Differential ion mobility spectrometry (DMS) is a method to detect volatile organic compounds (VOC) in the ppt range. This study assessed whether VOC analysis using DMS could discriminate subjects with an experimentally induced chronic intestinal infection caused by Mycobacteria from non-infected controls. The animal model consisted of two groups of goats orally infected with two different doses of Mycobacterium avium subspecies paratuberculosis (MAP) and one group of non-infected healthy controls (each group: n = 6). Using DMS, exhaled breath and headspace of feces were analyzed on-line on an individual basis 9 months after inoculation of MAP. Data analysis included peak detection, cluster analysis, selection of discriminating VOC features (Mann-Whitney U test), and classification using a support-vector-machine. Taking the background of ambient air conditions into account, VOC analysis of exhaled breath as well as of feces revealed significant differences between chronically infected animals and non-infected controls. In both specimens, increasing as well as decreasing VOC features could be attributed to infection. Discrimination between infected and non-infected animals was sharper analyzing exhaled breath compared to headspace of feces. In exhaled breath, at least two VOC features were found to increase in a dose-dependent manner with increasing doses of MAP inoculated. Results of this study provide strong evidence that DMS analysis of exhaled breath has the potential to become a valuable tool for non-invasive assessment of VOC specifically related to certain diseases or infections.

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Measurement of leukotriene E 4 (LTE 4 ) in urine is a noninvasive method for assessing changes in the rate of total body cysteinyl leukotriene production. Eosinophil protein X (EPX) has been used to assess eosinophil activity and monitor inflammation in bronchial asthma. The aim of the study was to look for differences in urinary LTE 4 and EPX concentrations between children with stable atopic asthma and healthy controls and to compare asthmatic children with different disease severity. In addition the relationship was evaluated between urinary LTE 4 amd EPX levels and lung function.LTE 4 was also measured (enzyme immunoassay) together with EPX (radioimmunoassay) in urine and lung function tests were carried out in children with mild asthma (steroid-naive) (n=49), moderate to severe asthma (using inhaled steroids) (n=31) and healthy control subjects (n=28).Urinary leukotriene E 4 (LTE 4 ) was significantly higher in children with asthma than in controls (median [25±75 percentile] 238.5 (126.5±375.7) SD 191.8 versus 189 (51±253.2) SD 131.7 pg . mg -1 creatinine; p=0.021). Urinary EPX was also significantly increased in asthmatic children compared with controls (85.5 [64±131.5] SD 76.2 versus 48.5 [43.2±90] 112.1 mg . mmol -1 creatinine; p=0.006). There were no differences in urinary LTE 4 and EPX between the group of mild and the group of moderate to severe asthmatic children. There were significant associations between the urinary LTE 4 and intrathoracic gas volume (ITGV), residual volume (RV), forced expiratory volume in one second (FEV1), forced expiratory capacity (FVC) and maximum expiratory flow rate at 25% of vital capacity (MEF25).Urinary EPX was only correlated with maximum expiratory flow rate at 75% of vital capacity (MEF75). Thus measurement of urinary LTE 4 may predict the degree of airflow obstruction in asthmatic children. Urinary LTE 4 and EPX are useful markers of airway inflammation and can be helpful in guiding asthma management. There was no correlation between LTE 4 and EPX levels. Eur Respir J 2000; 16: 588±592.

Collection of exhaled condensate is tolerated well by calves and is an acceptable method for obtaining fluid from exhaled air originating from the lungs. This method provides alternatives for diagnosing and evaluating treatment of naturally acquired and experimentally induced diseases of the lungs and airways in calves.

Monitoring free IgE and omalizumab serum concentrations in patients treated with omalizumab does not predict clinical response nor does it add to the decision to continue or stop treatment. However, routine measurements of free IgE may be clinically relevant to demonstrate an adequate reduction in free IgE in patients not responding to omalizumab therapy.

This study was designed to assess the effect of differential leukocyte depletion during chemotherapy by monitoring the levels of exhaled hydrogen peroxide H 2 O 2 and nitric oxide (FeNO) present.In 39 patients with lung cancer (chronic obstructive pulmonary disorder up to stage II, median forced expiratory volume in one second 78% predicted), measurements were performed before a cycle of therapy (day 1), at least once during the cycle (day 8: n534; day 15: n519), and afterwards (days 21-29).There were significant changes in the level of H 2 O 2 , FeNO and peripheral blood cell differentials over the visits. The level of H 2 O 2 was decreased only on day 15, with a median (difference between the upper and lower quartiles) fall of 31 (57)%, while FeNO was reduced only on day 8, by 22 (40)%. Neutrophil numbers were unchanged on day 8 and decreased by 59 (48)% on day 15, while monocyte numbers were decreased on day 8 by 87 (39)%. On days 21-29, values had returned to baseline.Taken together with previous findings, the parallel course of levels of exhaled hydrogen peroxide and neutrophil counts suggests that a major part of exhaled hydrogen peroxide is due to neutrophils via the conducting airways. In contrast, the production of exhaled nitric oxide seems to be primarily associated with monocytes.

There is an urgent need for screening patients of having a communicable viral disease to cut infection chains. We could recently demonstrate that MCC-IMS of breath is able to identify Influenza-A infected patients. With decreasing Influenza epidemic and upcoming SARS-CoV-2 infections we extended our study to the analysis of patients with suspected SARS-CoV-2 infections. 51 patients, 23m, 28f, aged 64 +/- 16 years, were included in this study. Besides RT-PCR analysis of nasopharyngeal swabs all patients underwent MCC-IMS analysis of breath. 16 patients, 7m, 9f, were positive for SARS-CoV-2 by RT-PCR. There was no difference in gender or age according to the groups. Stepwise canonical discriminant analysis could correctly classify the infected and non- infected subjects in 98% by cross-validation. Afterwards we combined the Influenza-A sub study and the SARS-CoV-2- sub study for a total of 75 patients, 34m, 41f, aged 64.8 +/- 1.8 years, 14 positive for Influenza-A, 16 positive for SARS-CoV-2, the remaining 44 patients were used as controls. In one patient RT-PCR was highly suspicious of SARS-CoV-2 but inconclusive. There was no imbalance between the groups for age or gender. 97.3% of the patients could be correctly classified to the respective group by discriminant analysis. Even the inconclusive patient could be mapped to the SARS-CoV-2 group applying the discrimination function. Conclusion: MCC-IMS is able to detect SARS-CoV-2 infection and Influenza-A infection in breath. As this method provides exact, fast non-invasive diagnosis it should be further developed for screening of communicable viral diseases. Study registration: NCT04282135

As a noninvasive method, exhaled breath condensate (EBC) has gained importance to improve monitoring of lung diseases and to detect biomarkers. The aim of the study was to investigate, whether erythropoietin (EPO) is detectable in EBC. EBC was collected from 22 consecutive patients as well as from healthy individuals. Using a multiplex fluorescent bead immunoassay, we detected EPO in EBC, as well as tumour necrosis factor-α (TNF-α) in 13 out of 22 patients simultaneously (EPO 0.21 ± 0.03 in U/mL and TNF-α 34.6 ± 4.2 in pg/mL, mean ± SEM). No significant differences for EPO levels or correlation between EPO and TNF-α were found but TNF-α was significantly higher in patients with chronic obstructive pulmonary disease (COPD) than in non-COPD (obstructive sleep apnoea, OSA, and lung healthy patients). This is the first report of detection of EPO in EBC. Due to the small study size more data is needed to clarify the role of EPO in EBC.