Advances in the study of mesenchymal stem cells in obstructive sleep apnea hypoventilation syndrome / 中国临床药理学与治疗学

Mesenchymal stem cells (MSCs) are self-regenerating, rapidly proliferating pluripotent stem cells that depend primarily on their derived pro-angiogenic, inflammatory regulatory, and trophic factors to exert beneficial effects that attenuate deleterious inflammatory responses, reduce vascular damage, and promote tissue repair and regeneration. Obstructive sleep apnea hypoventilation syndrome (OSAHS) is a chronic disorder marked by oropharyngeal collapse during sleep, resulting in transient reduced airflow, large fluctuations in intrathoracic pressure, and intermittent hypoxia and hypercapnia. OSAHS subsequently cytokine-mediated inflammatory cascades, oxidative stress, and ischemia, recruit MSCs from inflamed and damaged tissues through MSCs-derived of anti-inflammatory and pro-angiogenic factor activity, reduce hypoxia, suppress inflammation, promote regeneration, and prevent fibrosis in OSAHS-injured tissues. In this paper, we will describe the pathogenesis of inflammation, oxidative stress, fibrosis and ischemia from the perspective of OSAHS, highlighting the current research progress on MSCs-dependent regulation of OSAHS-related pathology.

Correlation between exhaled nitric oxide and obstructive sleep apnea-hypopnea syndrome / 中国基层医药

Objective:To investigate the correlation between exhaled nitric oxide and obstructive sleep apnea-hypopnea syndrome (OSAHS).Methods:Eighty patients with OSAHS (OSAHS group) who received treatment in Pingxiang People's Hospital from September 2019 to September 2021 were included in this study. An additional 60 patients with snoring (snoring group) who concurrently received treatment in the same hospital were included in the control group. The value of exhaled nitric oxide was measured using an exhaled nitric oxide detector. The relationship between exhaled nitric oxide and apnea-hypopnea index, and the lowest oxygen saturation level during sleep (LSaO 2) was analyzed using Pearson correlation analysis. The optimal cut-off value of exhaled nitric oxide for predicting OSAHS was analyzed using the receiver operating characteristic curve. Results:Exhaled nitric oxide and apnea-hypopnea index in the OSAHS group were (18.61 ± 6.23) μg/L and (44.50 ± 16.15) times/hour, respectively, which were significantly greater than (11.17 ± 4.31) μg/L and (2.91 ± 0.79) times/hour in the snoring group ( t = 7.94, 14.08, both P < 0.05). LSaO 2 in the OSAHS group was significantly lower than that in the snoring group [(66.53 ± 10.17)% vs. (92.15 ± 1.62)%, t = -13.61, P < 0.05]. Correlation analysis showed that exhaled nitric oxide levels in patients with OSAHS were positively correlated with apnea-hyponea index ( r = 0.56, P = 0.001), and negatively correlated with the lowest oxygen saturation level ( r = -0.54, P = 0.002). The receiver operating characteristic curve analysis revealed that when the optimal cut-off value of exhaled nitric oxide was 11.5 μg/L, the area under the curve was 0.846, with sensitivity of 91.3%, and specificity of 63.3%. Conclusion:Patients with OSAHS have airway inflammatory reactions. The level of nitric oxide in exhaled air is positively correlated with the severity of OSAHS, which has a certain clinical value.

Effects of chronic obstructive pulmonary disease patients complicated with OSAHS on hypercapnia and related factors / 中华健康管理学杂志

Objective:To analyze the effects of chronic obstructive pulmonary disease (COPD) combined with obstructive sleep apnea hypopnea syndrome (OSAHS) on hypercapnia and its related factors.Methods:In this cross-sectional study, patients with stable COPD were continuously recruited from July 2016 to December 2018 in the Respiratory Department of Peking University Third Hospital. General clinical data of patients were collected, and lung function test, arterial blood gas analysis and portable sleep monitoring were also conducted. Patients with COPD complicated with apnea hypopnea index (AHI)≥10 times/h and apnea events being mainly blockage-type events, accompanied by snoring, sleep apnea, daytime sleepiness and other symptoms were defined as overlapping group, patients with COPD complicated with AHI<10 times/h were defined as simple COPD group. Correlation analysis and logistic regression model were used to explore the determinants of daytime hypercapnia in patients with COPD.Results:Compared with simple COPD group, the median arterial partial pressure of carbon dioxide (PaCO 2) was significantly higher in the overlapping group (42.00 vs 38.95 mmHg (1 mmHg=0.133 kPa), P<0.001), and the rate of daytime hypercapnia was significantly higher (23.3% vs 3.3%, P=0.002). PaCO 2 was correlated with forced vital capacity (FVC), percent predicted forced expiratory volume in one second (FEV 1%pred), the ratio of residual volume (RV) to total lung capacity (TLC), AHI, nocturnal average transcutaneous oxygen saturation (SpO 2), nocturnal minimum SpO 2 and the total sleep time spent with SpO 2≤90% (T90) (all P<0.05). In logistic regression analysis, after adjusting for age, sex, and body mass index (BMI), only severe OSAHS, GOLD Ⅲ-Ⅳ grade (FEV 1%pred<50%), and T90>1% were independent risk factors for hypercapnia. Conclusions:OSAHS can increase the risk of hypercapnia in patients with COPD. AHI, lung function injury and T90 are closely related to hypercapnia.

