Search Results (603)

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

Telehealth has the potential to improve access to healthcare, but teleassessment usability may be influenced by contextual factors beyond technology access alone. This study investigated factors associated with teleassessment usability among individuals with interstitial lung disease (ILD) in Brazil using a convergent mixed methods design with 31 adults from four Brazilian regions. Usability was assessed with the Telehealth Usability Questionnaire (TUQ-Brazil); associations with contextual variables were examined using Spearman’s correlation. Qualitative data were obtained through semi-structured interviews and analyzed using thematic analysis. Participants generally reported acceptable usability perceptions with predominance of agreement responses; greater dispersion was observed for items related to equivalence with in-person care and video quality. Usability was significantly associated with income (rho = 0.437; p = 0.014), perceived clinical feasibility (rho = −0.397; p = 0.027), and perceived intensity of access barriers (rho = −0.428; p = 0.016). Qualitative findings identified financial constraints, digital literacy, internet stability, third-party support dependence, and absence of physical examination as key experiential factors. Teleassessment was perceived as a complement for follow-up and triage rather than a substitute for face-to-face assessment. Usability in ILD is shaped by socioeconomic, clinical, and structural factors, underscoring the need to address digital inequalities in telehealth implementation. Full article

Introduction: Patients with rheumatoid arthritis (RA) have higher risk for pneumonia, interstitial lung disease (ILD) and pulmonary fibrosis (PF). However, the association between an ICD-10-coded pneumonia event (CPE) and the incidence of ILD or PF in the RA population remains unclear. Methods: We conducted a retrospective cohort study using the TriNetX database. Patients with ICD-10 for RA aged 50 or older who had a CPE within one year of RA diagnosis (CPE cohort, n = 4553) were matched 1:1 by propensity score for key factors, including demographics, comorbidities (i.e., COPD), and medication use (DMARDs, corticosteroids) to RA patients without a CPE (Control cohort, n = 4553). Cox proportional hazard models assessed the incidence of a composite ILD outcome, PF, and secondary complications over a 4-year follow-up after the index event defined as 1-year after RA diagnosis for both cohorts. Results: The CPE cohort showed an increased risk for all outcomes. Patients with CPE had a 2.48-fold increased risk for PF (HR = 2.48; 95% CI, 1.78–3.45; p < 0.01) and a 2.87-fold increased risk for the composite ILD outcome (HR = 2.87; 95% CI, 2.18–3.80; p < 0.01). The risk of rheumatoid lung disease was 4.15 times higher (HR = 4.15; 95% CI, 2.30–7.50; p < 0.01). Furthermore, the CPE group had a higher risk for all-cause mortality (HR = 1.82; 95% CI, 1.58–2.09; p < 0.01). Conclusions: The CPE within one year of RA diagnosis is associated with an increase in subsequent ILD-coded outcomes. While this retrospective design cannot establish causality, an unspecified pneumonia code in early RA may represent an early clinical manifestation of unrecognized ILD, serving as a high-risk marker that warrants pulmonary surveillance. Full article

Pulmonary fibrosis (PF), particularly idiopathic pulmonary fibrosis (IPF), is a progressive and often fatal interstitial lung disease characterised by complex genetic and molecular heterogeneity. Traditional diagnostic approaches, which rely on clinical, radiological and histopathological assessment, are frequently insufficient to capture the underlying biological diversity of the disease. The advent of next-generation sequencing (NGS) has substantially advanced the understanding of PF by enabling comprehensive genomic and transcriptomic profiling. NGS technologies, including whole-exome sequencing (WES), whole-genome sequencing (WGS), RNA sequencing (RNA-seq), and targeted gene panels, have uncovered key genetic determinants. These include mutations in telomere-related genes (TERT, TERC, RTEL1) and surfactant-related genes (SFTPC, SFTPA2), as well as common variants like the MUC5B promoter polymorphism. These discoveries have clarified disease pathogenesis, revealed polygenic risk models, and may improve diagnostic accuracy, particularly in distinguishing overlapping interstitial lung disease (ILD) phenotypes. Beyond genetics, transcriptomic analyses have identified dysregulated pathways, including TGF-β, Wnt/β-catenin, and PI3K/Akt signalling, and have enabled the discovery of novel biomarkers for prognosis and therapeutic response. In selected clinical settings, NGS is beginning to support patient stratification and inform management decisions. Emerging applications, including liquid biopsy and integration with artificial intelligence, further expand the potential clinical utility of NGS. Despite challenges related to cost, data interpretation and standardisation, NGS represents a powerful research tool in PF. Full article

Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is one of the most severe extra-articular manifestations of rheumatoid arthritis (RA), requiring reliable biomarkers for early detection. This scoping review synthesized current evidence regarding the diagnostic performance and clinical associations of anti-mutated citrullinated vimentin (anti-MCV) antibodies in patients with RA-ILD. A comprehensive literature search was conducted across PubMed/MEDLINE, Embase, Scopus, and the Cochrane Library. Following systematic screening, two observational studies met the predefined inclusion criteria. Both included studies reported significantly higher anti-MCV positivity rates and/or serum levels in patients with RA-ILD compared with RA patients without pulmonary involvement. Specifically, one study identified an independent association between anti-MCV positivity and RA-ILD, while the other demonstrated significant correlations between anti-MCV titers and pulmonary function impairment, as well as disease activity markers. However, substantial heterogeneity was observed across the studies regarding assay platforms, positivity thresholds, and diagnostic cut-offs, which limits the direct comparability of results. While anti-MCV antibodies represent promising candidate biomarkers for RA-ILD, current evidence remains limited and is insufficient to establish definitive diagnostic, prognostic, or pathogenic significance. Consequently, larger, prospective, and multi-center studies utilizing standardized anti-MCV assay protocols are necessary to rigorously evaluate the clinical utility of these antibodies in the management of RA-ILD. Full article

Background: This study aimed to comprehensively investigate the complex association between the use of fluoroquinolone (FQ) antibiotics and cancer risk, with a specific focus on patients with interstitial lung disease (ILD)—a unique clinical population characterized by a high inflammatory burden and a high susceptibility to infections. Methods: We conducted a large-scale retrospective cohort study using a high-quality clinical database. A total of 7906 matched patients (3953 pairs) were included after propensity score matching (PSM). Three complementary statistical models were applied: the standard Cox proportional hazards model, the time-dependent Cox regression model, and the Fine–Gray competing-risks model, to provide a multidimensional assessment of cancer risk. Results: A total of 7906 matched patients (3953 pairs) were followed. After strictly defining the index date to eliminate immortal time bias, FQ exposure was associated with an increased risk of all-cause cancer in the standard Cox model (adjusted HR 1.45; 95% CI, 1.20–1.76) and the competing risk model (adjusted SHR 1.28; 95% CI, 1.06–1.55). Site-specific analyses revealed elevated risks for certain malignancies, notably prostate cancer. Importantly, when modeled as a continuous variable, the cumulative dose of fluoroquinolones showed no significant dose–response relationship with overall cancer risk (adjusted HR 0.99; 95% CI, 0.99–1.00). Conclusions: After correcting for immortal time bias, the previously hypothesized protective effect of fluoroquinolones on cancer risk was not observed. The increased risk observed in categorical models, coupled with a lack of a continuous dose–response, strongly suggests that these findings are driven by confounding by indication and reverse causation (i.e., frequent infections masking undiagnosed malignancies or reflecting severe underlying ILD), rather than a direct pharmacological effect. Full article

Aim: This study aims to analyze the self-management needs of patients with interstitial lung disease, clarify the types and characteristics of their needs, and provide a scientific basis for nursing staff to formulate personalized continuing care plans. Method: The Q-methodology was adopted in this study. Semi-structured interviews with 13 patients with ILD and systematic literature retrieval were performed to qualitatively explore and summarize patients’ authentic home self-management needs. The Q-set of representative statement items was further established based on the integrated results of interviews and literature analysis. Subsequently, another 15 patients with ILD were enrolled as the P-set to complete the Q-sort ranking of all statement items. By-person factor analysis was conducted to extract potential self-management demand patterns and refine the typology and core characteristics of patients’ self-management needs. Result: Factor analysis identified four common factors, representing four types of home self-management needs in interstitial lung disease patients. These types differ in symptom management, information preferences, and psychological rehabilitation needs, while sharing core common needs. Conclusions: Patients with interstitial lung diseases have both common and individual self-management needs, with no universal model. Nurses should develop personalized continuing care plans to improve care precision and adaptability. Full article