Altitude and Breathing during Sleep in Healthy Persons and Sleep Disordered Patients: A Systematic Review.

Objetive The aim of this systematic review is to analyze the recent scientific evidence of the clinical effects of altitude on breathing during sleep in healthy persons and sleep disordered patients. Material and Methods A search was carried out in PubMed and Scopus looking for articles published between January 1, 2010 and December 31, 2021, in English and Spanish, with the following search terms: "sleep disorders breathing and altitude". Investigations in adults and carried out at an altitude of 2000 meters above mean sea level (MAMSL) or higher were included. The correlation between altitude, apnea hypopnea index (AHI) and mean SpO2 during sleep was calculated. Results 18 articles of the 112 identified were included. A good correlation was found between altitude and AHI (Rs = 0.66 P = 0.001), at the expense of an increase in the central apnea index. Altitude is inversely proportional to oxygenation during sleep (Rs = -0.93 P = 0.001), and an increase in the desaturation index was observed (3% and 4%). On the treatment of respiratory disorders of sleeping at altitude, oxygen is better than servoventilation to correct oxygenation during sleep in healthy subjects and acetazolamide controlled respiratory events and oxygenation during sleep in patients with obstructive sleep apnea under treatment with CPAP. Conclusions Altitude increases AHI and decreases oxygenation during sleep; oxygen and acetazolamide could be an effective treatment for sleep-disordered breathing at altitude above 2000 MAMSL.

Documento internacional de consenso sobre apnea obstructiva del sueño / International Consensus Document on Obstructive Sleep Apnea

El objetivo principal de este documento internacional de consenso sobre apnea obstructiva del sueño es proporcionar unas directrices que permitan a los profesionales sanitarios tomar las mejores decisiones en la asistencia de los pacientes adultos con esta enfermedad según un resumen crítico de la literatura más actualizada. El grupo de trabajo de expertos se ha constituido principalmente por 17 sociedades científicas y 56 especialistas con amplia representación geográfica (con la participación de 4 sociedades internacionales), además de un metodólogo experto y un documentalista del Centro Cochrane Iberoamericano. El documento consta de un manuscrito principal, con las novedades más relevantes, y una serie de manuscritos online que recogen las búsquedas bibliográficas sistemáticas de cada uno de los apartados del documento internacional de consenso. Este documento no cubre la edad pediátrica ni el manejo del paciente en ventilación mecánica crónica no invasiva (que se publicarán en sendos documentos de consenso aparte). Palabras clave: Apnea obstructiva del sueño Diagnóstico Tratamiento

The main aim of this international consensus document on obstructive sleep apnea is to provide guidelines based on a critical analysis of the latest literature to help health professionals make the best decisions in the care of adult patients with this disease. The expert working group was formed primarily of 17 scientific societies and 56 specialists from a wide geographical area (including the participation of 4 international societies), an expert in methodology, and a documentalist from the Iberoamerican Cochrane Center. The document consists of a main section containing the most significant innovations and a series of online manuscripts that report the systematic literature searches performed for each section of the international consensus document. This document does not discuss pediatric patients or the management of patients receiving chronic non-invasive mechanical ventilation (these topics will be addressed in separate consensus documents). Keywords: Obstructive sleep apnea Diagnosis Treatment

International Consensus Document on Obstructive Sleep Apnea. / Documento internacional de consenso sobre apnea obstructiva del sueño.

The main aim of this international consensus document on obstructive sleep apnea is to provide guidelines based on a critical analysis of the latest literature to help health professionals make the best decisions in the care of adult patients with this disease. The expert working group was formed primarily of 17 scientific societies and 56 specialists from a wide geographical area (including the participation of 4 international societies), an expert in methodology, and a documentalist from the Iberoamerican Cochrane Center. The document consists of a main section containing the most significant innovations and a series of online manuscripts that report the systematic literature searches performed for each section of the international consensus document. This document does not discuss pediatric patients or the management of patients receiving chronic non-invasive mechanical ventilation (these topics will be addressed in separate consensus documents).

Leukocytes from Patients with Drug-Sensitive and Multidrug-Resistant Tuberculosis Exhibit Distinctive Profiles of Chemokine Receptor Expression and Migration Capacity.

