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.

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.

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.

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.

Inflammation and Infection in Cystic Fibrosis: Update for the Clinician.

Inflammation and infection play an important role in the pathophysiology of cystic fibrosis, and they are significant causes of morbidity and mortality in CF. The presence of thick mucus in the CF airways predisposes to local hypoxia and promotes infection and inflammation. A vicious cycle of airway obstruction, inflammation, and infection is of critical importance for the progression of the disease, and new data elucidate the different factors that influence it. Recent research has been focused on improving infection and inflammation in addition to correcting the basic gene defect. This review aims to summarize important advances in infection and inflammation as well as the effect of new treatments modulating the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein. New approaches to target infection and inflammation are being studied, including gallium, nitric oxide, and phage therapy for infection, along with retinoids and neutrophil elastase inhibitors for inflammation.

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.

Changes in Ventilatory Support Requirements of Spinal Muscular Atrophy (SMA) Patients Post Gene-Based Therapies.

Spinal muscular atrophy (SMA) is a genetic neuromuscular disease resulting in global muscular weakness and, frequently, in respiratory failure and premature death. Gene-based therapies like Nusinersen are now available for patients with SMA. The aim of this review was to assess in "real world" studies, whether novel treatments would have a positive impact on the mechanical ventilatory support requirements of SMA patients, already initiated on ventilatory support prior to treatment administration. A literature search was performed in Pubmed using multiple combinations of MESH terms and the snowball procedure. A total of 14 publications were discussed in this review. Considering all patients included in the published studies who were on ventilatory support and were treated with Nusinersen, 13/172 (7.5%) had reduced needs for ventilatory support, 1/172 (0.6%) did not need ventilation post-treatment, and 122/172 (70.9%) were maintained on the same ventilator settings. Moreover, 2/41 (4.9%) children who were offered gene therapy had no need for further ventilatory support and 12/41 (29.2%) had reduced requirements. In conclusion, available evidence suggests that among children with SMA, who are on mechanical respiratory support either noninvasively or via tracheostomy at the time of gene-based treatment, only a few will be weaned off the ventilator or have reduced ventilator needs per 24 h. Children will usually require the same level of support as before treatment.

Autoimmune pulmonary alveolar proteinosis in children.

In childhood, a multitude of causes lead to pulmonary alveolar proteinosis (PAP), an excessive surfactant accumulation in the alveolar space, limiting gas exchange. Autoantibodies against granulocyte-macrophage colony-stimulating factor (GM-CSF) causing autoimmune PAP, the principal aetiology in adults, are rare. In this first case series on autoimmune PAP, we detail the presentation and management issues of four children. Whereas three children presented insidiously with progressive dyspnoea, one was acutely sick with suspected pneumonia. During management, one patient was hospitalised with coronavirus disease 2019, noninvasively ventilated, and recovered. All treatment modalities known from adults including whole-lung lavage, augmentation of GM-CSF by inhaled GM-CSF, removal of neutralising antibody by plasmapheresis and interruption of antibody production using rituximab were considered; however, not all options were available at all sites. Inhaled GM-CSF appeared to be a noninvasive and comfortable therapeutic approach. The management with best benefit-to-harm ratio in autoimmune PAP is unknown and specialised physicians must select the least invasive and most effective treatment. To collect this cohort in a rare condition became feasible as patients were submitted to an appropriate registry. To accelerate the authorisation of novel treatments for autoimmune PAP, competent authorities should grant an inclusion of adolescents into trials in adults.

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.

Low- and High-Attenuation Lung Volume in Quantitative Chest CT in Children without Lung Disease.

