was 2.65% (3324 of 125 600) and was strongly associated with older age (P < .001). The lung cancer incidence rate was higher in the ILA group (2009 vs 412 per 100 000 person-years, P < .001; incidence rate ratio, 4.88), as was the all-cause mortality rate (2334 vs 712 per 100 000 person-years, P < .001; incidence rate ratio, 3.28). During a median follow-up of 2.9 years, IPF was diagnosed in 3.55% (118 of 3324) of individuals with ILAs (incidence rate, 1344 per 100 000 person-years in group with ILAs vs 18 per 100 000 person-years in group without ILAs, P < .001; incidence rate ratio, 73.24). In multivariable analyses, individuals with ILAs had a threefold higher risk of lung cancer (adjusted hazard ratio, 3.18 [95% CI: 2.71, 3.73]; P < .001) and twofold higher all-cause mortality (adjusted hazard ratio, 2.37 [95% CI: 2.09, 2.69]; P < .001). Individuals with ILAs showed a markedly higher risk of IPF diagnosis, with more than 60-fold higher risk (adjusted hazard ratio, 63.4 [95% CI: 45.9, 87.7]; P < .001). Conclusion The presence of ILAs was associated with higher risks of lung cancer, IPF, and mortality. © RSNA, 2025 Supplemental material is available for this article. See also the editorial by Baruah and Kabakus in this issue.

PMID:40423536 | DOI:10.1148/radiol.243651

Toxins (Basel). 2025 Apr 24;17(5):213. doi: 10.3390/toxins17050213.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease characterized by the fibrotic thickening of the alveolar walls, resulting in compromised gas exchange, restricted ventilation, and respiratory failure. It has been indicated that elastase inhibitors reduced the severity of IPF by neutralizing excessive elastase levels in the lungs. ShSPI is an elastase inhibitor derived from centipede toxin. The present study evaluates the therapeutic effects of ShSPI in a bleomycin-induced idiopathic pulmonary fibrosis model. According to the results, ShSPI markedly reduced the weight loss, showing the improvement of health status in bleomycin-induced mice. Its robust antifibrotic effects were evidenced by the mitigation of alveolar structural damage, reduction in inflammatory cell infiltration, inhibition of collagen deposition, and suppression of fibrotic nodule formation. ShSPI effectively attenuated inflammatory responses by downregulating pro-inflammatory factors (IL-6, IL-1β, and MCP-1) and upregulating the anti-inflammatory factor interleukin-10 (IL-10). After delivered via inhalation, ShSPI exhibited favorable pharmacokinetic properties. It could be detected at 8 h at doses of 1 mg/kg and achieved maximum plasma concentrations (Cmax) of 188.00 ± 64.40 ng/mL in vivo. At high doses (160 mg/kg), ShSPI maintained a strong safety profile, with no detectable toxicity observed. This feature shows the therapeutic potential of ShSPI in the treatment of idiopathic pulmonary fibrosis and provides valuable evidence for its development as a novel peptide-based therapy.

PMID:40423296 | DOI:10.3390/toxins17050213

J Pers Med. 2025 May 21;15(5):213. doi: 10.3390/jpm15050213.

ABSTRACT

Interstitial lung disease (ILD) prevalence and survival are increasing due to improvement in scientific research together with clinical complications typical of advanced disease. Lung cancer (LC) is described as a possible event occurring in lung parenchyma in the context of fibrotic abnormalities that worsen patients' prognosis. This growth of malignant cells on a fibrotic background has also been called scar-cinoma. For this reason, not only an early diagnosis but also personalized decisions on the best treatment approach should be considered for each patient in a multidisciplinary discussion, since in some cases chemotherapy or surgery could be detrimental for patients with pulmonary fibrosis. LC and lung fibrosis may share common pathogenetic mechanisms like an altered healing process in response to repeated tissue damage from environmental exposure in genetically susceptible individuals. Smoking history and air pollution together with mutations in telomere and surfactant protein genes lead to the production of cytokines and nitro derivatives in the microenvironment that facilitate the carcinomatous transformation during fibrogenesis. The evolution of LC therapy and the implementation of immunotherapy acting on targetable immune checkpoints have raised interest in evaluating ILD-LC actionable mutations. The main pathogenetic mechanisms, clinical presentations and treatment implications are presented in this review.

PMID:40423084 | DOI:10.3390/jpm15050213

BMC Pulm Med. 2025 May 26;25(1):263. doi: 10.1186/s12890-025-03706-w.

