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.

Expert consensus on the use of systemic glucocorticoids for managing eosinophil-related diseases.

Eosinophil-related diseases represent a group of pathologic conditions with highly heterogeneous clinical presentation and symptoms ranging from mild to critical. Both systemic and localized forms of disease are typically treated with glucocorticoids. The approval of novel biologic therapies targeting the interleukin-5 pathway can help reduce the use of systemic glucocorticoids (SGC) in eosinophilic diseases and reduce the risk of SGC-related adverse effects (AEs). In this article, a panel of experts from different medical specialties reviewed current evidence on the use of SGC in two systemic eosinophilic diseases: Eosinophilic Granulomatosis with PolyAngiitis (EGPA) and HyperEosinophilic Syndrome (HES); and in two single-organ (respiratory) eosinophilic diseases: Chronic RhinoSinusitis with Nasal Polyps (CRSwNP) and Severe Asthma with Eosinophil Phenotype (SA-EP), and contrasted it with their experience in clinical practice. Using nominal group technique, they reached consensus on key aspects related to the dose and tapering of SGC as well as on the initiation of biologics as SGC-sparing agents. Early treatment with biologics could help prevent AEs associated with medium and long-term use of SGC.

N-acetylcysteine for prevention and treatment of COVID-19: Current state of evidence and future directions.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes coronavirus disease 2019 (COVID-19) and can be associated with serious complications, including acute respiratory distress syndrome. This condition is accompanied by a massive release of cytokines, also denominated cytokine storm, development of systemic oxidative stress and a prothrombotic state. In this context, it has been proposed a role for acetylcysteine (NAC) in the management of patients with COVID-19. NAC is a molecule classically known for its mucolytic effect, but it also has direct and indirect antioxidant activity as a precursor of reduced glutathione. Other effects of NAC have also been described, such as modulating the immune and inflammatory response, counteracting the thrombotic state, and having an antiviral effect. The pharmacological activities of NAC and its effects on the mechanisms of disease progression make it a potential therapeutic agent for COVID-19. NAC is safe, tolerable, affordable, and easily available. Moreover, the antioxidant effects of the molecule may even prevent infection and play an important role as a complement to vaccination. Although the clinical efficacy and dosing regimens of NAC have been evaluated in the clinical setting with small series of patients, the results are promising. In this article, we review the pathogenesis of SARS-CoV-2 infection and the current knowledge of the mechanisms of action of NAC across disease stages. We also propose NAC posology strategies to manage COVID-19 patients in different clinical scenarios.

Defining the Profile of Obstructive Sleep Apnea in Women Compared to Men.

Background: The importance of understanding the presentation of obstructive sleep apnea (OSA) in women has been increasingly recognized. Although there is some insight that there are significant differences in presentation between women and men, the consequences of such differences, particularly for treatment have not yet been fully identified. Thus, the objective of this study was to determine the phenotype of OSA in women. Materials and Methods: Study of a population-based clinical cohort of 2022 patients with OSA confirmed by polygraphy or polysomnography (apnea-hypopnea index [AHI] >5/hour). Comorbidities, symptoms, physical examination, current medical treatments, and sleep parameters were recorded. Results: A total of 709 women and 1313 men were included in this study. After adjustment for anthropometric characteristics, morphological alterations, and previous treatment, women were found to have lower AHI values (25.3 ± 1.2 vs. 35.0 ± 0.9; p < 0.001), desaturation index (24.4 ± 1.2 vs. 33.2 ± 0.9; p < 0.001), and saturation time <90% (18.8 ± 1.3 vs. 24.1 ± 1.0; p < 0.001) compared with men. Furthermore, women had a lower risk of witnessed apnea (odds ratio adjusted [ORa] for baseline characteristics and sleep parameters), (ORa: 0.53, 95% confidence interval [CI]: 0.40-0.71), reduced sensation of restful sleep (ORa: 0.50, 95% CI: 0.38-0.66), greater fatigue (ORa: 2.68, 95% CI: 1.86-3.86), headache (ORa: 3.00, 95% CI: 2.26-3.97), memory disorders (ORa: 1.836, 95% CI: 1.40-2.41), insomnia (ORa: 2.09, 95% CI: 1.50-2.93), and excessive daytime sleepiness (ORa: 1.41, 95% CI: 1.03-1.92), with interference in their daily activities (ORa: 1.54, 95% CI: 1.17-2.03). Likewise, after adjustment for anthropometric characteristics and sleep parameters, women also showed higher risk of depression (ORa: 4.31, 95% CI: 3.15-5.89) and anxiety (ORa: 3.18, 95% CI: 2.38-4.26). Conclusions: Our findings suggest that women present a specific OSA phenotype, with a probable implication for clinical, diagnostic, and therapeutic management.

