Risk factors for intensive care admission in children with severe acute asthma in the Netherlands:a prospective multicentre study

Rationale: Severe acute asthma (SAA) can be fatal, but is often preventable. We previously observed in a retrospective cohort study, a three-fold increase in SAA paediatric intensive care (PICU) admissions between 2003 and 2013 in the Netherlands, with a significant increase during those years of numbers of children without treatment of inhaled corticosteroids (ICS). Objectives: To determine whether steroid-naïve children are at higher risk of PICU admission among those hospitalised for SAA. Furthermore, we included the secondary risk factors tobacco smoke exposure, allergic sensitisation, previous admissions and viral infections. Methods: A prospective, nationwide multicentre study of children with SAA (2-18 years) admitted to all Dutch PICUs and four general wards between 2016 and 2018. Potential risk factors for PICU admission were assessed using logistic regression analyses. Measurements and main results: 110 PICU and 111 general ward patients were included. The proportion of steroid-naïve children did not differ significantly between PICU and ward patients. PICU children were significantly older and more exposed to tobacco smoke, with symptoms >1 week prior to admission. Viral susceptibility was not a significant risk factor for PICU admission. Conclusions: Children with SAA admitted to a PICU were comparable to those admitted to a general ward with respect to ICS treatment prior to admission. Preventable risk factors for PICU admission were >7 days of symptoms without adjustment of therapy and exposure to tobacco smoke. Physicians who treat children with asthma must be aware of these risk factors

Population Pharmacokinetics of Intravenous Salbutamol in Children with Refractory Status Asthmaticus

Background: Intravenous salbutamol is used to treat children with refractory status asthmaticus, however insufficient pharmacokinetic data are available to guide initial and subsequent dosing recommendations for its intravenous use. The pharmacologic activity of salbutamol resides predominantly in the (R)-enantiomer, with little or no activity and even concerns of adverse reactions attributed to the (S)-enantiomer. Objective: Our aim was to develop a population pharmacokinetic model to characterize the pharmacokinetic profile for intravenous salbutamol in children with status asthmaticus admitted to the pediatric intensive care unit (PICU), and to use this model to study the effect of different dosing schemes with and without a loading dose. Methods: From 19 children (median age 4.9 years [range 9 months–15.3 years], median weight 18 kg [range 7.8–70 kg]) treated with continuous intravenous salbutamol at the PICU, plasma samples for R- and S-salbutamol concentrations (111 samples), as well as asthma scores, were collected prospectively at the same time points. Possible adverse reactions and patients’ clinical data (age, sex, weight, drug doses, liver and kidney function) were recorded. With these data, a population pharmacokinetic model was developed using NONMEM 7.2. After validation, the model was used for simulations to evaluate the effect of different dosing regimens with or without a loading dose. Results: A two-compartment model with separate clearance for R- and S-salbutamol (16.3 L/h and 8.8 L/h, respectively) best described the data. Weight was found to be a significant covariate for clearance and volume of distribution. No other covariates were identified. Simulations showed that a loading dose can result in higher R-salbutamol concentrations in the early phase after the start of infusion therapy, preventing accumulation of S-salbutamol. Conclusions: The pharmacokinetic model of intravenous R- and S-salbutamol described the data well and showed that a loading dose should be considered in children. This model can be used to evaluate the pharmacokinetic–pharmacodynamic relationship of intravenous salbutamol in children, and, as a next step, the effectiveness and tolerability of intravenous salbutamol in children with severe asthma

Children with asthma on inhaled corticosteroids managed in general practice or by hospital paediatricians: Is there a difference?

Aim: To investigate whether there are differences in asthma characteristics between two populations of children with moderate asthma requiring inhaled corticosteroids (ICS) who are treated in general practice or in hospital practice. Patients and Methods: 45 children from general practice and 62 from hospital practice, diagnosed with asthma and treated with ICS, were analysed in terms of lung function parameters, asthma control (ACQ), and use of medication. Results: Children in general practice did not differ significantly from those in paediatric practice with respect to mean age, lung function tests, and corrected daily dose of ICS. The median ACQ score was higher (representing poorer control) in the general practice group than in the paediatric practice group (0.67 and 0.33 respectively, p < 0.05). Fewer children (22.7%) from the general practice group than from the paediatric group (98.4%) had planned review visits (p< 0.01). Prescriptions for a combination ICS/long-acting β2-agonist (LABA) inhaler were 28.9% in the general practice group and 6.5% in the paediatric group (p<0.05). Conclusion: The hospital-based group was better controlled with less frequent use of combination therapy. Our observations stress the necessity for regular review visits for children with moderately severe asthma especially in general practice

Children with asthma on inhaled corticosteroids managed in general practice or by hospital paediatricians: is there a difference?

