K.D.G. van de Kant

Exhaled nitric oxide and biomarkers in exhaled breath condensate indicate the presence, severity and control of childhood asthma

Background Exhaled nitric oxide and inflammatory biomarkers in exhaled breath condensate may be useful to diagnose and monitor childhood asthma. Their ability to indicate an asthma diagnosis, and to assess asthma severity and control, is largely unknown.

Symptoms, but Not a Biomarker Response to Inhaled Corticosteroids, Predict Asthma in Preschool Children with Recurrent Wheeze

Background. A reliable asthma diagnosis is challenging in preschool wheezing children. As inhaled corticosteroids (ICS) are more effective in asthmatics than in children with transient wheeze, an ICS response might be helpful in early asthma diagnosis. Methods. 175 children (aged two–four years) with recurrent wheeze received 200 μg Beclomethasone extra-fine daily for eight weeks. Changes in Exhaled Breath Condensate (EBC) biomarkers (pH, interleukin (IL)-1α, IL-2, IL-4, IL-5, IL-10, IFN-γ, sICAM, and CCL-11), Fractional exhaled Nitric Oxide (FeNO), airway resistance, and symptoms were assessed. At six years of age a child was diagnosed as transient wheezer or asthmatic. Adjusted logistic regression analysis was performed with multiple testing correction. Results. 106 transient wheezers and 64 asthmatics were analysed at six years of age. Neither changes in EBC biomarkers, nor FeNO, airway resistance, or symptoms during ICS trial at preschool age were related to asthma diagnosis at six years of age. However, asthmatics had more airway symptoms before the start of the ICS trial than transient wheezers (P < 0.01). Discussion. Although symptom score in preschool wheezing children at baseline was associated with asthma at six years of age, EBC biomarkers, airway resistance, or symptom response to ICS at preschool age could not predict asthma diagnosis at six years of age.

Can exhaled inflammatory markers predict a steroid response in wheezing preschool children

Background The efficacy of inhaled corticosteroids (ICS) varies among wheezing preschool children. Currently, it is not possible to predict which fraction of wheezing children will benefit from an ICS treatment.

Biomarkers to predict asthma in wheezing preschool children

Wheezing in preschool children is a very common symptom. An adequate prediction of asthma in these children is difficult and cannot be reliably assessed with conventional clinical tools. The study of potential predictive biomarkers in various media, ranging from invasive sampling (e.g. bronchoscopy) to non‐invasive sampling (lung function testing and exhaled breath analysis), was comprehensively reviewed. The evolution in biomarker discovery has resulted in an ‘omics’ approach, in which hundreds of biomarkers in the field of genomics, proteomics, metabolomics, and ‘breath‐omics’ can be simultaneously studied. First, results on gene expression and exhaled breath profiles in predicting an early asthma diagnosis are promising. However, many hurdles need to be overcome before clinical implementation is possible. To reliably predict asthma in a wheezing child, probably a holistic approach is needed, combining clinical information with blood sampling, lung function tests, and potentially exhaled breath analysis. The further development of predictive, non‐invasive biomarkers may eventually improve an early asthma diagnosis in wheezing preschool children and assist clinicians in early treatment decision‐making.

Global condensation: a "climate change" towards better standardisation of exhaled breath condensate measurements

To the Editors : We read with great interest the letter by Liu et al. 1 and fully agree that exhaled breath condensate (EBC) collection devices significantly affect EBC biomarker levels, and that absolute values from different devices are not directly comparable 1, 2. We also agree that one single (currently available) collection device may not be ideal for all applications and that, in future studies, each marker may need to be tested by a variety of devices in order to determine the optimal collection apparatus 2. In our opinion, some additional considerations of EBC methodology should be made. We believe that these may change our current view on the variability associated with the measurement of exhaled markers in EBC. In turn, this altered consciousness may provide a tentative way out of current methodological controversies and, by consequence, it may offer new perspectives towards the standardisation of EBC methodology 3. First, the levels of nitrogen oxides and total protein measured by Liu et al. 1 in EBC were expressed as nmol or μg “per …

