Prevalence of pulmonary hypertension in children with obstructive sleep apnea living at high altitude.

Introduction: The prevalence of obstructive sleep apnea (OSA) is 1-4 %. Some reports describe its association with pulmonary hypertension (PH), but its prevalence is unknown. No studies at high altitude have determined the relationship between OSA and PH. The aim of this study was to establish the prevalence of PH in children diagnosed with OSA living in a high-altitude city at 2640 m above sea level. Methods: Children between 2 and 16 years of age referred to the Sleep Laboratory of the Fundación Neumológica Colombiana in Bogotá with a positive polysomnogram for OSA were included, and a two-dimensional transthoracic echocardiogram (TTE) was performed to evaluate PH. Statistical analysis was performed using median, interquartile range, chi-squared test, and Kruskall-Wallis test. Results: Of the 55 patients (n: 55), 63.6 % were male, with a median age of 6 years, 14 children (25.5 %) were overweight; 12 children (21.8 %) had mild OSA, 12 (21.8 %) had moderate OSA and 31 (56.4 %) severe OSA. In patients with severe OSA, the minimum saturation during events was 78 % with a desaturation index (DI) of 33.8/hour (p < 0.01). T90 and T85 increased proportionally with OSA severity (p < 0.05). Of the 55 patients with OSA, none had PH according to echocardiography; 4 patients (7.2 %) had pulmonary artery systolic pressure (PASP) at the upper limit of normal (ULN), and it was not related to a higher body mass index (BMI). Conclusions: We found no association between OSA and PH in children with OSA at high altitude.

Sleep physiological network analysis in children.

Objective: Physiological networks have recently been employed as an alternative to analyze the interaction of the human body. Within this option, different systems are analyzed as nodes inside a communication network as well how information fows. Several studies have been proposed to study sleep subjects with the help of the Granger causality computation over electroencephalographic and heart rate variability signals. However, following this methodology, novel approximations for children subjects are presented here, where comparison between adult and children sleep is followed through the obtained connectivities. Methods: Data from ten adults and children were retrospectively extracted from polysomnography records. Database was extracted from people suspected of having sleep disorders who participated in a previous study. Connectivity was computed based on Granger causality, according to preprocessing of similar studies in this feld. A comparison for adults and children groups with a chi-square test was followed, employing the results of the Granger causality measures. Results: Results show that differences were mainly established for nodes inside the brain network connectivity. Additionally, for interactions between brain and heart networks, it was brought to light that children physiology sends more information from heart to brain nodes compared to the adults group. Discussion: This study represents a frst sight to children sleep analysis, employing the Granger causality computation. It contributes to understand sleep in children employing measurements from physiological signals. Preliminary fndings suggest more interactions inside the brain network for children group compared to adults group.

Intermittent hypoxia and respiratory patterns during sleep of preterm infants aged 3 to 18 months residing at high altitude.

STUDY OBJECTIVES: The aim of this study was to determine the impact of apneas on oxygen saturation and the presence of intermittent hypoxia, during sleep of preterm infants (PTIs) born at high altitudes and compare with full-term infants (FTIs) at the same altitude. METHODS: PTIs and FTIs from 3 to 18 months were included. They were divided into three age groups: 3-4 months (Group 1); 6-7 months (Group 2), and 10-18 months (Group 3). Polysomnography parameters and oxygenation indices were evaluated. Intermittent hypoxia was defined as brief, repetitive cycles of decreased oxygen saturation. Kruskal-Wallis test for multiple comparisons, t-test or Mann-Whitney U-test were used. RESULTS: 127 PTI and 175 FTI were included. Total apnea-hypopnea index (AHI) was higher in PTI that FTI in all age groups (Group 1: 33.5/h vs. 12.8/h, p = 0.042; Group 2: 27.0/h vs. 7.4/h, p < 0.001; and Group 3: 11.6/h vs. 3.1/h, p < 0.001). In Group 3, central-AHI (8.0/h vs. 2.3/h, p < 0.001) and obstructive-AHI (1.8/h vs. 0.6/h, p < 0.008) were higher in PTI than FTI. T90 (7.0% vs. 0.5, p < 0.001), oxygen desaturation index (39.8/h vs. 11.3, p < 0.001) were higher in PTI than FTI, nadir SpO2 (70.0% vs. 80.0, p<0.001) was lower in PTI. CONCLUSION: At high altitude, compared to FTI, PTI have a higher rate of respiratory events, greater desaturation, and a delayed resolution of these conditions, suggesting the persistence of intermittent hypoxia during the first 18 months of life. This indicates the need for follow-up of these infants for timely diagnosis and treatment of respiratory disturbances during sleep.