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains as a leading infectious cause of death worldwide. The increasing number of multidrug-resistant TB (MDR-TB) cases contributes to the poor control of the TB epidemic. Currently, little is known about the immunological requirements of protective responses against MDR-TB. This is of major relevance to identify immune markers for treatment monitoring and targets for adjuvant immunotherapies. Here, we hypothesized that MDR-TB patients display unique immunophenotypical features and immune cell migration dynamics compared to drug-sensitive TB (DS-TB). Hence, we prospectively conducted an extensive characterization of the immune profile of MDR-TB patients at different time points before and after pharmacological therapy. For this purpose, we focused on the leukocyte expression of chemokine receptors, distribution of different monocyte and lymphocyte subsets, plasma levels of chemotactic factors, and in vitro migration capacity of immune cells. Our comparative cohort consisted of DS-TB patients and healthy volunteer donors (HD). Our results demonstrate some unique features of leukocyte migration dynamics during MDR-TB. These include increased and prolonged circulation of CD3+ monocytes, CCR4+ monocytes, EM CD4+ T cells, EM/CM CD8+ T cells, and CXCR1+CXCR3+ T cells that is sustained even after the administration of anti-TB drugs. We also observed shared characteristics of both MDR-TB and DS-TB that include CCR2+ monocyte depletion in the blood; high plasma levels of MPC-1, CCL-7, and IP-10; and increased responsiveness of leukocytes to chemotactic signals in vitro. Our study contributes to a better understanding of the MDR-TB pathobiology and uncovers immunological readouts of treatment efficacy.

Accessibility and adherence to positive airway pressure treatment in patients with obstructive sleep apnea: a multicenter study in Latin America.

PURPOSE: Information on access and adherence to positive airway pressure (PAP) treatment is lacking at the regional level in Latin America. This study characterized access and adherence to PAP in patients with moderate-severe obstructive sleep apnea (OSA) in Latin America. METHODS: Cross-sectional study, conducted at 9 sleep centers across Argentina, Brazil, Chile, Colombia, Mexico, and Peru. Adults diagnosed with moderate-severe OSA (apnea-hypopnea index [AHI] ≥ 15/h) in the previous 12-18 months were eligible. Anthropometrics, health coverage, and OSA severity data were collected. Data on access to therapy, barriers to access, adherence, and factors related to non-compliance were obtained via standardized telephone survey. RESULTS: Eight hundred eighty patients (70% male, 54 ± 13 years, AHI 49 ± 28/h, body mass index 32 ± 7 kg/m2) were included. Four hundred ninety patients (56%) initiated PAP, 70 (14%) discontinued therapy during the first year (mainly due to intolerance), and 420 (48%) were still using PAP when surveyed. Health insurance was private in 36.9% of patients, via the social security system in 31.1%, and via the state in 13.3%, and 18.7% did not have any coverage; 49.5% of patients had to pay all equipment costs. Reasons for not starting PAP were unclear or absent indication (42%), coverage problems (36%), and lack of awareness of OSA burden (14%). Patients with better adherence were older (55.3 ± 13 vs 52 ± 13; p = 0.002) and had more severe OSA (AHI 51.8 ± 27 vs 45.6 ± 27; p = 0.001). CONCLUSIONS: Less than half moderate-severe OSA patients started and continue to use PAP. Unclear or absent medical indication and financial limitations were the most relevant factors limiting access to therapy.

Quality of an ambulatory monitoring technique for diagnosing obstructive sleep apnea under conditions of limited resources.

OBJECTIVES: To: 1) evaluate the quality of an ambulatory monitoring technique for diagnosing Obstructive Sleep Apnea Syndrome (OSAS) while patients move through the city; and 2) identify factors that lead to data loss. METHODS: Clinical histories were reviewed and ambulatory portable monitorings of adults with high pretest probability for OSAS were included, the signals monitored were pulse oximetry, heart rate, nasal pressure, snoring, chest band and body position. The equipment was connected from 14:00-20:00 h and then patients moved through the city turning it off and on at home. Results were analyzed visually to record all the minutes lost. A good-quality study was defined as recording time 240 min and signal loss <20%. A cost/benefit analysis was performed using Golpe et al.'s methodology. RESULTS: A total of 70 recordings were analyzed. Most subjects were obese men with severe OSAS. Signal quality was determined to be good with a median signal loss of 4.9 min (0-405) that represented 1% (0-99) of total recording time. The signal lost most often was pulse oximetry at 1.8 min (0-403, p=0.0001). Of the 70 studies performed, 57 (81%) met the definition of good quality, while 13 (19%) had to be repeated. Men lost the pulse oximetry signal more often than women. This technique could represent savings of 65-75%. CONCLUSIONS: Placing a portable OSAS monitor during the day while patients move around the city turning it on and off at home does not affect the quality of the study results obtained and is a cost-effective method.

