Search Results (501)

Background/Objectives: Idiopathic pulmonary fibrosis (IPF) is a fibrotic interstitial lung disease (ILD) with a poor prognosis. The prognosis of ILDs showing progressive pulmonary fibrosis (PPF) is poor, similar to that of IPF. Diarrhea is the most frequently observed adverse event in ILDs treated with nintedanib. Managing diarrhea is important for maintaining nintedanib use and improving the prognosis of ILDs. Methods: Between October 2022 and March 2025, we enrolled patients with severe nintedanib-induced diarrhea that was uncontrolled by loperamide and/or probiotics. Other drugs were administered to control diarrhea, and the patients were prospectively observed to evaluate stool frequency, stool form score (scores 3, 2, and 1 for watery stool, soft stool without form, and soft stool with form, respectively), quality of life (QOL) using the Japanese version of the irritable bowel syndrome (IBS)-QOL questionnaire, adverse events, and laboratory findings. Results: Eleven patients (IPF, n = 5; PPF, n = 6) were enrolled, and all patients were treated with ramosetron, a 5-hydroxytryptamine type 3 receptor (5-HT₃) antagonist. Ramosetron was terminated within 3 weeks, before sufficient evaluation, because of insufficient efficacy (n = 1) and the discontinuation of nintedanib due to pneumothorax (n = 1). Stool frequency and stool form scores decreased significantly after the initiation of ramosetron therapy; however, IBS-QOL did not improve significantly. IBS-QOL correlated with shortness of breath scores but not with stool frequency. No prominent adverse events were associated with ramosetron administration. Conclusions: Ramosetron, a 5-HT₃ antagonist, improved stool frequency and stool form in patients with severe nintedanib-induced diarrhea. Full article

An early and accurate diagnosis of connective tissue diseases-related interstitial lung disease (CTD-ILD) is crucial for delaying lung fibrosis, but its unknown etiology and the limitations of clinical tools make it challenging for clinicians. PDGF and TGFB are the main profibrotic genes. We evaluated PDGFA, TGFB1, TGFB2, and TGFB3 role in the diagnosis of ILD associated with rheumatoid arthritis (RA), systemic sclerosis (SSc), and inflammatory myopathies (IM). Blood was collected from 289 patients:33 RA-ILD, 31 SSc-ILD, 29 IM-ILD; and 22 RA-nonILD, 18 SSc-nonILD, 8 IM-nonILD; and 148 idiopathic pulmonary fibrosis (IPF). The relative expression was quantified by qPCR. Lower PDGFA, TGFB1, and TGFB2 expression differentiated RA-ILD from RA-nonILD patients, acting as ILD early diagnostic biomarkers in RA with cut-offs of <0.01153, <0.3185, and <0.001410, respectively. SSc-ILD patients revealed decreased TGFB2 expression compared to SSc-nonILD patients, with a cut-off of <0.0018 identifying ILD in SSc. PDGFA and TGFB2 expression discriminated IM-ILD from IPF acting as accurate diagnostic biomarkers with cut-offs of >0.0166 and >0.001547, respectively. PDGFA and TGFB2, as well as TGFB2 and TGFB3 expression were associated with RA-ILD and SSc-ILD prognosis, respectively. PDGFA and TGFB are promising blood biomarkers with clinical value for the early and accurate CTD-ILD diagnosis. Full article

