Management of Persistent, Post-adenotonsillectomy Obstructive Sleep Apnea in Children: An Official American Thoracic Society Clinical Practice Guideline.

Background: Obstructive sleep apnea (OSA) is the most common sleep-related breathing disorder. Although adenotonsillectomy is first-line management for pediatric OSA, up to 40% of children may have persistent OSA. This document provides an evidence-based clinical practice guideline on the management of children with persistent OSA. The target audience is clinicians, including physicians, dentists, and allied health professionals, caring for children with OSA. Methods: A multidisciplinary international panel of experts was convened to determine key unanswered questions regarding the management of persistent pediatric OSA. We conducted a systematic review of the relevant literature. The Grading of Recommendations, Assessment, Development, and Evaluation approach was used to rate the quality of evidence and the strength of the clinical recommendations. The panel members considered the strength of each recommendation and evaluated the benefits and risks of applying the intervention. In formulating the recommendations, the panel considered patient and caregiver values, the cost of care, and feasibility. Results: Recommendations were developed for six management options for persistent OSA. Conclusions: The panel developed recommendations for the management of persistent pediatric OSA based on limited evidence and expert opinion. Important areas for future research were identified for each recommendation.

Nocturnal oximetry parameters as predictors of sleep apnea severity in resource-limited settings.

Nocturnal oximetry is an alternative modality for evaluating obstructive sleep apnea syndrome (OSAS) severity when polysomnography is not available. The Oxygen Desaturation (≥3%) Index (ODI3) and McGill Oximetry Score (MOS) are used as predictors of moderate-to-severe OSAS (apnea-hypopnea index-AHI >5 episodes/h), an indication for adenotonsillectomy. We hypothesised that ODI3 is a better predictive parameter for AHI >5 episodes/h than the MOS. All polysomnograms performed in otherwise healthy, snoring children with tonsillar hypertrophy in a tertiary hospital (November 2014 to May 2019) were analysed. The ODI3 and MOS were derived from the oximetry channel of each polysomnogram. Logistic regression was applied to assess associations of ODI3 or MOS (predictors) with an AHI >5 episodes/h (primary outcome). Receiver operating characteristic (ROC) curves and areas under ROC curves were used to compare the ODI3 and MOS as predictors of moderate-to-severe OSAS. The optimal cut-off value for each oximetry parameter was determined using Youden's index. Polysomnograms of 112 children (median [interquartile range] age 6.1 [3.9-9.1] years; 35.7% overweight) were analysed. Moderate-to-severe OSAS prevalence was 49.1%. The ODI3 and MOS were significant predictors of moderate-to-severe OSAS after adjustment for overweight, sex, and age (odds ratio [OR] 1.34, 95% confidence interval [CI] 1.19-1.51); and OR 4.10, 95% CI 2.06-8.15, respectively; p < 0.001 for both). Area under the ROC curve was higher for the ODI3 than for MOS (0.903 [95% CI 0.842-0.964] versus 0.745 [95% CI 0.668-0.821]; p < 0.001). Optimal cut-off values for the ODI3 and MOS were ≥4.3 episodes/h and ≥2, respectively. The ODI3 emerges as preferable or at least a complementary oximetry parameter to MOS for detecting moderate-to-severe OSAS in snoring children when polysomnography is not available.

Adenotonsillectomy: the good, the bad and the unknown.

PURPOSE OF REVIEW: Adenotonsillar hypertrophy is the most common pathogenetic contributor to obstructive sleep apnea syndrome (OSAS) in childhood, and adenotonsillectomy is the standard initial treatment. Here, we summarize the most recent evidence on the efficacy and complications of adenotonsillectomy and explore knowledge gaps in clinical management. RECENT FINDINGS: Favorable adenotonsillectomy effects have been reported in children with very severe OSAS [apnea-hypopnea index (AHI) >20 episodes/h] and extremely severe OSAS (AHI >100 episodes/h), without postoperative mortality, need for endotracheal intubation, prolonged hospital stay or re-admission after hospital discharge. However, the risk of residual OSAS after adenotonsillectomy, which may reach 30-60%, has not been thoroughly established. Behavior, OSAS-related symptoms and quality of life improve postoperatively even in children with AHI 1-5 episodes/h. Natural history of enuresis resolution is accelerated postadenotonsillectomy and office-based systemic blood pressure is decreased in OSAS and hypertension. However, which children younger than 2 years should undergo adenotonsillectomy instead of adenoidectomy only to prevent recurrence of OSAS symptoms and revision surgery remains unclear. Adenotonsillectomy in children with Prader-Willi syndrome is frequently accompanied by postoperative residual OSAS while complications are not uncommon. SUMMARY: In the last 2 years, several studies have provided evidence supporting the efficacy and safety of adenotonsillectomy as treatment intervention for otherwise healthy children with OSAS.