Cost-utility analysis of an integrated care program for children with asthma in a medium-income country.

OBJECTIVE: To evaluate the cost-utility of an integrated care program (ASMAIRE Infantil Program [PAI]) for children with asthma compared with standard of care. METHODS: A decision-analytic model was used to compare an integrated care program compared to the standard of care in children with asthma in Bogota, Colombia. Baseline characteristics of the patients were established according to the distribution of patients in the PAI database. Other inputs were obtained from published meta-analysis, local registries, medical bills, general mortality data, and expert opinion. Costs were presented in 2017 Colombian pesos. Outcomes included quality-adjusted life-years (QALYs). Costs and outcomes were discounted by 5% per year. Incremental cost-utility ratios were presented for PAI compared with standard of care. Univariate and multivariate probabilistic sensitivity analyses were conducted to assess model robustness to parameter uncertainty. RESULTS: The model predicted that patients that are part of the PAI would accrue more QALYs than patients on standard of care. The incremental results suggest that the PAI is a cost-effective treatment (incremental cost-utility ratio of Colombian pesos $33 753 817/QALY) compared with standard of care. Sensitivity analyses suggest that results are most sensitive to cost of care (with and without PAI) and costs of severe exacerbation. However, the PAI is cost-effective irrespective of variation in any of the input parameters. CONCLUSION: Our model predicted that an integrated intervention for the management of asthma in pediatric patients improves QALYs, reduces number of disease related exacerbations compared to standard therapy and is cost-effective for the long-term control of the disease in Colombia.

Allergic Rhinitis and OSA in Children Residing at a High Altitude.

BACKGROUND: OSA affects 2% to 4 % of the pediatric population; allergic rhinitis (AR) has been identified as a risk factor in sleep-disordered breathing, but no studies evaluating such an association have been conducted in high-altitude environments. The goal of this study was to assess whether the severity of AR is associated with the severity of OSA in children undergoing polysomnography (PSG) in the high-altitude city of Bogotá, Colombia. METHODS: A cross-sectional observational study of children with AR was conducted. Severity of AR was evaluated by using the AR health-related quality of life questionnaire for children (ESPRINT-15) and the Allergic Rhinitis and its Impact on Asthma (ARIA) classification. Diagnosis and severity of OSA were established by using PSG. Potential associations between AR severity and OSA severity were assessed by using binary logistic regression and the Spearman correlation coefficient (ρ). RESULTS: A total of 99 children (mean age, 7.9 years; 45% female) were included; 53% had OSA. An ESPRINT-15 score was associated with severe OSA (OR, 2.0; 95% CI, 1.12-6.04; P = .01). Patients with moderate/severe persistent rhinitis according to ARIA exhibited a 10.1-fold greater risk of severe OSA (OR, 10.15; 95% CI, 1.15-89.0). Furthermore, the apnea-hypopnea index was associated with the ESPRINT-15 score (ρ = 0.215; P = .03) and with the ARIA severity scale (P = .04; ρ = 0.203). CONCLUSIONS: In symptomatic children with AR residing at a high altitude, increasing AR severity is associated with more severe OSA.

Impulse oscillometry reference values and bronchodilator response in three- to five-year old children living at high altitude.

