Functional respiratory imaging provides novel insights into the long-term respiratory sequelae of bronchopulmonary dysplasia.

RATIONALE: Bronchopulmonary dysplasia (BPD) is a common complication of preterm birth. Lung function and imaging are classically used to assess BPD. Functional respiratory imaging (FRI) combines a structural and functional assessment of the airways and their vasculature. We aimed to assess BPD using FRI and to correlate these findings with the clinical presentation. METHODS: We included 37 adolescents with a history of preterm birth (22 BPD cases and 15 preterm controls). The study protocol included a detailed history, lung function testing and computed tomography (CT) (at total lung capacity (TLC) and functional residual capacity (FRC)) with FRI. CT images were also assessed using the Aukland scoring system. RESULTS: BPD patients had lower forced expiratory volume in 1 s to forced vital capacity ratio (p=0.02) and impaired diffusion capacity (p=0.02). Aukland CT scores were not different between the two groups. FRI analysis showed higher lobar volumes in BPD patients at FRC (p<0.01), but not at TLC. Airway resistance was significantly higher in the BPD group, especially in the distal airways. Additionally, FRI showed more air trapping in BPD patients, in contrast to findings on conventional CT images. CONCLUSION: This study is the first to use FRI in research for BPD. FRI analysis showed higher lobar volumes in BPD patients, indicating air trapping and reduced inspiratory capacity. In contrast to Aukland CT scores, FRI showed more air trapping in the BPD group, suggesting that FRI might be a more sensitive detection method. Importantly, we also showed increased distal airway resistance in BPD patients. By combining structural and functional assessment, FRI may help to better understand the long-term sequelae of BPD.

Respiratory support in the absence of abdominal muscles: A case study of ventilatory management in prune belly syndrome.

Prune belly syndrome (PBS) results in a total lack of abdominal musculature. Abdominal muscles have an important function during inspiration and expiration. This puts the patient at risk for respiratory complications since they have a very limited ability to cough up secretions. Patients in an intensive care unit (ICU) with PBS who receive mechanical ventilation are at even greater risk for respiratory complications. We review the function of the abdominal muscles in breathing and delineate why they are important in the ICU. We include an illustrative case of a long-term ventilated patient with PBS and offer respiratory management options.

A combined intrapleural administration of dornase alfa and tissue plasminogen activator is safe in children with empyema - A pilot study.

OBJECTIVE: There is still no consensus regarding the treatment of empyema in children. Intrapleural combination of tissue plasminogen activator and dornase alfa is a promising treatment for empyema in adults. The aim of this pilot study was to determine whether this combination is safe and successful in pediatric empyema. METHODS: Previous well children diagnosed with empyema as classified by the British Thoracic Society. After chest tube insertion, intrapleurally dornase alfa 2.5 mg for 2 days and tissue plasminogen activator 0.15 mg/kg for 3 days was given after which the chest tube was clamped for 4 h. Primary outcome was safety. RESULTS: Ten consecutive children were included (4 boys, aged 3.2 (1.3-15.0) years old). No serious adverse events were seen. One child developed urticaria but additional intervention or cessation of the trial was not needed. There was no bleeding or mortality and no additional procedures were performed. The median hospital stay after intervention was 7.5 days. CONCLUSIONS: The intrapleural treatment of dornase alfa and tissue plasminogen activator as treatment of empyema was safe in ten children with empyema. If confirmed in further studies, this combination of intrapleural therapy may improve the management of pediatric empyema.

Nebulised hypertonic saline in children with bronchiolitis admitted to the paediatric intensive care unit: A retrospective study.