Accuracy of the sleep clinical record for the diagnosis of pediatric moderate-to-severe obstructive sleep apnea syndrome.

PURPOSE: The sleep clinical record (SCR) has been used to diagnose obstructive sleep apnea syndrome (OSAS) in children when access to polysomnography (PSG) is limited. Our aim was to determine the best SCR score that could facilitate diagnosis of moderate-to-severe OSAS in children with snoring. METHODS: Healthy children with history of snoring, who were referred for PSG, were prospectively recruited. The SCR score was calculated. Receiver operating characteristic curves (ROCs) were plotted to determine the area under curve (AUC), and the optimum SCR cutoff value was determined using the Youden index (J). RESULTS: Two hundred and seventy-three children were recruited (mean age 6.3 ± 2.5 years; median obstructive apnea-hypopnea index 1.5 episodes/h; range 0-61.1). The mean SCR score was 6.9 ± 3.6. Forty-six children had moderate-to-severe OSAS. Subjects with moderate-to-severe OSAS had a significantly higher mean SCR score (10.2 ± 2.9) than those with mild OSAS (6.2 ± 3.3; P < 0.001). Based on the plotted ROC, the AUC was 0.811 (95% confidence interval: 0.747-0.876; P < 0.001). Calculation of J, based on its ROC coordinates, indicated that the optimum cutoff SCR score to predict moderate-to-severe OSAS was 8.25, corresponding to a sensitivity of 83% and a specificity of 70%. CONCLUSION: Among children with history of snoring, an SCR score above 8.25 can identify those with moderate-to-severe OSAS.

Comparison of International Growth Standards for Assessing Nutritional Status in Cystic Fibrosis: The GreeCF Study.

OBJECTIVE: The aim of the study was to compare 3 international growth references and explore their differences in assessing growth in Greek school-aged patients with cystic fibrosis (CF). METHODS: Sample included 114 patients (50 boys, age 11.5 ±â€Š3.9 years), provided care at Aghia Sofia Children's Hospital, Greece. Anthropometrics and predicted forced expiratory volume in 1 second (FEV1%) were measured. Body mass index (BMI) and height z scores were computed according to the Centers for Disease Control and Prevention (CDC), World Health Organization (WHO), and International Obesity Task Force (IOTF) references. Agreement between methods was analyzed with kappa statistics, repeated-measures analysis of variance, and Bland-Altman analysis. The relationship between FEV1% and BMI was explored with linear regression. RESULTS: Mean CDC BMI z score was the lowest (0.06 ±â€Š1.08), followed by WHO (0.17 ±â€Š1.14) and IOTF (0.35 ±â€Š1.05) (P ≤ 0.001 for all). The CDC and WHO growth references highly agreed for most weight status strata and stunting; all other comparisons produced lower agreements. Except for CDC and IOTF BMI z scores, all other comparisons produced wide levels of agreement and proportional bias. CDC reference classified more children as attaining low or normal weight, against WHO or IOTF (P ≤ 0.001 for all). Lowest prevalence of ideal and excess weight was recorded by CDC, compared to all other standards (P ≤ 0.001 for all). All BMI z scores provided moderate associations with FEV1%. CONCLUSION: Large variations across weight status classification were present when employing 3 growth standards in school-aged patients . Given than BMI z-scores from all references provided comparable associations with pulmonary function, our data indicate that no studied reference is better than others in assessing growth in CF.

