Search Results (609)

Systemic sclerosis (SSc) is a heterogeneous autoimmune connective tissue disease characterized by immune activation, vasculopathy and progressive fibrosis of the skin and internal organs. Immunosuppressive treatment is commonly used in early inflammatory disease and in SSc-associated interstitial lung disease (SSc-ILD), yet the optimal first-line agent depends on the dominant clinical phenotype. Methotrexate (MTX) and mycophenolate mofetil (MMF) are two widely used conventional immunomodulatory options. This review summarizes the clinical trial evidence from the last four decades and places it into the context of contemporary guideline recommendations and real-world comparative effectiveness data. Two randomized placebo-controlled trials support a modest role for MTX in early diffuse cutaneous SSc, particularly for skin and musculoskeletal manifestations, but evidence for lung benefit is limited. MMF has stronger evidence for SSc-ILD, principally from the Scleroderma Lung Study II, a randomized double-blind trial showing comparable efficacy to oral cyclophosphamide with better tolerability, and from subsequent pilot, open-label, and real-world studies. Overall, the current evidence supports a phenotype-driven approach: MTX may be considered when skin or joint disease predominates without clinically relevant ILD, whereas MMF is generally preferred for SSc-ILD and systemic inflammatory disease. Direct head-to-head MTX versus MMF trials are lacking and remain an important research priority. Full article

Background and Objectives: Krebs von den Lungen-6 (KL-6) is a promising biomarker of interstitial lung disease (ILD), but data in immune-mediated ILD remain limited. We aimed to evaluate the clinical, functional, and radiological correlates of serum KL-6 levels in a real-world cohort of patients with immune-mediated ILD. Materials and Methods: We conducted a retrospective, cross-sectional, single-center study including adults with multidisciplinary follow-up for immune-mediated ILD and at least one serum KL-6 determination between January 2023 and September 2025. Clinical, laboratory, radiological, and pulmonary function data closest to the index KL-6 measurement were collected. KL-6 was analyzed as both a continuous variable and a categorical variable using a predefined cutoff of 500 U/mL. Correlation analyses and multivariable logistic regression were performed to identify factors independently associated with elevated KL-6 levels. Results: A total of 112 patients were included; 72.3% were women, with a median age of 70 years (IQR 63–77). The most frequent underlying diseases were systemic sclerosis (30.4%), rheumatoid arthritis (25.9%), and inflammatory myopathy (14.3%). Median KL-6 concentration was 770.5 U/mL (IQR 437.3–1148.5). Patients with FVC < 80% predicted and DLCO < 60% predicted had significantly higher KL-6 levels than those with better lung function (p = 0.001 and p = 0.004, respectively). KL-6 levels correlated inversely with DLCO (% predicted) (ρ = −0.388, p < 0.001) and FVC (% predicted) (ρ = −0.328, p < 0.001) but not with the presence of radiological fibrosis. In the multivariable analysis, lower DLCO (% predicted) (OR 0.919, 95% CI 0.884–0.955; p < 0.001) and older age (OR 1.063, 95% CI 1.014–1.115; p = 0.012) were independently associated with elevated KL-6 levels. Conclusions: Elevated serum KL-6 concentrations were associated with impaired gas transfer as measured by DLCO % predicted in this cross-sectional cohort. Longitudinal studies are required to determine whether KL-6 can predict functional decline, disease progression, or clinical outcomes. Full article

Interstitial lung disease (ILD) is a frequent manifestation and a leading cause of morbidity and mortality in idiopathic inflammatory myopathies (IIM), particularly in antisynthetase syndrome (ASyS) and anti-melanoma differentiation-associated protein 5 (MDA5) dermatomyositis. Although these disorders share common features of interstitial lung diseases, they differ substantially in pathogenesis, clinical phenotype, prognosis, and therapeutic response. There is also variability amongst the different subtypes of IIM-ILD. Recognition of these distinctions is essential for accurate diagnosis and treatment; delays in care, especially in cases of rapidly progressive ILD (RP-ILD), can be associated with high mortality. This review focuses on ILD in IIM, focusing on ASyS and anti-MDA5 dermatomyositis, highlighting similarities and key differences in disease mechanisms, clinical presentation, diagnostic evaluation, prognostic biomarkers, and management strategies. Full article

