Could the Crosstalk Between Myeloid-Derived-Suppressor Cells and Regulatory T Cells Have a Role in Beta-Thalassemia?

Background: Secondary iron overload, alloimmunization, and increased risk of infection are common complications in patients with transfusion-dependent thalassemia (TDT). Regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) play an essential role in preventing excessive immune response. This research aimed to study the interaction between Tregs and MDSCs in TDT patients and to evaluate the association of these cell types with disease severity. Methods: This case-control study included 26 patients with TDT and 23 healthy, age- and sex-matched controls. All patients were investigated for complete blood count (CBC), serum ferritin, and flow cytometric analysis of peripheral blood to detect Tregs, MDSCs, and MDSC subsets. Results: A significant increase was observed in the frequencies of Tregs and MDSCs, particularly monocytic MDSCs (MO-MDSCs), in TDT patients compared with controls. The frequencies of these cells showed a direct association with ferritin level and total leukocyte count and an inverse association with hemoglobin level. Furthermore, a positive correlation was observed between Tregs and each of the total MDSCs and MO-MDSCs. Conclusions: Levels of Tregs and MDSCs increased in TDT and may probably have a role in suppressing the active immune systems of TDT patients.

Invasive Mechanical Ventilation for Acute Viral Bronchiolitis: Retrospective Multicenter Cohort Study.

OBJECTIVES: Bronchiolitis is a leading cause of PICU admission and a major contributor to resource utilization during the winter season. Management in mechanically ventilated patients with bronchiolitis is not standardized. We aimed to assess whether variations exist in management between the centers and then to assess if differences in PICU outcomes are found. DESIGN: Retrospective cohort study. SETTING: Three tertiary PICUs (Centers A, B, and C) in London, United Kingdom. PATIENTS: Patients under 1 year of age (n = 462) who received invasive mechanical ventilation for acute viral bronchiolitis from 2012-2016. INTERVENTIONS: None. DESIGN: Retrospective cohort study. MEASUREMENTS AND MAIN RESULTS: Data collected include all sedative agents administered, 48 hour cumulative fluid balance and location of endotracheal tube (oral or nasal). Primary outcome was duration of invasive mechanical ventilation. A generalized linear model was used to test for differences in duration of invasive mechanical ventilation between centers after adjustment for confounders: corrected gestational age, oxygen saturation index, bacterial coinfection, prematurity, respiratory syncytial virus status, risk of mortality score and comorbidity. Baseline characteristics were similar, other than a higher risk of mortality score at center A and higher admission oxygen saturation index at center C. Center A was associated with utilization of the most benzodiazepine and opiate sedation, the fewest nasal endotracheal tubes, and the highest mean cumulative fluid balance at 48 hours.Center A had an adjusted mean duration of invasive mechanical ventilation that was 44% longer than center C (95% CI, 25-66%; p < 0.001).The majority of confounders had an association with the duration of invasive mechanical ventilation; all were biologically plausible. Corrected gestational age was negatively associated with the duration of invasive mechanical ventilation for preterm infants less than 32 weeks, but not for term or 32-37 week infants (interaction effect). This meant that at a corrected age of 0 months, a less than 32-week infant had a mean duration that was 55% greater than a term infant: this effect had disappeared by 8 months old. CONCLUSIONS: Between-center variations exist in both practices and outcomes. The relationship between these two findings could be further tested through implementation science with "optimal care bundles."

Acute viral bronchiolitis as a cause of pediatric acute respiratory distress syndrome.

The Pediatric Acute Lung Injury Consensus Conference (PALICC) published pediatric-specific guidelines for the definition, management, and research in pediatric acute respiratory distress syndrome (PARDS). Acute viral bronchiolitis (AVB) remains one of the leading causes of admission to PICU. Respiratory syncytial virus (RSV) is the most common cause of AVB. We aimed to evaluate the incidence of PARDS in AVB and identify the risk of RSV as a trigger pathogen for PARDS. This study is a retrospective single-center observational cohort study including children < 2 years of age admitted to the pediatric intensive care unit at St Mary's Hospital, London, and presented with AVB in 3 years (2016-2018). Clinical and demographic data was collected; PALICC criteria were applied to define PARDS. Data was expressed as median (IQR range); non-parametric tests were used. In this study, 144 infants with acute viral bronchiolitis were admitted to PICU in the study period. Thirty-nine infants fulfilled criteria of PARDS with RSV as the most common virus identified. Bacterial infection was identified as a risk factor for development of PARDS in infants with AVB.Conclusion: AVB is an important cause of PARDS in infants. RSV is associated with a higher risk of PARDS in AVB. Bacterial co-infection is a significant risk factor for development of PARDS in AVB. What is Known: • Bronchiolitis is a common cause of respiratory failure in children under 2 years. • ARDS is a common cause of PICU admission. What is New: • Evaluation of bronchiolitis as a cause of PARDS according to the PALLIC criteria. • Evaluation of different viruses' outcome in PARDS especially RSV as a commonest cause of AVB.

