Omalizumab therapy in severe asthma: experience from the Spanish registry--some new approaches.

OBJECTIVE: The efficacy of omalizumab in severe asthma has been widely demonstrated. The main objective of this study was to evaluate the efficacy and tolerability of omalizumab in a real-life setting in Spain, particularly in those patients with immunoglobulin E (IgE) levels out of range. METHODS: Totally 266 uncontrolled severe asthma patients receiving high-dose inhaled corticosteroids (ICSs) plus long-acting ß2-agonist (LABA) were recruited. Main efficacy outcomes were asthma exacerbation rate (AER), asthma control test (ACT), and global evaluation of treatment effectiveness (GETE). RESULTS: AER was reduced from 3.6 (3.6) in previous year to 0.67 (1.2) at 4 months (p < .05) and to 1.04 (1.8) at 2 years (p < .05). ACT increased significantly from 14.3 (4.7) at baseline to 18.4 (4.4) at 4 months (p < .05) and to 20.3 (4.0) (p < .05) at 2 years. After 4 months, 74.6% of patients had reached a good or excellent rate on the GETE scale (p < .05). This rate continued increasing up to 81.6% at 2 years. These efficacy results were similar for patients with "off-label" IgE > 700 IU/ml. At follow-up, maintenance treatment with oral steroids was discontinued in a considerable number of patients: from 89 to 19 (p < .05). Omalizumab was discontinued because of lack of efficacy only in 28/266 (10.5%) patients. Overall, 30 patients (11.4%) reported adverse events. Severe adverse events were not observed. CONCLUSION: This real-life study confirms that omalizumab is very efficacious and very well tolerated in patients with uncontrolled severe asthma. Results did not vary in the subgroup of patients with IgE levels >700 IU/ml.

Increased Urinary Erythropoietin Excretion in Severe Sleep Apnea-Hipoapnea Syndrome: The Effect of CPAP. / El síndrome de apneas-hipoapneas del sueño (SAHS) grave incrementa la excreción urinaria de eritropoyetina. Efecto del tratamiento con CPAP.

INTRODUCTION: Tissue hypoxia stimulates the production of erythropoietin (EPO), the main effect of which is, in turn, to stimulate erythropoiesis. Sleep apnea-hypopnea syndrome (SAHS) is an entity characterized by repeated episodes of hypoxemia during sleep. OBJECTIVE: To analyze whether hypoxemia stimulated increased urinary excretion of EPO, and if so, to evaluate if treatment with continuous positive airway pressure (CPAP) can inhibit this phenomenon. METHODS: We studied 25 subjects with suspected SAHS who underwent a polysomnography study (PSG). EPO levels in first morning urine (uEPO) and blood creatinine and hemoglobin were determined in all patients. Patients with severe SAHS repeated the same determinations after CPAP treatment. RESULTS: Twelve subjects were diagnosed with severe SAHS (mean ± SD, AHI 53.1 ± 22.7). Creatinine and hemoglobin levels were normal in all subjects. uEPO was 4 times higher in the SAHS group than in the control group (1.32 ± 0.83 vs. 0.32 ± 0.35 UI/l, p <.002). CPAP treatment reduced uEPO to 0.61 ± 0.9 UI/l (p <.02), levels close to those observed in healthy subjects. No dose-response relationship was observed between severity of PSG changes and uEPO values. CONCLUSIONS: Patients with severe SAHS show increased uEPO excretion, but this normalizes after treatment with CPAP.

Long-term Impact of Continuous Positive Airway Pressure Therapy on Arrhythmia and Heart Rate Variability in Patients With Sleep Apnea.

INTRODUCTION: Autonomic dysfunction can alter heart rate variability and increase the incidence of arrhythmia. We analyzed the impact of continuous positive airway pressure (CPAP) on this pathophysiological phenomenon in patients with severe sleep apnea-hypopnea syndrome. METHODS: Consecutive patients with recently diagnosed severe sleep apnea-hypopnea syndrome were prospectively considered for inclusion. Incidence of arrhythmia and heart rate variability (recorded on a 24-hour Holter monitoring device) were analyzed before starting CPAP therapy and 1 year thereafter. RESULTS: A total of 26 patients were included in the study. CPAP was administered for 6.6 ± 1.8 hours during Holter monitoring. After starting CPAP, we observed a marginally significant reduction in mean HR (80 ± 9 to 77 ± 11 bpm, p=.05). CPAP was associated with partial modulation (only during waking hours) of r-MSSD (p=.047) and HF (p=.025) parasympathetic parameters and LF (p=.049) sympathetic modulation parameters. None of these parameters returned completely to normal levels (p<.001). The number of unsustained episodes of atrial tachycardia diminished (p=.024), but no clear effect on other arrhythmias was observed. CONCLUSIONS: CPAP therapy only partially improves heart rate variability, and exclusively during waking hours, and reduces incidence of atrial tachycardia, both of which can influence cardiovascular morbidity and mortality in sleep apnea-hypopnea syndrome patients.

