Exploring the link between a novel approach for computer aided lung sound analysis and imaging biomarkers: a cross-sectional study.

BACKGROUND: Computer Aided Lung Sound Analysis (CALSA) aims to overcome limitations associated with standard lung auscultation by removing the subjective component and allowing quantification of sound characteristics. In this proof-of-concept study, a novel automated approach was evaluated in real patient data by comparing lung sound characteristics to structural and functional imaging biomarkers. METHODS: Patients with cystic fibrosis (CF) aged > 5y were recruited in a prospective cross-sectional study. CT scans were analyzed by the CF-CT scoring method and Functional Respiratory Imaging (FRI). A digital stethoscope was used to record lung sounds at six chest locations. Following sound characteristics were determined: expiration-to-inspiration (E/I) signal power ratios within different frequency ranges, number of crackles per respiratory phase and wheeze parameters. Linear mixed-effects models were computed to relate CALSA parameters to imaging biomarkers on a lobar level. RESULTS: 222 recordings from 25 CF patients were included. Significant associations were found between E/I ratios and structural abnormalities, of which the ratio between 200 and 400 Hz appeared to be most clinically relevant due to its relation with bronchiectasis, mucus plugging, bronchial wall thickening and air trapping on CT. The number of crackles was also associated with multiple structural abnormalities as well as regional airway resistance determined by FRI. Wheeze parameters were not considered in the statistical analysis, since wheezing was detected in only one recording. CONCLUSIONS: The present study is the first to investigate associations between auscultatory findings and imaging biomarkers, which are considered the gold standard to evaluate the respiratory system. Despite the exploratory nature of this study, the results showed various meaningful associations that highlight the potential value of automated CALSA as a novel non-invasive outcome measure in future research and clinical practice.

COCCOS study: Developing a transition program for adolescents with chronic conditions using Experience-Based Co-Design. A study protocol.

BACKGROUND: During adolescence, adolescents and young adults (AYAs) are expected to transfer their care from the pediatric environment towards an adult-focused setting. To prevent an abrupt transfer of care, it is recommended to provide AYAs with chronic conditions an adequate transition program. The aim of this paper is to describe the study protocol for the development of a transition program for AYAs with common chronic conditions (COCCOS study), using the Experience-Based Co-Design (EBCD) methodology. METHODS AND ANALYSIS: A qualitative, participatory study is conducted in Flanders (Belgium). Study participants are AYAs (n≥15, 14-25 years old, diagnosed with type 1 diabetes, asthma, or obesity), their families, and healthcare providers (n≥15). The study is composed of eight EBCD stages: clinical site observations, in-depth interviews, trigger film, healthcare providers' feedback event, AYAs' feedback event, joint event, co-design workshops, and a celebration event. Photovoice will take place as a starting point of EBCD. Data will be analyzed using thematic analysis. RESULTS: Data collection has started in January 2023 and is expected to be completed in May 2024. As of August 2023, over 15 clinical site observations have been conducted. A total of 18 AYAs, two parents, six healthcare providers have been enrolled and a total of 20 interviews have been conducted. CONCLUSION: Advancing transitional care is essential for tackling negative health outcomes. Applying the innovative participatory EBCD methodology will reveal key elements of transitional care for AYAs with common chronic conditions in the development of a person-centered transition program. PRACTICE IMPLICATIONS: Study findings will apply key elements of transitional care of AYAs with chronic conditions in the development of an adequate transition program.

Breathing across ages: a systematic review on challenges and components of transitional care for young people with asthma.

