BACKGROUND AND AIM:Our study aimed to determine the in-hospital mortality rate among granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) hospitalizations complicated with acute respiratory failure (ARF) in the US and determine prognostic factors during hospitalization. METHOD:We performed a retrospective cohort analysis utilizing the National In-patient Sample (NIS) database to identify hospitalizations of patients with GPA or MPA associated with ARF from 2016 to 2021. The outcomes included in-hospital mortality, requirement of invasive procedures, and hospital length of stay. Univariable and multivariable analysis were used to identify prognostic factors associated with in-hospital mortality. RESULTS:We identified 21,430 weighted (4,283 unweighted) hospitalizations with diagnosis of GPA or MPA associated with ARF in the United States from 2016 to 2021. 78.3% of those were diagnosed with GPA, 19.2% with MPA, and 2.5% with both ICD-10 codes. The mean age was 63.7 years, 53.6% were female, and 73.3% were White. The rate of hemodialysis was 21.5%, plasmapheresis 7.4%, and extracorporeal membrane oxygenation in 0.5% of hospitalizations. The overall in-hospital mortality was 15.4%, compared to 35.9% in the subgroup requiring invasive mechanical ventilation (IMV). Independent prognostic factors associated with increased in-hospital mortality were higher age, acute kidney injury (AKI), sepsis, requirement of non-invasive mechanical ventilation, interstitial lung disease (ILD), history of stroke, shock, and requirement of IMV. CONCLUSION:GPA or MPA hospitalizations complicated with ARF were found to be associated with a high in-hospital mortality rate. At hospital-level prognostication assessment, we found that higher age, AKI, sepsis, shock, history of ILD, history of stroke, and requirement of mechanical ventilation were independently associated with increased in-hospital mortality.
BACKGROUND AND AIM:Hypersensitivity pneumonitis (HP) is a complex, immüne mediated interstitial lung disease in which accurate diagnosis and long term management require integration of clinical, radiologic, and exposure-related information. Patients increasingly use artificial intelligence (AI) based chatbots to obtain disease related information; however, the quality, readability, and patient usability of such content remain unclear. This study aimed to evaluate the quality, reliability, readability, and patient-centered usability of AI chatbot generated information on HP. MATERIALS AND METHODS:Using Google Trends, we identified four of the most frequently searched patient-oriented questions regarding HP: (1) What is HP and what causes it? (2) What are the clinical features of HP? (3) How is HP treated? (4) How is HP diagnosed? These questions were submitted verbatim to eight AI chatbots (ChatGPT-5.1, Claude 3, Microsoft Copilot, DeepSeek V3, Gemini Pro, Grok 4, Kimi K2, Perplexity AI). A total of 32 responses were independently evaluated in a blinded fashion by four pulmonology professors specializing in interstitial lung diseases. Content quality and reliability were assessed using DISCERN; understandability and actionability with PEMAT-P; global written readability with the Written Readability Rating (WRR); and structural readability with the Flesch-Kincaid Grade Level (FKGL). RESULTS:All chatbot outputs required advanced literacy, with FKGL scores ranging from 20.17 to 29.07 and a mean of approximately 24-25, indicating college or postgraduate reading level. No chatbot produced content within the recommended patient-appropriate range (FKGL ≤ 8). WRR scores declined with increasing clinical complexity, from 67.85 for definitional content (Q1) to 51.227 for diagnostic explanations (Q4). DISCERN scores varied substantially across models (35.001-57.103), with most chatbots falling into the "fair-good" range, reflecting partially reliable but incomplete information. [..] Conclusion: AI chatbots can generate clinically rich explanations of HP but currently produce content that is too complex and insufficiently actionable for most patients. [..].