[Global muscle dysfunction and exacerbation of COPD: a cohort study]. / Disfunción muscular global durante la exacerbación de la EPOC: un estudio de cohortes.

BACKGROUND AND OBJECTIVE: The purpose of this study was to evaluate on a prospective fashion the effects of clinical relapses of chronic obstructive pulmonary disease (COPD) on both peripheral and respiratory skeletal muscle functions. PATIENTS AND METHOD: We included 49 patients (males, 63 [11] years) who were assigned to three cohorts: a) COPD patients who were hospitalized in a conventional ward because of a relapse of their disease; b) patients hospitalized in conventional wards because of another lung disease or a pulmonary nodule; and c) COPD patients whose disease was stabilized (outpatients). Sequential measurements were made by means of anthropometry, serum biochemistry and body bioimpedance (BIA). In COPD patients with a disease relapse, we assessed changes in the function of peripheral muscles [force (Fhand) and resistance (Tlimhand) of hands], inspiratory muscles (PImax) and respiratory muscles (PEmax). RESULTS: Patients were evaluated during a 6 [2] days period. Patients with a COPD relapse displayed a global and progressive functional muscle impairment, which was expressed as a decrease of PEmax (17 [12]%), F hand-D (6 [9]%), F hand-ND (7 [8]%), Tlim hand-D (28 [26]%) and Tlim hand-ND (23 [16]%). These changes showed a linear trend. BIA exhibited a loss of lean mass (7 [6]%, p < 0.05) which would have been unnoticeable if only the body weight was quantified. Pneumonia cases showed similar changes in BIA. On the other hand, the cohort of patients with stable COPD did not have changes in both muscle function and BIA. CONCLUSIONS: COPD exacerbation is associated with an acute and global impairment of the function of respiratory and peripheral skeletal muscles. It is possible that these changes are related to an acute loss of muscular mass (proteolysis). This muscle dysfunction is not detected if only the inspiratory muscular function is evaluated--possibly because of the coexistence of transitory mechanic factors.

Obstructive sleep apnea in patients with typical atrial flutter: prevalence and impact on arrhythmia control outcome.

BACKGROUND: The clinical yield of cavotricuspid isthmus (CTI) radiofrequency ablation of atrial flutter (AF) is limited by a high incidence of atrial fibrillation (AFib) in the long term. Among other acknowledged variables, the association of obstructive sleep apnea (OSA) could favor incomplete arrhythmia control in this setting. We assessed the impact of CPAP in reducing the occurrence of AFib after CTI ablation. METHODS: Consecutive patients with AF who were undergoing CTI ablation were screened for OSA. Relationship of the following variables with the occurrence of AFib during follow-up (12 months) was investigated: CPAP initiation, hypertension, BMI, underlying structural heart disease, left atrial diameter, and AFib documentation prior to ablation. RESULTS: We prospectively included 56 patients (mean age: 66 (± 11) years; 12 female patients), of whom 46 (82%) had OSA and 25 (45%) had severe OSA. Twenty-one patients (38%) had AFib during follow-up after CTI ablation. Both freedom from AFib prior to ablation and CPAP initiation in those patients without previously documented AFib at inclusion were associated with a reduction of AFib episodes during follow-up (P = .019 and P = .025, respectively). Inversely, CPAP was not protective from AFib recurrence when this arrhythmia was documented prior to ablation (P = .25). CONCLUSIONS: OSA is a prevalent condition in patients with AF. Treatment with CPAP is associated with a lower incidence of newly diagnosed AFib after CTI ablation. Screening for OSA in patients with AF appears to be a reasonable clinical strategy.

El síndrome de apneas-hipoapneas del sueño (SAHS) grave incrementa la excreción urinaria de eritropoyetina. Efecto del tratamiento con CPAP / Increased Urinary Erythropoietin Excretion in Severe Sleep Apnea-Hipoapnea Syndrome: The Effect of CPAP

