Association between age at disease onset of anti-neutrophil cytoplasmic antibody-associated vasculitis and clinical presentation and short-term outcomes

Objectives: ANCA-associated vasculitis (AAV) can affect all age groups. We aimed to show that differences in disease presentation and 6 month outcome between younger- A nd older-onset patients are still incompletely understood. Methods: We included patients enrolled in the Diagnostic and Classification Criteria for Primary Systemic Vasculitis (DCVAS) study between October 2010 and January 2017 with a diagnosis of AAV. We divided the population according to age at diagnosis: <65 years or ≥65 years. We adjusted associations for the type of AAV and the type of ANCA (anti-MPO, anti-PR3 or negative). Results: A total of 1338 patients with AAV were included: 66% had disease onset at <65 years of age [female 50%; mean age 48.4 years (s.d. 12.6)] and 34% had disease onset at ≥65 years [female 54%; mean age 73.6 years (s.d. 6)]. ANCA (MPO) positivity was more frequent in the older group (48% vs 27%; P = 0.001). Younger patients had higher rates of musculoskeletal, cutaneous and ENT manifestations compared with older patients. Systemic, neurologic,cardiovascular involvement and worsening renal function were more frequent in the older-onset group. Damage accrual, measured with the Vasculitis Damage Index (VDI), was significantly higher in older patients, 12% of whom had a 6 month VDI ≥5, compared with 7% of younger patients (P = 0.01). Older age was an independent risk factor for early death within 6 months from diagnosis [hazard ratio 2.06 (95% CI 1.07, 3.97); P = 0.03]. Conclusion: Within 6 months of diagnosis of AAV, patients >65 years of age display a different pattern of organ involvement and an increased risk of significant damage and mortality compared with younger patients

Increased blood levels of cellular fibronectin in asthma: Relation to the asthma severity, inflammation, and prothrombotic blood alterations

Background: Recently, we have reported that asthma is characterized by prothrombotic blood alterations, which were related to the low-grade inflammatory state. Inflammation, however, may also lead to vascular dysfunction. The aim of this study was to evaluate plasma levels of cellular fibronectin (cFN), a marker of vascular injury in asthmatics, and to analyze their impact on described previously prothrombotic blood alterations. Methods: In a cross-sectional study, we investigated 164 adult stable asthmatics and 72 matched controls. Plasma cFN was measured using an ELISA. Its relations to inflammation, thrombin generation, fibrinolytic capacity, expressed as clot lysis time (CLT), and platelet markers were evaluated. Results: Asthma was associated with 50.1% higher plasma cFN levels as compared with controls (p < 0.001, after adjustment for potential confounders). There was a positive association of cFN with asthma severity and inverse with the FEV1/VC index (beta=0.2 [95% CI: 0.13-0.28] and beta=-0.15 [95% CI: -0.23 to -0.07], respectively). In asthmatics cFN positively correlated with high-sensitivity C-reactive protein (beta= 0.24 [95% CI: 0.16-0.32]), fibrinogen (beta= 0.13 [95% CI: 0.04-0.21]), interleukin-6 (beta= 0.23 [95% CI: 0.15-0.3]), platelet factor 4 (beta= 0.14 [95% CI: 0.06-0.21]), plasminogen (beta= 0.11 [95% CI: 0.04-0.19]) and CLT (beta= 0.35 [95% CI: 0.28-0.42]). In both groups cFN was related to the endogenous thrombin potential (ETP) (beta= 0.51 [95% CI: 0.44-0.57], and beta= 0.17 [95% CI: 0.07-0.27], respectively). Multiple regression models showed that cFN was the most potent independent predictor of both ETP and CLT in asthmatics. Conclusion: Presented study is the first to show increased plasma cellular fibronectin in asthma, which is associated with disease severity, inflammation, and prothrombotic blood alterations. This novel observation suggests a previously unknown modulator of prothrombotic plasma properties in asthmatics