Short and Long-Term Impact of COVID-19 Infection on Previous Respiratory Diseases.

On March 11, 2020, the World Health Organization declared Coronavirus Disease 2019 (COVID-19) a pandemic. Till now, it affected 452.4 million (Spain, 11.18 million) persons all over the world with a total of 6.04 million of deaths (Spain, 100,992). It is observed that 75% of hospitalized COVID-19 patients have at least one COVID-19 associated comorbidity. It was shown that people with underlying chronic illnesses are more likely to get it and grow seriously ill. Individuals with COVID-19 who have a past medical history of cardiovascular disorder, cancer, obesity, chronic lung disease, diabetes, or neurological disease had the worst prognosis and are more likely to develop acute respiratory distress syndrome or pneumonia. COVID-19 can affect the respiratory system in a variety of ways and across a spectrum of levels of disease severity, depending on a person's immune system, age and comorbidities. Symptoms can range from mild, such as cough, shortness of breath and fever, to critical disease, including respiratory failure, shock and multi-organ system failure. So, COVID-19 infection can cause overall worsening of these previous respiratory diseases, such as asthma, chronic obstructive pulmonary disease (COPD), interstitial lung disease, etc. This review aims to provide information on the impact of the COVID-19 disease on pre-existing lung comorbidities.

Cost-effectiveness analysis of anti-IL-5 therapies of severe eosinophilic asthma in Spain.

AIM: To analyse the cost-effectiveness of MEP with standard of care (SoC) versus other anti-IL-5 therapies approved for the treatment of severe eosinophilic asthma (SEA) patients, within the Spanish National Health System (NHS) perspective. METHODS: A Markov model with a 4-week cycle length was used to compare MEP with BEN and RES as therapies added to SoC in the management of SEA, in terms of cost per QALY gained and incremental cost-effectiveness ratio (ICER). Costs (€2019) were obtained from public sources, while utilities and transition probabilities were retrieved from literature, e.g. network meta-analysis. Continuation criteria for biological treatment and reduction of oral corticosteroids (OCS) was set at 50% minimum reduction of exacerbation rate. Adverse events related to chronic OCS use included diabetes, osteoporosis, cataracts, acute myocardial infarct, and peptic ulcer. The analysis was performed over a 5-year time horizon from the National Healthcare System (NHCS) perspective, with a yearly discount rate of 3% applied to both costs and QALYs. Probabilistic sensitivity analysis and univariate deterministic sensitivity analysis were performed to address uncertainty around the cost-effectiveness results. RESULTS: On top of SoC, the model indicates that MEP is dominant (lower cost, higher benefit) compared to BEN and RES: For BEN and RES, respectively, treatment with MEP had a point estimate of 0.076 and 0.075 additional QALYs, and savings of €3,173.47 and €7,772.95 per patient. The findings were robust to variation as estimated using sensitivity analysis. CONCLUSIONS: MEP is a cost-effective treatment in comparison with BEN and RES added to SoC for patients with SEA in the Spanish setting.

Clinical and Economic Consequences of Inhaled Corticosteroid Doses and Particle Size in Triple Inhalation Therapy for COPD: Real-Life Study.

