Breath tests cover the fraction of nitric oxide in expired gas (F_ENO), volatile organic compounds (VOCs), variables in exhaled breath condensate (EBC) and other measurements. For EBC and forF_ENO, official recommendations for standardised procedures are more than 10 years old and there is none for exhaled VOCs and particles. The aim of this document is to provide technical standards and recommendations for sample collection and analytic approaches and to highlight future research priorities in the field. For EBC andF_ENO, new developments and advances in technology have been evaluated in the current document. This report is not intended to provide clinical guidance on disease diagnosis and management.Clinicians and researchers with expertise in exhaled biomarkers were invited to participate. Published studies regarding methodology of breath tests were selected, discussed and evaluated in a consensus-based manner by the Task Force members.Recommendations for standardisation of sampling, analysing and reporting of data and suggestions for research to cover gaps in the evidence have been created and summarised.Application of breath biomarker measurement in a standardised manner will provide comparable results, thereby facilitating the potential use of these biomarkers in clinical practice.

Disability and mortality burden of non-communicable diseases (NCDs) have risen worldwide; however, the NCD burden among adolescents remains poorly described in the EU. Estimates were retrieved from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. Causes of NCDs were analysed at three different levels of the GBD 2019 hierarchy, for which mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) were extracted. Estimates, with the 95% uncertainty intervals (UI), were retrieved for EU Member States from 1990 to 2019, three age subgroups (10–14 years, 15–19 years, and 20–24 years), and by sex. Spearman's correlation was conducted between DALY rates for NCDs and the Socio-demographic Index (SDI) of each EU Member State. In 2019, NCDs accounted for 86·4% (95% uncertainty interval 83·5–88·8) of all YLDs and 38·8% (37·4–39·8) of total deaths in adolescents aged 10–24 years. For NCDs in this age group, neoplasms were the leading causes of both mortality (4·01 [95% uncertainty interval 3·62–4·25] per 100 000 population) and YLLs (281·78 [254·25–298·92] per 100 000 population), whereas mental disorders were the leading cause for YLDs (2039·36 [1432·56–2773·47] per 100 000 population) and DALYs (2040·59 [1433·96–2774·62] per 100 000 population) in all EU Member States, and in all studied age groups. In 2019, among adolescents aged 10–24 years, males had a higher mortality rate per 100 000 population due to NCDs than females (11·66 [11·04–12·28] vs 7·89 [7·53–8·23]), whereas females presented a higher DALY rate per 100 000 population due to NCDs (8003·25 [5812·78–10 701·59] vs 6083·91 [4576·63–7857·92]). From 1990 to 2019, mortality rate due to NCDs in adolescents aged 10–24 years substantially decreased (–40·41% [–43·00 to –37·61), and also the YLL rate considerably decreased (–40·56% [–43·16 to –37·74]), except for mental disorders (which increased by 32·18% [1·67 to 66·49]), whereas the YLD rate increased slightly (1·44% [0·09 to 2·79]). Positive correlations were observed between DALY rates and SDIs for substance use disorders (r_s=0·58, p=0·0012) and skin and subcutaneous diseases (r_s=0·45, p=0·017), whereas negative correlations were found between DALY rates and SDIs for cardiovascular diseases (r_s=–0·46, p=0·015), neoplasms (r_s=–0·57, p=0·0015), and sense organ diseases (r_s=–0·61, p=0·0005). NCD-related mortality has substantially declined among adolescents in the EU between 1990 and 2019, but the rising trend of YLL attributed to mental disorders and their YLD burden are concerning. Differences by sex, age group, and across EU Member States highlight the importance of preventive interventions and scaling up adolescent-responsive health-care systems, which should prioritise specific needs by sex, age, and location. Bill & Melinda Gates Foundation.

Obstructive sleep apnoea (OSA) is associated with cardiovascular and metabolic comorbidities, including hypertension, dyslipidaemia, insulin resistance and atherosclerosis. Strong evidence suggests that OSA is associated with an altered lipid profile including elevated levels of triglyceride-rich lipoproteins and decreased levels of high-density lipoprotein (HDL). Intermittent hypoxia; sleep fragmentation; and consequential surges in the sympathetic activity, enhanced oxidative stress and systemic inflammation are the postulated mechanisms leading to metabolic alterations in OSA. Although the exact mechanisms of OSA-associated dyslipidaemia have not been fully elucidated, three main points have been found to be impaired: activated lipolysis in the adipose tissue, decreased lipid clearance from the circulation and accelerated de novo lipid synthesis. This is further complicated by the oxidisation of atherogenic lipoproteins, adipose tissue dysfunction, hormonal changes, and the reduced function of HDL particles in OSA. In this comprehensive review, we summarise and critically evaluate the current evidence about the possible mechanisms involved in OSA-associated dyslipidaemia.