Introduction: Asthma is a chronic condition that affects millions of adolescents and young adults (AYA) worldwide. The transition from pediatric to adult care presents unique challenges for this population, affecting their self-management, quality of life and overall health outcomes. This systematic review aims to consolidate the available evidence on challenges encountered by AYA with asthma during the transition period from child to AYA and on the key elements of transitional care for AYAs with asthma including the outcomes achieved, ultimately enhancing outcomes. Methodology: A systematic literature search was performed in PubMed, Embase, Medline, Scopus, and Web of Science from their inception to October 2, 2023, to provide an overview of currently available literature. Primary quantitative and qualitative studies, published in peer-reviewed journals that focused on AYA with a confirmed diagnosis of asthma were considered if they focused on challenges encountered by AYA with asthma during the transition process and/or components of transitional care and their outcomes assessed. Results: A total of 855 studies were initially identified and 6 articles were included in this systematic literature review. Several challenges experienced by AYA with asthma were identified including maintaining medication adherence, the need to take responsibility and being involved, understanding their condition and its severity, feeling left out of the care system, and experiencing a lack of engagement. The identified transitional care components included a standardized form for medical data transmission, a joint consultation and to offer several longer consultations. Conclusion: Several international guidelines for asthma care recommend implementing transition programs in the care for AYA with asthma. Such transition programs should include a comprehensive and individualized approach addressing several challenges faced, to ensure optimal outcomes post-transition. However, to date, data on effective components of transitional care facilitating good outcomes were found to be limited. This systematic review underscores the need for larger studies evaluating the effect of the components of transition programs.

Role of upper airway evaluation in the multidisciplinary management of obstructive sleep apnea in children below two years of age.

BACKGROUND: Diagnosis and treatment of obstructive sleep apnea (OSA) in infants and young children is challenging because of its clinical heterogeneity and lack of age-specific guidelines. AIM: We report the management and treatment outcome of OSA in children below 2 years of age. Treatment decisions were based upon the pattern of upper airway (UA) obstruction, clinical presentation and OSA severity. METHODS: Retrospective, non-randomized observational cohort study at a tertiary center. Children with OSA who underwent an UA evaluation (drug-induced sleep endoscopy or direct laryngoscopy) were included. RESULTS: We studied 100 patients, 57 boys and 43 girls, age 0.72 years (0.0-2.0) and OSA confirmed by polysomnography. Multilevel UA collapse was present in 26%, (adeno)tonsillar hypertrophy in 31% and 21% had laryngomalacia. Laryngomalacia was more common in children below 6 months of age and adenotonsillar hypertrophy was observed mainly in children >1.5 year of age. Surgical and nonsurgical treatment guided by UA findings, improved OSA severity at group level with a significant reduction (p < 0.001) in obstructive apnea/hypopnea index from 10.8/h (2.1-99.1) to 1.7/h (0.0-73.0), an improvement in mean oxygen saturation from 96.9% (88.9-98.4) to 97.4% (92.3-99.0), in minimal oxygen saturation from 85.4% (37.0-96.0) to 88.8% (51.0-95.5) and oxygen desaturation index from 5.1/h (0.2-52.0) to 1.3/h (0.0-47.8). CONCLUSION: Multidisciplinary management of young children with OSA guided by the pattern of UA obstruction and OSA severity, reduces OSA severity. The pattern of UA obstruction changes in the first 2 years of life from a dynamic collapse to structural abnormalities.

Managing Pediatric Asthma Exacerbations: The Role of Timely Systemic Corticosteroid Administration in Emergency Care Settings-A Multicentric Retrospective Study.

BACKGROUND: Asthma is the most prevalent chronic respiratory condition in children. An asthma exacerbation (AE) is a frequent reason for emergency department (ED) visits. An important step in the management of a moderate to severe AE is the administration of systemic corticosteroids (SCS) within 1 h after ED presentation. This study aimed to determine the timing of SCS administration and correlate this with the length of stay and oxygen therapy duration and to explore factors predicting timely administration. METHODS: This study used a retrospective multicenter observational design based on electronic medical records review. Children aged < 18 years, presenting to the ED with a moderate to severe AE were included. RESULTS: 205 patients were included. Only 28 patients received SCS within 60 min after ED arrival. The median time to SCS administration was 169 min (Q1 92-Q3 380). A correlation was found between timing and oxygen treatment duration (r = 0.363, p < 0.001) and length of stay (r = 0.368, p < 0.001). No patient characteristics predicted timely SCS administration. CONCLUSIONS: Three in four children who presented with a moderate to severe AE at the ED did not receive SCS within the first hour. A prolonged timing of SCS administration correlated with a prolonged length of stay and extended need for oxygen support.

Positioning the preventive potential of microbiome treatments for cystic fibrosis in the context of current therapies.