Introducción: La hipoxia tisular estimula la producción de eritropoyetina (EPO) que tiene como principal función estimular la eritropoyesis. El SAHS es una entidad caracterizada por la presencia de episodios repetidos de hipoxemia durante el sueño. Objetivo: Analizar si dicha hipoxemia es un estímulo suficiente para incrementar la excreción urinaria de EPO. Si la respuesta fuera positiva, valorar si el tratamiento con presión continua positiva de la vía aérea (CPAP) la inhibiría. Métodos: Se han estudiado 25 sujetos con sospecha de SAHS, a los que se les realizó un estudio polisomnográfico. En todos ellos se determinaron los niveles de EPO en la primera orina de la mañana (uEPO), así como los niveles de creatinina y hemoglobina en sangre. En los pacientes con SAHS grave se repitieron las mismas determinaciones tras el tratamiento con CPAP. Resultados: Doce sujetos fueron diagnosticados de SAHS grave (media ± SD, IAH de 53,1 ± 22,7). La creatinina y la hemoglobina fueron normales en todos los sujetos. La uEPO fue cuatro veces superior en el grupo SAHS respecto a los controles (1,32 ± 0,83 vs. 0,32 ± 0,35 IU/l, p < 0,002). El tratamiento con CPAP descendió la uEPO hasta 0,61 ± 0,49 IU/l (p < 0,02), acercándose al valor de los sujetos sanos. No se observó una relación dosis-respuesta entre la gravedad de las alteraciones de la PSG y los valores de uEPO. Conclusiones: Los pacientes con SAHS grave muestran un incremento en su excreción de uEPO, que se normaliza tras el tratamiento con CPAP

Introduction: Tissue hypoxia stimulates the production of erythropoietin (EPO), the main effect of which is, in turn, to stimulate erythropoiesis. Sleep apnea-hypopnea syndrome (SAHS) is an entity characterized by repeated episodes of hypoxemia during sleep. Objective: To analyze whether hypoxemia stimulated increased urinary excretion of EPO, and if so, to evaluate if treatment with continuous positive airway pressure (CPAP) can inhibit this phenomenon. Methods: We studied 25 subjects with suspected SAHS who underwent a polysomnography study (PSG). EPO levels in first morning urine (uEPO) and blood creatinine and hemoglobin were determined in all patients. Patients with severe SAHS repeated the same determinations after CPAP treatment. Results: Twelve subjects were diagnosed with severe SAHS (mean ± SD, AHI 53.1 ± 22.7). Creatinine and hemoglobin levels were normal in all subjects. uEPO was 4 times higher in the SAHS group than in the control group (1.32 ± 0.83 vs. 0.32 ± 0.35 UI/l, p <.002). CPAP treatment reduced uEPO to 0.61 ± 0.9 UI/l (p <.02), levels close to those observed in healthy subjects. No dose-response relationship was observed between severity of PSG changes and uEPO values. Conclusions: Patients with severe SAHS show increased uEPO excretion, but this normalizes after treatment with CPAP

Impacto a largo plazo del tratamiento con presión positiva continua en la vía aérea superior sobre la incidencia de arritmias y la variabilidad de frecuencia cardiaca en pacientes con apnea del sueño / Long-term Impact of Continuous Positive Airway Pressure Therapy on Arrhythmia and Heart Rate Variability in Patients With Sleep Apnea

Introducción: La disfunción del sistema nervioso autonómico produce alteraciones en la variabilidad de la frecuencia cardiaca y aumenta la incidencia de arritmias. Analizamos este fenómeno fisiopatológico en pacientes con síndrome de apnea/hipoapnea del sueño severo y el impacto sobre el mismo del tratamiento con presión positiva continua en la vía aérea (CPAP). Métodos: Pacientes consecutivos con síndrome de apnea/hipoapnea del sueño severo de reciente diagnóstico fueron prospectivamente considerados para inclusión. Se analizó la incidencia de arritmias y la variabilidad de la frecuencia cardiaca (obtenidos mediante registro Holter de 24 horas) antes de iniciarse tratamiento con CPAP y tras un año del mismo. Resultados: Se incluyeron 26 pacientes. El tiempo de uso de CPAP durante el registro Holter fue de 6,6 ± 1,8 horas. Tras inicio de CPAP, se apreció una reducción marginalmente significativa en la FC media (80 ± 9 a 77 ± 11 lpm, p = 0,05). El uso de CPAP se asoció a una modulación parcial y exclusivamente en horas de vigilia de los parámetros de modulación parasimpáticar-MSSD (p = 0,047) y HF (p = 0,025) y de modulación simpática LF (p = 0,049). Ninguno de estos revirtió completamente a la normalidad (p < 0,001). Se observó una reducción de los episodios no sostenidos de taquicardia auricular (p = 0,024), sin efecto demostrativo sobre otras arritmias. Conclusiones: El tratamiento con CPAP se asocia a una mejora solo parcial y diurna de la variabilidad de la frecuencia cardiaca y disminuye la incidencia de taquicardia auricular. Ambos efectos podrían influir en la morbimortalidad cardiovascular de los pacientes con síndrome de apnea/hipoapnea del sueño