Background and Objectives: Interstitial lung disease (ILD) is an uncommon but clinically important manifestation of systemic lupus erythematosus (SLE). We aimed to identify factors associated with SLE–ILD, evaluate factors associated with clinical outcomes in established disease, and quantitatively synthesize comparable data. Materials and Methods: PubMed, Web of Science, Scopus, and the Cochrane Central Register of Controlled Trials were searched from inception through July 2026. English-language observational studies of adults with SLE reporting factors associated with ILD occurrence or outcomes in established SLE–ILD were eligible. Random-effects meta-analyses were conducted when at least three studies reported comparable data. Results: Eight observational studies were included. Across five studies, patients with SLE–ILD were older than those without ILD (mean difference 8.49 years, 95% confidence interval [CI] 5.52–11.46; p < 0.0001; I² = 66.9%). Across three studies, SLE–ILD was associated with higher odds of Raynaud phenomenon (odds ratio, 3.01; 95% CI, 1.49–6.09; p = 0.0022; I² = 28.8%). Other study-level associations included smoking, serositis, features of overlap connective tissue diseases, selected autoantibodies, and Krebs von den Lungen-6 (KL-6). In established SLE–ILD, baseline forced vital capacity and cohort-specific clinical and imaging features were associated with outcomes, while population-based cohorts linked ILD with increased mortality. Conclusions: Older age and Raynaud phenomenon were the factors most consistently associated with SLE–ILD across the available comparative studies. Because most included studies were observational, these findings should be interpreted as associations rather than evidence of causality. Prognostic evidence remains limited and heterogeneous. Full article

Background and Objectives: Antibody–drug conjugates (ADCs) have become a major therapeutic platform in breast cancer and other solid tumors. Trastuzumab deruxtecan (T-DXd), trastuzumab emtansine (T-DM1), and sacituzumab govitecan (SG) differ substantially in antibody target, linker, payload, drug-to-antibody ratio, and bystander effect, resulting in heterogeneous pulmonary and cardiac toxicity profiles. This narrative review critically compares interstitial lung disease (ILD)/pneumonitis and cardiotoxicity associated with these three agents, aiming to prevent inappropriate extrapolation of toxicity algorithms and to provide a practical, agent-specific framework for multidisciplinary care. Materials and Methods: A targeted narrative search of PubMed/MEDLINE, Google Scholar, ClinicalTrials.gov, regulatory product information, and oncology/cardio-oncology guidance was performed and updated on 24 August 2026. Priority was given to regulatory documents, pivotal trials, pooled safety analyses, real-world cohorts, systematic reviews, and multidisciplinary recommendations. Pharmacovigilance data and case reports were included only to characterize rare events. Results: T-DXd is associated with a clinically important ILD/pneumonitis risk (approximately 12–15% in pooled analyses), predominantly grade 1–2 but occasionally fatal, requiring proactive surveillance, immediate interruption for suspected disease, and grade-directed corticosteroid therapy. T-DM1 shows a low but established pneumonitis incidence of approximately 1%, with permanent discontinuation recommended upon diagnosis. SG-related pneumonitis is rare and incompletely defined, without a T-DXd-like surveillance mandate. Both T-DM1 and T-DXd retain trastuzumab-derived cardiac monitoring requirements; symptomatic heart failure remains uncommon, although protocol-defined LVEF declines appear more frequent with T-DXd. SG lacks an established cardiomyopathy signal. Conclusions: Cardiopulmonary toxicity of ADCs is agent-specific rather than a class effect. Monitoring intensity, diagnostic thresholds, and management pathways must be tailored to the individual drug, regimen, indication, dose, patient comorbidity, and prior therapy. Close collaboration among oncology, radiology, pulmonology, and cardio-oncology is essential to preserve both treatment efficacy and patient safety. Full article

