Background Risk factors that are associated with a higher risk of subclinical atherosclerosis (SCA) in psoriatic arthritis (PsA) have never been examined in longitudinal studies. Objectives The aim of this study is to examine the progression of SCA in patients with PsA, and to identify risk factors associated with the development of atherosclerotic plague for this patient population. Methods 81 PsA patients participated in this prospective cohort study. All patients underwent carotid ultrasonography at 2 time points separated by a mean ± SD of 78±7 months. The longitudinal presence of carotid plaque and intima-media thickness (IMT) were measured at baseline and follow up. The associations of baseline clinical and demographic parameters, and cardiovascular risk factors with the presence of baseline or progressive plaque, were explored. Results In total, 38 out of 81 (46.9%) of PsA patients demonstrated ≥1 carotid plaque on the baseline or follow up ultrasound. At the follow up ultrasound, 23/81 (28.4%) patients had plaque progression (new plaque, incidence rate 4.37 per 100 person-years), while 12/81 (14.8%) patients had stable plaque (plaque at baseline and follow up). Three patients (3.7%) had plaque regression (plaque at baseline but no plaque at follow up). Univariate analysis revealed that the following variables were associated with carotid plaque with a p-value of <0.1 (table 1): older age, older age at PsA and psoriasis diagnosis, longer disease duration, increased fasting sugar, total cholesterol and apolipoprotein (Apo) B levels. Other traditional CV risk factors including blood pressure, body mass index, waist hip ratio, high density lipoprotein (HDL)- cholesterol (C), low density lipoprotein (LDL)-C, Apo A1 and insulin level and Framingham risk score; disease related parameters including number of tender and swollen joints, ESR, hsCRP, whether patient achieved minimal disease activity and novel cytokines (interleukin [IL]-33, soluble ST2, IL-17 and IL-23) levels were not associated with the presence of plaque. All of the potential explanatory variables with p<0.1 in the univariate analysis were analyzed using logistic regression. Independent explanatory variables associated with the presence of baseline or progressive plaque in PsA patients included older age (OR 1.071, 95% CI 1.007–1.140, P=0.03) and increased Apo B levels (OR 1.056, 95% CI 1.013–1.101, P=0.01). Conclusions High Apo B level confers an increased risk of the presence of any current, progressive or acquired carotid plaque in PsA patients even after adjusting for age and other traditional CV risk factors. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.3137
Rationale: Oxidative stress is thought to induce negative health effects associated with exposure to DE and may result from altered innate immunity. Therefore, anti-oxidant supplementation may modify DE-related changes in phagocytosis in airways. Methods: 12 participants (4 mild asthmatics and 8 healthy controls) completed a double-blinded, randomized, crossover, counter-balanced study of 3 exposure conditions, each separated by a 2-wk washout period: (1) DE (300ug PM 2.5 /m 3 for 2 hours) with anti-oxidant (N-acetylcysteine 600mg 3x/day for 5 days preceding, and on the day of the exposure) [“DEN”], (2) DE with placebo [“DEP”], or (3) filtered air with placebo [“FAP”]. Induced sputum was collected 6 hours after each exposure. Sputum neutrophils and macrophages were analyzed by flow cytometry for changes in innate immune response (phagocytosis). Those with PC20≤8 were defined as “reactive” and those with PC20>8 as “non-reactive”. Results: Phagocytosis in sputum macrophages was greater after DEP than after FAP (mean phagocytosis units = 22.8 and 15.8, respectively) and this difference was attenuated by DEN (mean phagocytosis units = 17.8 units). 6 subjects were methacholine-reactive at baseline; reactivity status did not modify phagocytosis. Conclusions: DE-associated increase in phagocytosis in human airways appears mitigated by anti-oxidant supplementation (N-acetylcysteine). The suggestion that DE upregulates the innate immune response in sputum macrophages, and that this is mediated by oxidative stress, parallels novel data from our lab regarding changes in airway reactivity to methacholine in response to FAP, DEP, and DEN.
RATIONALE: Oxidative stress is thought to underlie negative health effects associated with exposure to DE. Our objective was to test the efficacy of anti-oxidant supplementation in preventing DE-related changes in airway function in a susceptible population (asthmatics). METHODS: A double-blinded, randomized, crossover, counter-balanced study was implemented with 3 exposure conditions, each separated by a 2-wk washout period: (1) DE (300ug PM2.5/m3 for 2 hours) with anti-oxidant (N-acetylcysteine 600mg 3x/day for 5 days preceding, and on the day of the exposure) [“DEN”], (2) DE with placebo [“DEP”], or (3) filtered air with placebo [“FAP”]. To date, 5 healthy participants and 3 asthmatics have been studied. Airway reactivity to methacholine (PC20) was assessed and induced sputum collected 30 h after each exposure. Inflammatory cells were analyzed by flow cytometry for changes in intracellular oxidative burst using the Fc OxyBURST reagent assay. RESULTS: Compared to FAP, PC20 decreased 53±21% (mean ± SE) after DEP but only 7±2% after DEN in asthmatics; anti-oxidant prevented 83% of the increase in airway reactivity. DE did not cause changes in PC20 in healthy participants. In all participants, oxidative activity was reduced 12% in neutrophils and 20% in macrophages in DEN compared to DEP. CONCLUSIONS: Preliminary data suggests that DE-associated increases in airway reactivity are mitigated by anti-oxidant supplementation in asthmatics. This may be mediated by DE-induced oxidative burst in airway macrophages and neutrophils which is also attenuated by N-acetylcysteine. The study will continue until data is obtained on a total of 10 healthy subjects and 20 mild asthmatics.
