Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a lethal lung developmental disorder caused by heterozygous point mutations or genomic deletion copy-number variants (CNVs) of FOXF1 or its upstream enhancer involving fetal lung-expressed long noncoding RNA genes LINC01081 and LINC01082. Using custom-designed array comparative genomic hybridization, Sanger sequencing, whole exome sequencing (WES), and bioinformatic analyses, we studied 22 new unrelated families (20 postnatal and two prenatal) with clinically diagnosed ACDMPV. We describe novel deletion CNVs at the FOXF1 locus in 13 unrelated ACDMPV patients. Together with the previously reported cases, all 31 genomic deletions in 16q24.1, pathogenic for ACDMPV, for which parental origin was determined, arose de novo with 30 of them occurring on the maternally inherited chromosome 16, strongly implicating genomic imprinting of the FOXF1 locus in human lungs. Surprisingly, we have also identified four ACDMPV families with the pathogenic variants in the FOXF1 locus that arose on paternal chromosome 16. Interestingly, a combination of the severe cardiac defects, including hypoplastic left heart, and single umbilical artery were observed only in children with deletion CNVs involving FOXF1 and its upstream enhancer. Our data demonstrate that genomic imprinting at 16q24.1 plays an important role in variable ACDMPV manifestation likely through long-range regulation of FOXF1 expression, and may be also responsible for key phenotypic features of maternal uniparental disomy 16. Moreover, in one family, WES revealed a de novo missense variant in ESRP1, potentially implicating FGF signaling in etiology of ACDMPV.

OBJECTIVES: It remains uncertain whether treatment with adenotonsillectomy for obstructive sleep apnea in children improves cognitive function. The Preschool Obstructive Sleep Apnea Tonsillectomy and Adenoidectomy study was a prospective randomized controlled study in which researchers evaluated outcomes 12 months after adenotonsillectomy compared with no surgery in preschool children symptomatic for obstructive sleep apnea.METHODS: A total of 190 children (age 3-5 years) were randomly assigned to early adenotonsillectomy (within 2 months) or to routine wait lists (12-month wait, no adenotonsillectomy [NoAT]). Baseline and 12-month assessments included cognitive and behavioral testing, medical assessment, polysomnography, and audiology. The primary outcome was global IQ at 12-month follow-up, measured by the Woodcock Johnson III Brief Intellectual Ability (BIA). Questionnaires included the Pediatric Sleep Questionnaire, Parent Rating Scale of the Behavioral Assessment System for Children-II, and Behavior Rating Inventory of Executive Function, Preschool Version.RESULTS: A total of 141 children (75.8%) attended baseline and 12-month assessments, and BIA was obtained at baseline and 12-month follow-up for 61 and 60 participants in the adenotonsillectomy versus NoAT groups, respectively. No cognitive gain was found after adenotonsillectomy compared with NoAT, adjusted for baseline; BIA scores at 12-month follow-up were as follows: adenotonsillectomy, 465.46 (17.9) versus NoAT, 463.12 (16.6) (mean [SD]). Improvements were seen for polysomnogram arousals and apnea indices and for parent reports of symptoms (Pediatric Sleep Questionnaire), behavior (Behavior Assessment System for Children behavioral symptoms, P = .04), overall health, and daytime napping. CONCLUSIONS: Structured testing showed no treatment-attributable improvement in cognitive functioning of preschool children 12 months after adenotonsillectomy compared with NoAT. Improvements were seen after adenotonsillectomy in sleep and behavior by using polysomnogram monitoring and parental questionnaires.WHAT'S KNOWN ON THIS SUBJECT: Studies to evaluate changes in neurocognition after adenotonsillectomy for obstructive sleep apnea suggest that younger children may have potential for greater improvement. The previous study with a randomized design was in school-aged children.WHAT THIS STUDY ADDS: This randomized study of preschool children showed reduced frequency of day naps and confirmed polysomnographic and behavioral improvements after adenotonsillectomy compared with those still awaiting surgery, but our primary analysis showed no improvement in global IQ.

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Given the difficulties in diagnosing, or even defining, asthma in children, claims of a pediatric asthma epidemic in Canada and other developed countries are accepted with surprisingly little critical examination. We reviewed a broad range of data sources to understand how the epidemic evolved during the last 50 years and also to assess the reliability of the conclusions drawn from that data. We obtained Canadian National and Provincial data from Statistics Canada National Population Health Survey, and the British Columbia Ministry of Health respiratory database. International data were obtained by extensive review of pediatric asthma epidemiological surveys published during the last 50 years. In many developed countries, there have been three separate epidemics involving different aspects of pediatric asthma during the last 50 years: a double peaked mortality epidemic (1960s and 1980s), a hospital admission epidemic (peaked around 1990) and a steadily growing epidemic of children who report asthmatic symptoms on questionnaires. Canadian pediatric rates for asthma mortality (1-2/million/year) and hospital admission (1-2/thousand/year) are low and have fallen for the last 20 years. Rates based on questionnaire studies are high (10-15/hundred) and rose steadily over the same period. Objective reductions in asthma deaths and hospital admission likely reflect improved education and treatment programmes. Current claims of an epidemic based largely on subjective self-reported symptoms require more careful analysis. The possibility that symptom misperception, disease fashions, and poor recall, may be part of the explanation for the current high levels of self-reported symptoms deserves more attention.

Aims In infants with chronic neonatal lung disease (CNLD), we aimed to identify predictors of home oxygen duration, predictors of discharge oxygen flow rates, and the association of oxygen flow rates with respiratory outcomes. Methods Infants with CNLD requiring home oxygen in 2016 and 2017 were retrospectively reviewed. Hazard ratios (HR) were estimated from Cox proportional hazards regression models in the cohort. A multinomial logistic regression model examined the effects of maternal and infant variables on discharge oxygen flow rates. Kruskal–Wallis test with univariate linear regression and Fisher's exact test with binomial univariate logistic regression were used to examine associations between oxygen flow groups and post‐discharge clinical variables. Results One hundred and forty‐nine infants were included. Median corrected gestational age (CGA) at oxygen cessation was 6.8 months (interquartile range, 4.4) with 87.2% of infants weaned by 12 months CGA. Shorter initial neonatal intensive care unit (NICU) stay predicted faster oxygen weaning at 9 months (HR, 0.99; 95% confidence interval [CI], 0.98–1.00, p = .02) and 12 months (HR, 0.99; 95% CI, 0.98–1.00, p = .02). Infants with hypercarbia at discharge or discharged from NICU at higher CGA had higher odds of requiring ≥ 200 ml/min relative to ≤ 125 ml/min oxygen. Infants discharged with > 250 ml/min oxygen were more likely to have a respiratory‐related admission before 2 years chronological age. Conclusion Shorter initial NICU stay was the best predictor of earlier home oxygen cessation. At NICU discharge, infants with hypercarbia or a higher CGA may require more home oxygen and experience more respiratory‐related hospital admission in the first 2 years of chronological age.

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The goal of this position paper on ventilatory support at home for children is to provide expert consensus from Australia and New Zealand on optimal care for children requiring ventilatory support at home, both non-invasive and invasive. It was compiled by members of the Thoracic Society of Australia and New Zealand (TSANZ) and the Australasian Sleep Association (ASA). This document provides recommendations to support the development of improved services for Australian and New Zealand children who require long-term ventilatory support. Issues relevant to providers of equipment and areas of research need are highlighted.

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