Background/Objectives: Fibrosing interstitial lung disease (F-ILD) is associated with progressive respiratory impairment and substantial symptom burden. Diaphragmatic ultrasound (DUS) is a non-invasive method for assessing diaphragmatic structure and function, but its clinical role in F-ILD remains uncertain. This systematic review evaluated the available evidence on DUS in adults with F-ILD. Methods: This systematic review was conducted and reported according to the PRISMA guidelines. MEDLINE, Embase, CINAHL, and the Cochrane Library were searched and observational studies evaluating DUS in adults with F-ILD were included. Risk of bias was assessed using the QUADAS-2, and outcome-level certainty of evidence was evaluated by GRADE framework. Results: Six cross-sectional observational studies involving 232 participants were included. Diaphragmatic excursion (DE) was assessed in all six studies, while diaphragm thickness (DT) and thickening fraction (TF) were evaluated in four. Some studies reported abnormalities in DUS parameters during deep breathing and cross-sectional associations with pulmonary function, exercise capacity, dyspnoea, or radiological severity. Substantial heterogeneity in study populations, ultrasound protocols, and outcome reporting precluded meta-analysis. The certainty of evidence was very low. Conclusions: Current evidence suggests that DUS may detect diaphragmatic abnormalities in patients with F-ILD and may have future complementary value alongside established clinical assessments. However, the evidence is limited, heterogeneous, and of very low certainty and does not establish diagnostic accuracy, prognostic value, or usefulness for longitudinal monitoring. Accordingly, DUS cannot currently be recommended for routine clinical implementation in F-ILD, and prospective longitudinal validation is required. Full article

Systemic sclerosis-associated interstitial lung disease (SSc-ILD) is the leading cause of mortality in patients with systemic sclerosis and a major clinical challenge due to its heterogeneous presentation and variable disease course. Reliable biomarkers may improve disease assessment, risk stratification, and therapeutic decision-making. This narrative review summarizes current evidence on established and emerging serum and molecular biomarkers in SSc-ILD and their potential clinical applications. Recent advances have shifted the focus from single-marker assessment toward integrated biomarker profiling, reflecting the complex pathogenesis of pulmonary fibrosis. KL-6 and surfactant protein D (SP-D) have been associated with pulmonary involvement and radiographic features of SSc-ILD. Inflammatory mediators, including interleukin-6 (IL-6), and autoantibodies such as anti-topoisomerase I (anti-Scl-70) have been associated with disease severity and an increased risk of pulmonary progression. Emerging biomarkers related to epithelial injury, extracellular matrix remodelling, and vascular dysfunction may provide additional insights into the biological mechanisms underlying SSc-ILD. Current evidence highlights the potential of circulating and molecular biomarkers to refine risk stratification and prognostic assessment in SSc-ILD. Prospective validation and methodological standardization remain necessary to determine their clinical utility and potential integration into personalized disease management. Full article

Pulmonary involvement in primary Sjögren’s syndrome (pSS) is common and exhibits significant clinical heterogeneity, particularly in cases where interstitial lung disease (pSS-ILD) develops. Reported variability in prevalence, radiologic phenotypes, and clinical outcomes indicates both underlying biological diversity and differences in classification criteria, case ascertainment, and diagnostic approaches. Pulmonary manifestations may be subclinical, and early interstitial abnormalities are frequently undetected due to the limited sensitivity of chest radiography. Presentations such as ILD-first or non-sicca onset, seronegative disease, and coexisting or mimicking conditions, including lymphoproliferative disorders and amyloidosis, increase the difficulty of diagnosis. High-resolution computed tomography (HRCT) demonstrates a wide range of patterns, including inflammatory, fibrotic, and mixed phenotypes, which often overlap and change over time. Reliance on pattern-based categorization may not adequately reflect the underlying pathobiology; for example, those with usual interstitial pneumonia (UIP)-like morphology have significant prognostic implications within the pSS spectrum. A structured, multidomain assessment that integrates symptoms, pulmonary function, and HRCT findings, ideally inside a multidisciplinary discussion (MDD), may boost diagnostic accuracy and risk stratification. Nevertheless, heterogeneity in definitions and reporting continues to impede comparability across patient cohorts. Additional research is necessary to standardize phenotyping frameworks and identify predictors of disease progression to inform individualized diagnostic and management strategies. Full article

