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.

Abstract SARS-CoV-2 infection triggers an acute reaction that can severely impair lung function. However, the underlying molecular processes are poorly understood. Our findings showed that the pM115T polymorphism of TROP1/EPCAM associates with COVID-19 severity. The p.M115T polymorphism of TROP1/EPCAM gene had been associated with higher frequency of early-onset breast cancer. However, the functional role of Thr115 Trop-1/EpCAM remained essentially unknown. We explored whether the Thr115 Trop-1/EpCAM acts as a driver of cell proliferation and whether this can play a role in lung pathology / lesion repair in COVID-19 patients. TROP1/EPCAM knockout embryonic stem cells showed altered proliferation. The Trop-1/EpCAM Thr115 allele was found to drive hyperproliferative capacity in murine fibrosarcoma cells, whereas the Met115 allele did not. A corresponding role was assessed in human colon cancer cells, through CRISPR-Cas9 ablation of the endogenous TROP1/EPCAM and comparative transfection of Trop-1/EpCAM Thr115 or Met115 alleles. The Trop-1/EpCAM Thr115 was shown to induce colon cancer cell hyperproliferation, whereas the Met115 allele was devoid of cell growth-driving capacity. Trop-1/EpCAM Thr115 was correspondingly shown to drive the main pathological mechanisms that lead to oxygen-exchange impairment in COVID-19. Morphometric analysis of autoptic lung samples, immunohistochemistry analysis for Trop-1/EpCAM expression, Ki67 proliferation index and comparative computational image analysis were utilized to analyze SARS-CoV-2-infected lungs at autopsy. This showed hyperproliferation of Thr115 Trop-1/EpCAM+ epithelial cells over the alveolar epithelium damaged by the infection. This correlated with Thr115 Trop-1/EpCAM+ inflammatory cells hyperproliferation and alveolar hyaline membrane formation. These multi-layered barriers were computed to reduce oxygen diffusion by up to 100-fold versus normal alveolar structures, with a critical pathological impact. Our findings identify a novel mechanism of induction of cancer cell proliferation by a polymorphic, wild-type Trop-1/EpCAM. A corresponding process was shown to operate in COVID-19 patients, causing an aberrant lung repair, via Trop-1/EpCAM Thr115-induced cell overproliferation. These findings indicate unexpected parallels between inflammation-driven wound-repair in the lungs and cancer cell hyperproliferation as driven by via Trop-1/EpCAM Thr115. Novel diagnostic/ prognostic/ therapeutic opportunities are suggested in Thr115 Trop-1/EpCAM+ COVID-19 patients, and in Thr115 Trop-1/EpCAM+ cancer patients. Acknowledgments: Grant PNRR - Tuscany Health Ecosystem (THE), Next Generation EU, Missione 4, Componente 2, Inv. 1.5, CUP B63C22000680007. Citation Format: Saverio Alberti, Milena Baldassarri, Marco Trerotola, Giulia Brunelli, Laura Bergantini, Giulia Benedetta tella, Rollo, Emanuela Guerra, Ludovica martina ceci, Pantalone, Elena Bargagli, Rossano Lattanzio, Antonino Moschella, Federica M. Previtera, Cristiana Bellan, Nicola La Francesca, Cristoforo Pomara, Network for Italian Genomes, GEN-COVID Multicenter Study, Alessandra Renieri, Chiara Fallerini. Trop-1/EpCAM Thr115 is a novel inducer of cancer cell proliferation and drives hyperproliferative lung damage in COVID-19 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 3335.

