European Respiratory Society clinical practice guidelines for the diagnosis of asthma in children aged 5-16†years.

BACKGROUND: Diagnosing asthma in children represents an important clinical challenge. There is no single gold-standard test to confirm the diagnosis. Consequently, over- and under-diagnosis of asthma is frequent in children. METHODS: A task force supported by the European Respiratory Society has developed these evidence-based clinical practice guidelines for the diagnosis of asthma in children aged 5-16 years using nine Population, Intervention, Comparator and Outcome (PICO) questions. The task force conducted systematic literature searches for all PICO questions and screened the outputs from these, including relevant full-text articles. All task force members approved the final decision for inclusion of research papers. The task force assessed the quality of the evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. RESULTS: The task force then developed a diagnostic algorithm based on the critical appraisal of the PICO questions, preferences expressed by lay members and test availability. Proposed cut-offs were determined based on the best available evidence. The task force formulated recommendations using the GRADE Evidence to Decision framework. CONCLUSION: Based on the critical appraisal of the evidence and the Evidence to Decision framework, the task force recommends spirometry, bronchodilator reversibility testing and exhaled nitric oxide fraction as first-line diagnostic tests in children under investigation for asthma. The task force recommends against diagnosing asthma in children based on clinical history alone or following a single abnormal objective test. Finally, this guideline also proposes a set of research priorities to improve asthma diagnosis in children in the future.

A case report of an unusual non-mucinous papillary variant of CPAM type 1 with KRAS mutations.

BACKGROUND: congenital pulmonary airway malformation (CPAM) is the most frequent congenital lung disorder. CPAM type 1 is the most common subtype, typically having a cystic radiological and histological appearance. Mucinous clusters in CPAM type 1 have been identified as premalignant precursors for mucinous adenocarcinoma. These mucinous adenocarcinomas and the mucinous clusters in CPAM commonly harbor a specific KRAS mutation. CASE PRESENTATION: we present a case of a 6-weeks-old girl with CPAM type 1 where evaluation after lobectomy revealed a highly unusual complex non-mucinous papillary architecture in all cystic parts, in which both mucinous clusters and non-mucinous papillary areas harbored the known KRAS mutation. CONCLUSIONS: we found that a KRAS mutation thought to be premalignant in mucinous clusters only, was also present in the other cyst lining epithelial cells of this unusual non-mucinous papillary variant of CPAM type 1, warranting clinical follow-up because of uncertain malignant potential.

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.

Monitoring asthma in children.

The goal of asthma treatment is to obtain clinical control and reduce future risks to the patient. To reach this goal in children with asthma, ongoing monitoring is essential. While all components of asthma, such as symptoms, lung function, bronchial hyperresponsiveness and inflammation, may exist in various combinations in different individuals, to date there is limited evidence on how to integrate these for optimal monitoring of children with asthma. The aims of this ERS Task Force were to describe the current practise and give an overview of the best available evidence on how to monitor children with asthma. 22 clinical and research experts reviewed the literature. A modified Delphi method and four Task Force meetings were used to reach a consensus. This statement summarises the literature on monitoring children with asthma. Available tools for monitoring children with asthma, such as clinical tools, lung function, bronchial responsiveness and inflammatory markers, are described as are the ways in which they may be used in children with asthma. Management-related issues, comorbidities and environmental factors are summarised. Despite considerable interest in monitoring asthma in children, for many aspects of monitoring asthma in children there is a substantial lack of evidence.

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

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.

Paediatrics in Barcelona.

This update will describe the paediatric highlights from the 2013 European Respiratory Society (ERS) annual congress in Barcelona, Spain. Abstracts from the seven groups of the ERS Paediatric Assembly (Respiratory Physiology and Sleep, Asthma and Allergy, Cystic Fibrosis, Respiratory Infection and Immunology, Neonatology and Paediatric Intensive Care, Respiratory Epidemiology, and Bronchology) have been chosen by group officers and are presented in the context of current literature.

Evaluation of Target Attainment for Tobramycin in Children and Adults with Cystic Fibrosis.