Overview of prevention and management of acute bronchiolitis due to respiratory syncytial virus.

INTRODUCTION: Respiratory Syncytial Virus (RSV) is the most common cause of Acute Bronchiolitis (AVB) in infants. AVB causes significant morbidity and mortality worldwide, most deaths occurring in the developing world. AVB causes respiratory distress in infants, leading to respiratory failure in some cases. Disease is more severe in infants with risk factors, such as prematurity, chronic cardiac and lung disease and immunodeficiency. Areas covered: Despite major advances in supportive care in the developed world, which has led to a significant reduction in mortality, treatment remains symptomatic and supportive. No specific antiviral treatment has yet proven to be effective. Prevention of disease with monoclonal antibodies has proven to reduce illness severity in those with risk factors, however, this is prohibitively expensive, particularly for the developing world. Prospects for vaccine development are improving. However, because most disease is in young infants, maternal immunization is necessary. However, due to the transient nature of RSV immunity and the circulation of multiple subtypes, vaccines proven to be effective in adult challenge models have yet to be translated to protection in infants. Expert commentary: Despite advances in preventative treatments, adherence to evidence-based guidelines provides the best prospect for successful reduction in morbidity and mortality.

Reduced Nasal Viral Load and IFN Responses in Infants with Respiratory Syncytial Virus Bronchiolitis and Respiratory Failure.

RATIONALE: Respiratory syncytial virus (RSV) bronchiolitis is a major cause of morbidity and mortality in infancy. Severe disease is believed to result from uncontrolled viral replication, an excessive immune response, or both. OBJECTIVES: To determine RSV load and immune mediator levels in nasal mucosal lining fluid by serial sampling of nasal fluids from cases of moderate and severe bronchiolitis over the course of infection. METHODS: Infants with viral bronchiolitis necessitating admission (n = 55) were recruited from a pediatric center during 2016 and 2017. Of these, 30 were RSV infected (18 "moderate" and 12 mechanically ventilated "severe"). Nasal fluids were sampled frequently over time using nasosorption devices and nasopharyngeal aspiration. Hierarchical clustering of time-weighted averages was performed to investigate cytokine and chemokine levels, and gene expression profiling was conducted. MEASUREMENTS AND MAIN RESULTS: Unexpectedly, cases with severe RSV bronchiolitis had lower nasal viral loads and reduced IFN-γ and C-C chemokine ligand 5/RANTES (regulated upon activation, normal T cell expressed and secreted) levels than those with moderate disease, especially when allowance was made for disease duration (all P < 0.05). Reduced cytokine/chemokine levels in severe disease were also seen in children with other viral infections. Gene expression analysis of nasopharyngeal aspiration samples (n = 43) confirmed reduced type-I IFN gene expression in severe bronchiolitis accompanied by enhanced expression of MUC5AC and IL17A. CONCLUSIONS: Infants with severe RSV bronchiolitis have lower nasal viral load, CXCL10 (C-X-C motif chemokine ligand 10)/IP-10, and type-I IFN levels than moderately ill children, but enhanced MUC5AC (mucin-5AC) and IL17A gene expression in nasal cells.

Characteristics of children admitted to intensive care with acute bronchiolitis.

To assess factors associated with outcome in children admitted to paediatric intensive care (PIC) with bronchiolitis. A retrospective study of children admitted to the PICU at St Mary's Hospital, London with bronchiolitis over a 6-year period (2011-2016). All bronchiolitis admissions < 2 years were included. Data collected particularly noted risk factors for severity, demographics, microbiology and outcome. We compared respiratory syncytial virus (RSV) with non-RSV status. Multivariate analysis was performed. Two hundred seventy-four patients were identified. Median age was 60 days (IQR 28-150 days), 63% were male, 90% were invasively ventilated and 42% were previously healthy. Pre-existing co-morbidities were present in 38%. The most frequently isolated pathogens were RSV (60%) and rhinovirus (26%). Co-infection was present in 45%, most commonly with RSV, rhinovirus and bacterial pathogens. Median length of stay (LOS) was 6 days (IQR 4.75-10). Younger age, prematurity, RSV, co-infection and co-morbidity were identified as significant risk factors for prolonged LOS. Six children died. Five of these had documented co-morbidities. CONCLUSION: RSV causes more severe bronchiolitis than other viruses. Nearly half of children admitted to PICU with RSV were previously healthy. Current guidelines for immunoprophylaxis of RSV bronchiolitis should be re-considered. What is Known: • Bronchiolitis is one of the most common reasons for unplanned PICU admission. The most common virus causing bronchiolitis is RSV • Bronchiolitis severe enough to require admission to PICU is associated with frequent morbidity but has low mortality. What is New: • RSV causes more severe bronchiolitis than other viruses. • Nearly half of all children admitted to PICU with RSV were previously healthy.