Antibiotics and cystic fibrosis transmembrane conductance regulator (CFTR) modulators play a pivotal role in cystic fibrosis (CF) treatment, but both have limitations. Antibiotics are linked to antibiotic resistance and disruption of the airway microbiome, while CFTR modulators are not widely accessible, and structural lung damage and pathogen overgrowth still occur. Complementary strategies that can beneficially modulate the airway microbiome in a preventive way are highly needed. This could be mediated via oral probiotics, which have shown some improvement of lung function and reduction of airway infections and exacerbations, as a cost-effective approach. However, recent data suggest that specific and locally administered probiotics in the respiratory tract might be a more targeted approach to prevent pathogen outgrowth in the lower airways. This review aims to summarize the current knowledge on the CF airway microbiome and possibilities of microbiome treatments to prevent bacterial and/or viral infections and position them in the context of current CF therapies.

The role of adipose tissue and subsequent liver tissue hypoxia in obesity and early stage metabolic dysfunction associated steatotic liver disease.

BACKGROUND: Obesity is linked to several health complication, including Metabolic Dysfunction Associated Steatotic Liver Disease (MASLD). Adipose tissue hypoxia has been suggested as an important player in the pathophysiological mechanism leading to chronic inflammation in obesity, and in the progression of MASLD. The study aims to investigate the effect of progressive obesity on adipose and liver tissue hypoxia. METHODS: Male 8-week-old C57BL/6J mice were fed a high-fat high-fructose diet (HFHFD) or control diet (CD) for 4, 8, 12, 16 and 20 weeks. Serum ALT, AST and lipid levels were determined, and glucose and insulin tolerance testing was performed. Liver, gonadal and subcutaneous adipose tissue was assessed histologically. In vivo tissue pO2 measurements were performed in gonadal adipose tissue and liver under anesthesia. A PCR array for hypoxia responsive genes was performed in liver and adipose tissue. The main findings in the liver were validated in another diet-induced MASLD mice model, the choline-deficient L-amino acid defined high-fat diet (CDAHFD). RESULTS: HFHFD feeding induced a progressive obesity, dyslipidaemia, insulin resistance and MASLD. In vivo pO2 was decreased in gonadal adipose tissue after 8 weeks of HFHFD compared to CD, and decreased further until 20 weeks. Liver pO2 was only significantly decreased after 16 and 20 weeks of HFHFD. Gene expression and histology confirmed the presence of hypoxia in liver and adipose tissue. Hypoxia could not be confirmed in mice fed a CDAHFD. CONCLUSION: Diet-induced obesity in mice is associated with hypoxia in liver and adipose tissue. Adipose tissue hypoxia develops early in obesity, while liver hypoxia occurs later in the obesity development but still within the early stages of MASLD. Liver hypoxia could not be directly confirmed in a non-obese liver-only MASLD mice model, indicating that obesity-related processes such as adipose tissue hypoxia are important in the pathophysiology of obesity and MASLD.

Pseudomonas aeruginosa in children with cerebral palsy: a prospective study.

Introduction: Children with cerebral palsy (CP) often present with chronic respiratory symptoms. Pseudomonas aeruginosa (PA), is a known pathogen associated with more severe respiratory disease. Preventive actions to eradicate this bacterium and to improve the respiratory condition of children with CP could be very valuable. Therefore, we assessed the prevalence of PA and its association with respiratory disease. Methods: Throat swabs were taken in children with CP, aged 0-18 years. Data from patient records were extracted from the electronic medical records. Follow-up of respiratory symptoms was done by the Liverpool respiratory symptom questionnaire (LRSQ) after 3 months. Results: A throat swab and a completed LRSQ after 3 months were received from 79 children with CP. Twenty-eight patients (35.4%) were found to have at least one positive respiratory culture. Only 4 patients (5.1%) were contaminated with PA. Gram negative bacteria were isolated in 21.5% of the positive throat swabs, S. aureus was found in 13.9%. Most pathogens were found in patients with higher GMFCS score (GMFCS IV and V). Results of the LRSQ showed that 52.1% of these patients reported having 1 cold in the past 3 months. Discussion: The prevalence of PA in our population of children with CP is low, gram-negative bacteria were most commonly found. The respiratory consequences of being colonized with these bacteria were limited. These results may have been affected by the COVID-19 pandemic. Further research is recommended.

