Cureus. 2024 Oct 28;16(10):e72572. doi: 10.7759/cureus.72572. eCollection 2024 Oct.

ABSTRACT

Pulmonary fibrosis is a chronic condition typically affecting both lungs; however, cases of unilateral pulmonary fibrosis are exceedingly rare and often result from specific unilateral inflammatory conditions like radiation pneumonitis or infection. An even rarer occurrence is the unilateral proximal interruption of a pulmonary artery (PIPA), a developmental anomaly resulting from the failed connection of the sixth aortic arch to the pulmonary trunk. This condition can manifest alone or alongside other cardiac abnormalities. There are limited reports of pulmonary fibrosis associated with PIPA. In this case, a 33-year-old male with chronic mild asthma presented with bilateral shoulder pain. Initial radiographs showed reticular opacities and volume loss in the right lung with a rightward mediastinal shift, suggesting possible fibrosis. Further investigations with chest Computed Tomography (CT) and CT angiogram confirmed right-sided pulmonary fibrosis and the absence of the right pulmonary artery, with no other significant cardiopulmonary symptoms reported. This case highlights the complexity of diagnosing and managing rare unilateral pulmonary conditions.

PMID:39606523 | PMC:PMC11602208 | DOI:10.7759/cureus.72572

medRxiv [Preprint]. 2024 Nov 16:2024.11.15.24317403. doi: 10.1101/2024.11.15.24317403.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a rare disease that is challenging to diagnose. Patients with IPF often spend years awaiting a diagnosis after the onset of initial respiratory symptoms, and only a small percentage receive antifibrotic treatment. In this study, we examine the associations between social determinants of health (SDoH) and two critical factors: time to IPF diagnosis following the onset of initial respiratory symptoms, and whether the patient receives antifibrotic treatment. To approximate individual SDoH characteristics, we extract demographic-specific averages from zip code-level data using the American Community Survey (via the U.S. Census Bureau API). Two classification models are constructed, including logistic regression and XGBoost classification. The results indicate that for time-to-diagnosis, the top three SDoH factors are education, gender, and insurance coverage. Patients with higher education levels and better insurance are more likely to receive a quicker diagnosis, with males having an advantage over females. For antifibrotic treatment, the top three SDoH factors are insurance, gender, and race. Patients with better insurance coverage are more likely to receive antifibrotic treatment, with males and White patients having an advantage over females and patients of other ethnicities. This research may help address disparities in the diagnosis and treatment of IPF related to socioeconomic status.

PMID:39606330 | PMC:PMC11601738 | DOI:10.1101/2024.11.15.24317403

bioRxiv [Preprint]. 2024 Apr 30:2024.04.30.591719. doi: 10.1101/2024.04.30.591719.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a devastating pulmonary disease with no curative treatment other than lung transplantation. IPF results from maladaptive responses to lung epithelial injury, but the underlying mechanisms remain unclear. Here, we show that deficiency in the innate immune receptor, toll-like receptor 5 (TLR5), is associated with IPF in humans and with increased susceptibility to epithelial injury and experimental fibrosis in mice, while activation of lung epithelial TLR5 through a synthetic flagellin analogue protects from experimental fibrosis. Mechanistically, epithelial TLR5 activation induces antimicrobial gene expression and ameliorates dysbiosis after lung injury. In contrast, TLR5 deficiency in mice and IPF patients is associated with lung dysbiosis. Elimination of the microbiome in mice through antibiotics abolishes the protective effect of TLR5 and reconstitution of the microbiome rescues the observed phenotype. In aggregate, TLR5 deficiency is associated with IPF and dysbiosis in humans and in the murine model of pulmonary fibrosis. Furthermore, TLR5 protects against pulmonary fibrosis in mice and this protection is mediated by effects on the microbiome.

ONE-SENTENCE SUMMARY: Deficiency in the innate immune receptor TLR5 is a risk factor for pulmonary fibrosis, because TLR5 prevents microbial dysbiosis after lung injury.

PMID:39605370 | PMC:PMC11601505 | DOI:10.1101/2024.04.30.591719

Eur Respir J. 2024 Nov 27:2401070. doi: 10.1183/13993003.01070-2024. Online ahead of print.

ABSTRACT

OBJECTIVE: Gene expression (transcriptomics) studies have revealed potential mechanisms of interstitial lung disease (ILD), yet sample sizes of studies are often limited and between-subtype comparisons are scarce. The aim of this study was to identify and validate consensus transcriptomic signatures of ILD subtypes.

