Results in clinical practice in the treatment of severe eosinophilic asthma with mepolizumab: a real-life study.

OBJECTIVE: Add-on therapy with monoclonal antibodies is the recommended therapy for severe asthmatic patients refractory to maintenance treatment. In randomized control trials, mepolizumab reduced the number of exacerbations, the need of oral corticosteroids (OCS), increased asthma control, and lung function in a population of uncontrolled severe eosinophilic asthmatic patients. In this piece of work, we aimed to assess mepolizumab efficacy and safety in a cohort of patients with severe eosinophilic asthma in real-life conditions. METHODS: A retrospective study was carried out at eight hospitals from Asturias (Spain). The sample included patients treated with mepolizumab from 1 January 2016 to 31 March 2019. Demographic and clinical variables were collected, including OCS use, asthma control, lung function, and exacerbation rate. RESULTS: Sixty-nine patients (72% women) with mean age 56 ± 13 years were included. Annual exacerbation rate decreased from 4.7 (SD 3.7) to 1.3 (SD 2.5) (p < 0.001). The number of patients requiring OCS treatment decreased from 25 patients (36%, mean prednisone dose = 18 mg/day) to 13 patients (19%, mean prednisone dose = 9 mg/day) (p < 0.001). Twelve patients (48%) stopped OCS treatment. Forced expired volume in one second (FEV1) as percentage increased from 68% (SD 20) to 76% (SD 21) (p < 0.001). Fifty-six patients (81%) were considered responders to mepolizumab. No serious adverse events were detected during the study period. CONCLUSIONS: Overall, this study demonstrates mepolizumab efficacy and safety in a cohort of patients with uncontrolled severe eosinophilic asthma in routine clinical practice.

COMET: a multicomponent home-based disease-management programme versus routine care in severe COPD.

The COPD Patient Management European Trial (COMET) investigated the efficacy and safety of a home-based COPD disease management intervention for severe COPD patients.The study was an international open-design clinical trial in COPD patients (forced expiratory volume in 1 s <50% of predicted value) randomised 1:1 to the disease management intervention or to the usual management practices at the study centre. The disease management intervention included a self-management programme, home telemonitoring, care coordination and medical management. The primary end-point was the number of unplanned all-cause hospitalisation days in the intention-to-treat (ITT) population. Secondary end-points included acute care hospitalisation days, BODE (body mass index, airflow obstruction, dyspnoea and exercise) index and exacerbations. Safety end-points included adverse events and deaths.For the 157 (disease management) and 162 (usual management) patients eligible for ITT analyses, all-cause hospitalisation days per year (mean±sd) were 17.4±35.4 and 22.6±41.8, respectively (mean difference -5.3, 95% CI -13.7 to -3.1; p=0.16). The disease management group had fewer per-protocol acute care hospitalisation days per year (p=0.047), a lower BODE index (p=0.01) and a lower mortality rate (1.9% versus 14.2%; p<0.001), with no difference in exacerbation frequency. Patient profiles and hospitalisation practices varied substantially across countries.The COMET disease management intervention did not significantly reduce unplanned all-cause hospitalisation days, but reduced acute care hospitalisation days and mortality in severe COPD patients.

Snoring as a Determinant Factor of Oxidative Stress in the Airway of Patients with Obstructive Sleep Apnea.

PURPOSE: In obstructive sleep apnea-hypopnea syndrome (OSAS), airway collapses and vibrations cause local and systemic inflammatory response and oxidative stress (OS). Our objective was to determine the presence of OS in the airway of patients with OSAS compared with controls without OSAS and determine its relation to treatment with CPAP and other clinical variables. METHOD: We performed a prospective observational case-control study with repeated measures. We recruited consecutive patients with SAHS diagnosed using complete polysomnography, and a parallel control group. We collected a sample of exhaled breath condensate (EBC) prior to nasal continuous positive airway pressure (CPAP) treatment and again after 4 months. The marker of OS used was 8-isoprostane (8-IPN). The variables analyzed were age, sex, anthropometric variables, apnea-hypopnea index (AHI), snoring, oxygenation, and polysomnographic variables. RESULTS: The study included 20 patients and 10 controls. In cases, the initial value of 8-IPN was 6.8 (1.9), and after nasal CPAP, it was 5.3 (1.2) pg/ml (p = 0.02). In controls, the value of 8-IPN was 5.6 (1.1) pg/ml (p = 0.04 compared to initial values). 8-IPN showed significant correlation with snoring, AHI, BMI, nocturnal desaturation index, and non-REM sleep. On multivariate analysis, only snoring was a significant predictor of 8-IPN. CONCLUSIONS: Snoring, and not OSAS severity, could be the phenomenon underlying the presence of local OS measured in the airway of patients with OSAS.