Self-control training supplementing inpatient multidisciplinary obesity treatment in children and adolescents.

Research points to self-control as a possible mechanism for facilitating health behaviour and weight loss. The dual pathway model underpins the role of strong bottom-up reactivity towards food and weak top-down executive functions in obesity. Despite flourishing lab studies on attention bias modification or inhibition trainings, relatively few focused on training both processes to improve self-control in children and adolescents in inpatient multidisciplinary obesity treatment (MOT). Being part of the WELCOME project, this study investigated the effectiveness of Brain Fitness training (using the Dot Probe and Go/No-Go) as an adjunct to inpatient MOT in 131 Belgian children and adolescents. Changes in self-control (performance-based inhibitory control and attention bias as well as self-reported eating behaviour) in the experimental group were compared to sham training. Multiple Imputation was used to handle missing data. Inhibitory control and external eating improved over time (pre/post/follow-up), but we found no evidence for a significant interaction between time and condition. Future research should pay more attention to the role of individual variability in baseline self-control, sham training, and ecological validity of self-control training to improve real-life health behaviour and treatment perspectives for children and adolescents with weight problems.

Body composition helps to elucidate the different origins of low serum magnesium in children with obesity compared to children with type 1 diabetes.

Hypomagnesemia in patients with type 1 diabetes (T1D) as well as in obesity has been related to insulin resistance in adults, but not yet in pediatric patients. In this observational single-center study, we aimed to investigate the relation between the magnesium homeostasis, insulin resistance, and body composition in children with T1D and in children with obesity. Children with T1D (n = 148) and children with obesity and proven insulin resistance (n = 121) and healthy controls (n = 36) were included in this study. Serum and urine samples were collected to determine magnesium and creatinine. The total daily dose of insulin (for children with T1D), results from the oral glucose tolerance test (OGTT, for children with obesity), and biometric data were extracted from the electronic patient files. Furthermore, body composition was measured via bioimpedance spectroscopy. Serum magnesium levels were decreased in both children with obesity (0.87 ± 0.07 mmol/l) and children with T1D (0.86 ± 0.07 mmol/l) compared to healthy controls (0.91 ± 0.06; p = 0.005). A lower magnesium level was associated with more severe adiposity in children with obesity, while a worse glycemic control was associated with lower magnesium levels in children with T1D.   Conclusion: Children with T1D and children with obesity have decreased serum magnesium levels. An increased fat mass is associated with lower magnesium levels in childhood obesity, indicating that the adipose tissue is an important factor in magnesium homeostasis. In contrast, glycemic control was the main determining factor for serum magnesium levels in children with T1D. What is Known: • Hypomagnesaemia has been related to insulin resistance in both adults with T1D and adults with obesity. • There is an increasing prevalence of obesity and T1D in childhood, but little is known about the relationship between magnesium and insulin resistance in these children. What is New: • Both children with T1D and children with obesity have decreased serum magnesium levels. • In childhood obesity an increased fat mass is associated with lower magnesium levels, while glycaemic control is the main determining factor for serum magnesium in children with T1D.

Predicting hypercapnia and hypoxia by the ventilator's built-in software in children on long-term non-invasive ventilation: A pilot study.