Frequency of moderate-to-severe obstructive sleep apnea syndrome among children with snoring and blood pressure in the hypertensive range.

BACKGROUND: It is recommended that children with hypertension and loud snoring should be referred for polysomnography. We aimed to compare the frequency of moderate-to-severe obstructive sleep apnea syndrome (OSAS) among snorers with and without hypertension. Thus, it was hypothesized that systolic or diastolic hypertension among children with snoring is a risk factor for moderate-to-severe OSAS. METHODS: Data of children with snoring and adenotonsillar hypertrophy and/or obesity referred for polysomnography were retrospectively analyzed. Blood pressure (BP) was measured three times in the morning after polysomnography and percentiles were calculated for the average of the second and third measurement. Association of systolic or diastolic hypertension with moderate-to severe OSAS (apnea-hypopnea index-AHI > 5 episodes/h) adjusted for age and obesity was assessed by logistic regression. RESULTS: Data of 646 children with snoring (median age, 6.5 years; 3-14.9 years; 25.7% obese) were analyzed. Prevalence of systolic or diastolic hypertension was 14.1% and 16.1%, respectively and frequency of AHI > 5 episodes/h was 18.3%. Systolic hypertension was a significant predictor of moderate-to-severe OSAS (OR 1.87; 95% CI 1.10 to 3.17; P = 0.02) after adjustment for age and obesity, but diastolic hypertension was not (OR, 0.96; 0.55 to 1.67; P > 0.05). Odds of AHI > 5 episodes/h prior to considering systolic hypertension was 0.25 and after considering its presence, increased to 0.46 (Bayes' theorem), or for every three children with systolic hypertension and snoring tested, one had AHI > 5 episodes/h. CONCLUSIONS: In the context of systolic hypertension and snoring, referral for polysomnography to rule out moderate-to-severe OSAS is a clinically productive practice.

Nocturnal Oximetry-based Evaluation of Habitually Snoring Children.

RATIONALE: The vast majority of children around the world undergoing adenotonsillectomy for obstructive sleep apnea-hypopnea syndrome (OSA) are not objectively diagnosed by nocturnal polysomnography because of access availability and cost issues. Automated analysis of nocturnal oximetry (nSpO2), which is readily and globally available, could potentially provide a reliable and convenient diagnostic approach for pediatric OSA. METHODS: Deidentified nSpO2 recordings from a total of 4,191 children originating from 13 pediatric sleep laboratories around the world were prospectively evaluated after developing and validating an automated neural network algorithm using an initial set of single-channel nSpO2 recordings from 589 patients referred for suspected OSA. MEASUREMENTS AND MAIN RESULTS: The automatically estimated apnea-hypopnea index (AHI) showed high agreement with AHI from conventional polysomnography (intraclass correlation coefficient, 0.785) when tested in 3,602 additional subjects. Further assessment on the widely used AHI cutoff points of 1, 5, and 10 events/h revealed an incremental diagnostic ability (75.2, 81.7, and 90.2% accuracy; 0.788, 0.854, and 0.913 area under the receiver operating characteristic curve, respectively). CONCLUSIONS: Neural network-based automated analyses of nSpO2 recordings provide accurate identification of OSA severity among habitually snoring children with a high pretest probability of OSA. Thus, nocturnal oximetry may enable a simple and effective diagnostic alternative to nocturnal polysomnography, leading to more timely interventions and potentially improved outcomes.

ERS statement on obstructive sleep disordered breathing in 1- to 23-month-old children.

