Respir Care. 2023 Dec 28;69(1):114-127. doi: 10.4187/respcare.11298.

ABSTRACT

BACKGROUND: People with interstitial lung disease (ILD) want to actively manage their condition; however, the effects of self-management interventions (SMIs) in this population have not been synthesized. This review summarizes the effects of SMIs on health-related quality of life (HRQOL), functional status, psychological and social factors, symptoms, exacerbations, health care utilization, and survival in people with ILD.

METHODS: The protocol of this systematic review was registered (PROSPERO ID: CRD42022329199). Six digital databases were searched in May 2022 with monthly updates until August 2023. Studies implementing SMIs in people with any type of ILD were included. Risk of bias (RoB) and quality of evidence were assessed with the Cochrane tool for RoB assessment and the grading of recommendations, assessment, development, and evaluations. Meta-analysis was used to summarize the results.

RESULTS: Four studies that examined 217 participants (81% male, 71 y old, 91% idiopathic pulmonary fibrosis) were included. SMIs were highly heterogeneous. Meta-analysis showed no difference in HRQOL (standardized mean difference: 0.08 [95% CI -0.21 to 0.37], P .58) nor in the secondary outcomes. No evidence for the effects of SMIs on functional capacity, exacerbations, and survival was found. The quality of evidence ranged from low to very low.

CONCLUSIONS: There is low to very low-quality evidence that SMIs have no effect in people with ILD. However, this conclusion is limited by high methodological heterogeneity. A consensus definition of SMIs is needed to implement more comparable interventions and strengthen results.

PMID:39878768 | DOI:10.4187/respcare.11298

Biochem Cell Biol. 2025 Jan 1;103:1-7. doi: 10.1139/bcb-2024-0221.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a progressive and irreversible lung disease with high mortality and limited treatment options. While single-dose bleomycin-induced models are commonly used to investigate the pathogenesis of IPF, they fail to adequately replicate the complex pathological features in human patients, thereby hindering comprehensive investigations. Previous studies utilizing repetitive bleomycin injections have demonstrated a closer resemblance to human IPF pathology; however, the time- and resource-intensive nature of this approach presents significant drawbacks. Here, we propose a novel methodology involving twice-repeated oropharyngeal administration of bleomycin in mice, which closely mirrors the pathological manifestations observed in IPF patients. This model exhibited the honeycomb-like cyst formation, fibroblastic foci, bronchiolization of alveolar epithelium, emergence of metaplastic alveolar KRT5+ basal cells, and sustainability of these fibrotic phenotypes, thereby providing a robust model for IPF. Our findings establish a more efficient and translatable preclinical platform for investigating IPF pathogenesis and exploring potential therapeutic strategies.

PMID:39878201 | DOI:10.1139/bcb-2024-0221

HGG Adv. 2025 Jan 27:100410. doi: 10.1016/j.xhgg.2025.100410. Online ahead of print.

ABSTRACT

Most genetic variants identified through genome-wide association studies (GWAS) are suspected to be regulatory in nature, but only a small fraction colocalize with expression quantitative trait loci (eQTLs, variants associated with expression of a gene). Therefore, it is hypothesized but largely untested that integration of disease GWAS with context-specific eQTLs will reveal the underlying genes driving disease associations. We used colocalization and transcriptomic analyses to identify shared genetic variants and likely causal genes associated with critically ill COVID-19 and idiopathic pulmonary fibrosis. We first identified five genome-wide significant variants associated with both diseases. Four of the variants did not demonstrate clear colocalization between GWAS and healthy lung eQTL signals. Instead, two of the four variants colocalized only in cell-type and disease-specific eQTL datasets. These analyses pointed to higher ATP11A expression from the C allele of rs12585036, in monocytes and in lung tissue from primarily smokers, which increased risk of IPF and decreased risk of critically ill COVID-19. We also found lower DPP9 expression (and higher methylation at a specific CpG) from the G allele of rs12610495, acting in fibroblasts and in IPF lungs, and increased risk of IPF and critically ill COVID-19. We further found differential expression of the identified causal genes in diseased lungs when compared to non-diseased lungs, specifically in epithelial and immune cell types. These findings highlight the power of integrating GWAS, context-specific eQTLs, and transcriptomics of diseased tissue to harness human genetic variation to identify causal genes and where they function during multiple diseases.