ABSTRACT

Intestitial lung diseases (ILDs) include a group of inflammatory and fibrotic pulmonary disorders with different etiologies which in several patients might lead to a progressive reduction of respiratory capacities and chronic respiratory failure. Nowadays, biomarkers for predicting the ILD progression and response to therapies are lacking. Adiponectin, the most abundant peptide secreted by adipocytes, has emerged as a potential response biomarker in fibrotic progressive ILDs. The aim of this observational prospective single-center cross-sectional study is therefore to verify whether serum adiponectin levels were altered in patients with fibrotic ILDs (f-ILDs) and its correlation with clinical and pulmonary function data. Sixty-four f-ILDs patients - divided in three subgroups IPF, CTD-ILDs and other f-ILDs - and 45 healthy subjects were recruited. Serum adiponectin concentration were measured by enzyme-linked immunosorbent assay (ELISA). Pulmonary function tests and clinical data were systematically collected. The results showed that patients with f-ILDs have reduced circulating levels of serum adiponectin (12.5 [10.8-15.4] versus 19.3 [17.3-20.8] p < 0.001). No significant difference in adiponectin levels were observed in the different f-ILDs subgroups (p = 0.619). Adiponectin levels were not associated with progression of f-ILDs (p = 0.745). High molecular weight adiponectin isoform was highly reduced in patients with f-ILDs. In patients with CTD-ILDs - but not in other subgroups - adiponectin levels were associated with pulmonary function and GAP index. These resuls support a potential role of adiponectin as diagnostic and prognostic biomarker of f-ILDs.

PMID:40420027 | DOI:10.1186/s12890-025-03706-w

Cell Mol Life Sci. 2025 May 27;82(1):214. doi: 10.1007/s00018-025-05729-2.

ABSTRACT

Long non-coding RNAs (lncRNAs) play critical roles in the process of lung tissue injury and repair which abnormal repair leads to disease including fibrosis, yet the physiopathology remains elusive. Here, we identified the lncRNA SYISL as a key regulator that is markedly upregulated in idiopathic pulmonary fibrosis (IPF) patients and bleomycin (BLM)-induced murine fibrotic lungs. Inhibition of SYISL significantly attenuates TGF-β1-driven fibroblast myofibroblast transition (FMT), a process confers to tissue injury repair and regeneration. Which demonstrates SYISL interaction with miR-23a function as a potent suppressor of fibrotic activation. Mechanistically, SYISL acts as a competing endogenous RNA (ceRNA) that directly binds miR-23a, thereby derepressing TRIO and F-actin binding protein (TRIOBP) via targeting its 3' untranslated region (UTR). Knockdown of TRIOBP amplifies the anti-fibrotic effects of miR-23a mimics while abolishing the pro-fibrotic activity of miR-23a inhibitors, establishing TRIOBP as a downstream effector of the SYISL/miR-23a axis. In vivo, intratracheal delivery of SYISL-targeting shRNA via adeno-associated virus (AAV) robustly reduces collagen deposition, hydroxyproline content, and expression of fibrotic markers in BLM-induced mice. Our findings elucidate a lncRNA-driven regulatory circuit in which SYISL promotes pulmonary fibrosis by sequestering miR-23a to elevate TRIOBP expression, nominating this axis as a novel therapeutic target for IPF.

PMID:40419807 | DOI:10.1007/s00018-025-05729-2

Cell Signal. 2025 May 24:111886. doi: 10.1016/j.cellsig.2025.111886. Online ahead of print.

ABSTRACT

TRIM7, a member of the E3 ubiquitin ligase family, has garnered significant attentions in different research fields since its discovery. This enzyme plays indispensable roles in various pathophysiological processes through ubiquitination-mediated degradation of diverse protein substrates. This review systematically summarizes the current knowledge on the protein structure and biological functions of TRIM7. Structurally, TRIM7 features a conserved RBCC motif (RING, B-box, and coiled-coil domains) coupled with a variable C-terminal region that dictates the substrate specificity. In infectious contexts, TRIM7 is required for the pathogen-specific regulation, and exerts paradoxical effects by either promoting host defense or facilitating viral pathogenesis depending on pathogen type. Within oncology, TRIM7 manifests tumor-suppressive properties through regulating metastasis, apoptosis, and tumor immunology. In addition, it might serve as a reliable biomarker for monitoring the progression of idiopathic pulmonary fibrosis and also inhibits the progression of atherosclerosis. In summary, TRIM7 plays critical roles in different pathophysiological processes, and it might be a predictive and therapeutic target in certain human diseases.

