In-plane reorientation induced single laser pulse magnetization reversal.

Single Pulse All Optical Switching represents the ability to reverse the magnetization of a nanostructure using a femtosecond single laser pulse without any applied field. Since the first switching experiments carried out on GdFeCo ferrimagnets, this phenomena has been only recently extended to a few other materials, MnRuGa alloys and Tb/Co multilayers with a very specific range of thickness and composition. Here, we demonstrate that single pulse switching can be obtained for a large range of rare earth-transition metal multilayers, making this phenomenon much more general. Surprisingly, the threshold fluence for switching is observed to be independent of the laser pulse duration. Moreover, at high laser intensities, concentric ring domain structures are induced. These striking features contrast to those observed in Gd based materials pointing towards a different reversal mechanism. Concomitant with the demonstration of an in-plane magnetization reorientation, a precessional reversal mechanism explains all the observed features.

Increased breath naphthalene in children with asthma and wheeze of the All Age Asthma Cohort (ALLIANCE).

Exhaled breath contains numerous volatile organic compounds (VOCs) known to be related to lung disease like asthma. Its collection is non-invasive, simple to perform and therefore an attractive method for the use even in young children. We analysed breath in children of the multicenter All Age Asthma Cohort (ALLIANCE) to evaluate if 'breathomics' have the potential to phenotype patients with asthma and wheeze, and to identify extrinsic risk factors for underlying disease mechanisms. A breath sample was collected from 142 children (asthma: 51, pre-school wheezers: 55, healthy controls: 36) and analysed using gas chromatography-mass spectrometry (GC/MS). Children were diagnosed according to Global Initiative for Asthma guidelines and comprehensively examined each year over up to seven years. Forty children repeated the breath collection after 24 or 48 months. Most breath VOCs differing between groups reflect the exposome of the children. We observed lower levels of lifestyle-related VOCs and higher levels of the environmental pollutants, especially naphthalene, in children with asthma or wheeze. Naphthalene was also higher in symptomatic patients and in wheezers with recent inhaled corticosteroid use. No relationships with lung function or TH2 inflammation were detected. Increased levels of naphthalene in asthmatics and wheezers and the relationship to disease severity could indicate a role of environmental or indoor air pollution for the development or progress of asthma. Breath VOCs might help to elucidate the role of the exposome for the development of asthma. The study was registered at ClinicalTrials.gov (NCT02496468).

Left heart function in COPD : Impact of lung deflation.

Chronic obstructive pulmonary disease (COPD) primarily affects the lungs; however, cardiovascular conditions are among the most common extrapulmonary comorbidities. Besides shared risk factors such as cigarette smoking, pathophysiological connections between the lung and the heart have been identified as mediators of reduced cardiac output. Recent research has focused on hyperinflation of the lung as a pulmonary cause for heart dysfunction. Hyperinflation is a typical lung abnormality seen in COPD; it is characterized by increased residual volume, intrathoracic gas volume, and total lung capacity while vital capacity is decreased. The degree of hyperinflation with airway obstruction is inversely related to left ventricular filling, stroke volume, and cardiac output. The underlying mechanisms are assumed to be compression of the pulmonary veins and thus reduced preload of the left heart as well as decreased pulmonary microvascular blood flow due to compression of the pulmonary vasculature. Treatment with a dual bronchodilator antagonizes this detrimental lung-heart unbalance effectively: Pulmonary blood flow, left ventricular end-diastolic volume, and stroke volume increase in COPD patients without cardiac abnormalities. Similar effects, yet less pronounced, were reported with single bronchodilator therapy. Future work needs to investigate whether these promising findings can be reproduced in COPD patients with cardiovascular diseases.

Breath volatile organic compounds of lung transplant recipients with and without chronic lung allograft dysfunction.

INTRODUCTION: Chronic lung allograft dysfunction with its clinical correlative of bronchiolitis obliterans syndrome (BOS) remains the major limiting factor for long-term graft survival. Currently there are no established methods for the early diagnosis or prediction of BOS. To assess the feasibility of breath collection as a non-invasive tool and the potential of breath volatile organic compounds (VOC) for the early detection of BOS, we compared the breath VOC composition between transplant patients without and different stages of BOS. METHODS: 75 outpatients (25 BOS stage 0, 25 BOS stage 1 + 2, 25 BOS stage 3) after bilateral lung transplantation were included. Exclusion criteria were active smoking, oxygen therapy and acute infection. Patients inhaled room air through a VOC and sterile filter and exhaled into an aluminum reservoir tube. Breath was loaded directly onto Tenax® TA adsorption tubes and was subsequently analyzed by gas-chromatography/mass-spectrometry. RESULTS: The three groups were age and gender matched, but differed with respect to time since transplantation, the spectrum of underlying disease, and treatment regimes. Relative to patients without BOS, BOS stage 3 patients showed a larger number of different VOCs, and more pronounced differences in the level of VOCs as compared to BOS stage 1 + 2 patients. Logistic regression analysis found no differences between controls and BOS 1 + 2, but four VOCs (heptane, isopropyl-myristate, ethyl-acetate, ionone) with a significant contribution to the discrimination between controls and BOS stage 3. A combination of these four VOCs separated these groups with an area under the curve of 0.87. CONCLUSION: Breath sample collection using our reservoir sampler in the clinical environment was feasible. Our results suggest that breath VOCs can discriminate severe BOS. However, convincing evidence for VOCs with a potential to detect early onset BOS is lacking.

