Dysregulation in CD39/CD73 Axis May Trigger the Upsurge of the Immune Suppressive Agent Adenosine in OSA Patients

Introduction Although higher incidence of cancer represents a major burden for obstructive sleep apnea (OSA) patients, the molecular pathways driving this association are not completely understood. Interestingly, adenosinergic signaling has emerged as a powerful immune checkpoint driving tumor development and progression. Methods Here, we explored the expression of the adenosinergic ecto-enzymes CD39 and CD73 in T-lymphocytes of OSA patients without any evidence of cancer, as well as their soluble forms in plasma (sCD39 and sCD73), along with adenosine. In addition, we explored the role of intermittent hypoxia (IH) in this context by in vitro models. Results Our results showed that CD39 is upregulated while CD73 is downregulated in OSA T-cells’ membrane. Moreover, our findings suggest that IH, through HIF-1, mediates the upregulation of both CD39 and CD73; and that CD73 downregulation could be mediated by a higher release of sCD73 by OSA T-lymphocytes. Importantly, we found that both sCD39 and sCD73 are upregulated in OSA plasma, suggesting T-lymphocytes as a potential source for plasmatic sCD73. Finally, our data propose the alterations in CD39/CD73 axis could underlie the upsurge of adenosine levels in the plasma of OSA patients. Conclusion Our study reveals a hypoxia-mediated alteration of the CD39/CD73 axis in OSA patients, which could trigger ADO upregulation, thus potentially contributing to the immune suppressive environment and ultimately facilitating tumor development and progression. Therefore, our data highlights the need for new longitudinal studies evaluating CD39 and/or CD73 as potential cancer-risk prognostic biomarkers in OSA patients. (AU)

Dysregulation in CD39/CD73 Axis May Trigger the Upsurge of the Immune Suppressive Agent Adenosine in OSA Patients.

INTRODUCTION: Although higher incidence of cancer represents a major burden for obstructive sleep apnea (OSA) patients, the molecular pathways driving this association are not completely understood. Interestingly, adenosinergic signaling has emerged as a powerful immune checkpoint driving tumor development and progression. METHODS: Here, we explored the expression of the adenosinergic ecto-enzymes CD39 and CD73 in T-lymphocytes of OSA patients without any evidence of cancer, as well as their soluble forms in plasma (sCD39 and sCD73), along with adenosine. In addition, we explored the role of intermittent hypoxia (IH) in this context by in vitro models. RESULTS: Our results showed that CD39 is upregulated while CD73 is downregulated in OSA T-cells' membrane. Moreover, our findings suggest that IH, through HIF-1, mediates the upregulation of both CD39 and CD73; and that CD73 downregulation could be mediated by a higher release of sCD73 by OSA T-lymphocytes. Importantly, we found that both sCD39 and sCD73 are upregulated in OSA plasma, suggesting T-lymphocytes as a potential source for plasmatic sCD73. Finally, our data propose the alterations in CD39/CD73 axis could underlie the upsurge of adenosine levels in the plasma of OSA patients. CONCLUSION: Our study reveals a hypoxia-mediated alteration of the CD39/CD73 axis in OSA patients, which could trigger ADO upregulation, thus potentially contributing to the immune suppressive environment and ultimately facilitating tumor development and progression. Therefore, our data highlights the need for new longitudinal studies evaluating CD39 and/or CD73 as potential cancer-risk prognostic biomarkers in OSA patients.

Dynamic hyperinflation is a risk factor for mortality and severe exacerbations in COPD patients.

