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.

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.

Process and outcome evaluation of a social norms approach intervention on alcohol use among Flemish university students: a quasi-experimental study.

BACKGROUND: Alcohol consumption is prevalent among students, with a common tendency to overestimate peers' alcohol use, contributing to increased consumption. This misperception is evident among Flemish students. This study aimed to develop and assess a Social Norms Approach (SNA) intervention targeting Flemish students to correct misperceptions and subsequently reduce alcohol use. METHODS: The 'Alcoholfacts' social media campaign was implemented using a quasi-experimental design from November 2022 to March 2023. A process evaluation followed Medical Research Council guidance, and intervention effects were evaluated using baseline and post-intervention surveys. Multiple linear regression with a Difference-in-Difference approach was performed for outcome assessment, using an intention-to-treat approach. RESULTS: The process evaluation showed that 36.3% of the intervention group had seen the campaign and that most of the exposed students found the campaign credible (73.3%). However, 54.8% of the exposed students did not find the campaign appealing. Results of the outcome assessment indicated that students of the intervention group at endline estimated students' alcohol consumption significantly lower (bootstrapped p = 0.013; B = -1.93, bootstrapped CI = -3.620 to -0.565) compared to students of the control group. However, no significant intervention effect on student's alcohol consumption was found (bootstrapped p = 0.741; B = -0.32, bootstrapped CI = -2.101 to 1.534). CONCLUSIONS: The study supports the efficacy of an SNA campaign in correcting misperceptions but did not yield an immediate reduction in alcohol consumption. Future research should involve the target group in campaign material development to enhance attractiveness and impact.

Adjuvant Wilms' tumour 1-specific dendritic cell immunotherapy complementing conventional therapy for paediatric patients with high-grade glioma and diffuse intrinsic pontine glioma: protocol of a monocentric phase I/II clinical trial in Belgium.

INTRODUCTION: Diffuse intrinsic pontine glioma (DIPG) and paediatric high-grade glioma (pHGG) are aggressive glial tumours, for which conventional treatment modalities fall short. Dendritic cell (DC)-based immunotherapy is being investigated as a promising and safe adjuvant therapy. The Wilms' tumour protein (WT1) is a potent target for this type of antigen-specific immunotherapy and is overexpressed in DIPG and pHGG. Based on this, we designed a non-randomised phase I/II trial, assessing the feasibility and safety of WT1 mRNA-loaded DC (WT1/DC) immunotherapy in combination with conventional treatment in pHGG and DIPG. METHODS AND ANALYSIS: 10 paediatric patients with newly diagnosed or pretreated HGG or DIPG were treated according to the trial protocol. The trial protocol consists of leukapheresis of mononuclear cells, the manufacturing of autologous WT1/DC vaccines and the combination of WT1/DC-vaccine immunotherapy with conventional antiglioma treatment. In newly diagnosed patients, this comprises chemoradiation (oral temozolomide 90 mg/m2 daily+radiotherapy 54 Gy in 1.8 Gy fractions) followed by three induction WT1/DC vaccines (8-10×106 cells/vaccine) given on a weekly basis and a chemoimmunotherapy booster phase consisting of six 28-day cycles of oral temozolomide (150-200 mg/m2 on days 1-5) and a WT1/DC vaccine on day 21. In pretreated patients, the induction and booster phase are combined with best possible antiglioma treatment at hand. Primary objectives are to assess the feasibility of the production of mRNA-electroporated WT1/DC vaccines in this patient population and to assess the safety and feasibility of combining conventional antiglioma treatment with the proposed immunotherapy. Secondary objectives are to investigate in vivo immunogenicity of WT1/DC vaccination and to assess disease-specific and general quality of life. ETHICS AND DISSEMINATION: The ethics committee of the Antwerp University Hospital and the University of Antwerp granted ethics approval. Results of the clinical trial will be shared through publication in a peer-reviewed journal and presentations at conferences. TRIAL REGISTRATION NUMBER: NCT04911621.

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.

Air pollution and bronchiolitis: a case-control study in Antwerp, Belgium.

This case-control study aimed to investigate the association between short-term (1 to 5 days) and medium-term (31 days) exposure to air pollutants (PM2.5, PM10, BC, NO2) at home/daycare and the risk of 'severe bronchiolitis' (defined as 'requiring hospitalization for bronchiolitis') in children under 2 years in Antwerp, Belgium. We included 118 cases and 79 controls admitted to three general hospitals from October 2020 to June 2021. Exposure levels were predicted using an interpolation model based on fixed measuring stations. We used unconditional logistic regression analysis to assess associations, with adjustment for potential confounders. There were hardly any significant differences in the day-to-day air pollution values between cases and controls. Medium-term (31 days) exposure to PM2.5, PM10, and NO2 was however significantly higher in cases than controls in univariate analysis. Logistic regression revealed an association between severe bronchiolitis and interquartile range (IQR) increases of PM2.5 and PM10 at home and in daycare, as well as IQR increases of NO2 in daycare. Controls were however overrepresented in low pollution periods. Time-adjustment reduced the odds ratios significantly at home for PM2.5 and PM10 (aOR 1.54, 95%CI 0.51-4.65; and 2.69, 95%CI 0.94-7.69 respectively), and in daycare for. PM2.5 (aOR 2.43, 95%CI 0.58-10.1). However, the association between severe bronchiolitis and medium-term air pollution was retained in daycare for IQR increases of PM10 (aOR 5.13, 95%CI 1.24-21.28) and NO2 (aOR 3.88, 95%CI 1.56-9.61) in the time-adjusted model.  Conclusion: This study suggests a possible link between severe bronchiolitis and medium-term (31 days) air pollution exposure (PM10 and NO2), particularly in daycare. Larger studies are warranted to confirm these findings. What is Known: • Bronchiolitis is a leading cause of hospitalization in infants globally and causes a yearly seasonal wave of admissions in paediatric departments worldwide. • Existing studies, mainly from the USA, show heterogeneous outcomes regarding the association between air pollution and bronchiolitis. What is New: • There is a possible link between severe bronchiolitis and medium-term (31 days) air pollution exposure (PM10 and NO2), particularly in daycare. • Larger studies are needed to validate these trends.

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.

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.

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.