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In contrast to blood and urine samples, breath is invisible and ubiquitous in the environment. Different precautions are now necessary beyond the usual ‘Universal Precautions’. In the era of COVID-19, breath (especially the aerosol fraction) can no longer be considered as harmless in the clinic or laboratory. As Journal of Breath Research is a primary resource for breath-related research, we (the editors) are presently developing safety guidance applicable to all breath research , not just for those projects that involve known COVID-19 infected subjects. We are starting this process by implementing requirements on reporting safety precautions in research papers and notes. This editorial announces that authors of all new submissions to JBR henceforth must state clearly the procedures undertaken for assuring laboratory and clinical safety, much like the existing requirements for disclosing Ethics Committee or Institutional Review Board protocols for studies on human subjects. In the following, we additionally make some recommendations based on best practices drawn from our experience and input from the JBR Editorial Board.

Breath analysis is the study of volatile organic compounds (VOC's) in exhaled breath. This analysis provides information on the body's condition. In this study we investigated the relationship between 22 VOC's detected in exhaled breath and plasma headspace using a selected ion flow tube mass spectrometer (SYFT-MS). We compared pairs of exhaled breath and plasma samples from patients with pulmonary hypertension inflammatory bowel disease (IBD), and IBD patients after J-pouch surgery (pouch group). Half of the measured VOC's from exhaled breath were significantly associated with the VOC's from plasma headspace. Interestingly, six breath VOC's (trimethyl amine (FDR p = 0.02), hydrogen sulfide (FDR p = 7.64 × 10-30), ethanol (FDR p = 1.56 × 10-4), dimethyl sulfide (FDR p = 5.70 × 10-19), benzene (FDR p = 8.40 × 10-27), and acetaldehyde (FDR p = 4.27 × 10-17)) and two plasma headspace VOC's (1-Octene (FDR p = 0.02) and 2-propanol (FDR p = 2.47 × 10-9)) were able to differentiate between the three groups. Breath and plasma headspace share a similar signature with significant association in half of the measured VOCs. The disease discriminatory capacity of breath and plasma headspace appear to be different. Therefore, using the VOC's print from both breath and plasma headspace may better help diagnose patients.

Many uremic solutes retained in chronic kidney disease are volatile, and can be detected by breath testing. We compared the exhaled breath of subjects with end stage renal disease (ESRD) to healthy volunteers to identify volatile compounds that can serve as a potential breathprint for renal failure. We analyzed the exhaled breath of 86 ESRD subjects and 25 healthy volunteers using selected-ion flow-tube mass spectrometry (SIFT-MS). Using a random forests classification model, we identified three known volatiles (2-propanol, ammonia, acetaldehyde) and two unknown volatiles ( NO+76) that were highly significant for discriminating individuals with renal failure from individuals without renal failure (C statistic > 0.99). This study provides preliminary support for the use of exhaled breath as a potential noninvasive screening tool in renal failure.

With each breath we exhale, thousands of molecules are expelled in our breath and each one of us has a ‘breathprint’ that can tell a lot about his or her state of health. While this may be news to some, it should not be to people in medicine. For one can argue that the field of breath analysis is as old as the field of medicine itself. Hippocrates described fetor oris and fetor hepaticus in his treatise on breath aroma and disease, Lavoisier and Laplace in 1784 showed that respiration consumes oxygen and eliminates carbon dioxide [1], Nebelthau in the mid 1800s showed that diabetics emit breath acetone [2], and Anstie in 1874 isolated ethanol from breath (which is the basis of breath alcohol testing today) [3].

The measurement of exhaled nitric oxide (NO) made its way as a new lung function from basic discovery to clinical application in less than a decade. As was the case with spirometry, after the initial bloom of the field, making and following basic discoveries, contradictory findings and unexpected discoveries brought the area to a halt, and scientists have been prompted to take a fresh look at all of the available data and the future horizon. The following four articles on this topic in this issue provide a cutting-edge update of recent developments and interpretation of our current understanding of the field. International experts accepted our invitation to contribute to this dedicated section and to cover those areas where there have been major changes in recent years. The paper by Le-Dong et al provides an exciting summary of methodological challenges, advances and recent technological developments on the measurement of FENO in small animal models. It summarizes data using these measurements in discovering many different functions of NO signalling in the respiratory field. Recent discoveries concerning measurement of FENO in chronic obstructive pulmonary disease (COPD) and their implication in phenotyping and treating the disease are expertly summarized by Arthur Gelb and colleagues, while Robin Taylor provides a clinically oriented overview on the appropriate placing of FENO as a biomarker in clinical decision making. Moving beyond single FENO measurements, the promises and pitfalls of extended FENO analysis are carefully addressed by Marieann Hogman. All authors provided not only a state-of-the-art summary but also gave a personal viewpoint to their writing. We hope their approach will facilitate your enthusiasm to share your personal opinion, or perhaps critical view, openly with the research community. We can work together to identify and plan future research focusing on additional studies that are now needed to clarify the unsettled issues in this field, and can identify new areas of research for the future. Since FENO is in the vanguard of breath analysis, we recommend this special section to anyone interested in exhaled biomarkers and biomarker-based clinical decision making, and hope that you enjoy reading these excellent reviews as much as we did.