Objective: To determine the clinical and economic consequences of inhaled corticosteroid doses and particle size in patients on triple-inhalation therapy for COPD. Methods: Patients aged ≥40 years who initiated treatment with multi-inhaler triple-inhaled therapy between 1 January 2015 and 31 March were included and followed for 1 year. Patients were grouped according to inhaled corticosteroid (ICS) dose (low/medium/high) and particle size device (extrafine/non-extrafine particles). Outcome variables were moderate and severe exacerbations, pneumonia and healthcare resource use (HCRU) costs. A multivariate analysis was performed for model correction (p<0.05). Results: A total of 2185 patients (mean age 72.3 years, 82.9% male) were analysed. Of these, 849 (38.9%) patients received low-dose ICS, 612 medium-dose ICS (28.0%) and 724 (33.1%) high-dose ICS. Exacerbations occurred more frequently with increasing IC dose (low: 26.4%, medium: 28.7% and high: 30.4%; p=0.047), as did the proportion of pneumonia (3.4%, 4.2% and 6.9%, respectively (p=0.041)). The annual mean cost/unit was € 2383 for low dose, € 2401 for medium dose and € 2625 for high dose (p=0.024). Four hundred and sixty-two (31.6%) patients used an extrafine particle device and 999 (68.4%) a non-extrafine particle device: the proportion of exacerbations was 24.0% vs 30.4% (p=0.012), and the annual mean cost/unit was € 2090 vs € 2513, respectively (p<0.001). The number of exacerbations was directly correlated with FEV1 (ß= -0.157), age (ß=0.071), Charlson index (ß=0.050) and device type (extrafine: ß=0.049) (p<0.02). Conclusion: In patients with COPD receiving multi-inhaler triple therapy, higher ICS doses were not associated with a further reduction in exacerbations, whereas we found an increased risk of pneumonia. The use of inhaler devices delivering extrafine ICS particle was associated with a lower rate of exacerbations, resulting in lower overall HCRU costs.

Cost-Effectiveness Analysis of a Once-Daily Single-Inhaler Triple Therapy for Patients with Chronic Obstructive Pulmonary Disease (COPD) Using the FULFIL Trial: A Spanish Perspective.

Purpose: To evaluate the cost-effectiveness of once-daily fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) vs twice-daily budesonide/formoterol (BUD/FOR) in patients with symptomatic chronic obstructive pulmonary disease (COPD) at risk of exacerbations, from the Spanish National Healthcare System perspective. Patients and Methods: The validated GALAXY-COPD model was used to simulate disease progression and predict healthcare costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs) over a 3-year time horizon for a Spanish population. Patient characteristics from published literature were supplemented by data from FULFIL (NCT02345161), which compared FF/UMEC/VI vs BUD/FOR in patients with symptomatic COPD at risk of exacerbations. Treatment effects, extrapolated to 3 years, were based on Week 24 results in the FULFIL intent-to-treat population, including change in forced expiratory volume in 1 second, St. George's Respiratory Questionnaire score, and exacerbation rates. Treatment, exacerbations, and COPD management costs (2019€) were informed by Spanish public sources and published literature. A 3% discount rate for costs and benefits was applied. One-way sensitivity and scenario analyses, and probabilistic sensitivity analysis (PSA), were performed. Results: FF/UMEC/VI treatment led to fewer moderate and severe exacerbations (2.126 and 0.306, respectively) vs BUD/FOR (2.608 and 0.515, respectively), with a mean incremental cost of €69 and gain of 0.107 QALYs, which resulted in an ICER of €642 per QALY gained. In sensitivity analyses, the ICER was most sensitive to treatment effect variations in exacerbations and healthcare resource utilization/event costs. Overall, 95% of 1000 PSA simulations resulted in an ICER less than €11,000 per QALY gained for FF/UMEC/VI vs BUD/FOR, confirming robustness of the results. The probability of FF/UMEC/VI being cost-effective vs BUD/FOR was 100% at a willingness-to-pay threshold of €30,000 per QALY gained. Conclusion: At the accepted Spanish ICER threshold of €30,000, FF/UMEC/VI represents a cost-effective treatment option vs BUD/FOR in patients with symptomatic COPD at risk of exacerbations.

