Am J Hosp Palliat Care. 2025 Mar 14:10499091251325566. doi: 10.1177/10499091251325566. Online ahead of print.

ABSTRACT

BackgroundDyspnea is a prevalent and distressing symptom in interstitial lung diseases with significant effects on patients' quality of life and associated with poorer prognosis. Guidelines recommend a multidimensional dyspnea assessment tool. We developed a validated 9-item scale, the Edmonton Dyspnea Inventory (EDI), in which dyspnea severity is rated across different settings including at rest, during activities of daily living, and self-reported exercise and crises. The standardized, multidimensional tool captures dyspnea intensity for specific contexts, which clinicians can use to manage dyspnea more individually and effectively. Early studies support the feasibility to use the EDI in outpatient settings. The purpose of this study was to explore perceptions of the EDI by community health care professionals.MethodsWe conducted a qualitative study using an inductive approach and open coding for content analysis. Email invitations were sent to community health care professionals and informed consent obtained from the twelve participants. Two focus groups and one key informant interview were conducted. Themes were extracted from transcripts and field note analyses.ResultsFour main themes described their dyspnea assessment with the EDI: the EDI is a meaningful clinical assessment tool; they explicitly engage and educate patients to effectively use the EDI; they use the EDI to personalize and evaluate dyspnea management; and the EDI is valuable for communication and interprofessional collaboration.ConclusionCommunity health care professionals perceived the EDI as valuable to assess dyspnea and personalize management. They recommended it be used in clinical practice and healthcare education for interprofessional dyspnea management for ILD patients.

PMID:40085021 | DOI:10.1177/10499091251325566

J Rehabil Med Clin Commun. 2025 Mar 6;8:40698. doi: 10.2340/jrm-cc.v8.40698. eCollection 2025.

ABSTRACT

OBJECTIVE: To evaluate the benefits of inpatient rehabilitation for a patient with post-COVID-19 pulmonary fibrosis and to provide guidance for rehabilitation professionals, as many conventional therapeutic interventions are not tolerated and are poorly defined.

DESIGN: A case report.

SUBJECTS/PATIENTS: A 72-year-old man with a COVID-19-related idiopathic pulmonary fibrosis exacerbation.

RESULTS: The patient was admitted to inpatient rehabilitation with hypoxia and poor endurance for functional activities. Rehabilitation activities were focused on providing patient/family education, energy conservation, low level activities to build strength, problem solving for mobility, and discharge planning within safe medical parameters. Rehabilitation therapies were graded to meet the patient's physiologic needs and focused on patient and family training. The patient made limited functional gains and continued to have high oxygen needs but achieved his goal of returning home.

CONCLUSION: Patients with COVID-19-related idiopathic pulmonary fibrosis exacerbations can be treated in acute rehabilitation effectively. With more patients developing post-COVID-19 pulmonary fibrosis, appropriate rehabilitation strategies are important for safe discharge planning. Prioritizing patient/family education may allow these more medically fragile patients to return home.

PMID:40083891 | PMC:PMC11905151 | DOI:10.2340/jrm-cc.v8.40698

Ther Adv Respir Dis. 2025 Jan-Dec;19:17534666251326743. doi: 10.1177/17534666251326743. Epub 2025 Mar 14.

ABSTRACT

BACKGROUND: Pulmonary fibrosis is a severe, progressive form of interstitial lung disease associated with increased morbidity and mortality. Pulmonary hypertension often accompanies severe pulmonary fibrosis and is also associated with worse outcomes. Antifibrotic therapy and pulmonary vasodilator therapy have demonstrated clinical benefits in pulmonary fibrosis and pulmonary hypertension, respectively. However, the benefit of combined antifibrotic and pulmonary vasodilator therapy in patients with both pulmonary fibrosis and pulmonary hypertension is less established.

OBJECTIVES: We aimed to determine the effectiveness of a combination pulmonary vasodilator and antifibrotic therapy with regard to transplant-free survival and six-minute walk distance improvement in patients with pulmonary fibrosis and pulmonary hypertension.

DESIGN: This was a retrospective cohort study of patients with pulmonary fibrosis (idiopathic pulmonary fibrosis, combined pulmonary fibrosis and emphysema, and other fibrotic interstitial lung disease) and pulmonary hypertension diagnosed via right heart catheterization. Patients received antifibrotic therapy with or without pulmonary vasodilator therapy.