Asociación e interacciones de la apnea obstructiva del sueño (AOS) y del síndrome de hipoventilación obesidad (SHO) / Metabolic associations of the obstructive sleep apnea (AOS) and hypoventilation obesity syndrome

La apnea obstructiva del sueño (AOS) y el síndrome hipoventilación-obesidad (SHO) son patologías que se encuentran estrechamente asociadas a la obesidad como principal factor de riesgo, hasta un 70% de los pacientes con AOS son obesos. Ambas patologías comparten procesos fisiopatológicos comunes, donde destaca la inflamación sistémica, lo que, sumado a la hipoxia crónica intermitente y la fragmentación del sueño característicos de la AOS, aumenta considerablemente el riesgo de presentar comorbilidades metabólicas como síndrome metabólico, alteraciones en el metabolismo de la glucosa (resistencia a la insulina y diabetes mellitus tipo 2), y hígado graso metabólico. En esta revisión narrativa, se describirán los mecanismos identificados en estas asociaciones, así como la prevalencia y la evidencia sobre el tratamiento de la AOS y del SHO

Obstructive sleep apnea (OSA) and obesity-hypoventilation syndrome (OHS) are pathologies that are closely associated with obesity as the main risk factor, up to 70% of patients with OSA are obese. Both pathologies share common pathophysiological processes, where systemic inflammation stands out, which, added to the intermittent chronic hypoxia and sleep fragmentation characteristic of OSA, considerably increases the risk of presenting metabolic comorbidities such as metabolic syndrome, alterations in the metabolism of the glucose (insulin resistance and type 2 diabetes mellitus), and metabolic fatty liver. In this narrative review, the mechanisms identified in these associations will be described, as well as the prevalence and evidence on the treatment of OSA and OHS

Deterioro del intercambio gaseoso en sujetos con incremento del índice de masa corporal a una altitud de 2, 240 metros sobre el nivel del mar / Deterioration of gas exchange in subjects with an increase in body mass index at an altitude of 2, 240 meters above sea level

Resumen Introducción: Las alteraciones del intercambio gaseoso se han reconocido en la obesidad mórbida; sin embargo, no se conoce su comportamiento conforme se incrementa el índice de masa corporal. Objetivo: Conocer el comportamiento del intercambio gaseoso a la altura de la Ciudad de México en el desarrollo de obesidad mórbida. Métodos: Mediante un diseño transversal analítico se estudió a sujetos pareados por género y edad de cuatro grupos diferentes de índice de masa corporal (kg/m2): normal (18.5-24.9), sobrepeso (25-29.9), obesidad (30-39.9) y obesidad mórbida (≥ 40). Se obtuvieron sus antecedentes patológicos y demográficos, variables de gasometría arterial y espirometría simple. Las variables se determinaron de acuerdo con las características de la muestra; las diferencias entre grupos se realizaron mediante Anova de una vía con ajuste de Bonferroni, así como la correlación de Pearson para las variables relacionadas. Una p < 0.05 se consideró con significación estadística. Resultados: Se estudió a 560 pacientes en cuatro grupos. La edad promedio fue de 49 ± 11 años. La mayor frecuencia de diabetes mellitus (34.29%), hipertensión arterial (50%) e hiperlipidemia (36.43%) se registró en el grupo de obesidad, y la de roncador (73.57%) en la obesidad mórbida. Se identificaron diferencias desde el grupo normal respecto de la obesidad mórbida: PaCO2 31.37 ± 2.08 vs. 38.14 ± 5.10 mmHg; PaO2 68.28 ± 6.06 vs. 59.86 ± 9.28 mmHg y SaO2 93.51 ± 1.93 vs. 89.71 ± 5.37%, todas con p = 0.0001. Correlación IMC-PaCO2: 0.497, e IMC-PaO2: -0.365, p = 0.0001, respectivamente. Conclusiones: A la altitud de la Ciudad de México y con índice de masa corporal > 30 kg/m2, las variables relacionadas con el intercambio gaseoso y espirometría simple comienzan a deteriorarse; son evidentes con IMC > 40 kg/m2.

