Obstructive Sleep Apnoea Syndrome, Endothelial Function and Markers of Endothelialization. Changes after CPAP

Study objectives This study tries to assess the endothelial function in vivo using flow-mediated dilatation (FMD) and several biomarkers of endothelium formation/restoration and damage in patients with obstructive sleep apnoea (OSA) syndrome at baseline and after three months with CPAP therapy. Design Observational study, before and after CPAP therapy. Setting and Patients We studied 30 patients with apnoea/hypopnoea index (AHI) > 15/h that were compared with themselves after three months of CPAP therapy. FMD was assessed non-invasively in vivo using the Laser-Doppler flowmetry. Circulating cell-free DNA (cf-DNA) and microparticles (MPs) were measured as markers of endothelial damage and the vascular endothelial growth factor (VEGF) was determined as a marker of endothelial restoration process. Measurements and results After three month with CPAP, FMD significantly increased (1072.26 +/- 483.21 vs. 1604.38 +/- 915.69 PU, p<0.005) cf-DNA and MPs significantly decreased (187.93 +/- 115.81 vs. 121.28 +/- 78.98 pg/ml, p<0.01, and 69.60 +/- 62.60 vs. 39.82 +/- 22.14 U/mu L, p<0.05, respectively) and VEGF levels increased (585.02 +/- 246.06 vs. 641.11 +/- 212.69 pg/ml, p<0.05). These changes were higher in patients with more severe disease. There was a relationship between markers of damage (r = -0.53, p< 0.005) but not between markers of damage and restoration, thus suggesting that both types of markers should be measured together. Conclusions CPAP therapy improves FMD. This improvement may be related to an increase of endothelial restoration process and a decrease of endothelial damage

Uso de pulsos de metilprednisolona de repetición en adultos hospitalizados por neumonía y síndrome de distrés respiratorio agudo por COVID-19: un estudio preliminar de tipo antes-después (estudio CortiCOVID)

[EN] Introduction: The use of systemic corticosteroids in severely ill patients with coronavirus disease 2019 (COVID-19) is controversial. We aimed to evaluate the efficacy and safety of corticosteroid pulses in patients with COVID-19 pneumonia. Methods: A quasi-experimental study, before and after, was performed in a tertiary referral hospital, including admitted patients showing COVID-19-associated pneumonia. The standard treatment protocol included targeted COVID-19 antiviral therapy from 23rd March 2020, and additionally pulses of methylprednisolone from 30th March 2020. The primary outcome was a composite endpoint combining oro-tracheal intubation (OTI) and death within 7 days. Results: A total of 24 patients were included. Standard of care (SOC) (before intervention) was prescribed in 14 patients, while 10 received SOC plus pulses of methylprednisolone (after intervention). The median age of patients was 64.5 years and 83.3% of the patients were men. The primary composite endpoint occurred in 13 patients (92.9%) who received SOC vs. 2 patients (20%) that received pulses of methylprednisolone (odds ratio, 0.02; 95% confidence interval, 0.001 to 0.25; p = 0.019). Length of hospitalization in survivors was shorter in the corticosteroids group (median, 14.5 [8.5–21.8] days vs. 29 [23–31] days, p = 0.003). There were no differences in the development of infections between both groups. There were 3 deaths, none of them in the corticosteroids group. Conclusions: In patients with severe pneumonia due to COVID-19, the administration of methylprednisolone pulses was associated with a lower rate of OTI and/or death and a shorter hospitalization episode.[ES] Introducción: El uso de corticosteroides sistémicos en pacientes gravemente enfermos por enfermedad coronavírica de 2019 (covid-19) es controvertido. Nuestro objetivo fue evaluar la eficacia y la seguridad de los pulsos de corticoesteroides en los pacientes con neumonía por covid-19. Métodos: Se realizó un ensayo cuasiexperimental, tipo antes y después, en un hospital terciario de referencia que incluyó a pacientes ingresados por neumonía asociada a covid-19. El protocolo de tratamiento estándar incluía un tratamiento antiviral dirigido contra el virus de la covid-19 desde el 23 de marzo de 2020 y añadió pulsos de metilprednisolona desde el 30 de marzo de 2020. El resultado primario fue un criterio combinado compuesto por la intubación orotraqueal y el fallecimiento durante los siguientes siete días. Resultados: Se incluyó un total de 24 pacientes. El protocolo de tratamiento (antes de la intervención) se prescribió en 14 pacientes, mientras que 10 recibieron el protocolo de tratamiento además de los pulsos de metilprednisolona (después de la intervención). La edad media de los pacientes fue de 64,5 años y el 83,3% de los pacientes eran hombres. El resultado combinado primario tuvo lugar en 13 pacientes (92,9%) que recibieron el protocolo de tratamiento frente a 2 pacientes (20%) que recibieron los pulsos de metilprednisolona (odds ratio = 0,02; intervalo de confianza del 95% = 0,001-0,25; p = 0,019). La duración de la hospitalización en los supervivientes fue más corta en el grupo que recibió corticoesteroides (media = 14,5 [8,5-21,8] días frente a 29 [23-31] días, p = 0,003). No hubo diferencias en el desarrollo de infecciones entre ambos grupos. Hubo tres fallecimientos, ninguno de ellos en el grupo que recibió corticoesteroides. Conclusiones: En los pacientes con neumonía grave por covid-19, la administración de pulsos de metilprednisolona se asoció a unas tasas menores de intubación orotraqueal y/o muerte y a episodios de hospitalización más cortos