METHODS: Patients who received combination antifibrotic therapy and pulmonary vasodilator therapy were compared to those prescribed antifibrotic therapy alone. Transplant-free survival and change in six-minute walk distance were compared between the two groups. Multivariable Cox regression was performed to determine predictors of transplant-free survival.

RESULTS: Patients who received antifibrotic and pulmonary vasodilator therapy had significantly improved transplant-free survival (log rank p = 0.001). Treatment with antifibrotic and pulmonary vasodilator therapy was significantly and independently associated with reduced risk of death or lung transplantation (HR 0.24, 95% CI 0.06-0.93, p = 0.04). These patients had worse pulmonary hemodynamics than those receiving antifibrotic therapy alone.

CONCLUSION: We found a potential survival benefit when pulmonary vasodilator therapy was given in combination with antifibrotic therapy in patients with pulmonary fibrosis and pulmonary hypertension. This may be reflective of a pulmonary vascular phenotype among those with pulmonary fibrosis and pulmonary hypertension. Further trials are needed to better elucidate which patients benefit from combination therapy.

PMID:40083194 | DOI:10.1177/17534666251326743

Thorax. 2025 Mar 13:thorax-2024-221537. doi: 10.1136/thorax-2024-221537. Online ahead of print.

ABSTRACT

BACKGROUND: The diagnosis of interstitial lung disease (ILD) can pose a challenge as the pulmonary function test (PFT) is only minimally affected at the onset. To improve early diagnosis, this study aims to explore the potential of artificial intelligence (AI) software in assisting pulmonologists with PFT interpretation for ILD diagnosis. The software provides an automated description of PFT and disease probabilities computed from an AI model.

STUDY METHODS: In study phase 1, a cohort of 60 patients, 30 of whom had ILD, were retrospectively diagnosed by 25 pulmonologists (8 junior physicians and 17 experienced pneumologists) by evaluating a PFT (body plethysmography and diffusion capacity) and a short medical history. The experts screened the cohort twice, without and with the aid of AI (ArtiQ.PFT, V.1.4.0, ArtiQ, BE) software and provided a primary diagnosis and up to three differential diagnoses for each case. In study phase 2, 19 pulmonologists repeated the protocol after using ArtiQ.PFT for 4-6 months.

RESULTS: Overall, AI increased the diagnostic accuracy for various lung diseases from 41.8% to 62.3% in study phase 1. Focusing on ILD, AI improved the detection of lung fibrosis as the primary diagnosis from 42.8% without AI to 72.1% with AI (p<0.0001). Phase 2 yielded a similar outcome: using AI increased ILD diagnosis based on primary diagnosis (53.2% to 75.1%; p<0.0001). ILD detections without AI support significantly increased between phase 1 and phase 2 (p=0.028) but not with AI (p=0.24).

INTERPRETATION: This study shows that AI-based decision support on PFT interpretation improves accurate and early ILD diagnosis.

PMID:40081903 | DOI:10.1136/thorax-2024-221537

Tuberc Respir Dis (Seoul). 2025 Mar 13. doi: 10.4046/trd.2024.0181. Online ahead of print.

ABSTRACT

Rare forms of interstitial lung diseases (ILDs) present with unique clinical features and require different treatment strategies. Respiratory bronchiolitis-associated ILD mainly affects smokers, showing ground-glass opacities on chest computed tomography (CT) scans and pigmented macrophages in the bronchoalveolar lavage fluid. Smoking cessation is essential for treatment, with corticosteroids used for severe cases. Desquamative interstitial pneumonia, also related to smoking, is characterized by exertional dyspnea, dry cough, restrictive lung function, and ground-glass opacities on high-resolution CT. Lymphoid interstitial pneumonia involves lymphocytic proliferation and is associated with autoimmune diseases or infections, treated with corticosteroids. Acute interstitial pneumonia resembles acute respiratory distress syndrome but occurs without a clear cause and is managed with supportive care. Idiopathic pleuroparenchymal fibroelastosis results in fibrosis in the upper lobes, primarily in nonsmokers, and is diagnosed through clinical and imaging findings, with no effective treatment to improve survival. Each condition has distinct pathological features, clinical presentations, and treatment approaches, along with variable prognoses.