PMID:40419231 | DOI:10.1016/j.cellsig.2025.111886

J Vis Exp. 2025 May 9;(219). doi: 10.3791/67953.

ABSTRACT

Interstitial lung disease (ILD) represents a broad spectrum of disorders characterized by the progressive and often irreversible scarring of the lung parenchyma, the most common being idiopathic pulmonary fibrosis (IPF). Several animal models of IPF have been developed, with the bleomycin murine model being the most widely used. Bleomycin is a chemotherapeutic known to induce DNA damage in the alveolar epithelium, resulting in acute lung injury and pulmonary fibrosis in humans. Rodent models of IPF use bleomycin administration via various methods, the most common being intratracheal (IT). Recently, the oropharyngeal aspiration (OA) technique has been shown to be equally efficacious as IT for multiple fibrosing agents, with considerably fewer side effects and an easier route of delivery. This protocol details the OA method of bleomycin delivery into the murine lung and highlights examples of potential downstream applications for data quantification. This methodology offers a simple, quick, and safe way to utilize this widely used animal model for studying the molecular mechanisms underlying IPF.

PMID:40418675 | DOI:10.3791/67953

Nat Sci Sleep. 2025 May 19;17:975-985. doi: 10.2147/NSS.S506975. eCollection 2025.

ABSTRACT

BACKGROUND: Obstructive sleep apnea (OSA) is prevalent in patients with idiopathic pulmonary fibrosis (IPF). This study evaluated the prognostic significance of Krebs von den Lungen-6 (KL-6) levels in patients with comorbid OSA and IPF.

METHODS: This retrospective research included 115 individuals diagnosed with IPF between January 2015 and December 2020, all of whom completed sleep tests and underwent measurement of serum KL-6 levels during hospitalization. To ascertain the risk factors associated with all-cause death, a multivariate Cox regression model was employed, adjusted for confounding variables of age, sex, and pulmonary function.

RESULTS: During the 40-month follow-up, 24 (20.9%) deaths occurred, with 17 (28.8%) in the OSA group and 7 (12.5%) in the non-OSA group. Patients with OSA had higher baseline KL-6 levels than did those without OSA. Both apnea-hypopnea index (hazard ratio [HR] = 1.023, 95% confidence interval [CI] 1.000-1.047, p = 0.049) and serum KL-6 levels (HR = 1.001, 95% CI 0.999-1.002, p = 0.032) were identified as independent risk factors for death in multivariable Cox analysis. For the overall cohort of patients with IPF, those with a KL-6 levels ≥1200 U/mL had a higher risk of death in both univariate analysis (HR = 5.694, 95% CI 1.945-16.669, p = 0.002) and adjusted models (HR = 5.245, 95% CI 1.775-15.494, p = 0.003). In the subgroup analysis, the independent prognostic significance of KL-6 levels ≥1200 U/mL for death was evident only in IPF patients with concurrent OSA (HR = 4.887, 95% CI 1.082-22.067, p = 0.039), whereas it was not observed yet in IPF patients without OSA (HR = 4.652, 95% CI 0.616-35.131, p = 0.136).

CONCLUSION: KL-6 level is of prognostic value in patients with comorbid IPF and OSA. These findings underscore the need for sleep tests and KL-6 measurement for IPF patients at high risk.

PMID:40417308 | PMC:PMC12101450 | DOI:10.2147/NSS.S506975

Am J Physiol Cell Physiol. 2025 May 24. doi: 10.1152/ajpcell.00022.2025. Online ahead of print.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a fatal aging-related disease characterized by aberrant lung remodeling and progressive scarring, leading to organ failure and death. Current FDA approved anti-fibrotic treatments are unable to reverse established disease, highlighting the need for innovative therapeutic approaches targeting novel pathways and cell types. Mounting evidence, including our own, has recently highlighted the pathogenic role of aging-related endothelial abnormalities, including vascular inflammation and oxidative stress, in the progression of lung fibrosis, offering new therapeutic opportunities to block IPF progression. Unexplored, however, are the modalities to restore vascular abnormalities associated with progressive lung fibrosis, representing a critical gap to effective treatments for IPF. In this study, we demonstrate that circulating extracellular vesicles (cEVs) isolated from young mice are capable of reversing the aging-associated transcriptional alterations of the pulmonary vasculature, reducing transcripts associated with innate immunity, oxidative stress and senescence, while simultaneously increasing transcripts linked to endothelial identity. Using the bleomycin model of persistent lung fibrosis in aged mice, we then demonstrate that the pre-treatment with cEVs improves the vascular response to injury and attenuates lung fibrosis progression, as demonstrated by reduced lung collagen content and preserved vascular network and lung architecture. These findings support the efficacy of interventions targeting endothelial aging-associated transcriptional alterations, such as young cEV delivery, in mitigating pulmonary fibrosis progression in animal models of persistent fibrosis and indicate the potential benefits of combined therapies that simultaneously address vascular and non-vascular aspects of IPF.