La neumología en tiempos de COVID-19 / Pneumology in the Days of COVID-19

No disponible

Type 2 Diabetes Mellitus, Glycated Hemoglobin Levels, and Cardiopulmonary Exercise Capacity in Patients With Ischemic Heart Disease.

PURPOSE: Diabetes mellitus (DM) is associated with long-term cardiovascular complications, including ischemic heart disease (IHD). Nonetheless, DM may directly impair myocardial and lung structure and function. The aim of this study was to assess the impact of type 2 DM (T2DM) and glycemic control on cardiopulmonary exercise capacity in patients with IHD. METHODS: The study involved a cross-sectional analysis of 91 consecutive patients (57 ± 10 yr, 90% men) who underwent a cardiopulmonary exercise test at the beginning of an exercise-based standard phase-II cardiac rehabilitation program, 2 to 3 mo after an acute coronary syndrome. Association of T2DM with cardiopulmonary exercise test parameters was assessed using multiple linear regression analysis controlling for prespecified potential confounders. RESULTS: There were 26 (29%) diabetic subjects among IHD patients included in the study. After adjustment, T2DM was an independent predictor of a reduced peak oxygen uptake ((Equation is included in full-text article.)O2peak) (P = .005), a reduced pulse O2 trajectory (P = .001), a steeper minute ventilation to carbon dioxide output (VE/(Equation is included in full-text article.)CO2) slope (P = .046), and an increased dead space-to-tidal volume ratio (VD/VT) at peak exercise (P = .049). Glycated hemoglobin (HbA1c) levels were significantly associated with a reduced forced expiratory volume in the first second of expiration (FEV1) (P = .013), VE (P = .001), and VT (P = .007). (Equation is included in full-text article.)O2peak (P trend < .001), (Equation is included in full-text article.)O2 at anaerobic threshold (P trend < .001), and pulse O2 trajectory (P trend < .001) decreased among HbA1c tertiles. CONCLUSIONS: Patients with IHD and a previous diagnosis of T2DM had a reduced aerobic capacity and a ventilation- perfusion mismatch compared with nondiabetic patients. Poor glycemic control in men further deteriorates aerobic capacity probably due to ventilatory inefficiency.

Paciente exacerbador con enfermedad pulmonar obstructiva crónica: recomendaciones en procesos diagnósticos, terapéuticos y asistenciales / Patients with Chronic Obstructive Pulmonary Disease Exacerbations: Recommendations for Diagnosis, Treatment and Care

Objetivo: Describir un acuerdo entre expertos basado en la evidencia y la experiencia sobre los aspectos más relevantes del paciente exacerbador con EPOC. Métodos: Se siguió la metodología Delphi. Tras revisar la evidencia por un comité científico y 60 expertos, se elaboró un cuestionario con 3 apartados: diagnóstico del paciente exacerbador; tratamiento, y proceso asistencial. La encuesta fue respondida online en 2 rondas por 60 neumólogos. El grado de acuerdo siguió la escala Likert de 1 (total desacuerdo) a 9 (total acuerdo), definiéndose acuerdo y desacuerdo como una puntuación de 7-9 o 1-3, respectivamente, otorgada por más de dos tercios de los participantes. Resultados: Se incluyeron un total de 48 aseveraciones, una añadida en la segunda ronda. Hubo consenso en 37 (78,7%) tras la primera ronda (acuerdo), y en 43 (89,5%) tras la segunda (42 acuerdo y 1 desacuerdo). Las afirmaciones con mayor proporción de expertos en el rango de acuerdo se refirieron a que, en el paciente exacerbador, la infección bronquial crónica favorece el deterioro de la función pulmonar (93,1%), a que no se deben retirar los broncodilatadores de larga duración (93,1%), a la conveniencia de personalizar el tratamiento si se dan nuevas exacerbaciones pese a un tratamiento broncodilatador óptimo (96,6%), o al cuidado y manejo de este paciente, que debe ser coordinado entre atención primaria y neumología (93,1%) y controlado en programas integrados específicos multicomponente (94,8%). Conclusiones: La información proporcionada por este consenso puede facilitar el diagnóstico y tratamiento del paciente exacerbador con EPOC en nuestro ámbito