BackgroundLung donors are increasingly older and marginal. Polytrauma donors (PD) represent a potentially valuable resource due to their younger age, although trauma-related lung injury raises concerns regarding graft quality. This study aimed to evaluate early and mid-term outcomes after lung transplantation using lungs from PDs compared with non-polytrauma donors (NPD).MethodsWe retrospectively analyzed 125 lung transplant recipients from brain-dead donors between January 2013 and June 2024. Perioperative outcomes, primary graft dysfunction (PGD), and pulmonary function at 1, 3, and 6 months were compared between PD (n = 36) and NPD (n = 89) groups. To account for baseline differences, a 1:1 propensity score matching (PSM) was performed based on donor age, recipient age, and ischemic time.ResultsIn the overall cohort, PDs were younger and more frequently male, with a higher prevalence of pulmonary contusions. Early postoperative outcomes, including PGD, ICU stay, and perioperative complications, were comparable between groups. At 6 months, overall survival was higher in the PD group (91.7 vs. 75.3%, p = 0.048). After PSM, no significant differences were observed in survival (p = 0.66), perioperative outcomes, or pulmonary function. Functional recovery and CLAD rates were similar between groups across all time points.ConclusionsLung transplantation using grafts from polytrauma donors is not associated with worse perioperative or mid-term outcomes. After adjustment for baseline differences, outcomes were comparable to those from non-polytrauma donors, supporting the safe and selective use of these grafts as a strategy to expand the donor pool.

Introduction: Sarcoidosis is a systemic granulomatous disorder classified among interstitial lung diseases (ILDs). While the lungs and intrathoracic lymph nodes are most affected, the disease can involve multiple organs. The heterogeneity of clinical presentation arises from complex interactions between environmental exposures and immune responses in genetically susceptible individuals. Sex-dependent genetic variations are associated with differences in phenotype and organ localization. Gender-related factors also influence the impact of sarcoidosis on quality of life and health perception, contributing to variability in disease burden and outcomes. Aim of the study: to provide an overview of sex- and gender-related differences in sarcoidosis, focusing on pathophysiological and clinical implications. Material and Methods: The systematic search was conducted on Medline database through Pubmed search engine. We included all clinical studies from 1992 to the present, and imposed language restrictions, accepting only English publications. Case reports, reviews, and pre-print studies were excluded. Results: A total of 35 studies were included. Sex differences significantly influenced both age of onset and clinical presentation of the disease. Women received a diagnosis of sarcoidosis at an older age and exhibited more frequently extrapulmonary localizations, with predominant involvement of the eyes, skin, and extra-thoracic lymph nodes. In contrast, men more commonly presented with limited pulmonary forms. Löfgren syndrome was more prevalent among women and appeared to be associated with sex-specific genetic variations, particularly within the MHC region. Gender differences also impacted quality of life and disease perception: women reported a lower quality of life and were more susceptible to anxiety and depression throughout the disease course. Conclusions: This report confirms that clinical presentation of sarcoidosis is significantly influenced by sex and gender. The identification of sex- and gender-specific clinical patterns supports a personalized medicine framework, in which diagnostic assessment, monitoring strategies, and therapeutic approaches may be tailored according to individual biological and gender-related characteristics.

Although guidelines recommend a multidisciplinary team (MDT) approach for the diagnosis and management of systemic autoimmune rheumatic disease-associated interstitial lung disease (SARD-ILD), they lack guidance on MDT composition and function. This Delphi consensus project aimed to define a shared MDT model for managing patients with SARD-ILD. A questionnaire was circulated to an expert panel of 77 Italian pulmonologists, rheumatologists, immunologists, and internal medicine specialists, with statements rated over two voting rounds using a 5-point Likert scale. Response rates were 73

Background/Objective: Little is known about the efficacy of biologics and in particular Dupilumab in patients with severe asthma associated with COPD (SA-COPD) features. The objective of this study was to determine whether Dupilumab has similar clinical/functional efficacy in individuals with SA-COPD and in those with pure severe asthma (SA). Methods: We retrospectively selected 11 consecutive patients with SA with COPD features (smoking history of at least 15 pack/years; emphysema on chest CT scan; FEV1 < 80%; RV and TLC > 130%; DLCO < 70; salbutamol reversibility test < 12%) treated with Dupilumab for at least 1 year. These subjects were compared with 33 consecutive patients with SA alone who were also treated with the same biologic for at least 12 months. Results: FEV1 and FEF25-75 changes after treatment were 10 ± 18.3% and 18.6 ± 26.5% in the SA group, whereas they were 4.8 ± 7.6% and 7.2 ± 6.8% in individuals with SA-COPD (p = 0.909 and p = 0.102 respectively). Similarly, ACT (5.3 ± 3.1 vs. 5.6 ± 3.7; p = 0.783) and exacerbation changes (-2.97 ± 1.3 vs. -4 ± 4.3; p = 0.960) after Dupilumab were similar in the two groups. No differences were also found in FeNO and BEC changes (-18 ± 22 vs. -21.3 ± 21.1 ppb and -63.6 ± 415 vs. -142 ± 299 cells/µL respectively; p = 0.984 and p = 0.481). The percentages of subjects that reduced and stopped OC therapy and those that stepped down the level of ICS dose after treatment were also similar in the two populations. After adjustment for multiple confounding factors, changes in all evaluated outcomes also remained comparable between patients with SA-COPD and those with SA. Conclusions: In our experience, Dupilumab is effective both in patients with SA alone and in those with asthma-COPD overlap. We must always consider T2 inflammation in the management of such patients in order to provide the most appropriate treatment.

