New Approaches to the Management of Cardiovascular Risk Associated with Sleep Respiratory Disorders in Pediatric Patients.

Exposure to risk factors in youth can exacerbate the development of future cardiovascular disease (CVD). Obstructive sleep apnea (OSA), characterized by repetitive episodes of airway obstructions, could trigger said CVD acting as a modifiable risk factor. Measurements from echocardiography have shown impairments in the anatomy and function of the heart related to the severity of OSA. Therefore, the aim of this review was to propose a new clinical approach to the management of cardiovascular risk (CVR) in children based on treating OSA. The review includes studies assessing echocardiographic parameters for cardiac function and structure in pediatric OSA diagnosed using the apnea-hypopnea index (AHI) ≥ 1/h using polysomnography (PSG) and conducted within a year. Based on the reviewed evidence, in addition to PSG, echocardiography should be considered in OSA children in order to indicate the need for treatment and to reduce their future CVR. A follow-up echocardiography after treatment could be performed if impairments in the anatomy and function were found. Prioritizing parameters intimately connected to comorbidity could propel more effective patient-centered care. In conclusion, a reevaluation of pediatric OSA strategies should be considered, emphasizing comorbidity-related parameters in the cardiovascular field. Further studies are needed to assess this approach, potentially leading to enhanced protocols for more effective pediatric OSA treatment and CVR prevention.

Impact of obstructive sleep apnea in cardiovascular risk in the pediatric population: A systematic review.

While the association of obstructive sleep apnea (OSA) with an increased cardiovascular risk (CVR) in the adult population is well known, there is insufficient evidence to affirm something similar in the pediatric population. On the other hand, adenotonsillectomy has been shown to be an effective treatment. Our objective was to evaluate the association of sleep respiratory disorders in children with increased CVR and the impact of adenotonsillectomy in the literature. To this aim, a literature search was conducted, between 2002 to the present. After carrying out a systematic review, the following results were provided: thoracic echocardiography after surgery found improvements in terms of cardiac function and structure; blood pressure (BP) measurement, verified a tendency to higher BP values in the OSA pediatric population, which improved after surgery; different biomarkers of CVR, were increased in OSA patients and improved after treatment and finally; some studies found endothelial dysfunction in pediatric OSA, a measurement of vascular system function, was reversible with adenotonsillectomy. Increases in BP parameters, biological markers related to CVR and alterations in cardiac function structure, have been reported in pediatric patients with OSA. At least, some of these parameters would be reversible after adenotonsillectomy, reflecting a possible reduction in CVR.

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.

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.

Prevalence of High Blood Pressure in Pediatric Patients with Sleep-Disordered Breathing, Reversibility after Treatment: The KIDS TRIAL Study Protocol.

Current data support an increase in the prevalence of high blood pressure (HBP) in pediatric patients with sleep-disordered breathing (SDB). Adeno-tonsillectomy has been shown to be an effective treatment for most patients. Our objective was to determine the prevalence of HBP in pediatric patients with SDB and the impact of adeno-tonsillectomy with a multicenter, longitudinal, and prospective study that included 286 children referred for suspected SDB. The diagnosis of SDB was established by polysomnography (PSG) and the diagnosis of HBP by 24-h ambulatory blood pressure monitoring (ABPM). In patients without SDB and SDB without treatment indication, these tests were repeated six months after the baseline visit. For patients with medical treatment for SDB, the tests were repeated six months after the treatment initiation. Finally, in patients with surgery indication, ABPM was performed just before surgical treatment and ABPM and PSG six months after the intervention. The study contributes to elucidating the association between SDB and HBP in pediatric patients. Moreover, it contributes to determining if intervention with adeno-tonsillectomy is associated with BP reduction. The results have direct implications for the management of SDB, providing essential information on treatment indications for existing clinical guidelines. NCT03696654.

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.