OBJECTIVE: To assess if dynamic hyperinflation is an independent risk factor for mortality and severe exacerbations in COPD patients. METHODS: A cohort of 141 patients with stable COPD and moderate to very severe airflow limitation, treated according to conventional guidelines, was followed for a median of 9 years. Clinical characteristics were recorded and arterial blood gases, pulmonary function tests, 6-min walk and incremental exercise test with measurement of respiratory pattern and operative lung volumes were performed. Endpoints were all-cause mortality and hospitalization for COPD exacerbation. RESULTS: 58 patients died during the follow-up period (1228 patients x year). The mortality rate was higher in patients with dynamic hyperinflation (n = 106) than in those without it (n = 35) (14.6; 95% CI, 14.5-14.8 vs. 7.2; 95% CI, 7.1-7.4 per 1000 patients-year). After adjusting for sex, age, body mass index, pack-years and treatment with inhaled corticosteroids, dynamic hyperinflation was associated with a higher mortality risk (adjusted hazard ratio [aHR], 2.725; 95% CI, 1.010-8.161), and in a multivariate model, comorbidity, peak oxygen uptake and dynamic hyperinflation were retained as independent predictors of mortality. The time until first severe exacerbation was shorter for patients with dynamic hyperinflation (aHR, 3.961; 95% CI, 1.385-11.328), and dynamic hyperinflation, FEV1 and diffusing capacity were retained as independent risk factors for severe exacerbation. Moreover, patients with dynamic hyperinflation had a higher hospitalization risk than those without it (adjusted incidence rate ratio, 1.574; 95% CI, 1.087-2.581). CONCLUSION: In stable COPD patients, dynamic hyperinflation is an independent prognostic factor for mortality and severe exacerbations.

Sleep apnoea increases biomarkers of immune evasion, lymphangiogenesis and tumour cell aggressiveness in high-risk patients and those with established lung cancer.

Background: Intermittent hypoxaemia and obstructive sleep apnoea (OSA) have been linked to lung cancer through as yet unidentified pathophysiological mechanisms. This study evaluates the effect of OSA on serum levels of biomarkers of immunosurveillance, lymphangiogenesis and intrinsic tumour cell aggressiveness in high-risk individuals screened for lung cancer and patients with established lung cancer. Methods: Serum samples from individuals participating in a lung cancer screening cohort (SAILS study) or with newly diagnosed lung cancer (SAIL study) were analysed. All patients underwent home sleep apnoea testing. Soluble levels of programmed cell death-1 (PD-1), programmed cell death ligand-1 (PD-L1), cytotoxic T-lymphocyte antigen-4, midkine (MDK), paraspeckle component-1 (PSPC1), transforming growth factor-ß1 (TGF-ß1), SMAD3, matrix metalloproteinase-2 and co-stimulus receptor of the tumour necrosis factor family of receptors (CD137) were determined by ELISA. Results: The presence of moderate-to-severe OSA was associated with increased levels of PSPC1, MDK, PD-L1 and PD-1 in screened individuals, and with higher values of PSPC1, TGF-ß1, PD-L1 and PD-1 in patients with established lung cancer. The findings correlated with nocturnal intermittent hypoxaemia indices. Conclusion: Moderate-to-severe OSA is associated with increased expression of serum biomarkers of immune evasion, lymphangiogenesis and tumour cell aggressiveness in high-risk individuals screened for lung cancer and those with established disease.

SARS-CoV-2 S protein activates NLRP3 inflammasome and deregulates coagulation factors in endothelial and immune cells.

BACKGROUND: Hyperinflammation, hypercoagulation and endothelial injury are major findings in acute and post-COVID-19. The SARS-CoV-2 S protein has been detected as an isolated element in human tissues reservoirs and is the main product of mRNA COVID-19 vaccines. We investigated whether the S protein alone triggers pro-inflammatory and pro-coagulant responses in primary cultures of two cell types deeply affected by SARS-CoV-2, such are monocytes and endothelial cells. METHODS: In human umbilical vein endothelial cells (HUVEC) and monocytes, the components of NF-κB and the NLRP3 inflammasome system, as well as coagulation regulators, were assessed by qRT-PCR, Western blot, flow cytometry, or indirect immunofluorescence. RESULTS: S protein activated NF-κB, promoted pro-inflammatory cytokines release, and triggered the priming and activation of the NLRP3 inflammasome system resulting in mature IL-1ß formation in both cell types. This was paralleled by enhanced production of coagulation factors such as von Willebrand factor (vWF), factor VIII or tissue factor, that was mediated, at least in part, by IL-1ß. Additionally, S protein failed to enhance ADAMTS-13 levels to counteract the pro-coagulant activity of vWF multimers. Monocytes and HUVEC barely expressed angiotensin-converting enzyme-2. Pharmacological approaches and gene silencing showed that TLR4 receptors mediated the effects of S protein in monocytes, but not in HUVEC. CONCLUSION: S protein behaves both as a pro-inflammatory and pro-coagulant stimulus in human monocytes and endothelial cells. Interfering with the receptors or signaling pathways evoked by the S protein may help preventing immune and vascular complications driven by such an isolated viral element. Video Abstract.