Background: Combined Pulmonary Fibrosis and Emphysema (CPFE) is a distinct syndrome characterized by upper-lobe emphysema and lower-lobe fibrosis, predominantly in older male smokers. Despite often preserved spirometric volumes, patients exhibit severely reduced diffusing capacity and high susceptibility to complications, including pulmonary hypertension (PH), acute exacerbations, and lung cancer, contributing to poor prognosis. Purpose: This review aims to synthesize current evidence on CPFE, focusing on clinical phenotype, functional impairment, differential diagnosis, complications, and emerging management strategies, highlighting distinctions from idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD). Methods: A narrative review of observational cohorts, retrospective series, and clinical studies examining CPFE patients was performed. Data on demographics, smoking history, symptomatology, pulmonary function, radiology, comorbidities, complications, and treatment approaches were extracted and integrated. Results: CPFE affects mainly males aged 65–70, with >90% reporting > 40 pack–years smoking history. Dyspnea is the cardinal symptom (>95%), often disproportionate to preserved FVC and TLC, accompanied by chronic cough in 30–70%. Exercise-induced desaturation is frequent, correlating with PH, observed in 47–90% of patients. Pulmonary function tests reveal preserved volumes, normal or near-normal FEV1/FVC, and severely reduced DLCO (35–45%), distinguishing CPFE from COPD and IPF. HRCT confirms the combined emphysematous and fibrotic pattern, critical for differential diagnosis. Acute exacerbations occur in 20–28% of cases, lung cancer in 22–46% (mostly squamous cell), and long-term oxygen therapy is required in >70%. Five-year survival is 35–55%, lower than emphysema alone and comparable or worse than IPF. Management focuses on smoking cessation, antifibrotics, oxygen therapy, and complication-specific treatments, and selected patients may undergo lung transplantation. Conclusions: CPFE is a clinically and functionally unique entity with a high burden of pulmonary and systemic complications. Accurate recognition using HRCT and DLCO, along with early intervention and tailored management, is essential to improve patient outcomes and guide prognostic stratification. Full article

Background: There have been no previous comprehensive reports on interstitial lung diseases (ILD) in Israeli population, that may have unique epidemiological features. We aimed to explore ILD in Israel, with an emphasis on disparities between different regions of the country. Methods: The study included consecutive patients with a multidisciplinary diagnosis of ILD, using data from registries of four tertiary medical centers (MC) located in Central and Northern Israel. Multivariate regression models were used to assess the region of residence (peripheral vs. central) as an independent predictor for ILD subtypes. Results: Included were 927 patients with ILD (mean age 67 ± 13, 40% females). Most patients (56–61%) reported working in at least one job that involved relevant inhalational exposures. Despite the geographic proximity of MCs (all within 100 km), significant variations in demographic and clinical characteristics were observed, including age, sex, exposures, and ILD diagnoses (p < 0.01). The most prevalent diagnoses were Idiopathic pulmonary fibrosis (IPF, range 13–58%) and autoimmune-related ILD (11–30%). In peripheral areas, the diagnosis of IPF was more frequent (53% vs. 24%, p < 0.01), while exposure-related ILD (5% vs. 16%, p < 0.01) and autoimmune-related ILD (16% vs. 25%, p < 0.01) were more frequent in central Israel. In multivariate analysis, peripheral residence remained an independent predictor for IPF (AOR 2.95, 95% CI 2.1–4.1) and central residence for exposure-related ILD (AOR 0.46, 95% CI 0.33–0.63). Conclusions: Variations in ILD characteristics were observed between centers in close geographic proximity, highlighting disparities between peripheral and central Israel, and the need for personalized assessment based on local frequencies and exposures. Full article

Background: Hypersensitivity pneumonitis (HP) is an interstitial lung disease (ILD) characterized by inflammation of the lung parenchyma, alveoli and bronchioles induced by inhalation of organic compounds. Bird-related-HP (BRHP) is the most common type of HP, occurring in susceptible people in regular contact with birds, although a genetic susceptibility is unclear. This study investigates the impact of environmental volatile organic compounds (VOCs) on the development of HP and other pulmonary diseases, and their relationship with pulmonary inflammatory cell composition and patient outcomes. Methods: Geospatial environmental levels of VOCs (benzene, toluene, ethylbenzene, m,p-xylene and o-xylene) in patients’ homes were related to bronchoalveolar lavage (BAL) leukocyte profiles analyzed by flow cytometry of 1515 patients with different lung diseases in the region of Murcia (southeastern Spain). Results: Ethylbenzene levels over the threshold limit of 10 µg/m³ (EB10) were associated with HP (23.9% vs. 15.2%, p < 0.05). A strong association with HP was observed in patients in contact with birds living in areas with EB10 (63.0% vs. 27.4%, p < 0.001). Linear regression analysis showed that age (B = −0.058, p < 0.012), smoking (B = −0.125, p < 0.001), bird contact (B = 0.275, p < 0.001) and EB10 (B = 0.109, p < 0.001) were independent variables associated with HP. In HP patients, BAL CD4/CD8-ratio > 1.5 was associated with shorter overall survival (8.9 years vs. not-reached, p < 0.011), probably due to lower CD8+ T-lymphocyte counts observed in HP fibrotic patients (11.65 ± 2.8% vs. 23.6 ± 2.9%, p = 0.008) and in those who died during follow-up (10.0 ± 1.9% vs. 23.8 ± 2.7%, p = 0.012), suggesting a protective role for CD8+ T cells. Conclusions: High environmental ethylbenzene is strongly associated with BRHP. CD8+ T-lymphocytes could have a protective role in HP, preventing fibrosis and increasing overall survival. Full article