Introduction: Patients with cystic fibrosis (CF) commonly experience pulmonary exacerbations, and it is recommended by the TOPIC study to treat this with tobramycin at a dose of 10 mg/kg once daily. The aim of this study was to evaluate the target attainment of the current dosing regimen. Methods: A single-center retrospective cohort study of child and adult patients with CF who received tobramycin between 2019 and 2022 was conducted. Descriptive statistics and linear mixed models were used to assess target attainment for tobramycin. Results: In total, 25 patients (53 courses), of which 10 were children (12 courses) and 15 were adults (41 courses), were included. Those 25 patients all received 10 mg/kg/day. The tobramycin peak concentrations were supratherapeutic in 82.9% and therapeutic in 100.0% of adults and children, respectively. The trough concentrations were outside the target range in 0% and 5.1% of children and adults, respectively. We found lower tobramycin concentrations with the same dose in children compared to adults. Conclusions: This study illustrates the need to validate dosing advice in a real-world setting, as supratherapeutic concentrations of tobramycin were prevalent in adults with CF.

Asthma medication delivery: mists and myths.

Asthma is usually treated with inhaled corticosteroids (ICS) and bronchodilators generated from pressurized metered dose inhalers (pMDI), dry powder inhalers (DPI), or nebulizers. The target areas for ICS and beta 2-agonists in the treatment of asthma are explained. Drug deposition not only depends on particle size, but also on inhalation manoeuvre. Myths regarding inhalation treatments lead to less than optimal use of these delivery systems. We discuss the origin of many of these myths and provide the background and evidence for rejecting them.

Ciclesonide versus other inhaled corticosteroids for chronic asthma in children.

BACKGROUND: Inhaled corticosteroids (ICS) are the cornerstone of asthma maintenance treatment in children. Particularly among parents, there is concern about the safety of ICS as studies in children have shown reduced growth. Small-particle-size ICS targeting the smaller airways have improved lung deposition and effective asthma control might be achieved at lower daily doses.Ciclesonide is a relatively new ICS. This small-particle ICS is a pro-drug that is converted in the airways to an active metabolite and therefore with potentially less local (throat infection) and systemic (reduced growth) side effects. It can be inhaled once daily, thereby possibly improving adherence. OBJECTIVES: To assess the efficacy and adverse effects of ciclesonide compared to other ICS in the management of chronic asthma in children. SEARCH METHODS: We searched the Cochrane Airways Group Register of trials with pre-defined terms. Additional searches of MEDLINE (via PubMed), EMBASE and Clinical study results.org were undertaken. Searches are up to date to 7 November 2012. SELECTION CRITERIA: Randomised controlled parallel or cross-over studies were eligible for the review. We included studies comparing ciclesonide with other corticosteroids both at nominally equivalent doses or lower doses of ciclesonide. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. Study authors were contacted for additional information. Adverse effects information was collected from the trials. MAIN RESULTS: Six studies were included in this review (3256 children, 4 to 17 years of age). Two studies were published as conference abstracts only. Ciclesonide was compared to budesonide and fluticasone.Ciclesonide compared to budesonide (dose ratio 1:2): asthma symptoms and adverse effect were similar in both groups. Pooled results showed no significant difference in children who experience an exacerbation (risk ratio (RR) 2.20, 95% confidence interval (CI) 0.75 to 6.43). Both studies reported that 24-hour urine cortisol levels showed a statistically significant decrease in the budesonide group compared to the ciclesonide group.Ciclesonide compared to fluticasone (dose ratio 1:1): no significant differences were found for the outcome asthma symptoms. Pooled results showed no significant differences in number of patients with exacerbations (RR 1.37, 95% CI 0.58 to 3.21) and data from a study that could not be pooled in the meta-analysis reported similar numbers of patients with exacerbations in both groups. None of the studies found a difference in adverse effects. No significant difference was found for 24-hour urine cortisol levels between the groups (mean difference 0.54 nmol/mmol, 95% CI -5.92 to 7.00).Ciclesonide versus fluticasone (dose ratio 1:2) was assessed in one study and showed similar results between the two corticosteroids for asthma symptoms. The number of children with exacerbations was significantly higher in the ciclesonide group (RR 3.57, 95% CI 1.35 to 9.47). No significant differences were found in adverse effects (RR 0.98, 95% CI 0.81 to 1.14) and 24-hour urine cortisol levels (mean difference 1.15 nmol/mmol, 95% CI 0.07 to 2.23).The quality of evidence was judged 'low' for the outcomes asthma symptoms and adverse events and 'very low' for the outcome exacerbations for ciclesonide versus budesonide (dose ratio 1:1). The quality of evidence was graded 'moderate' for the outcome asthma symptoms, 'very low' for the outcome exacerbations and 'low' for the outcome adverse events for ciclesonide versus fluticasone (dose ratio 1:1). For ciclesonide versus fluticasone (dose ratio 1:2) the quality was rated 'low' for the outcome asthma symptoms and 'very low' for exacerbations and adverse events (dose ratio 1:2). AUTHORS' CONCLUSIONS: An improvement in asthma symptoms, exacerbations and side effects of ciclesonide versus budesonide and fluticasone could be neither demonstrated nor refuted and the trade-off between benefits and harms of using ciclesonide instead of budesonide or fluticasone is unclear. The resource use or costs of different ICS should therefore also be considered in final decision making. Longer-term superiority trials are needed to identify the usefulness and safety of ciclesonide compared to other ICS. Additionally these studies should be powered for patient relevant outcomes (exacerbations, asthma symptoms, quality of life and side effects). There is a need for studies comparing ciclesonide once daily with other ICS twice daily to assess the advantages of ciclesonide being a pro-drug that can be administered once daily with possibly increased adherence leading to increased control of asthma and fewer side effects.