Defining the Heterogeneity of Sleep Apnea Syndrome: A Cluster Analysis With Implications for Patient Management / Definiendo la heterogeneidad del Síndrome de Apneas del Sueño: un análisis de clúster con implicaciones en el manejo del paciente

Introduction Obstructive sleep apnea (OSA) is a complex pathology with heterogeneity that has not been fully characterized to date. Our objective is to identify groups of patients with common clinical characteristics through cluster analysis that could predict patient prognosis, the impact of comorbidities and/or the response to a common treatment. Methods Cluster analysis was performed using the hierarchical cluster method in 2025 patients in the apnea-HUGU cohort. The variables used for building the clusters included general data, comorbidity, sleep symptoms, anthropometric data, physical exam and sleep study results. Results Four clusters were identified: (1) young male without comorbidity with moderate apnea and otorhinolaryngological malformations; (2) middle-aged male with very severe OSA with comorbidity without cardiovascular disease; (3) female with mood disorder; and (4) symptomatic male with established cardiovascular disease and severe OSA. Conclusions The characterization of these four clusters in OSA can be decisive when identifying groups of patients who share a special risk or common therapeutic strategies, orienting us toward personalized medicine and facilitating the design of future clinical trials.

Introducción La Apnea Obstructiva del Sueño (AOS) es una patología compleja en la que su heterogeneidad no ha sido completamente caracterizada hasta la fecha. Nuestro objetivo es identificar grupos de pacientes con características clínicas comunes, por medio de análisis de clúster, que pudieran se predictivos de un pronóstico, impacto de comorbilidades y/o respuesta a un tratamiento común. Métodos Se realizó un análisis de clúster por el método de conglomerados jerárquico en 2025 pacientes de la cohorte apnea-HUGU. Las variables utilizadas para la construcción de los clúster incluían datos generales, comorbilidad, síntomas de sueño, datos antropométricos, exploración física y resultados del estudio de sueño. Resultados Se identificaron 4 clúster: 1) varón joven sin comorbilidad con apnea moderada y alteraciones de la esfera otorrinolaringológica (ORL) 2) Varón de edad media con AOS muy grave sintomático con comorbilidad sin enfermedad cardiovascular desarrollada. 3) Mujer con alteraciones en el estado de ánimo 4) Varón sintomático con enfermedad cardiovascular establecida y AOS grave. Conclusiones La caracterización de estos cuatro clúster en la AOS puede ser determinante a la hora de identificar grupos de pacientes que comparten un especial riesgo o estrategias terapéuticas comunes orientándonos hacia la medicina personalizada y facilitando el diseño de futuros ensayos clínicos.

[Intermediate Respiratory Care Units: Questions and Answers]. / Unidades de Cuidados Respiratorios Intermedios: preguntas y respuestas.

The intermediate respiratory care units (UCRI) are areas of monitoring and specialized care of patients with acute or chronic-exacerbated respiratory failure, whose severity does not require admission to an intensive care unit, but which due to their complexity cannot be treated in conventional hospitalization. Although the COVID-19 pandemic has proven its usefulness in the management of critical respiratory patients, the historical trajectory of the UCRI comes from many years ago, in which its cost-effectiveness has been demonstrated by far. This document presents a series of questions and answers on the history of the UCRI, in addition to the criteria for admission, infrastructure, human and technical resources, and the types of existing Units. Within the UCRI year 2021-2022 designated by the Spanish Society of Pneumology and Thoracic Surgery, any scientific dissemination linked to the in-depth knowledge of these units is timely, where multidisciplinarity and the work of professionals related to the care of critical respiratory patients converge.

Defining the Heterogeneity of Sleep Apnea Syndrome: A Cluster Analysis With Implications for Patient Management.