PMID:39876559 | DOI:10.1016/j.xhgg.2025.100410

J Occup Environ Med. 2025 Jan 22. doi: 10.1097/JOM.0000000000003324. Online ahead of print.

ABSTRACT

OBJECTIVE: This study aimed to share the process of epidemiologic survey and demonstrate the decisive factors for evaluating work-related Idiopathic interstitial pneumonias (IIPs) in Korea.

METHODS: Data and reports of epidemiologic surveys were investigated and completed during 2010-2022.

RESULTS: A total of 228 idiopathic pulmonary fibrosis (IPF) cases requested for an epidemiologic survey, of which 153 (67.1%) were work-related. The level of exposure intensity was more than intermediate and the exposure duration was more than 10 years in the work-related IPF, so the decisive factors for work-related IPF were exposure substances, intensity and duration.The main factors for work-related acute interstitial pneumonia or cryptogenic organising pneumonia were exposure latency and exposure intensity.

CONCLUSIONS: The results of this study indicated the process of the epidemiologic survey and important factors for evaluating work-related IIPs.

PMID:39875335 | DOI:10.1097/JOM.0000000000003324

Front Immunol. 2025 Jan 13;15:1479458. doi: 10.3389/fimmu.2024.1479458. eCollection 2024.

ABSTRACT

INTRODUCTION: Diffuse parenchymal lung diseases (DPLD) cover heterogeneous types of lung disorders. Among many pathological phenotypes, pulmonary fibrosis is the most devastating and represents a characteristic sign of idiopathic pulmonary fibrosis (IPF). Despite a poor prognosis brought by pulmonary fibrosis, there are no specific diagnostic biomarkers for the initial development of this fatal condition. The major hallmark of lung fibrosis is uncontrolled activation of lung fibroblasts to myofibroblasts associated with extracellular matrix deposition and the loss of both lung structure and function.

METHODS: Here, we used this peculiar feature in order to identify specific biomarkers of pulmonary fibrosis in bronchoalveolar lavage fluids (BALF). The primary MRC-5 human fibroblasts were activated with BALF collected from patients with clinically diagnosed lung fibrosis; the activated fibroblasts were then washed rigorously, and further incubated to allow secretion. Afterwards, the secretomes were analysed by mass spectrometry.

RESULTS: In this way, the CD44 protein was identified; consequently, BALF of all DPLD patients were positively tested for the presence of CD44 by ELISA. Finally, biochemical and biophysical characterizations revealed an exosomal origin of CD44. Receiver operating characteristics curve analysis confirmed CD44 in BALF as a specific and reliable biomarker of IPF and other types of DPLD accompanied with pulmonary fibrosis.

PMID:39872532 | PMC:PMC11769834 | DOI:10.3389/fimmu.2024.1479458

Respir Med Case Rep. 2025 Jan 2;53:102165. doi: 10.1016/j.rmcr.2025.102165. eCollection 2025.

ABSTRACT

BACKGROUND: Anti-Ku antibodies are autoantibodies directed against the Ku protein complex involved in DNA repair. They are typically associated with overlap syndromes featuring polymyositis and systemic sclerosis. Isolated pulmonary involvement without myositis is exceedingly rare.

CASE PRESENTATION: We report the case of a 70-year-old male, a former smoker with an 18-year smoking history who quit 20 years ago, presenting with a one-year history of progressive dyspnea and dry cough. High-resolution computed tomography (HRCT) revealed pulmonary fibrosis with areas of ground-glass opacities. Laboratory tests showed antinuclear antibodies at a titer of 1:2560 with a speckled pattern and positivity for anti-Ku antibodies. Creatine phosphokinase levels were within normal limits. There were no clinical signs of myositis, myalgia, skin manifestations, or Raynaud's phenomenon.

CONCLUSION: This case underscores the rarity of pulmonary fibrosis as the sole clinical manifestation associated with anti-Ku antibody positivity in the absence of myositis. Clinicians should consider testing for anti-Ku antibodies in patients with idiopathic interstitial lung disease, even when muscular and cutaneous symptoms are absent.

PMID:39867941 | PMC:PMC11759561 | DOI:10.1016/j.rmcr.2025.102165

Cureus. 2024 Dec 27;16(12):e76454. doi: 10.7759/cureus.76454. eCollection 2024 Dec.