Association between occupational exposure and chronic obstructive pulmonary disease and respiratory symptoms in the Spanish population.

INTRODUCTION: The aim of this study was to analyze the impact of occupational exposure on chronic obstructive pulmonary disease (COPD) and respiratory symptoms in the general Spanish population. METHODS: This was a study nested in the Spanish EPISCAN II cross-sectional epidemiological study that included participants who had completed a structured questionnaire on their occupational history, a questionnaire on respiratory symptoms, and forced spirometry. The data were analyzed using Chi-square and Student's t tests and adjusted models of multiple linear regression and logistic regression. RESULTS: We studied 7502 subjects, 51.1% women, with a mean age of 60±11 years. Overall, 53.2% reported some respiratory symptoms, 7.9% had respiratory symptoms during their work activity, 54.2% were or had been smokers, and 11.3% (851 subjects) met COPD criteria on spirometry. A total of 3056 subjects (40.7%) reported exposure to vapors, gases, dust or fumes (VGDF); occupational exposure to VGDF was independently associated with the presence of COPD (OR 1.22, 95% CI: 1.03-1.44), respiratory symptoms (OR 1.45, 95%: CI 1.30-1.61), and respiratory symptoms at work (OR 4.69, 95% CI: 3.82-5.77), with a population attributable fraction for COPD of 8.2%. CONCLUSIONS: Occupational exposure is associated with a higher risk of COPD and respiratory symptoms in the Spanish population. These results highlight the need to follow strict prevention measures to protect the respiratory health of workers.

Continuous Positive Airway Pressure Effect on Progression of Retinal Disease in Patients with Sleep Apnea and Nonproliferative Diabetic Retinopathy: A Randomized Clinical Trial.

Rationale: Obstructive sleep apnea (OSA) is associated with impaired glycemic control and a higher risk of vascular complications, such as diabetic retinopathy. However, the effect of apnea-hypopnea suppression on retinal disease progression is unclear. Objectives: To evaluate the efficacy and safety of continuous positive airway pressure (CPAP) for the reduction of retinal lesions in patients with non-proliferative diabetic retinopathy (NPDR) and OSA. Methods: This open-label, parallel-group, randomized controlled trial was conducted between October 2016 and February 2020 at a university hospital in Spain. The date of final follow-up was March 2, 2021. Eighty-three patients with OSA and mild to moderate NPDR receiving stable treatment were randomized to receive CPAP and usual care (43 patients with 79 available eyes) or usual care alone (40 patients with 67 available eyes) for 52 weeks. The primary outcomes were the change in the percentage of eyes with retinal exudates and the number of retinal microhemorrhages from baseline to week 52. We also assessed the effects of both interventions on retinal thickness by means of optical coherence tomography, serum concentrations of glycated hemoglobin, blood pressure, lipid concentrations, sleepiness, and quality of life. Results: Fifty-two weeks of CPAP treatment was associated with reductions from baseline in the percentage of eyes with hard exudates (overall difference, -21.7%; P = 0.035) and in optical coherence tomography indices of retinal edema, including central subfield thickness and cube volume. However, in patients who met prespecified criteria for CPAP adherence, treatment was also associated with a higher number of retinal microhemorrhages at 52 weeks (intergroup adjusted difference, 6.0 [95% confidence interval, 0.6-11.5]; P = 0.029), which was directly related to prescribed pressure levels. CPAP treatment also improved glycemic control, sleepiness, and general health-related quality of life. Conclusions: In patients with OSA and NPDR, long-term CPAP treatment in addition to usual care may result in slower progression of retinal disease, although it could also induce an increase in retinal microhemorrhages. Clinical trial registered with www.clinicaltrials.gov (NCT02874313).

PSGL-1: a novel immune checkpoint driving T-cell dysfunction in obstructive sleep apnea.

