There is an increasing interest in the potential of exhaled biomarkers, such as volatile organic compounds (VOCs), to improve accurate diagnoses and management decisions in pulmonary diseases. The objective of this manuscript is to systematically review the current knowledge on exhaled VOCs with respect to their potential clinical use in asthma, lung cancer, chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), and respiratory tract infections. A systematic literature search was performed in PubMed, EMBASE, Cochrane database, and reference lists of retrieved studies. Controlled, clinical, English-language studies exploring the diagnostic and monitoring value of VOCs in asthma, COPD, CF, lung cancer and respiratory tract infections were included. Data on study design, setting, participant characteristics, VOCs techniques, and outcome measures were extracted. Seventy-three studies were included, counting in total 3,952 patients and 2,973 healthy controls. The collection and analysis of exhaled VOCs is non-invasive and could be easily applied in the broad range of patients, including subjects with severe disease and children. Various research groups demonstrated that VOCs profiles could accurately distinguish patients with a pulmonary disease from healthy controls. Pulmonary diseases seem to be characterized by a disease specific breath-print, as distinct profiles were found in patients with dissimilar diseases. The heterogeneity of studies challenged the inter-laboratory comparability. In conclusion, profiles of VOCs are potentially able to accurately diagnose various pulmonary diseases. Despite these promising findings, multiple challenges such as further standardization and validation of the diverse techniques need to be mastered before VOCs can be applied into clinical practice.

Asthma is the most common chronic disease in childhood, characterized by chronic airway inflammation. There are problems with the diagnosis of asthma in young children since the majority of the children with recurrent asthma-like symptoms is symptom free at 6 years, and does not have asthma. With the conventional diagnostic tools it is not possible to differentiate between preschool children with transient symptoms and children with asthma. The analysis of biomarkers of airway inflammation in exhaled breath is a non-invasive and promising technique to diagnose asthma and monitor inflammation in young children. Moreover, relatively new lung function tests (airway resistance using the interrupter technique) have become available for young children. The primary objective of the ADEM study (Asthma DEtection and Monitoring study), is to develop a non-invasive instrument for an early asthma diagnosis in young children, using exhaled inflammatory markers and early lung function measurements. In addition, aetiological factors, including gene polymorphisms and gene expression profiles, in relation to the development of asthma are studied.

The aetiology of childhood asthma is complex. An early dysfunction in the immunological development of the innate immune system in combination with environmental factors possibly triggers asthma. CD14 and toll-like receptors are important components of the innate immune system. The aim of this systematic review was to obtain a better insight into the relation between CD14 and toll-like receptors and childhood asthma in Caucasians. We searched PubMed and EMBASE for relevant articles. In total, 44 articles were included. The quality of the selected studies was independently assessed by the first two authors using the Newcastle-Ottawa quality assessment scale. Toll-like receptor 2, toll-like receptor 6, toll-like receptor 9, and toll-like receptor 10 appear to have some association with childhood asthma in Caucasians. The evidence for a relation of CD14 with childhood asthma is limited. In conclusion, there is no convincing evidence yet for a role of CD14 and toll-like receptors in relation to childhood asthma. Future studies should include haplotype analysis and take environmental factors into account to further clarify the role of CD14 and toll-like receptors on childhood asthma.

The Coronavirus pandemic stresses the importance of eHealth techniques to monitor patients at home. Home monitoring of lung function in asthma and cystic fibrosis (CF) may help to detect deterioration of lung function at an early stage, but the reliability is unclear. We investigated whether lung function measurements at home were comparable to measurements during clinical visits. We analysed prospectively collected data of two one-year observational cohort studies in 117 children (36 with CF and 81 with asthma). All patients performed forced expiratory volume in one second (FEV₁) measurements with a monitor at home. Paired FEV₁ measurements were included if the measurement on the home monitor was performed on the same day as the FEV₁ measurement on the pneumotachometer during a two monthly clinical visit. Bland-Altman plots and linear mixed model analysis were used. The mean difference (home measurement was subtracted from clinical measurement) in FEV₁ was 0.18 L in CF (95% confidence interval (CI) 0.08–0.27 L; p < 0.001) and 0.12 L in asthma (95%CI 0.05–0.19 L; p < 0.001). FEV₁ measurements at home were significantly lower than clinically obtained FEV₁ measurements, which has implications for the application of this technique in the daily clinical situation.

There are limited data on health-related quality of life (HRQoL) changes over time in children with cystic fibrosis (CF). We investigated associations between clinical and treatment variables with changes in HRQoL during 1 year. Forty-nine children with CF aged 6–18 years were followed in this multicentre, observational cohort study during 1 year. HRQoL was measured by the validated disease specific cystic fibrosis questionnaire-revised (CFQ-R). The CFQ-R total score as well as most domain scores improved significantly (8.0 points and [3.3–31.7] points respectively) during the one-year follow-up. Age at baseline demonstrated a strong longitudinal association with the change of CFQ-R total score (2.853 points decrease of CFQ-R total score per year increase in age) and several domain scores. Below 12 years of age, CFQ-R total score improved in most children, whereas a deterioration was observed in most children above 12 years. The number of PEx was associated with an increase of treatment burden score (4.466 points decrease per extra PEx). Conclusion: In the group as a whole, HRQoL improved significantly over time. However, changes over time were significantly influenced by age: below 12 years of age, HRQoL improved in most patients whereas a deterioration was observed in most children >12 years. Strategies how to preserve or ideally to improve HRQoL in adolescence should be developed. What is known: • Quality of life in patient with CF is diminished • Although CF is a chronic disease, longitudinal data on QoL in children with CF are scarce. What is new: • Below 12 years of age, quality of life improved in most children during the 1-year follow-up whereas a deterioration in quality of life was observed in most children above 12 years. • the treatment burden score of QoL correlated with the exacerbation rate

Managing pediatric asthma includes optimizing both asthma control and asthma-specific quality of life (QoL). However, it is unclear to what extent asthma-specific QoL is related to asthma control or other clinical characteristics over time. The aims of this study were to assess in children longitudinally: (1) the association between asthma control and asthma-specific QoL and (2) the relationship between clinical characteristics and asthma-specific QoL. In a 12-month prospective study, asthma-specific QoL, asthma control, dynamic lung function indices, fractional exhaled nitric oxide, the occurrence of exacerbations, and the use of rescue medication were assessed every 2 months. Associations between the clinical characteristics and asthma-specific QoL were analyzed using linear mixed models. At baseline, the QoL symptom score was worse in children with asthma and concomitant chronic rhinitis compared to asthmatic children without chronic rhinitis. An improvement of asthma control was longitudinally associated with an increase in asthma-specific QoL (p-value < 0.01). An increased use of β₂-agonists, the occurrence of wheezing episodes in the year before the study, the occurrence of an asthma exacerbation in the 2 months prior to a clinical visit, and a deterioration of lung function correlated significantly with a decrease in the Pediatric Asthma Quality of Life Questionnaire (PAQLQ) total score (p-values ≤ 0.01). Chronic rhinitis did not correlate with changes in the PAQLQ score over 1 year. The conclusion was that asthma control and asthma-specific QoL were longitudinally associated, but were not mutually interchangeable. The presence of chronic rhinitis at baseline did influence QoL symptom scores. β₂-agonist use and exacerbations before and during the study were inversely related to the asthma-specific QoL over time.