ABSTRACT

Background Interstitial lung diseases (ILDs) are a group of non-infectious diseases characterized by interstitial inflammation and fibrosis on histological examination. Gastroesophageal reflux disease (GERD) is common in this patient population, but whether there is a causal or coincidental relationship is not yet clear. It still remains unsettled how to diagnose GERD, and the role of different treatment modalities for GERD, in these lung disorders. Furthermore, most of the work is done to find the association of GERD with idiopathic pulmonary fibrosis (IPF) only. The aim of this study was to determine the prevalence of GERD in ILD patients presenting to an ILD clinic. Methods Prospective study of registered ILD patients during a period of eight months (May-December 2016). Diagnosis of GERD was made on a clinical basis (presentation with typical symptoms of heartburn and regurgitation). Current use of acid-reducing medications and steroids was also recorded. Results A total of 79 patients were included in the study. Females (58, 73.41%) outnumbered males (21, 26.58%). The heaviest burden of ILD was contributed by IPF (32, 40.50%), followed by non-specific interstitial pneumonia (NSIP) (26, 32.91%), hypersensitivity pneumonitis (HP) (8, 10.12%), sarcoidosis (5, 6.3%), silicosis (3, 3.8%), desquamative interstitial pneumonia (DIP) (2, 2.5%), and Langerhans cell histiocytosis (LCH) (3, 3.79%). Fifty (63.29%) patients were on steroids, and 29 (36.70%) were already taking anti-reflux medications at presentation. GERD was reported in 21 (65.6%) IPF, 12 (46.15%) NSIP, one (12.5%) HP, one (33.3%) silicosis, two (40%) sarcoidosis, and all (2,100%) of DIP patients. The overall prevalence of GERD was 39 (49.36%) in ILD patients. Conclusion The prevalence of abnormal acid reflux in ILD patients is high. It may be one of the underlying etiologies of lung fibrosis. Long-term follow-up is necessary to determine if control of reflux alters the natural history of these lung disorders. GERD must be investigated and managed optimally for patients with ILD.

PMID:39866988 | PMC:PMC11769694 | DOI:10.7759/cureus.76454

Heliyon. 2025 Jan 2;11(1):e41628. doi: 10.1016/j.heliyon.2025.e41628. eCollection 2025 Jan 15.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive interstitial lung disease. It is characterized by inflammation and fibrosis in the lung parenchyma and interstitium. Given its poor prognosis and limited treatment options, understanding the underlying molecular mechanisms is crucial. Recent evidence suggests that lipid metabolism plays a pivotal role in IPF pathogenesis, however, the precise mechanisms remain poorly understood. To address this, we analyzed 12 bulk RNA-seq and 2 single-cell RNA-seq datasets from the GEO database using machine learning approaches. As a result, we identified four key lipid-related genes-PPARG, SPP1, CASP3, and PECAM1-that are expressed across various cell types. Specifically, in alveolar macrophages (AMs), we observed that PPARG was significantly downregulated, while SPP1 was highly expressed. Importantly, PPARG serves as a transcriptional regulator of SPP1, which in turn mediates intercellular signaling via CD44. Based on these findings, we propose a novel PPARG/SPP1/CD44 signaling pathway in AMs, which modulates lipid metabolism and likely contributes to the progression of fibrosis in IPF. Moreover, network pharmacology analysis identified several herbal compounds that target PPARG, offering potential therapeutic opportunities. In conclusion, these findings highlight the critical role of lipid metabolism in IPF and present novel molecular targets for the development of future therapeutic strategies.

PMID:39866448 | PMC:PMC11761845 | DOI:10.1016/j.heliyon.2025.e41628

Life (Basel). 2025 Jan 16;15(1):106. doi: 10.3390/life15010106.

ABSTRACT

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease with a median survival of 3-5 years. Antifibrotic therapies like pirfenidone and nintedanib slow progression, but the outcomes vary. Gender may influence disease presentation, progression, and response to treatment. This study evaluates the impact of gender on the 5-year survival, pharmacological management, and clinical outcomes of patients with IPF.