Objective: To describe an evidence- and experience-based expert consensus on the most relevant issues of patients with COPD exacerbations. Methods: The Delphi technique was used. Evidence was reviewed by a scientific committee and 60 experts. A questionnaire was prepared containing 3 sections: diagnosis of the exacerbator; treatment, and healthcare processes. The survey was answered in 2 rounds by 60 pneumologists on an online platform. Statements were scored on a Likert scale from 1 (total disagreement) to 9 (total agreement). Agreement and disagreement were defined as a score of 7-9 or 1-3, respectively, given by more than two thirds of the participants. Results: A total of 48 statements were included, one of which was added in the second round. Consensus was reached in 37 items (78.7%) after the first round (agreement), and in 43 (89.5%) after the second round (42 agreement, 1 disagreement). The statements with the highest proportion of experts agreeing were as follows: in exacerbators, chronic bronchial infection favors lung function decline (93.1%); long-acting bronchodilators should not be withdrawn (93.1%); treatment must be personalized if new exacerbations occur despite optimal bronchodilator treatment (96.6%); management must be coordinated between primary care and the respiratory medicine department (93.1%), and patients must be followed up in specific integrated multicomponent programs (94.8%). Conclusions: The findings of this study could assist in the diagnosis and treatment of COPD exacerbators in our area

Patients with Chronic Obstructive Pulmonary Disease Exacerbations: Recommendations for Diagnosis, Treatment and Care. / Paciente exacerbador con enfermedad pulmonar obstructiva crónica: recomendaciones en procesos diagnósticos, terapéuticos y asistenciales.

OBJECTIVE: To describe an evidence- and experience-based expert consensus on the most relevant issues of patients with COPD exacerbations. METHODS: The Delphi technique was used. Evidence was reviewed by a scientific committee and 60 experts. A questionnaire was prepared containing 3 sections: diagnosis of the exacerbator; treatment, and healthcare processes. The survey was answered in 2 rounds by 60 pneumologists on an online platform. Statements were scored on a Likert scale from 1 (total disagreement) to 9 (total agreement). Agreement and disagreement were defined as a score of 7-9 or 1-3, respectively, given by more than two thirds of the participants. RESULTS: A total of 48 statements were included, one of which was added in the second round. Consensus was reached in 37 items (78.7%) after the first round (agreement), and in 43 (89.5%) after the second round (42 agreement, 1 disagreement). The statements with the highest proportion of experts agreeing were as follows: in exacerbators, chronic bronchial infection favors lung function decline (93.1%); long-acting bronchodilators should not be withdrawn (93.1%); treatment must be personalized if new exacerbations occur despite optimal bronchodilator treatment (96.6%); management must be coordinated between primary care and the respiratory medicine department (93.1%), and patients must be followed up in specific integrated multicomponent programs (94.8%). CONCLUSIONS: The findings of this study could assist in the diagnosis and treatment of COPD exacerbators in our area.

Respuesta a omalizumab en paciente con neumonía eosinófila crónica y mala respuesta al tratamiento con corticoides / Response to Omalizumab in a Patient With Chronic Eosinophilic Pneumonia and Poor Response to Corticosteroids

No disponible

Futuro de los marcadores biológicos en la EPOC / The Future of Biololgical Markers in COPD

No disponible