In contrast to studies of adults with emphysema, application of fixed thresholds to determine low- and high-attenuation areas (air-trapping and parenchymal lung disease) in pediatric quantitative chest CT is problematic. We aimed to assess age effects on: (i) mean lung attenuation (full inspiration); and (ii) low and high attenuation thresholds (LAT and HAT) defined as mean attenuation and 1 SD below and above mean, respectively. Chest CTs from children aged 6-17 years without abnormalities were retrieved, and histograms of attenuation coefficients were analyzed. Eighty examinations were included. Inverse functions described relationships between age and mean lung attenuation, LAT or HAT (p < 0.0001). Predicted value for LAT decreased from -846 HU in 6-year-old to -950 HU in 13- to 17-year-old subjects (cut-off value for assessing emphysema in adults). %TLCCT with low attenuation correlated with age (rs = -0.31; p = 0.005) and was <5% for 9-17-year-old subjects. Inverse associations were demonstrated between: (i) %TLCCT with high attenuation and age (r2 = 0.49; p < 0.0001); (ii) %TLCCT with low attenuation and TLCCT (r2 = 0.47; p < 0.0001); (iii) %TLCCT with high attenuation and TLCCT (r2 = 0.76; p < 0.0001). In conclusion, quantitative analysis of chest CTs from children without lung disease can be used to define age-specific LAT and HAT for evaluation of pediatric lung disease severity.

Effects of the COVID-19 lockdown on sleep duration in children and adolescents: A survey across different continents.

BACKGROUND: A parent survey was conducted to assess the sleep habits of children residing in various countries before and during the SARS-CoV-2 pandemic. It was hypothesized that lockdown would be associated with increased sleep duration. METHODS: Outcomes were changes in bedtime, wake time, and sleep duration in the pandemic compared to before. Logistic regression was applied to evaluate the effects of age and covariates on outcomes. RESULTS: A total of 845 questionnaires completed from May 1 to June 10, 2020 were analyzed (45.8% female; age 3-17 years). During the pandemic, 23.1% of preschoolers, 46.2% of school-age children, and 89.8% of adolescents were going to bed after 10 p.m. on weekdays compared to 7.1%, 9.4%, and 57.1% respectively before the pandemic, with these proportions being higher on weekends. Likewise, 42.5% of preschoolers, 61.3% of school-age children, and 81.2% of adolescents were waking after 8 a.m. on weekdays (11.6%, 4.9%, and 10.3%, before) with these proportions being greater on weekends. Sleep duration did not change in 43% of participants on weekdays and in 46.2% on weekends. The 14-17 years group had fourfold increased odds for longer sleep duration on weekdays (p < .01), and children aged 6-13 years had twofold increased odds for longer sleep duration on weekends relative to the 3-5 years age group (p = .01). CONCLUSIONS: Although lockdown was associated with later bedtime and wake time, this shift did not alter sleep duration in more than 40% of children. Yet, compared to preschoolers, high school-aged children were more likely to sleep more on weekdays and primary school children on weekends.

Phenotypic variance in pediatric obstructive sleep apnea.

It is crucial that clinicians understand what underpins the considerable phenotypic variance in pediatric obstructive sleep apnea syndrome (OSAS), if they are to implement individually tailored phenotype-based approaches to diagnosis and management. This review summarizes the current literature on how disease severity, comorbidities, genetic and environmental/lifestyle factors interact to determine the overall OSAS phenotype. The first part discusses the impact of these factors on OSAS-related morbidity in the context of otherwise healthy children, whilst the second half details children with complex conditions, particularly focusing on the anatomical and functional abnormalities predisposing to upper airway obstruction unique to each condition. One can then understand the need for a multidimensional assessment strategy for pediatric OSAS; one that incorporates the history, physical examination, sleep study results, and biomarkers to enable precise stratification, so vital for effective determination of the timing and the nature of the therapeutic interventions required.

Lung hyperinflation quantitated by chest CT in children with bronchiolitis obliterans syndrome following allogeneic hematopoietic cell transplantation.

OBJECTIVES: Bronchiolitis obliterans syndrome (BOS) diagnosis in children following allogeneic hematopoietic stem cell transplantation (post-HSCT) is based on detection of airway obstruction on spirometry and air-trapping, small airway thickening or bronchiectasis on chest CT. We assessed the relationship between spirometry indices and low-attenuation lung volume at total lung capacity (TLC) on CT. METHODS: Data of children post-HSCT with and without BOS were analyzed. An age-specific, low-attenuation threshold (LAT) was defined as average of (mean-1SD) lung parenchyma attenuation of 5 control subjects without lung disease matched to each age subgroup of post-HSCT patients. % CT lung volume at TLC with attenuation values

Triage for Malnutrition Risk among Pediatric and Adolescent Outpatients with Cystic Fibrosis, Using a Disease-Specific Tool.