AIM: Bronchiolitis is one of the most common lower respiratory tract infections in young children, associated with significant morbidity, but limited therapeutic options. Nebulised hypertonic saline (HS) has been a supportive treatment until current guidelines advised against its routine use. Accordingly, the University Hospital of Antwerp recently changed their policies to stop using it, allowing us to evaluate retrospectively if HS influences the duration of respiratory support. Because, to our knowledge, the effect of HS on children with severe bronchiolitis admitted to a paediatric intensive care unit (PICU) has not been studied yet, we aimed to investigate the effect in this specific patient group. METHODS: Retrospective study including children up to the age of 2, admitted to the PICU with bronchiolitis from October 2013 until March 2016. The primary end point is the duration of respiratory support, including high flow nasal cannula, continuous positive airway pressure and invasive ventilation. RESULTS: A total of 104 children admitted to the PICU with bronchiolitis were included, with an average age of 3.4 months. In respiratory syncytial virus (RSV) positive patients, the use of nebulised HS was correlated with a decrease in the duration of respiratory support and the length of stay by factors 0.72 (P = 0.01) and 0.81 (P = 0.04), respectively. CONCLUSIONS: A significant correlation was found between the use of HS and a decreased duration of respiratory support and admission in the PICU in patients with RSV bronchiolitis. This finding may warrant new prospective studies investigating HS specifically in children with severe bronchiolitis.

The role of Th17 and Treg responses in the pathogenesis of RSV infection.

The respiratory syncytial virus (RSV) represents the leading cause of viral bronchiolitis and pneumonia in children worldwide and is associated with high morbidity, hospitalization rate, and significant mortality rates. The immune response elicited by RSV is one of the main factors contributing to the pathogenesis of the disease. Two subsets of the cellular immune response, the T helper 17 cell (Th17) and the regulatory T-cell (Treg), and more particularly the balance between these two subsets, might play a significant role in the pathogenesis of the RSV infection. The developmental pathways of Th17 and Treg cells are closely and reciprocally interconnected and plasticity has been demonstrated from Treg toward Th17. During an RSV infection, the functions of both subsets are opposed to one another regarding viral clearance and clinical severity. Th17 and Treg cells offer a promising new view on the pathogenesis of an RSV infection and deserve further exploration.

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.

Characteristics of Adolescents Admitted with Acute Alcohol Intoxication: A Retrospective Multicentre Study in Antwerp, Belgium, in the Period 2015-2021.

Binge drinking among adolescents is common in Belgium, posing a risk of serious health consequences. Until today, only estimations of the prevalence of acute alcohol intoxication (AAI) in adolescents have been made. Research into potential risk factors has not yet been conducted in Belgium. Therefore, this study aims to gain more insight into the prevalence, medical characteristics and potential risk factors of AAI among adolescents. A retrospective multicentre chart study was performed on adolescents aged 10-17 years with AAI in Antwerp, Belgium (2015-2021). Patient's demographics, medical characteristics and information regarding the context of the AAI were collected from medical charts. Over the study period, a total of 1016 patients were admitted with AAI in Antwerp, having a median age of 16.6 years old, a median blood alcohol concentration of 1.95 g/L and combined drug use in 10% of cases. These findings did not significantly change over the study period. Multiple linear regression analysis indicated that after correcting for covariates, higher age, no combined drug use and decreased consciousness at admission were associated with more severe AAI cases (higher blood alcohol concentration). This study shows that AAI is prevalent among Belgian adolescents, and better targeted preventive measures and policies are needed. Our findings could be taken into account when developing preventive measures. However, data addressing the demographics and context of AAI were mostly missing. Therefore, prospective research is required to further investigate potential risk factors associated with AAI.

Risk Factors Associated with Severe RSV Infection in Infants: What Is the Role of Viral Co-Infections?