Introduction: Follow-up of children on long-term non-invasive ventilation (NIV) could be improved by telemonitoring, using the ventilator's built-in software (BIS) parameters as alternative for in-hospital sleep studies to reduce costs, enhance patient independence and contribute to early detection of infections. This pilot study investigated whether analysis of BIS parameters can predict abnormal nocturnal transcutaneous CO2 (TcCO2) and saturation (SpO2) measurements in children on long-term NIV. Methods: Children on long-term NIV in follow-up at the Antwerp University Hospital were retrospectively included. Nocturnal TcCO2 and SpO2 measurements were collected together with BIS parameters at three different time points: the night of the sleep study (BIS1), mean values from 48 h (BIS2) and 72 h (BIS3) before the sleep study. Predictions were calculated for following outcome measures: % recording time TcCO2 > 46.9 mmHg (%RT TcCO2; abnormal if ≥2%), recording time SpO2 < 93% (RT SpO2; abnormal if >1 h), abnormal TcCO2 or SpO2, mean TcCO2, mean SpO2. Results: 69 patients were included. %RT TcCO2 was separately predicted by reached tidal volume2 [OR 0.97 (0.93; 1.00); p = 0.051; AUC = 30%] and reached IPAP1 [OR 1.05 (1.00; 1.10); p = 0.050; AUC = 66%]. Leak1 predicted RT SpO2 [OR 1.21 (1.02; 1.43); p = 0.025; AUC = 84%]. Mean TcCO2 correlated with reached tidal volume2 (R2 0.10, p = 0.033). Discussion: Certain BIS parameters can predict nocturnal hypercapnia and desaturation in children on long-term NIV. Future studies with larger sample sizes are warranted to further investigate the predictive value of the identified BIS parameters.

Urinary epidermal growth factor reflects vascular health in boys with either obesity or type 1 diabetes. A role for renin, or beyond?

An increased blood pressure is a known comorbidity of both type 1 diabetes (T1DM) and obesity in children. Increasing evidence suggests a subtle interplay between epidermal growth factor (EGF) and renin along the juxtaglomerular system, regulating the impact of blood pressure on kidney health and the cardiovascular system. In this study, we investigated the relation between urinary EGF, serum renin and blood pressure in children with obesity or T1DM. 147 non-obese children with T1DM and 126 children with obesity, were included. Blood pressure was measured and mean arterial pressure (MAP) and the pulse pressure (PP) were calculated. Serum renin and urinary EGF levels were determined with a commercial ELISA kit. Partial Spearman rank correlation coefficients and multiple linear regression models were used to study the association between renin, the urinary EGF/urinary creatinine ratio and blood pressure parameters. The urinary EGF/urinary creatinine ratio is correlated with the SBP and the MAP in boys with obesity as well as in boys with T1DM. Multiple regression analysis showed that sex and pulse pressure in male subjects were found to be independently associated with renin. Sex, the presence of diabetes, age, the glomerular filtration rate and both pulse pressure and mean arterial pressure in male subjects were independently associated with urinary EGF/urinary creatinine. In conclusion, in boys with either obesity or diabetes, pulse pressure and mean arterial pressure are negatively associated with the functional integrity of the nephron, which is reflected by a decreased expression of urinary EGF.

The Belgian Diabetes in Pregnancy Follow-Up Study (BEDIP-FUS): A Multi-Centric Prospective Cohort Study on the Long-Term Metabolic Risk across Different Degrees of Gestational Glucose Intolerance: Methodology and Design.

The Belgian Diabetes in Pregnancy follow-up study (BEDIP-FUS) aims to investigate the impact of body mass index (BMI), adiposity and different degrees of glucose intolerance on the metabolic profile and future risk for type 2 diabetes (T2D) in women and offspring five years after delivery in the BEDIP study. The BEDIP study was a prospective cohort study to evaluate different screening strategies for gestational diabetes (GDM) based on the 2013 WHO criteria. The aim of the BEDIP-FUS is to recruit 375 women-offspring pairs, stratified according to three different subgroups based on the antenatal result of the glucose challenge test (GCT) and oral glucose tolerance test (OGTT) during the BEDIP pregnancy. The follow-up visit consists of a 75 g OGTT, anthropometric measurements and questionnaires for the mothers, and a fasting blood sample with anthropometric measurements for the child. Primary outcome for the mother is glucose intolerance defined by the American Diabetes Association criteria and for the offspring the BMI z-score. Recruitment began in January 2021. The BEDIP-FUS study will help to better individualize follow-up in women with different degrees of hyperglycemia in pregnancy and their offspring.

Rare Heterozygous PCSK1 Variants in Human Obesity: The Contribution of the p.Y181H Variant and a Literature Review.