METHODS: We performed a systematic review and meta-analysis of fibrotic ILD transcriptomics studies using an individual participant data approach, and included studies examining bulk transcriptomics of human adult ILD samples and excluding those focusing on individual cell populations. Patient-level data and expression matrices were extracted from 43 studies and integrated using a multivariable integrative algorithm to develop ILD classification models.

RESULTS: Using 1459 samples from 24 studies, we identified transcriptomic signatures for idiopathic pulmonary fibrosis (IPF), hypersensitivity pneumonitis (HP), idiopathic nonspecific interstitial pneumonia (NSIP), and systemic sclerosis-associated ILD (SSc-ILD) against control samples, which were validated on 308 samples from 8 studies (area under receiver operating curve [AUC]=0.99 [95% CI: 0.99-1.00], HP AUC=0.91 [0.84-0.99], NSIP AUC=0.94 [0.88-0.99], SSc-ILD AUC=0.98 [0.93-1.00]). Significantly, meta-analysis allowed, for the first time, identification of robust lung transcriptomics signatures to discriminate IPF (AUC=0.71 [0.63-0.79]) and HP (AUC=0.76 [0.63-0.89]) from other fibrotic ILDs, and unsupervised learning algorithms identified putative molecular endotypes of ILD associated with decreased forced vital capacity (FVC) and diffusing capacity of the lungs for carbon monoxide (DLCO) % predicted. Transcriptomics signatures were reflective of both cell-specific and disease-specific changes in gene expression.

CONCLUSION: We present the first systematic review and largest meta-analysis of fibrotic ILD transcriptomics to date, identifying reproducible transcriptomic signatures with clinical relevance.

PMID:39603671 | DOI:10.1183/13993003.01070-2024

Eur Respir J. 2024 Nov 27;100(101):0000001. doi: 10.1183/13993003.0000-0000. Print 2023 Dec.

NO ABSTRACT

PMID:39603667 | DOI:10.1183/13993003.0000-0000

Biochem Biophys Res Commun. 2024 Nov 20;741:151038. doi: 10.1016/j.bbrc.2024.151038. Online ahead of print.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is fatal interstitial lung disease characterized by excessive scarring of the lung tissue and declining respiratory function. Given its short prognosis and limited treatment options, novel strategies to investigate emerging experimental treatments are urgently needed. Macrophages, as the most abundant immune cell in the lung, have key implications in wound healing and lung fibrosis. However, they are highly plastic and adaptive to their surrounding microenvironment, and thus to maximize translation of research to lung disease, there is a need to study macrophages in multifaceted, complex systems that are representative of the lung. Precision-cut lung slices (PCLS) are living tissue preparations derived from the lung that are cultured ex vivo, which bypass the need for artificial recapitulation of the lung milieu and architecture. Macrophage programming studies are traditionally conducted using isolated cells in vitro, thus our objective was to establish and validate a moderate-throughput, biologically-translational, viable model to study profibrotic polarization of pulmonary-resident macrophages using murine PCLS. To achieve this, we used a polarization cocktail (PC), consisting of IL-4, IL-13, and IL-6, over a 72-h time course. We first demonstrated no adverse effects of the PC on PCLS viability and architecture. Next, we showed that multiple markers of macrophage profibrotic polarization, including Arginase-1, CD206, YM1, and CCL17 were induced in PCLS following PC treatment. Through tissue microarray-based histological assessments, we directly visualized and quantified Arginase-1 and CD206 staining in PCLS in a moderate-throughput manner. We further delineated phenotype of polarized macrophages, and using high-plex immunolabelling with the Iterative Bleaching Extends Multiplexity (IBEX) method, showed that the PC effects both interstitial and alveolar macrophages. Substantiating the profibrotic properties of the system, we also showed expression of extracellular matrix components and fibrotic markers in stimulated PCLS. Finally, we demonstrated that clodronate treatment diminishes the PC effects on profibrotic macrophage readouts. Overall, our findings support a suitable complex model for studying ex vivo profibrotic macrophage programming in the lung, with future capacity for investigating experimental therapeutic candidates and disease mechanisms in pulmonary fibrosis.

PMID:39603027 | DOI:10.1016/j.bbrc.2024.151038

Lung. 2024 Nov 27;203(1):1. doi: 10.1007/s00408-024-00773-4.