Background/Objectives: In patients with idiopathic pulmonary fibrosis (IPF), a progressive disease characterized by lung tissue scarring, the impact of comorbidities is only partially understood. In particular, the prognostic implications of pulmonary hypertension (PH) are yet to be fully disclosed. Methods: To identify distinct IPF phenotypes on the basis of comorbidities and functional data, we performed cluster mixed data retrospective analysis, as well as recursive partitioning analysis on a dataset of 324 patients from the European IPF Registry (eurIPFreg); all patients were classified as IPF on the basis of established guidelines. Diagnosis of PH was based on echocardiographic and right heart catheter criteria as indicated in the 2022 ESC/ERS guidelines. Results: Two distinct clinical clusters with significant survival differences were identified (p < 0.001). Cluster 1, with fewer comorbidities, had a median survival of 4.41 years, whereas Cluster 2, with higher rates of arterial hypertension, diabetes mellitus, cardiovascular disease, PH, and dyslipidemia, showed a shorter median survival of 2.85 years. Multivariate Cox regression analysis confirmed PH as a significant predictor of reduced survival (HR 2.03). Recursive partitioning (RP) revealed that FVC was the strongest prognostic indicator: FVC below 50% predicted poor survival, and among patients with a FVC above 50%, the presence of PH indicated a significantly worse outcome. Conclusions: In this real-world IPF cohort, comorbidity cluster and RP analysis identified PH as the most relevant comorbidity. The findings suggest that PH may be more prevalent and impactful in IPF than previously recognized, with implications for clinical management. Full article

This document provides an updated overview of the molecular mechanisms underlying pulmonary fibrosis associated with Systemic Sclerosis (SSc). It summarizes current knowledge on how immune activation, vascular injury, and impaired tissue repair contribute to interstitial lung disease (ILD), which is the most serious and life-threatening complication of SSc. SSc is a rare autoimmune disorder involving vascular dysfunction and progressive fibrosis of the skin and internal organs. In the lungs, the interaction between immune and vascular abnormalities and excessive extracellular matrix deposition leads to irreversible structural damage. These processes occur through complex, multifactorial mechanisms that are only partially understood. The review examines recent evidence on the cellular mediators, signaling pathways, and epigenetic alterations involved in ILD-SSc pathogenesis. It also discusses the potential roles of genetic predisposition, environmental factors, and autoantibody profiles in disease heterogeneity. Finally, it highlights emerging therapeutic strategies that target these molecular mechanisms. This work aims to integrate these advances to provide a clearer understanding of the biological basis of SSc-associated pulmonary fibrosis and support the development of novel diagnostic and therapeutic approaches that may improve patient outcomes. Full article

Pulmonary fibrosis is a progressive interstitial lung disease that involves stimulated growth of fibroblasts, over-deposition of extracellular matrix (ECM), and permanent damage of the lung structure. Among its various forms, idiopathic pulmonary fibrosis (IPF) is the most common and life-threatening type with few treatment options and a poor prognosis. Such obstacles highlight the urgency to find new molecular targets by better understanding the cellular and signaling processes that contribute to the pathogenesis of the disease. Chemerin is an adipokine and chemoattractant protein that has recently come into the limelight as a major controller of immune cell trafficking, inflammation, and tissue remodeling. Its biological activity is mainly mediated by binding to its receptors Chemokine-like receptor 1 (CMKLR1), G protein-coupled receptor 1 (GPR1), and C-C chemokine receptor-like 2 (CCRL2), and has been linked to numerous pathological conditions, such as metabolic diseases, cancer, and inflammatory diseases. Emerging data now indicate that chemerin can also be a key factor in the initiation and progression of pulmonary fibrosis. The aim of the review is to overview the existing evidence regarding regulatory processes of chemerin expression, signaling pathways, and effects of this protein in cells in the fibrotic lung microenvironment. Moreover, we will comment on the findings of in vitro and in vivo experiments supporting the possibility of chemerin as a promising molecular target in basic research on pulmonary fibrosis. Full article