RATIONALE: The predictors of recovery from occupational asthma, after removal from the asthmagen-exposure setting, are poorly understood. Our hypothesis is that those recovering have less active inflammation and airway remodeling. METHODS: 20 subjects with Western red cedar asthma, previously documented by specific inhalational challenge, returned after exposure cessation for induction of sputum, on which cell counts and supernatant-based assays for IL-5, IL-10, IL-12, IL-13, and interferon-gamma were performed. ATS criteria for impairment rating in asthma were evaluated to generate an impairment score and class. RESULTS: Eosinophils, as a percentage of all cells, were associated with impairment score (p=0.02). Interferon-gamma was significant associated with higher impairment class (for Class 2 and Class 1, mean concentration 1.6 and 0.6 pg/ml respectively, p = 0.03). Other cytokines demonstrated a similar pattern. CONCLUSIONS: In those with occupational asthma due to Western red cedar, having been removed from the offending asthmagen, impairment is associated with sputum eosinophilia and inflammatory cytokines.
Objective: Quantitative magnetic resonance imaging (qMRI) of knee cartilage morphology is a powerful research tool but relies on expensive and often inaccessible 1.5 T whole-body equipment. Here we examine the reproducibility and accuracy of qMRI at 1.0 T by direct comparison with previously validated technology.Methods: Coronal images of the knee were obtained in six healthy and six osteoarthritic participants. Two data sets were acquired with a 1.5 T whole-body magnetic resonance imaging (MRI) system and two with a 1.0 T peripheral MRI system, with repositioning between scans. Proprietary software was used to analyze surface area, volume, and thickness of femoral and tibial cartilage.Results: At 1.0 T, precision errors for surface areas (root-mean-square (RMS) coefficient of variation (CV%) = 1.7-2.6%) were higher than those at 1.5 T (1.0-2.1%). For volume and thickness, precision errors were 2.9-5.5% at 1.0 T compared to 1.6-3.4% at 1.5 T. High levels of agreement were found between the two scanners over all plates. With the exception of lateral femoral cartilage (volume and thickness), no statistically significant systematic bias was found between 1.0 T and 1.5 T.Conclusions: This is the first reported study to show that knee cartilage morphology can be determined with a reasonable degree of accuracy and precision using a 1.0 T peripheral scanner. Peripheral MRI is less costly, can be performed in clinical offices, and is associated with higher patient comfort and tolerance than 1.5 T whole-body MRI. Implementation of qMRI with peripheral systems may thus permit its more widespread use in clinical research and patient care. (C) 2006 Ostecarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
Objective: To investigate the relationships between bone mineral density (BMD) in the hip, spine, distal femur and proximal tibia and minimum joint space width (mJSW) in the knees of healthy women.Methods: Women 22-68 years old without a history of knee pain, bone or joint disease or injury underwent a single, fixed-flexion knee X-ray. Radiographs were graded according to the Kellgren-Lawrence scale and analyzed for mJSW using a computer algorithm. Dual X-ray absorptiometry scans of the spine, hip, distal femur and proximal tibia were also acquired for each participant. Femur and tibia scans were acquired and analyzed using a modified version of the lumbar spine software.Results: Forty-five females, mean [standard deviation (SD)] age and body mass index (BMI) of 40.1 (13.9) years and 24.6 (4.5) kg/m(2), respectively, participated. The mean (SD) mJSW was 4.64 (0.68) mm. Linear regression analyses controlling for age and BMI revealed that BMD in the femoral trochanter and the central two regions of the tibia (T2 and T3) was significantly related to mJSW in the knee. A backwards regression analysis performed to determine which region of interest is most significantly related to mJSW revealed that femoral trochanter BMD (beta-value = 0.416) is the most significant.Conclusions: In contrast to the suggestion that BMD is negatively correlated with mJSW in the knees of osteoarthritic individuals, these results suggest that increasing BMD in the femoral trochanter and tibia is significantly associated with increasing mJSW in healthy females. Further investigation of this relationship is warranted. (c) 2005 OsteoArthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
Objective: To estimate the prevalence of bone and soft tissue abnormalities in asymptomatic knees using peripheral magnetic resonance imaging (pMRI) and to examine the relationship between these abnormalities and Kellgren-Lawrence (K-L) graded X-rays.Method. Volunteers (20-68 years) with no history of knee pain, injury or bone or joint disease were recruited. Individuals underwent a single MRI scan and radiograph of their non-dominant knee. pMR images were acquired in sagittal plane using a 3-D gradient-echo protocol. Two radiologists graded the presence and severity of cartilage degeneration, osteophytosis, meniscal and ligamentous abnormalities, bone marrow edema and subchondral cysts. X-rays were acquired using a fixed-flexion technique and graded using the K-L scale.Results: Forty-four individuals, mean age (SD) 41.1 (14.2) years, participated. K-L grading of X-rays revealed 29 individuals were grade 0, 12 were grade 1 and 3 were grade 2. Five individuals showed evidence of cartilage lesions, the femoral trochlea, medial femur and patella being those regions most commonly affected. Twelve individuals (27.3%) showed evidence of osteophytosis, nine of whom did not show evidence on X-ray. Forty-three individuals showed evidence of at least one meniscal abnormality while 27 individuals (61.4%) had abnormalities in at least three of the four regions of the knee.Conclusion: Our results suggest that osteophytes may be more prevalent in this population than radiographic data suggests due to the limitations of two-dimensional imaging. Meniscal degeneration or tears, a risk factor for knee osteoarthritis, are highly prevalent in asymptomatic individuals with the medial anterior and posterior horns being the most commonly affected regions. (c) 2004 OsteoArthritis Research Society International. Published by Elsevier Ltd. All rights reserved.