BACKGROUND:Clinical remission on biologic treatment has emerged as a relevant target in severe asthma management. Simple and widely available type 2 (T2) biomarkers, such as fractional exhaled nitric oxide (FeNO) and blood eosinophil count (BEC), may help stratify patients in real-world practice. OBJECTIVE:To explore whether the combined baseline assessment of FeNO and BEC is associated with clinical remission at 12 months in patients with severe eosinophilic asthma (SEA) treated with biologic therapy. METHODS:In this prospective real-world single-center study, 69 patients with severe asthma initiating benralizumab (n = 26), mepolizumab (n = 16), or dupilumab (n = 27) were enrolled. At baseline, patients were classified as dual high biomarker T2 (DHB-T2: FeNO50 ≥ 25 ppb and BEC ≥300 cells/µL) or heterogeneous/no biomarker T2 (HNB-T2: all other biomarker combinations). Clinical remission at 12 months was defined by the simultaneous fulfilment of the following criteria: absence of maintenance oral corticosteroids, zero exacerbations, FEV1 ≥ 80% predicted, and Asthma Control Test (ACT) score ≥20. RESULTS:At 12 months, 42 of 69 patients (60.8%) achieved clinical remission. DHB-T2 status was associated with a higher likelihood of remission (univariate OR 4.58, p = 0.005; multivariate OR 12.67, p = 0.002). The DHB-T2 classification showed a sensitivity of 73.33% and a specificity of 62.45% for identifying patients achieving remission. Isolated baseline elevation of either FeNO or BEC alone was not associated with clinical remission. CONCLUSIONS:In this real-world cohort of patients with severe eosinophilic asthma treated with biologics, concomitant baseline elevation of FeNO and blood eosinophils was associated with a higher likelihood of achieving clinical remission at 12 months.

Background Interstitial lung disease (ILD) is a frequent manifestation of connective tissue diseases (CTDs) and is associated with high morbidity and mortality. Clinical practice guidelines to standardise screening, diagnosis, treatment and follow-up for CTD-ILD are of high importance for optimised patient care. Methods A European Respiratory Society and European Alliance of Associations for Rheumatology task force committee, composed of pulmonologists, rheumatologists, pathologists, radiologists, methodologists and patient representatives, developed recommendations based on PICO (Patients, Intervention, Comparison, Outcomes) questions with grading of the evidence according to the GRADE (Grading of Recommendations, Assessment, Development and Evaluations) methodology and complementary narrative questions agreed on by both societies. For both PICO and narrative questions, the Evidence to Decision framework was used to formulate the recommendations. Results The task force committee concluded with recommendations for 25 PICO and 28 narrative questions, regarding ILD in the context of systemic sclerosis, rheumatoid arthritis (RA), idiopathic inflammatory myopathies, Sj & ouml;gren disease (SjD), systemic lupus erythematosus (SLE) and mixed connective tissue disease (MCTD). In four narrative questions, regarding screening and assessment of risk for ILD progression in MCTD, SjD and SLE and one PICO question regarding pirfenidone in CTD-ILD other than RA-ILD, the task force had insufficient evidence to support recommendations. Screening, diagnostic, monitoring and treatment algorithms were developed based on the recommendations and usual clinical practice. Conclusions We provide practical guidance by evidence-based recommendations to clinicians for each of the CTDs. In many cases there is low certainty or absence of evidence and we encourage further research to fill these gaps.

