Enhanced prothrombotic and proinflammatory activity of circulating extracellular vesicles in acute exacerbations of chronic obstructive pulmonary disease.

BACKGROUND: Acute exacerbations of chronic obstructive pulmonary disease (AE-COPD) are associated with a high rate of cardiovascular events. Thromboinflammation (the interplay between coagulation and inflammation) is probably involved in these events. Extracellular vesicles (EV) increase during AE-COPD, but their role in thromboinflammation in COPD is still unknown. We investigated EV-associated prothrombotic and proinflammatory activity in COPD. METHODS: Patients with AE-COPD, stable COPD (sCOPD) and age- and sex-matched subjects (controls) were enrolled. AE-COPD patients were evaluated at hospital admission and 8 weeks after discharge (recovery; longitudinal arm). In a cross-sectional arm, AE-COPD were compared with sCOPD and controls. EV-mediated prothrombotic activity was tested by measuring the concentration of EV-associated phosphatidylserine, as assessed by a prothrombinase assay, and tissue factor, as assessed by a modified one-stage clotting assay (EV-PS and EV-TF, respectively). Synthesis of interleukin-8 (IL-8) and C-C motif chemokine ligand-2 (CCL-2) by cells of the human bronchial epithelial cell line 16HBE incubated with patients' EV was used to measure EV-mediated proinflammatory activity. RESULTS: Twenty-five AE-COPD (median age [interquartile range] 74.0 [14.0] years), 31 sCOPD (75.0 [9.5] years) and 12 control (67.0 [3.5] years) subjects were enrolled. In the longitudinal arm, EV-PS, EV-TF, IL-8 and CCL-2 levels were all significantly higher at hospital admission than at recovery. Similarly, in the cross-sectional arm, EV-PS, EV-TF and cytokines synthesis were significantly higher in AE-COPD than in sCOPD and controls. CONCLUSIONS: EV exert prothrombotic and proinflammatory activities during AE-COPD and may therefore be effectors of thromboinflammation, thus contributing to the higher cardiovascular risk in AE-COPD.

Detecting the vulnerable carotid plaque: the Carotid Artery Multimodality imaging Prognostic study design.

BACKGROUND: Carotid artery disease is highly prevalent and a main cause of ischemic stroke and vascular dementia. There is a paucity of information on predictors of serious vascular events. Besides percentage diameter stenosis, international guidelines also recommend the evaluation of qualitative characteristics of carotid artery disease as a guide to treatment, but with no agreement on which qualitative features to assess. This inadequate knowledge leads to a poor ability to identify patients at risk, dispersion of medical resources, and unproven use of expensive and resource-consuming techniques, such as magnetic resonance imaging, positron emission tomography, and computed tomography. OBJECTIVES: The Carotid Artery Multimodality imaging Prognostic (CAMP) study will: prospectively determine the best predictors of silent and overt ischemic stroke and vascular dementia in patients with asymptomatic subcritical carotid artery disease by identifying the noninvasive diagnostic features of the 'vulnerable carotid plaque'; assess whether 'smart' use of low-cost diagnostic methods such as ultrasound-based evaluations may yield at least the same level of prospective information as more expensive techniques. STUDY DESIGN: We will compare the prognostic/predictive value of all proposed techniques with regard to silent or clinically manifest ischemic stroke and vascular dementia. The study will include ≥300 patients with asymptomatic, unilateral, intermediate degree (40-60% diameter) common or internal carotid artery stenosis detected at carotid ultrasound, with a 2-year follow-up. The study design has been registered on Clinicaltrial.gov on December 17, 2020 (ID number NCT04679727).

Sequential sensitization to different occupational compounds in a young woman.

BACKGROUND: Very few authors have reported sensitization to two or more different occupational sensitizers in a single patient. OBJECTIVE: To describe a subject with occupational asthma caused by sensitization to two different agents, exposure to which occurred in dierent time periods. METHODS: We studied a young woman with asthma-like symptoms predominantly in relationship to a sequential occupational exposure, first to methylene diisocyanate (MDI) and later to flour dust. In the first and second periods of occupational exposure, the patient was subjected to metbacholine challenge test (MCT), sputum analysis, and specific challenge test (SCT). RESULTS: At the first observation, MCT (PD20FEV1: 0.109 mg) and SCT with MDI were positive and induced sputum analysis showed a high percentage of eosinophils (32%). The patient reduced exposure to MDI but symptoms worsened with continuing occupational exposure. After one year, she started another job exposed to flour dust. After four years, asthma symptoms persisted despite treatment with inhaled corticosteroids and bronchodilators, and bronchial byperreactivity and sputum eosinophbilia were still present (PD2OFEV1: 0.067 mg; sputum eosinophils: 5.3%). The patient also developed rhinitis symptoms associated with dermatitis. A SCT with flour dust showed an immediate response (deltaFEV1: 33%). The subject left work and a year later was still symptomatic:pulmonary function was within normal limits under regular therapy and induced sputum showed absence of eosinophilia. CONCLUSIONS: This was an unusual case of double sensitization to different occupational compounds to which the patient was exposed in different time periodsj suggesting the role of a pre-existing occupational aSthma in the development and/or worsening of sensitization to other occupational agents.