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OBJECTIVE: To determine the frequency of sleep problems in low-income, urban pediatric populations in cities at different altitudes in Colombia. METHODS: A descriptive, cross-sectional population-based observational study was conducted in children aged between 2 and 12 years in the low income, urban areas of three cities in Colombia (Santa Marta, Bucaramanga, and Bogotá) located at 15, 959, and 2640 m above sea level, respectively. Sociodemographic data were collected, and the Spanish version of the Pediatric Sleep Questionnaire was used. RESULTS: 1989 children were surveyed, distributed as follows: Santa Marta (32.0%), Bucaramanga (33.4%), and Bogotá (34.6%). The overall prevalence of sleep problems was 39.0%. Children from Santa Marta had the highest frequency of parasomnias (58.0%); those from Bucaramanga had the highest frequency of attention deficit symptoms (4.0%) and apneic pauses witnessed by parents or caregivers (5.7%). Finally, Bogotá, the only high-altitude location, had the highest frequency of sleep disordered breathing (17.2%). CONCLUSIONS: The study found a high frequency of sleep problems in the pediatric population, especially at higher altitudes when compared to lower altitude settings. Sleep disorders warrant early detection and timely therapeutic intervention.

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Obstructive sleep apnea syndrome affects 1%-4% of all children worldwide. Currently, diagnosis of obstructive sleep apnea is based on sea-level guidelines, without taking into account the altitude at which the populations live. It has been shown that at 3,200 m of altitude there is an increase in obstructive events in healthy children aged 7 to 16 years; on the other hand, it is known that SpO2 dispersion between individuals becomes wider as altitude increases, a phenomenon that is more marked during sleep. About 17 million Colombians live in regions between 2,500 m and 2,700 m, as do significant populations in other Latin American countries. This research aimed to characterize respiratory polygraphy sleep parameters in healthy, non-snoring children aged 4-9 years living at 2,560 m. We carried out home respiratory polygraphy in 32 children with a mean age of 6.2 years (range 4-9 years). The average recorded sleep time was 7.8 h, the median apnea-hypopnea index was 9.2/h, the obstructive apnea-hypopnea index had a median of 8.8/h (p5 4.2 to p95 17.9) and central apnea a median of 0.4/h. The median SpO2 was 93% (p5 90.5 to p95 94) and transcutaneous CO2 had a median of 39.4 mmHg (p531.7 to p95 42.3). The median oxygen desaturation index ≥ 3% was 11.2 and median oxygen desaturation index ≥ 4% was 3.9. Normal measurements for respiratory polygraphy obtained at sea level do not apply to children at altitude. If such guidelines are used, obstructive sleep apnea will be over-diagnosed, resulting in unnecessary adenotonsillectomies, among other interventions.

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Background: Human respiratory physiology changes significantly in high altitude settings and these changes are particularly marked during sleep. It is estimated that 170 million people live above 2,500 m in environments where normal sleep parameters differ from those established at sea level or low altitude. Methods: We conducted a systematic review of publications reporting sleep studies in healthy children living at high altitude. For this purpose, data from PubMed, EMBASE, SciELO and Epistemomikos bases were retrieved up to August 2021. Results: Six articles met specified inclusion criteria; all reporting data were from South America involving 245 children (404 sleep studies) in children aged 0.6 months to 18 years, at altitudes between 2,560 to 3,775 m. The main results were: (1) Central apnea index decreased as the age increased. (2) The obstructive apnea/hypopnea index showed a bimodal profile with an increase in young infants up to age of 4 months, decreasing to 15 months of age, and then a second peak in children aged 4 to 9 years of age, dropping in older schoolchildren and adolescents. (3) Periodic breathing in the first months of life is more marked with increasing altitude and decreases with age. Conclusions: There are few studies of sleep physiology in children living at high altitude. The international parameters defining normal apnea indices currently used at low altitude cannot be applied to high altitude settings. The interpretation of sleep studies in children living at high altitude is complex because there are important developmental changes across childhood and a wide range of altitude locations. More normative data are required to determine thresholds for respiratory pathology at a variety of high altitude settings.