METHODS: A retrospective cohort study of 254 IPF patients was conducted, with 164 (131 males:33 females) having complete data. Patients underwent spirometry, DLCO, and 6 min walk tests. Data on comorbidities, smoking, antifibrotic therapy type, dosage adjustments, and adverse events were collected. We used Kaplan-Meier survival curves and logistic regression to assess gender-related differences in outcomes.

RESULTS: Men had worse lung function at diagnosis (FVC 74.9 ± 18.5 vs. 87.2 ± 20.1% of pred.; p < 0.001) and a higher smoking prevalence (74% vs. 30%; p < 0.001). Women had better survival (51.2 vs. 40.8 ± 19.2 months; p = 0.005) despite more frequent biopsy use (36% vs. 17%; p = 0.013). Women tolerated longer therapy better (p = 0.001). No differences were found between patients receiving reduced antifibrotic dosing and those receiving full dosing.

CONCLUSIONS: Gender has a significant impact on IPF outcomes, with women demonstrating better survival and tolerance to long-term therapy. In contrast, reducing antifibrotic treatment does not appear to significantly affect survival outcomes. These findings underscore the need for future research on gender-specific management approaches.

PMID:39860046 | DOI:10.3390/life15010106

Biomolecules. 2025 Jan 14;15(1):122. doi: 10.3390/biom15010122.

ABSTRACT

Diffuse interstitial lung diseases (ILD) include conditions with identifiable causes such as chronic eosinophilic pneumonia (CEP), sarcoidosis (SAR), chronic hypersensitivity pneumonitis (CHP), and connective tissue disease-associated interstitial pneumonia (CTD), as well as idiopathic interstitial pneumonia (IIP) of unknown origin. In non-IIP diffuse lung diseases, bronchoalveolar lavage (BAL) fluid appearance is diagnostic. This study examines lymphocyte subsets in BAL fluid and peripheral blood of 56 patients with diffuse ILD, excluding idiopathic pulmonary fibrosis (IPF), who underwent BAL for diagnostic purposes. Patients were classified into CEP, SAR, CHP, CTD, and IIP groups, and clinical data, BAL cell analysis, and peripheral blood mononuclear cell analysis were compared. Eosinophils and type 3 innate lymphocytes (ILC3s) were significantly increased in the BAL fluid of the CEP group. Receiver operating characteristic curve analysis identified eosinophils ≥ 8% in BAL cells and ILC3s ≥ 0.0176% in the BAL lymphocyte fraction as thresholds distinguishing CEP. SAR patients exhibited significantly elevated CD4/CD8 ratios in the BAL fluid, with a ratio of 3.95 or higher and type 1 innate lymphoid cell frequency ≥ 0.254% as differentiation markers. High Th1 cell frequency (≥17.4%) in BAL lymphocytes in IIP, elevated serum KL-6 (≥2081 U/mL) and SP-D (≥261 ng/mL) in CHP, and increased BAL neutrophils (≥2.0%) or a low CD4/CD8 ratio (≤1.2) in CTD serve as distinguishing markers for each ILD. Excluding CEP and SAR, CD4+ T cell frequencies, including Th1, Th17, and Treg cells in peripheral blood, may differentiate IIP, CHP, and CTD.

PMID:39858516 | DOI:10.3390/biom15010122

Pneumonia (Nathan). 2025 Jan 25;17(1):2. doi: 10.1186/s41479-024-00155-7.

ABSTRACT

BACKGROUND: A growing body of evidence suggests that prolonged use of inhaled corticosteroids (ICS) and proton pump inhibitors (PPIs) is associated with increased risks of pneumonia. A substantial proportion of people with idiopathic pulmonary fibrosis (IPF) are prescribed PPIs or ICS to treat common comorbidities, giving rise to concerns that use of these medications may be associated with potential harms in this patient population.

METHODS: We used UK Clinical Practice Research Datalink (CPRD) Aurum primary care data linked to national mortality and hospital admissions data to create a cohort of people diagnosed with IPF on or after 1 January 2010. Patients were assigned to one of three exposure categories according to their prescribing history in the 12 months prior to IPF diagnosis as follows: "regular" users (≥ 4 prescriptions), "irregular" users (1-3 prescriptions) and "non-users" (no prescriptions). We explored the association between PPI/ICS prescription and pneumonia hospitalisation and all-cause mortality using multinomial Cox regression models.