BACKGROUND AND AIM:We present a case of fast-growing, recurrent orbital mass which was ultimately diagnosed as sarcoidosis in a patient who lacked systemic symptoms. METHODS:A case report was conducted. RESULTS:A 58-year-old woman from Pakistan presented with a ortbial mass that is hyperintense orbital mass on MRI. Excisional biopsy and pathology revealed non-necrotizing granulomatous inflammation. Negative AFB culture, GMS, and flow cytometry ruled out TB and lymphoma. Chest X-ray was unremarkable. ACE and Lysozyme levels were marginally elevated. She presented with symptomatic recurrence of mass requiring repeat excision. Chest CT confirmed the presence of pulmonary nodules and hilar lymphadenopathy. She was started on corticosteroids and methotrexate with resolution of local inflammation and residual mass effect. CONCLUSIONS:Chest CT has higher sensitivity to aid definitive diagnosis in the setting of negative chest X-ray. Surgical treatment may be useful for diagnostic and therapeutic purposes. Subsequent long-term treatment with corticosteroids and antimetabolites has shown great response.
Background and aim: Idiopathic Pulmonary Fibrosis (IPF) is a progressive interstitial lung disease characterized by aberrant extracellular matrix remodeling. While type I and III collagens are known contributors, the broader transcriptional landscape of diverse collagen genes in IPF fibroblasts and their potential associations with clinical outcomes remain incompletely understood. This study aimed to comprehensively characterize gene expression of collagen genes in IPF fibroblasts and to explore its relationship with patient survival. Methods: RNA sequencing was conducted on primary lung fibroblasts from 33 IPF patients and 10 non-fibrotic controls. Differential expression of collagen genes was analyzed using EdgeR's exact test, with significance defined as false discovery rate-adjusted p < 0.05. Association with mortality was assessed using Cox regression analysis. Results: Among 17 collagen genes, 14 genes - including COL1A1, COL1A2, COL3A1, COL4A4, COL4A5, COL4A6, COL5A2, COL6A6, COL8A1, COL11A1, COL14A1, COL18A1, COL24A1, and COL27A1 - were significantly upregulated in IPF fibroblasts, while COL5A3, COL13A1, and COL16A1 were downregulated. COL3A1, COL4A4, and COL24A1 were associated with reduced survival in both Cox regression analysis and Kaplan-Meier plots. Among them, COL4A4 remained association with mortality in multivariable Cox model. Conclusions: This study delineates fibroblast-specific dysregulation across multiple collagen families in IPF, providing mechanistic insight into extracellular matrix remodeling. Although COL4A4 remained associated with mortality in multivariable Cox models, this finding should be interpreted as exploratory, given the limited number of events and the absence of experimental validation. Overall, our results highlight collagen transcript signatures as hypothesis-generating markers that warrant further validation to clarify their potential clinical relevance in IPF.
Background To investigate the clinical features of anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKI) -associated interstitial lung disease (ILD), and to provide a reference for the rational use of ALK TKI. Methods Cases of ALK TKI-associated ILD before December 31, 2025 were collected by searching the database and clinical data were collected for retrospective analysis. Result Fifty patients were included, with a median age of 54.5 years (range 33, 86). The median time of ILD occurrence was 50 days (range 2, 630). Dyspnea (56.0%), hypoxemia (38.0%), cough (36.0%) and fever (26.0%) were the main clinical symptoms, and there may also be no symptoms. Computed tomography mainly showed ground-glass opacities (98.0%). After the patients discontinued ALK-TKI and received systemic steroid treatment, 90.0% of the patients had symptom relief and improved imaging, and 10.0% of the patients died. Conclusion ILD is a rare and fatal adverse event of ALK-TKI. The possibility of ILD should be considered if dyspnea, hypoxemia, and cough occur during ALK-TKI use. After ILD recovery, patients could switch to the same ALK-TKI or another ALK-TKI under the protection of glucocorticoid.