PMID:40081337 | DOI:10.4046/trd.2024.0181

Respir Investig. 2025 Mar 12;63(3):334-341. doi: 10.1016/j.resinv.2025.03.005. Online ahead of print.

ABSTRACT

BACKGROUND: The 6-min walk test (6MWT) is frequently used in pulmonary fibrosis (PF) research. It evaluates an individual's sub-maximal exercise performance by measuring the distance they walk and their vital signs across 6 min. In research studies, the 6-min walk distance (6MWD) is often used as a surrogate marker for disease progression. The aim of this study was to systematically assess the association between 6MWT parameters and mortality in PF.

METHODS: MEDLINE, EMBASE, CINAHL, and CENTRAL databases were searched for studies reporting mortality and 6MWD in patients with PF. Study quality was assessed using a modified Newcastle-Ottawa Scale. Studies were included if they reported associations between the 6MWT in pulmonary fibrosis and mortality. Results were presented as a narrative synthesis.

RESULTS: 2312 studies were identified, 22 studies met the pre-defined inclusion criteria, comprising 5940 Idiopathic PF patients. Baseline 6MWD was found to be loosely associated with mortality (Ranges: univariate HR 0.89-4.72, multivariate HR 0.96-2.65), while a decrease in 6MWD across 24-weeks was correlated with a higher risk of mortality (Ranges: univariate HR 2.25-4.81, multivariate HR 1.72-4.3).

DISCUSSION: This review found that a low baseline 6MWD, and a 6-month decrease in 6MWD were strongly correlated with increased mortality in Idiopathic PF patients. As the 6MWT is a safe, easy-to-conduct test, it is appropriate for use as a marker of patient prognosis, in both clinical and research settings.

OPEN SCIENCE FRAMEWORK PROTOCOL REGISTRATION: DOI 10.17605/OSF.IO/3D7BV.

PMID:40081204 | DOI:10.1016/j.resinv.2025.03.005

Funct Integr Genomics. 2025 Mar 13;25(1):62. doi: 10.1007/s10142-025-01571-8.

NO ABSTRACT

PMID:40080215 | DOI:10.1007/s10142-025-01571-8

Radiol Cardiothorac Imaging. 2025 Apr;7(2):e240382. doi: 10.1148/ryct.240382.

ABSTRACT

Pleuroparenchymal fibroelastosis (PPFE) is an interstitial lung disease (ILD) characterized at CT by upper lobe-predominant pleural thickening and subpleural fibrosis and histologically by visceral pleural fibrosis and subpleural fibroelastosis. Although initially classified as a rare idiopathic interstitial pneumonia, many cases are related to known risk factors, particularly hematopoietic stem cell and lung transplant, or observed in association with other ILDs. This review summarizes the diagnostic criteria for PPFE and illustrates the CT and histologic manifestations, aiming to familiarize the radiologist with the range of findings suggestive of the diagnosis. Keywords: Conventional Radiography, CT, Pulmonary, Thorax, Lung, Pleura, Complications, Transplantation, Fibrosis © RSNA, 2025.

PMID:40079759 | DOI:10.1148/ryct.240382

Int J Mol Sci. 2025 Mar 5;26(5):2327. doi: 10.3390/ijms26052327.

ABSTRACT

Filtration bleb (FB) fibrosis represents the primary risk factor for glaucoma filtration surgery (GFS) failure. We reviewed the most recent literature on post-GFS fibrosis in humans, focusing on novel molecular pathways and antifibrotic treatments. Three main literature searches were conducted. First, we performed a narrative review of two models of extra-ocular fibrosis, idiopathic pulmonary fibrosis and skin fibrosis, to improve the comprehension of ocular fibrosis. Second, we conducted a systematic review of failed FB features in the PubMed, Embase, and Cochrane Library databases. Selected studies were screened based on the functional state and morphological features of FB. Third, we carried out a narrative review of novel potential antifibrotic molecules. In the systematic review, 11 studies met the criteria for analysis. Immunohistochemistry and genomics deemed SPARC and transglutaminases to be important for tissue remodeling and attributed pivotal roles to TGFβ and M2c macrophages in promoting FB fibrosis. Four major mechanisms were identified in the FB failure process: inflammation, fibroblast proliferation and myofibroblast conversion, vascularization, and tissue remodeling. On this basis, an updated model of FB fibrosis was described. Among the pharmacological options, particular attention was given to nintedanib, pirfenidone, and rapamycin, which are used in skin and pulmonary fibrosis, since their promising effects are demonstrated in experimental models of FB fibrosis. Based on the most recent literature, modern patho-physiological models of FB fibrosis should consider TGFβ and M2c macrophages as pivotal players and favorite targets for therapy, while research on antifibrotic strategies should clinically investigate medications utilized in the management of extra-ocular fibrosis.

