The in vitro identification and quantification of volatile biomarkers released by cystic fibrosis pathogens

There is interest in the development of exhaled breath tests for the detection of lower airway infection in children with cystic fibrosis. The first stage of this process is the identification of volatile organic compounds (VOCs) released into the gas phase by CF pathogens that can be used as breath test biomarkers. Selected ion flow tube mass spectrometry (SIFT-MS) is ideally suited to these in vitro studies as it allows simultaneous quantification of multiple VOCs in real time. We review a decade of in vitro experiments using SIFT-MS to analyse the VOCs released by respiratory pathogens. This includes identification and quantification of VOCs and the investigation of the in vitro factors that affect their production. We also report on how our culture methodology has been refined over the years to better account for variations in bacterial mass. Finally, we discuss how these in vitro findings have been translated into clinical trials and assess possible future applications

Tidal breathing parameters measured using structured light plethysmography in healthy children and those with asthma before and after bronchodilator

Structured light plethysmography (SLP) is a light‐based, noncontact technique that measures tidal breathing by monitoring displacements of the thoracoabdominal (TA) wall. We used SLP to measure tidal breathing parameters and their within‐subject variability (v) in 30 children aged 7–16 years with asthma and abnormal spirometry (forced expiratory volume in 1 sec [FEV1] <80% predicted) during a routine clinic appointment. As part of standard care, the reversibility of airway obstruction was assessed by repeating spirometry after administration of an inhaled bronchodilator. In this study, SLP was performed before and after bronchodilator administration, and also once in 41 age‐matched controls. In the asthma group, there was a significant increase in spirometry‐assessed mean FEV1 after administration of bronchodilator. Of all measured tidal breathing parameters, the most informative was the inspiratory to expiratory TA displacement ratio (IE50SLP, calculated as TIF50SLP/TEF50SLP, where TIF50SLP is tidal inspiratory TA displacement rate at 50% of inspiratory displacement and TEF50SLP is tidal expiratory TA displacement rate at 50% of expiratory displacement). Median (m) IE50SLP and its variability (vIE50SLP) were both higher in children with asthma (prebronchodilator) compared with healthy children (mIE50SLP: 1.53 vs. 1.22, P < 0.001; vIE50SLP: 0.63 vs. 0.47, P < 0.001). After administration of bronchodilators to the asthma group, mIE50SLP decreased from 1.53 to 1.45 (P = 0.01) and vIE50SLP decreased from 0.63 to 0.60 (P = 0.04). SLP‐measured tidal breathing parameters could differentiate between children with and without asthma and indicate a response to bronchodilator

Developing a handheld record for patients with cystic fibrosis

Patient handheld records (PHHRs) promote self-management and empower the holder to take a more active role in the management of their disease. They have been used successfully in improving preventative care for children and have contributed to improved adherence in a number of chronic illnesses. Despite the potential advantages, there are no standard PHHRs for patients with cystic fibrosis (CF). We report the consultation process that led to the development of a CF PHHR, describe the final document, and analyze the feedback from their use at our center. We have made the CF PHHR freely available online

Exhaled breath hydrogen cyanide as a marker of early Pseudomonas aeruginosa infection in children with cystic fibrosis

Hydrogen cyanide is readily detected in the headspace above Pseudomonas aeruginosa cultures and in the breath of cystic fibrosis (CF) patients with chronic (P. aeruginosa) infection. We investigated if exhaled breath HCN is an early marker of P. aeruginosa infection. 233 children with CF who were free from P. aeruginosa infection were followed for 2 years. Their median (interquartile range) age was 8.0 (5.0–12.2) years. At each study visit, an exhaled breath sample was collected for hydrogen cyanide analysis. In total, 2055 breath samples were analysed. At the end of the study, the hydrogen cyanide concentrations were compared to the results of routine microbiology surveillance. P. aeruginosa was isolated from 71 children during the study with an incidence (95% CI) of 0.19 (0.15–0.23) cases per patient-year. Using a random-effects logistic model, the estimated odds ratio (95% CI) was 3.1 (2.6–3.6), which showed that for a 1- ppbv increase in exhaled breath hydrogen cyanide, we expected a 212% increase in the odds of P. aeruginosa infection. The sensitivity and specificity were estimated at 33% and 99%, respectively. Exhaled breath hydrogen cyanide is a specific biomarker of new P. aeruginosa infection in children with CF. Its low sensitivity means that at present, hydrogen cyanide cannot be used as a screening test for this infection