INTRODUCTION: Obstructive sleep apnea (OSA) is a complex pathology with heterogeneity that has not been fully characterized to date. Our objective is to identify groups of patients with common clinical characteristics through cluster analysis that could predict patient prognosis, the impact of comorbidities and/or the response to a common treatment. METHODS: Cluster analysis was performed using the hierarchical cluster method in 2025 patients in the apnea-HUGU cohort. The variables used for building the clusters included general data, comorbidity, sleep symptoms, anthropometric data, physical exam and sleep study results. RESULTS: Four clusters were identified: (1) young male without comorbidity with moderate apnea and otorhinolaryngological malformations; (2) middle-aged male with very severe OSA with comorbidity without cardiovascular disease; (3) female with mood disorder; and (4) symptomatic male with established cardiovascular disease and severe OSA. CONCLUSIONS: The characterization of these four clusters in OSA can be decisive when identifying groups of patients who share a special risk or common therapeutic strategies, orienting us toward personalized medicine and facilitating the design of future clinical trials.

Effect of CPAP treatment on BP in resistant hypertensive patients according to the BP dipping pattern and the presence of nocturnal hypertension.

High heterogeneity in the blood pressure (BP) response to continuous positive airway pressure (CPAP) exists in patients with resistant hypertension (RH). Only nondipper normotensive and hypertensive patients exhibited BP reductions when treated with CPAP; the baseline BP dipping pattern has been proposed as a predictor of BP response to CPAP but has never been explored in patients with RH. This study aimed to assess the effect of CPAP on BP in subjects with RH with respect to BP dipping pattern or nocturnal hypertension. This is an ancillary study of the SARAH study. RH subjects with an apnea/hypopnea index (AHI) ≥ 15/h and who received CPAP treatment for 1 year were included. Subjects underwent a sleep study and ambulatory BP monitoring (ABPM) at baseline and at the 1-year follow-up. Eighty-nine RH subjects were included. The subjects were mainly male (77.5%) and obese, with a mean age of 66 years (25th-75th percentile; 59.0; 70.0) and an AHI of 32.7/h (25th-75th percentile; 25.0; 54.7). A total of 68.5% of participants were nondippers, and 71.9% had nocturnal hypertension. After 1 year of CPAP, no significant differences in ABPM parameters were observed between dippers and nondippers. According to nighttime BP, subjects with nocturnal normotension did not show significant changes in ABPM parameters, while nocturnal hypertensive subjects achieved a significant reduction in mean nighttime BP of -4.38 mmHg (-7.10 to -1.66). The adjusted difference between groups was 3.04 (-2.25 to 8.34), which was not significant. This study shows that the BP response to CPAP in patients with RH does not differ according to the BP dipping pattern (dipper and nondipper) and suggests a differential response according to the presence of nocturnal hypertension (ClinicalTrials.gov: NCT03002558).

Correlation between systemic iron parameters and substantia nigra iron stores in restless legs syndrome.

OBJECTIVE: To evaluate the relation between systemic iron parameters (SIP) and substantia nigra (SN) iron deposits, as assessed by transcranial sonography (TCS) in restless legs syndrome (RLS). METHODS: We conducted a cross-sectional study in RLS patients, from whom blood samples with SIP were obtained, consisting of total iron-binding capacity (TIBC), serum ferritin, hemoglobin, transferrin saturation (TSAT), serum iron, and serum transferrin. TCS was performed over the SN, and the substantia nigra echogenicity index (SNEI) was determined according to established methods. Symptom severity was evaluated using the international restless legs scale (IRLS). A Spearman correlation was performed. RESULTS: A total of 167 patients were studied. Correlations between SNEI and SIP were as follows: serum ferritin (R = 0.0422; n.s.), TSAT (R = 0.0883; n.s.), TIBC (R = -0.1091; n.s.), serum transferrin (R = -0.0420; n.s.), hemoglobin (R = 0.0185; n.s.), serum iron (R = 0.0389; n.s.). No correlation was found with age and IRLS (R = 0.1375; n.s. and R = 0.0880, n.s., respectively). CONCLUSIONS: SIP are not correlated with SN iron content in RLS, quantified by means of TCS. TCS of the SN might be a more valid estimate and could be useful in the evaluation of RLS patients.