The present statement was produced by a European Respiratory Society Task Force to summarise the evidence and current practice on the diagnosis and management of obstructive sleep disordered breathing (SDB) in children aged 1-23 months. A systematic literature search was completed and 159 articles were summarised to answer clinically relevant questions. SDB is suspected when symptoms or abnormalities related to upper airway obstruction are identified. Morbidity (pulmonary hypertension, growth delay, behavioural problems) and coexisting conditions (feeding difficulties, recurrent otitis media) may be present. SDB severity is measured objectively, preferably by polysomnography, or alternatively polygraphy or nocturnal oximetry. Children with apparent upper airway obstruction during wakefulness, those with abnormal sleep study in combination with SDB symptoms (e.g. snoring) and/or conditions predisposing to SDB (e.g. mandibular hypoplasia) as well as children with SDB and complex conditions (e.g. Down syndrome, Prader-Willi syndrome) will benefit from treatment. Adenotonsillectomy and continuous positive airway pressure are the most frequently used treatment measures along with interventions targeting specific conditions (e.g. supraglottoplasty for laryngomalacia or nasopharyngeal airway for mandibular hypoplasia). Hence, obstructive SDB in children aged 1-23 months is a multifactorial disorder that requires objective assessment and treatment of all underlying abnormalities that contribute to upper airway obstruction during sleep.

Body composition and lung function in children with cystic fibrosis and meconium ileus.

The aim of this study was to explore whether history of meconium ileus (MI) at birth in children and adolescents with cystic fibrosis (CF) adversely affects body composition and lung function in later life. Data of children and adolescents with CF who underwent spirometry and DXA as part of their routine care were analyzed. Associations between MI (explanatory variable) and areal bone mineral density (total body less head-TBLH aBMD), lean tissue mass (LTM), and fat mass (FM) (outcomes) were assessed using general linear models. Potential relationships of TBLH aBMD, LTM, and FM with FEV1 (additional outcome) were also explored. One hundred and one subjects with CF (mean age 14 ± 3 years) were included, 19 (18.8%) of whom had history of MI. Negative associations were demonstrated between history of MI and FEV1 (P = 0.04), TBLH aBMD (P = 0.03), and FM (P < 0.01) but not between history of MI and LTM (P = 0.07) after adjustment for other variables. Lung function was positively associated with TBLH aBMD (P < 0.01) and LTM (P = 0.02) but not with FM (P = 0.20). CONCLUSION: Among children and adolescents with CF, those with history of MI have lower bone mineral density, FM, and lung function. What is Known: • Among children and adolescents with cystic fibrosis, those with history of meconium ileus in the neonatal period are at risk of having lower body mass index percentile and FEV 1 percent predicted. What is New: • Children and adolescents with cystic fibrosis and history of meconium ileus have decreased bone mineral density and fat mass compared to patients without such history. • Lower lung function in children with MI coexists with suboptimal bone mineral density.

Obstructive sleep disordered breathing in 2- to 18-year-old children: diagnosis and management.

This document summarises the conclusions of a European Respiratory Society Task Force on the diagnosis and management of obstructive sleep disordered breathing (SDB) in childhood and refers to children aged 2-18 years. Prospective cohort studies describing the natural history of SDB or randomised, double-blind, placebo-controlled trials regarding its management are scarce. Selected evidence (362 articles) can be consolidated into seven management steps. SDB is suspected when symptoms or abnormalities related to upper airway obstruction are present (step 1). Central nervous or cardiovascular system morbidity, growth failure or enuresis and predictors of SDB persistence in the long-term are recognised (steps 2 and 3), and SDB severity is determined objectively preferably using polysomnography (step 4). Children with an apnoea-hypopnoea index (AHI) >5 episodes·h(-1), those with an AHI of 1-5 episodes·h(-1) and the presence of morbidity or factors predicting SDB persistence, and children with complex conditions (e.g. Down syndrome and Prader-Willi syndrome) all appear to benefit from treatment (step 5). Treatment interventions are usually implemented in a stepwise fashion addressing all abnormalities that predispose to SDB (step 6) with re-evaluation after each intervention to detect residual disease and to determine the need for additional treatment (step 7).

Home sleep testing for the diagnosis of pediatric obstructive sleep apnea: the times they are a changing...!

