Interstitial Lung Disease Due to Systemic Disease (Disorder)

Connective tissue disease-associated interstitial lung disease (CTD-ILD) is a rare and complex condition that affects some individuals with autoimmune disorders such as rheumatoid arthritis (RA). It can lead to inflammation and progressive scarring of the lungs, significantly affecting quality of life and overall prognosis.1 Current clinical guidelines recommend that patients with CTD-ILD receive care at specialized academic medical centers with multi-disciplinary teams experienced in managing interstitial lung disease (ILD).2 These centers, however, are often located in urban areas, making access particularly challenging for patients living in rural and underserved regions. In rural, medically underserved areas, the nearest ILD centers can be three or more hours away, posing substantial barriers to timely, consistent, and expert care. These logistical constraints make it difficult for patients residing in rural areas to access the high-quality, specialized care required to manage CTD-ILD effectively. The Teleconsultation Approach to CTD-ILD Care Delivery in Rural Underserved Communities (TRUST Initiative) it looking to address this gap in access to specialized care. The TRUST Initiative aims to evaluate whether integrating teleconsultation into a personalized, multidisciplinary care model, through regular, structured teleconsultation visits, can enhance the quality and coordination of treatment for patients and potentially other rural underserved patient populations. This model utilizes a regional rheumatologist, a regional pulmonologist and, an interstitial lung disease (ILD) specialist at the Mayo Clinic in Rochester, Minnesota. This model seeks to overcome the geographic and logistical challenges that prevent patients from accessing specialty care. It also offers a replicable care model for managing other complex chronic diseases in underserved rural communities by leveraging collaborative care, virtual health technology, and structured communication workflows. The study will not only track clinical outcomes such as pulmonary function but also evaluate patient satisfaction, highlighting both the effectiveness and acceptability of this care model. By addressing disparities in access to specialty care, the TRUST Initiative aims to inform future healthcare delivery strategies for rare and complex diseases in rural and underserved settings nationwide.

Lung involvement is one of the most frequent extra articular involvements of rheumatoid arthritis (RA). RA related lung involvement can affect parenchyma, airway, vascular tree and serosa. Among all possible manifestations of lung disease, interstitial lung disease is the most severe being able to compromise quality of life and survival and involves about 20% of patients with rheumatoid arthritis (RA). However, chest high resolution computed tomography (HRCT) features of RA, with or without interstitial lung involvement, have not been clearly defined. Such features have been mostly investigated on small populations of RA patients, often including patients with connective tissue diseases (CTDs), namely systemic sclerosis, mixed connective tissue disease, idiopathic inflammatory myopathies, making difficult to discriminate possible specific features of RA interstitial lung disease (ILD). The aims of this observational longitudinal study are to investigate: i) chest HRCT features of RA (frequency of radiologic HRCT patterns, fibrosis, nodules, bronchiectasis, etc.), associated or not to ILD; ii) possible associations between chest HRCT features and demographic, clinical and serologic characteristics of RA; iii) specific chest HRCT features of RA ILD, compared to idiopathic pulmonary fibrosis (IPF) and CTD ILD (i.e., primary Sjogren syndrome, idiopathic inflammatory myopathies, etc), according to the Centres availability. Consecutive, unselected, DICOM files of chest HRCT of adult RA patients (regardless a previous diagnosis of ILD) will be evaluated by an expert thoracic radiologist blinded to patients' clinical history. HRCT patterns, presence of fibrosis and other lung abnormalities (cysts, nodules, pleural effusion, etc) will be recorded. In patients with RA ILD possible associations with demographic and clinical disease features will be also analysed (such as sex, disease duration, disease duration at ILD diagnosis, presence of ACPA, rheumatoid factor, ANA), inclusion of previous therapies. After 2 years, new HRCT and lung function tests will be collected for each enrolled patients when available, to evaluate possible changes of lung involvement over time.

The AYLo study (AutoimmunitY and Loss of y - Investigating the Role of Hematopoietic Mutations and Mosaic Mutation in the Y Chromosome in Autoimmune Rheumatologic Diseases) aims to systematically investigate hematopoietic mutations, such as hematopoietic (mosaic) loss of the Y chromosome (mLOY), focusing on their underlying causes, pathophysiological significance, patterns of manifestation, and impact on disease progression in autoimmune, rheumatologic disorders. This research seeks to bridge existing knowledge gaps by exploring how such mutations influence immune homeostasis, cellular function, and susceptibility to inflammation-driven pathologies. Through the integration of advanced immunological profiling, the study aspires to uncover key mechanisms that drive the initiation, progression, and complications of autoimmune rheumatic diseases. These analyses will combine single nucleotide polymorphisms (SNP) arrays, multiplex assays, transcriptomics, and flow cytometry staining of peripheral blood mononuclear cells to delineate the interplay between hematopoietic mutations and immune dysregulation. A further objective is the development of a multimodal framework for disease-specific characterization, enabling precise mapping of mutation-driven phenotypes across diverse autoimmune conditions. This framework will incorporate clinical, molecular, and imaging data. Additionally, the AYLo study aims to explore the potential role of mLOY and other hematopoietic mutations as biomarkers for disease stratification, prognosis, and therapeutic response. The findings may open avenues for personalized treatment approaches, leveraging the molecular insights to inform targeted interventions and improve patient outcomes in autoimmune rheumatic disorders. By integrating translational and basic science approaches, this study has the potential to redefine current paradigms in autoimmune disease research and therapy.