Currently, many different methods are being used for pre-processing, statistical analysis and validation of data obtained by electronic nose technology from exhaled air. These various methods, however, have never been thoroughly compared. We aimed to empirically evaluate and compare the influence of different dimension reduction, classification and validation methods found in published studies on the diagnostic performance in several datasets. Our objective was to facilitate the selection of appropriate statistical methods and to support reviewers in this research area. We reviewed the literature by searching Pubmed up to the end of 2014 for all human studies using an electronic nose and methodological quality was assessed using the QUADAS-2 tool tailored to our review. Forty-six studies were evaluated regarding the range of different approaches to dimension reduction, classification and validation. From forty-six reviewed articles only seven applied external validation in an independent dataset, mostly with a case-control design. We asked their authors to share the original datasets with us. Four of the seven datasets were available for re-analysis. Published statistical methods for eNose signal analysis found in the literature review were applied to the training set of each dataset. The performance (area under the receiver operating characteristics curve (ROC-AUC)) was calculated for the training cohort (in-set) and after internal validation (leave-one-out cross validation). The methods were also applied to the external validation set to assess the external validity of the performance. Risk of bias was high in most studies due to non-random selection of patients. Internal validation resulted in a decrease in ROC-AUCs compared to in-set performance: -0.15,-0.14,-0.1,-0.11 in dataset 1 through 4, respectively. External validation resulted in lower ROC-AUC compared to internal validation in dataset 1 (-0.23) and 3 (-0.09). ROC-AUCs did not decrease in dataset 2 (+0.07) and 4 (+0.04). No single combination of dimension reduction and classification methods gave consistent results between internal and external validation sets in this sample of four datasets. This empirical evaluation showed that it is not meaningful to estimate the diagnostic performance on a training set alone, even after internal validation. Therefore, we recommend the inclusion of an external validation set in all future eNose projects in medicine.

Chronic obstructive pulmonary disease (COPD) is a progressive respiratory disorder that may lead to gas exchange abnormalities, including hypercapnia. Chronic hypercapnia is an independent risk factor of mortality in COPD, leading to epithelial dysfunction and impaired lung immunity. Moreover, chronic hypercapnia affects the cardiovascular physiology, increases the risk of cardiovascular morbidity and mortality, and promotes muscle wasting and musculoskeletal abnormalities. Noninvasive ventilation is a widely used technique to remove carbon dioxide, and several studies have investigated its role in COPD. In the present review, we aim to summarize the causes and effects of chronic hypercapnia in COPD. Furthermore, we discuss the use of domiciliary noninvasive ventilation as a treatment option for hypercapnia while highlighting the controversies within the evidence. Finally, we provide some insightful clinical recommendations and draw attention to possible future research areas.

Background: Exhaled breath volatile organic compound (VOC) analysis for airway disease monitoring is promising. However, contrary to nitric oxide the method for exhaled breath collection has not yet been standardized and the effects of expiratory flow and breath-hold have not been sufficiently studied. These manoeuvres may also reveal the origin of exhaled compounds. Methods: 15 healthy volunteers (34 ± 7 years) participated in the study. Subjects inhaled through their nose and exhaled immediately at two different flows (5 L/min and 10 L/min) into methylated polyethylene bags. In addition, the effect of a 20 s breath-hold following inhalation to total lung capacity was studied. The samples were analyzed for ethanol and acetone levels immediately using proton-transfer-reaction mass-spectrometer (PTR-MS, Logan Research, UK). Results: Ethanol levels were negatively affected by expiratory flow rate (232.70 ± 33.50 ppb vs. 202.30 ± 27.28 ppb at 5 L/min and 10 L/min, respectively, p < 0.05), but remained unchanged following the breath hold (242.50 ± 34.53 vs. 237.90 ± 35.86 ppb, without and with breath hold, respectively, p = 0.11). On the contrary, acetone levels were increased following breath hold (1.50 ± 0.18 ppm) compared to the baseline levels (1.38 ± 0.15 ppm), but were not affected by expiratory flow (1.40 ± 0.14 ppm vs. 1.49 ± 0.14 ppm, 5 L/min vs. 10 L/min, respectively, p = 0.14). The diet had no significant effects on the gasses levels which showed good inter and intra session reproducibility. Conclusions: Exhalation parameters such as expiratory flow and breath-hold may affect VOC levels significantly; therefore standardisation of exhaled VOC measurements is mandatory. Our preliminary results suggest a different origin in the respiratory tract for these two gasses.