Rheumatoid arthritis associated interstitial lung disease (RA-ILD) and idiopathic pulmonary fibrosis (IPF) are distinct diseases; however, they share several clinical, radiographic and genetic features. For instance, usual interstitial pneumonia (UIP), which is an ILD pattern required for a diagnosis of IPF, is also the most common ILD pattern in RA-ILD. The presence of UIP in RA-ILD is a poor prognostic sign with outcomes similar to those seen in IPF. The recent finding of a shared genetic susceptibility between IPF and RA-ILD has sparked additional interest in this relationship. This review outlines these similarities and differences in clinical presentation, appearance and outcomes in RA-ILD and IPF.In addition, this review highlights previous research in molecular biomarkers in both conditions, exploring areas of overlap and distinction. This focus on biomarkers in IPF and RA-ILD aims to highlight potential areas of discovery and clues to a potential shared pathobiology through investigation of novel molecular markers or the repurposing of biomarkers from one condition to the other.The drive to better understand RA-ILD by leveraging our knowledge of IPF is underscored by our divergent treatment paradigms for these conditions and the concern for potential harm. As a result of advancing our understanding of the links between IPF and RA-ILD, current strategies for diagnosis, screening and treatment of ILD may fundamentally change in the coming years. Until then, clinicians face difficult clinical questions regarding the co-management of the articular disease and the ILD in RA.

Matrix metalloproteinase-7 level is associated with worse baseline pulmonary function and worse transplant-free survival in scleroderma interstitial lung diseasehttps://bit.ly/3zZhja7

Background: Idiopathic interstitial pneumonias (IIPs), such as idiopathic pulmonary fibrosis and interstitial pneumonia with autoimmune features, present diagnostic and therapeutic challenges due to their heterogeneous nature. This study aimed to identify intrinsic molecular signatures within the lung microenvironment of these IIPs through proteomic analysis of bronchoalveolar lavage fluid (BALF).Methods: Patients with IIP (n=23) underwent comprehensive clinical evaluation including pre-treatment bronchoscopy and were compared with controls without lung disease (n=5). Proteomic profiling of BALF was conducted using label-free quantitative methods. Unsupervised cluster analyses identified protein expression profiles that were then analysed to predict survival outcomes and investigate associated pathways.Results: Proteomic profiling successfully differentiated IIP from controls. k-means clustering based on protein expression revealed three distinct IIP clusters, which were not associated with age, smoking history, or baseline pulmonary function. These clusters had unique survival trajectories and provided more accurate survival predictions than the Gender Age Physiology index (concordance index 0.794versus0.709). The cluster with the worst prognosis featured decreased inflammatory signalling and complement activation, with pathway analysis highlighting altered immune response pathways related to immunoglobulin production and B-cell-mediated immunity.Conclusions: The unsupervised clustering of BALF proteomics provided a novel stratification of IIP patients, with potential implications for prognostic and therapeutic targeting. The identified molecular phenotypes underscore the diversity within the IIP classification and the potential importance of personalised treatments for these conditions. Future validation in larger, multi-ethnic cohorts is essential to confirm these findings and to explore their utility in clinical decision-making for patients with IIP.

Background The defining radiological features of autoimmune interstitial lung disease (ILD) are ground glass opacification (GGO) and fibrosis. The associations between these features and physiological response to immunomodulation remain unclear. Methods This study leveraged three autoimmune ILD cohorts: two with systemic sclerosis (SSc) and one with rheumatoid arthritis (RA) which were selected for inherent differences in fibrotic extents/patterns. Linear regression models examined associations between baseline quantitative GGO, fibrosis, their ratio and forced vital capacity (FVC)%-predicted changes after 12 months of immunomodulatory therapy. Results Patients with SSc-ILD (N=262) exhibited a higher GGO-to-fibrosis ratio compared with patients with RA-ILD (N=130) (mean ratio 3.0 vs 0.25). Increased GGO-to-fibrosis was not associated with improved FVC%-predicted in any cohort. Conversely, in patients with SSc-ILD treated with cyclophosphamide (CYC), increased fibrosis (estimate 0.17 (95% CI 0.003, 0.33); p=0.04) and increased GGO (estimate 0.15 (95% CI 0.004, 0.30); p=0.044) were both significantly associated with FVC% improvement. Given the negative direction of the estimate for GGO-to-fibrosis ratio (estimate −0.33 (95% CI −0.61, –0.06); p=0.016), CYC was associated with greater FVC% improvement in patients with a higher degree of fibrosis relative to GGO. No significant correlation was seen in patients with SSc-ILD treated with mycophenolate (N=56) or in patients with RA-ILD treated with immunomodulation (N=130). Discussion Increased quantitative GGO relative to fibrosis was not significantly associated with improved response to immunomodulation in patients with RA-ILD and SSc-ILD. However, increased quantitative fibrosis and GGO extent were associated with improved response to CYC in SSc-ILD. More research is needed to understand how to use radiological features to guide treatment selection in ILD.

Rheumatoid arthritis (RA) affects roughly 1% of the population and commonly involves the lungs. Of lung involvement in RA, interstitial lung disease (ILD) is well known; however, airways disease in RA is relatively understudied. What are the baseline airways abnormalities in a prospective cohort of patients with RA based on pulmonary function testing (PFT) results, high-resolution CT (HRCT) scans, and computational imaging analysis and are there associations between these abnormalities and respiratory symptoms? In this single-center study, 188 patients with RA without a clinical diagnosis of ILD underwent HRCT imaging and PFT. Radiologists assessed HRCT scans for airway abnormalities. Computational imaging via VIDA Vision software and in-house quantitative CT imaging analysis was applied to 147 HRCT scans to quantify airway abnormalities. Airways obstruction (FEV₁ to FVC ratio < 0.7) was present in 20.7% of patients and was associated with older age, male sex, and higher smoking rate. Radiologists identified airway abnormalities in 61% of patients: 55% had bronchial wall thickening, 12% had bronchiectasis, and 5% had mosaic attenuation. These airways findings were associated with older age; male sex; lower FEV₁, FVC, and FEV₁ to FVC ratio; and higher rates of rheumatoid factor positivity. Prespecified quantitative CT scan metrics (wall thickening percentage and emphysema percentage) correlated with obstruction in PFT results and more severe respiratory symptoms, including shortness of breath and cough. High rates of airways abnormalities were found in this prospective RA cohort based on three methods of detection. Significant associations were identified between quantitative CT scan measures and respiratory symptoms. Airways disease may be an underrecognized extra-articular manifestation of RA and quantitative CT imaging may be a sensitive method to detect the clinical impact on respiratory symptoms.