PMID:40076946 | DOI:10.3390/ijms26052327

Int J Mol Sci. 2025 Feb 28;26(5):2218. doi: 10.3390/ijms26052218.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a rare disorder concerning elderly people, predominantly men, active or former smokers, with a progressive nature and leading to premature mortality. The cause of the disease is unknown. However, there are some risk factors, among which genetic predisposition plays a role. The aim of our single-centered observational study was to assess the correlation between single nucleotide polymorphism (SNP) of the MUC5B gene (rs35705950) and the disease course, antifibrotic treatment effect, and survival in patients with IPF. A total of 93 patients entered the study, of whom 88 were treated with either nintedanib or pirfenidone. The GG genotype was found in 28 (30.1%) subjects, while the GT or TT genotypes were found in the remaining 65 (63.4%) and 6 (6.5%) patients, respectively. The T allele minor allele frequency (MAF) accounted for 38.2% of the whole group. Patients with different genotypes did not differ significantly regarding age, sex, pulmonary function tests' results, response to the antifibrotic treatment, or survival. However, we found a survival advantage in female patients and patients with higher pre-treatment TL,co. Treatment with antifibrotics significantly decreased the magnitude of FVC and TL,co decline compared to the time before treatment initiation, regardless of MUC5B status. In conclusion, we found high prevalence of T allele of MUC5B gene in patients with IPF; however, it showed no influence on disease trajectory, survival, or antifibrotic treatment effect in the presented cohort.

PMID:40076835 | DOI:10.3390/ijms26052218

Sci Rep. 2025 Mar 13;15(1):8622. doi: 10.1038/s41598-025-93217-9.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a kind of interstitial lung disease (ILD). It has a high incidence rate and mortality. Its pathogenesis remains unclear. So far, no effective methods have been found for the early diagnosis of IPF. Ferroptosis has been reported to be critical in the initiation and progression of IPF. Therefore, our aim was to identify the hub gene related to ferroptosis co-expressed in the peripheral blood and pulmonary tissue of patients with IPF. Sequencing data were obtained from the Gene Expression Omnibus database. A comprehensive analysis was conducted on the differentially expressed genes (DEGs) to extract ferroptosis-related differentially expressed genes (FRDEGs). The results showed that ferroptosis-related signal paths were highly enriched in IPF, and 10 FRDEGs were identified.The hub gene was predicted through protein-protein interactions (PPI) and Cytoscape. The diagnostic utility of the hub gene was proven by enzyme-linked immunosorbent assay (ELISA) in serum and by immunohistochemistry (IHC) in pulmonary tissues. The results of ELISA indicated that the levels of ATM in the serum of patients with IPF were significantly lower than the normal levels. In contrast, the results of IHC showed that the expression of ATM in the pulmonary tissues of IPF patients exhibited a notably elevated trend. The immune status was assessed by the CIBERSORT method and so was the relevance between ATM and immune cells. These findings unveiled significant differences in various immune cell types in peripheral blood and pulmonary tissue between the IPF group and the control group. Furthermore, ATM was associated with various immune cells. This study suggests that as a ferroptosis-related gene, ATM assumes a pivotal role in the diagnosis and treatment of IPF. This discovery presents a novel approach for the clinical diagnosis and therapy of IPF.

PMID:40075162 | DOI:10.1038/s41598-025-93217-9

Lung. 2025 Mar 12;203(1):43. doi: 10.1007/s00408-025-00800-y.

ABSTRACT

PURPOSE: Toll-like receptor 4 (TLR4) is a transmembrane receptor promoting pro-inflammatory signalling, that is associated with the pathogenesis of pulmonary fibrosis. TLR4 is abundantly expressed on monocytes and the acceleration of TLR4 signalling induces the secretion of soluble TLR4 isoforms (sTLR4) in circulation. The aim of study was to evaluate the association of serum levels of sTLR4 with acute exacerbation (AE) and prognosis of patients with idiopathic pulmonary fibrosis (IPF).