Introduction: Although higher incidence of cancer represents a major burden for obstructive sleep apnea (OSA) patients, the molecular pathways driving this association are not completely understood. Recently, the adhesion receptor P-selectin glycoprotein-1 (PSGL 1) has been identified as a novel immune checkpoint, which are recognized major hallmarks in several types of cancer and have revolutionized cancer therapy. Methods: The expression of PSGL-1 and its ligands VISTA and SIGLEC-5 was assessed in the leucocytes of OSA patients and control subjects exploring the role of intermittent hypoxia (IH) using in vitro models. In addition, PSGL-1 impact on T-cells function was evaluated by ex vivo models. Results: Data showed PSGL-1 expression is upregulated in the T-lymphocytes from patients with severe OSA, indicating a relevant role of hypoxemia mediated by intermittent hypoxia. Besides, results suggest an inhibitory role of PSGL-1 on T-cell proliferation capacity. Finally, the expression of SIGLEC-5 but not VISTA was increased in monocytes from OSA patients, suggesting a regulatory role of intermittent hypoxia. Discussion: In conclusion, PSGL-1 might constitute an additional immune checkpoint leading to T-cell dysfunction in OSA patients, contributing to the disruption of immune surveillance, which might provide biological plausibility to the higher incidence and aggressiveness of several tumors in these patients.

Prevalence, Knowledge and Perceptions of Smoking and Tobacco Products and Vape Among SEPAR Members.

Introduction: The professional dedicated to respiratory health has an exemplary role in tobacco control, promoting smoking cessation in their patients. However, multiple circumstances cause a low implementation. Therefore, the objective of the study is to identify the consumption, knowledge and perception of tobacco and its emerging products in a representative sample of professionals involved in the treatment of respiratory patients integrated into the Spanish Society of Pneumology and Thoracic Surgery (SEPAR). Methods: Descriptive analysis of a structured online interview addressed to 5340 SEPAR members. Results: In a sample of 802 respondents, more than 33% have smoked at some time and 6.6% continue to smoke. More than 66% consider smoking as a chronic disease. More than 90% consider their role model important and advise their patients to quit smoking, but less than half carry out a smoking intervention. Only 35% of them believe that the ban on smoking in health centers is always complied. More than 75% do not consider nicotine delivery devices an option for smoking cessation or harm reduction. 22% are unaware of water pipes and 29% of heated tobacco. Conclusions: Professionals specialized in respiratory diseases are highly sensitized to smoking. Despite this, there are still weak points such as the insufficient implementation of smoking cessation interventions or the scant training in smoking and in new emerging products.

Introducción: El profesional dedicado a la salud respiratoria tiene un papel ejemplar en el control del tabaquismo, promoviendo el abandono del hábito tabáquico en sus pacientes. Sin embargo, múltiples circunstancias provocan una baja implementación. Por tanto, el objetivo del estudio es identificar el consumo, el conocimiento y la percepción sobre el tabaco y sus productos emergentes en una muestra representativa de profesionales implicados en el tratamiento de pacientes respiratorios integrados en la Sociedad Española de Neumología y Cirugía Torácica (SEPAR). Métodos: Análisis descriptivo de una entrevista estructurada en línea dirigida a 5.340 miembros de la SEPAR. Resultados: En una muestra de 802 encuestados, más del 33% ha fumado alguna vez y el 6.6% sigue fumando. Más del 66% considera el tabaquismo como una enfermedad crónica. Más del 90% considera importante su modelo a seguir y aconseja a sus pacientes que dejen de fumar, pero menos de la mitad realiza una intervención para dejar de fumar. Solo el 35% de ellos cree que la prohibición de fumar en los centros de salud se cumple siempre. Más del 75% no considera que los dispositivos de suministro de nicotina sean una opción para dejar de fumar o reducir los daños. El 22% desconoce las pipas de agua y el 29% el tabaco calentado. Conclusiones: Los profesionales especialistas en enfermedades respiratorias están altamente sensibilizados al tabaquismo. A pesar de ello, aún existen puntos débiles como la insuficiente implantación de intervenciones para dejar de fumar o la escasa formación en tabaquismo y en nuevos productos emergentes.

[A Study of the Prevalence of Asthma in the General Population in Spain]. / Estudio de prevalencia de asma en población general en España.