ABSTRACT

FOXM1, a key member of the FOX transcription factor family, maintains cell homeostasis by accurately controlling diverse biological processes, such as proliferation, cell cycle progression, differentiation, DNA damage repair, tissue homeostasis, angiogenesis, apoptosis, redox signaling, and drug resistance. In recent years, an increasing number of studies have focused on the role of FOXM1 in the occurrence of multiple diseases and various pathophysiological processes. In the field of pulmonary diseases, FOXM1 has a certain reparative effect by promoting cell proliferation, regulating cell cycle, antifibrosis, participating in inflammation regulation, and synergizing with other signaling pathways. On the basis of the repair properties of FOXM1, this review explores its therapeutic potential in acute lung injury/acute respiratory distress syndrome, asthma, chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, pulmonary arterial hypertension, lung cancer, and other lung diseases, with the goal of providing a new perspective for the analysis of FOXM1-related mechanism of action and the expansion of clinical treatment strategies.

PMID:39601876 | DOI:10.1007/s00408-024-00773-4

Am J Respir Cell Mol Biol. 2024 Dec;71(6):746-750. doi: 10.1165/rcmb.2024-0218LE.

NO ABSTRACT

PMID:39601536 | DOI:10.1165/rcmb.2024-0218LE

J Inflamm Res. 2024 Nov 22;17:9453-9467. doi: 10.2147/JIR.S493171. eCollection 2024.

ABSTRACT

PURPOSE: Idiopathic pulmonary fibrosis (IPF) is an irreversible respiratory disease. In this study, we evaluated the efficacy of salidroside (SAL), the main component of Rhodiola rosea, in treating IPF.

METHODS: The pharmacological effects of SAL against epithelial-mesenchymal transition (EMT) and IPF were assessed through in vivo and in vitro experiments. Targets for SAL in treating IPF were identified from various databases and a PPI network was constructed. Functional analyses of target genes were performed using GO, KEGG, DO, and GSEA. Core target genes were identified using LASSO logistic regression and support vector machine (SVM) analysis, followed by molecular docking simulations. Predicted targets and pathways were validated through Western blotting, qRT-PCR, and IHC.

RESULTS: Our results demonstrated that SAL ameliorated alveolar epithelial cells (AECs) EMT and mitigated bleomycin -induced pulmonary fibrosis. Through network pharmacology, we identified 74 targets for SAL in the treatment of IPF (PFDR<0.05) and analyzed their biological functions. Based on these findings, we further applied machine learning techniques to narrow down 9 core targets (PFDR<0.05). Integrating the results from molecular docking, KEGG, and GSEA analyses, we selected three key targets-IGF1, hypoxia-inducible factor 1-alpha (HIF-1α), and MAPK (PFDR<0.05)-for further investigation. Our study revealed that SAL inhibits the IGF1 signaling pathway, thereby improving AECs senescence and cell cycle arrest. By inhibiting the HIF-1α pathway, SAL alleviates endoplasmic reticulum stress and reduces intracellular ROS accumulation. Moreover, SAL suppresses the activation of the MAPK signaling pathway, leading to a decrease in inflammation markers in AECs and lung tissue.

CONCLUSION: Experimental results suggest that SAL effectively ameliorates BLM-induced EMT and IPF, likely through the inhibition of IGF1, HIF-1α, and MAPK signaling pathways. This study holds potential translational prospects and may provide new perspectives and insights for the use of traditional Chinese medicine in the treatment of IPF.

PMID:39600682 | PMC:PMC11590657 | DOI:10.2147/JIR.S493171

Pharmaceutics. 2024 Oct 29;16(11):1391. doi: 10.3390/pharmaceutics16111391.

ABSTRACT

Interstitial lung diseases (ILDs) encompass a heterogeneous group of over 200 disorders that require individualized treatment. Antifibrotic agents, such as nintedanib and pirfenidone, have remarkably revolutionized the treatment landscape of patients with idiopathic pulmonary fibrosis (IPF). Moreover, the approval of nintedanib has also expanded the therapeutic options for patients with progressive pulmonary fibrosis other than IPF. However, despite recent advances, current therapeutic strategies based on antifibrotic agents and/or immunomodulation are associated with non-negligible side effects. Therefore, several studies have explored the inhalation route aiming to spread higher local concentrations while limiting systemic toxicity. In this review, we examined the currently available literature about preclinical and clinical studies testing the efficacy and safety of inhalation-based antifibrotics, immunomodulatory agents, antioxidants, mucolytics, bronchodilators, and vasodilator agents in ILDs.

