特発性肺線維症

BACKGROUND: Pulmonary hypertension (PH) is a common comorbidity in patients with interstitial lung disease (ILD), with a negative prognostic impact. The main objective of this study was to develop and internally validate a nomogram to predict PH using real-life data from patients with fibrosing ILD. METHODS: Retrospective, cross-sectional, single-centre study including adult patients with a diagnosis of fibrosing ILD undergoing right heart catheterization (RHC). Bootstrap was used to select clinical, radiological, and functional predictors of precapillary PH. LASSO, Elastic Net, and CART were also performed to enhance robustness. The final model was presented using a nomogram and PH risk was stratified into three categories according to CART. RESULTS: Ninety patients were included. The most frequent ILD diagnoses were idiopathic pulmonary fibrosis (20%), connective tissue diseases-ILD (18.9%) and combined pulmonary fibrosis and emphysema (17.8%). Echocardiography identified high PH probability in 54.4% of patients. RHC confirmed PH in 64 (71%) patients and ruled out PH in 26 (29%). Pulmonary artery diameter, transfer coefficient of the lung for carbon monoxide (KCO) and six-minute walking test distance (meters) were retained in the final model, with an AUC [95% CI] of 0.857 [0.779-0.935]. PH predicted risk was classified in low- (< 36%), intermediate- (≥ 36-<73%) or high-risk (≥ 73%) categories. CONCLUSION: A simple model based on three non-invasive objective variables obtained during the routine care of patients with fibrosing ILD showed good internal discrimination in our derivation cohort. Following external validation, the proposed nomogram could support PH-ILD suspicion and optimize echocardiography and RHC referrals.

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease associated with fibroblast proliferation, excessive extracellular matrix deposition, and oxidative stress, with limited treatment options available. The present study aimed to isolate and evaluate a flavonoid from Cordia sinensis for its potential antifibrotic-associated activity using integrated in vitro and in silico approaches. The isolated compound, kaempferol-3-O-α-L-rhamnopyranosyl-(1 → 6)-β-D-glucopyranoside, was assessed for its effects on cell viability, intracellular reactive oxygen species (ROS) levels, and fibrosis-associated protein expression in MRC-5 human lung fibroblasts. Molecular docking study was performed against selected IPF-related targets, including NOX4, KEAP1, EGFR, and TGFBR1. The compound exhibited concentration-dependent effects on MRC-5 cell viability and reduced intracellular ROS accumulation under oxidative stress conditions. Western blot analysis demonstrated decreased expression of COL1A1 and α-SMA, which are proteins associated with fibrotic remodeling and fibroblast activation. Molecular docking suggested favorable binding interactions with NOX4 and KEAP1, providing computational evidence for potential interactions with proteins involved in oxidative stress regulation. Collectively, these findings suggest that the isolated flavonoid exhibited antioxidant-associated activity and modulates fibrosis-associated cellular responses under the experimental conditions. However, the underlying molecular mechanisms, cellular selectivity, and in vivo efficacy remain to be established through further experimental investigations.

Idiopathic pulmonary fibrosis (IPF) is a devastating interstitial lung disease (ILD) characterized by excessive inflammation and deposition of extracellular matrix (ECM) in the pulmonary niche, ultimately leading to decline of pulmonary function. Even though there are three food and drug administration (FDA) approved drugs for treatment of IPF, these drugs are ineffective against reversal of the disease but rather can only reduce the progression of the disease. As a result, the median survival rate for IPF is extremely low and new therapeutic strategies are urgently needed. Krueppel-like factors (KLFs) are zinc finger containing transcription factors that control the outcome associated with various types of diseases, given their critical role in cellular differentiation and proliferation. The role of KLFs is very cell specific and as a result it finely balances the inflammation associated with various diseases. Even though different members of the KLF family have been reported to have a role in IPF, this review summarizes the role of KLFs in regulation of inflammation associated with idiopathic pulmonary fibrosis.

OBJECTIVES: Histopathological usual interstitial pneumonia (UIP) features are associated with progressive fibrosis but may be overlooked in smokers, where emphysema and smoking-related fibrosis complicate CT-based UIP classification. This study aimed to develop and validate a CT-based score to detect histopathological UIP features and to evaluate its association with disease progression in smokers with fibrotic idiopathic interstitial pneumonia (IIP). MATERIALS AND METHODS: This retrospective multicentre study included two biopsy-proven cohorts of smokers with fibrotic IIP: derivation (n = 242; nationwide registry) and validation (n = 126; single-centre database, 2008-2013). Three predefined HRCT findings-upper-lobe irregular lines (U), irregularity of pleural surface (I), and pleural-based basal reticulation (P)-were scored (0/1) and summed as the U-I-P score (0-3). Associations with histopathological UIP features and outcomes were assessed using logistic regression, receiver operating characteristic analysis, Cox proportional hazards models, and bootstrap internal validation. RESULTS: Cohorts were similar (median age 65 vs. 64 years; 88% vs. 87% male). Histopathological UIP features were present in 208/242 (86%) and 109/126 (87%) patients. The U-I-P score independently predicted histopathological UIP features in both cohorts (area under the curve, 0.83 and 0.89; both p < 0.001). Bootstrap validation demonstrated minimal optimism, supporting model stability. The U-I-P score independently predicted disease progression at 1 and 2 years in the validation cohort (p = 0.002 and p = 0.001, respectively). CONCLUSION: The U-I-P score detects histopathological UIP features and predicts disease progression in smokers with fibrotic IIP, providing a practical imaging biomarker, even in cases with atypical CT patterns. KEY POINTS: Question: In smokers with fibrotic interstitial lung disease, emphysema and smoking-related fibrosis complicate CT pattern classification, limiting identification of usual interstitial pneumonia pathology. FINDINGS: The U-I-P (upper-lobe irregular lines, irregularity of pleural surface, pleural-based reticulation) score detected histopathological usual interstitial pneumonia features and predicted progression. CLINICAL RELEVANCE: The U-I-P score aids identification of smokers with usual interstitial pneumonia-type fibrosis and increased risk of progression when biopsy is unavailable, or CT patterns are atypical for usual interstitial pneumonia.