Eradication of Burkholderia cepacia complex in cystic fibrosis patients with inhalation of amiloride and tobramycin combined with oral cotrimoxazole.

This case series suggests that successful eradication therapy of BCC in cystic fibrosis can be done with a combination of inhaled and oral medication, which in many cases may eliminate the need for intensive treatment with intravenous antibiotics https://bit.ly/40oOMIn.

The pharmacokinetics of antibiotics in cystic fibrosis.

INTRODUCTION: Dosing of antibiotics in people with cystic fibrosis (CF) is challenging, due to altered pharmacokinetics, difficulty of lung tissue penetration, and increasing presence of antimicrobial resistance. AREAS COVERED: The purpose of this work is to critically review original data as well as previous reviews and guidelines on pharmacokinetics of systemic and inhaled antibiotics in CF, with the aim to propose strategies for optimization of antibacterial therapy in both children and adults with CF. EXPERT OPINION: For systemic antibiotics, absorption is comparable in CF patients and non-CF controls. The volume of distribution (Vd) of most antibiotics is similar between people with CF with normal body composition and healthy individuals. However, there are a few exceptions, like cefotiam and tobramycin. Many antibiotic class-dependent changes in drug metabolism and excretion are reported, with an increased total body clearance for ß-lactam antibiotics, aminoglycosides, fluoroquinolones, and trimethoprim. We, therefore, recommend following class-specific guidelines for CF, mostly resulting in higher dosages per kg bodyweight in CF compared to non-CF controls. Higher local antibiotic concentrations in the airways can be obtained by inhalation therapy, with which eradication of bacteria may be achieved while minimizing systemic exposure and risk of toxicity.

Eradication of Pseudomonas aeruginosa in cystic fibrosis patients with inhalation of dry powder tobramycin.