Abstract Introduction: Alterations of gas exchange have been recognized in morbid obesity, however, it is not known how their behavior would be as the body mass index increases. Objective: To know the behavior of gas exchange at the level of Mexico City in the development of morbid obesity. Methods: Through analytical design, subjects matched by gender and age were studied from four different groups of body mass index (kg/m2), normal (18.5-24.9), overweight (25-29.9), obesity (30-39.9) and morbid obesity (≥ 40). Their pathological and demographic antecedents, arterial blood gas and simple spirometry variables were obtained. The variables were shown according to their sample characteristic. The differences between groups were made using one way Anova with Bonferroni adjustment, as well as Pearson’s correlation for the related variables. Statistical significance was considered with p < 0.05. Results: 560 subjects were studied in 4 groups. The average age 49 ± 11 years old. The highest frequency of diabetes mellitus (34.29%), arterial hypertension (50%) and hiperlipidemia (36.43%) was in the obesity group, and being snoring (73.57%) in morbid obesity. There were differences from the normal group versus. morbid obesity: PaCO2 31.37 ± 2.08 versus. 38.14 ± 5.10 mmHg; PaO2 68.28 ± 6.06 versus. 59.86 ± 9.28 mmHg and SaO2 93.51 ± 1.93 versus. 89.71 ± 5.37%, all with p = 0.0001. The IMC-PaCO2 correlation: 0.497, and IMC-PaO2: −0.365, p = 0.0001 respectively. Conclusions: At the altitude of Mexico City and body mass index > 30 kg/m2 the variables related to gas exchange and simple spirometry begin to deteriorate; are evident with BMI > 40 kg/m2.

Marcapasos diafragmático en paciente pediátrico con síndrome de Hipoventilación Central Adquirido / Diaphragm pacing in a pediatric patient with Acquired Central Hypoventilation syndrome

Resumen: Introducción: El marcapasos diafragmático permite reducir o eliminar la necesidad de ventilación mecánica en pacientes con insuficiencia respiratoria crónica que conservan el eje nervio frénico-diafragma in tacto, siempre que no presenten enfermedad pulmonar intrínseca. Aunque su implantación ha sido practicada por décadas, su uso no está ampliamente difundido, y existe poca literatura pu blicada al respecto, la mayoría relacionada con lesión medular alta y síndrome de hipoventilación central congénito. Objetivo: Describir una experiencia de implantación de marcapasos diafragmático en paciente pediátrico con síndrome de hipoventilación central adquirido. Caso Clínico: Pa ciente femenino con síndrome de hipoventilación central secundario a lesión isquémica de tronco cerebral como resultado de disfunción de válvula de derivación ventrículo peritoneal, motivo por el cual durante 5 años se mantuvo con asistencia de ventilación mecánica intrahospitalaria. A los 7 años de edad se implantó marcapasos diafragmático mediante cirugía toracoscópica, lo que per mitió posterior a un periodo de rehabilitación y acondicionamiento respiratorio el destete de la ventilación mecánica y el egreso hospitalario. Conclusiones: El marcapasos diafragmático es una opción factible, potencialmente segura y costo efectiva para disminuir o eliminar la dependencia de ventilación mecánica y mejorar la calidad de vida en pacientes con síndrome de hipoventilación central adquirido.

Abstract: Introduction: Diaphragmatic pacemaker is a device that reduces or eliminates the need of mechanical ventilation in patients with chronic respiratory failure who keep the phrenic nerve-diaphragm axis intact, as long as they do not present intrinsic lung disease. Although its implantation has been practiced for deca des, its use is not widespread and to date, there is little published literature about it, mostly related to high spinal cord injury and congenital central hypoventilation syndrome. Objective: To describe an experience of diaphragmatic pacemaker implantation in a pediatric patient with acquired cen tral hypoventilation syndrome. Clinical Case: Female patient with central hypoventilation syndrome secondary to ischemic brainstem lesion as a result of ventriculoperitoneal shunt malfunction. For this reason, for 5 years she was supported by inpatient mechanical ventilation. At 7 years of age, a diaphragmatic pacemaker was implanted by thoracoscopic surgery, which allowed, after a period of rehabilitation and respiratory conditioning, mechanical ventilation withdrawal, and hospital dischar ge. Conclusions: Diaphragmatic pacemaker is a feasible, potentially safe, and cost-effective option for decreasing or eliminating mechanical ventilation dependence and improve life quality in patients with acquired central hypoventilation syndrome.

