ERS statement on protracted bacterial bronchitis in children.

This European Respiratory Society statement provides a comprehensive overview on protracted bacterial bronchitis (PBB) in children. A task force of experts, consisting of clinicians from Europe and Australia who manage children with PBB determined the overall scope of this statement through consensus. Systematic reviews addressing key questions were undertaken, diagrams in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement constructed and findings of relevant studies summarised. The final content of this statement was agreed upon by all members.The current knowledge regarding PBB is presented, including the definition, microbiology data, known pathobiology, bronchoalveolar lavage findings and treatment strategies to manage these children. Evidence for the definition of PBB was sought specifically and presented. In addition, the task force identified several major clinical areas in PBB requiring further research, including collecting more prospective data to better identify the disease burden within the community, determining its natural history, a better understanding of the underlying disease mechanisms and how to optimise its treatment, with a particular requirement for randomised controlled trials to be conducted in primary care.

Prophylactic ranitidine treatment in critically ill children--a population pharmacokinetic study.

AIMS: To characterize the population pharmacokinetics of ranitidine in critically ill children and to determine the influence of various clinical and demographic factors on its disposition. METHODS: Data were collected prospectively from 78 paediatric patients (n = 248 plasma samples) who received oral or intravenous ranitidine for prophylaxis against stress ulcers, gastrointestinal bleeding or the treatment of gastro-oesophageal reflux. Plasma samples were analysed using high-performance liquid chromatography, and the data were subjected to population pharmacokinetic analysis using nonlinear mixed-effects modelling. RESULTS: A one-compartment model best described the plasma concentration profile, with an exponential structure for interindividual errors and a proportional structure for intra-individual error. After backward stepwise elimination, the final model showed a significant decrease in objective function value (-12.618; P < 0.001) compared with the weight-corrected base model. Final parameter estimates for the population were 32.1 l h(-1) for total clearance and 285 l for volume of distribution, both allometrically modelled for a 70 kg adult. Final estimates for absorption rate constant and bioavailability were 1.31 h(-1) and 27.5%, respectively. No significant relationship was found between age and weight-corrected ranitidine pharmacokinetic parameters in the final model, with the covariate for cardiac failure or surgery being shown to reduce clearance significantly by a factor of 0.46. CONCLUSIONS: Currently, ranitidine dose recommendations are based on children's weights. However, our findings suggest that a dosing scheme that takes into consideration both weight and cardiac failure/surgery would be more appropriate in order to avoid administration of higher or more frequent doses than necessary.

Reducing oral steroid intolerability and drug costs for acute wheezers: A retrospective evaluation of a clinical management algorithm in a Pediatric Emergency Department.

PROJECT AIM: To retrospectively evaluate a clinical management algorithm for acute wheezers in a UK Pediatric Emergency Department (PED). OVERVIEW AND RATIONALE: Acute wheezing attacks are a leading cause of PED attendances and inpatient admissions. Prednisolone, a routine treatment, is intolerable in almost one-third of children, requiring repeated dosing, which may prolong length of stay (LOS). To address this problem, we: (1) developed an acute management algorithm (concise, single-sided flow-chart, instructing immediate management); (2) modified the OCS regime from prednisolone (1 mg/kg, 3-day course) to dexamethasone (600 then 300 mcg/kg); (3) and disseminated guidance regionally. Written information-handouts, e-mails, and posters-were followed-up with verbal reinforcement. We implemented the algorithm in 2017 and revised it further in 2018. EVALUATION: In 2019, we retrospectively collected data on 100 acute wheeze attendances (those requiring OCS, aged 2-14), between October and December in 2016, 2017, and 2018 (n = 300), and assessed outcomes. RESULTS: Over a 48-month period, we reduced OCS intolerability by 67.2% and OCS drug costs by 85.8% (saving £41,470.14), while not significantly influencing the other outcomes. CONCLUSIONS: Reduced intolerability and substantial cost savings can be achieved by implementing a structured acute pediatric wheeze algorithm and modifying the OCS to single-dose dexamethasone (300 mcg/kg).

Population pharmacokinetic model of canrenone after intravenous administration of potassium canrenoate to paediatric patients.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Little is known about the pharmacokinetics of potassium canrenoate/canrenone in paediatric patients WHAT THIS STUDY ADDS: A population pharmacokinetic model has been developed to evaluate the pharmacokinetics of canrenone in paediatric patients who received potassium canrenoate as part of their therapy in the intensive care unit. AIMS To characterize the population pharmacokinetics of canrenone following administration of potassium canrenoate to paediatric patients. METHODS: Data were collected prospectively from 23 paediatric patients (2 days to 10 years of age; median weight 4 kg, range 2.16-28.0 kg) who received intravenous potassium canrenoate (K-canrenoate) as part of their intensive care therapy for removal of retained fluids, e.g. in pulmonary oedema due to chronic lung disease and for the management of congestive heart failure. Plasma samples were analyzed by HPLC for determination of canrenone (the major metabolite and pharmacologically active moiety) and the data subjected to pharmacokinetic analysis using NONMEM. RESULTS: A one compartment model best described the data. The only significant covariate was weight (WT). The final population models for canrenone clearance (CL/F) and volume of distribution (V/F) were CL/F (l h(-1) ) = 11.4 × (WT/70.0)(0.75) and V/F (l) = 374.2 × (WT/70) where WT is in kg. The values of CL/F and V/F in a 4 kg child would be 1.33 l h(-1) and 21.4 l, respectively, resulting in an elimination half-life of 11.2 h. CONCLUSIONS: The range of estimated CL/F in the study population was 0.67-7.38 l h(-1) . The data suggest that adjustment of K-canrenoate dosage according to body weight is appropriate in paediatric patients.