Introduction: Asthma is a disease with high prevalence, which affects all age groups and generates high health and social care costs. Studies carried out in a number of populations show great variability in its prevalence, even in geographically close populations, with data suggesting a relevant influence of socio-economic factors. At present, we do not have reliable data on the prevalence of this disease in the adult population of Spain. The objectives of this study are to estimate the prevalence of asthma in the Spanish population for those aged 18-79, to describe the variability between autonomous communities, to estimate the prevalence of under and overdiagnosis, to analyse the prevalence of uncontrolled asthma and steroid-dependent asthma, to evaluate the health care cost, to identify the most frequent phenotypes and to establish a starting point to evaluate the temporal trend with subsequent studies. Methods: A cross-sectional, two-stage study will be carried out, including patients from 50 catchment areas. The study will be carried out in 3 phases: 1) screening and confirmation in the clinical history, in which patients with a previously correctly established diagnosis of asthma will be identified; 2) diagnosis of asthma to evaluate patients without a confirmed or excluded diagnosis; 3) characterization of asthma, where the characteristics of the asthmatic patients will be analysed, identifying the most frequent phenotypes. Discussion: It seems necessary and feasible to carry out an epidemiological study of asthma in Spain to identify the prevalence of asthma, to optimize healthcare planning, to characterize the most frequent phenotypes of the disease, and to evaluate inaccurate diagnoses.

European Respiratory Society/American Thoracic Society technical statement: standardisation of the measurement of lung volumes, 2023 update.

This document updates the 2005 European Respiratory Society (ERS) and American Thoracic Society (ATS) technical standard for the measurement of lung volumes. The 2005 document integrated the recommendations of an ATS/ERS task force with those from an earlier National Heart, Lung, and Blood Institute workshop that led to the publication of background papers between 1995 and 1999 and a consensus workshop report with more in-depth descriptions and discussion. Advancements in hardware and software, new research and emerging approaches have necessitated an update to the 2005 technical standard to guide laboratory directors, physiologists, operators, pulmonologists and manufacturers. Key updates include standardisation of linked spirometry, new equipment quality control and validation recommendations, generalisation of the multiple breath washout concept beyond nitrogen, a new acceptability and grading system with addition of example tracings, and a brief review of imaging and other new techniques to measure lung volumes. Future directions and key research questions are also noted.

Tobacco Patterns and Risk of Chronic Obstructive Pulmonary Disease: Results From a Cross-Sectional Study.

INTRODUCTION: There is still uncertainty about which aspects of cigarette smoking influence the risk of Chronic Obstructive Pulmonary Disease (COPD). The aim of this study was to estimate the COPD risk as related to duration of use, intensity of use, lifetime tobacco consumption, age of smoking initiation and years of abstinence. METHODS: We conducted an analytical cross-sectional study based on data from the EPISCAN-II study (n=9092). All participants underwent a face-to-face interview and post-bronchodilator spirometry was performed. COPD was defined as post-bronchodilator FEV1/FVC<70%. Parametric and nonparametric logistic regression models with generalized additive models were used. RESULTS: 8819 persons were included; 858 with COPD and 7961 without COPD. The COPD risk increased with smoking duration up to ≥50 years [OR 3.5 (95% CI: 2.3-5.4)], with smoking intensity up to ≥39cig/day [OR 10.1 (95% CI: 5.3-18.4)] and with lifetime tobacco consumption up to >29 pack-years [OR 3.8 (95% CI: 3.1-4.8)]. The COPD risk for those who started smoking at 22 or later was 0.9 (95% CI: 0.6-1.4). The risk of COPD decreased with increasing years of cessation. In comparison with both never smokers and current smokers, the lowest risk of COPD was found after 15-25 years of abstinence. CONCLUSION: COPD risk increases with duration, intensity, and lifetime tobacco consumption and decreases importantly with years of abstinence. Age at smoking initiation shows no effect. After 15-25 years of cessation, COPD risk could be equal to that of a never smoker. This work suggests that the time it takes to develop COPD in a smoker is about 30 years.

Diagnosis and Treatment of Sleep Apnea in Children: A Future Perspective Is Needed.

Obstructive sleep apnea (OSA) in children is a prevalent, but still, today, underdiagnosed illness, which consists of repetitive episodes of upper airway obstruction during sleep with important repercussions for sleep quality. OSA has relevant consequences in the pediatric population, mainly in the metabolic, cardiovascular (CV), and neurological spheres. However, contrary to adults, advances in diagnostic and therapeutic management have been scarce in the last few years despite the increasing scientific evidence of the deleterious consequences of pediatric OSA. The problem of underdiagnosis and the lack of response to treatment in some groups make an update to the management of OSA in children necessary. Probably, the heterogeneity of OSA is not well represented by the classical clinical presentation and severity parameters (apnea/hypopnea index (AHI)), and new strategies are required. A specific and consensus definition should be established. Additionally, the role of simplified methods in the diagnosis algorithm should be considered. Finally, the search for new biomarkers for risk stratification is needed in this population. In conclusion, new paradigms based on personalized medicine should be implemented in this population.