The respiratory syncytial virus (RSV) represents the leading cause of viral lower respiratory tract infections (LRTI) in children worldwide and is associated with significant morbidity and mortality rates. The clinical picture of an RSV infection differs substantially between patients, and the role of viral co-infections is poorly investigated. During two consecutive winter seasons from October 2018 until February 2020, we prospectively included children up to 2 years old presenting with an acute LRTI, both ambulatory and hospitalized. We collected clinical data and tested nasopharyngeal secretions for a panel of 16 different respiratory viruses with multiplex RT-qPCR. Disease severity was assessed with traditional clinical parameters and scoring systems. A total of 120 patients were included, of which 91.7% were RSV positive; 42.5% of RSV-positive patients had a co-infection with at least one other respiratory virus. We found that patients suffering from a single RSV infection had higher pediatric intensive care unit (PICU) admission rates (OR = 5.9, 95% CI = 1.53 to 22.74), longer duration of hospitalization (IRR = 1.25, 95% CI = 1.03 to 1.52), and a higher Bronchiolitis Risk of Admission Score (BRAS) (IRR = 1.31, 95% CI = 1.02 to 1.70) compared to patients with RSV co-infections. No significant difference was found in saturation on admission, O2 need, or ReSViNET-score. In our cohort, patients with a single RSV infection had increased disease severity compared to patients with RSV co-infections. This suggests that the presence of viral co-infections might influence the course of RSV bronchiolitis, but heterogeneity and small sample size in our study prevents us from drawing strong conclusions. IMPORTANCE RSV is worldwide the leading cause of serious airway infections. Up to 90% of children will be infected by the age of 2. RSV symptoms are mostly mild and typically mimic a common cold in older children and adolescents, but younger children can develop severe lower respiratory tract disease, and currently it is unclear why certain children develop severe disease while others do not. In this study, we found that children with a single RSV infection had a higher disease severity compared to patients with viral co-infections, suggesting that the presence of a viral co-infection could influence the course of an RSV bronchiolitis. As preventive and therapeutic options for RSV-associated disease are currently limited, this finding could potentially guide physicians to decide which patients might benefit from current or future treatment options early in the course of disease, and therefore, warrants further investigation.

Visceral leishmaniasis in a child infected with the human immunodeficiency virus in a non-endemic region.

We reported the case of a boy who fled from Chechnya to Belgium. He was diagnosed with a human immune deficiency virus (HIV)/Visceral leishmaniasis (VL) coinfection. In both countries, the prevalence of HIV-infected children is low and VL is not endemic. Migration of people results in confrontation with diseases that are not frequent in the countries of destination and becomes a challenge for pediatricians.

Isolation and Characterization of Clinical RSV Isolates in Belgium during the Winters of 2016-2018.

Respiratory Syncytial Virus (RSV) is a very important viral pathogen in children, immunocompromised and cardiopulmonary diseased patients and the elderly. Most of the published research with RSV was performed on RSV Long and RSV A2, isolated in 1956 and 1961, yet recent RSV isolates differ from these prototype strains. Additionally, these viruses have been serially passaged in cell culture, which may result in adaptations that affect virus-host interactions. We have isolated RSV from mucosal secretions of 12 patients in the winters 2016-2017 and 2017-2018, of which eight RSV-A subtypes and four RSV-B subtypes. Passage 3 of the isolates was assessed for viral replication kinetics and infectious virus production in HEp-2, A549 and BEAS-2B cells, thermal stability at 37 °C, 32 °C and 4 °C, syncytia formation, neutralization by palivizumab and mucin mRNA expression in infected A549 cells. We observed that viruses isolated in one RSV season show differences on the tested assays. Furthermore, comparison with RSV A2 and RSV B1 reveals for some RSV isolates differences in viral replication kinetics, thermal stability and fusion capacity. Major differences are, however, not observed and differences between the recent isolates and reference strains is, overall, similar to the observed variation in between the recent isolates. One clinical isolate (BE/ANT-A11/17) replicated very efficiently in all cell lines, and remarkably, even better than RSV A2 in the HEp-2 cell line.

Fatal diphtheria myocarditis in a 3-year-old girl-related to late availability and administration of antitoxin?

Sporadic cases of diphtheria are very rare throughout Europe. A 3-year-old incompletely vaccinated girl was admitted with pharyngotonsillitis caused by diphtheria. On day 9 of her illness, renal and cardiac failure with a third-degree AV-block occurred. Unfortunately, she died within 36 h of admission to intensive care, despite pacemaker placement, the administration of antibiotics and diphtheria antitoxin. The delayed antitoxin administration 7 days after admission to hospital was related to a lack of availability and knowledge of its availability in Europe and this is likely to have contributed to the unfavourable outcome.