Echocardiographic Changes with Positive Airway Pressure Therapy in Obesity Hypoventilation Syndrome. Long-Term Pickwick Randomized Controlled Clinical Trial

Spanish Sleep Network.[Rationale] Obesity hypoventilation syndrome (OHS) has been associated with cardiac dysfunction. However, randomized trials assessing the impact of long-term noninvasive ventilation (NIV) or continuous positive airway pressure (CPAP) on cardiac structure and function assessed by echocardiography are lacking. Rationale: Obesity hypoventilation syndrome (OHS) has been associated with cardiac dysfunction. However, randomized trials assessing the impact of long-term noninvasive ventilation (NIV) or continuous positive airway pressure (CPAP) on cardiac structure and function assessed by echocardiography are lacking.[Objectives] In a prespecified secondary analysis of the largest multicenter randomized controlled trial of OHS (Pickwick Project; N = 221 patients with OHS and coexistent severe obstructive sleep apnea), we compared the effectiveness of three years of NIV and CPAP on structural and functional echocardiographic changes.[Methods] At baseline and annually during three sequential years, patients underwent transthoracic two-dimensional and Doppler echocardiography. Echocardiographers at each site were blinded to the treatment allocation. Statistical analysis was performed using a linear mixed-effects model with a treatment group and repeated measures interaction to determine the differential effect between CPAP and NIV. Measurements and Main Results: A total of 196 patients were analyzed: 102 were treated with CPAP and 94 were treated with NIV. Systolic pulmonary artery pressure decreased from 40.5 ± 1.47 mm Hg at baseline to 35.3 ± 1.33 mm Hg at three years with CPAP, and from 41.5 ± 1.56 mm Hg to 35.5 ± 1.42 with NIV (P < 0.0001 for longitudinal intragroup changes for both treatment arms). However, there were no significant differences between groups. NIV and CPAP therapies similarly improved left ventricular diastolic dysfunction and reduced left atrial diameter. Both NIV and CPAP improved respiratory function and dyspnea.[Conclusions] In patients with OHS who have concomitant severe obstructive sleep apnea, long-term treatment with NIV and CPAP led to similar degrees of improvement in pulmonary hypertension and left ventricular diastolic dysfunction

Risk factors associated with pulmonary hypertension in obesity hypoventilation syndrome

Pulmonary hypertension (PH) is prevalent in obesity hypoventilation syndrome (OHS). However, there is a paucity of data assessing pathogenic factors associated with PH. Our objective is to assess risk factors that may be involved in the pathogenesis of PH in untreated OHS.Peer reviewe

Implications of a Change of Paradigm in Alpha1 Antitrypsin Deficiency Augmentation Therapy: From Biochemical to Clinical Efficacy

This article belongs to the Special Issue Rare Respiratory Diseases: A Personal and a Public Health Problem.Ever since the first studies, restoring proteinase imbalance in the lung has traditionally been considered as the main goal of alpha1 antitrypsin (AAT) replacement therapy. This strategy was therefore based on ensuring biochemical efficacy, identifying a protection threshold, and evaluating different dosage regimens. Subsequently, the publication of the results of the main clinical trials showing a decrease in the progression of pulmonary emphysema has led to a debate over a possible change in the main objective of treatment, from biochemical efficacy to clinical efficacy in terms of lung densitometry deterioration prevention. This new paradigm has produced a series controversies and unanswered questions which face clinicians managing AAT deficiency. In this review, the concepts that led to the approval of AAT replacement therapy are reviewed and discussed under a new prism of achieving clinical efficacy, with the reduction of lung deterioration as the main objective. Here, we propose the use of current knowledge and clinical experience to face existing challenges in different clinical scenarios, in order to help clinicians in decision-making, increase interest in the disease, and stimulate research in this field

Unidad de Cuidados Respiratorios Intermedios (UCRI) en la pandemia COVID-19 en España. La realidad

Debido a la pandemia por COVID-19 declarada por la OMS en marzo del 2020, la gran mayoría de los hospitales españoles han debido transformarse para adaptarse a este nuevo escenario, resultando en cambios en su infraestructura y organización, generando estrategias de colaboración y coordinación entre diferentes especialidades...El presente trabajo ha sido realizado gracias a la financiación por parte de Philips de la empresa externa IPSOS.Peer reviewe