PURPOSE OF REVIEW: The current paradigm shift in the diagnosis of sleep apnea in adults has further emphasized the urgent need for the development and validation of less inconvenient and laborious approaches than the in-laboratory nocturnal polysomnography for evaluation of children. RECENT FINDINGS: These efforts have been primarily centered around the following: first, refinements and validation of questionnaires; second, single-channel recordings such as oximetry, airflow, or ECG; third, home-based polysomnography and polygraphy; and fourth, biomarkers. The major overall findings emanating from such studies indicate that none of the approaches provides an ideal substitute to in-laboratory nocturnal polysomnography. Conversely, many of the proposed approaches enable effective screening in a cost-effective manner, and may be particularly suitable when access to pediatric sleep medicine facilities is limited or unavailable. SUMMARY: The overall improvements in technologies and in our understanding of pediatric sleep-disordered breathing should enable population-tailored effective home-based diagnostic approaches that reduce the overall burden to the family, while achieving high levels of diagnostic accuracy. Newer algorithms will have to be developed and validated to allow for effective implementation of such approaches.

Infants with viral bronchiolitis demonstrate two distinct patterns of nocturnal oxyhaemoglobin desaturation.

AIM: This study aimed to demonstrate that viral bronchiolitis is associated with intermittent oxygen saturation of haemoglobin (SpO2 ) drops (≥3%) and low basal SpO2 between episodes of haemoglobin desaturation. METHODS: Infants with bronchiolitis underwent pulse oximetry during the first night following hospital admission and a subgroup of them underwent repeat oximetry before hospital discharge. Oximetry was also performed in infants with partial upper airway obstruction (UAO) and without lung disease and in control participants without UAO or lung disease. RESULTS: We enrolled 53 infants: 21 with bronchiolitis, 11 with UAO and 21 healthy controls. Participants with bronchiolitis had lower basal SpO2 (median 93.7% [10th-90th percentiles: 91.1-96.8]) than the subjects with UAO (96.9% [95.3-98.1]; p < 0.01) or the controls (98.7% [96.9-99.3]; p < 0.01). The bronchiolitis group was not different from the UAO group regarding the desaturation index (23.3 episodes/hour [10.3-46.6] and 15.5 episodes/hour [5.4-36.4], respectively; p = 0.08), but differed significantly from the controls (3.1 episodes/hour [0.3-5.5]; p < 0.01). The basal SpO2 and desaturation index improved in 10 subjects with bronchiolitis who had follow-up oximetry before discharge, but these indices remained abnormal when compared to values in the control group. CONCLUSION: Bronchiolitis was characterised by low nocturnal basal SpO2 and intermittent SpO2 drops.

Parental history of adenotonsillectomy is associated with obstructive sleep apnea severity in children with snoring.

OBJECTIVE: To test the hypothesis that history of adenoidectomy and/or tonsillectomy (AT) in at least 1 of the parents during childhood, is a risk factor for moderate-to-severe obstructive sleep apnea (OSA) (apnea-hypopnea index [AHI] >5 episodes/hour) in the offspring with snoring. STUDY DESIGN: Data of children with snoring who were referred for polysomnography over 12 years by primary care physicians were reviewed. RESULTS: Data of 798 children without history of prior AT, neuromuscular, or genetic disorders or craniofacial abnormalities were analyzed. Of these children, 69.3% had tonsillar hypertrophy, 25.8% were obese, 26.8% had at least 1 parent with history of AT, and 22.1% had AHI >5 episodes/hour. Parental history of AT was significantly associated with moderate-to-severe OSA (logit model including sex, tonsillar hypertrophy, obesity, and physician-diagnosed wheezing; OR [95% CI], 1.70 [1.18-2.46]; P < .01). When significant variables from the logit model (tonsillar hypertrophy, obesity, parental history of AT) were considered independently or in combination, tonsillar hypertrophy combined with history of AT in at least 1 of the parents had high specificity (84.4%) and the highest positive likelihood ratio (1.78) for identifying children with AHI >5 episodes/hour. CONCLUSIONS: Among children with snoring who are referred for polysomnography by primary care physicians, those with tonsillar hypertrophy and parental history of AT have increased risk of moderate-to-severe OSA and represent 1 of the subgroups that should be prioritized for a sleep study in settings with limited resources.

Nocturnal enuresis is associated with moderate-to-severe obstructive sleep apnea in children with snoring.