PMID:39598515 | DOI:10.3390/pharmaceutics16111391

Life (Basel). 2024 Nov 19;14(11):1506. doi: 10.3390/life14111506.

ABSTRACT

BACKGROUND: The surgical treatment of concomitant lung cancer in patients with idiopathic pulmonary fibrosis is challenging due to the risk of life-threatening complications such as acute exacerbation development in the perioperative period. Few studies have investigated the role of anti-fibrotic drugs in this setting. The aim of this multicenter retrospective study was to evaluate the incidence of acute exacerbation, according to Collard, after lung resection in patients affected by concomitant idiopathic pulmonary fibrosis and lung cancer who were or were not on antifibrotic treatment. Secondary outcomes included: 30 and 90-day mortality and an estimation of overall and disease-free survival.

MATERIAL AND METHODS: The study population consisted of patients affected by idiopathic pulmonary fibrosis who received curative-intent lung surgery in three Italian academic centers between 2015 and 2022. Patients were divided into two groups based on whether they were on perioperative treatment with anti-fibrotic drugs (chronical or prophylactic use) or not. To define predictors of acute exacerbation, univariate and multivariable exact logistic regression analysis were performed. The Kaplan-Meier method with log-rank test was used to estimate survival.

RESULTS: During the study period, n = 55 patients underwent lung resection for lung cancer, including 29 patients who were treated with antifibrotic agents. Although the sample size was small and few events were studied, the incidence of acute exacerbation was significantly lower among patient on anti-fibrotic therapy (3.4% vs. 23.1%, p = 0.044); in addition, anti-fibrotic treatment was the strong factor preventing acute exacerbation at the multivariable analysis (OR 0.089, p = 0.038). Post-operative 30- and 90-day mortality rates were not significantly lower in the anti-fibrotic treatment group (0% and 0% vs. 7.7% and 11.5%, p = 0.21 and p = 0.099, respectively). Overall and disease-free survival rates were similar.

CONCLUSIONS: Considering the limitations of this retrospective study with a small sample size, anti-fibrotic perioperative treatment was associated with reduced incidence of acute exacerbation. Based on these real-world data, this pathway could be proposed as a prophylactic treatment in patients with concomitant idiopathic pulmonary fibrosis and cancer undergoing lung resection.

PMID:39598304 | DOI:10.3390/life14111506

J Clin Med. 2024 Nov 13;13(22):6823. doi: 10.3390/jcm13226823.

ABSTRACT

Objectives: Hepcidin is a biomarker produced by hepatocytes in chronic disease anemia and is known to increase during chronic inflammation. This study compares the hepcidin levels in idiopathic pulmonary fibrosis (IPF) patients and controls, evaluating its relationship with anemia and systemic inflammation in IPF patients. Methods: This study included 82 IPF patients and 31 controls. Hepcidin levels were compared between the two groups. In the IPF group, the hepcidin and anemia parameters were compared between anemic and non-anemic patients. The significance between the hepcidin and systemic inflammation parameters such as Erythrocyte Sedimentation Rate, CRP (C-reactive protein) levels, ferritin levels, and the Systemic Immune-Inflammation Index (SII) was investigated. Erythrocyte Sedimentation Rate, C-reactive protein (CRP) levels, and ferritin levels were measured using automated analyzers. Hepcidin and erythropoietin (EPO) levels were determined using ELISA kits. Results: A significant difference in hepcidin levels was found between the IPF and control groups (37.13 ± 14.92 vs. 25.77 ± 11.25, p < 0.001). No significant difference in hepcidin levels was found between anemic and non-anemic IPF patients (38.25 ± 16.2 vs. 36.7 ± 14.6, p = 0.719). No significant correlation was found between hepcidin levels and anemia parameters (serum iron, ferritin, vitamin B12, serum transferrin, transferrin saturation, total iron-binding capacity, hemoglobin, folate, and erythropoietin) in IPF patients. Despite significant differences in the systemic inflammation parameters (ferritin and CRP) between patients and controls, no significant correlation was found between their hepcidin and systemic inflammation parameters. Conclusions: Our study demonstrates that the hepcidin levels in IPF patients are elevated independently of anemia and systemic inflammation. We propose that hepcidin could be a potential biomarker to be investigated in IPF patients.

