Marielle W. Pijnenburg

Personalized medicine in children with asthma

Personalized medicine for children with asthma aims to provide a tailored management of asthma, which leads to faster and better asthma control, has less adverse events and may be cost saving. Several patient characteristics, lung function parameters and biomarkers have been shown useful in predicting treatment response or predicting successful reduction of asthma medication. As treatment response to the main asthma therapies is partly genetically determined, pharmacogenetics may open the way for personalized medicine in children with asthma. However, the number of genes identified for the various asthma drug response phenotypes remains small and randomized controlled trials are lacking. Biomarkers in exhaled breath or breath condensate remain promising but did not find their way from bench to bedside yet, except for the fraction of exhaled nitric oxide. E-health will most likely find its way to clinical practice and most interventions are at least non-inferior to usual care. More studies are needed on which interventions will benefit most individual children.

The clinical utility of reticular basement membrane thickness measurements in asthmatic children

Abstract Objective: Reticular basement membrane (RBM) thickness is one of the pathological features of asthma and can be measured in endobronchial biopsies. We assessed the feasibility of endobronchial biopsies in a routine clinical setting and investigated the clinical value of RBM thickness measurements for asthma diagnosis in children. Methods: We included all children who underwent bronchoscopy with endobronchial mucosal biopsies for clinical reasons and divided them into three subgroups: (1) no asthma, (2) mild–moderate asthma, and (3) problematic severe asthma. Results: In 152/214 (71%) patients, mean age 9.5 years (SD 4.6; range 0.1–18.7) adequate biopsies were retrieved in which RBM thickness could be measured. Mean (SD) RBM thickness differed significantly among children without asthma, with mild–moderate asthma, and with problematic severe asthma (p = 0.04), 4.68 (1.24) µm, 4.56 (0.89) µm, and 5.21 (1.10) µm respectively. This difference disappeared after adding exhaled nitric oxide to the multivariate model. Conclusions: This study confirms the difference in RBM thickness between children with and without asthma and between asthma severities in a routine clinical care setting. However, quantifying the RBM thickness appeared to have no added clinical diagnostic value for asthma in children.

Identification of asthma phenotypes in children

Educational aims Aid understanding of the complexity of linking clinical disease presentation of asthma with underlying mechanisms Outline possible advantages of improving this understanding Summary The lung is a highly complex organ that can only be understood by integrating the many aspects of its structure. There is increasing interest in defining childhood asthma phenotypes, following decades of research into understanding mechanisms of asthma development and their genetic background without significant breakthroughs. Despite the medical profession’s best efforts to define asthma, identify risk factors and natural development of asthma in birth cohorts, and find characteristics that distinguish one type of asthma from another, we still do not know the relevant characteristics of the various subgroups of childhood asthma. This review will briefly describe the importance of identifying childhood asthma phenotypes, the observable characteristics of the disease, and the previous and current approaches used to find them.

A virtual asthma clinic for children: Fewer routine outpatient visits, same asthma control

eHealth is an appealing medium to improve healthcare and its value (in addition to standard care) has been assessed in previous studies. We aimed to assess whether an eHealth intervention could improve asthma control while reducing 50% of routine outpatient visits. In a multicentre, randomised controlled trial with a 16-month follow-up, asthmatic children (6–16 years) treated in eight Dutch hospitals were randomised to usual care (4-monthly outpatient visits) and online care using a virtual asthma clinic (VAC) (8-monthly outpatient visits with monthly web-based monitoring). Outcome measures were the number of symptom-free days in the last 4 weeks of the study, asthma control, forced expiratory volume in 1 s, exhaled nitric oxide fraction, asthma exacerbations, unscheduled outpatient visits, hospital admissions, daily dose of inhaled corticosteroids and courses of systemic corticosteroids. We included 210 children. After follow-up, symptom-free days differed statistically between the usual care and VAC groups (difference of 1.23 days, 95% CI 0.42–2.04; p=0.003) in favour of the VAC. In terms of asthma control, the Childhood Asthma Control Test improved more in the VAC group (difference of 1.17 points, 95% CI 0.09–2.25; p=0.03). No differences were found for other outcome measures. Routine outpatient visits can partly be replaced by monitoring asthmatic children via eHealth. A virtual asthma clinic as an individualised online monitoring strategy can partly replace routine outpatient visits http://ow.ly/f9Vd30dqWvJ

Long-term functional airway assessment after open airway surgery for laryngotracheal stenosis

The purpose of this study was to evaluate our patient‐reported and objective long‐term outcomes of patients treated for laryngotracheal stenosis.