BACKGROUND:American Thoracic Society guidelines suggest serum specific IgG (sIgG) testing targeting potential antigens associated with hypersensitivity pneumonitis (HP). The diagnostic cutoffs of mold-sIgGs remain undefined and their performance based on pre- and post-test probabilities remain untested. METHODS:We conducted a diagnostic test accuracy study using a case-control design. We enrolled subjects with HP (cases), other interstitial lung diseases (ILDs, diseased controls), and healthy controls with/without mold exposure. We measured sIgG against Aspergillus fumigatus, Penicillium chrysogenum, Cladosporium herbarum, and Micropolyspora faeni using an automated, fluorescent enzyme immunoassay. Cutoffs were derived from the 95th percentile values among non-exposed healthy controls for individual sIgGs and Youden's J-statistic for pooled sIgG (sum of four levels). We evaluated the performance characteristics of sIgG levels for HP diagnosis among subjects with ILDs. RESULTS:We included 219 subjects (mean age, 51.4 years; 50.2% women): 105 HP, 64 non-HP ILDs, and 50 healthy controls (25 non-exposed, 25 exposed). Cutoffs (mgA/L) were 33, 22, 34, 8, and 53, for A. fumigatus, P. chrysogenum, C. herbarum, M. faeni, and pooled sIgG levels, respectively. The 4-mold panel (positive if any sIgG exceeded cutoff) showed 57.1% sensitivity and 78.1% specificity for HP diagnosis among ILD subjects. The pooled sIgG test (positive likelihood ratio, 3.29; negative likelihood ratio, 0.51) shifted post-test probability of HP diagnosis from 44% (for a negative test) to 84% (for a positive test). CONCLUSION:Mold-specific IgGs, when used at our proposed cutoffs, significantly alter post-test diagnostic probabilities; thus, can be used as an adjunct in multi-component HP diagnosis.
BACKGROUND AND AIM:Sarcoidosis-associated fatigue (SAF) occurs in approximately 30% to 90% of patients. While previous reviews examined select medications, these omitted nonpharmacological and emerging treatments that could significantly improve fatigue for individuals with sarcoidosis. Limited guidance exists for excluding alternative causes of fatigue and selecting between treatment options for these patients. This narrative review synthesized pharmacological and nonpharmacological interventions for SAF and interpreted evidence strength to guide clinical decision-making. METHODS:PubMed was queried in December 2025 for clinical trials, reviews, and meta-analyses published within the last 10 years. This yielded 41 results which were supplemented by manual review of bibliographies, clinical guidelines, and a search of the Cochrane Library. Evidence was interpreted and analyzed for quality using a modified GRADE-informed approach. RESULTS:Treatment of active disease with prednisone or methotrexate improves systemic inflammation but may paradoxically worsen fatigue with chronic use. Stimulants (e.g., dexmethylphenidate, armodafinil) display low-quality evidence for improving SAF and side effects may be prohibitive for some patients. TNF-α inhibitors (e.g., infliximab) have very low-quality evidence with few studies and negative findings. Pulmonary rehabilitation and exercise training show low-to-moderate quality evidence with few adverse effects but lack specific implementation protocols. CONCLUSIONS:Diagnosis of SAF requires exclusion of alternative causes which may be challenging. Active disease should be treated appropriately while monitoring for adverse effects. Despite low-to-moderate quality evidence for most interventions, nonpharmacological approaches (e.g., pulmonary rehabilitation, exercise) are recommended as first-line therapy given favorable risk-benefit profiles. Larger, well-designed RCTs are needed given the substantial disease burden.
BACKGROUND AND AIM:Hypersensitivity pneumonitis (HP) is a complex interstitial lung disease with heterogeneous presentations. In some patients, radiological coexistence of emphysema and fibrosis creates a distinct functional phenotype that complicates disease progression and management. To evaluate the functional impact of combined emphysema and fibrosis in HP patients and to identify clinical predictors associated with this dual pathology. METHODS:We retrospectively analyzed 215 patients diagnosed with HP between 2010 and 2023. Demographic data, exposure history, radiological findings (HRCT), and pulmonary function parameters (FVC, DLCO, FEV₁) were collected. Patients were classified into three groups: fibrotic HP, non-fibrotic HP, and combined emphysema with fibrosis (CE-HP). Statistical analyses were performed using SPSS v22.0. RESULTS:Of the 215 patients, 68 (31.6%) had fibrotic HP and 42 (19.5%) presented with CE-HP. Patients with CE-HP were significantly older (mean 66.2 ± 9.1 years) and more often male and smokers (p < 0.05). FVC and DLCO values were lower in CE-HP compared with non-fibrotic and fibrotic groups. A moderate negative correlation was found between extent of emphysema and DLCO (r = -0.56, p < 0.001). In multivariate analysis, age > 65 years, male gender, and smoking history were independent predictors of CE-HP development. CONCLUSIONS:The coexistence of emphysema and fibrosis in HP represents a distinct clinical phenotype with significant functional impairment. Recognition of this dual pathology is crucial for accurate prognostication and individualized management strategies.