PMID:39597967 | DOI:10.3390/jcm13226823

J Clin Med. 2024 Nov 6;13(22):6657. doi: 10.3390/jcm13226657.

ABSTRACT

Interstitial lung disease (ILD) encompasses a diverse group of parenchymal lung diseases characterized by varying degrees of inflammation and/or fibrosis. Patients with ILD frequently require hospitalization, with many needing intensive care unit (ICU) admission, most often due to respiratory failure. The diagnosis and management of ILD in the ICU present unique challenges. Diagnosis primarily relies on chest CT imaging to identify fibrosis and inflammation. Acute exacerbations, whether in idiopathic pulmonary fibrosis (IPF) or non-IPF ILD, require careful evaluation of potential triggers and differential diagnoses. Bronchoalveolar lavage may provide valuable information, such as the identification of infections, but carries risks of complications. Biopsies, whether transbronchial or surgical, can also be informative but pose significant procedural risks. Corticosteroids are the cornerstone of treatment for acute exacerbations of IPF, with higher doses potentially benefiting non-IPF ILD. Additional immunosuppressive agents may be used in cases with evidence of inflammation. Oxygen supplementation, particularly with high-flow nasal cannula, is often employed to manage severe hypoxemia, while noninvasive ventilation can be useful for worsening hypoxemia and/or hypercapnia. When mechanical ventilation is used, it is recommended to target low tidal volumes to minimize lung injury; high PEEP may be less effective and even associated with increased mortality. Prone positioning can improve oxygenation in severely hypoxemic patients. In addition to ventilatory strategies, careful fluid management and addressing concomitant pulmonary hypertension are essential components of care. Extracorporeal membrane oxygenation is a high-risk intervention reserved for the most severe cases. Lung transplantation may be considered for end-stage ILD patients in the ICU, with outcomes dependent on the urgency of transplantation and the patient's overall condition. Managing ILD in the ICU requires a multidisciplinary approach, and despite recent advances, mortality remains high, emphasizing the need for continued research and individualized treatment strategies.

PMID:39597801 | DOI:10.3390/jcm13226657

Biomedicines. 2024 Nov 10;12(11):2572. doi: 10.3390/biomedicines12112572.

ABSTRACT

Patients with interstitial lung diseases (ILDs) associate a large variety of comorbidities that have a significant impact on their clinical outcomes and survival. Among these comorbidities is neurological impairment. This review highlights what is known about the cognitive function, central nervous system (CNS), depression, and anxiety in patients with specific forms of fibrosing ILDs, such as idiopathic pulmonary fibrosis, sarcoidosis, hypersensitivity pneumonitis, connective tissue diseases, etc. The most common pathogenic mechanisms for neurocognitive dysfunction as well as the screening methods and tools for their identification are also described in this review.

PMID:39595138 | DOI:10.3390/biomedicines12112572

Biomedicines. 2024 Oct 24;12(11):2439. doi: 10.3390/biomedicines12112439.

ABSTRACT

Objective: Antifibrotics can improve the outcome of patients with idiopathic pulmonary fibrosis (IPF) and other fibrosing interstitial lung diseases (F-ILDs), but predictive biomarkers at diagnosis are needed to guide the use of immunomodulating and antifibrotic therapies. Methods: Flow cytometry quantification of lymphocytes and neutrophils in bronchoalveolar lavage (BAL) of 145 IPFs, 561 non-IPF-ILDs (125 F-ILDs), and 112 BAL controls were retrospectively correlated with the incidence of fibrosis and third-quartile overall survival (Q3-OS). Results: The incidence of IPF was directly proportional (9.6%, 22.2%, and 42.6%, p < 0.001) to BAL neutrophil counts (<5%, 5-15%, and >15%), but inversely proportional (34.1%, 18.6%, and 8.8%, p < 0.001) to BAL lymphocyte counts (<7%, 7-20%, and >20%). Elevated neutrophils (>5%) with low lymphocytes (<7%) were associated with an increasingly higher incidence of IPF (10.0-56.3%, p < 0.001) in patients aged 40 to 80, compared to the rest of patients (13.0-17.1%). Lymphocytes >20% compared to lymphocytes <7% strongly protected patients with neutrophils >15% (59.7% vs. 20.7%, p < 0.001) from IPF. In contrast, the incidence of F-ILD was not clearly related to BAL lymphocyte/neutrophil counts. Although, IPF and F-ILD showed a shorter Q3-OS (1.8 ± 0.3 and 4.6 ± 0.8 years; p < 0.001) than non-fibrotic-ILDs (11.1 ± 1.3 years), lymphocyte and neutrophil counts were associated with a longer and shorter Q3-OS of non-fibrotic-ILDs (p < 0.03) and F-ILDs (p < 0.04), respectively, but not with a Q3-OS of IPF patients (p < 0.708). Corticosteroids in patients with fibrosis showed a shorter Q3-OS than other immunomodulators (2.4 ± 0.3 vs. 4.0 ± 1.8 years, p = 0.011). Conclusions: Accurate counting of BAL lymphocytes and neutrophils by flow cytometry in ILD patients at diagnosis could help guide immunomodulatory and antifibrotic therapies.