Atopy, home environment and the risk of childhood-onset type 1 diabetes: a population-based case-control study.

BACKGROUND: The marked increases in the incidence of type 1 diabetes in recent decades strongly suggest the role of environmental influences. These environmental influences remain largely unknown. OBJECTIVE: To investigate atopy and home environment (such as children living at home, sharing a bedroom and house moves) as potential risk factors for type 1 diabetes. SUBJECTS AND METHOD: In Northern Ireland, 175 children with type 1 diabetes and 4859 control children completed a questionnaire on atopy experience, family composition and home environment. Control children from two age groups (6-8 yr old and 13-14 yr old) were identified from randomly selected primary and secondary schools across Northern Ireland. Cases were identified from a population-based type 1 diabetes register. RESULTS: There was little evidence of a difference in the proportion of participants with a history of atopy in the cases compared with controls. There was a significant reduction in the risk of diabetes in children who lived with more siblings {odds ratio (OR) = 0.58 [95% confidence interval (95% CI) 0.39-0.85] in children who lived with three or more siblings compared with one or none} and in children who moved house more often [OR = 0.59 (95% CI 0.40-0.88) in children who moved house twice or more compared with never]. CONCLUSION: The reduced risk of type 1 diabetes in children living with siblings, sharing a bedroom and moving house more often could reflect the protection afforded by exposure to infections in early life and consequently may provide support for the hygiene hypothesis.

A meta-analysis of the association between childhood type 1 diabetes and atopic disease.

OBJECTIVE: To review the published literature and perform a meta-analysis summarizing the evidence in support of an inverse association between type 1 diabetes and the atopic disorders: asthma, eczema, and allergic rhinitis in children. RESEARCH DESIGN AND METHODS: MEDLINE, Web of Science, and PubMed were searched to identify relevant studies. These were assessed on quality criteria, and odds ratios (ORs) and 95% CIs were calculated for each study from the reported prevalences of atopy in children with diabetes and in control children. Meta-analysis was then used to derive a combined OR and test for heterogeneity in findings between studies. RESULTS: Twenty-five studies were identified. Heterogeneity in the findings from different studies was evident but was considerably reduced when the asthma and rhinitis analyses were restricted to those studies judged to be of adequate design. The meta-analysis revealed an inverse association between asthma and type 1 diabetes, but the finding only attained significance when analysis was restricted to the studies of adequate design (OR 0.82, 95% CI 0.68-0.99). In this subset an association of similar magnitude was observed between eczema and type 1 diabetes (0.82, 0.62-1.10) although this failed to attain statistical significance, and heterogeneity between studies was still present. There was little evidence of an association between rhinitis and type 1 diabetes (0.97, 0.82-1.16) in this subset of studies. CONCLUSIONS: Our analysis suggests that there is a small but significant reduction in the prevalence of asthma in children with type 1 diabetes, but the findings for the other atopic diseases are less conclusive.

Potassium canrenoate treatment in paediatric patients: a population pharmacokinetic study using novel dried blood spot sampling.

OBJECTIVE: To characterize the population pharmacokinetics of canrenone following administration of potassium canrenoate (K-canrenoate) in paediatric patients. METHODS: Data were collected prospectively from 37 paediatric patients (median weight 2.9 kg, age range 2 days-0.85 years) who received intravenous K-canrenoate for management of retained fluids, for example in heart failure and chronic lung disease. Dried blood spot (DBS) samples (n=213) from these were analysed for canrenone content and the data subjected to pharmacokinetic analysis using nonlinear mixed-effects modelling. Another group of patients (n=16) who had 71 matching plasma and DBS samples was analysed separately to compare canrenone pharmacokinetic parameters obtained using the two different matrices. RESULTS: A one-compartment model best described the DBS data. Significant covariates were weight, postmenstrual age (PMA) and gestational age. The final population models for canrenone clearance (CL/F) and volume of distribution (V/F) in DBS were CL/F (l/h) = 12.86 ×  (WT/70.0) × e [0.066 ×  (PMA - 40]) and V/F (l) = 603.30 ×  (WT/70) × (GA/40) where weight is in kilograms. The corresponding values of CL/F and V/F in a patient with a median weight of 2.9 kg are 1.11 l/h and 20.48 l, respectively. Estimated half-life of canrenone based on DBS concentrations was similar to that based on matched plasma concentrations (19.99 and 19.37 h, respectively, in 70 kg patient). CONCLUSION: The range of estimated CL/F in DBS for the study population was 0.12-9.62 l/h; hence, bodyweight-based dosage adjustment of K-canrenoate appears necessary. However, a dosing scheme that takes into consideration both weight and age (PMA/gestational age) of paediatric patients seems more appropriate.