Breath tests cover the fraction of nitric oxide in expired gas (FENO), volatile organic compounds (VOCs), variables in exhaled breath condensate (EBC) and other measurements. For EBC and for FENO, 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 and FENO, 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.

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A European respiratory society technical standard : exhaled biomarkers in lung disease

Solid-state gas sensors for breath analysis: a review.

Several volatile organic compounds have been identified in exhaled breath in healthy subjects and patients with respiratory diseases by gas chromatography/mass spectrometry. Identification of selective patterns of volatile organic compounds in exhaled breath could be used as a biomarker of inflammatory lung diseases. An electronic nose (e-nose) is an artificial sensor system that generally consists of an array of chemical sensors for detection of volatile organic compound profiles (breathprints) and an algorithm for pattern recognition. E-noses are handheld, portable devices that provide immediate results. E-noses discriminate between patients with respiratory disease, including asthma, COPD and lung cancer, and healthy control subjects, and also among patients with different respiratory diseases. E-nose breathprints are associated with airway inflammation activity. In combination with other 'omics' platforms, e-nose technology might contribute to the identification of new surrogate markers of pulmonary inflammation and subphenotypes of patients with respiratory diseases, provide a molecular basis to a personalized pharmacological treatment, and facilitate the development of new drugs.

/pdf/the-electronic-nose-in-respiratory-medicine-1fijomfmkz.pdf

The electronic nose in respiratory medicine.

Exhaled air contains many volatile organic compounds (VOCs) that are the result of normal and disease-associated metabolic processes anywhere in the body. Different omics techniques can assess the pattern of these VOCs. One such omics technique suitable for breath analysis is represented by electronic noses (eNoses), providing fingerprints of the exhaled VOCs, called breathprints. Breathprints have been shown to be altered in different disease states, including in asthma and COPD. This review describes the current status on clinical validation and application of breath analysis by electronic noses in the diagnosis and monitoring of chronic airways diseases. Furthermore, important methodological issues including breath sampling, modulating factors and incompatibility between eNoses are raised and discussed. Next steps towards clinical application of electronic noses are provided, including further validation in suspected disease, assessment of the influence of different comorbidities, the value in longitudinal monitoring of patients with asthma and COPD and the possibility to predict treatment responses. Eventually, a Breath Cloud may be constructed, a large database containing disease-specific breathprints. When collaborative efforts are put into optimization of this technique, it can provide a rapid and non-invasive first line diagnostic test.

Exhaled breath analysis by electronic nose in airways disease. Established issues and key questions.

Electronic noses (e-noses) represent an easy and cheap method for exhaled volatile compound analysis. Various electronic noses are available which differ in material and thus analytical performance. In this review, we describe a wide range of electronic noses and summarize data on the methodological issues in electronic nose research. We also review studies which show the ability of electronic noses to distinguish pulmonary and extrapulmonary disorders from health.

https://iopscience.iop.org/article/10.1088/1752-7155/9/3/034001/pdf

Established methodological issues in electronic nose research: how far are we from using these instruments in clinical settings of breath analysis?

Context: Pregnancy-linked accelerated metabolism and oxidative stress may alter the exhaled volatile compound pattern (“breathprint”). Electronic noses can distinguish “breathprints” associated with different disorders.Objective: This is the first study assessing alterations in “breathprint” during gestation.Material and methods: 130 women participated in our study (78 pregnant vs. 52 non-pregnant). Breath samples were processed by an electronic nose and analyzed using principal component analysis.Results: Significant differences were found in exhaled breath pattern between pregnant and non-pregnant women (p = 0.001).Conclusion: Pregnancy-induced changes in exhaled gases need to be considered when pregnant women with respiratory disorders carry out breath tests.

Exhaled breath volatile alterations in pregnancy assessed with electronic nose

The klotho protein is secreted primarily by the kidneys. It is responsible for phosphate homeostasis and has an anti-aging, anti-inflammatory, and anti-oxidative stress role. Obstructive sleep apne...