Home mechanical ventilation through mask: monitoring leakage and nocturnal oxygenation at home.

BACKGROUND: Leakage is common in patients receiving home mechanical ventilation (HMV) via a face mask. Although pressure ventilators have partial compensatory capacity, excessive leakage can compromise the effectiveness of treatment. Home ventilators are equipped with built-in software which provides information on leakage. However, the values of leakage and their effects in routine clinical practice are currently little known. OBJECTIVE: To measure leakage in stable patients on nocturnal HMV and its impact on treatment effectiveness. METHODS: Consecutive outpatients on HMV were recruited. Nocturnal pulse oximetry was performed at home and leakage was measured using the ventilator's built-in software. We measured: mean SpO(2), percentage of time with SpO(2) <90% (T90), mean leakage (meanL), maximum leakage (maxL), and minimum leakage (minL) during the ventilation session. We estimated ventilator capacity to compensate for leakage according to inspiratory positive airway pressure and divided the patients into two groups: those with leak compensation and those without. RESULTS: The study included 41 patients [mean age, 64 years (SD 11.9); 23 (56%) women]. Nocturnal pulse oximetry showed an SpO(2) of 94% (±2.9) and a T90 of 10% (±21.7). Leakage (in l/min) was: meanL, 32.2 (±15.3); maxL, 64.8 (±28.5), and minL, 18.8 (±10.6). Seven cases (17%) had leakage greater than the ventilator compensatory capacity, but no significant difference in SpO(2) or T90 was observed between patients with or without leak compensation. CONCLUSIONS: A wide variation between maxL and minL was observed in our series; 17% of cases had higher leakage values than the compensatory capacity of the ventilator, but this did not affect nocturnal oxygenation.

Obesity-Hypoventilation Syndrome: Baseline Hemodynamic Status and Impact of non-Invasive Ventilation. / Síndrome de obesidad-hipoventilación: situación hemodinámica basal e impacto de la ventilación no invasiva.

INTRODUCTION: Obesity-hypoventilation syndrome (OHS) is a risk factor for heart failure (HF). Some studies associate the use of non-invasive ventilation (NIV) with changes in hemodynamic parameters. Our objective was to describe the hemodynamic status of a group of patients with OHS and to study the effect of NIV. PATIENTS AND METHODS: Patients with stable OHS treated with NIV were included in this cross-sectional repeated measurements study. Hemodynamics were measured by bioimpedance: 30minutes at baseline and another 30minutes on NIV. Cardiac output (CO), cardiac index, and systolic volume were measured. The CO calculated for each patient expressed as a percentage of the lower limit of normal (LLN) was taken as reference, and 2 groups were formed: patients without HF and normal CO (≥ 100% of LLN) and patients with HF and low CO (< 100% of LLN). The Mann-Whitney U test was used to compare independent variables and the Wilcoxon test was used for paired variables, with significance set at P<.05. RESULTS: The final sample comprised 36 patients, aged 66 (± 8) years, 19 (52%) men. In 17 (46%) patients, HF was detected with a CO of 3.7 l/min (66%) compared to the group without HF, whose CO was 7 l/min (107%). After NIV, patients with HF showed improvement in CO (4.5 l/min (77%), P=.009, while the non-HF group remained unchanged, with CO 6.8 l/min (104%), P=.2. CONCLUSION: A total of 46% of patients with stable OHS present HF; NIV improves hemodynamics and does not affect patients with normal CO.

Clinical Impact of a Pleural Unit in a Tertiary Level Hospital. / Impacto clínico de una unidad de patología pleural en un hospital de tercer nivel.