Background/Objectives: Combined pulmonary fibrosis and emphysema (CPFE) is associated with poor outcomes. We investigated the association of antifibrotic therapy on patients with CPFE. Methods: This retrospective study included adult patients, older than 18 years, with a diagnosis of CPFE between 2015 and 2019 using TrinetX database. CPFE was defined as a diagnosis of pulmonary fibrosis (PF) and emphysema or chronic obstructive pulmonary disease. Propensity score matching was performed to compare baseline characteristics for CPFE patients on antifibrotic therapy (nintendanib and pirfenidone) with those not on antifibrotic therapy. The outcomes studied included all-cause mortality, major adverse cardiac event (MACE, [myocardial infarction, unstable angina]), hypoxic and hypercapnic respiratory failure, and stroke. These outcomes were compared at one-, three-, and five-year follow-ups. Results: Patients were divided into two cohorts: those on antifibrotic therapy (cohort 1, n = 861) and those without antifibrotic therapy (cohort 2, n = 861). Although not statistically significant, there was a trend towards increased mortality in cohort 1 at the 5-year follow-up (HR 1.14; CI 0.99–1.33). There was also an increased incidence of MI (HR 1.68; CI 0.88–1.47) and hypoxic respiratory failure (HR 1.17; CI 0.99–1.39). Notably, there was also a trend towards decreased incidence of stroke (HR 0.73; CI 0.51–1.05), and no difference in unstable angina (HR 0.94; CI 0.47–1.86) and hypercapnic respiratory failure (HR 0.99; CI 0.67–1.47). Conclusions: For patients with CFPE, antifibrotic use demonstrated a trend towards increased risk of mortality at 5-year follow-up, raising concerns for “sicker patient” bias. Prospective studies should be designed to include patients with CPFE and evaluate the benefits of antifibrotics. Full article

Interstitial lung disease associated with connective tissue disease (CTD-ILD) is a severe condition characterized by inflammation and progressive lung fibrosis, with limited treatment options. Previous studies have demonstrated the anti-inflammatory and antifibrotic properties of human umbilical cord-derived mesenchymal stem cells (huMSCs), suggesting their potential as novel therapeutic agents. Therefore, we investigated the dose-dependent therapeutic effects of huMSCs on CTD-ILD. A bleomycin-induced mouse model of interstitial lung disease, in which female C57BL/6J mice developed diffuse pulmonary lesions following continuous subcutaneous infusion of bleomycin, was used. Mice subsequently received intravenous huMSCs at doses of 1.0 × 10³, 1.0 × 10⁴, or 1.0 × 10⁵ cells. The medium dose (1.0 × 10⁴ cells) showed the most pronounced effects on pulmonary fibrosis and collagen deposition, while significantly suppressing pro-inflammatory cytokines, including interleukin-1β and interleukin-6; however, this effect was not consistent across all measured outcomes. The treatment also enhanced beneficial matrix remodeling by downregulating TIMP-1 and upregulating MMP-9 expression. Furthermore, huMSC administration modulated macrophage polarization and inhibited the pro-inflammatory M1 phenotype. These findings highlight the therapeutic potential of huMSCs for CTD-ILD and underscore the importance of dose optimization to balance efficacy and safety. Full article

Canine idiopathic pulmonary fibrosis (CIPF) is an interstitial lung disease reported in West Highland white terriers (WHWTs). B-mode ultrasonography (US) is used in human medicine as an adjunct tool for interstitial lung disease, including idiopathic pulmonary fibrosis. In veterinary medicine, thoracic US has been described as helpful for the diagnosis of various pulmonary diseases. The aim of this study was to describe the thoracic B-mode US findings in CIPF WHWTs, compared with those in control WHWTs. Twenty-seven WHWTs, including CIPF and control WHWTs, were prospectively enrolled. Standardised thoracic B-mode US was performed. The presence of an irregular pleural surface, ring-down artefact and peripheral nodules was assessed and scored for each location. An overall cumulative score was calculated by adding the individual scores of each location. WHWTs affected with CIPF had significantly higher overall scores compared to the control group. The ring-down artefact score was significantly higher in the CIPF group compared to the control group. No preferential location for the lesions was observed. A cut-off value of 15 ring-down artefacts for the entire thorax predicted CIPF in WHWTs with a sensitivity of 76.5% and a specificity of 80% (AUC 0.815). The present study describes B-mode US findings in CIPF WHWTs. Full article