METHODS: This retrospective cohort study included 97 patients with IPF and 76 healthy participants. The association of serum sTLR4 levels with the onset of AE and the prognosis in 97 patients with IPF was analyzed.

RESULTS: No significant difference in sTLR4 serum level was observed between the patients with IPF and healthy participants. Kaplan-Meier curves showed that patients with sTLR4 ≥ 2.2 ng/mL had a significantly higher incidence of AE-IPF and a significantly lower 5-year survival rate. Univariate and multivariate Cox hazard analyses demonstrated that sTLR4 ≥ 2.2 ng/mL was significantly associated with higher incidence of AE and poorer survival. In an exploratory analysis, a weak correlation was observed between sTLR4 levels and monocyte counts, and the incidence of AE-IPF was the highest in the patients with sTLR4 ≥ 2.2 ng/mL and monocyte counts ≥ 381/μL.

CONCLUSION: High sTLR4 level is associated with an increased incidence of AE-IPF and poor prognosis in patients with IPF. The combination of sTLR4 level and monocyte count might be used to stratify patients with IPF according to the risk for AE via reflecting monocyte activation.

PMID:40074958 | DOI:10.1007/s00408-025-00800-y

J Pharmacol Exp Ther. 2025 Feb 5;392(3):103396. doi: 10.1016/j.jpet.2025.103396. Online ahead of print.

ABSTRACT

Pulmonary fibrosis encompasses different chronic interstitial lung diseases, and the predominant form, idiopathic pulmonary fibrosis, remains to have a poor prognosis despite 2 approved therapies. Although the exact pathobiological mechanisms are still incompletely understood, epithelial injury and aberrant wound healing responses contribute to the gradual change in lung architecture and functional impairment. Lysophosphatidic acid (LPA)-induced lysophosphatidic receptor 1 (LPA1) signaling was proposed to be a driver of lung fibrosis, and LPA1 antagonists have shown promising antifibrotic profiles in early clinical development. The novel, potent, and selective LPA1 antagonist, ACT-1016-0707, displayed insurmountable LPA1 antagonism in vitro with slow off-rate kinetics, leading to efficient inhibition of LPA1 signaling even in presence of high concentrations of LPA. This binding property translated into potent and highly efficient prevention of LPA-induced skin vascular leakage by ACT-1016-0707 in vivo, differentiating the compound from surmountable LPA1 antagonists. Furthermore, ACT-1016-0707 attenuated proinflammatory and profibrotic signaling in different lung fibrosis models in vitro and in the bleomycin-induced lung fibrosis model in vivo. Based on these data, ACT-1016-0707 shows potential as best-in-class LPA1 antagonist for treatment of fibrotic diseases. SIGNIFICANCE STATEMENT: ACT-1016-0707 is a potent, selective, and insurmountable lysophosphatidic receptor 1 (LPA1) antagonist demonstrating robust antifibrotic and anti-inflammatory activity in different lung fibrosis models in vitro and in vivo. This study is the first to demonstrate functional in vivo evidence of insurmountable LPA1 antagonist superiority by side-by-side comparison with surmountable LPA1 antagonists in highly controlled conditions, suggesting potential for ACT-1016-0707 as best-in-class LPA1 antagonist for treatment of fibrotic diseases.

PMID:40073729 | DOI:10.1016/j.jpet.2025.103396

HCA Healthc J Med. 2025 Feb 1;6(1):11-21. doi: 10.36518/2689-0216.1802. eCollection 2025.