BACKGROUND AND AIM:In this pragmatic, uncontrolled service evaluation in clinically stable idiopathic pulmonary fibrosis (IPF), we assessed primary service outcomes (feasibility and safety) and prespecified exploratory within-participant changes following a four-week supervised home-based tele-exercise program via the USTEP platform and a four-week detraining period. METHODS:Thirteen participants were assessed at three prespecified time points (baseline: T0; post-intervention: T1; post-detraining: T2) using the six-minute walk test (6MWT), SF-36, HADS, and pulse-respiration quotient (PRQ). Primary service outcomes were captured as session attendance/adherence and exercise-related adverse events. RESULTS:Adherence was 92% (median 11/12 sessions completed) and there were no exercise-related adverse events. The 6MWT distance increased by 8.4% from T0-T1 (Bonferroni-adjusted p=0.004, d=-1.15) but declined towards baseline at T2. SF-36 physical health scores increased at T1 (+5.2%) but decreased at T2 (Bonferroni-adjusted T1-T2 p=0.004, d=1.17). For several exploratory patient-reported outcomes (fatigue, pain and HADS), Bonferroni-adjusted comparisons were non-significant, while unadjusted testing suggested small T0-T1 changes; these are reported as exploratory signals. PRQ changed over time (χ²(2)=8.60, p=0.014), with a shift at T1 and a return to baseline at T2. CONCLUSIONS:In this small uncontrolled service evaluation, the program was feasible and safe and within-participant improvements were observed in 6MWT distance and selected patient-reported and physiological measures. These findings are exploratory and hypothesis-generating and should be confirmed in adequately powered controlled studies that include prespecified maintenance strategies.
Background: Differentiating mediastinal lymphadenopathy (LAP) due to tuberculosis, sarcoidosis, and reactive causes remains challenging because of overlapping clinical and radiological features. This study aimed to evaluate the diagnostic value of the systemic inflammation composite index (SICI), the platelet inflammation composite index (PICI), and other hematological indices for this differentiation. Methods: This retrospective study included 223 patients who underwent endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for mediastinal LAP between 2020 and 2025. Pre-procedural laboratory data were used to calculate the platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), and the newly defined SICI and PICI. Results: PLR, NLR, SII, SICI, and PICI levels were highest in the tuberculosis group and were significantly higher in patients with granulomatous LAP than in those with reactive LAP (p < 0.001 for all). In differentiating tuberculosis from sarcoidosis, a SICI cut-off value of 10966.6 yielded a sensitivity of 83% and a specificity of 63%, while a PICI cut-off value of 2.2 yielded a sensitivity of 85% and a specificity of 60%. For distinguishing granulomatous from reactive LAP, the optimal cut-off values were 77.4 for PLR (sensitivity 98%, specificity 67%), 2721.5 for SICI (sensitivity 89%, specificity 63%), and 0.69 for PICI (sensitivity 87%, specificity 61%). Conclusion: SICI and PICI, introduced for the first time in the literature, are readily available composite indices that may aid in differentiating tuberculosis-, sarcoidosis-, and reactive LAP-related mediastinal LAP.