RESULTS: A total of 17,105 people met our study inclusion criteria; 62.6% were male and 15.9% were current smokers. Median age at IPF diagnosis was 76.7 years (IQR: 69.6-82.7). 19.9% were regularly prescribed PPIs, and 16.0% ICS, prior to IPF diagnosis. Regular prescribing of PPIs and ICS was positively associated with hospitalisation for pneumonia; the adjusted HR for pneumonia hospitalisation comparing regular PPI users with non-users was 1.14 (95%CI: 1.04-1.24); for regular ICS users the corresponding HR was 1.40 (95%CI: 1.25-1.55). We also observed a small increased risk for all-cause mortality in the "regular ICS user" group compared with the "non-user" control group (HRadj = 1.19, 1.06-1.33). We found no evidence of an association between PPI prescribing and all-cause mortality.

CONCLUSION: Prolonged prescription of medications used to treat common comorbidities in IPF may be associated with increased risks for severe respiratory infections. These findings point to a need to adopt an adequate risk-benefit balance approach to the prescribing of ICS-containing inhalers and PPIs in people with IPF without evidence of comorbidities, especially older patients and/or those with more advanced disease in whom respiratory infections are more likely to result in poorer outcomes.

PMID:39856755 | DOI:10.1186/s41479-024-00155-7

BMC Pulm Med. 2025 Jan 24;25(1):36. doi: 10.1186/s12890-025-03506-2.

ABSTRACT

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is the most common Interstitial Lung Disease (ILD). It is characterized by dyspnoea and a progressive decline in lung function, which negatively affects life. This study aimed to evaluate Health-Related Quality of Life (HRQoL) in IPF patients in Latin American countries.

METHODS: Six countries (Argentina, Bolivia, Colombia, Chile, Mexico, and the Dominican Republic) enrolled patients with IPF. They answered the Saint George's Respiratory Questionnaire for Idiopathic Pulmonary Fibrosis (SGRQ-I) and the Hospital Anxiety and Depression Scale (HADS). Demographic characteristics, the Torvan index, and a lung function test were also assessed. IPF was diagnosed according to the ATS/ERS/JRS/ALAT 2018 criteria.

RESULTS: We enlisted 75 patients diagnosed with IPF; 81% were male, with an average age of 74 ± 7. The total SGRQ-I score was 49 ± 23, with a higher score in the activity domain of 70 ± 23. Torvan index average was 17 ± 6. We found that 28% presented anxiety and 35% depression. Besides, we observed that patients requiring oxygen had a worse quality of life (total SGRQ-I 62 ± 22 vs. 45 ± 22, p = 0.003) without finding differences in antifibrotic therapy. We did not find differences in HRQoL when dividing groups according to their altitude above sea level, except for a higher frequency of anxiety in patients living at sea level.

CONCLUSIONS: We found similar data compared to those reported in real-life European populations. We also found that anxiety and depression are prevalent. However, they are often underdiagnosed and, therefore, left untreated.

PMID:39856586 | DOI:10.1186/s12890-025-03506-2

Gene. 2025 Jan 22:149271. doi: 10.1016/j.gene.2025.149271. Online ahead of print.

ABSTRACT

OBJECTIVE: Idiopathic pulmonary fibrosis (IPF) is an irreversible and fatal interstitial lung disease, characterized by excessive extracellular matrix (ECM) secretion that disrupts normal alveolar structure. This study aims to explore the potential molecular mechanisms underlying the promotion of IPF development.

METHODS: Firstly, we compared the transcriptome and single-cell sequencing data from lung tissue samples of patients with IPF and healthy individuals. Subsequently, we conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses on the differentially expressed genes (DEGs). Furthermore, we employed sodium alginate hydrogels with varying degrees of crosslinking to provide differential mechanical stress, mimicking the mechanical microenvironment in vivo during lung fibrosis. On this basis, we examined cytoskeletal remodeling in fibroblasts MRC-5, mRNA expression of multiple related genes, immunofluorescence localization, and cellular proliferation capacity.