La diabetes se asocia con reacciones adversas graves en la tuberculosis multirresistente / Diabetes is Associated with Severe Adverse Events in Multidrug-Resistant Tuberculosis

Introducción: La diabetes mellitus (DM), una enfermedad muy frecuente en México, es un factor de riesgo bien conocido para el desarrollo de tuberculosis (TB). Sin embargo, se desconoce en qué medida la DM predispone al desarrollo de reacciones adversas (RA) a los fármacos anti-tuberculosis y/o si predispone a un peor resultado en pacientes con pacientes con TB multirresistente (TB-MR) y TB extremadamente resistente (TB-XR). El objetivo principal de este estudio fue describir los resultados del tratamiento anti-tuberculosis, el impacto de la DM y la prevalencia de RA en una cohorte de pacientes con TB pulmonar MR/XR tratados en el centro de referencia nacional para TB, en la Ciudad de México. Resultados: Entre 2010 y 2015 se incluyeron 90 pacientes -73 con TB-MR (81,1%), 11 con TB pre-XR (12,2%) y 6 (6,7%) con TB-XR-, 49 (54,4%) de los cuales tenían DM y 3 con co-infección por el virus de la inmunodeficiencia humana (VIH) (3,3%). El diagnóstico se realizó mediante cultivo y pruebas de fármaco-sensibilidad (PFS) en el 98% de los pacientes y mediante prueba molecular en un caso. La presencia de DM se asoció con un mayor riesgo de RA graves, tales como nefrotoxicidad (odds ratio [OR] = 6,5; intervalo de confianza del 95% [IC 95%]: 1,9-21,8) e hipotiroidismo (OR = 8,8; IC 95%: 1,8-54,2), aunque no con peor resultado del tratamiento. onclusiones: Nuestros datos sugieren que la DM no tiene un impacto sobre los resultados del tratamiento anti-tuberculosis de segunda línea, pero los pacientes con DM tienen mayor riesgo de presentar RA graves secundarias al tratamiento, tales como nefrotoxicidad e hipotiroidismo

Introduction: Diabetes mellitus (DM), a very common disease in Mexico, is a well-known risk factor for tuberculosis (TB). However, it is not known by which extent DM predisposes to adverse events (AE) to anti-TB drugs and/or to worse outcomes in patients with multidrug-resistant (MDR-TB) and extensively drug-resistant TB (XDR-TB). The main objective of this study was to describe the outcomes of TB treatment, the impact of DM and the prevalence of AE in a cohort of patients with MDR-/XDR pulmonary TB treated at the national TB referral centre in Mexico City. Results: Ninety patients were enrolled between 2010 and 2015: 73 with MDR-TB (81.1%), 11 with pre-XDR-TB (12.2%) and 6 (6.7%) with XDR-TB, including 49 (54.4%) with DM, and 3 with Human Immunodeficiency Virus (HIV) co-infection (3.3%). In 98% of patients, diagnosis was made by culture and drug susceptibility testing, while in a single case the diagnosis was made by a molecular test. The presence of DM was associated with an increased risk of serious drug-related AEs, such as nephrotoxicity (Odds Ratio [OR] = 6.5; 95% Confidence Interval [95% CI]: 1.9-21.8) and hypothyroidism (OR = 8.8; 95% CI: 1.8-54.2), but not for a worse outcome. Conclusions: Our data suggest that DM does not impact second-line TB treatment outcomes, but patients with DM have a higher risk of developing serious AEs to drug-resistant TB treatment, such as nephrotoxicity and hypothyroidism

Diabetes is Associated with Severe Adverse Events in Multidrug-Resistant Tuberculosis. / La diabetes se asocia con reacciones adversas graves en la tuberculosis multirresistente.

INTRODUCTION: Diabetes mellitus (DM), a very common disease in Mexico, is a well-known risk factor for tuberculosis (TB). However, it is not known by which extent DM predisposes to adverse events (AE) to anti-TB drugs and/or to worse outcomes in patients with multidrug-resistant (MDR-TB) and extensively drug-resistant TB (XDR-TB). The main objective of this study was to describe the outcomes of TB treatment, the impact of DM and the prevalence of AE in a cohort of patients with MDR-/XDR pulmonary TB treated at the national TB referral centre in Mexico City. RESULTS: Ninety patients were enrolled between 2010 and 2015: 73 with MDR-TB (81.1%), 11 with pre-XDR-TB (12.2%) and 6 (6.7%) with XDR-TB, including 49 (54.4%) with DM, and 3 with Human Immunodeficiency Virus (HIV) co-infection (3.3%). In 98% of patients, diagnosis was made by culture and drug susceptibility testing, while in a single case the diagnosis was made by a molecular test. The presence of DM was associated with an increased risk of serious drug-related AEs, such as nephrotoxicity (Odds Ratio [OR]=6.5; 95% Confidence Interval [95% CI]: 1.9-21.8) and hypothyroidism (OR=8.8; 95% CI: 1.8-54.2), but not for a worse outcome. CONCLUSIONS: Our data suggest that DM does not impact second-line TB treatment outcomes, but patients with DM have a higher risk of developing serious AEs to drug-resistant TB treatment, such as nephrotoxicity and hypothyroidism.