Recently, it was reported that heterozygous PCSK1 variants, causing partial PC1/3 deficiency, result in a significant increased risk for obesity. This effect was almost exclusively generated by the rare p.Y181H (rs145592525, GRCh38.p13 NM_000439.5:c.541T>C) variant, which affects PC1/3 maturation but not enzymatic capacity. As most of the identified individuals with the heterozygous p.Y181H variant were of Belgian origin, we performed a follow-up study in a population of 481 children and adolescents with obesity, and 486 lean individuals. We identified three obese (0.62%) and four lean (0.82%) p.Y181H carriers (p = 0.506) through sanger sequencing and high resulting melting curve analysis, indicating no association with obesity. Haplotype analysis was performed in 13 p.Y181H carriers, 20 non-carriers (10 with obesity and 10 lean), and two p.Y181H families, and showed identical haplotypes for all heterozygous carriers (p < 0.001). Likewise, state-of-the-art literature concerning the role of rare heterozygous PCSK1 variants implies them to be rarely associated with monogenic obesity, as first-degree carrier relatives of patients with PC1/3 deficiency are mostly not reported to be obese. Furthermore, recent meta-analyses have only indicated a robust association for scarce disruptive heterozygous PCSK1 variants with obesity, while clinical significance is less or sometimes lacking for most nonsynonymous variants.

The Predictive Value of Adipokines and Metabolic Risk Factors for Dropouts and Treatment Outcomes in Children With Obesity Treated in a Pediatric Rehabilitation Center.

Background: Inpatient pediatric obesity treatments are highly effective, although dropouts and weight regain threaten long-term results. Preliminary data indicate that leptin, adiponectin, and cardiometabolic comorbidities might predict treatment outcomes. Previous studies have mainly focused on the individual role of adipokines and comorbidities, which is counterintuitive, as these risk factors tend to cluster. This study aimed to predict the dropouts and treatment outcomes by pre-treatment patient characteristics extended with cardiometabolic comorbidities (individually and in total), leptin, and adiponectin. Methods: Children aged 8-18 years were assessed before, immediately after and 6 months after a 12-month inpatient obesity treatment. Anthropometric data were collected at each visit. Pre-treatment lipid profiles; glucose, insulin, leptin, and adiponectin levels; and blood pressure were measured. The treatment outcome was evaluated by the change in body mass index (BMI) standard deviation score (SDS) corrected for age and sex. Results: We recruited 144 children with a mean age of 14.3 ± 2.2 years and a mean BMI of 36.7 ± 6.2 kg/m2 corresponding to 2.7 ± 0.4 BMI SDS. The 57 patients who dropped out during treatment and the 44 patients who dropped out during aftercare had a higher pre-treatment BMI compared to the patients who completed the treatment (mean BMI, 38.3 ± 6.8 kg/m2 vs 35.7 ± 5.5 kg/m2) and those who completed aftercare (mean BMI, 34.6 ± 5.3 kg/m2 vs 37.7 ± 6.3 kg/m2) (all p<0.05). Additionally, aftercare attenders were younger than non-attenders (mean age, 13.4 ± 2.3 years vs 14.9 ± 2.0, p<0.05).Patients lost on average 1.0 ± 0.4 SDS during treatment and regained 0.4 ± 0.3 SDS post-treatment corresponding to regain of 43 ± 27% (calculated as the increase in BMI SDS post-treatment over the BMI SDS lost during treatment). A higher BMI and more comorbidities inversely predicted BMI SDS reduction in linear regression (all p<0.05).The absolute BMI SDS increase after returning home was predicted by pre-treatment leptin and systolic blood pressure, whereas the post-treatment BMI SDS regain was predicted by pre-treatment age, leptin, and adiponectin levels (all p<0.05) in multivariate linear regressions. Conclusion: Patients who need treatment the most are at increased risk for dropouts and weight regain, emphasizing the urgent need for interventions to reduce dropout and support inpatients after discharge. Furthermore, this study is the first to report that pre-treatment leptin and adiponectin levels predict post-treatment BMI SDS regain, requiring further research.

Nocturnal pulse oximetry as a possible screening method for obstructive sleep apnea in infants with laryngomalacia.