Spinal anesthesia and postoperative epidural analgesia in a patient with congenital central hypoventilation syndrome: a case report / 대한마취과학회지

BACKGROUND: Congenital central hypoventilation syndrome (CCHS) is a rare disorder characterized by alveolar hypoventilation and autonomic dysregulation. Patients with CCHS have adequate ventilation while awake but exhibit hypoventilation while asleep. More severely affected patients exhibit hypoventilation both when awake and when asleep. CASE: Here, we report a case of successful spinal anesthesia and postoperative epidural analgesia in a patient with CCHS who underwent orthostatic surgery. CONCLUSIONS: In patients with CCHS, anesthesia is used with the goal of minimizing respiratory depression to avoid prolonged mechanical ventilation. Regional anesthesia should be considered where appropriate. Continuous oxygen saturation and end-tidal carbon dioxide monitoring must be available.

Central Hypoventilation Syndrome in Posterior Circulation Stroke Treated by Respiratory Rehabilitation: a Case Report

Central hypoventilation syndrome is a rare and fatal condition resulting from various central nervous system disorders that is characterized by a failure of automatic breathing. We report a case of central hypoventilation syndrome following posterior circulation stroke whose pulmonary function was improved by respiratory rehabilitation. A 59-year-old woman with a history of hemorrhagic stroke of the bilateral cerebellum was hospitalized due to pneumonia. A portable ventilator was applied via tracheostomy, recurrent episodes of apnea and hypercapnia impeded weaning. A respiratory rehabilitation program including chest wall range of motion exercise, air stacking exercise, neuromuscular electrical stimulation (NMES) on abdominal muscles, upper extremity ergometer, locomotor training, high-frequency chest wall oscillator, mechanical insufflation, and exsufflation was employed, as spirometry showed a severe restrictive pattern. A spontaneous breathing trial was started, and a portable ventilator was applied for 8 hours, only during nighttime, to prevent sudden apneic event. After 4 weeks of treatment, follow-up spirometry showed much improved respiratory parameters. This case suggests that respiratory rehabilitation can improve pulmonary function parameters and quality of life in central hypoventilation syndrome.

Analysis of C-reactive protein, fibrinogen and erythrocyte sedimentation rate in patients with obstructive sleep apnea hypopnea syndrome / 中国基层医药

Objective To investigate the changes of C-reactive protein (CRP),fibrinogen (FIB) and erythrocyte sedimentation rate (ESR) in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS),and their relationship with sleep respiratory parameters.Methods From June 2015 to August 2018,70 OSAHS patients [observation group,apnea hypopnea index (AHI) ≥ 5/h] and 20 persons in the snoring control group (control group,AHI ＜ 5/h) who received the monitor of polysomnography in the Pingxiang People's Hospital were enrolled.The levels of CRP,FIB and ESR were measured and compared between the two groups.The correlations were analyzed between the levels of inflammatory markers and sleep breathing parameters.Results The two groups had no statistically significant differences in age,gender and BMI(all P ＞ 0.05).The CRP,FIB and ESR of the observation group were (4.5 ± 3.0) mg/L,(3.3 ± 0.9) g/L,(11.4 ± 5.4) mm/h,respectively,which were significantly higher than those of the control group [(2.0 ± 1.5) mg/L,(2.9 ± 0.5) g/L,(7.6 ± 2.6) mm/h] (t =5.12,2.68,4.36,all P ＜ 0.05).The level of CRP was positively correlated with AHI,oxygen desaturation index (ODI) (r =0.285,P ＜ 0.05 and r =0.282,P ＜ 0.05),and negatively correlated with the lowest SaO2 and the average SaO2 (r =-0.257,P ＜ 0.05 and r =-0.259,P ＜ 0.05).The level of FIB was positively correlated with AHI,ODI (r =0.430,P ＜ 0.01 and r =0.311,P ＜0.01),and negatively correlated with the lowest SaO2 (r =-0.287,P ＜0.01).There were no correlations between ESR and sleep breathing parameters.Conclusion The levels of CRP,FIB and ESR are increased in OSAHS patients,and the levels of CRP and FIB are proportional to the severity of OSAHS,suggesting that OSAHS patients has systemic inflammatory response.