ABSTRACT

Description Idiopathic pulmonary fibrosis (IPF) is a progressive disease characterized by gradual destruction and replacement of pulmonary parenchyma with fibrous tissue, which occurs in conjunction with chronic inflammation. It is often considered a prototypical interstitial lung disease and is both the most prevalent and perhaps the most dangerous in that family. Although the disease is uncommon in the general population, its prevalence increases with age and is typically diagnosed around the age of 65. This does not preclude the development of IPF in younger individuals, and the mean survival is 2 to 5 years post-diagnosis regardless of age. Contemporary studies have provided insight into how altered pulmonary parenchyma results in increased susceptibility to opportunistic infections. It has also been demonstrated that pulmonary insults that cause inflammation, such as pneumonia, may accelerate the progression of IPF. Eosinophilic pneumonias are a collection of pulmonary diseases in which eosinophil-mediated inflammation results in respiratory compromise. Early recognition and appropriate intervention are imperative to minimize the risk of residual pulmonary function deficits, a risk that is increased in individuals with separate pulmonary risk factors. While prompt diagnosis and pharmacologic interventions are associated with improved outcomes, patients with IPF remain at risk of deterioration to the point of requiring lung transplantation. Early screening for those at risk continues to be a topic of interest. Despite the prevalence of IPF, its pathogenesis remains poorly understood and few management options are available. In this article, we document a unique case of previously undiagnosed IPF in a young individual that acutely worsened in the setting of acute eosinophilic pneumonia and the involvement of an opportunistic organism, Aspergillus niger. The case section will serve as a transition into a discussion of each of the major pathologic factors at play, supported by a review of recent literature.

PMID:40071189 | PMC:PMC11892399 | DOI:10.36518/2689-0216.1802

Clin Respir J. 2025 Mar;19(3):e70061. doi: 10.1111/crj.70061.

ABSTRACT

INTRODUCTION: Anti-neutrophil cytoplasmic antibody (ANCA) seropositivity strongly correlates to ANCA-associated vasculitis. Patients with idiopathic interstitial pneumonias (IIPs) without systemic vasculitis are sometimes ANCA-positive. Radiological and pathological differences between patients with myeloperoxidase (MPO)-ANCA-positive and those with proteinase 3 (PR3)-ANCA-positive IIPs remain unclear. To determine whether high-resolution computed tomography (HRCT) features and pathology findings differ by ANCA subtype in ANCA-positive IIP patients in a national database. Clinical, radiological, and pathological data were examined along with a web-based multidisciplinary discussion.

METHODS: We reviewed records of 10 MPO-ANCA-positive and 9 PR3-ANCA-positive IIP patients who underwent HRCT and surgical lung biopsy between April 2009 and March 2014. Pulmonologists, chest radiologists, and pathologists evaluated HRCT scans and pathological findings independently. Patterns were classified using ATS/ERS/JRS/ALAT 2011 guidelines for idiopathic pulmonary fibrosis.

RESULTS: HRCT patterns were definite usual interstitial pneumonia (UIP) (n = 8; 42.1%), possible UIP (n = 6; 31.6%), and inconsistent with UIP (n = 5; 26.3%). Pathological patterns were definite UIP (n = 5; 26.3%), probable UIP (n = 8; 42.1%), possible UIP (n = 4; 21.1%), and not UIP (n = 2; 10.5%). HRCT and pathological patterns did not differ between MPO-ANCA-positive and PR3-ANCA-positive IIPs. Radiological features were reticulation (n = 13; 68.4%), nodules (n = 12; 63.1%), honeycombing (n = 10; 52.6%), and increased attenuation around honeycombing (n = 7; 36.8%). Pathological findings were cysts (n = 12; 63.1%), lymphoid follicles with germinal centers (n = 11; 57.9%), and peribronchiolar wall lymphocytic infiltration (n = 11; 57.9%).

CONCLUSION: HRCT and pathological patterns did not differ between MPO-ANCA-positive and PR3-ANCA-positive IIPs. This absence of significant differences suggests a similar mechanism underlying both types of interstitial pneumonia.

PMID:40070290 | DOI:10.1111/crj.70061

Ann Am Thorac Soc. 2025 Mar 11. doi: 10.1513/AnnalsATS.202406-625OC. Online ahead of print.