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OBJECTIVES: The aims of this study were to determine, in Australian pulmonary rehabilitation programs for people with COPD: (1) whether oxygen saturation (SpO2) was monitored during exercise testing; (2) whether supplemental oxygen was available during exercise testing and/or training; (3) whether oxygen was prescribed during exercise training; and the reason for providing oxygen; (4) whether a protocol was available for supplemental oxygen prescription during exercise training. METHODS: This was a cross-sectional multi-center study using a purposed-designed survey. De-identified survey data were analyzed and the absolute number and percentage of responses were recorded for each question. RESULTS: The survey was sent to 261 pulmonary rehabilitation programs and 142 surveys (54%) were available for analysis. Oxygen saturation was monitored during exercise testing in 92% of programs. Supplemental oxygen was available in the majority of programs during exercise testing (82%) and training (84%). The rationale cited by 87 programs (73%) for prescribing oxygen during exercise training was maintaining SpO2 above a threshold ranging from SpO2 80-88%. Forty-five (32%) programs had a protocol for oxygen prescription during exercise training. CONCLUSION: While monitoring of SpO2 during exercise testing and using supplemental oxygen during testing and training is common in Australian pulmonary rehabilitation programs, few programs had a protocol in place for the prescription of supplemental oxygen for people with COPD who were not on long-term oxygen therapy. This may be due to lack of strong evidence to support the use of supplemental oxygen during exercise training.

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BACKGROUND: A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. METHODS: This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. FINDINGS: Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0-75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4-97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8-80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3-4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. INTERPRETATION: ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials. FUNDING: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, Bill & Melinda Gates Foundation, Lemann Foundation, Rede D'Or, Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca.

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Background: It is well known that oxygen saturation as measured by pulse oximetry (SpO2) decreases as altitude increases. However, how SpO2 changes across childhood, and more specifically during sleep/wake states, at different high altitudes are less well understood. We aimed to perform a systematic review of all studies with direct SpO2 measurement in healthy children living at high altitude (>2500 meters above sea level) to address these questions. Methods: MEDLINE, EMBASE, and SciELO databases were searched up to December 2018. Two independent reviewers screened the literature and extracted relevant data. Results: Of 194 references, 20 studies met the eligibility criteria. Meta-analysis was not possible due to the use of different oximeters and/or protocols for data acquisition and reporting of different SpO2 central tendency and dispersion measures. The most relevant findings from the data were: (1) SpO2 is lower as altitude increases; (2) at high altitude, SpO2 improves with age through childhood; (3) SpO2 is lower during sleep and feeding in comparison to when awake, this SpO2 gap between wake and sleep states is more evident in the first months of life and narrows later in life; (4) SpO2 dispersion (interindividual variation) is higher at younger ages, and more so during sleep; (5) In 6/20 studies, the SpO2 values were nonnormally distributed with a consistent left skew. Conclusions: At high altitude, the mean/median SpO2 increases in children with aging; a significant gap between wake and sleep states is seen in the first months of life, which narrows as the infant gets older; SpO2 dispersion at high altitude is wider at younger ages; at high altitude, SpO2 shows a nonnormal distribution skewed to the left; this bias becomes more evident as altitude increases, at younger ages and during sleep.

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STUDY OBJECTIVES: To compare polysomnographic parameters in high altitude (HA) native Andean children with low altitude (LA) native peers in order to explain the nocturnal oxyhemoglobin saturation (SpO2) instability reported in HA native children and to study the effect on sleep quality. METHODS: Ninety-eight healthy children aged 7-10 y and 13-16 y were recruited at LA (500 m) or HA (3,650 m) above sea level. Physical examination was undertaken and genetic ancestry determined from salivary DNA to determine proportion of European ancestry, a risk factor for poor HA adaptation. Attended polysomnography was carried out over 1 night for 58 children at their resident location. RESULTS: Of 98 children recruited, 85 met inclusion criteria, 58 of 85 (68.2%) completed polysomnography, of which 56 were adequate for analysis: 30 at LA (17 male) and 26 at HA (16 male). There were no altitude differences in genetic ancestry, but a high proportion of European admixture (median 50.6% LA; 44.0% HA). SpO2 was less stable at HA with mean 3% and 4% oxygen desaturation indices greater (both P < 0.001) than at LA. This was not explained by periodic breathing. However, more obstructive hypopnea was observed at HA (P < 0.001), along with a trend toward more central apnea (P = 0.053); neither was explained by clinical findings. There was no difference in sleep quality between altitudes. CONCLUSIONS: HA native Andean children have more respiratory events when scoring relies on SpO2 desaturation due to inherent SpO2 instability. Use of American Academy of Sleep Medicine scoring criteria may yield false-positive results for obstructive sleep-disordered breathing at HA.