Analysis of C-reactive protein, fibrinogen and erythrocyte sedimentation rate in patients with obstructive sleep apnea hypopnea syndrome / 中国基层医药

Objective@#To investigate the changes of C-reactive protein(CRP), fibrinogen(FIB) and erythrocyte sedimentation rate(ESR) in patients with obstructive sleep apnea-hypopnea syndrome(OSAHS), and their relationship with sleep respiratory parameters.@*Methods@#From June 2015 to August 2018, 70 OSAHS patients[observation group, apnea hypopnea index(AHI)≥5/h]and 20 persons in the snoring control group(control group, AHI<5/h) who received the monitor of polysomnography in the Pingxiang People′s Hospital were enrolled.The levels of CRP, FIB and ESR were measured and compared between the two groups.The correlations were analyzed between the levels of inflammatory markers and sleep breathing parameters.@*Results@#The two groups had no statistically significant differences in age, gender and BMI(all P>0.05). The CRP, FIB and ESR of the observation group were (4.5±3.0)mg/L, (3.3±0.9)g/L, (11.4±5.4)mm/h, respectively, which were significantly higher than those of the control group[(2.0±1.5)mg/L, (2.9±0.5)g/L, (7.6±2.6)mm/h](t=5.12, 2.68, 4.36, all P<0.05). The level of CRP was positively correlated with AHI, oxygen desaturation index(ODI)(r=0.285, P<0.05 and r=0.282, P<0.05), and negatively correlated with the lowest SaO2 and the average SaO2(r=-0.257, P<0.05 and r=-0.259, P<0.05). The level of FIB was positively correlated with AHI, ODI(r=0.430, P<0.01 and r=0.311, P<0.01), and negatively correlated with the lowest SaO2(r=-0.287, P<0.01). There were no correlations between ESR and sleep breathing parameters.@*Conclusion@#The levels of CRP, FIB and ESR are increased in OSAHS patients, and the levels of CRP and FIB are proportional to the severity of OSAHS, suggesting that OSAHS patients has systemic inflammatory response.

Obesity hypoventilation syndrome: a current review / Síndrome de obesidade-hipoventilação: uma revisão atual

ABSTRACT Obesity hypoventilation syndrome (OHS) is defined as the presence of obesity (body mass index ≥ 30 kg/m²) and daytime arterial hypercapnia (PaCO2 ≥ 45 mmHg) in the absence of other causes of hypoventilation. OHS is often overlooked and confused with other conditions associated with hypoventilation, particularly COPD. The recognition of OHS is important because of its high prevalence and the fact that, if left untreated, it is associated with high morbidity and mortality. In the present review, we address recent advances in the pathophysiology and management of OHS, the usefulness of determination of venous bicarbonate in screening for OHS, and diagnostic criteria for OHS that eliminate the need for polysomnography. In addition, we review advances in the treatment of OHS, including behavioral measures, and recent studies comparing the efficacy of continuous positive airway pressure with that of noninvasive ventilation.

RESUMO A síndrome de obesidade-hipoventilação (SOH) é definida pela presença de obesidade (índice de massa corpórea ≥ 30 kg/m2) e hipercapnia arterial diurna (PaCO2 ≥ 45 mmHg), na ausência de outras causas. A SOH é frequentemente negligenciada e confundida com outras patologias associadas à hipoventilação, em particular à DPOC. A importância do reconhecimento da SOH se dá por sua elevada prevalência, assim como alta morbidade e mortalidade se não tratada. Na presente revisão, abordamos os recentes avanços na fisiopatologia e no manejo da SOH. Revisamos a utilidade da medição do bicarbonato venoso como rastreamento e os critérios diagnósticos que descartam a necessidade de polissonografia. Destacamos ainda os avanços no tratamento da SOH, incluindo medidas comportamentais, e estudos recentes que comparam a eficácia do uso de pressão positiva contínua nas vias aéreas e de ventilação não invasiva.

Obstructive sleep apnea hypopnea syndrome and alveolar hypoventilation syndrome in motor neuron disease: A case report and literature review / 中南大学学报(医学版)

Objective:To investigate the clinical characteristics of a patient with motor neuron disease,which caused sleep-disordered breathing (SDB) and alveolar hypoventilation syndrome,and to improve the diagnosis rate for this disease.Methods:Retrospectively analyze the diagnosis and treatment process for a 52 year-old male patient,who was accepted by the Second Xiangya Hospital,Central South University because of dyspnea,shortness of breath and malaise for 4 months,and eventually was diagnosed as motor neuron disease associated with obstructive sleep apnea hypopnea syndrome and alveolar hypoventilation syndrome.In addition,we searched CNKI,Wanfang and PubMed databases to review relevant literature with keywords (motor neuron disease or amyotrophic lateral sclerosis or progressive bulbar palsy or progressive muscular atrophy or primary lateral sclerosis) AND (sleep apnea or sleep disordered breathing) from January 1990 to May 2017.Results:The major clinical manifestation of motor neuron disease induded impaired upper and lower motor neuron displayed with proximal musde weakness,musde tremor,amyotrophy,bulbar symptoms and pyramidal sign.It was a chronic,progressive disease with worse prognosis,low survival and difficult in diagnosis.Electroneuromyography was a vital way for diagnosis.Furthermore,sleep disordered breathing was common in patients with motor neuron disease,which was featured as decreased rapid eye movement sleep,increased awaking time,apnea and hypopnea.The main mechanism for sleep disordered breathing in motor neuron disease might be due to the disturbed central nervous system and paralysis of diaphragm and respiratory muscle.Moreover,the patient suffered from restrictive ventilatory dysfunction,alveolar hypoventilation and subsequent partial pressure of carbon dioxide and hypoxernia.Therefore,respiratory failure was the most frequent cause of death for patients with motor neuron disease.Non-invasive positive pressure ventilation was suggested to apply to such patients,whose forced vital capability was less than 75 percent of predicted value.Conclusion:Sleep disordered breathing is common in patients with motor neuron disease.Hence,polysomnography is suggested as a routine examination to confirm the potential complications and give timely therapy.Treatment with non-invasive positive pressure ventilation is important for patients to improve life qualit,survival rate and prognosis.