Background and aim: Sarcoidosis is a systemic condition with various clinical manifestations including end-stage lung disease. The aim of this study was to evaluate the characteristics and outcomes of patients with sarcoidosis undergoing lung transplantation. Methods: A single center retrospective review was performed of 63 sarcoidosis patients who underwent lung transplantation between January 1, 2000 and April 30, 2025. Patients were divided into arbitrary eras by year (Era 1 2000-2007; Era 2 2007-2013; Era 3 2013-2025). Results: The median age of the cohort was 53 years, 51% were female, 79% were black, 33% had blood type A, and the median body mass index was 24.4 kg/m2 (21.3-28.2). The majority (93%) of patients had pulmonary sarcoidosis stage IV by Scadding staging, and 89% had pulmonary hypertension. Baseline median six-minute walk test distance (6MWD) was 235 m (133-306). The median FVC% was 45% (34-50), median FEV1 was 37% (26-45), median FEV1/FVC was 73% (62-83) and median DLCO% was 26% (18-32). The median mean pulmonary artery pressure (mPAP) was 35 (26-44) mmHg, and the median pulmonary vascular resistance (PVR) was 4 (3-6) Wood Units (WU). Chronic lung allograft dysfunction (CLAD) occurred in 38% of patients at a median 85 months post-transplant. Overall survival was 87.6%, 66% and 50.6% at 1, 3, and 5 years, respectively. There was no statistically significant difference in mortality across eras: era 1 vs era 3 (HR 0.888, 95% CI 0.407-1.94, p=0.766). Conclusions: Outcomes of sarcoidosis patients who undergo lung transplantation are similar to patients with other underlying diagnoses. Timely referral should be made to specialized centers.
BACKGROUND:Sarcoidosis is a multisystemic granulomatous disease that can involve the skeletal system, although bone manifestations are considered relatively uncommon and often underdiagnosed. OBJECTIVES:To describe the prevalence, clinical characteristics, and treatment outcomes of bone involvement in a large multicenter Italian cohort of patients with sarcoidosis. METHODS:This retrospective, two-center observational study included 867 patients with histologically confirmed sarcoidosis followed at two Italian referral centers (2018-2025). Bone localization was identified by imaging (PET/CT, MRI, X-ray) and/or biopsy. Clinical, functional, laboratory, and therapeutic data were collected. RESULTS:Bone involvement was found in 46 patients (5.3%), predominantly women (58.7%), with mean age at diagnosis of 49.7 ± 12.2 years. Osseous lesions were most frequently localized in the axial skeleton, particularly pelvis (54.3%) and vertebrae (52.2%). Bone sarcoidosis was significantly associated with extra-thoracic lymphadenopathy, hepatic, and splenic involvement (p < 0.001), reflecting a pattern of clustered multi-organ disease. Osteoporosis and osteopenia were present in 15.2% and 13.0% of cases, respectively. Corticosteroid monotherapy was the most common initial treatment (56.5%), while 30.4% received combination therapy with csDMARDs or biologics. At one-year PET/CT re-evaluation, 56.5% showed a reduction of SUV at bone sites, with no significant correlation between therapeutic regimen and metabolic response. CONCLUSIONS:Bone involvement in sarcoidosis, though relatively rare, represents a clinically relevant phenotype strongly associated with hepatosplenic and lymphatic disease and characterized by a preferential axial skeleton localization. Recognition of this pattern is essential for diagnosis and management. Given the retrospective design and the limited follow-up sample, these findings should be interpreted with caution. Close radiological monitoring and tailored therapeutic strategies are warranted to improve outcomes.
BACKGROUND:Sarcoidosis is a systemic granulomatous disease with heterogeneous clinical manifestations and unclear pathogenesis. Although genome-wide association studies (GWAS) have identified several immune-related loci, the functional interpretation of these signals remains limited. Integrative transcriptome-wide approaches may uncover novel susceptibility genes and provide mechanistic insights. OBJECTIVES:The primary objective of this study was to identify novel susceptibility genes for sarcoidosis and provide mechanistic insights into its pathogenesis through a comprehensive, cross-tissue transcriptome-wide approach. METHODS:We conducted a cross-tissue transcriptome-wide association study (TWAS) using the UTMOST framework, followed by single-tissue TWAS via FUSION. Candidate genes identified in both analyses were further evaluated using Multi-marker Analysis of Genomic Annotation (MAGMA), Mendelian randomization (MR), and Bayesian colocalization. Functional characterization was explored through gene-chemical-disease associations from the Comparative Toxicogenomics Database (CTD) and phenome-wide association studies (PheWAS) in the UK Biobank. RESULTS:Cross-tissue TWAS identified 48 genes. Integrative analyses prioritized four novel susceptibility genes: RNF215, PLCL1, FAM117B, and RFTN2. MR and colocalization supported causal effects of RNF215 (risk-increasing), FAM117B and RFTN2 (protective), and tissue-dependent effects for PLCL1. CTD analyses revealed interactions of these genes with environmental chemicals including bisphenol A and tetrachlorodibenzodioxin, while PheWAS demonstrated pleiotropic associations with immune, respiratory, hematological, and cardiovascular traits. CONCLUSIONS:This comprehensive integrative study identifies four biologically plausible susceptibility genes for sarcoidosis, expanding the genetic architecture of sarcoidosis and suggest potential targets for mechanistic and therapeutic investigation.