Role of Sleep Apnea and Long-Term CPAP Treatment in the Prognosis of Patients With Melanoma: A Prospective Multicenter Study of 443 Patients.

BACKGROUND: OSA has been associated with increased incidence and aggressiveness of melanoma. However, the long-term impact of OSA and CPAP treatment on the prognosis of melanoma remains unexplored. RESEARCH QUESTION: Are OSA and CPAP treatment associated independently with a poor prognosis for cutaneous melanoma? STUDY DESIGN AND METHODS: Four hundred forty-three patients with a diagnosis of cutaneous melanoma (2012-2015) underwent a sleep study within 6 months of diagnosis. The main 5-year outcome of the study was a composite of melanoma recurrence, metastasis, or mortality. Patients were divided into four groups: baseline apnea-hypopnea index (AHI) of fewer than 10 events/h (no OSA; control group), OSA treated with CPAP and good adherence, untreated or poor CPAP adherence in moderate (AHI, 10-29 events/h), and severe OSA (AHI, ≥ 30 events/h). Survival analysis was used to determine the independent role of OSA and CPAP treatment on melanoma composite outcome. RESULTS: Three hundred ninety-one patients (88.2%) were available for analysis at 5-year follow-up (mean age, 65.1 ± 15.2 years; 49% male; Breslow index, 1.7 ± 2.5 mm). One hundred thirty-nine patients had AHI of fewer than 10 events/h (control group); 78 patients with OSA were adherent to CPAP; and 124 and 50 patients had moderate and severe OSA, respectively, without CPAP treatment. Median follow-up was 60 months (interquartile range, 51-74 months). During follow-up, 32 relapses, 53 metastases, and 52 deaths occurred (116 patients showed at least one of the main composite outcomes). After adjusting for age, sex, sentinel lymph nodes affected at diagnosis, BMI, diabetes, nighttime with an oxygen saturation below 90%, Breslow index, Epworth sleepiness scale scores, and melanoma treatment, moderate (hazard ratio [HR], 2.45; 95% CI, 1.09-5.49) and severe OSA (HR, 2.96; 95% CI, 1.36-6.42) were associated with poorer prognosis of melanoma compared with the control group. However, good adherence to CPAP avoided this excess risk (HR, 1.66; 95% CI, 0.71-3.90). INTERPRETATION: Moderate to severe untreated OSA is an independent risk factor for poor prognosis of melanoma. Treatment with CPAP is associated with improved melanoma outcomes compared with untreated moderate to severe OSA.

SMAD4 Expression in Monocytes as a Potential Biomarker for Atherosclerosis Risk in Patients with Obstructive Sleep Apnea.

Obstructive sleep apnea (OSA) patients are at special risk of suffering atherosclerosis, leading to major cardiovascular diseases. Notably, the transforming growth factor (TGF-ß) plays a crucial role in the development and progression of atherosclerosis. In this context, the central regulator of TGF-ß pathway, SMAD4 (small mother against decapentaplegic homolog 4), has been previously reported to be augmented in OSA patients, which levels were even higher in patients with concomitant cardiometabolic diseases. Here, we analyzed soluble and intracellular SMAD4 levels in plasma and monocytes from OSA patients and non-apneic subjects, with or without early subclinical atherosclerosis (eSA). In addition, we used in vitro and ex vivo models to explore the mechanisms underlying SMAD4 upregulation and release. Our study confirmed elevated sSMAD4 levels in OSA patients and identified that its levels were even higher in those OSA patients with eSA. Moreover, we demonstrated that SMAD4 is overexpressed in OSA monocytes and that intermittent hypoxia contributes to SMAD4 upregulation and release in a process mediated by NLRP3. In conclusion, this study highlights the potential role of sSMAD4 as a biomarker for atherosclerosis risk in OSA patients and provides new insights into the mechanisms underlying its upregulation and release to the extracellular space.

Analysis of the Ischemia-Modified Albumin as a Potential Biomarker for Cardiovascular Damage in Obstructive Sleep Apnea Patients with Acute Coronary Syndrome.