Progress of diagnosis and treatment of congenital central hypoventilation syndrome / 中华实用儿科临床杂志

Congenital central hypoventilation syndrome (CCHS) is a rare genetic disorder characterized by ventilatory insensitivity to hypercapnia and hypoxemia during sleep and/or wakefulness presenting in infancy,childhood or adulthood.Paired-like homeobox 2B (PHOX2B) is the disease-defining gene for CCHS,which includes 2 mutation types,polyalanine repeat expansion mutation(PARM) and non-PARM.The CCHS-phenotype is associated with PHOX2B genotype.Children with CCHS typically have normal breathing when awake,while have progressive shallow breathing,cyanosis,hypercapnia and hypoxemia when asleep,but they don't response with respiratory effort.CCHS patients mainly present at birth,some may present in adult years.CCHS is also associated with generalized dysfunction of the autonomic nervous system,and Hirschsprung disease and tumors of neural crest origin are associated with the disease.Non-invasive ventilation is an effective treatment and it can increase the quality of life for CCHS patient.

Congenital central hypoventilation syndrome: a report of four cases / 中国新生儿科杂志

Objective To study the molecular genetic mechanism of congenital central hypoventilation syndrome ( CCHS).Method The clinical data and molecular genetics results of CCHS diagnosed in neonatology department from 2014 to 2016 were analyzed retrospectively.The relationship between genotypes and clinical phenotypes in patients of CCHS was analyzed , and the diagnostic thinkings , follow－up and prognosis were summarized.Result A total of 4 infants with CCHS were included in this study.Among them, 2 were boys and the other 2 were girls.They were all full－term neonates without asphyxia at birth , but they soon sufferd from dyspnea and cyanosis , required assisted ventilation.One case had difficult defecation. All 4 cases had difficulty in weaning.The respiratory rhythm became weak developed apnea and carbon dioxide retention was detected in blood gas analysis.All the 4 cases died after withdrawal of treatment.The results of molecular genetic testing were as follows.There was a 38bp heterozygous deletion mutation in exon 3 of gene PHOX2B ( e.756＿776 del21bp).Three cases were found small fragment insertion in exon 3 of gene PHOX2B, which attributed to polyalanine repeat expansion mutations (PARMs).One case belonged to type 20/27 and another 2 cases belonged to type 20/26.Conclusion The main manifestation of CCHS in the neonatal period is ventilator dependant , which can combined with megacolon and atypical autonomic nerve disorder.According to the literature, more than 95%of CCHS are caused by the PHOX2B mutation. The symptom is severe when it got a non－PARMs mutation.It′s useful to make a definite diagnosis with genetic diagnosis results , which could be helpful for treating and predicting.Only effective respiratory support and standardized follow－up system can improve the quality of life in patients of CCHS.

Caracterización socio-demográfica y clínica de pacientes adultos en ventilación mecánica no invasiva domiciliaria. Ministerio de Salud. Chile / Socio-demographic and clinical characterization of adult patients in non-invasive home mechanical ventilation. Ministry of Health. Chile