INTRODUCTION: Pleural disease involves a large number of admissions and long hospital stays. In order to improve this situation, a Pleural Unit (PU) was created in our hospital. Our aim was to analyze the clinical impact of this unit. MATERIAL AND METHODS: In this prospective study, we included patients admitted to the PU of the Hospital Universitario Central de Asturias for primary spontaneous pneumothorax (PSP), secondary spontaneous pneumothorax (SSP), complicated parapneumonic pleural effusion (CPPE), and malignant pleural effusion (MPE) between January 2015 and December 2018. We analyzed descriptive parameters, mean length of stay, readmissions at 1 month, need for surgery, and in the CPPE group, in-hospital mortality. The data were compared with those of patients admitted to the respiratory medicine department for the same diseases during the previous two years (2013-2014). We also describe all procedures performed in the PU, in both inpatients and outpatients. RESULTS: A total of 741 patients were included, We observed a progressive decrease in total admissions for pleural diseases and mean length of stay (days) (with the exception of MPE), as follows: PSP: from 6.2 to 4.2 (P=.004); SSP: 13.2 to 8.6 (P=.005), MPE: 10.3 to 12.3 (P=.05); and CPPE: 18.3 to 11.3 (P=.001) There was a reduction in hospital readmissions at 1 month and in in-hospital mortality due to CPPE in the PU period (14.9% to 5.5%) (P=.021). CONCLUSIONS: The creation of a PU could decrease the number of unnecessary admissions, and reduce mean lengths of stay and, in the case of CPPE, in-hospital mortality.

Silicosis in Artificial Quartz Conglomerate Workers. / Silicosis en trabajadores con conglomerados artificiales de cuarzo.

INTRODUCTION: Silicosis is a chronic progressive disease caused by inhalation of crystalline silica. Most cases develop in underground mine workers and in subjects involved in the extraction of natural stone (slate and granite). In view of the progressive emergence of new cases of silicosis in artificial quartz conglomerate workers, we performed a study to analyze the characteristics of silicosis produced by this new agent in Spain. METHODS: The study consisted of a series of 96 cases of silicosis diagnosed according to international criteria during the period 2010-2017. We analyzed clinical, radiological, pathological and functional characteristics. RESULTS: Mean age of participants was 45 years; 55% had simple silicosis and 45% had complicated silicosis. Ten patients were diagnosed with accelerated silicosis, with a mean age of 33 years. Mean time of exposure to conglomerates was 15 years, and 77% had not used appropriate protection measures. Half of the patients were asymptomatic and presented different classic forms on chest X-ray and chest high-resolution computed tomography, along with ground-glass images. No lung function changes were recorded. CONCLUSIONS: Silicosis in artificial quartz conglomerate workers occurs in a young, actively employed population, a considerable percentage of whom present an accelerated form. They have few symptoms and no functional limitations. Protection measures are scarce. It is important to characterize these features to provide early diagnosis and implement the necessary preventive measures.

Deposition and Clinical Impact of Inhaled Particles in the Lung

Particles suspended in the air we breathe are deposited in the airways as a function of the properties of the particle itself (shape, size and hydration), inspiratory air flow, airway anatomy, breathing environment, and mucociliary clearance. The scientific study of the deposition of inhaled particles in the airways has been conducted using traditional mathematical models and imaging techniques with particle markers. In recent years, the integration of statistical and computer methods, giving rise to a new discipline called digital microfluidics, has led to significant advances. In routine clinical practice, these studies are of great use for optimizing inhaler devices in line with particular characteristics of the drug to be inhaled and the pathology of the patient. (AU)

Hypercapnia Response in Patients with Obesity-Hypoventilation Syndrome Treated with Non-Invasive Ventilation at Home. / Respuesta a la hipercapnia en pacientes con síndrome obesidad-hipoventilación en tratamiento con ventilación no invasiva en domicilio.

INTRODUCTION: Respiratory center (RC) dysfunction has been implicated in the pathogenesis of obesity-hypoventilation syndrome (OHS), and often requires treatment with home non-invasive ventilation (NIV). Our objective was to measure the effect of NIV on RC function in patients with OHS, and the factors that determine such an effect. METHODS: We performed a prospective, repeated measures study to evaluate hypercapnia response (HR) by determining the p01/pEtCO2 ratio slope at baseline and after 6months of treatment with NIV in a group of OHS patients. A threshold of 0.22cmH2O/mmHg had previously been established in a control group, in order to differentiate optimal RC response from suboptimal RC response. RESULTS: A total of 36 cases were included, 19 men (52%) aged 65 (SD 9) years, 63% of whom had p01/pEtCO2 below the reference value. Baseline p01/pEtCO2 was 0.17 (SD: 0.14) cmH2O/mmHg and, after 6 months of NIV, 0.30 (SD: 0.22) cmH2O/mmHg (p=0.011). After 6months of treatment with NIV, depressed RC function persisted in 12 cases (33%). CONCLUSION: In total, 63% of OHS patients had RC dysfunction. The application of NIV improves RC function but not in all cases.