INTRODUCTION: Impulse oscillometry (IOS) is used to measure airway impedance. It is an effective tool for diagnosing and treating respiratory diseases, and it has the advantage that it does not require forced respiratory maneuvers. IOS reference values are required for each population group. OBJECTIVE: This study aimed to determine the IOS reference values and bronchodilator response in healthy preschool children living in Bogotá, Colombia. METHODS: We performed a cross-sectional study in preschool children who had no history of respiratory disease; 96 children fit the parameters for testing to determine normal values according to the American Thoracic Society and European Respiratory Society criteria. RESULTS: Values for respiratory resistance (Rrs) and reactance (Xrs) at 5, 10, and 20 Hz, respiratory impedance (Zrs, and resonance frequency (Fres) were established. Height was the most influential independent variable for IOS values; an increase in height led to a reduction in Rrs5 and Rrs20 and an increase in Xrs5. After the administration of 400 mcg of salbutamol the values for Rrs5(-17.48%), Rrs20(-8.63%), Fres (-10.68%), and area of reactance (-35.44%) were reduced, meanwhile Xrs5 (15.35%) was increased. CONCLUSIONS: Normal IOS values before and after the administration of 400 mcg of salbutamol were determined for a population of children aged 3-5 years at 2,640 m. Reference IOS equations for these children are presented. A relative change of up to -28% and 36% after the use of salbutamol for respiratory resistance and reactance, respectively, should be considered as an upper limit of the normal range, and possible appropriate cut-off values for defining significant response for evaluating therapeutic interventions.

High prevalence of house dust mite sensitization in children with severe asthma living at high altitude in a tropical country.

BACKGROUND: Some studies, mainly in Europe, have shown a low level of sensitization to house dust mite (HDM) allergens at high altitude (HA). Differently, some others in tropical countries have shown a higher level. The aim of this study was to evaluate allergens sensitization, including HDM, in children with severe asthma (SA), residents at HA in a tropical middle-income developing country. METHODS: Observational, analytical, cross-sectional study in children aged 6-15 years old with SA at HA (2640 m). Skin prick tests (SPT), serum IgE, exhaled fraction of nitric oxide (FENO ), spirometry, and asthma questionnaire (ACT) were performed. Associations were explored by Pearson or Spearman coefficients. RESULTS: We included 61 children. Most patients were male (61.3%), median age: 10 years (Interquartile range [IQR]: 8-12), median BMI: 17 kg/m2 (IQR: 16-20); Median of positive SPT: 2 (IQR: 2-3). At least one SPT was positive in 88.7% of patients and 87.9% were positive for at least one HDM. Serum IgE: 348 UI/mL (IQR: 154-760) and FENO : 22 ppb (IQR: 9-41). Prebronchodilator values were (% predicted): FVC: 109.7% (±15.5%), FEV1 : 98.4% (±16.3); FEV1 /FVC: 82% (±8%). SPT were inversely correlated with the FEV1 /FVC (Rho: -0.34; 95% CI: -0.55 a -0.09; P = 0.008). CONCLUSIONS: These children with SA living at HA in a tropical middle-income developing country have a high prevalence of HDM sensitization. One explanation for this might be that tropical conditions, such as temperature and humidity, could modify the effect of the altitude on asthma.

Virus and Mycoplasma pneumoniae prevalence in a selected pediatric population with acute asthma exacerbation.

OBJECTIVE: To determine the prevalence of viral and atypical bacteria Mycoplasma pneumoniae infection in children experiencing asthma exacerbation and compare positive and negative subjects with regard to exacerbation severity, need for hospitalization, and treatment. METHODS: One hundred sixty-nine asthmatic children aged 2-15 years old who were admitted to emergency rooms in Bogota, Colombia for acute asthma exacerbation were interviewed. Nasopharyngeal aspirates were taken for DNA and RNA extraction. M. pneumoniae and virus were detected by PCR using specific primers. RESULTS: The prevalence of M. pneumoniae and viral infection in the study population was 12.4% and 83.7%, respectively. All subjects positive for M. pneumoniae were also positive for viral infection. Rhinovirus was the most frequently detected viral agent. No significant differences in severity of asthma exacerbations or in need for hospitalization between the virus or M. pneumoniae positive and negative groups were observed. A significantly lower percentage of M. pneumoniae positive subjects had used inhaled steroids over the six months prior to asthma exacerbation compared to M. pneumoniae negative subjects (38.1% vs. 68.2%), suggesting that inhaled corticosteroids may have a protective effect against M. pneumoniae infections. CONCLUSIONS: The M. pneumoniae and virus prevalence found in this study were similar to those described in the literature. The 100% co-infection rate observed suggests that viral infection can predispose patients to M. pneumoniae infection, and that this interaction may trigger asthmatic exacerbation. Further studies should be done to confirm the protective effect of inhaled corticosteroids on M. pneumoniae infection in patients with asthma exacerbations.