Decreased Levels of Anti-Aging Klotho in Obstructive Sleep Apnea

Background: The close follow up of lung transplant patients is essential in the recognition of both early and late complications, however today these can be confirmed only by invasive techniques. Analysis of exhaled breath might be promising, as various studies showed relationship between breath components and the development of BOS in lung transplant recipients. Electronic nose is able to analyse the molecular pattern of breath (breathprint), and it discriminated different lung diseases successfully, however lung transplant patients were not studied yet.

Aim: To investigate the relationship between breathprint and various clinical parameters in lung transplant recipients.

Methods: Sixteen patients following lung transplantation participated in our study (mean age 39±14). The study had a model (N=25 samples) and a validation part (N=35 samples). Hence, in average 3.7±2.5 samples per patient were analysed. During their scheduled follow up at the outpatient clinic exhaled breath collection for E-nose measurement (Cyranose 320) as well as blood test and lung function was performed. Breathprints were analysed using principal component analysis and the relationship between breathprint and clinical parameters was assessed by linear regression.

Results: A significant relationship was detected between the breathprint and MEF50 as well as between breath pattern and tacrolimus plasma levels (p<0.05) which was confirmed by the validation set.

Conclusions: The analysis of exhaled breath can be useful in the follow-up of lower airway obstruction in lung transplant recipients. The relation with the drug level draws attention to the interfering effect of treatment and to the possibility of monitoring drug level by exhaled breath testing.

Follow up of lung transplant recipients using electronic nose

Chronic obstructive pulmonary disease (COPD) is associated with the accelerated aging of the lung. The protein klotho has been implicated in longevity, and there is some evidence that it might be involved in the pathomechanism of chronic respiratory diseases. Therefore, we aimed to examine whether the clinical condition of COPD patients is reflected in plasma klotho concentration. As plasma concentration of the protein is modulated by physiological factors that are generally improved during pulmonary rehabilitation, we hypothesized that a complex rehabilitation program may alter plasma klotho concentration. Blood samples were taken from 31 stable COPD patients. Clinical parameters such as respiratory function, 6-minute walking distance (6MWD), impact of disease (CAT), dyspnea, grip strength, chest expansion and breath holding time, smoking history, and body mass index (BMI) were evaluated. 19 patients who participated in a 3-week inpatient rehabilitation program had blood sample collection on the ...

Assessment of the Anti-Aging Klotho Protein in Patients with COPD Undergoing Pulmonary Rehabilitation

The anti-aging factor, klotho has been identified as a tumor suppressor in various human cancers, including lung cancer. In vitro studies provided evidence that klotho expression influences the characteristics of lung cancer cells, however, in vivo results are lacking. The aim of our study was to evaluate whether circulating klotho protein might serve as a potential biomarker of lung cancer. Blood samples were taken from 45 newly diagnosed lung cancer patients (31 NSCLC, 14 SCLC) and 43 control subjects. Plasma klotho concentration was measured using ELISA. No difference in plasma klotho values was detected between patients and control subjects (366.3 (257.9–486.8) vs. 383.5 (304.6–489.7) pg/ml respectively (median (IQR)); p > 0.05). Plasma klotho levels in patients with distant metastasis did not differ from less advanced stage disease (354.2 (306.9–433.3 vs. 328.5 (242.5–419.7) pg/ml, p > 0.05). In contrast, analyzed with one-way ANOVA, significant difference (p = 0.04) was found between the examined histological types of lung cancer: adenocarcinoma (353 (329.4–438.5) pg/ml), squamous cell carcinoma (308 (209.6–348.1) pg/ml) and small cell lung cancer (388.8 (289.9–495.4) pg/ml). However, Tukey’s post hoc test did not reveal significant difference between any pairs of histological groups. There was no difference between any histological subtype and health either. Our results suggest that circulating klotho protein cannot be considered as a biomarker for lung cancer. Further studies are warranted in order to examine the relationship between klotho expression in lung tissue and circulating levels of the protein, and to explore its mechanism of action in lung cancer.

Judit Pako

Papers

Exhaled breath volatile alterations in pregnancy assessed with electronic nose

Decreased Levels of Anti-Aging Klotho in Obstructive Sleep Apnea

Follow up of lung transplant recipients using electronic nose

Assessment of the Anti-Aging Klotho Protein in Patients with COPD Undergoing Pulmonary Rehabilitation

Assessment of the circulating klotho protein in lung cancer patients