Pulmonary Hypertension (PH) in patients with Interstitial Lung Disease (ILD) is a critical, yet underrecognized, complication that affects patients’ quality of life and increases mortality. Emerging evidence further suggests that PH-ILD is not merely a consequence of hypoxia and parenchymal fibrosis, as the severity of pulmonary vascular disease often correlates poorly with the extent of fibrotic lung involvement, indicating more complex underlying pathophysiological mechanisms. Diagnosis requires a high index of suspicion when symptoms appear “disproportionate” to the degree of parenchymal lung disease. Key indicators include diffusing capacity for carbon monoxide (DLCO) < 45%, a forced vital capacity to diffusing capacity for carbon monoxide ratio (FVC/DLCO) > 1.6, and radiological findings of increased pulmonary artery diameter. While echocardiography and circulating biomarkers serve as useful screening tools, right heart catheterization remains the gold standard for definitive diagnosis. Early identification is essential for risk stratification, lung transplant evaluation, and determining eligibility for targeted pharmacological interventions, as this group of patients remains one of the most therapeutically challenging forms of pulmonary vascular disease. Ongoing research and advances in diagnostic tools are increasingly focused on refining phenotypic classification, identifying valuable biomarkers, and elucidating molecular drivers that may enable personalized treatment strategies in this heterogeneous patient group. Full article

Cardiovascular comorbidities complicate interstitial lung disease (ILD) and represent potential therapeutic targets, yet the prevalence and clinical impact of left ventricular diastolic dysfunction (LVDD) remain poorly characterized. We aimed to evaluate LVDD as a potential treatable trait within a prospective cohort. Using data from an ILD registry (January 2021–October 2024), we defined clinically relevant LVDD as echocardiographic grade 2 or 3 diastolic dysfunction. Out of 276 patients (median age 69, 44% female), 14% had LVDD, which was almost entirely in patients with fibrosis (97%, p = 0.045) and associated with lower diffusing capacity for carbon monoxide. Survival and clinical analyses restricted to the fibrotic ILD subgroup (n = 241) showed that LVDD was independently associated with a higher hazard for a combined adverse outcome of acute exacerbation, lung transplantation, or death (adjusted HR 1.82, 95% CI 1.03–3.38, p = 0.043), which persisted after 1:2 propensity score matching (HR 2.04). LVDD also independently predicted increased all-cause mortality (adjusted HR 2.10) and reduced 6-min walk distance (median 413 vs. 465 m, β = −0.14, p = 0.036). In conclusion, LVDD is prevalent in fibrotic ILD and carries significant prognostic implications. Given its objective measurability and actionable treatment pathways, LVDD represents a potentially important treatable trait requiring multi-disciplinary care. Full article

Background: Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is an important extra-articular manifestation of rheumatoid arthritis and is associated with impaired pulmonary function and poor clinical outcomes. Although interstitial abnormalities in RA-ILD have been widely studied, airway involvement, particularly small airway dysfunction, has received less attention. This study aimed to evaluate small airway function and impulse oscillometry parameters in patients with RA-ILD and to explore their potential associations with disease severity. Methods: This is a hospital-based cross-sectional comparative observational study using retrospectively collected clinical data. The patients with RA-ILD included in this study were treated at Beijing Jishuitan Hospital, Capital Medical University, between January 2021 and December 2025. Age- and sex-matched healthy individuals without pulmonary disease were included as controls. Clinical data, high-resolution computed tomography (HRCT) findings, pulmonary function parameters, and impulse oscillometry indices were collected. Small airway function was assessed using MEF25–75%, MEF50%, and MEF25%. Disease severity was evaluated using HRCT visual scores, the gender–age–physiology (GAP) score, and the composite physiologic index (CPI). Subgroup analyses were performed according to the presence of small airway dysfunction, HRCT subtype, and history of RA-related joint surgery. Correlations between airway function parameters and disease severity indices were analyzed. Multiple linear regression analyses were performed. Results: A total of 255 patients with RA-ILD were included, including 85 men (33.3%), with a mean age of 67.53 years. Compared with controls, patients with RA-ILD had significantly lower BMI, FVC%, TLC%, and DLCO% (all p < 0.05). Small airway function parameters, including MEF25–75%, MEF50%, and MEF25%, were significantly reduced in the RA-ILD group. Impulse oscillometry showed significantly higher Z5, R5–R20, R5/R20, and Fres, and significantly lower X5 in patients with RA-ILD compared with controls. Patients with RA-ILD and small airway dysfunction had lower FVC% than those without small airway dysfunction (87.7% vs. 95.46%, p = 0.015), and their GAP scores tended to be higher, although the difference did not reach statistical significance (2.59 vs. 1.79, p = 0.055). Among different ILD subtypes, only MEF50% differed significantly among the UIP, NSIP, and other-pattern groups. No significant differences in airway function or disease severity were observed between patients with and without a history of RA-related joint surgery. Correlation analysis showed that MEF25–75%, MEF50%, and MEF25% were negatively correlated with GAP score and positively correlated with FVC%. MEF25–75% and MEF50% were also positively correlated with DLCO%. Conclusions: In this study, patients with RA-ILD showed evidence of small airway dysfunction, with altered impulse oscillometry parameters suggesting increased airway resistance and reduced airway compliance. Small airway function parameters were associated with FVC% and GAP score, indicating that small airway dysfunction may be related to disease severity in RA-ILD. Full article