Diagnostic Value of the Morphometric Model and Adjusted Neck Circumference in Adults with Obstructive Sleep Apnea Syndrome.

BACKGROUND: Obstructive sleep apnea syndrome is a major public health problem. The morphometric model and the Sleep Apnea Clinical Score are widely used to evaluate adults; however, neither of these tools has been validated in a Mexican population. OBJECTIVE: To determine the diagnostic value of the morphometric model and the Sleep Apnea Clinical Score and compare them with conventional clinical instruments. METHODS: A total of 97 individuals were recruited prospectively. Initial screening excluded 36, of whom nine were subjects without apnea; the remaining 52 were consecutive patients with obstructive sleep apnea syndrome diagnosed by nocturnal polysomnography. Diagnostic values of each test were calculated. RESULTS: Obstructive sleep apnea syndrome patients had significantly higher scores with both instruments than controls: morphometric model: 61.3 (95% CI: 45.5-75.3) vs. 41.0 (95% CI: 35.6-45.6); Sleep Apnea Clinical Score: 45.3 (95% CI: 39.5-40.3) vs. 36 (95% CI: 34.0-36.5), respectively. For severe cases, the best cutoff point for morphometric model was 46, with a sensitivity of 81% (95% CI: 62.5-92.6) and specificity of 46.7% (95% CI: 66.4-100), while for Sleep Apnea Clinical Score it was > 48, with a sensitivity of 61% (95% CI: 46.1-74.2) and specificity of 80.4% (95% CI: 66-90.6). CONCLUSIONS: A morphometric model value of ≥ 46 or an adjusted neck circumference (Sleep Apnea Clinical Score) > 48 were adequate for diagnosing obstructive sleep apnea syndrome.

Síndrome de hipoventilación alveolar central congénita / Congenital central alveolar hypoventilation syndrome

ResumenIntroducción: El síndrome de hipoventilación alveolar central congénita (SHACC) es un raro trastorno respiratorio del dormir, aunque cada vez más frecuentemente diagnosticado en clínicas de sueño y servicios de neumología pediátrica. Si bien se desconoce su epidemiología, en la literatura médica existen cerca de 300 casos reportados, y su incidencia es de 1 caso por cada 200,000 recién nacidos vivos. Se caracteriza por hipoventilación alveolar que se presenta o empeora durante el sueño. Es secundario a la disminución/ausencia de la respuesta ventilatoria a la hipercapnia o hipoxemia, y en el 90% de los casos es debido a una mutación tipo PARM del gen PHOX2B. Su tratamiento incluye ventilación mecánica y marcapasos diafragmático. Si la terapéutica no se inicia en forma temprana, el paciente desarrollará insuficiencia respiratoria crónica, hipertensión arterial pulmonar, cor pulmonale y la muerte.Casos clínicos: Se presentan tres casos de SHACC diagnosticados, tratados y en seguimiento en la Clínica de Trastornos Respiratorios del Dormir del Instituto Nacional de Enfermedades Respiratorias.Conclusiones: El diagnóstico temprano es importante para el inicio del soporte ventilatorio, y para prevenir el desarrollo de complicaciones y reducir la mortalidad.

AbstractBackground: Congenital central alveolar hypoventilation syndrome (CCAHS) is a rare sleep-related breathing disorder. Although increasingly frequently diagnosed in sleep clinics and pediatric pulmonology services, its epidemiology is not known. There are about 300 reported cases reported in the literature with an incidence of 1 case per 200,000 live births. CCAHS is characterized by alveolar hypoventilation that occurs or worsens during sleep and is secondary to a reduction/absence of the ventilatory response to hypercapnia and/or hypoxemia. In 90% of the cases it is due to a PARM-type mutation of the PHOX2B gene. Treatment includes mechanical ventilation and diaphragmatic pacemaker. If therapy is not initiated promptly the patient can evolve to chronic respiratory failure, pulmonary hypertension, cor pulmonale and death.Case reports: In this paper we present three cases of CCAHS diagnosed, treated and followed up at the Sleep Disorders Clinic of the National Institute of Respiratory Diseases in Mexico.Conclusions: Early diagnosis is important to initiate ventilatory support so as to prevent any complications and to reduce mortality.