RESULTS: Bioinformatics analysis revealed a series of DEGs associated with IPF. Further functional and pathway enrichment analyses indicated that these DEGs were primarily enriched in ECM-related biological processes. Single-cell sequencing data revealed that fibroblasts and myofibroblasts are the main contributors to excessive ECM secretion and suggested activation of mechanotransduction and the Hippo/YAP signaling pathway in myofibroblasts. Cellular experiments demonstrated that sodium alginate hydrogels with different stiffness can simulate different mechanical stress environments, thereby affecting cytoskeletal rearrangement and Hippo/YAP pathway activity in MRC-5 lung fibroblasts. Notably, high levels of mechanical stress promoted YAP nuclear translocation, increased expression of type I collagen and α-SMA, and enhanced proliferative capacity. Additionally, we also found that fibroblasts primarily participate in mechanotransduction through the Rho/ROCK and Integrin/FAK pathways under high mechanical stress conditions, ultimately upregulating the gene expression of CCNE1/2, CTGF, and FGF1.

CONCLUSION: Our study uncovers the crucial role of cytoskeletal mechanotransduction in myofibroblast transformation and IPF development through activation of the Hippo/YAP pathway, providing new insights into understanding the pathogenesis of IPF.

PMID:39855369 | DOI:10.1016/j.gene.2025.149271

Am J Pathol. 2025 Jan 22:S0002-9440(25)00028-8. doi: 10.1016/j.ajpath.2024.12.015. Online ahead of print.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) and other progressive fibrotic interstitial lung disease have limited treatment options. Fibroblasts are key effector cells that sense matrix stiffness through conformation changes in mechanically sensitive receptors, leading to activation of downstream profibrotic pathways. Here we investigate the role of Piezo2, a mechanosensitive ion channel, in human and mouse lung fibrosis, and its function in myofibroblast differentiation in primary human lung fibroblasts (HLFs). Human samples from patients with IPF and mouse tissue from bleomycin induced pulmonary fibrosis was assessed. Primary HLFs from non-fibrotic donors were grown on substrates of different stiffness to induce myofibroblast differentiation and treated with a Piezo2 inhibitor. Piezo2 expression is upregulated in tissue from patients with IPF and in fibrotic mouse lung tissue. Additionally, interrogation of published single-cell RNAseq data showed that Piezo2 is expressed in the pro-fibrotic Cthrc1+ fibroblast subpopulation. Myofibroblast differentiation was increased in HLFs grown on substrates with fibrotic levels of stiffness compared to that seen in softer substrates. Piezo2 inhibition reduced stiffness-induced expression alpha smooth muscle actin and fibronectin in HLFs. Piezo2 expression is elevated in fibrotic lung disease in both patients and rodents and its presence is key in the differentiation of fibroblasts to the pro-fibrotic myofibroblasts. Blocking Piezo2 may play a key role in fibrosis and thus be a novel therapeutic approach to treat pulmonary fibrosis.

PMID:39855300 | DOI:10.1016/j.ajpath.2024.12.015

Medicine (Baltimore). 2025 Jan 24;104(4):e41320. doi: 10.1097/MD.0000000000041320.

ABSTRACT

While recent studies suggested a potential causal link between type 1 diabetes mellitus (T1DM) but not type 2 diabetes mellitus (T2DM) and idiopathic pulmonary fibrosis (IPF), the involved mechanism remains unclear. Here, using a Mendelian randomization (MR) approach, we verified the causal relationship between the two types of diabetes mellitus and IPF and investigated the possible role of inflammation in the association between diabetes mellitus and IPF. Based on genome-wide association study (GWAS) summary data of T1DM, T2DM, and IPF, the univariable MR, multivariable MR (MVMR), and mediation MR were successively used to analyze the causal relationship. Inverse variance weighted was used as the main method to infer the causal effect, together with a series of sensitivity analyses. The univariable MR showed that only T1DM increased the risk of IPF, and there was no significant causal relationship between T2DM and IPF. The MVMR further verified that there was an independent direct causal effect of T1DM on IPF. Further mediation analysis showed that this effect was partly mediated by increasing C-X-C motif chemokine ligand 10 (CXCL10) and interleukin-12 subunit beta (IL-12B). In conclusion, T1DM is related to an increased risk of IPF. Notably, the causal effect was partially mediated by CXCL10 and IL-12B. Hence, monitoring T1DM patients may help in the early detection and prevention of IPF.

PMID:39854757 | DOI:10.1097/MD.0000000000041320

Sports (Basel). 2025 Jan 8;13(1):9. doi: 10.3390/sports13010009.