Background/Objectives: The diagnosis of interstitial lung disease (ILD) is challenging and frequently delayed. Clinically accessible and minimally invasive diagnostic tools are needed to expedite the diagnosis of ILD while minimizing risk to patients. Fibresolve is an imaging artificial intelligence (AI) tool recently approved by the Food and Drug Administration (FDA) for use in ILD diagnosis and made available to clinicians. The objective of this study was to describe its utility in clinical practice. Methods: We conducted a prospective, observational study of patients across the United States (US) in whom Fibresolve was utilized during routine clinical practice between July 2024 and June 2026. Information on patient demographics, Fibresolve test results (positive = suggestive of idiopathic pulmonary fibrosis (IPF); negative = unsupportive of IPF), and disease management pre- and post-Fibresolve utilization were collected, including the use of ILD-specific pharmacotherapy and planned and/or completed invasive diagnostic procedures. Results: There were 209 patients that underwent evaluation with Fibresolve across 47 medical centers. Of those, 16 were academic centers (n = 57 patients), and 31 were community-based (n = 152 patients). Fibresolve was positive in 89/209 (42.6%) patients. The percentage of patients receiving ILD-specific pharmacotherapy increased significantly following Fibresolve utilization (12.5% to 44.4%, p < 0.001). Pre-Fibresolve, 59/154 (38.3%) patients had an invasive diagnostic procedure planned; post-Fibresolve, only 12/77 (15.6%) patients had an invasive procedure performed (p < 0.001). Conclusions: In this real-world study evaluating the use of an FDA-authorized imaging tool for ILD diagnosis in diverse clinical practices across the US, we found that following utilization of Fibresolve, there was a statistically significant increase in the percentage of patients receiving guideline-directed therapy for ILD, and previously-planned invasive diagnostic procedures were avoided in many cases. These findings support the use of Fibresolve as an adjunct for ILD diagnosis in clinical practice. Full article

Background: Pulmonary hypertension (PH)-complicating interstitial lung disease (ILD) is a devastating condition that severely limits exercise capacity, diminishes quality of life (QOL), and ultimately determines survival. The pathophysiological assessment of ILD-PH has traditionally focused on right ventricular (RV) parameters reflecting RV pressure overload and dysfunction. However, under extreme RV pressure overload where blood supply to the left heart is severely restricted, the prognostic role of left ventricular (LV) function—which is ultimately responsible for maintaining systemic cardiac output—remains poorly understood. This study aimed to comprehensively evaluate the hemodynamics of ILD patients using non-invasive transthoracic echocardiography, to determine the prognostic importance of LV functional parameters, particularly left ventricular ejection fraction (LVEF). Methods: This single-center, retrospective, observational study included 415 ILD patients diagnosed and treated at the Kanagawa Cardiovascular Respiratory Center. All patients underwent transthoracic echocardiography at diagnosis, from which parameters such as estimated right ventricular systolic pressure (RVSP), tissue Doppler-derived Average e’, and LVEF were obtained. A multivariable Cox proportional hazards model was applied to evaluate the association between these echocardiographic parameters and all-cause mortality. To account for the prognostic impact of the underlying disease, we conducted a stratified analysis of idiopathic pulmonary fibrosis (IPF) and non-IPF cohorts. Furthermore, to evaluate LV function under the most severe hemodynamic compromise, a subgroup analysis was restricted to IPF patients with elevated RVSP (≥median). Results: During a median follow-up of 27.2 months, 75 (18.1%) of the 415 patients died. In the multivariable Cox analysis of the overall cohort, a decreased Average e’ (HR 0.861, p = 0.0038) emerged as a strong independent predictor of poor prognosis. Stratified analysis revealed that in the non-IPF group (n = 208, 15 events), none of the variables achieved statistical significance. Conversely, in the IPF group (N = 207, 60 events), both LV diastolic function (Average e’, p = 0.0199) and LV systolic function (LVEF, HR 0.969, 95% CI 0.940–0.998, p = 0.0305) were extracted as significant prognostic predictors. Most notably, in the stepwise multivariable model restricted to the “IPF with high RVSP” subgroup (N = 104), the prognostic significance of diastolic function (Average e’) was lost (p = 0.4577), whereas LVEF (HR 0.965, 95% CI 0.936–0.995, p = 0.0229) emerged as the sole independent predictor of mortality. Conclusions: In the overall ILD-PH cohort, reduced LV diastolic function (Average e’) is a strong independent predictor of mortality. While elevated RVSP and low BMI showed a trend toward worsening prognosis, they were not statistically significant in multivariable analysis. The prognostic contribution of LV function is primarily driven by the IPF patient group, which has an inherently poor prognosis. Furthermore, in the severe subgroup of IPF patients heavily burdened by right heart overload, LV pump function (LVEF) becomes an independent, critical determinant of ultimate survival. Therefore, routine measurement and careful monitoring of the universal parameter LVEF are of paramount importance for the risk stratification of high-risk patients under such complex hemodynamics. Full article