Background/Objectives: Idiopathic pulmonary fibrosis (IPF) is the most common form of pulmonary fibrosis (PF) and serves as a key reference for disease severity. Progressive pulmonary fibrosis (PPF), a distinct yet heterogeneous entity arising from various interstitial lung diseases (ILDs), shares similar pathogenetic mechanisms and clinical courses driven by self-perpetuating fibrosis. Antifibrotic therapy, notably nintedanib, can slow disease progression. However, real-world data on antifibrotic therapy’s impact on survival, especially in PPF, are limited. This study aims to compare IPF and PPF regarding phenotype, radiological patterns, comorbidities, prognostic factors, and response to nintedanib, focusing on identifying the patient subsets most likely to benefit. Outcomes assessed include safety, survival, and disease progression over one year, considering various prognostic factors. Methods: This retrospective observational study evaluated patients with fibrosing ILD, affected by either IPF or PPF, and treated with nintedanib. Data collected encompassed clinical, radiological, functional, and treatment-related information. Assessments included chest CT, pulmonary function tests, comorbidities, and survival analysis, utilizing standardized methods and statistical tools to interpret outcomes and tolerability. Results: The study population was composed of 97 patients: 64 were diagnosed with IPF and 33 with PPF. The analysis showed that in PPF patients, ongoing antifibrotic treatment resulted in higher survival (71.1 months vs. 27.4 months, p < 0.001), while no statistically significant differences were found in the IPF group (67.4 months vs. 52.5 months, p = 0.216). Nintedanib was generally well tolerated. Gastrointestinal side effects, predominantly diarrhea, were reported in 61% of patients with IPF and 50% of those with PPF. Dose reduction occurred in 43.75% of IPF patients and 36% of PPF patients, while treatment discontinuation was required in 21.87% of IPF and 21% of PPF patients. Conclusions: This study highlights that in PPF patients, antifibrotic therapy with nintedanib can improve survival. This statement underlines that the primary outcome of antifibrotic treatment should focus on improving patients’ survival. Full article

Background: Patients with fibrotic interstitial lung disease (ILD) are at increased risk of lung cancer, yet the impact of antifibrotic therapy on oncologic outcomes remains unclear. Objective: This study aimed to explore associations between antifibrotic therapy and overall survival (OS) and acute exacerbations of ILD (AE-ILD) in patients with fibrotic ILD who develop lung cancer. Methods: We retrospectively analyzed 61 patients from multiple Italian centers: 35 received antifibrotic therapy (pirfenidone or nintedanib) and 26 did not. Outcomes included OS from cancer diagnosis and post-treatment AE-ILD. Results: Mean OS was 17.9 months in the antifibrotic group and 33.2 months in the non-antifibrotic group; no adjusted survival analyses were possible due to missing censoring data, and these descriptive values should not be overinterpreted. AE-ILD occurred in 11.4% of antifibrotic-treated patients and 11.5% of those without antifibrotics. PD-L1 expression was detected in 24.1% vs. 21.8% of tumors in the two groups, and autoantibody positivity was observed in 22.8% vs. 30.7%, respectively, reflecting differences in ILD subtypes. Conclusions: In this heterogeneous real-world cohort, antifibrotic therapy was not associated with increased AE-ILD risk, and descriptive OS comparisons showed no clear survival advantage. These exploratory findings warrant confirmation in larger, prospective studies. Full article

Interstitial lung diseases (ILDs) are chronic respiratory disorders often leading to dyspnoea, reduced exercise tolerance, and poor quality of life. Pulmonary rehabilitation (PR) improves symptoms and function but remains underused in Portugal, with only ~1% of eligible patients enrolled. This study retrospectively analysed 61 ILD patients at Hospital Garcia de Orta (July–December 2024) to identify PR candidates. Most had idiopathic pulmonary fibrosis (44%), exertional dyspnoea (67.2%), and moderate lung impairment (49%). Comorbidities and risk factors were common. Findings highlight a significant gap between clinical need and access, reinforcing the urgency of structured referral strategies to expand PR availability. Full article