OBJECTIVE: Laryngomalacia can be an important cause of obstructive sleep apnea (OSA) in infants. Nocturnal oximetry is a cheap and safe method in comparison to polysomnography for the detection of sleep-disordered breathing. The aim of this study is to evaluate the validity of nocturnal oximetry as a diagnostic tool for OSA in infants with laryngomalacia. METHODS: This retrospective study included infants with laryngomalacia and a clinical suspicion of OSA who underwent a polysomnography at the Antwerp University Hospital. The oximetry was rescored manually, blinded to the polysomnography results, according to four different scoring methods. An obstructive apnea-hypopnea index (oAHI) ≥ 2/h on polysomnography was used to define OSA. RESULTS: This study included 53 patients with laryngomalacia (51% boys, mean age 3.72 ± 0.26 months). A diagnosis of OSA was established in 46 patients (87%) by polysomnography. Among the four different scoring methods, the scoring according to Brouillette et al., yielded the highest diagnostic accuracy with a sensitivity and specificity of 91% and 25% respectively and with a negative and positive predictive value of 25% and 91%, respectively. Correlations and the Bland-Altman plot showed a wide limit of agreement for laboratory polysomnography oAHI and nocturnal oximetry ODI. CONCLUSION: Our data show that overnight pulse oximetry has a high sensitivity and PPV to diagnose OSA in infants with laryngomalacia. However, the low specificity and NPV indicate that PSG is still needed to exclude OSA in cases with normal oximetry.

The short-term effects of ORKAMBI (lumacaftor/ivacaftor) on regional and distal lung structures using functional respiratory imaging.

BACKGROUND: Lumacaftor/ivacaftor (LUM/IVA) has shown modest benefits in previous research, but the exact effects in the cystic fibrosis (CF) lung remain unclear. This study aims to offer novel information on the mode of action of the cystic fibrosis transmembrane conductance regulator (CFTR)-modulating drug by assessing lung structure and function using functional respiratory imaging (FRI). METHODS: CF patients aged ⩾12 years homozygous for F508del were recruited in an open-label study. Before and after 12 weeks of treatment with LUM/IVA, FRI was used to visualize regional information, such as air trapping, lobar volume and airway wall volume. Secondary outcomes included the CF-CT scoring system, spirometry, the Cystic Fibrosis Questionnaire-Revised (CFQ-R) questionnaire, exercise tolerance and nutritional status. RESULTS: Of the 12 patients enrolled in the study, 11 completed all study visits. Concerning the FRI parameters, hyperinflation of the lung decreased, indicated by a reduction in air trapping and lobar volume at expiration. Also, a decrease in airway wall volume and a redistribution of pulmonary blood volume were noted, which might be related to a decrease in mucus impaction. Airway resistance, airway volume, internal airflow distribution and aerosol deposition pattern did not show significant changes. No significant improvements were found in any of the CF-CT scores or in the spirometric parameters. Other secondary outcomes showed similar results compared with previous research. Correlations at baseline were found between FRI and conventional outcomes, including physical functioning, spirometry and CF-CT scores. CONCLUSIONS: LUM/IVA decreased lung hyperinflation in combination with a potential decrease in mucus impaction, which can be related to an improved mucociliary transport. These results indicate that several FRI parameters, reflecting regional and distal lung structures, are more sensitive to changes caused by LUM/IVA than conventional respiratory outcomes.

Lower airway microbiota in children with Down syndrome compared to controls with similar respiratory symptomatology.

BACKGROUND: Children with Down syndrome (DS) often present with chronic or recurrent respiratory symptoms and generally have a more severe and prolonged disease course in case of infection. This can be caused by anatomical and/or immunological predisposition. With this study, we aim to compare microbial composition in the lower airways of patients with DS versus controls, to see if we can explain the difference in disease course. METHODS: All endoscopic procedures under general anesthesia in patients with DS were reviewed retrospectively. We compared the microbiological data from bronchoalveolar lavage fluid (BALF) cultures (when available) to a cohort of children with chronic respiratory symptoms but without any other relevant medical history. RESULTS: Endoscopic data were available for 65 DS patients, BAL cultures for 47 out of 65 patients (72%). The "control" group consisted of 150 children without significant underlying disease, who were matched for age and sex. BAL culture results were available for 135 out of 150 patients (90%). Microorganisms were categorized and compared between both groups, with no statistical differences. Among the microorganisms tested, the most frequently reported were typical bacteria such as Haemophilus influenzae, Moraxella catarrhalis, Streptococci and Staphylococci. CONCLUSIONS: No significant differences in lower airways microbial composition of children with DS and chronic respiratory symptoms were found when compared to controls presenting similar symptomatology. A suggestion for future research may be to investigate possible differences in drug sensitivity.