Resumen Introducción: La ventilación mecánica no invasiva domiciliaria (VMNID) se entrega en Chile desde el año 2008 mediante un programa público. Incluye equipamiento y profesionales. Objetivos: 1) Caracterizar el perfil socio-demográfico y clínico del usuario adulto con VMNID y 2) Proponer mejoras de atención socio-sanitaria. Método. Estudio descriptivo transversal, mediante entrevista presencial domiciliaria y revisión de bases de datos oficiales. Muestra de 267 sujetos, ambos géneros, mayores de 20 años, con Falla Respiratoria Global Crónica (FRGC) en VMNID. En 2016 había 413 pacientes activos. Resultados: Mujeres 144 (53,9%), edad media 58,6 ± 18 años. 25,5% tienen EPOC y 24% síndrome hipoventilación obesidad, la PaCO2 promedio de ingreso al programa fue de 59 ± 11 mmHg. Ventilados desde 3,2 ± 2,4 años, por 7,6 ± 2,4 h/día. Sujetos "sin instrucción" y con "educación básica incompleta" representan el 40,7% de la muestra. 46,4% eran jubilados, 3% vive en mediaguas, 19,8% reside como allegado, 49% no contaba con pareja, el 4,8% vivía solo, 68,6% eran dependientes de oxígeno. Test de Golberg estuvo alterado en un 40%. 17,7% "posee mayor limitación, incapaz de realizar el autocuidado". Conclusiones: Nuestros pacientes tienen un deterioro socio-demográfico y clínico severo, por baja escolaridad, predominio de adultos mayores, mayor incapacidad laboral, son enfermos más graves con niveles basales de PaCO2 más altos, en comparación a estudios europeos. Los programas de VMNID deben adoptar un enfoque socio-sanitario y estar insertos en la red de salud tanto en servicio social, salud cardiovascular y mental.

Introduction: Non-invasive home mechanical ventilation (NIHMV) is delivered in Chile since 2008 throughout a public program, including equipment and professionals. Objectives: 1) Characterize the socio-demographic and clinical profile of the adult patient under NIHMV and 2) Propose improvements in social health care. Methodology: Descriptive cross-sectional study, through face-to-face home interview and review of official databases. Sample of 267 subjects, both gender, over 20 years-old, with Chronic Global Respiratory Failure (CGRF) in NIHMV. In 2016 there were 413 active patients. Results: Women 144 (53.9%), mean age 58.6 ± 18 years-old; 25.5% had COPD and 24% had a hypoventilation obesity syndrome, average PaCO2 at the time of admission to program was 59 ± 11 mmHg, they were ventilated since 3.2 ± 2.4 years, 7.6 ± 2.4 h a day. Subjects "without instruction" and with "incomplete basic education" represents 40.7% of the sample. 46.4% were retired persons; 3% lived in a precarious hut; 19.8% cohabited with relatives or close friends; 49% did not have a partner; 4.8% lived alone; 68.6% was oxygen dependent; 40% had an altered Golberg test; 17.7% "has a major limitation, unable to perform self-care". Conclusions: Our patients have a severe socio-demographic and clinical deterioration, due to low schooling level, predominance of older adults, a major incapacity for working and patients have a more severe disease with higher baseline PaCO2 levels, compared to European studies. NIHMV programs must adopt a social health approach and be inserted into the health network in social service, and cardiovascular and mental health programs.

Haddad Syndrome: A case report in a Filipino infant

@#Haddad syndrome is a rare congenital disorder in which congenital central hypoventilation syndrome (CCHS) occurs with Hirschsprung’s disease. It is extremely rare with only more than 60 cases reported in the worldwide literature. We report on a Filipino newborn male infant who presented with signs and symptoms of progressive abdominal enlargement, bowel obstruction, and recurrent hypoventilation. The diagnosis of Haddad syndrome was made clinically and confirmed by sequence analysis of the PHOX2B gene which showed a 27repeat heterozygous expansion of the polyalanine-coding region. All CCHS patients require assisted ventilation especially during sleep to prevent lung atelectasis and other complications. An early diagnosis and confirmation by genetic testing is vital for proper management of affected patients.

Congenital central hypoventilation syndrome diagnosis and treatment / 国际儿科学杂志

Congenital central hypoventilation syndrome (CCHS)is a rare disorder characterized by hypoventilation during sleep and blunted ventilatory responses to hypercapnia and hypoxemia.It is normally found in neonatal and infant.Late-onset cases have been reported recently.The paired-like homeobox gene PHOX2B is the disease-defining gene for CCHS;a mutation in the PHOX2B gene is requisite to the diagnosis of CCHS.As a lifelong disease,the key treatment is ensuring adequate ventilation and oxygenation,effective modalities include positive pressure ventilation,negative pressure ventilation and diaphragmatic pacing.The strategy of anti-mutant protein and the use of progestin open up clinical perspectives to enhance ventilation in CCHS patients.