BACKGROUND: Conflicting data suggest that prevalence of monosymptomatic primary nocturnal enuresis (NE) increases with increasing severity of obstructive sleep apnea (OSA) in childhood and especially in girls. We hypothesized that NE is associated with increased risk of moderate-to-severe OSA (obstructive apnea-hypopnea index (AHI) >5 episodes/hour) among children with snoring. METHODS: Data of children (≥5 y old) with snoring who were referred for polysomnography over 12 y were reviewed. RESULTS: Data of 525 children with mean age (±SD) 7.5 (± 2.2) y and median obstructive AHI (10th-90th percentiles) 1.9 (0.4-7.3) episodes/hour were analyzed. Three hundred and fifty-five children (67.6%) had NE and 87 (16.6%) had moderate-to-severe OSA. There was no interaction between NE and gender regarding the association with moderate-to-severe OSA (P > 0.05). NE was associated significantly with presence of moderate-to-severe OSA after adjustment for tonsillar hypertrophy, obesity, gender, and age (adjusted odds ratio = 1.92 (1.08-3.43); P = 0.03). Presence of NE had high sensitivity (78.2%) and low positive predictive value (19.2%) for detecting moderate-to-severe OSA and low specificity (34.5%) and high negative predictive value (88.8%) for ruling it out. CONCLUSION: Children with snoring and without NE referred for polysomnography are less likely to have moderate-to-severe OSA compared to those with NE.

Atopy does not affect the frequency of adenotonsillar hypertrophy and sleep apnoea in children who snore.

AIM: Viral respiratory infections and atopy have been implicated in the pathogenesis of adenotonsillar hypertrophy and obstructive sleep apnoea (OSA), but the role of atopy is controversial. We aimed to test our hypothesis that atopy, expressed as physician-diagnosed eczema, was associated with adenotonsillar hypertrophy and OSA among children who snored. METHODS: Data on children who snored and were referred for polysomnography were reviewed. The primary outcome measures were adenotonsillar hypertrophy and OSA. RESULTS: We analysed data on 855 children with a mean age (±standard deviation) of 6.3 (±2.5) years and median obstructive apnoea-hypopnea index of 2.1 episodes per hour. Of the 855 subjects, 133 (15.6%) had physician-diagnosed eczema, 591 (69.1%) had adenoidal hypertrophy, 605 (70.8%) had tonsillar hypertrophy, 219 (25.6%) were obese and 470 (55%) had OSA. Eczema was not related to adenoidal or tonsillar hypertrophy after adjustment for gender and age, with odds ratios (OR) of 1.00 (95% confidence interval 0.67-1.49; p = 0.98) and 0.88 (95% confidence interval 0.59-1.32; p = 0.54), respectively. Similarly, eczema did not affect OSA frequency after adjustment for adenoidal and tonsillar hypertrophy, obesity, gender and age, with an adjusted OR of 0.82 (0.56-1.21; p = 0.32). CONCLUSIONS: Atopy was not related to adenotonsillar hypertrophy or OSA in children who snore.

An update on diagnosis and management of obstructive sleep apnoea in the first 2†years of life.

The aim of this review is to summarise evidence that became available after publication of the 2017 European Respiratory Society statement on the diagnosis and management of obstructive sleep apnoea syndrome (OSAS) in 1- to 23-month-old children. The definition of OSAS in the first 2 years of life should probably differ from that applied in children older than 2 years. An obstructive apnoea-hypopnoea index >5 events·h-1 may be normal in neonates, as obstructive and central sleep apnoeas decline in frequency during infancy in otherwise healthy children and those with symptoms of upper airway obstruction. A combination of dynamic and fixed upper airway obstruction is commonly observed in this age group, and drug-induced sleep endoscopy may be useful in selecting the most appropriate surgical intervention. Adenotonsillectomy can improve nocturnal breathing in infants and young toddlers with OSAS, and isolated adenoidectomy can be efficacious particularly in children under 12 months of age. Laryngomalacia is a common cause of OSAS in young children and supraglottoplasty can provide improvement in children with moderate-to-severe upper airway obstruction. Children who are not candidates for surgery or have persistent OSAS post-operatively can be treated with positive airway pressure (PAP). High-flow nasal cannula may be offered to young children with persistent OSAS following surgery, as a bridge until definitive therapy or if they are PAP intolerant. In conclusion, management of OSAS in the first 2 years of life is unique and requires consideration of comorbidities and clinical presentation along with PSG results for treatment decisions, and a multidisciplinary approach to treatment with medical and otolaryngology teams.