Low-density granulocytes (LDGs) have been implicated in the pathogenesis of several autoimmune diseases, yet their role in Sjögren’s disease (SjD) remains poorly understood. We enrolled 90 SjD patients and 30 healthy controls (HCs) and identified LDGs as CD14^−/lowCD15⁺ cells by flow cytometry, with intracellular interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) staining, and further analyzed CD16 as a maturation marker in LDGs and T helper 17 (Th17) cell frequency. LDG percentages were significantly elevated in active SjD compared with inactive patients (p < 0.001) and HCs (p < 0.0001), and correlated positively with EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI) (r = 0.355, p = 0.0006), erythrocyte sedimentation rate (ESR) (r = 0.325, p = 0.0061), γ-globulin (r = 0.334, p = 0.0177), and Th17 frequency (r = 0.537, p = 0.0068). LDG expansion was accompanied by enrichment of immature CD16^−/low cells (r = −0.798, p = 0.0100). Patients with renal or pulmonary involvement showed higher LDG levels (p = 0.0004), and in SjD -associated interstitial lung disease (SjD-ILD) patients, LDG percentage showed a positive but non-significant trend with serum Krebs von den Lungen-6 (KL-6) levels (r = 0.497, p = 0.102). LDG levels decreased following treatment in longitudinally followed patients, and LDGs from active patients exhibited higher IL-6 and TNF-α production ratios relative to monocytes than those from inactive patients. Stratification by LDG levels revealed significant associations with disease activity, laboratory parameters, and organ involvement. These findings suggest that LDGs are associated with disease activity and organ involvement, may serve as potential biomarkers, and may contribute to the pathogenesis of SjD. Full article

Interstitial lung diseases (ILDs) comprise a heterogeneous group of pulmonary disorders associated with substantial morbidity and mortality. We examined mortality attributed to selected J84-coded ILDs in the United States from 1999 to 2024 using CDC WONDER underlying-cause-of-death data. Age-adjusted mortality rates (AAMRs) per 100,000 population were standardized to the 2000 U.S. population and stratified by sex and race. Joinpoint regression was used to identify changes in temporal slope and estimate annual percent change (APC), average annual percent change (AAPC), 95% confidence intervals (CIs), and p-values. After the removal of overlapping years between the CDC WONDER database series, 444,573 unique deaths occurred. Annual deaths increased from 11,358 in 1999 to 22,849 in 2024, while AAMR increased from 4.2 to 5.1 per 100,000. Overall, AAMR increased during 1999–2004 (APC 2.32%, 95% CI 1.39–3.26; p < 0.001) and more slowly during 2004–2024 (APC 0.36%, 95% CI 0.16–0.56; p = 0.001), with an overall AAPC of 0.75% (95% CI 0.60–0.90; p < 0.001). Male AAMRs remained higher than female AAMRs, while race-specific trends were heterogeneous. No temporal reduction in population mortality coincided with the introduction of antifibrotic therapies; however, this ecological analysis cannot evaluate treatment effectiveness or individual treatment exposure. Full article