Congenital central hypoventilation syndrome associated with Hirschsprung's Disease: case report and literature review / Síndrome de hipoventilação central congênita associada à doença de Hirschsprung: relato de caso e revisão de literatura

Abstract Objective: To report the case of a newborn with recurrent episodes of apnea, diagnosed with Congenital Central hypoventilation syndrome (CCHS) associated with Hirschsprung's disease (HD), configuring Haddad syndrome. Case description: Third child born at full-term to a non-consanguineous couple through normal delivery without complications, with appropriate weight and length for gestational age. Soon after birth he started to show bradypnea, bradycardia and cyanosis, being submitted to tracheal intubation and started empiric antibiotic therapy for suspected early neonatal sepsis. During hospitalization in the NICU, he showed difficulty to undergo extubation due to episodes of desaturation during sleep and wakefulness. He had recurrent episodes of hypoglycemia, hyperglycemia, metabolic acidosis, abdominal distension, leukocytosis, increase in C-reactive protein levels, with negative blood cultures and suspected inborn error of metabolism. At 2 months of age he was diagnosed with long-segment Hirschsprung's disease and was submitted to segment resection and colostomy through Hartmann's procedure. A genetic research was performed by polymerase chain reaction for CCHS screening, which showed the mutated allele of PHOX2B gene, confirming the diagnosis. Comments: This is a rare genetic, autosomal dominant disease, caused by mutation in PHOX2B gene, located in chromosome band 4p12, which results in autonomic nervous system dysfunction. CCHS can also occur with Hirschsprung's disease and tumors derived from the neural crest. There is a correlation between phenotype and genotype, as well as high intrafamilial phenotypic variability. In the neonatal period it can simulate cases of sepsis and inborn errors of metabolism.

Resumo Objetivo: Relatar caso de neonato com episódios de apneias recorrentes, diagnosticado com síndrome de hipoventilação central congênita (SHCC) associada à doença de Hirschsprung (DH), o que configurou síndrome de Haddad. Descrição do caso: Terceiro filho de casal não consanguíneo, nascido a termo, parto normal sem intercorrências, peso e comprimento adequados para idade gestacional. Logo após o nascimento apresentou bradipneia, bradicardia e cianose, foi submetido à intubação orotraqueal e iniciada antibioticoterapia empírica devido à suspeita de sepse neonatal precoce. Durante internação em UTI neonatal evoluiu com dificuldade de extubação devido a episódios de dessaturação durante sono e vigília. Apresentou quadros recorrentes de hipoglicemia, hiperglicemia, acidose metabólica, distensão abdominal, leucocitose, aumento de proteína C reativa, com hemoculturas negativas e suspeita de erro inato do metabolismo. Aos dois meses foi diagnosticada doença de Hirschsprung de segmento longo, foi submetido à ressecção do segmento e colostomia à Hartmann. Feita pesquisa genética por reação em cadeia da polimerase para pesquisa de SHCC, que evidenciou alelo mutado do gene PHOX2B e confirmou o diagnóstico. Comentários: Trata-se de doença genética rara, de herança autossômica dominante, causada por mutação no gene PHOX2B, localizado na banda cromossômica 4p12, que resulta em disfunção do sistema nervoso autônomo. A SHCC também pode cursar com doença de Hirschsprung e tumores derivados da crista neural. Há correlação entre fenótipo e genótipo, além de grande variabilidade fenotípica intrafamiliar. No período neonatal pode simular quadros de sepse e erros inatos do metabolismo.

The research development of congenital central hypoventilation syndrome / 中国小儿急救医学

Congenital central hypoventilation syndrome,also known as “Ondine′s curse”,is charac-terized by hypoventilation during sleep and impaired ventilatory responses to hypercapnia and hypoxemia. This disorder is associated with a malfunction of the nerves that control involuntary body functions and abnor-mal development of early embryonic cells that form the spinal cord. This review summarized the latest pro-gression in the pathogenesis,clinical symptoms,diagnosis,treatment and prognosis.

Analysis of the relation between dental arch size and upper airway morphology in patients with obstructive sleep apnea hypoventilation syndrome / 实用口腔医学杂志

Objective:To study the anatomical correlation between dental arch and the volume of upper airway in patients with obstruc-tive sleep apnea hypoventilation syndrome(OSAHS). Methods: Dental arch architecture and upper airway volume were measured by cone beam CT(CBCT) in the subjects with OSAHS(n=22) and without OSAHS(n=19). The correlation between dental arch and the supper airway volume in OSAHS patients was analyzed. Results:The length of the upper dental arch and the height of palate in OSAHS patients were larger than those of the controls(All, P<0. 05). Cross-sectional area of nasopharynx and retropalatal and the total volume of upper airway were negatively correlated with the palatal height and upper dental arch length(P<0. 05), while positively correlated with upper dental arch of molar regions(P<0. 05). Conclusion:The abnormal shape of upper dental arch is related to the airway vol-ume of nasopharynx and retropalatal region in patients with OSAHS.