ABSTRACT

Background The epidemiology of adult interstitial lung disease (ILD) is uncertain, given heterogeneous estimates from prior studies. The objective of this study was to define the incidence, prevalence, and mortality of ILD over a 10-year period using population-based data. Methods We created an administrative ILD cohort in Alberta, Canada between 2010-2019 using population-based administrative data (inpatient, ambulatory, and outpatient physician billing databases) for a repeat cross-sectional study. Case definitions were developed from an established ILD cohort and applied to the general population, with performance characteristics tested using a nested case-control design. Age-and sex-standardized annual incidence and point prevalence rates were estimated for ILD overall and within diagnostic sub-groups, with trends over time, per 100,000 at-risk adults and to permit comparisons with other studies, per 100,000 total population. Cox models estimated risk of death or lung transplantation. Results Between 2010-2019, 31,492 incident and 42,549 prevalent adult ILD cases were identified. The case definition for ILD performed well with 96.8% sensitivity, 98.5% specificity, and positive predictive value 94.3% in the population cohort. Mean age-standardized ILD incidence was 107.9/100,000 at-risk adults, 90.9/100,000 for females and 129.1/100,000 for males. Age-standardized ILD point prevalence increased from 416.5/100,000 at-risk adults in 2010 to 789.7/100,000 in 2019, higher in males vs females, and in rural vs urban areas. Age-standardized mean idiopathic pulmonary fibrosis (IPF) incidence was 36.9/100,000 at-risk and point prevalence was 205.3/100,000 at-risk in 2019. Mean age-standardized ILD incidence and prevalence was 84 and 516.9/100,000 total population, respectively. One-year all-cause mortality for ILD patients decreased from 14.5% in 2011 to 11.7% in 2018 (adjusted rate ratio (RR) for 2018 vs 2011, 0.76; 95%CI 0.67-0.86). One-year all-cause mortality for IPF similarly decreased from 20.9% in 2011 to 14.7% in 2018 (adjusted RR for 2018 vs 2011, 0.71; 95%CI 0.59-0.85), representing improved survival. Conclusions In this population-based cohort, claims-based case definitions derived from a established ILD cohort performed well to develop an administrative cohort. Incidence remained stable over time, while prevalence increased and mortality decreased, for ILD overall and within the IPF subgroup. These estimates are higher than most prior reports, suggesting an overall underestimate of ILD burden.

PMID:40068156 | DOI:10.1513/AnnalsATS.202406-625OC

Cureus. 2025 Mar 9;17(3):e80290. doi: 10.7759/cureus.80290. eCollection 2025 Mar.

ABSTRACT

OBJECTIVE: This retrospective study aimed to determine the prevalence of progression in fibrotic interstitial lung disease (ILD) and the findings at diagnosis most associated with progression after two years of follow-up in a large Brazilian cohort.

METHODS: This was a retrospective multicenter observational study in Brazil. Progression was defined after two years of follow-up. We excluded patients with an initial peripheral oxygen saturation (SpO2) of less than 88% or an initial forced vital capacity (FVC) of less than 45%. Diagnoses were made by multidisciplinary discussion. Patients with idiopathic pulmonary fibrosis were included for comparison. At least one of the following events was indicative of progressive ILD: (1) a relative decrease in FVC of 10% or more, (2) worsening dyspnea, (3) a greater extent of fibrotic findings on high-resolution computed tomography (HRCT), (4) initiation of oxygen, and (5) death attributed to ILD. Logistic regression analysis was used to identify risk factors for progressive fibrosis.

RESULTS: The mean age of patients was 61.7±12.3 years, and 69.5% had Velcro crackles. The mean FVC was 71.6±15.8%, and 26.1% showed honeycombing on HRCT. After two years of follow-up, 40.5% of patients (n=154) showed disease progression. Fibrotic hypersensitivity pneumonitis (FHP) was the most progressive disease (52%), and connective tissue disease-associated ILD (CTD-ILD) was the least progressive (25%). Multivariate analysis showed that a higher score for dyspnea, crackles, and SpO2 at rest ≤94% and ≤85% at the end of exercise were significant indicators of progression. Diffusing lung capacity for carbon monoxide (DLCO) was measured in 172 cases, with values <55% predicting a high odds ratio for progression (OR=4.03; 2.10-7.69).

CONCLUSION: In Brazil, FHP is the most progressive disease and CTD-ILD is the least progressive after two years of follow-up. The degree of dyspnea, crackles, SpO2 at rest and during exercise, and DLCO at baseline are associated with progressive disease.

PMID:40066320 | PMC:PMC11892080 | DOI:10.7759/cureus.80290

Front Med (Lausanne). 2025 Feb 24;12:1542400. doi: 10.3389/fmed.2025.1542400. eCollection 2025.