Background and aim: Sarcoidosis is a systemic inflammatory syndrome of unknown cause characterized by granulomas, heterogeneous presentation, and variable clinical course. Diagnosis is often delayed, contributing to patient distress, increased healthcare costs, and potentially worse outcomes. Prior estimates of diagnostic delays rely largely on case-based studies, which may overestimate delays by failing to account for baseline care practices and common alternative diagnoses that may resemble sarcoidosis. Methods: We conducted a retrospective population-based cohort study to characterize healthcare utilization before a sarcoidosis diagnosis and to identify risk factors associated with a diagnostic delay. Using longitudinal commercial, Medicare, and Medicaid healthcare insurance claims data from 2001-2022, we identified patients with sarcoidosis and evaluated diagnostic delay frequency, time to diagnosis, and potential missed opportunities for diagnosis. Secondary analysis compared diagnostic differences between pulmonary and cutaneous sarcoidosis. Results: 87,092 sarcoidosis cases were identified, of which 56% experienced at least one healthcare visit with a symptomatically similar diagnosis before sarcoidosis was diagnosed. The mean time to diagnosis was 44 days, defined as the interval between increased baseline healthcare utilization and a sarcoidosis diagnosis. Patients had an average of 2.5 visits prior to sarcoidosis diagnosis that represented potential missed diagnostic opportunities. Pulmonary involvement was associated with longer time to diagnosis and more missed opportunities compared to cutaneous sarcoidosis. Risk factors for delays included obesity, outpatient evaluation, weekend visits, Medicaid insurance, and treatment for symptoms commonly attributable to sarcoidosis. Diagnosis was unaffected by age,season, or rural vs urban setting. Within Medicaid, white individuals had the highest risk for a missed diagnostic opportunity, while Black individuals had the lowest. Conclusions: In this large population-based study, diagnostic delays in sarcoidosis were shorter than previously reported, yet substantial missed opportunities remain. Identifying patient-and system-level risk factors may help reduce delays, prevent disease progression, and improve outcomes in sarcoidosis.
Background and aim: There is a substantial body of literature that discusses the potential relationship between sarcopenia and sarcoidosis. This study aimed to evaluate the muscle mass of sarcoidosis patients without any treatment at the time of diagnosis using computed tomography (CT) images. Methods: This retrospective study included only female patients, as the vast majority of sarcoidosis cases in our dataset were female, and this approach allowed us to minimize gender-related confounding. The sarcoidosis group consisted of newly diagnosed, untreated female patients who underwent abdominal CT as part of their diagnostic work-up. The control group comprised female patients with a comparable age distribution to the sarcoidosis cohort, who presented to the emergency department with non-chronic, unrelated conditions and had no history of chronic illness or medication use known to affect muscle mass. Total skeletal muscle (TSM), skeletal muscle index (SMI), and psoas muscle index (PMI) at the L3 vertebral level were measured using manual segmentation. SMIbased sex-, age-, and BMI-specific thresholds from the literature were used to define sarcopenia. Results: A total of 168 female patients were evaluated. Sarcoidosis patients were significantly older and shorter than controls. TPM (p = 0.003), TSM (p = 0.027), SMI (p = 0.037), and PMI (p = 0.001) values were significantly lower in the sarcoidosis group. However, the prevalence of sarcopenia based on SMI criteria did not significantly differ between groups. Notably, significant muscle mass differences were most evident in the 50-60 age group. Conclusions: Our findings suggest that muscle loss may already be present at the time of diagnosis in female sarcoidosis patients, becoming more apparent with age. Further studies with broader populations and prospective designs are needed to clarify the association between sarcoidosis and sarcopenia.
