Marta Forner

Upper airway and systemic inflammation in obstructive sleep apnoea.

Obstructive sleep apnoea (OSA) is associated with pharyngeal inflammation, but the coexistence of systemic inflammation is controversial. This study investigated whether local and systemic inflammatory biomarkers are related in patients with OSA. An uncontrolled extension to the study assessed the response to effective treatment. We recruited 89 patients with OSA (apnoea/hypopnoea index (AHI) ≥5 events·h−1), 28 snorers and 26 healthy controls. Pharyngeal lavage (PHAL) and plasma samples were collected at baseline and after a 1-year follow-up. Inflammatory cells were evaluated by flow cytometry; interleukin (IL)-6, IL-8 and tumour necrosis factor-α were evaluated by immunoassay. In PHAL, CD4+ T-cells, IL-6 and IL-8 were higher in OSA patients than in snorers or healthy controls (p<0.05). The AHI correlated with CD4+, IL-6 and IL-8 in PHAL (all p-values <0.05). There were no differences in the inflammatory biomarkers in plasma between the study groups and no relationship between plasma and PHAL biomarkers. Biomarkers decreased significantly in PHAL but not in plasma after 1 year of therapy with continuous positive airway pressure or surgery. In patients with OSA, increased levels of inflammatory biomarkers were found in PHAL, which were reduced with effective treatment. No simultaneous increase in plasma inflammatory biomarkers was found. Pharyngeal lavage, but not plasma, shows high levels of inflammatory markers in OSA that were normalised by treatment http://ow.ly/pKYd301hs6A

Stability of Circulating Exosomal miRNAs in Healthy Subjects

Exosomes are nano-vesicles present in the circulation that are involved in cell-to-cell communication and regulation of different biological processes. MicroRNAs (miRNAs) are part of their cargo and are potential biomarkers. Methods of exosome isolation and the inter-individual and intra-individual variations in circulating miRNA exosomal cargo have been poorly investigated. This study aims for comparing two exosome isolation methods and to assess the stability of eleven plasma exosomal miRNAs over time. In addition to evaluate miRNA variability of both kits, the effect of freezing plasma before exosome isolation or freezing isolated exosomes on miRNA stability was also evaluated. MiRNA levels were tested in 7 healthy subjects who underwent four different blood extractions obtained in 4 consecutive weeks. One of the isolation kits displayed generally better amplification signals, and miRNAs from exosomes isolated after freezing the plasma had the highest levels. Intra-subject and inter-subject coefficients of variance were lower for the same isolation kit after freezing plasma. Finally, miRNAs that showed an acceptable expression level were stable across the consecutive extractions. This study shows for the first time the stability over time of miRNAs isolated from circulating plasma exosomes, establishing a key step in the use of exosomal miRNAs as biomarkers.

Interaction between body weight obstructive sleep apnea (OSA) on C-reactive protein (CRP) in an otherwise healthy population: The EPIOSA study

Background: CRP is an inflammatory biomarker associated with atherosclerosis and cardiovascular disease (CVD). Obesity is an important OSA risk factor. To determine the independent roles of OSA and obesity in CVD is complicated by their coexistence. Aim: To assess association of OSA with CRP levels in a clinical cohort of otherwise healthy OSA patients and specifically to assess if it depends on body weight. Methods: Data from Epigenetics modifications in Obstructive Sleep Apnea (EPIOSA), a prospective clinical-based study on mechanisms of CVD damage in patients with OSA (ClinicalTrials.gov NCT02131610). CRP was measured in 183 subjects, 25-60 years old, who underwent sleep study. Smokers and participants with body mass index (BMI)>35 kg/m 2 or with any comorbid condition other than OSA were excluded. OSA classified according to apnea-hypopnea index (AHI). Results: Cohort of 183: 38 controls (AIH 2 ), multiple liner regression model with interaction terms showed independent association of AHI with CRP among those with BMI 2 and no interaction between AHI and BMI among patients with OSA and obesity (BMI>30 kg/m 2 ). Conclusions: In an otherwise healthy population, OSA severity is an independent predictor of levels CRP but interacts with obesity so that association is found only in non-obese patients. Supported by: ISCIII (PI12/01275), SEPAR (071/2012) and SADAR (02/2013).