Introduction: Autonomic dysfunction can alter heart rate variability and increase the incidence of arrhythmia. We analyzed the impact of continuous positive airway pressure (CPAP) on this pathophysiological phenomenon in patients with severe sleep apnea-hypopnea syndrome. Methods: Consecutive patients with recently diagnosed severe sleep apnea-hypopnea syndrome were prospectively considered for inclusion. Incidence of arrhythmia and heart rate variability (recorded on a 24-hour Holter monitoring device) were analyzed before starting CPAP therapy and 1 year thereafter. Results: A total of 26 patients were included in the study. CPAP was administered for 6.6 ± 1.8 hours during Holter monitoring. After starting CPAP, we observed a marginally significant reduction in mean HR (80 ± 9 to 77 ± 11 bpm, p = .05). CPAP was associated with partial modulation (only during waking hours) of r-MSSD (p = .047) and HF (p = .025) parasympathetic parameters and LF (p = .049) sympathetic modulation parameters. None of these parameters returned completely to normal levels (p < .001). The number of unsustained episodes of atrial tachycardia diminished (p = .024), but no clear effect on other arrhythmias was observed. Conclusions: CPAP therapy only partially improves heart rate variability, and exclusively during waking hours, and reduces incidence of atrial tachycardia, both of which can influence cardiovascular morbidity and mortality in sleep apnea-hypopnea syndrome patients

[Safety and tolerability of bronchodilators in chronic obstructive pulmonary disease]. / Tolerabilidad y seguridad de los broncodilatadores en la EPOC.

The most effective bronchodilators in chronic obstructive pulmonary disease (COPD) are beta(2)-adrenergic and anticholinergic agents. When administered via inhalation and at recommended doses, these drugs are well tolerated and generally safe. beta-Adrenergic agents show systemic effects such as an increase in heart rate, QT prolongation, hypopotassemia and tremor. These effects have little clinical significance. Nevertheless, patients with cardiac comorbidity or respiratory insufficiency can be at greater risk of arrhythmia and other adverse cardiac events. Long action beta(2)-adrenergic agents have not been shown to increase mortality in COPD. The most frequent adverse effect of anticholinergic agents is dryness of the mouth; these drugs also increase the risk of glaucoma and urinary retention. Anticholinergic agents may increase cardiovascular risk, although the evidence is inconsistent. The use of methylxanthines is limited by frequent gastrointestinal adverse effects and by the narrow therapeutic range of these drugs.

Tolerabilidad y seguridad de los broncodilatadores en la EPOC / Safety and tolerability of bronchodilators in chronic obstructive pulmonary disease

Los broncodilatadores más efectivos en la enfermedad pulmonar obstructiva crónica (EPOC) son los β2- adrenérgicos y los anticolinérgicos. Por vía inhalatoria y a las dosis recomendadas son bien tolerados y, en general, seguros. Los β-adrenérgicos muestran efectos sistémicos de clase, como aumento de la frecuencia cardíaca, alargamiento del QT, hipopotasemia y temblor. Estos efectos tienen escasa relevancia clínica. No obstante, los pacientes con comorbilidad cardíaca o insuficiencia respiratoria pueden tener un mayor riesgo de arritmias y otros acontecimientos cardíacos adversos. No se ha demostrado que los β2-adrenérgicos de acción prolongada incrementen la mortalidad en la EPOC. Los anticolinérgicos tienen como efecto secundario más frecuente la sequedad de boca; también potencian el riesgo de glaucoma y retención urinaria. Se ha sugerido que los anticolinérgicos aumentan el riesgo cardiovascular, aunque la evidencia al respecto no es consistente. La utilización de las metilxantinas está limitada por efectos secundarios frecuentes de tipo digestivo y por su estrecho rango terapéutico (AU)

The most effective bronchodilators in chronic obstructive pulmonary disease (COPD) are β2-adrenergic and anticholinergic agents. When administered via inhalation and at recommended doses, these drugs are well tolerated and generally safe. β-Adrenergic agents show systemic effects such as an increase in heart rate, QT prolongation, hypopotassemia and tremor. These effects have little clinical significance. Nevertheless, patients with cardiac comorbidity or respiratory insufficiency can be at greater risk of arrhythmia and other adverse cardiac events. Long action β2-adrenergic agents have not been shown to increase mortality in COPD. The most frequent adverse effect of anticholinergic agents is dryness of the mouth; these drugs also increase the risk of glaucoma and urinary retention. Anticholinergic agents may increase cardiovascular risk, although the evidence is inconsistent. The use of methylxanthines is limited by frequent gastrointestinal adverse effects and by the narrow therapeutic range of these drugs (AU)