Malnutrition prevails in considerable proportions of children with Cystic Fibrosis (CF), and is often associated with adverse outcomes. For this, routine screening for malnutrition is pivotal. In the present cross-sectional study, we aimed to assess the risk for malnutrition in pediatric outpatients with CF. A total of 76 outpatients (44 girls, 11.9 ± 3.9 years old, 39.5% adolescents) were recruited and anthropometric, clinical, dietary and respiratory measures were collected. All outpatients were screened for malnutrition risk with a validated disease-specific instrument. Most children exhibited a low risk for malnutrition (78.9%), whereas none of the participants were characterized as having a high malnutrition risk. In the total sample, malnutrition risk was positively associated with age (r = 0.369, p = 0.001), and inversely related to the body mass index (r = -0.684, p < 0.001), height z-score (r = -0.264, p = 0.021), and forced expiratory volume (FEV1%, r = -0.616, p < 0.001). Those classified as having a low malnutrition risk were younger (p = 0.004), heavier (p < 0.001) and taller (p = 0.009) than their counterparts with a moderate risk. On the other hand, patients in the moderate risk group were more likely pubertal (p = 0.034), with a reduced mid-upper arm fat area (p = 0.011), and worse pulmonary function (p < 0.001). Interestingly, none of the children attaining ideal body weight were classified as having a moderate malnutrition. risk, whereas 37.5% of the patients allocated at the moderate risk group exhibited physiological lung function. In this cohort of outpatients with CF that were predominantly well-nourished and attained physiological lung function, malnutrition risk was identified only in small proportions of the sample. Our data support that patients that are older, pubertal, or have diminished fat mass are at greater risk for malnutrition.

Adherence to Dietary Recommendations, Nutrient Intake Adequacy and Diet Quality among Pediatric Cystic Fibrosis Patients: Results from the GreeCF Study.

Nutrition is an important component of cystic fibrosis (CF) therapy, with a high-fat diet being the cornerstone of treatment. However, adherence to the dietary recommendations for CF appears suboptimal and burdensome for most children and adolescents with CF, leading to malnutrition, inadequate growth, compromised lung function and increased risk for respiratory infections. A cross-sectional approach was deployed to examine the degree of adherence to the nutrition recommendations and diet quality among children with CF. A total of 76 children were recruited from Aghia Sophia's Children Hospital, in Athens, Greece. In their majority, participants attained their ideal body weight, met the recommendations for energy and fat intake, exceeding the goal for saturated fatty acids consumption. Carbohydrate and fiber intake were suboptimal and most participants exhibited low or mediocre adherence to the Mediterranean diet prototype. It appears that despite the optimal adherence to the energy and fat recommendations, there is still room for improvement concerning diet quality and fiber intake.

Nebulizer Care and Inhalation Technique in Children with Cystic Fibrosis.

Nebulizers are used by the great majority of cystic fibrosis patients for delivery of cornerstone treatments. Inhalation technique and adequate disinfection and maintenance are important for optimizing medication delivery. In this study, inhalation technique and nebulizer disinfection/maintenance were assessed in cystic fibrosis patients by direct observation in clinic and completion of a scoring sheet. A total of 108 patients were recruited. The maximum inhalation technique score was attained by 30.5% and adequate inhalation technique score by 74.08% of patients. The inhalation technique score was best with the vibrating mesh nebulizer (p = 0.038), while patient age and number of nebulized medications did not affect ITS significantly (p > 0.05). Nebulizer disinfection/maintenance score was excellent in only 31.48%. Most families kept the nebulizer clean and used appropriate disinfection method, but only half of them replaced the nebulizer and nebulizer cup at the recommended time intervals. Nebulizer disinfection/maintenance score was positively affected by a number of nebulized medications and negatively by years of equipment use (p = 0.009 and p = 0.001, respectively). Even though inhalation technique and disinfection/maintenance practices were found to be adequate in a large proportion of cases, there is still a need for regular review and education. The type of nebulizer was associated with improved inhalation technique, but more data are required before making specific recommendations.