Exhaled breath condensate (EBC) is a potential rich source for countless biomarkers that can provide valuable information about respiratory as well as systemic diseases. EBC has been studied in a variety of diseases including allergic rhinitis, asthma, chronic obstructive lung disease, cystic fibrosis, lung cancer, and obstructive sleep apnea syndrome. Although numerous biomarkers have been discovered and studied in EBC, the methods of collection and biomarker detection have not been fully standardized. While leaving standardization methods up to individual labs for the present time is optimal for the continued discovery of new biomarkers in EBC, this decreases the reproducibility and generalizability of the findings. In this review we will discuss specific biomarkers studied in specific diseases as well as some of the related technical issues including collection, processing and analysis.

The aerospace industry requires the development of a range of chemical sensor technologies for such applications as leak detection, emission monitoring, fuel leak detection, environmental monitoring, and fire detection. A family of chemical sensors are being developed based on micromachining and microfabrication technology to fabricate microsensors with minimal size, weight, and power consumption, and the use of nanomaterials and structures to develop sensors with improved stability combined with higher sensitivity. However, individual sensors are limited in the amount of information that they can provide in environments that contain multiple chemical species. Thus, sensor arrays are being developed to address detection needs in such multi-species environments. These technologies and technical approaches have direct relevance to breath monitoring for clinical applications. This paper gives an overview of developing cutting-edge sensor technology and possible barriers to new technology implementation. This includes lessons learned from previous microsensor development, recent work in development of a breath monitoring system, and future directions in the implementation of cutting edge sensor technology. Clinical applications and the potential impact to the biomedical field of miniaturized smart gas sensor technology are discussed.

Breath testing is increasingly being used as a non-invasive diagnostic tool for disease states across medicine. The purpose of this study was to compare the levels of volatile organic compounds (VOCs) as measured by mass spectrometry in healthy children and children with chronic liver disease (CLD). Patients between the ages of 6 and 21 were recruited for the study. Control subjects were recruited from a general pediatric population during well-child visits, while patients with CLD were recruited from pediatric gastroenterology clinic visits. The diagnosis of CLD was confirmed by clinical, laboratory, and/or histologic data. A single exhaled breath was collected and analyzed by means of selected-ion flow-tube mass spectrometry per protocol. A total of 104 patients were included in the study (49 with CLD and 55 healthy controls). Of the patients with CLD, 20 had advanced liver fibrosis (F3-F4). In the CLD cohort, levels of exhaled 1-decene, 1-heptene, 1-octene and 3 methylhexane were found to be significantly higher when compared to the control population (p < 0.001, p = 0.035, p < 0.001 and p = 0.004, respectively). Exhaled 1-nonene, (E)-2-nonene, and dimethyl sulfide levels were found to be significantly lower in patients with CLD patients when compared to controls (p < 0.001, p < 0.001 and p = 0.007, respectively). By utilizing a combination of five of the VOCs, the accuracy for predicting the presence of CLD was excellent (AUROC = 0.97). Our study demonstrates that children with CLD have a unique pattern of exhaled VOCs. Utilization of a combination of these VOCs represents a promising non-invasive diagnostic tool and may provide further insight into the pathophysiologic processes and pathways leading to pediatric liver disease. Further analysis of these compounds in external cohorts are needed to validate our findings.