Restless Legs Syndrome - Clinical Features.

Restless legs syndrome (RLS) is one of the most common neurologic conditions, with an estimated prevalence in European and North American heritage populations of about 2% to 5%. Because RLS diagnosis is essentially clinical, a careful evaluation of the symptoms is mandatory. It is important to exclude RLS mimics and evaluate factors that could exacerbate RLS symptoms. It is mandatory to evaluate systemic iron parameters, because the initial treatment depends on this result. Other complementary tests could help support the diagnosis or exclude mimics. The decision about when and how to treat should be carefully tailored to each patient.

Low risk of iron overload or anaphylaxis during treatment of restless legs syndrome with intravenous iron: a consecutive case series in a regular clinical setting.

OBJECTIVE: To evaluate the incidence of iron overload and anaphylaxis following intravenous (IV) iron treatment of restless legs syndrome (RLS). METHODS: A total of 58 consecutive RLS patients, meeting clinical requirements for IV iron treatment according to current IRLSSG guidelines were recruited. IV iron treatment consisted of two 500 mg infusions of ferric carboxymaltose (FCM) administered five days apart. During each of the three follow-up visits we obtained blood samples, substantia nigra echogenity index (SNEI) by means of transcranial sonography (TCS), and assessed the severity of RLS symptoms (IRLS scale). "Iron overload risk" was defined as transferrin saturation (TSAT) > 45% on two consecutive follow-up visits. In patients who had a reduction in systemic iron levels following treatment, an additional 500 mg of FCM was administered when feasible. In such cases an additional two follow-up visits were performed. RESULTS: Among the total sample, only 2/58 participants met criteria for iron overload risk. They had no evidence of liver damage and did not require additional treatment. Among the 21 patients receiving an additional 500 mg infusion after, only one patient was diagnosed with iron overload risk. Among these three patients, only one was a hemochromatosis gene carrier. No anaphylaxis or other side-effects were reported. CONCLUSIONS: In real-life clinical conditions, the risk of iron overload is low when IV FCM is administered according to the safety limits defined in the current RLS treatment guidelines. However, a close clinical follow-up with periodic blood sampling for iron status, is needed.

Emerging Concepts of the Pathophysiology and Adverse Outcomes of Restless Legs Syndrome.

Restless legs syndrome (RLS), also known as Willis-Ekbom disease (WED), is a common neurological disorder affecting up to 5% to 10% of the population, but it remains an underdiagnosed condition. RLS/WED is characterized by uncomfortable sensations, mainly in the legs, which appear during inactivity and worsen in the evening or at night. The prevalence of RLS/WED and periodic leg movements (PLMs) is increased in patients with sleep-disordered breathing, particularly in those with OSA, the most common sleep disorder encountered in sleep centers. New advances in the pathophysiology of RLS/WED have shown important implications for various genetic markers, neurotransmitter dysfunction, and iron deficiency. A practical approach to RLS/WED management includes an accurate diagnosis, the identification of reversible contributing factors, and the use of nonpharmacological therapies, including iron substitution (oral or IV) therapy. Many pharmacological agents are effective for the treatment of RLS/WED. Until recently, the first-line treatment of RLS/WED consisted of low-dose dopamine agonists (DA). However, given the fact that DAs cause high rates of augmentation of symptoms, international guidelines recommend that whenever possible the initial treatment of choice should be an α2δ ligand, and avoidance of dopaminergic agents unless absolutely necessary. If necessary, the lowest effective dose should be used for only the shortest possible time. The symptoms of RLS/WED can disrupt the quality of sleep as well as the quality of life. IV iron therapy may be considered in patients with refractory RLS. A better understanding of RLS/WED pathophysiology will allow patients to receive tailored therapy, resulting in an improved quality of life.