Obstructive sleep apnea (OSA) has been identified as a cardiovascular (CV) risk factor. The potential of OSA promoting the synthesis of CV biomarkers in acute coronary syndrome (ACS) is unknown. Ischemia-modified albumin (IMA) has been identified as a specific CV biomarker. The aim of this study was to evaluate the role of IMA as a potential biomarker for determining the impact of OSA in ACS patients. A total of 925 patients (15.5% women, age: 59 years, body mass index: 28.8 kg/m2) from the ISAACC study (NCT01335087) were included. During hospitalization for ACS, a sleep study for OSA diagnosis was performed and blood samples extraction for IMA determination were obtained. IMA values were significantly higher in severe OSA (median (IQR), 33.7 (17.2-60.3) U/L) and moderate (32.8 (16.9-58.8) U/L) than in mild/no OSA (27.7 (11.8-48.6) U/L) (p = 0.002). IMA levels were very weakly related to apnea-hypopnea index (AHI) as well as hospital and intensive care unit stay, although they only maintained a significant relationship with days of hospital stay after adjusting for sex, age and BMI (ß = 0.410, p = 0.013). The results of the present study would suggest a potentially weaker role of OSA in the synthesis of the CV risk biomarker IMA in patients with ACS than in primary prevention.

How accurate are medical CT and micro-CT techniques compared to classical histology when addressing the growth of the internal rib parameters?

Rib internal anatomy and its cross-sectional morphology inform about important biomechanical or even evolutionary aspects. Classic histological studies require destructive techniques that are reprehensible depending on the case (e.g., fossils). In the last years, non-destructive CT-based methods are contributing to complementing previous knowledge without damaging the bone. Even though these methods have been proved to be useful to understand adult variation, we do not know whether these methods are useful to cover ontogenetic variation. This work compares classical histological methods with medical- and micro-CT to quantify the amount of mineral area at the rib midshaft (% Min. Ar.), a proxy for bone density. We compared cross-sections from an ontogenetic sample of 14 human first ribs ranging from perinates to adults using a) classical histology, b) HD (9-17 microns) and SD micro-CT (90 microns), and c) standard medical-CT (0.66 mm). We found that all the CT-based methods provide a larger % Min. Ar. compared to the histological techniques, but the HD micro-CT resolution is the only capable of producing results comparable to classical histology (p > 0.01), with the SD micro-CT and the medical-CT producing statistically larger results compared to classical histology (p < 0.01). In addition, it is important to state that the resolution of a standard medical-CT is not high enough to differentiate between mineral and non-mineral areas of the cross-sections for perinates and infants. These results could have important implications to avoid (when necessary) destructive techniques that are not appropriate in the case of highly valuable specimens such as fossils.

Trends of COPD in Spain: Changes Between Cross Sectional Surveys 1997, 2007 and 2017

Introduction: We aim to describe the changes in prevalence and risk factors associated to chronic obstructive pulmonary disease (COPD) in Spain, comparing three population-based studies conducted in three timepoints. Methods: We compared participants from IBERPOC conducted in 1997, EPISCAN conducted in 2007 and EPISCAN II in 2017. COPD was defined as a postbronchodilator FEV1/FVC (forced expiratory volume in 1s/forced vital capacity) ratio <0.70, according to GOLD criteria; subsequently, also as the FEV1/FVC below the lower limit of normal (LLN). Results: COPD prevalence in the population between 40 and 69 years decreased from 21.6% (95% CI 20.7%–23.2%) in 1997 to 8.8% (95% CI 8.2%–9.5%) in 2017, a 59.2% decline (p<0.001). In 2007, the prevalence was 7.7% (95% CI 6.8%–8.7%) with an upward trend of 1.1 percentage points in 2017 (p=0.073). Overall COPD prevalence decreased in men and women, although a significant increase was observed in the last decade in females (p<0.05). Current smokers significantly increased in the last decades (25.4% in 1997, 29.1% in 2007 and 23.4% in 2017; p<0.001). Regrettably, COPD underdiagnosis was constantly high, 77.6% in 1997, 78.4% in 2007, and to 78.2% in 2017 (p=0.95), higher in younger ages (40–49 yrs and 50–59 yrs) and also higher in women than in men in all three studies (p<0.05). Conclusions: We report a significant reduction of 59.2% in the prevalence of COPD in Spain from 1997 to 2017 in subjects aged 40–69 years. Our study highlights the significant underdiagnosis of COPD, particularly sustained in women and younger populations. (AU)