Background and aim: Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease characterized by aberrant fibroblast activation and extracellular matrix accumulation. Although ROR2 signaling via Wnt ligands has been implicated in fibrosis, their integrated clinical relevance in IPF remains unclear. This study investigated the clinical significance of ROR2 and its ligands-WNT1, WNT5A, and WNT7A-in IPF development and prognosis. Methods: Bronchoalveolar lavage (BAL) fluid was collected from 124 IPF patients and 17 controls. Protein levels of ROR2, WNT1, WNT5A, and WNT7A were measured using ELISA. Immunofluorescence staining was performed to evaluate cellular localization. Cox proportional hazards analysis with backward elimination was used to identify mortality risk factors. Kaplan-Meier and log-rank tests were used to compare cumulative mortality between subgroups. Results: The levels of ROR2 and WNT7A were significantly higher in IPF compared to controls (p < 0.001 and p = 0.030, respectively). Among the proteins analyzed (ROR2, WNT1, WNT5A, and WNT7A), only elevated ROR2 levels were independently associated with increased mortality (hazard ratio [HR] = 2.32, p = 0.026), whereas WNT1, WNT5A, and WNT7A did not show significant associations with survival after correction for multiple comparisons using the Benjamini-Hochberg false discovery rate (FDR) method. Immunofluorescence analysis demonstrated co-localization of ROR2 with COL1A1-positive fibroblasts, as well as with WNT1, WNT5A, and WNT7A. Exploratory stratification based on combined ROR2 and WNT5A expression identified a subgroup with low ROR2 / high WNT5A levels that showed a trend toward better prognosis. Conclusion: ROR2 levels in BAL fluid are independently associated with IPF pathogenesis and prognosis, and may serve as a useful biomarker for identifying molecular endotypes and assessing clinical risk. Exploratory findings suggest that ROR2 and its ligand may modulate prognosis in a subset of patients.
BACKGROUND AND AIM:Sjögren's disease(SjD) exhibits heterogeneous clinical phenotypes influenced by age at onset. This study aimed to evaluate the impact of onset age on the clinical and serological characteristics of SjD in a Turkish cohort. METHODS:We retrospectively analyzed 411 patients diagnosed with SjD between 2013 and 2024, fulfilling the 2002 AECG or 2016 ACR/EULAR criteria. Patients were classified as young-onset (<40 years; YoSjD), adult-onset (40-60 years; AoSjD), or elderly-onset (>60 years; EoSjD). Demographic, clinical, laboratory, and treatment characteristics were compared among groups. RESULTS:The cohort comprised predominantly females (93.4%) with a median age of 55 years. RF positivity was significantly higher in EoSjS (35.5%) compared to YoSjD (27.9%) and AoSjD (19.2%, p=0.007). Inflammatory markers (ESR, CRP) were more frequently elevated in EoSjD. Interstitial lung disease (ILD) prevalence was highest in EoSjD (25.8%, p<0.05), particularly in males. Artropathy was more frequent in EoSjD (80.6%) and YoSjD (76%) than in AoSjD (64.5%, p=0.007). Anemia was more common in EoSjD (20.4%, p=0.040). Hydroxychloroquine was widely used (86.6%), with glucocorticoid and azathioprine use significantly higher in EoSjD. CONCLUSIONS:Elderly-onset SjD demonstrates a distinct phenotype characterized by higher ILD prevalence, increased RF positivity, greater inflammatory activity, and more frequent artropathy and anemia compared to younger-onset groups. These findings highlight the need for age-tailored diagnostic vigilance, proactive ILD screening, and cautious use of immunosuppressants in older patients. Prospective multicenter studies are warranted to refine management strategies in this subgroup.
