Developmental changes in obstructive sleep apnea and sleep architecture in Down syndrome.

BACKGROUND: Down syndrome (DS, also known as Trisomy 21) is a condition associated with abnormal neurodevelopment and a higher risk for sleep apnea. Our study sought to better understand and characterize the age-related developmental differences in sleep architecture and obstructive sleep apnea (OSA) severity in children with DS compared to euploid individuals. METHODS: Retrospective review of polysomnograms in over 4151 infants, children, and adolescents in the pediatric sleep center at Children's National Hospital in Washington D.C. (0-18 years) including 218 individuals with DS. RESULTS: The primary findings of our study are that: (1) severe OSA (obstructive apnea-hypopnea index ≥ 10/h) was more prevalent in the DS group (euploid 18% vs. DS 34%, p < 0.001) with the highest OSA severity being present in young children (<3 years old) and adolescents (>10 years old), (2) abnormalities in sleep architecture in children with DS were characterized by a prolonged rapid-eye movement (REM) sleep onset latency (SOL) (euploid 119 min vs. DS 144 min, p < 0.001) and greater arousal indexes (euploid 10.7/h vs. DS 12.2/h, p < 0.001), (3) developmental changes in the amount of REM sleep or slow wave sleep were not different in DS individuals relative to euploid children, (4) multivariate analyses showed that OSA and REM sleep latency differences between DS and euploid individuals were still present after adjusting by age, biological sex, and body mass index. CONCLUSION: Severe OSA is highly prevalent in children with DS and follows an age-dependent "U" distribution with peaks in newborns/infants and children >10 years of age. Children with DS also have disturbances in sleep architecture characterized by a longer REM SOL and elevated arousal indexes. As sleep cycle generation and continuity play crucial roles in neuroplasticity and cognitive development, these findings offer clinically relevant insights to guide anticipatory guidance for infants, children, and adolescents with DS.

Real-world data evaluation of PAP responsiveness in pediatric obstructive sleep apnea.

STUDY OBJECTIVES: The use of positive airway pressure (PAP) in children is a complex process determined by multiple factors. There are limited data on the response of the pediatric population to PAP therapy at home. The goal of the study was to examine real-world responses using PAP home monitoring in children with obstructive sleep apnea. METHODS: The study included PAP therapy data for 195 children aged between 1 month and 18 years with obstructive sleep apnea and polysomnogram baseline study. We collected demographics, clinical variables, and polysomnogram parameters in all study participants. The individual response to PAP therapy was calculated comparing the apnea-hypopnea index (AHI) in the initial polysomnogram with the mean AHI provided by the download of PAP devices. Multivariate models (logistic regression) were used to examine the predictors of positive PAP response defined as a reduction in AHI ≥ 75%. RESULTS: We found excellent responses to PAP therapy in children (median 85% AHI reduction). However, there was substantial heterogeneity in AHI reductions while on PAP therapy. The best PAP responses were linked to more severe obstructive sleep apnea and higher PAP levels. We also identified that the response to PAP was higher in obese children and lower in males. The best predictive model for individual PAP response was biological sex, obesity, and obstructive AHI ≥ 20 events/h (area under the receiver operating characteristic curve of 0.791). CONCLUSIONS: Real-world data show that PAP is overall an effective therapy in children but the response is heterogeneous. Obstructive sleep apnea parameters and individual factors can be used to predict individual AHI reductions while on PAP and optimize PAP responses at home. CITATION: Aguilar H, Kahanowitch R, Weiss M, et al. Real-world data evaluation of PAP responsiveness in pediatric obstructive sleep apnea. J Clin Sleep Med. 2023;19(7):1313-1319.

The Next Frontier of Prematurity: Predicting Respiratory Morbidity During the First Two Years of Life in Extremely Premature Babies.