PMID:39595006 | DOI:10.3390/biomedicines12112439

Respir Res. 2024 Nov 26;25(1):415. doi: 10.1186/s12931-024-03048-x.

ABSTRACT

BACKGROUND: Few data are available on acute exacerbation (AE) in patients with progressive pulmonary fibrosis (PPF) besides idiopathic pulmonary fibrosis (IPF). This study aimed to investigate the AE incidence and outcomes among patients with PPF.

METHODS: Clinical data of patients with PPF (n = 133) were retrospectively collected at a single center. PPF was defined based on the criteria used in the INBUILD trial. AE was defined as a worsening of dyspnea typically within 30 days with new bilateral lung infiltration and no evidence of cardiac failure or fluid overload.

RESULTS: Among patients with PPF, the mean age was 60.6 years old, 57.1% were females, and the most common etiology was connective tissue disease-related ILDs (63%). During the follow-up (median: 38.0 months) after PPF diagnosis, 42 patients (31.6%) experienced AE. The 1-, 3-, and 5-year AE incidences were 12.5%, 30.3%, and 38.0%, respectively. Older age, rheumatoid arthritis associated ILD, fibrotic hypersensitivity pneumonitis, and lower lung diffusing capacity for carbon monoxide were AE risk factors. Patients with AE demonstrated worse survival (median survival: 30 months vs. not reached; p < 0.001) after PPF diagnosis than those without. AE was independently associated with mortality in patients with PPF (hazard ratio [HR], 2.194; 95% confidence interval [CI], 1.285-3.747; p = 0.004) in the multivariable Cox analysis, along with older age, lower lung diffusing capacity for carbon monoxide, and the usual interstitial pneumonia-like pattern on high-resolution computed tomography.

CONCLUSIONS: Our results suggest AE is not uncommon and significantly impacts on survival in patients with PPF.

PMID:39593055 | DOI:10.1186/s12931-024-03048-x

Ann Am Thorac Soc. 2024 Nov 26. doi: 10.1513/AnnalsATS.202401-022OC. Online ahead of print.

ABSTRACT

RATIONALE: Idiopathic pulmonary fibrosis (IPF) is a complex and heterogeneous disease. Given this, we reasoned that differences in genetic profiles may be associated with unique clinical and radiologic features. Computational image analysis, sometimes referred to as radiomics, provides objective, quantitative assessments of radiologic features in subjects with pulmonary fibrosis.

OBJECTIVE: To determine if the genetic risk profile of patients with IPF identifies unique computational imaging phenotypes.

METHODS: Participants with IPF were included in this study if they had genotype data and CT scans of the chest available for computational image analysis. Extent of lung fibrosis and likelihood of a usual interstitial pneumonia (UIP) pattern were scored automatically by using two separate, previously validated deep learning techniques for CT analysis. UIP pattern was also classified visually by radiologists according to established criteria.

MEASUREMENTS AND MAIN RESULTS: Among 334 participants with IPF, MUC5B, FAM13A and ZKSCAN1 were independently associated with the deep learning-based UIP score. None of the common variants were associated with fibrosis extent by computational imaging. We did not find an association between MUC5B, FAM13A or ZKSCAN1 and visually assessed UIP pattern.

CONCLUSIONS: Select genetic variants are associated with computer-based classification of UIP on CT among patients with IPF. Analysis of radiologic features using deep learning may enhance our ability to identify important genotype-phenotype associations in fibrotic lung diseases.

PMID:39591102 | DOI:10.1513/AnnalsATS.202401-022OC

Respirol Case Rep. 2024 Nov 25;12(11):e01413. doi: 10.1002/rcr2.1413. eCollection 2024 Nov.