Quantitative transcranial sonography of the substantia nigra as a predictor of therapeutic response to intravenous iron therapy in restless legs syndrome.

OBJECTIVE: To analyze changes in substantia nigra (SN) iron deposits, assessed by quantitative transcranial sonography (TCS), to obtain and compare substantia nigra echogenicity indices (SNEI) at baseline and after intravenous (IV) iron therapy in patients with restless legs syndrome (RLS)/Willis-Ekbom disease (WED). METHODS: A total of 30 consecutive subjects diagnosed with RLS/WED were recruited and underwent IV iron treatment. The SNEI, total daily dose of dopamine equivalents, and International Restless Legs Syndrome Rating Scale (IRLS) scores were obtained at baseline and following IV iron administration. Comparative statistics were performed by means of nonparametric testing. RESULTS: The sample was stratified into two groups according to the median baseline SNEI and the grade of SN hypoechogenicity: severely hypoechogenic (HE) (n = 13) and moderately HE (n = 17). Following IV iron, the increase in SNEI among severely HE subjects was 19% (0.038 ± 0.046 cm2; P < 0.01), whereas in moderately HE subjects it was 10% (0.021 ± 0.069 cm2; P = 0.28). Among severely HE subjects, the average reduction in IRLS following IV iron was 10 ± 7.12 points (P < 0.01), in contrast to 1.85 ± 9.85 (not significant) among moderately HE subjects. Finally, we quantified the percentage of patients in each group who were able to reduce by ≥30% their total daily dopaminergic requirements (TDR) after IV iron, with a 57.14% reduction in the severely HE group vs 25% in the moderately HE group (P = 0.1). Three of 30 subjects (17%) were able to completely cease all dopaminergic treatment. CONCLUSION: Intravenous iron caused changes in SNEI in both groups of patients, reflecting an increase in brain iron stores. However, the increase in SNEI was greater in patients previously defined as severely HE. Furthermore, RLS/WED symptoms also improved more in severely HE subjects, and there was a greater reduction in TDR. This study highlights the role of TCS in quantifying brain iron deposits and in predicting which patients will likely benefit from IV iron.

Obstructive Sleep Apnea: Emerging Treatments Targeting the Genioglossus Muscle.

Obstructive sleep apnea (OSA) is characterized by repetitive episodes of upper airway obstruction caused by a loss of upper airway dilator muscle tone during sleep and an inadequate compensatory response by these muscles in the context of an anatomically compromised airway. The genioglossus (GG) is the main upper airway dilator muscle. Currently, continuous positive airway pressure is the first-line treatment for OSA. Nevertheless, problems related to poor adherence have been described in some groups of patients. In recent years, new OSA treatment strategies have been developed to improve GG function. (A) Hypoglossal nerve electrical stimulation leads to significant improvements in objective (apnea-hypopnea index, or AHI) and subjective measurements of OSA severity, but its invasive nature limits its application. (B) A recently introduced combination of drugs administered orally before bedtime reduces AHI and improves the responsiveness of the GG. (C) Finally, myofunctional therapy also decreases AHI, and it might be considered in combination with other treatments. Our objective is to review these therapies in order to advance current understanding of the prospects for alternative OSA treatments.

Treating restless legs syndrome in the context of sleep disordered breathing comorbidity.

Obstructive sleep apnoea (OSA) and restless legs syndrome (RLS) are two of the most prevalent sleep disorders and can coexist within the same patient. Nonetheless, the recognition of RLS among OSA patients has important clinical implications, since RLS can disrupt sleep despite adequate treatment of sleep disordered breathing and should be treated accordingly. Furthermore, the presence of OSA can also increase the severity of RLS. Therefore, it is important to be able to correctly identify both disorders and treat them effectively. The present article reviews our current knowledge on this comorbidity and discusses potential treatment options for RLS in the context of OSA.