High levels of CXCL8 in tracheal aspirate samples taken at birth are associated with adverse respiratory outcome only in preterm infants younger than 28 weeks gestation.

We investigated the relation between perinatal endotracheal colonization, the associated cytokine response and respiratory outcome in ventilated preterm neonates. Between September 1999 and March 2002, a cohort of 141 neonates with a gestational age <31 weeks requiring ventilation directly after birth, were followed prospectively. All were admitted to the Neonatal Intensive Care Unit, University Hospital of Antwerp, Belgium. A tracheal aspirate (TA) sample was collected soon after birth and was processed for microbiological examination, leukocyte count, and cytokine analysis (interleukins [IL] IL-1beta, IL-6, CXCL8 (formerly called IL-8), IL-10, IL-12p70 and tumor necrosis factor alpha [TNF-alpha]). Together with the prospectively registered patient's comorbidities and severity of disease, these inflammatory parameters were analyzed in a multivariate Cox proportional hazards model with time of extubation and duration of oxygen therapy as main outcome measures. Of the 141 patients included, 31 (22%) died before discharge from the unit and 37 (26%) had a positive TA culture. Independent predictors of duration of mechanical ventilation were: gestational age <28 weeks, degree of respiratory distress syndrome (RDS) at birth, significant patent ductus arteriosus (PDA), the SNAP-score, and high levels of CXCL8 (>4,153 pg/ml) in TA only in neonates with a gestational age <28 weeks. Variables associated with extended duration of oxygen therapy were gestational age <28 weeks, birth weight <1,000 g, degree of RDS at birth, and duration of mechanical ventilation.

Red cell distribution width (RDW) as a biomarker for respiratory failure in a pediatric ICU.

BACKGROUND: The red cell distribution width (RDW) is a widely available, inexpensive, and highly reproducible test that reflects the range of the red cell sizes. Any process that releases reticulocytes in the circulation will result in an increase in RDW. Elevated RDW values are linked to worsened pulmonary function in the adult population. We performed a retrospective cohort study to describe the association between RDW and respiratory failure in critically ill children in a in a pediatric intensive care unit (PICU) in a tertiary university hospital. SUBJECTS: All patients admitted between January 2009 and June 2015 were considered eligible for inclusion. METHODS: Retrospective cohort study. RESULTS: In total, 960 patients were included in the cohort analysis. Of those patients, 149 (15.5%) had elevated RDW values. RDW on admission was associated with lower 28 day ventilator-free days. The highest quintile of RDW was associated with the need for mechanical ventilation, even when correcting for anaemia, age and Pediatric Risk of Mortality (PRISM) scores. In the subgroup of ventilated patients, RDW was associated with nadir PaO2/FiO2(P/F) ratios. CONCLUSION: The RDW value on admission of our PICU patients is associated with a greater need for invasive mechanical ventilation, lower 28 day ventilator-free days and lower nadir P/F ratios in the patients with highest RDW values on admission. RDW may be a valuable, cheap and universally available, prognostic parameter for respiratory dysfunction in the PICU.

Sepsis Caused by Achromobacter Xylosoxidans in a Child with Cystic Fibrosis and Severe Lung Disease.

BACKGROUND Achromobacter xylosoxidans is an aerobic, motile, Gram-negative, opportunistic pathogen that can be responsible for various severe nosocomial and community-acquired infections. It has been found in immunocompromised patients and patients with several other underlying conditions, but the clinical role of this microorganism in cystic fibrosis is unclear. CASE REPORT We describe a case of septic shock caused by A. xylosoxidans in a 10-year-old child with cystic fibrosis and severe lung disease. CONCLUSIONS As the prevalence of A. xylosoxidans in cystic fibrosis patients is rising and patient-to-patient transmission is highly probable, further studies are warranted to determine its role and to document the appropriate treatment strategy for eradication and long-term treatment of this organism.