[Congenital central alveolar hypoventilation syndrome]. / Síndrome de hipoventilación alveolar central congénita.

BACKGROUND: Congenital central alveolar hypoventilation syndrome (CCAHS) is a rare sleep-related breathing disorder. Although increasingly frequently diagnosed in sleep clinics and pediatric pulmonology services, its epidemiology is not known. There are about 300 reported cases reported in the literature with an incidence of 1 case per 200,000 live births. CCAHS is characterized by alveolar hypoventilation that occurs or worsens during sleep and is secondary to a reduction/absence of the ventilatory response to hypercapnia and/or hypoxemia. In 90% of the cases it is due to a PARM-type mutation of the PHOX2B gene. Treatment includes mechanical ventilation and diaphragmatic pacemaker. If therapy is not initiated promptly the patient can evolve to chronic respiratory failure, pulmonary hypertension, cor pulmonale and death. CASE REPORTS: In this paper we present three cases of CCAHS diagnosed, treated and followed up at the Sleep Disorders Clinic of the National Institute of Respiratory Diseases in Mexico. CONCLUSIONS: Early diagnosis is important to initiate ventilatory support so as to prevent any complications and to reduce mortality.

Anxiety and depression symptoms in patients with sleep-disordered breathing.

INTRODUCTION: Information concerning the frequency of anxiety and depression symptoms in patients with sleep-disordered breathing (SDB) is controversial. Hence, the objectives of this study were to: determine the frequency of anxiety and depression symptoms in patients with SDB; explore whether the frequency of anxiety and depression symptoms rises with increasing parameters of SDB severity; and investigate the factors potentially associated with anxiety and depression. MATERIALS AND METHODOLOGY: Data was collected from consecutive adult patients referred to the National Institute of Respiratory Diseases' Sleep Medicine Unit from October 2008 to October 2009. SDB diagnoses were established using standard polysomnography or simplified respiratory polygraphy. All patients routinely completed the Hospital Anxiety and Depression Scale (HADS) on their first visit to the Sleep Medicine Unit. RESULTS: 382 patients with SDB were included. Mean age was 50.8±13.6 years, 62% were male. Anxiety symptoms were acknowledged by 71 patients (18.5%), while 29 (7.6%) had depression symptoms, and 116 (30.4%) had symptoms of anxiety plus depression. Patients who reported anxiety and depression symptoms scored higher on the Epworth Sleepiness Scale (ESS, 16±7) than those with no symptoms (11±6) (p<0.0001). Patients with symptoms of anxiety plus depression also had higher BMIs (36 ± 8 K/m(2)) than patients with SDB without anxiety or depression. No other differences were observed, not even with respect to the parameters of the severity of their SDB. CONCLUSIONS: Our results support the recommendation that due to their high frequency and potential importance for long-term adherence to CPAP, anxiety and depression symptoms should be included in the routine evaluation of all adults with SDB.

Accuracy and linearity of positive airway pressure devices: a technical bench testing study.

STUDY OBJECTIVES: To analyze the accuracy and linearity of different CPAP devices outside of the manufacturers' own quality control environment. METHODS: Accuracy (how well readings agree with the gold standard) and linearity were evaluated by comparing programmed pressure to measured CPAP pressure using an instrument established as the gold standard. Comparisons were made centimeter-by-centimeter (linearity) throughout the entire programming spectrum of each device (from 4 to 20 cm H2O). RESULTS: A total of 108 CPAP devices were tested (1836 measurements); mean use of the devices was 956 hours. Twenty-two of them were new. The intra-class correlation coefficient (ICC) decreased from 0.97 at pressures programmed between 4 and 10 cm H2O, to 0.84 at pressures of 16 to 20 cm H2O. Despite this high ICC, the 95% agreement limit oscillated between -1 and 1 cm H2O. This same behavior was observed in relation to hours of use: the ICC for readings taken on devices with < 2,000 hours of use was 0.99, while that of the 50 measurements made on devices with > 6,000 hours was 0.97 (the agreement limit oscillated between -1.3 and 2.5 cm H2O). "Adequate adjustments" were documented in 97% of measurements when the definition was +/- 1 cm H2O of the programmed pressure, but this index of adequate adjustment readings decreased to 85% when the +/- 0.5 cm H2O criterion was applied. CONCLUSIONS: In general, the CPAP devices were accurate and linear throughout the spectrum of programmable pressures; however, strategies to assure short- and long-term equipment reliability are required in conditions of routine use.