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STUDY OBJECTIVES: Physiological adaptation to high altitude hypoxia may be impaired in Andeans with significant European ancestry. The respiratory 'burden' of sleep may challenge adaptation, leading to relative nocturnal hypoxia. Developmental aspects of sleep-related breathing in high-altitude native children have not previously been reported. We aimed to determine the influence of development on diurnal-nocturnal oxyhemoglobin differences in children living at high altitude. METHODS: This was a cross-sectional, observational study. Seventy-five healthy Bolivian children aged 6 mo to 17 y, native to low altitude (500 m), moderate high altitude (2,500 m), and high altitude (3,700 m) were recruited. Daytime resting pulse oximetry was compared to overnight recordings using Masimo radical oximeters. Genetic ancestry was determined from DNA samples. RESULTS: Children had mixed European/Amerindian ancestry, with no significant differences between altitudes. Sixty-two participants had ≥ 5 h of nocturnal, artifact-free data. As predicted, diurnal mean oxyhemoglobin saturation decreased across altitudes (infants and children, both P < 0.001), with lowest diurnal values at high altitude in infants. At high altitude, there was a greater drop in nocturnal mean oxyhemoglobin saturation (infants, P < 0.001; children, P = 0.039) and an increase in variability (all P ≤ 0.001) compared to low altitude. Importantly, diurnal to nocturnal altitude differences diminished (P = 0.036), from infancy to childhood, with no further change during adolescence. CONCLUSIONS: Physiological adaptation to high-altitude living in native Andeans is unlikely to compensate for the significant differences we observed between diurnal and nocturnal oxyhemoglobin saturation, most marked in infancy. This vulnerability to sleep-related hypoxia in early childhood has potential lifespan implications. Future studies should characterize the sleep- related respiratory physiology underpinning our observations.

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We calculated the population density of the critically endangered Callicebus oenanthe in the Ojos de Agua Conservation Concession, a dry forest area in the department of San Martin, Peru. Results showed significant differences (p < 0.01) in group densities between forest boundaries (16.5 groups/km2, IQR = 21.1-11.0) and forest interior (4.0 groups/km2, IQR = 5.0-0.0), suggesting the 2,550-ha area harbours roughly 1,150 titi monkeys. This makes Ojos de Agua an important cornerstone in the conservation of the species, because it is one of the largest protected areas where the species occurs.

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OBJECTIVES: To assess cognition in populations born and living at high altitude (HA; 3,700 m) and low altitude (LA; 500 m) in Bolivia, who were similar for both socioeconomic status and genetic ancestry. To determine whether HA hypoxia influences cognitive decline across the life span. METHOD: In total, 191 healthy participants aged 4 to 85 years were assessed at HA (N = 94; 33; 35% male) and LA (N = 97; 46, 47% male) on a battery of cognitive tasks: fluid intelligence, attention, short- and long-term memory, and psychomotor speed. Saliva samples were obtained for evaluation of genetic ancestry. RESULTS: HA participants were significantly slower on measures of processing speed and speed of attention than individuals born and living at LA. HA participants had slightly higher percentage of native Andean ancestry than LA participants, but this was not associated with cognitive performance. CONCLUSIONS: This is the first study of HA residence and neurocognition across the life span. Given the physiological challenges of HA living, the impact on cognition appears to be subtle and related only to the speed of more complex cognitive operations, rather than to their accuracy. Moreover, the impact on cognition does not appear to differ with increasing age or for different degrees of genetic admixture. Further studies recruiting HA participants with a broader range of native Andean ancestry will help to address the issue of to what extent Amerindian ancestry provides neuroprotection to chronic hypoxia in those living at HA.

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