[Noninvasive, indirect measurement of pulmonary artery pressure]. / Determinación indirecta y no invasiva de la presión arterial pulmonar.

OBJECTIVE: The gold standard for measuring pulmonary artery pressure (PAP) is right heart catheterization. However, the usefulness of this technique is limited in patients with lung disease because of a poor acoustic window. The aim of this study was to assess PAP in a group of healthy persons using a noninvasive, indirect measurement procedure derived from the venous return flow velocity wave. MATERIAL AND METHODS: Twenty-three healthy volunteers with a mean (SD) age of 34 (9) years were evaluated. Measurements were made with a Hitachi EUB 5000 ultrasound device (3.5 MHz wave). The subject was placed in supine decubitus with neck hyperextended and head turned to one side. B-mode images were used to locate the point in the internal jugular vein 1 cm higher than its union with the subclavian vein. A color flow image was obtained of the vessel and a pulsed wave was then used to measure velocities. After 5 identical cycles, an estimate of PAP was derived from the ratio of maximum diastolic and systolic flow rates. RESULTS: On the right side, the mean (SD) ratio between flow rates was 0.50 (0.08), corresponding to a mean PAP of 15 (2.4) mm Hg. On the left side, the ratio was 0.55 (0.09), corresponding to a mean PAP of 16 (2.8) mm Hg. The nonsignificant difference between mean PAP values on the right and left was 1.3 (3.1) mm Hg, and higher values were on the left. CONCLUSIONS: Mean PAP values obtained with the described procedure are within the normal range for a healthy population. Transcutaneous venous Doppler ultrasound is useful for estimating PAP in healthy individuals.

[Benefits of a home-based pulmonary rehabilitation program for patients with severe chronic obstructive pulmonary disease]. / Beneficios de un programa de rehabilitación respiratoria domiciliaria en pacientes con EPOC grave.

OBJECTIVE: The benefits of a domiciliary program of pulmonary rehabilitation for patients with severe to very severe chronic obstructive pulmonary disease (COPD) are uncertain. We aimed to assess the short- and medium-term efficacy of such a program in this clinical setting. PATIENTS AND METHODS: Patients with severe COPD (stages III-IV, classification of the Global Initiative for Chronic Obstructive Lung Disease) and incapacitating dyspnea (scores 3-5, Medical Research Council [MRC] scale) were randomized to a control or domiciliary rehabilitation group. The 9-week supervised pulmonary rehabilitation program included educational sessions, respiratory physiotherapy, and muscle training in weekly sessions in the patient's home. We assessed the following variables at baseline, 9 weeks, and 6 months: lung function, exercise tolerance (3-minute walk test), dyspnea (MRC score), and health-related quality of life with the Chronic Respiratory Questionnaire (CRQ). RESULTS: Thirty-eight patients with a mean (SD) age of 68 (6) years were enrolled. The mean MRC score was 4 (0.8) and mean forced expiratory volume in 1 second was 29% of reference. Twenty-nine patients completed the study (6 months). Distance covered on the walk test increased significantly in the rehabilitation group (P=.001) and the difference was maintained at 6 months. Dyspnea also improved significantly with rehabilitation (P<.05), but the reduction was not evident at 6 months. Statistically significant improvements in symptoms related to 2 CRQ domains were detected between baseline and 9 weeks: dyspnea (3.1 [0.8] vs 3.6 [0.7]; P=.02) and fatigue (3.7 [0.8] vs 4.2 [0.9]; P=.002). A clinically relevant but not statistically significant change in mastery over disease was detected (from 4.3 to 4.9). All improvements were maintained at 6 months. CONCLUSIONS: Home-based pulmonary rehabilitation for patients with severe to very severe COPD and severe functional incapacity leads to improvements in exercise tolerance and health-related quality of life that are maintained at 6 months.

Grafeno y pulmón / Graphene and Lung

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[Translated article] Graphene and Lung / Grafeno y pulmón

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La neumología pos-COVID-19 / Post COVID-19 pneumology

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El currículum oculto ligeramente al descubierto / A Glimpse Behind the Hidden Curriculum

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