AIM: To investigate whether there are differences in asthma characteristics between two populations of children with moderate asthma requiring inhaled corticosteroids (ICS) who are treated in general practice or in hospital practice. PATIENTS AND METHODS: 45 children from general practice and 62 from hospital practice, diagnosed with asthma and treated with ICS, were analysed in terms of lung function parameters, asthma control (ACQ), and use of medication. RESULTS: Children in general practice did not differ significantly from those in paediatric practice with respect to mean age, lung function tests, and corrected daily dose of ICS. The median ACQ score was higher (representing poorer control) in the general practice group than in the paediatric practice group (0.67 and 0.33 respectively, p < 0.05). Fewer children (22.7%) from the general practice group than from the paediatric group (98.4%) had planned review visits (p <0.01). Prescriptions for a combination ICS/long-acting beta2-agonist (LABA) inhaler were 28.9% in the general practice group and 6.5% in the paediatric group (p <0.05). CONCLUSION: The hospital-based group was better controlled with less frequent use of combination therapy. Our observations stress the necessity for regular review visits for children with moderately severe asthma especially in general practic

Nurse versus physician-led care for the management of asthma

Background Asthma is the most common chronic disease in childhood and prevalence is also high in adulthood, thereby placing a considerable burden on healthcare resources. Therefore, effective asthma management is important to reduce morbidity and to optimise utilisation of healthcare facilities. Objectives To review the effectiveness of nurse-led asthma care provided by a specialised asthma nurse, a nurse practitioner, a physician assistant or an otherwise specifically trained nursing professional, working relatively independently from a physician, compared to traditional care provided by a physician. Our scope included all outpatient care for asthma, both in primary care and in hospital settings. Search methods We carried out a comprehensive search of databases including The Cochrane Library, MEDLINE and EMBASE to identify trials up to August 2012. Bibliographies of relevant papers were searched, and handsearching of relevant publications was undertaken to identify additional trials. Selection criteria Randomised controlled trials comparing nurse-led care versus physician-led care in asthma for the same aspect of asthma care. Data collection and analysis We used standard methodological procedures expected by The Cochrane Collaboration. Main results Five studies on 588 adults and children were included concerning nurse-led care versus physician-led care. One study included 154 patients with uncontrolled asthma, while the other four studies including 434 patients with controlled or partly controlled asthma. The studies were of good methodological quality (although it is not possible to blind people giving or receiving the intervention to which group they are in). There was no statistically significant difference in the number of asthma exacerbations and asthma severity after treatment (duration of follow-up from six months to two years). Only one study had healthcare costs as an outcome parameter, no statistical differences were found. Although not a primary outcome, quality of life is a patient-important outcome and in the three trials on 380 subjects that reported on this outcome, there was no statistically significant difference (standardised mean difference (SMD) -0.03; 95% confidence interval (CI) -0.23 to 0.17). Authors' conclusions We found no significant difference between nurse-led care for patients with asthma compared to physician-led care for the outcomes assessed. Based on the relatively small number of studies in this review, nurse-led care may be appropriate in patients with well-controlled asthma. More studies in varied settings and among people with varying levels of asthma control are needed with data on adverse events and health-care cost

Episodic viral wheeze and multiple-trigger wheeze in preschool children are neither distinct nor constant patterns. A prospective multicenter cohort study in secondary care

Objectives To evaluate whether episodic viral wheeze (EVW) and multiple-trigger wheeze (MTW) are clinically distinguishable and stable preschool wheezing phenotypes. Methods Children of age 1 to 4 year with recurrent, pediatrician-confirmed wheeze were recruited from secondary care; 189 were included. Respiratory and viral upper respiratory tract infection (URTI) symptoms were recorded weekly by parents in an electronic diary during 12 months. Every 3 months, diary-based symptoms were classified as EVW or MTW and compared to phenotypes assigned by pediatricians based on clinical history. We collected nasal samples for respiratory virus PCR during URTI, respiratory symptoms and in absence of symptoms. Results Of 660 3-month periods, the diary-based phenotype was EVW in 11%, MTW in 54% and 35% were free from respiratory episodes. Pediatrician-based classification showed 59% EVW and 26% MTW. The Kappa measure of agreement between diary-based and pediatrician-assigned phenotypes was very low (0.12, 95%CI, 0.07-0.17). Phenotypic instability was observed in 32% of cases. PCR was positive in 71% during URTI symptoms, 66% during respiratory symptoms and 38% in the absence of symptoms. Conclusion This study shows that EVW and MTW are variable over time within patients. Pediatrician classification of these phenotypes based on clinical history does not correspond to prospectively recorded symptom patterns. The applicability of these phenotypes as a basis for therapeutic decisions and prognosis should be questioned