Age-dependent changes in the size of adenotonsillar tissue in childhood: implications for sleep-disordered breathing.

OBJECTIVE: To analyze age-associated changes in linear and cross-sectional area (CSA) measurements of adenoid, tonsils, and pharyngeal lumen. STUDY DESIGN: Measurements were completed in head magnetic resonance imaging examinations performed for diagnostic purposes. Linear and nonlinear regression models were applied to describe the effect of age on the size of soft tissues and upper airway. RESULTS: Magnetic resonance imaging data were analyzed in 149 children without snoring (aged 0-15.9 years) and in 33 children with snoring (aged 1.6-15 years). In the children without snoring, adenoid size increased during the first 7-8 years of life and then decreased gradually [% (adenoid oblique width/mental spine-clivus length) = 11.38 + 1.52 (age) - 0.11 (age)(2), R(2) = 0.22, P < .01; adenoid CSA = 90.75 + 41.93 (age) - 2.47 (age)(2); R(2) = 0.50; P < .01]. Nasopharyngeal airway CSA increased slowly up to age 8 years and rapidly thereafter. Similar patterns were noted for the tonsils and oropharyngeal airway. In contrast, in children with snoring, adenoid and tonsils were large irrespective of age, and nasopharyngeal airway size increased slowly with age. CONCLUSIONS: In children without snoring, growing adenotonsillar tissue narrows the upper airway lumen to variable degrees only during the first 8 years of life. In contrast, in children with snoring, appreciable pharyngeal lymphoid tissue enlargement is present during the preschool years and persists beyond the eighth birthday.

Low-grade albuminuria in children with obstructive sleep apnea.

Small urinary protein loss (low-grade albuminuria or microalbuminuria) may reflect altered permeability of the glomerular filtration barrier. In the present study, it was hypothesized that children with obstructive sleep apnea have an increased risk of microalbuminuria compared with control subjects without sleep-disordered breathing. Albumin-to-creatinine ratio was measured in morning spot urine specimens collected from consecutive children with or without snoring who were referred for polysomnography. Three groups were studied: (i) control subjects (no snoring, apnea-hypopnea index < 1 episode h(-1) ; n = 31); (ii) mild obstructive sleep apnea (snoring, apnea-hypopnea index = 1-5 episodes h(-1) ; n = 71); and (iii) moderate-to-severe obstructive sleep apnea (snoring, apnea-hypopnea index > 5 episodes∙h(-1) ; n = 27). Indications for polysomnography in control subjects included nightmares, somnambulism and morning headaches. An albumin-to-creatinine ratio > median value in the control group (1.85 mg of albumin per g of creatinine) was defined as elevated. Logistic regression analysis revealed that children with moderate-to-severe obstructive sleep apnea, but not those with mild obstructive sleep apnea, had increased risk of elevated albumin-to-creatinine ratio relative to controls (reference) after adjustment for age, gender and presence of obesity: odds ratio 3.8 (95% confidence interval 1.1-12.6); P = 0.04 and 1.5 (0.6-3.7); P > 0.05, respectively. Oxygen desaturation of hemoglobin and respiratory arousal indices were significant predictors of albumin-to-creatinine ratio (r = 0.31, P = 0.01; and r = 0.43, P < 0.01, respectively). In conclusion, children with moderate-to-severe obstructive sleep apnea are at significantly higher risk of increased low-grade excretion of albumin in the morning urine as compared with control subjects without obstructive sleep apnea. These findings may reflect altered permeability of the glomerular filtration barrier related to nocturnal hypoxemia and sympathetic activation which are induced by obstructive sleep apnea.