PMID:40411768 | DOI:10.1152/ajpcell.00022.2025

BMC Pulm Med. 2025 May 23;25(1):259. doi: 10.1186/s12890-025-03719-5.

ABSTRACT

BACKGROUND: Cryptogenic organizing pneumonia (COP), a rare interstitial lung disease, can mimic community-acquired pneumonia (CAP), often leading to delayed diagnosis. This case highlights the importance of recognizing COP in elderly patients and brings attention to pulmonary embolism (PE) as a potential but underrecognized complication associated with glucocorticosteroid therapy, providing novel insights into hypercoagulability risks during treatment.

CASE PRESENTATION: An 80-year-old woman from Xinjiang presented with a 4-week history of cough, dyspnea, and weight loss that was unresponsive to antibiotics. Chest Computed tomography (CT) revealed bilateral subpleural consolidations with air bronchograms. Bronchoscopy ruled out infection, and a multidisciplinary evaluation confirmed COP based on clinical, radiological, and pathological correlation. Oral prednisone at 0.75 mg/kg/day led to symptom resolution within 14 days. However, during steroid tapering (10% weekly reduction), she developed hypoxemia at 3 months. CT angiography revealed segmental PE, despite the absence of conventional thrombosis risk factors. Treatment with anticoagulation and continued glucocorticoid therapy resulted in full recovery after 6 months.

CONCLUSIONS: Clinicians should consider COP in elderly patients with pneumonia unresponsive to antibiotics, confirm the diagnosis through biopsy, and remain vigilant for hypercoagulable states during glucocorticoid tapering. Anticoagulation should be tailored even in the absence of traditional thrombosis risk factors. The temporal association between steroid tapering and PE suggests that glucocorticoids may modulate endothelial function and coagulation pathways, highlighting the need for mechanistic studies to inform thromboembolic surveillance in COP management.

PMID:40410735 | DOI:10.1186/s12890-025-03719-5

Brain Res Bull. 2025 May 21:111402. doi: 10.1016/j.brainresbull.2025.111402. Online ahead of print.

ABSTRACT

BACKGROUND: The mechanistic relationship between respiratory disorders and brain function remains poorly understood, despite growing evidence of cognitive and neurological manifestations in respiratory diseases. We aim to identify whether specific brain network connectivity patterns causally influence respiratory disease susceptibility, while respiratory conditions might reciprocally affect brain network architecture.

METHODS: We performed bidirectional Mendelian randomization analyses using genome-wide association studies (GWAS) of brain network connectivity from UK Biobank resting-state functional MRI data (N=31,453) and GWAS data from ten major respiratory conditions: chronic obstructive pulmonary disease (COPD), asthma, idiopathic pulmonary fibrosis (IPF), sleep apnea syndrome (SAS), lung squamous carcinoma (LUSC), lung adenocarcinoma (LUAD), small cell lung carcinoma (SCLC), hospitalized COVID-19, very severe COVID-19, and bronchiectasis. Five MR methods, inverse variance weighted (IVW) with multiplicative random-effect model, weighted median, weighted mode, MR Egger, and MR-robust adjusted profile score (MR-RAPS) were employed to ensure causal inference.

RESULTS: In forward analysis, five respiratory disorders - asthma, IPF, SAS, LUSC, and very severe COVID-19 - showed significant causal associations (p<1.31×10-4) with 11 rs-fMRI phenotypes, spanning multiple brain networks including the central executive, subcortical-cerebellum, motor, limbic, attention, salience, visual, and default mode networks. In reverse analysis, twelve brain functional networks demonstrated genetic associations with eight respiratory conditions (COPD, asthma, IPF, SAS, LUSC, SCLC, hospitalized COVID-19, and very severe COVID-19), predominantly involving attention, salience, default mode, visual, and central executive networks.

CONCLUSIONS: Our study provides preliminary genetic evidence suggesting potential causal relationships between brain network connectivity and respiratory disorders, contributing to our understanding of the lung-brain axis. While the identification of disease-specific network alterations offers promising insights, further clinical validation is needed before these findings can be translated into therapeutic interventions.

PMID:40409599 | DOI:10.1016/j.brainresbull.2025.111402