BACKGROUND: Pseudomonas aeruginosa (Pa) is the predominant pulmonary pathogen in patients with cystic fibrosis (CF). Tobramycin nebulization is used for the eradication of Pa infection. Nowadays, tobramycin dry powder inhalation (DPI) is available as well. This study reports the results of eradicating Pa with tobramycin DPI versus nebulization. METHODS: Adult CF patients with a Pa isolation between September 2010 and September 2017 from the University Medical Centre Groningen (UMCG), the Netherlands, were included in this retrospective study. RESULTS: In total 27 Pa isolations were recorded. In 13 of these, eradication was attempted with tobramycin, 7 with DPI and 6 with nebulization. DPI eradicated Pa successfully in six isolations (85.7%). Of these, one patient received additional oral ciprofloxacin and one received intravenous ceftazidime. Nebulization eradicated three Pa isolations (50.0%), in two of these, additional oral ciprofloxacin was given. CONCLUSION: Eradication rates of DPI tobramycin are comparable with those for nebulized tobramycin reported in the literature. This study suggests that DPI tobramycin is an alternative to nebulized tobramycin for eradication of Pa. TRIAL REGISTRATION: The Medical Ethics Committee of the UMCG granted a waiver (METC2017-349), as they concluded that this study was not subject to the Medical Research Involving Human Subjects Act. The reviews of this paper are available via the supplemental material section.

Anti-inflammatory drug therapy in asthma.

Asthma is a disease with chronic inflammation of the airways and and-inflammatory treatment is a logical treatment. Inhaled corticosteroids [ICS] remain the cornerstone of anti-inflammatory therapy in recent international guidelines. Asthma cannot be cured by any medication: if the drug is discontinued, the disease manifestations return. This has been proven at all ages. In preschool children the diagnosis of asthma is difficult to establish. In this heterogeneous group ICS or leukotriene receptor antagonists [LTRA] are just as effective as placebo; in the future it will hopefully be possible to describe characteristics of responders. LTRA are an alternative in mild asthma, especially when mono-triggered viral related wheeze is present. Theophylline is effective and also has bronchodilatory properties, which need to be balanced against the relatively frequent side effects. The working mechanisms of anti-inflammatory asthma medications including ICS, LTRA, cromones, macrolides and theophylline are described.

Key paediatric messages from the 2018 European Respiratory Society International Congress.

In this article, the Group Chairs and early career members of the European Respiratory Society (ERS) Paediatric Assembly highlight some of the most interesting findings in the field of paediatrics which were presented at the 2018 international ERS Congress.

Prerequisites for a dry powder inhaler for children with cystic fibrosis.

Correct inhalation technique is essential for effective use of dry powder inhalers (DPIs), as their effectiveness largely depends on the patient's inhalation manoeuvre. Children are an especially challenging target population for DPI development due to the large variability in understanding and inspiratory capacities. We previously performed a study in which we determined the prerequisites for a paediatric DPI in a mostly healthy paediatric population, for which we used an empty test inhaler with variable internal airflow resistance and mouthpiece. In the current study we investigated what specifications are required for a DPI for children with cystic fibrosis (CF), for which we expanded on our previous findings. We recorded flow profiles of 35 children with CF (aged 4.7-14.7 years) at three airflow resistances (0.031-0.045 kPa0.5.min.L-1) from which various inspiratory parameters were computed. Obstructions in the mouth during inhalation were recorded with a sinuscope. All children were able to perform a correct inhalation manoeuvre, although video analysis showed that children did not place the inhaler correctly in the mouth in 17% of the cases. No effect was found of medium to high airflow resistance on total inhaled volume, which implies that the whole resistance range tested is suitable for children with CF aged 4-14 years. No effect could be established of either mouthpiece design or airflow resistance on the occurrence of obstructions in the mouth cavity. This study confirms our previous conclusion that the development of DPIs specifically for children is highly desired. Such a paediatric DPI should function well at 0.5 L inhaled volume and a peak inspiratory flow rate of 20 to 30 L/min, depending on the internal airflow resistance. This resistance can be increased up to 0.045 kPa0.5.min.L-1 (medium-high) to reduce oropharyngeal deposition. A higher resistance may be less favourable due to its compromising effect on PIF and thereby on the energy available for powder dispersion.

Key paediatric messages from the 2016 European Respiratory Society International Congress.

In this article, the Group Chairs of the Paediatric Assembly of the European Respiratory Society (ERS) highlight some of the most interesting abstracts presented at the 2016 ERS International Congress, which was held in London.