Background Advances in perinatal and neonatal medicine have led to an increasing number of infants surviving extreme prematurity (≤27 weeks gestational age, GA). The goal of this study was to examine the respiratory outcomes after neonatal intensive care unit (NICU) discharge of this vulnerable population. We hypothesized that the rates of respiratory hospitalizations are disproportionally higher in the subset of infants born ≤27 weeks GA relative to premature infants born 28-32 weeks GA. Methodology A retrospective longitudinal study of severe premature children (≤32 weeks GA, n = 183) was conducted. We subdivided our sample into extremely preterm infants (≤27 weeks GA; n = 101) and those born very preterm (28-32 weeks GA; n = 82). Our main outcome was the presence of respiratory hospitalizations within 24 months of NICU discharge. Results Extremely premature infants had more than three times higher odds of respiratory hospitalization at 24 months relative to infants born 28-32 weeks GA (adjusted odds ratio = 3.4; 95% confidence interval = 1.8, 6.4; p < 0.01). The increased risk of respiratory hospitalization in extremely premature infants was independent of GA. Regression models identified that the duration of supplemental oxygen and Black/African American ethnicity were significant predictors of respiratory hospitalizations in both prematurity groups independent of gender and birth weight. Conclusions The results support that babies born ≤27 weeks GA represent a distinct high-risk group of severely premature infants that needs novel preventive strategies and targeted interventions to improve their respiratory outcomes after NICU discharge.

Chest X-ray lung imaging features in pediatric COVID-19 and comparison with viral lower respiratory infections in young children.

RATIONALE: Chest radiography (CXR) is a noninvasive imaging approach commonly used to evaluate lower respiratory tract infections (LRTIs) in children. However, the specific imaging patterns of pediatric coronavirus disease 2019 (COVID-19) on CXR, their relationship to clinical outcomes, and the possible differences from LRTIs caused by other viruses in children remain to be defined. METHODS: This is a cross-sectional study of patients seen at a pediatric hospital with polymerase chain reaction (PCR)-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (n = 95). Patients were subdivided in infants (0-2 years, n = 27), children (3-10 years, n = 27), and adolescents (11-19 years, n = 41). A sample of young children (0-2 years, n = 68) with other viral lower respiratory infections (LRTI) was included to compare their CXR features with the subset of infants (0-2 years) with COVID-19. RESULTS: Forty-five percent of pediatric patients with COVID-19 were hospitalized and 20% required admission to intensive care unit (ICU). The most common abnormalities identified were ground-glass opacifications (GGO)/consolidations (35%) and increased peribronchial markings/cuffing (33%). GGO/consolidations were more common in older individuals and perihilar markings were more common in younger subjects. Subjects requiring hospitalization or ICU admission had significantly more GGO/consolidations in CXR (p < .05). Typical CXR features of pediatric viral LRTI (e.g., hyperinflation) were more common in non-COVID-19 viral LRTI cases than in COVID-19 cases (p < .05). CONCLUSIONS: CXR may be a complemental exam in the evaluation of moderate or severe pediatric COVID-19 cases. The severity of GGO/consolidations seen in CXR is predictive of clinically relevant outcomes. Hyperinflation could potentially aid clinical assessment in distinguishing COVID-19 from other types of viral LRTI in young children.

Airway Remodeling Factors During Early-Life Rhinovirus Infection and the Effect of Premature Birth.

Background: Early rhinovirus (RV) infection is a strong risk factor for asthma development. Airway remodeling factors play a key role in the progression of the asthmatic condition. We hypothesized that RV infection in young children elicits the secretion of growth factors implicated in airway remodeling and asthma progression. Methods: We examined the nasal airway production of remodeling factors in children ( ≤ 2 years old) hospitalized due to PCR-confirmed RV infection. Airway remodeling proteins included: MMP-1, MMP-2, MMP-7, MMP-9, MMP-10, TIMP-1, TIMP-2, EGF, Angiopoietin-2, G-CSF, BMP-9, Endoglin, Endothelin-1, Leptin, FGF-1, Follistatin, HGF, HB-EGF, PLGF, VEGF-A, VEGF-C, VEGF-D, FGF-2, TGF-ß1, TGF-ß2, TGF-ß3, PDGF AA, PDGF BB, SPARC, Periostin, OPN, and TGF-α. Results: A total of 43 young children comprising RV cases (n = 26) and uninfected controls (n = 17) were included. Early RV infection was linked to (1) enhanced production of several remodeling factors (e.g., HGF, TGFα), (2) lower MMP-9/TIMP-2 and MMP-2/TIMP-2 ratios, and (3) increased MMP-10/TIMP-1 ratios. We also found that relative to term infants, severely premature children had reduced MMP-9/TIMP-2 ratios at baseline. Conclusion: RV infection in young children elicits the airway secretion of growth factors implicated in angiogenesis, fibrosis, and extracellular matrix deposition. Our results highlight the potential of investigating virus-induced airway remodeling growth factors during early infancy to monitor and potentially prevent chronic progression of respiratory disorders in all ages.