Increased levels of tumor necrosis factor-alpha and decreased levels of interleukin-12 p 70 in tracheal aspirates, within 2 hrs after birth, are associated with mortality among ventilated preterm infants.

OBJECTIVE: To determine the association of antibacterial interleukin (IL)-12 p 70 levels as well as the pathogen-induced proinflammatory cytokine response in tracheal aspirate (TA) to respiratory failure and mortality among ventilated preterm infants. DESIGN: A prospective observational clinical cohort study with measurements of cytokine levels and microbial cultures of TA from ventilated preterm neonates. Interleukin (IL)-1 beta, IL-8, IL-6, IL-10, IL-12 p 70, and tumor necrosis factor (TNF)-alpha were measured in TA within 2 hrs of birth, and comorbidity characteristics were recorded prospectively. The association between cytokine levels in TA and neonatal mortality was determined, with correction for comorbidity factors by means of multivariate stepwise logistic regression. SETTING: A single tertiary neonatal intensive care unit at the University Hospital of Antwerp, Belgium. PATIENTS: One hundred forty-one neonates born before a gestational age of 31 wks and who required ventilation were enrolled in the study; 31 (22%) died and 37 (26%) had airway colonization. MEASUREMENTS AND MAIN RESULTS: The airway colonization rate was significantly greater among deceased neonates (45% vs. 21%; chi-square, 7.4; p=.007). Neonates who died had a significantly lower IL-12 p 70 cytokine level (6 pg/mL vs. 11 pg/mL; p<.05) in their TA. Neonates with a low IL-12 p 70 cytokine level had more pronounced respiratory failure (significantly higher oxygenation index, higher degree of radiologic respiratory distress syndrome, higher critical index for babies score, and more surfactant use). Multivariate analysis revealed that, after correction for severity of disease by critical index for babies score, the degree of intraventricular hemorrhage (odds ratio, 5.0 [95% confidence interval, 2.6-9.7]), low IL-12 p 70 levels (odds ratio, 4.9 [95% confidence interval, 2.1-11.7]), and high TNF-alpha levels in TA (odds ratio, 3.5 [95% confidence interval, 1.6-7.5]) were significantly associated with neonatal mortality. CONCLUSIONS: Pathogen-induced excessive production of the proinflammatory cytokine TNF-alpha and lack of antibacterial IL-12 p 70 response in the TA are associated with increased neonatal mortality among ventilated preterm infants.

Vascular Complications of Varicella: Description of 4 Cases and a Review of Literature.

Stroke and deep venous thrombosis are rare complications of varicella zoster infection. We report 3 cases of children with a stroke and 1 case of a boy with a deep venous thrombosis after recent chicken pox.

A spinal arteriovenous fistula in a 3-year old boy.

We present a case of a 3-year-old boy with neurodegeneration. Family history reveals Rendu-Osler-Weber disease. Magnetic resonance imaging (MRI) of the spinal cord and spinal angiography showed a spinal arteriovenous fistula with venous aneurysm, causing compression of the lumbar spinal cord. Embolisation of the fistula was executed, resulting in clinical improvement. A week after discharge he was readmitted with neurologic regression. A second MRI scan revealed an intraspinal epidural haematoma and increase in size of the aneurysm with several new arterial feeders leading to it. Coiling of the aneurysm and fistulas was performed. Postoperative, the spinal oedema increased despite corticoids, causing more extensive paraplegia of the lower limbs and a deterioration of his mental state. A laminectomy was performed and the aneurysm was surgically removed. Subsequently, the boy recovered gradually. A new MRI scan after two months showed less oedema and a split, partly affected spinal chord. This case shows the importance of excluding possible arteriovenous malformations in a child presenting with progressive neurodegeneration. In particular when there is a family history for Rendu-Osler-Weber disease, scans should be performed instantly to rule out this possibility. The case also highlights the possibility of good recovery of paraplegia in paediatric Rendu-Osler-Weber patients.