ABSTRACT

Chronic lung diseases such as Chronic Obstructive Pulmonary Disease, Interstitial Lung Disease (ILD), and Pulmonary Hypertension (PH) are characterized by progressive symptoms such as dyspnea, fatigue, and muscle weakness, often leading to physical inactivity, and reduced quality of life. Many patients also experience significantly impaired exercise tolerance. While pulmonary, cardiovascular, respiratory, and peripheral muscle dysfunction contribute to exercise limitations, recent evidence suggests that hypoxia and impairments in cerebral oxygenation may also play a role in exercise intolerance. This narrative review (i) summarizes studies investigating cerebral oxygenation responses during exercise in patients with different types of chronic lung diseases and (ii) discusses possible mechanisms behind the blunted cerebral oxygenation during exercise reported in many of these conditions; however, the extent of cerebral desaturation and the intensity at which it occurs can vary. These differences depend on the specific pathophysiology of the lung disease and the presence of comorbidities. Notably, reduced cerebral oxygenation during exercise in fibrotic-ILD has been linked with the development of dyspnea and early exercise termination. Understanding the effects of chronic lung disease on cerebral oxygenation during exercise may improve our understanding of exercise intolerance mechanisms and help identify therapeutic strategies to enhance brain health and exercise capacity in these patients.

PMID:39852605 | DOI:10.3390/sports13010009

J Med Case Rep. 2025 Jan 23;19(1):32. doi: 10.1186/s13256-025-05031-6.

ABSTRACT

BACKGROUND: Dyskeratosis congenita is a rare genetic disease due to telomere biology disorder and characterized by heterogeneous clinical manifestations and severe complications. "Porto-sinusoidal vascular disease" has been recently proposed, according to new diagnostic criteria, to replace the term "idiopathic non-cirrhotic portal hypertension." TERT plays an important role in telomeric DNA repair and replication. A TERT c.2286 + 1G/A mutation in a splicing consensus site was identified in a patient with pulmonary fibrosis. Recently, a pathogenic de novo TERT c.280A > T variant was associated with diffuse lung disease in an infant.

CASE PRESENTATION: A 16-year-old Han male patient experienced unexplained black stool for 7 days, accompanied by dizziness and fatigue. On examination, there were mesh pigmentations on the exposed areas of the skin on both hands and feet. Laboratory testing revealed moderate hemorrhagic anemia and mild elevation of alanine aminotransferase. A computed tomography scan showed portal hypertension, esophageal and gastric varices, and splenomegaly. The liver stiffness measurement by FibroScan was 6.0 kPa. Liver biopsy revealed typical features of porto-sinusoidal vascular disease. Whole exome sequencing identified a heterozygous TERT c.2286 + 1G > A de novo mutation and quantitative polymerase chain reaction revealed very short telomeres (less than the first percentile for his age). The patient was diagnosed as TERT de novo mutation-related dyskeratosis congenita and porto-sinusoidal vascular disease. He underwent esophageal and gastric variceal ligation treatment and received a carvedilol tablet (12.5 mg) every morning. After 6 months, he has moderate iron deficiency anemia and has started receiving polysaccharide iron complex therapy.

CONCLUSION: When discovering reticular rash and unknown portal hypertension, it is necessary to perform whole exome sequencing and chromosome length testing to clarify the possibility of dyskeratosis congenita/telomere biology disorder with porto-sinusoidal vascular disease.

PMID:39849589 | DOI:10.1186/s13256-025-05031-6

Sci Rep. 2025 Jan 23;15(1):3007. doi: 10.1038/s41598-025-87474-x.