Natural Killer (NK) cells contribute to airway inflammation in severe eosinophilic asthma (SEA). IL-33, elevated in SEA, may modulate NK cell function, but its effects are unclear. We analyzed peripheral blood NK cell subsets from five SEA patients and five healthy controls using flow cytometry, assessing CD56/CD16-defined subsets and markers, CD57, NKG2A, CD62L, and ICAM-1, at baseline and after 72 h IL-33 stimulation. SEA patients showed reduced mature cytotoxic NK cells and altered expression of adhesion and regulatory molecules. IL-33 selectively increased ICAM-1 and NKG2A in mature NK cells, while decreasing these markers in immature subsets. These findings indicate that IL-33 differentially regulates NK-cell phenotype and function, highlighting NK cells as dynamic mediators of inflammation in SEA.

Background Acute lung allograft dysfunction (ALAD) is a recently defined post-transplant clinical entity characterized by acute, potentially reversible graft dysfunction. The aim of this study was to describe the clinical and radiological features of ALAD in which no identifiable underlying cause could be recognized, hereafter referred to as idiopathic ALAD (i-ALAD). Methods Among all bronchoscopies with bronchoalveolar lavage and transbronchial lung biopsy performed in a single-center cohort of lung transplant recipients between 2013 and 2024 (n = 497), we retrospectively identified episodes of i-ALAD. These patients were subsequently evaluated for clinical characteristics and high-resolution computed tomography (HRCT) findings. For exploratory purposes, imaging findings were compared with those of a cohort of lung transplant recipients with biopsy-proven acute cellular rejection (ACR). Results Among 158 lung transplant recipients, 20 cases of i-ALAD were identified, corresponding to an incidence of 12.4%. ALAD was reversible in most patients, although 2 progressed to chronic lung allograft dysfunction (CLAD). Six patients (30%) met criteria for baseline lung allograft dysfunction (BLAD), and 6 had a history of recurrent ACR. HRCT most frequently demonstrated bronchial wall thickening (85%), smooth interlobular septal thickening, and pulmonary micronodules (80%), with characteristic lobar distribution patterns. Compared with ACR, i-ALAD was associated with a significantly higher prevalence of bronchiectasis/bronchiolectasis, air trapping, and pleural effusion. Conclusions ALAD is a relatively frequent and potentially reversible complication after lung transplantation but may represent a risk factor for subsequent CLAD development. Distinctive HRCT features may assist in identifying ALAD of unknown cause and stratifying patients according to the risk of disease progression. Prospective, multicenter studies are warranted to validate these findings and further refine the clinical and radiological characterization of i-ALAD.

Pulmonary nodules are increasingly detected during high-resolution computed tomography (HRCT) surveillance in patients with fibrosing interstitial lung diseases (fILD). However, nodule risk stratification is challenging in fibrotic lungs, and evidence guiding clinical management remains limited. We aimed to characterize the longitudinal behaviour of HRCT-detected nodules in fILD and identify predictors of malignancy. We conducted a retrospective observational study at a tertiary ILD referral centre. All HRCT examinations performed between January 2018 and January 2022 in patients with multidisciplinary-diagnosed fILD were reviewed. Nodules (≤ 30 mm) were classified as low- or high-risk according to the 2017 Fleischner Society Guidelines. Nodules were adjudicated as malignant based on histopathology; benign nodules were defined by histological confirmation or long-term radiological stability (≥ 24 months). Clinical, functional, and radiological variables were analysed using univariate and multivariable logistic regression. Among 789 screened fILD patients, 91 (11.5

Acute cellular rejection (ACR) is a common complication after lung transplantation (LTX) and it is considered a risk factor for chronic lung allograft dysfunction (CLAD). Lung transbronchial biopsy is still the gold standard for a correct diagnosis of ACR. The aim of the present study was to evaluate the predictive role of bronchoalveolar lavage (BAL) cellular composition in combination with CT scan features for the diagnosis of ACR. We retrospectively evaluated all LTX recipients who underwent transbronchial biopsies combined with BAL procedures and CT scan at a single Institution between January 2019 and October 2024 (n = 169). ACR histological diagnosis was made according to current guidelines, BAL analysis included percentage of cellular composition, lymphocytes’ typing and microbiology. A qualitative analysis of specific CT was conducted by an expert thoracic radiologist. Among the 169 biopsies analyzed, 34