'Life is not measured by the number of breaths we take, but by the ones we analyze' As the headspace of the blood, our exhaled breath contains a vast array of substances and molecules that hold great promise for monitoring our health and for the diagnosis and management of various lung and systemic diseases. With recent advances in technology, essentially anything in the blood that is potentially volatile or has a volatile metabolite can be measured in exhaled breath. This includes substances we produce endogenously as part of our normal (or disease-related) metabolism whether this is local in the lung or systemic in origin. Since we are constantly inhaling air from our environment as we breathe in the ambient air, exhaled breath can also reflect our environmental exposure(s). Furthermore, our breath contains volatile compounds produced by our 'internal environment': the bacteria in our gut and mouth. Add to all of those volatile byproducts generated from our diet, medications, drugs, or toxins that we are exposed to and you get a very rich matrix that has great potential to revolutionize and personalize medicine. But in order to unlock the great potential of this highly complex resource, we need to find ways to understand its complexity and control or account for the sources of ambiguity.

Breath analysis techniques offer a potential revolution in health care diagnostics, especially if these techniques can be brought into standard use in the clinic and at home. The advent of microsensors combined with smart sensor system technology enables a new generation of sensor systems with significantly enhanced capabilities and minimal size, weight and power consumption. This paper discusses the microsensor/smart sensor system approach and provides a summary of efforts to migrate this technology into human health breath monitoring applications. First, the basic capability of this approach to measure exhaled breath associated with exercise physiology is demonstrated. Building from this foundation, the development of a system for a portable asthma home health care system is described. A solid-state nitric oxide (NO) sensor for asthma monitoring has been identified, and efforts are underway to miniaturize this NO sensor technology and integrate it into a smart sensor system. It is concluded that base platform microsensor technology combined with smart sensor systems can address the needs of a range of breath monitoring applications and enable new capabilities for healthcare.

The measurement of nitric oxide (NO) in exhaled breath has given us the ability to learn about and monitor the inflammatory status of the airway through a non-invasive method that is easy to perform and repeat. This has been most useful in the diagnosis and management of asthma and has promised a seemingly unlimited potential for evaluating the airways and how clinical decisions are made (Grob N M and Dweik R A 2008 Chest133 837-9). The exhaled NO field was initially limited, however, due to the absence of standardized methodology. The ATS and ERS jointly released recommendations for standardized methods of measuring and reporting exhaled NO in 1999 that were revised in 2005 (1999 Am. J. Respir. Crit. Care. Med. 160 2104-17; 2005 Am. J. Respir. Crit. Care. Med. 171 912-30). In this paper, we summarize the literature that followed this standardization. We searched the literature for all papers that included the term 'exhaled nitric oxide' and selected those that followed ATS guidelines for online measurement for further review. We also reviewed cut-off values suggested by groups studying exhaled nitric oxide. We found a wide range of NO values reported for normal and asthma populations. The geometric mean for FE(NO) ranged from 10 ppb to 33 ppb in healthy adult control populations. For asthma, the FE(NO) geometric mean ranged from 6 ppb to 98 ppb. This considerable variation likely reflects the different clinical settings and purposes of measurement. Exhaled NO has been used for a multitude of reasons that range from screening, to diagnosis, to monitoring the effect of therapy. The field of exhaled NO has made undeniable progress since the standardization of the measurement methods. Our challenge now is to have guidelines to interpret exhaled NO levels in the appropriate context. As the utility of exhaled NO continues to evolve, it can serve as a good example of the crucial role of the standardization of collection and measurement methods to propel any new test in the right direction as it makes its way from a research tool to a clinically useful test.

Exhaled NO (FE(NO)) measurements have been utilized as a marker to diagnose asthma as well as a non-invasive tool for monitoring airway inflammation and the response to anti-inflammatory medications. One area where this non-invasive monitoring may be helpful is for asthmatic athletes as they train for competitive events. We hypothesized that in the course of training an asthmatic individual may experience worsening of lung inflammation reflected in FE(NO) levels that may be too subtle to detect by conventional methods like spirometry. Data were collected from an asthmatic patient (n = 1) over the course of endurance training using both the desktop (NIOX) and the portable NO (MINO) analyzers daily for eight weeks. We found that average NO levels measured in the desktop system correlated well with the two portable analyzers (r(2) =0.73, r(2) = 0.74 p0.0001); additionally, there was a strong correlation between the two MINO devices (r(2) = 0.88; p0.0001). A strong negative relationship existed between the number of miles run and NO, regardless of the device used. FEV(1) and PEF, however, did not change significantly as the miles run increased. Exercise training in asthmatics was associated with a decrease (improvement) in NO levels but no significant change in FEV(1) and PEF. This suggests that exhaled NO levels may be more sensitive to changes in the airway as a result of exercise than traditional pulmonary function testing.