ABSTRACT

The traditional Chinese medicine compound preparation known as Jinbei Oral Liquid (JBOL) consists of 12 herbs, including Astragalus membranaceus (Fisch.) Bge, Codonopsis pilosula (Franch.) Nannf, et al. Having been used for over 30 years in the treatment of pulmonary diseases, JBOL was evaluated in this study in order to assess its effect on idiopathic pulmonary fibrosis as well as its safety (ChiCTR2000035351, Chictr.org.cn.09/08/2020). A double-blind, multicenter, randomized, proof-of-concept trial was conducted to assess the efficacy of oral JBOL 40 ml and Corbrin Capsules 1 g compared to a placebo and Corbrin Capsules in patients with idiopathic pulmonary fibrosis (IPF). Over a 26-week period, patients received the active treatment or placebo three times daily, in a 1:1 ratio. This clinical study uses a randomized method, with a cycle of every 4 patients. TCM doctors at or above the deputy director level of the research center conduct TCM dialectics on IPF patients. To assess efficacy, over the duration of the trial, we measured serial changes in a composite indicator encompassing time to first acute exacerbation of IPF (first hospitalization or death due to respiratory cause), total lung capacity (TLC) (mL), predicted forced vital capacity (FVC%), forced vital capacity (FVC) (mL), predicted diffusing capacity of the lungs for carbon monoxide (predicted DLco%), 6-minute walk distance (6MWD), St. George's Respiratory Questionnaire (SGRQ) total score, and arterial oxygen partial pressure (PaO2) from baseline to week 26 versus placebo. A total of 103 patients were screened, and 72 received the study medication. Of these, 68 patients were included in the analysis set, with 34 receiving JBOL and 34 receiving a placebo. After 26 weeks, a statistically significant reduction in total lung capacity (TLC) was observed for the JBOL group, with a change of 136 mL compared to -523 mL for the placebo group (difference 659 mL, 95% CI -1215 to -104 mL, p = 0.02). The study found that the change in FVC% predicted was - 1.48% and - 3.58% for the JBOL and placebo groups, respectively (difference of 2.10%, 95% CI -7.13 to 2.93, p = 0.41). Additionally the differences between the two groups in changes in FVC (mL), DLCO % predicted, PaO2 (mmHg) measures were - 67 mL (95% CI -238 to 104), -7.74% (95% CI -17.26 to 1.79), and - 3.57 mmHg (95% CI -10.02 to 2.87), respectively. Treatment with JBOL compared to placebo resulted in sequential changes in acute exacerbation, with no significant difference in SGRQ scores. It was not found that there was a statistically significant difference between the JBOL and placebo groups in TEAE reporting and serious TEAE reporting. Compared to the placebo group, there was a statistically significant reduction (p < 0.021) in TLC (mL) after 26 weeks for JBOL. The rates of FVC % predicted, FVC, DLCO % predicted, and PaO2 in the group treatment with JBOL were numerically lower than those in the placebo treatment group, although these differences did not reach statistical significance. JBOL exhibited comparable safety to placebo. This study has preliminarily shown the efficacy and safety of JBOL for IPF, but this is an exploratory clinical trial, more patient-involved studies should be needed in the near future.Trial registration: Chictr.org.cn ChiCTR2000035351; the trial was prospective clinical studies registered on August 9, 2020.

PMID:39849152 | DOI:10.1038/s41598-025-87474-x

Thorax. 2025 Jan 22:thorax-2024-222754. doi: 10.1136/thorax-2024-222754. Online ahead of print.

NO ABSTRACT

PMID:39848685 | DOI:10.1136/thorax-2024-222754

Int J Biochem Cell Biol. 2025 Jan 21:106739. doi: 10.1016/j.biocel.2025.106739. Online ahead of print.

ABSTRACT

Lung fibrosis, including idiopathic pulmonary fibrosis (IPF), is a complex and devastating disease characterised by the progressive scarring of lung tissue leading to compromised respiratory function. Aberrantly activated fibroblasts deposit extracellular matrix components into the surrounding lung tissue, impairing lung function and capacity for gas exchange. Both genetic and epigenetic factors have been found to play a role in the pathogenesis of lung fibrosis, with emerging evidence highlighting the interplay between these two regulatory mechanisms. This review provides an overview of the current understanding of the interplay between genetics and epigenetics in lung fibrosis. We discuss the genetic variants associated with susceptibility to lung fibrosis and explore how epigenetic modifications such as DNA methylation, histone modifications, and non-coding RNA expression contribute to disease. Insights from genome-wide association studies (GWAS) and epigenome-wide association studies (EWAS) are integrated to explore the molecular mechanisms underlying lung fibrosis pathogenesis. We also discuss the potential clinical implications of genetics and epigenetics in lung fibrosis, including the development of novel therapeutic targets. Overall, this review highlights the importance of considering both genetic and epigenetic factors in the understanding and management of lung fibrosis.

PMID:39848439 | DOI:10.1016/j.biocel.2025.106739