NO kidding: exhaled nitric oxide fraction in preschool children

Wheeze is one of the most prevalent symptoms in preschool children with huge impacts on children and their families, on healthcare utilisation and hence costs [1]. While most children will become asymptomatic by 5–6 years of age, some will develop asthma or, even more importantly, severe problematic asthma and/or will experience an accelerated decline in lung function. Several studies have shown that lung function in asthmatic children at 6 years of age is already reduced compared with nonasthmatic children, in particular among children with allergic asthma [2]. This impaired lung function seems to be present soon after birth in children who are at risk of asthma [3]. Hence, the preschool years and the prenatal period seem of the utmost importance if we are looking for a window of opportunity to prevent asthma or to identify those children who are at risk for severe disease. FeNO may be helpful in predicting future asthma in preschool wheezing children, but more longitudinal data are needed http://ow.ly/DXKxR

Will Symptom-Based Therapy Be Effective for Treating Asthma in Children?

Traditionally, symptoms are important patient-oriented outcomes in asthma treatment, and assessment of symptoms is an essential component of assessing asthma control. However, variable airways obstruction, airways hyperresponsiveness and chronic inflammation are key components of the asthma syndrome, and correlations among these hallmarks and symptoms are weak or even absent. Therefore, it might be questioned if symptom-based therapy is effective for treating asthma in (all) children. To date, there is no firm indication that monitoring asthma based on repetitive lung function measurement or markers of airway inflammation is superior to monitoring based on symptoms only. In the majority of patients, symptom-based asthma management may well be sufficient, and in preschool children, symptoms are presently the only feasible outcome. Nevertheless, there is some evidence that selected groups might benefit from an approach that takes into account individual phenotypic characteristics. In patients with poor perception, those with a discordant phenotype and those with persistent severe asthma, considering lung function, airways hyperresponsiveness and inflammatory markers in treatment decisions might improve outcomes.

Extrafine aerosols and peripheral airway function in asthma.

To test the hypothesis that extrafine HFA-beclomethasone would improve small airway function, in the most interesting study by Eid and Morton 20 asthmatic children stable on conventional inhaled corticosteroids (ICS) were switched to extrafine HFA-Beclomethasone (HFA-BDP) with a subsequent improvement in peripheral airway function. The intriguing question remains, however, how to interpret that improvement. The most attractive explanation, also supported by the authors, is that extrafine aerosol has an overall better lung deposition and might selectively improve peripheral lung function. As treatment was not randomized, not blinded and uncontrolled, other mechanisms may play a role here as well: (i) The mere fact that children, parents and doctors were aware of being involved in a clinical study may have (positively) affected adherence to treatment and inhaler technique and thus, explain the improvement. This could not be addressed in the study of Eid et al., because a run-in phase was lacking. (ii) Details regarding protocol and actual results are lacking: the switch from conventional ICS treatment to the new dose of HFA-BDP is not well described, but may have resulted in a higher daily dose. (iii) Regression to the mean may have accounted for the increase in FEF25-75. Overall, the observational nature of this study severely limits interpretation of the results. However, the question remains important; therefore, the findings really call for a well-designed study in which the issues raised above are addressed appropriately. Hence, this study of Eid andMorton cannot be taken as evidence, but should inspire researchers to embark onwell designed studies that can actually test the hypothesis that extrafine aerosol inhaled corticosteroids provide added value in pediatric pulmonology. Sincerely,

Online asthma management for children is cost-effective

eHealth interventions have been proposed as an appealing method to improve health outcomes and reduce healthcare costs [1–3]. However, the development of an eHealth intervention is associated with high costs and this investment needs to be balanced by increased clinical effectiveness and related cost savings. Unfortunately, solid evidence for the effectiveness of eHealth with regard to health improvement is still limited [2–5], as is evidence regarding cost-effectiveness. This causes uncertainty about the effectiveness of eHealth and constitutes a barrier towards successful implementation in daily practice [6, 7]. Thus, it is necessary to assess both effectiveness and cost-effectiveness to convince colleagues and policymakers of its added value. Online asthma management in children can (partly) substitute routine outpatient visits and is cost-effective http://ow.ly/oabk30f7Sre

Pharmacogenetics of inhaled long-acting beta2-agonists in asthma: A systematic review

Long‐acting beta2‐agonists (LABA) are recommended in asthma therapy; however, not all asthma patients respond well to LABA. We performed a systematic review on genetic variants associated with LABA response in patients with asthma.