Introduction: Sarcoidosis is a systemic granulomatous disease characterized by heterogeneous clinical presentation and variable organ involvement. Beyond pulmonary manifestations, extrapulmonary disease and associated comorbidities substantially contribute to disease burden and clinical complexity. Although sex-related differences in sarcoidosis phenotype have been reported, data on sex-specific patterns of systemic comorbidities remain limited. Methods: We retrospectively analyzed 1,313 patients with sarcoidosis followed at five Italian referral centers. Systemic comorbidities, disease phenotype, and treatment exposure were systematically recorded and analyzed according to biological sex. Organ involvement was assessed using the WASOG Sarcoidosis Organ Assessment Instrument. Results: Female patients showed a significantly higher prevalence of autoimmune, bone, and psychiatric comorbidities, as well as a greater burden of extrapulmonary sarcoidosis, particularly cutaneous and ocular involvement. Extrapulmonary disease was associated with increased systemic comorbidity burden. Malignancy occurred within the broader context of systemic comorbidities, was more frequent among female patients, and was not associated with treatment exposure. Conclusion: Sarcoidosis is characterized by sex-specific patterns of systemic comorbidities and disease expression that extend beyond pulmonary involvement. These findings support the relevance of sex-aware clinical assessment and highlight the need for prospective studies to better define comorbidity trajectories and inform personalized management strategies.

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive respiratory rare disease characterized by an irreversible loss of lung function, with unknown etiology and poor prognosis. A population registry-based study was conducted to provide estimates of prevalence, incidence and survival of IPF. The study included all cases diagnosed with IPF in the years 2000–2022 and residing in Tuscany, Italy. Prevalence as of December 31, 2022, was calculated by sex and age class. Incidence was calculated across the period 2018–2022. Survival at 1, 5 and 10 years from diagnosis with 95

Background and objectiveSarcoidosis is a multisystem granulomatous disease with a variable clinical course. While many patients experience spontaneous remission, a substantial proportion develop chronic or relapsing disease requiring prolonged systemic therapy, most commonly corticosteroids. In real-world practice, treatment initiation, tapering strategies, and duration of therapy are heterogeneous, and data on the long-term impact of treatment on comorbidity burden are limited. MethodsWe conducted a retrospective, monocentric observational study including adults with sarcoidosis followed at a tertiary center from January 2010 to November 2025. Demographic, clinical, radiological and therapeutic data were extracted from records. Baseline strategies, corticosteroid exposure, and initiation of immunosuppression were recorded. Associations between treatment exposure and comorbidities were evaluated using regression. ResultsA total of 835 patients were included. At baseline, 81.8% received pharmacologic treatment, most commonly corticosteroids alone. Extrapulmonary involvement was present in 45.4% of patients and was the main determinant of treatment initiation and escalation to immunosuppressive therapy. During follow-up, 664 patients received systemic corticosteroids for a mean cumulative duration of 38.4 ± 64.3 months, and 25.9% required immunosuppressive agents, predominantly methotrexate. Hypertension and bone mineral density impairment were the most frequent comorbidities. Cumulative corticosteroid exposure, but not baseline dose, was independently associated with both hypertension and bone disease. Immunosuppressive therapy was not associated with overall comorbidity burden. ConclusionTreatment decisions were driven primarily by disease phenotype, particularly extrapulmonary involvement. Cumulative corticosteroid exposure was independently associated with hypertension and bone disease. These findings support earlier steroid-sparing strategies and the need for more standardized long-term management.