Effect of Hypertonic Saline on Lung Function as Add-on Treatment in People With Cystic Fibrosis Receiving Dornase Alfa: A Cystic Fibrosis Foundation Patient Registry Analysis.

BACKGROUND: Introduction of novel therapies for cystic fibrosis (CF) raises the question of whether traditional treatments can be withdrawn. Nebulized hypertonic saline (HS) potentially could be discontinued in patients receiving dornase alfa (DA). RESEARCH QUESTION: In the era before modulators, did people with CF who are F508del homozygous (CFF508del) and who received DA and HS have better preserved lung function than those treated with DA only? STUDY DESIGN AND METHODS: Retrospective analysis of the Cystic Fibrosis Foundation Patient Registry data (2006-2014). Among 13,406 CFF508del with data for at least 2 consecutive years, 1,241 CFF508del had spirometry results and were treated with DA for 1 to 5 years without DA or HS during the preceding (baseline) year. Absolute FEV1 % predicted change while receiving DA and HS, relative to treatment with DA only, was the main outcome. A marginal structural model was applied to assess the effect of 1 to 5 years of HS treatment while controlling for time-dependent confounding. RESULTS: Of 1,241 CFF508del, 619 patients (median baseline age, 14.6 years; interquartile range, 6-53 years) received DA only and 622 patients (median baseline age, 14.55 years; interquartile range, 6-48.1 years) were treated with DA and HS for 1 to 5 years. After 1 year, patients receiving DA and HS showed FEV1 % predicted that averaged 6.60% lower than that in patients treated with DA only (95% CI, -8.54% to -4.66%; P < .001). Lower lung function in the former relative to the latter persisted throughout follow-up, highlighting confounding by indication. After accounting for baseline age, sex, race, DA use duration, baseline and previous year's FEV1 % predicted, and time-varying clinical characteristics, patients treated with DA and HS for 1 to 5 years were similar to those treated with DA only regarding FEV1 % predicted (year 1: mean FEV1 % predicted change, +0.53% [95% CI, -0.66% to +1.71%; P = .38]; year 5: mean FEV1 % predicted change, -1.82% [95% CI, -4.01% to +0.36%; P = .10]). INTERPRETATION: In the era before modulators, CFF508del showed no significant difference in lung function when nebulized HS was added to DA for 1 to 5 years.

Oxidative stress and inflammatory markers in the exhaled breath condensate of children with OSA.

INTRODUCTION: Obstructive sleep apnea (OSA) in children has been associated with systemic inflammation and oxidative stress. Limited evidence indicates that pediatric OSA is associated with oxidative stress and inflammation in the airway. OBJECTIVE: The objective of this study is to assess the hypothesis that levels of oxidative stress and inflammatory markers in the exhaled breath condensate (EBC) of children with OSA are higher than those of control subjects. METHODS: Participants were children with OSA and control subjects who underwent overnight polysomnography. Morning levels of hydrogen peroxide (H(2)O(2)) and sum of nitrite and nitrate (NO(x)) in EBC of participants were measured. RESULTS: Twelve subjects with moderate-to-severe OSA (mean age ± standard deviation: 6.3 ± 1.7 years; apnea-hypopnea index--AHI, 13.6 ± 10.1 episodes/h), 22 subjects with mild OSA (6.7 ± 2.1 years; AHI, 2.8 ± 1 episodes/h) and 16 control participants (7.7 ± 2.4 years; AHI, 0.6 ± 0.3 episodes/h) were recruited. Children with moderate-to severe OSA had higher log-transformed H(2)O(2) concentrations in EBC compared to subjects with mild OSA, or to control participants: 0.4 ± 1.1 versus -0.9 ± 1.3 (p = 0.015), or versus -1.2 ± 1.2 (p = 0.003), respectively. AHI and % sleep time with oxygen saturation of hemoglobin <95% were significant predictors of log-transformed H(2)O(2) after adjustment by age and body mass index z score (p < 0.05). No significant differences were demonstrated between the three study groups in terms of EBC NO(x) levels. CONCLUSIONS: Children with moderate-to-severe OSA have increased H(2)O(2) levels in morning EBC, an indirect index of altered redox status in the respiratory tract.