CD14/Toll-like receptors interact with bacteria and regulatory T-cells in the development of childhood asthma

To the Editor: The susceptibility to asthma development in childhood is influenced by genetic as well as environmental factors, and interactions between these factors [1–3]. However, at present, their exact role is still largely undetermined. Genetic variations in the innate immune system may lead to different adaptive immune responses to bacteria and may therefore vary the development of asthma [2, 4, 5]. We performed a prospective longitudinal study in preschool children, in which we determined polymorphisms in Toll-like receptors ( TLR s) and CD14 , the presence of bacteria, and the proportion of regulatory T-cells (Treg) all in relation to an asthma diagnosis at 6 years of age. We hypothesise that specific genetic variants in genes that affect the innate immune system influence the response to bacteria and the recruitment of Treg in preschool children, leading to an increased likelihood of asthma at 6 years of age. The Asthma DEtection and Monitoring (ADEM) study is a long-term prospective case–control study. A detailed protocol of this study has previously been published [6]. A total of 202 children who had experienced at least two wheezing episodes during their lifetime (International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire) [7] and 50 children without wheezing episodes were included at 2–4 years of age. The children were randomly selected from a random population sample in Limburg, the Netherlands, based on the presence or absence of recurrent wheeze [6]. During the initial visit, saliva or buccal cells (DNA), nasal and throat swabs (bacterial cultures), and blood (Treg) were collected. Participants were genotyped for six single nucleotide polymorphisms in TLR2 , TLR4 , TLR9 and CD14 (Sequenom …

Effects of tobacco exposure on lung health and pulmonary biomarkers in young, healthy smokers aged 12–25 years: a systematic review

Chronic obstructive pulmonary disease (COPD) is associated with high personal and societal burden and mortality. COPD is usually diagnosed during middle or late adult life, but the starting point for a ‘COPD career’ may be found earlier in life, during adolescence: first, because of smoking initiation and subsequent accumulation of risk, and second, because of the adverse effects of cigarette smoking on lung-function development. The objective of this paper is to systematically review the literature on the effects of active smoking on lung health in 12–25-year-old healthy boys and girls, measured with simple and noninvasive methods: lung function by spirometry, exhaled gases (including nitric oxide, carbon monoxide and hydrocarbons) and exhaled breath condensate. The identification of biomarkers may be useful for early detection of tobacco-related respiratory disease in this population, for targeted smoking prevention or smoking-cessation programs and, in the long term, for a reduction of personal and societal impact of COPD and other smoking-related diseases.

Introduction of a new paediatric asthma guideline: Effects on asthma control levels

In 2008, a new national paediatric asthma management guideline based on the international Global Initiative for Asthma (GINA) guideline was launched in the Netherlands. We studied whether asthma control and treatment regimens improved after introduction of the guideline by comparing survey data before and after the guideline introduction.

Predictive value of serum sST2 in preschool wheezers for development of asthma with high FeNO

Wheezing is common in childhood. However, current prediction models of pediatric asthma have only modest accuracy. Novel biomarkers and definition of subphenotypes may improve asthma prediction. Interleukin‐1‐receptor‐like‐1 (IL1RL1 or ST2) is a well‐replicated asthma gene and associates with eosinophilia. We investigated whether serum sST2 predicts asthma and asthma with elevated exhaled NO (FeNO), compared to the commonly used Asthma Prediction Index (API). Using logistic regression modeling, we found that serum sST2 levels in 2‐3 years‐old wheezers do not predict doctors’ diagnosed asthma at age 6 years. Instead, sST2 predicts a subphenotype of asthma characterized by increased levels of FeNO, a marker for eosinophilic airway inflammation. Herein, sST2 improved the predictive value of the API (AUC=0.70, 95% CI 0.56‐0.84), but had also significant predictive value on its own (AUC=0.65, 95% CI 0.52‐0.79). Our study indicates that sST2 in preschool wheezers has predictive value for the development of eosinophilic airway inflammation in asthmatic children at school age.