Idiopathic pulmonary fibrosis (IPF) and lung cancer (LC) are distinct pathological entities; however, growing evidence indicates that they share convergent cellular and molecular mechanisms. As central post-transcriptional regulators microRNAs (miRNAs) orchestrate critical pathogenetic processes including epithelial-mesenchymal transition (EMT), TGF-β signaling, fibroblast activation, and extracellular matrix remodeling. Circulating miRNA signatures represents a promising class of minimally invasive biomarkers for early detection, risk stratification, and disease monitoring, while emerging therapeutic strategies based on miRNA mimics or inhibitors have shown encouraging results in preclinical models. Understanding the complex interplay of miRNAs at the interface between fibrogenesis and oncogenesis may facilitate the development of novel translational approaches, ultimately improving patient outcomes in both IPF and LC. Dysregulation of specific miRNAs has been implicated in both IPF and LC, some of which with concordant expression patterns, such as miR-21,miR-155, and miR-200 promoting fibrosis and tumor progression, and others exhibiting divergent roles, including miR-204 5-p and members of the miR-20a e miR-425, exerting opposing effects in fibrotic and neoplastic contexts. By systematically integrating mechanistic and regulatory evidence, this review provides a framework for understanding miRNA dysregulation in IPF and LC, with direct implications for biomarker validation and therapeutic targeting.

Pulmonary fibrosis is a chronic respiratory disorder characterised by an overproduction and aberrant deposition of fibrotic tissue in the lungs. This narrative review focuses on the pivotal role played by epithelial alarmins, primarily thymic stromal lymphopoietin, interleukin (IL)-25 and IL-33, in the pathogenesis of idiopathic pulmonary fibrosis and connective tissue disease-associated interstitial lung disease. It considers their function as damage-associated molecular patterns and the attraction of both innate and adaptive immune cells that these patterns elicit, thereby playing a significant role in the immune response to fibrosis. Epithelial alarmins play a dynamic role in regulating fibroblast-macrophage interactions during lung injury and this process influences macrophage polarisation and drives the epithelial-mesenchymal transition. It is evident that these epithelial alarmins play a key role in activating the type 2 immune network and, given the established importance of type 2 inflammatory responses in pulmonary fibrosis, there is significant interest in the study of epithelial alarmins and their contribution to profibrotic type 2 immune responses. A deeper understanding of this area could result in the conceptualisation of new targeted therapies.

Background: Interstitial lung disease (ILD) is an increasingly recognized manifestation of ANCA-associated vasculitis (AAV) and is associated with substantial morbidity and mortality. The marked biological and clinical heterogeneity of AAV-associated ILD (AAV-ILD) poses major challenges for diagnosis, prognostic stratification, and therapeutic decision-making. Circulating biomarkers have emerged as promising tools for improving disease characterization; however, the available evidence remains limited and fragmented. Methods: We performed a scoping review to summarize the current evidence on circulating biomarkers investigated in AAV-ILD. Peer-reviewed studies evaluating biomarkers associated with ILD occurrence, disease activity, radiological progression, pulmonary function decline, mortality, or treatment response were systematically identified and qualitatively analyzed. Results: Six observational studies met the inclusion criteria, comprising four retrospective and two prospective cohorts. The identified biomarkers could be broadly classified into three biological categories: epithelial injury biomarkers (KL-6 and surfactant protein D [SP-D]), immune–fibrotic biomarkers (C-C motif chemokine ligand 2 [CCL2] and C-X-C motif chemokine ligand 6 [CXCL6]), and epithelial remodelling biomarkers (carbohydrate antigen 19-9 [CA19-9], cancer antigen 125 [CA125], and cytokeratin-19 fragment [CYFRA21-1]). KL-6 and SP-D were consistently associated with pulmonary involvement, disease activity, and relapse, whereas CCL2 and CXCL6 reflected inflammatory and profibrotic pathways linked to disease progression. Tumour-associated biomarkers were associated with radiological abnormalities and mortality,suggesting that they may reflect aberrant epithelial remodelling rather than malignancy. Across studies, circulating biomarkers showed potential utility for disease detection, prognostic stratification, longitudinal monitoring, and therapeutic guidance. However, the current evidence is limited by small sample sizes, retrospective study designs, and substantial clinical heterogeneity. Conclusions: Circulating biomarkers represent a promising approach for improving the biological characterization of AAV-ILD and may facilitate more personalized management strategies by distinguishing inflammatory from fibrotic disease phenotypes. Prospective multicentre studies with independent validation cohorts are required before biomarker-guided management can be implemented in routine clinical practice.