ABSTRACT

Rheumatoid arthritis (RA) is a systemic autoimmune disease that affects millions of people worldwide and is characterized by persistent inflammation, pain, and joint destruction. In RA, the dysregulation of the immune system is well documented. However, the genetic basis of the disease is not fully understood, especially when extra-articular organs are involved. Interstitial lung disease (ILD) is a major cause of morbidity and mortality in patients with RA. Notably, RA-ILD shares several risk factors with idiopathic pulmonary fibrosis (IPF), namely male gender, smoking history, usual interstitial pneumonia (UIP) pattern of fibrosis, and association with the MUC5B rs35705950 polymorphism. In addition, other genetic susceptibilities are reported in RA-ILD for some HLA alleles and other less studied polymorphisms. However, the pathobiology of RA-ILD, particularly whether and to what extent genetic and environmental factors interact to determine the disease, remains elusive. In this review, we summarize and critically discuss the most recent literature on the genetics and pathogenesis of RA-ILD. The main clinical aspects of RA-ILD are also discussed.

PMID:40066169 | PMC:PMC11891064 | DOI:10.3389/fmed.2025.1542400

Clin Transl Sci. 2025 Mar;18(3):e70179. doi: 10.1111/cts.70179.

ABSTRACT

SC1011 (sufenidone) is a novel pyridone derivative with therapeutic potential for idiopathic pulmonary fibrosis (IPF). Two Phase 1 studies evaluated the safety and pharmacokinetics of single (SAD) and multiple ascending doses (MAD) of SC1011 immediate-release (IR) and modified-release (MR) oral formulations in healthy adult subjects. In Phase 1a, subjects were randomized to receive oral SC1011 IR or placebo in SAD (50 mg-300 mg) or MAD (100 mg and 200 mg) twice daily for 7 days. The Phase 1b study consisted of three treatment groups that received 100, 150, or 200 mg SC1011 MR twice daily for 7 days. SC1011 IR was absorbed rapidly (mean time to maximum concentration, Tmax ≤ 1 h) and eliminated rapidly (mean terminal half-life, t1/2: 1.23-2.64 h) following 50-300 mg single-dose administrations. Reduced maximum plasma concentration (Cmax), delayed Tmax, and comparable total exposure were observed with the MR formulation compared with the IR formulation. Both formulations demonstrated dose-proportional pharmacokinetics at the applied dose ranges, and no obvious accumulation of systemic exposure was observed upon repeated administration. All treatment-emergent adverse events (TEAEs) with both formulations were mild or moderate in severity, and gastrointestinal reactions were the most frequently reported TEAEs. The tolerability of SC1011 was markedly improved with the MR formulation. Exposure-adverse event (AE) analysis with the most frequent AEs identified Cmax rather than total exposure as a good predictor of AEs. Compared to the IR formulation, SC1011 MR demonstrated improved exposure and tolerability, supporting its further development in patients with IPF.

PMID:40065557 | DOI:10.1111/cts.70179

Respir Res. 2025 Mar 10;26(1):97. doi: 10.1186/s12931-025-03164-2.

ABSTRACT

BACKGROUND/RATIONALE: Idiopathic Pulmonary Fibrosis (IPF) is a chronic, progressive disease of unknown origin. Establishing the epidemiology of IPF has been challenging due to diagnostic complexity, poor survival, low prevalence, and heterogeneity of ascertainment methodologies.

OBJECTIVES: This research aimed to estimate the rates of IPF in central and western Pennsylvania and to pilot the use of capture recapture (CR) methods to estimate the disease incidence.

METHODS: We identified adults ≥ 30 years old diagnosed with IPF (by ICD-9/10 coding) between 2013 to 2021 from two health systems (UPMC Health System and Penn State Health) participating in the PaTH Clinical Research Network. We extracted information on patients' sex, race, date of birth and 3-digit zip code from electronic health records (EHR). Incidence rate of IPF among Pennsylvania residents was calculated using three case definitions (broad and two restricted) and piloted the use of CR in estimating IPF incidence.

RESULTS: IPF incidence rates were 8.42, 6.95 and 4.4 per 100,000 person-years for the unrestricted (n = 3148), partially restricted (n = 2598) and fully restricted (n = 1661) samples, respectively. Low case overlap between two sites resulted in a highly inflated estimate of IPF incidence, using the CR methodology.

CONCLUSIONS: The rate of IPF in central and western Pennsylvania was similar to previously published statistics. The application of CR to IPF epidemiology could be further investigated in health systems with greater overlap of patients utilizing more than one system.

PMID:40065350 | DOI:10.1186/s12931-025-03164-2