The impact of obstructive sleep apnea on endothelial function during weight loss in an obese pediatric population.

BACKGROUND: Childhood obesity is an increasing problem with substantial comorbidities such as obstructive sleep apnea (OSA) and increased cardiovascular morbidity. Endothelial dysfunction is an underlying mechanism related to both obesity and OSA. RESEARCH QUESTION: To investigate the effect of weight loss on endothelial function and OSA in obese children and to determine whether a change in endothelial function can be linked to an improvement in OSA. METHODS: Obese children between 8 and 18 years of age were recruited while entering a 12-month inpatient weight loss program. Patients were followed at 3 study visits: baseline, after 10 months of weight loss, and 6 months after ending the program (18 months). Anthropometry and endothelial function (EndoPAT) were determined at all study visits. At baseline, sleep screening with a portable device (ApneaLink) was performed. This was repeated after 10 months if OSA was diagnosed at baseline. RESULTS: At baseline, 130 children were included, of which 87 had OSA (67%). Seventy-two patients attended the follow-up visit at 10 months, and 28 patients attended the follow-up visit at 18 months. The BMI z-score decreased after 10 months (from 2.7 (1.4-3.4) to 1.7 (0.5-2.7); p < 0.001) and remained stable at 18 months. Endothelial function improved significantly after weight loss, evidenced by a shorter time to peak response (TPR) and higher reactive hyperemia index (p = 0.02 and p < 0.001), and remained improved after 18 months (p < 0.001 and p = 0.007). After 10 months of weight loss, 10 patients had residual OSA. These patients had a higher TPR at 10 months (225 (75-285)s) than those without OSA (135 (45-225)s) and patients with a normalized sleep study (105 (45-285)s; p = 0.02). Linear mixed models showed that more severe OSA was associated with a worse TPR at baseline and less improvement after weight loss. CONCLUSION: Weight loss improves endothelial function in an obese pediatric population. However, even after weight loss, endothelial function improved less in the presence of OSA.

Obstructive Sleep Disorders in Down Syndrome's Children with and without Lower Airway Anomalies.

(1) Background: Obstructive sleep apnea (OSA) and lower airway anomalies are both highly prevalent in children with Down syndrome (DS). However, little is known on the interaction between both. We aim to investigate the co-occurrence of OSA (defined as obstructive apnea/hypopnea index (oAHI) ≥ 2/h) and lower airway anomalies in children with DS and explore their impact on OSA severity and treatment outcome. (2) Methods: Retrospective analysis of data from airway endoscopy and polysomnography (PSG) in a cohort of children with DS. (3) Results: Data on both lower airway evaluation and PSG were available for 70 patients with DS. Our study population was relatively young (mean age 3.5 years), not obese and presented with severe OSA (mean oAHI 13.1/h). Airway anomalies were found in 49/70 children (70%), most frequently laryngomalacia, tracheomalacia or a combined airway malformation. In the remaining 21 cases (30%), endoscopy was normal. A comparison between both groups showed a similar distribution of gender, age and BMI z-scores. The prevalence of OSA was not significantly higher in DS patients with airway anomalies (89.6% vs 71.4%, p = 0.078). Additionally, OSA severity or treatment choice (conservative, upper airway surgery or CPAP) were not significantly different. Follow-up data (available for 49/70 patients) showed a significant improvement of OSA in both groups. There is a not significant tendency to more patients with persistent OSA among those with lower airway anomalies (34.3% vs 7.1%, p = 0.075). (4) Conclusions: We found no significant differences in OSA severity, treatment choice or outcome between children with DS with and without lower airway anomalies. Further studies should investigate the role of DISE-directed treatment and compare the outcome of different treatment modalities in larger patient groups.