Exhaled breath profiling using broadband quantum cascade laser-based spectroscopy in healthy children and children with asthma and cystic fibrosis.

Exhaled breath analysis is a potential non-invasive tool for diagnosing and monitoring airway diseases. Gas chromatography-mass spectrometry and electrochemical sensor arrays are the main techniques to detect volatile organic compounds (VOC) in exhaled breath. We developed a broadband quantum cascade laser spectroscopy technique for VOC detection and identification. The objective of this study was to assess the repeatability of exhaled breath profiling with broadband quantum cascade laser-based spectroscopy and to explore the clinical applicability by comparing exhaled breath samples from healthy children with those from children with asthma or cystic fibrosis (CF). Healthy children and children with stable asthma or stable CF, aged 6-18 years, were included. Two to four exhaled breath samples were collected in Tedlar bags and analyzed by quantum cascade laser spectroscopy to detect VOCs with an absorption profile in the wavenumber region between 832 and 1262.55 cm(-1). We included 35 healthy children, 39 children with asthma and 15 with CF. Exhaled breath VOC profiles showed poor repeatability (Spearman's rho = 0.36 to 0.46) and agreement of the complete profiles. However, we were able to discriminate healthy children from children with stable asthma or stable CF and identified VOCs that were responsible for this discrimination. Broadband quantum cascade laser-based spectroscopy detected differences in VOC profiles in exhaled breath samples between healthy children and children with asthma or CF. The combination of a relatively easy and fast method and the possibility of molecule identification makes broadband quantum cascade laser-based spectroscopy attractive to investigate the diagnostic and prognostic potential of volatiles in exhaled breath.

The analysis of volatile organic compounds in exhaled breath and biomarkers in exhaled breath condensate in children - clinical tools or scientific toys?

Current monitoring strategies for respiratory diseases are mainly based on clinical features, lung function and imaging. As airway inflammation is the hallmark of many respiratory diseases in childhood, noninvasive methods to assess the presence and severity of airway inflammation might be helpful in both diagnosing and monitoring paediatric respiratory diseases. At present, the measurement of fractional exhaled nitric oxide is the only noninvasive method available to assess eosinophilic airway inflammation in clinical practice. We aimed to evaluate whether the analysis of volatile organic compounds (VOCs) in exhaled breath (EB) and biomarkers in exhaled breath condensate (EBC) is helpful in diagnosing and monitoring respiratory diseases in children. An extensive literature search was conducted in Medline, Embase and PubMed on the analysis and applications of VOCs in EB and EBC in children. We retrieved 1165 papers, of which nine contained original data on VOCs in EB and 84 on biomarkers in EBC. These were included in this review. We give an overview of the clinical applications in childhood and summarize the methodological issues. Several VOCs in EB and biomarkers in EBC have the potential to distinguish patients from healthy controls and to monitor treatment responses. Lack of standardization of collection methods and analysis techniques hampers the introduction in clinical practice. The measurement of metabolomic profiles may have important advantages over detecting single markers. There is a lack of longitudinal studies and external validation to reveal whether EB and EBC analysis have added value in the diagnostic process and follow-up of children with respiratory diseases. In conclusion, the use of VOCs in EB and biomarkers in EBC as markers of inflammatory airway diseases in children is still a research tool and not validated for clinical use.

Multicomponent gas analysis using broadband quantum cascade laser spectroscopy.

We present a broadband quantum cascade laser-based spectroscopic system covering the region between 850 and 1250 cm(-1). Its robust multipass cavity ensures a constant interaction length over the entire spectral region. The device enables the detection and identification of numerous molecules present in a complex gas mixture without any pre-treatment in two minutes. We demonstrate that we can detect sub-ppmv concentration of acetone in presence of 2% of water at the same wavenumber region.

Exhaled nitric oxide and the risk of wheezing in infancy: the Generation R Study.

We assessed whether exhaled nitric oxide fraction (F(eNO)), a marker of eosinophilic airway inflammation, at 6 months was associated with the risk of wheezing during the first 2 yrs of life. In the Generation R birth cohort, pre- and post-natal risk factors for respiratory morbidity and respiratory symptoms were assessed by questionnaires at 6 and 24 months. In 428 infants, off-line mixed oral/nasal F(eNO) was successfully measured during tidal breathing at 6 months. Complete data on F(eNO) and respiratory symptoms within the first 6 months of life were available for 294 infants. F(eNO) was higher in males, was positively associated with age and was negatively associated with upper and lower respiratory symptoms within the first 6 months. Logistic regression analysis showed that for every ppb increase of F(eNO) measured at 6 months, infants had a 1.06 (95% confidence interval 1.01-1.11)-fold increased risk of wheezing in the second year of life. High F(eNO) (>17.5 ppb) showed a limited added value in predicting wheezing in the second year. We conclude that F(eNO) at 6 months is positively associated with the risk of wheezing, but has limited added value in predicting wheezing in the second year of life in individual children.