ABSTRACT

This study examines the radiological and clinical evolution of a case involving mixed idiopathic pulmonary fibrosis and chronic hypersensitivity pneumonitis, utilizing conventional CT imaging and artificial intelligence tool. Through a series of exams and clinical assessments, the patient was followed for over 3 years, highlighting the challenge in differentiating these interstitial pathologies and the importance of a multidisciplinary approach. The radiological progression towards pulmonary fibrosis was correlated with clinical symptoms, emphasizing the significance of early diagnosis and regular follow-up. The combined use of advanced technologies offers a more comprehensive framework in managing complex lung diseases, enhancing the quality of care and understanding of interstitial pathologies.

PMID:39588330 | PMC:PMC11588411 | DOI:10.1002/rcr2.1413

ERJ Open Res. 2024 Nov 25;10(6):00550-2024. doi: 10.1183/23120541.00550-2024. eCollection 2024 Nov.

ABSTRACT

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic, fibrosing and progressive interstitial lung disease of unknown aetiology with a pathogenesis still partly unknown. Several microvascular and macrovascular abnormalities have been demonstrated in the pathogenesis of IPF and related pulmonary hypertension (PH), a complication of the disease.

METHODS: We carried out a non-systematic, narrative literature review aimed at describing the role of the vasculature in the natural history of IPF.

RESULTS: The main molecular pathogenetic mechanisms involving vasculature (i.e. endothelial-to-mesenchymal transition, vascular remodelling, endothelial permeability, occult alveolar haemorrhage, vasoconstriction and hypoxia) and the genetic basis of vascular remodelling are described. The prevalence and clinical relevance of associated PH are highlighted with focus on the vasculature as a prognostic marker. The vascular effects of current antifibrotic therapies, the role of pulmonary vasodilators in the treatment of disease, and new pharmacological options with vascular-targeted activity are described.

CONCLUSIONS: The vasculature plays a key role in the natural history of IPF from the early phases of disease until development of PH in a subgroup of patients, a complication related to a worse prognosis. Pulmonary vascular volume has emerged as a novel computed tomography finding and a predictor of mortality, independent of PH. New pharmacological options with concomitant vascular-directed activity might be promising in the treatment of IPF.

PMID:39588083 | PMC:PMC11587140 | DOI:10.1183/23120541.00550-2024

Food Funct. 2024 Nov 26. doi: 10.1039/d4fo01474j. Online ahead of print.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a chronic age-related lung disease with a high mortality rate. Kaempferol (KMP), an active ingredient in common plants and foods with anti-inflammatory, antioxidant and immunomodulatory properties, has been shown to be effective against fibrotic diseases. However, the molecular mechanisms underlying the treatment of IPF with KMP remain unclear. Therefore, IPF mice were established by intratracheal instillation of bleomycin (BLM) to explore the efficacy and underlying mechanism of KMP in the treatment of IPF. We found that KMP improved the body weight changes of BLM-induced IPF mice, alleviated inflammatory infiltration and collagen deposition, and decreased the expression levels of hydroxyproline, α-SMA, Col3a1, Mmp2, Timp1, Vim, Fn, TNF-α, TGF-β1, IL-6 and IL-8, while up-regulating the expression E-cadherin in lung tissues. The transcriptomic results showed that KMP may exert therapeutic effects against IPF by regulating the PPARG/TNC signaling pathway to reduce extracellular matrix (ECM) deposition. Interestingly, ROC curve analysis suggested that TNC and PPARG had good diagnostic performance for IPF, and TF prediction revealed that PPARG is an important upstream gene regulating TNC, and the IF experiment confirmed the co-localization of TNC and PPARG. Molecular docking showed that KMP bound well to PPARG and TNC, and IF results revealed that KMP significantly reduced the interaction between PPARG and TNC. Furthermore, RT-PCR, WB, IHC and IF experiments confirmed that KMP elevated the expression of PPARG and inhibited the expression of TNC, thus inhibiting the ECM-receptor interaction pathway and ultimately serving as a therapeutic treatment for IPF mice. These findings revealed that KMP reduced inflammatory infiltration and collagen deposition in the lungs of IPF mice and that the PPARG/TNC signaling pathway may be an important mechanism for the treatment of IPF with KMP, which provides a new perspective for the development of therapeutic approaches for IPF.

PMID:39587935 | DOI:10.1039/d4fo01474j