Overnight Polysomnographic Characteristics and Oxygen Saturation of Healthy Infants, 1 to 18 Months of Age, Born and Residing At High Altitude (2,640 Meters).

BACKGROUND: Approximately 8% of the world population resides above 1,600 m, with about 10 million people living above 2,500 m in Colombia. However, reference values for polysomnography (PSG) and oxygen saturation (Spo2) of children < 2 years old residing at high altitude are currently unavailable. METHODS: Healthy infants aged 1 to 18 months born and residing at high altitude (Bogotá: 2,640 m) underwent overnight PSG. Four age groups were defined: group 1, < 45 days; group 2, 3 to 4 months; group 3, 6 to 7 months; and group 4, 10 to 18 months. Of 122 children enrolled, 50 had three consecutive PSG tests and were analyzed as a longitudinal subcohort. RESULTS: A total of 281 PSG tests were performed in 122 infants (56% girls): group 1, 106 PSG tests; group 2, 89 PSG tests; group 3, 61 PSG tests; and group 4, 25 PSG tests. Active sleep diminished and quiet sleep increased with maturation. Apnea-hypopnea indexes (total, central, and obstructive) were highest in group 1 (21.4, 12.4, and 6.8/h total sleep time, respectively) and diminished with age (P < .001). Mean Spo2 during waking and sleep increased with age (P < .001). Nadir Spo2 values during respiratory events were lower in younger infants. Longitudinal assessments of 50 infants confirmed the temporal trends described for the cross-sectional dataset. CONCLUSIONS: Healthy infants (≤ 18 months old) born and residing at high altitude show preserved sleep architecture but higher apnea-hypopnea indexes and more prominent desaturation with respiratory events than do those living at low altitude. The current study findings can be used as reference values for infants at high altitude.

Sleep apnea and oxygen saturation in adults at 2640 m above sea level.

PURPOSE: To describe the SpO2 in wakefulness, sleep and during the apnea-hypopnea in adults living in Bogotá, located at 2640 m above sea level. METHODS: Descriptive observational study in adults referred for polysomnogram (PSG). A normal Apnea hypopnea index (AHI) was defined as ≤5 and obstructive sleep apnea (OSA) was classified as mild (AHI 5-15), moderate (AHI 15-30), and severe (AHI >30). T-test or ANOVA test for SpO2 differences between groups was used. RESULTS: 1799 patients, 33% women. 222 (12.8%) did not have OSA (normal IAH), 268 (14.9%) mild OSA, 315 (17.5%) moderate ,and 993 (55.2%) severe. In all cases a low SpO2 (SpO2<90%) was found. The SpO2 was lower when the AHI was higher, in wakefulness, in non-REM and in REM (p<0.001). For all grades of severity, SpO2 decreased significantly from wakefulness to non-REM sleep and to REM sleep (p<0.001). Patients with severe OSA had higher desaturation during wakefulness (85.2±6.6%), non-REM sleep (83.1±7.7%), REM sleep (78.8±10.2), and during events (75.1±9.1%). CONCLUSIONS: Patients with OSA at 2640 m have nocturnal desaturation lower than 88%, which decreases with higher severity of OSA. The clinical impact of sleep disorders at this point may be greater than at sea level and should be studied.