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Background Rheumatoid arthritis (RA)-associated lung disease (LD) associates with significantly increased morbidity and mortality. Although oxidative stress plays an important role in the inflammatory responses in other forms of lung disease, minimal work has evaluated its role in RA-LD. The current work examines the relationship between the anti-oxidant HDL-associated enzyme paraoxonase-1 (PON1), the PON1 Q192R polymorphism, and a targeted oxylipin panel with RA-LD. Methods This study was conducted as a retrospective chart review of a longitudinal single-center cohort of 250 RA patients. CT scans of the chest were reviewed by the interpreting radiologist and classified as small airways disease (SAD), interstitial lung disease (ILD), and bronchiectasis. PON1 activity was measured by its lactonase, arylesterase, and paraoxonase functions. The PON1 Q192R polymorphism and a targeted lipidomics panel were performed as previously reported. Results 43.2% of the 250 RA patient cohort (n = 108) had available CT scans, including 48 patients (44.4%) with SAD, 27 patients (25.0%) with bronchiectasis, and 16 patients (14.8%) with ILD. Patients with SAD had significantly lower baseline PON1 activity by its arylesterase, and lactonase functions, as well as higher 15-HETE, LTB4, and PGE2 levels compared to those without SAD. These predictors of SAD remained significant after multivariate analysis including known risk factors for RA-LD. Suppressed PON1 activity also correlated with higher levels of 15-HETE and 12-HETE. Conclusion In a single-center RA cohort, suppressed baseline PON1 activity and elevation in the oxylipins 15-HETE, LTB4, and PGE2 predicted the presence of RA-SAD in longitudinal follow-up. Key Points• Small airways disease (SAD) was present in 44.4% of this rheumatoid arthritis (RA) cohort.• Patients with SAD had significantly lower baseline PON1 activity, as well as higher levels of the oxylipins 15-HETE, LTB4, and PGE2 levels compared to those without SAD.• Further work is warranted to confirm these findings and further define the role of PON1 and lipid oxidation in RA lung disease.

The objective of this study was to evaluate oxidation products of arachidonic acid and linoleic acid in lipoproteins and synovial fluid (SF) from patients with active rheumatoid arthritis (RA) compared to non-RA controls. High-density lipoproteins (HDL) and low-density lipoproteins (LDL) were isolated from plasma using fast protein liquid chromatography and HDL was isolated from SF using dextran sulfate precipitation. 5-Hydroxyeicosatetraenoic acid (HETE), 12-HETE, 15-HETE, 9 hydroxyoctadecadienoic (HODE), and 13-HODE levels were measured in HDL, LDL, and SF by liquid chromatography-tandem mass spectrometry. HDL's anti-inflammatory function, cholesterol levels, myeloperoxidase (MPO) and paraoxonase 1 (PON1) activities were determined as previously. 5-HETE, 15-HETE, 9-HODE, and 13-HODE levels were significantly increased in HDL and LDL from patients with active RA (n=10) compared to healthy controls (n=8) and correlated significantly with measures of systemic inflammation, particularly in HDL (r=0.65-0.80, p values

To describe the use of oral cyclophosphamide (PO CYC) in a single center longitudinal cohort of patients with idiopathic inflammatory myopathies (IIM). Patients using PO CYC were identified through a retrospective chart review of a myositis cohort at a single academic center. PO CYC dose, duration, adverse events, and disease activity measures before and after CYC were analyzed. Disease activity measures included muscle enzymes, manual muscle testing (MMT8), 100-mm visual analog scale (VAS), and 1-4 Likert scale for physician global assessment. Fourteen patients were treated with PO CYC within the cohort between 2008 and 2017; 9 dermatomyositis (DM), 3 polymyositis (PM), and 2 with immune-mediated necrotizing myopathy (IMNM). Age was 51.1 (40-72) years and the cumulative dose of PO CYC was 41 (2-131) grams over duration of 12.4 (0.5-43) months, mean (range) for all. All patients had severe refractory IIM, 10 (72%) with ILD, 3 (21%) with cardiac involvement and 4 (29%) were dependent in most activities of daily living. Median number of prior failed therapies was 4.5 (range 3-6) including intravenous CYC in 5 patients. Disease activity measures significantly improved following CYC use and concomitant daily prednisone dose decreased. The most common adverse events during CYC therapy were infections. We report the first cohort study of PO CYC use in IIM patients with severe, treatment refractory disease. Further trials are needed to verify these results as well as to evaluate long-term safety outcomes.

Recent data suggest that atherosclerotic disease is increased in patients with idiopathic inflammatory myositis (IIM) and that dyslipidemia is a significant risk factor for cardiovascular events. Lipid-lowering agents may be associated with myopathic side effects. The current work evaluates the use of lipid-lowering therapy in patients with IIM treated by IIM specialists belonging to the International Myositis Assessment and Clinical Studies (IMACS) Group. The IMACS Group is a multidisciplinary coalition of experts with significant interest and experience in IIM. IMACS members were asked to complete an 18-item online survey detailing their clinical practice on monitoring and treating hypercholesterolemia in IIM patients. Specific questions regarding the types of lipid-lowering therapies used in IIM patients and any side effects associated with treatment were asked. Sixty-three IMACS members representing 23 countries and a minimum of 1,641 IIM patients participated in the online survey. Seventy-six percent of these specialists treating adult IIM patients use lipid-lowering therapies in their patients. HMG co-enzymeA reductase inhibitors (statins) were the most commonly used agents (93 %). Thirty-six cases of worsening myositis associated with statin use were reported in over 300 patients using lipid-lowering therapies. Seven of eight responders who reported worsening in myositis with lipid-lowering therapies reported cases in which the myositis improved after holding therapy. This survey suggests that statins are commonly used by physicians specializing in the treatment of patients with IIM and that some myositis patients worsen with statin use and may improve on dechallenge. More research regarding the safety of lipid-lowering agents in patients with IIM is warranted.