Dose-response relationship of a new Timothy grass pollen allergoid in comparison with a 6-grass pollen allergoid.

BACKGROUND: Subcutaneous allergen immunotherapy with grass pollen allergoids has been proven to be effective and safe in the treatment of patients with allergic rhinoconjunctivitis. Based on the extensive cross-reactivity among Pooideae species, it has been suggested that grass pollen extracts could be prepared from a single species, rather than from a multiple species mixture. OBJECTIVE: To find the optimal dose of a Phleum pratense (P. pratense) allergoid preparation and compare its efficacy and safety to a 6-grass pollen allergoid preparation. METHODS: In this double-blind, placebo-controlled study (EudraCT: 2011-000674-58), three doses of P. pratense allergoid (1800 therapeutic units (TU), standard-dose 6000 TU and 18 000 TU) were compared with placebo and the marketed 6-grass pollen allergoid (6000 TU). In a pre-seasonal dosing regimen, 102 patients were randomized to five treatment groups and received nine subcutaneous injections. The primary efficacy endpoint was the change in weal size (late-phase reaction [LPR]) in response to the intracutaneous testing (ICT) before and after treatment, comparing the active allergoids to placebo. Secondary outcomes were the change in Total Nasal Symptom Score (TNSS) assessed in the allergen exposure chamber (AEC), the changes in P. pratense-serum-specific IgG4 and the incidence of adverse events (AEs). RESULTS: All three doses of the P. pratense and the 6-grass pollen allergoid preparations were significantly superior to placebo for the primary outcome, whereas there were no significant differences in the change in TNSS. Compared to the standard-dose, the high-dose of P. pratense did not produce any additional significant benefit, but showed a slight increase in AEs. Yet this increase in AEs was lower than for the 6-grass pollen preparation. CONCLUSIONS & CLINICAL RELEVANCE: The standard-dose of the new P. pratense allergoid was comparable to the marketed 6-grass pollen preparation at equal dose for the parameters measured.

Allergen exposure chambers: harmonizing current concepts and projecting the needs for the future - an EAACI Position Paper.

BACKGROUND: Allergen exposure chambers (AECs) are clinical facilities allowing for controlled exposure of subjects to allergens in an enclosed environment. AECs have contributed towards characterizing the pathophysiology of respiratory allergic diseases and the pharmacological properties of new therapies. In addition, they are complementary to and offer some advantages over traditional multicentre field trials for evaluation of novel therapeutics. To date, AEC studies conducted have been monocentric and have followed protocols unique to each centre. Because there are technical differences among AECs, it may be necessary to define parameters to standardize the AECs so that studies may be extrapolated for driving basic immunological research and for marketing authorization purposes by regulatory authorities. METHODS: For this task force initiative of the European Academy of Allergy and Clinical Immunology (EAACI), experts from academia and regulatory agencies met with chamber operators to list technical, clinical and regulatory unmet needs as well as the prerequisites for clinical validation. RESULTS: The latter covered the validation process, standardization of challenges and outcomes, intra- and interchamber variability and reproducibility, in addition to comparability with field trials and specifics of paediatric trials and regulatory issues. CONCLUSION: This EAACI Position Paper aims to harmonize current concepts in AECs and to project unmet needs with the intent to enhance progress towards use of these facilities in determining safety and efficacy of new therapeutics in the future.

Safety, efficacy and repeatability of a novel house dust mite allergen challenge technique in the Fraunhofer allergen challenge chamber.

BACKGROUND: Efficacy testing of immunotherapy in field studies is often hampered by variation of airborne allergens. Standardized allergen exposure in challenge chamber settings might be an alternative. Therefore, we developed a universal technique to create an atmosphere loaded with allergen particles of adjustable size from aqueous solutions of licensed allergen extracts. OBJECTIVE: The aim of this study was to apply this technique and test the safety and efficacy of challenges with house dust mite (HDM) allergen in the Fraunhofer allergen challenge chamber. METHODS: Aerosol particles carrying HDM allergen were produced by spray-drying of an aqueous solution containing HDM allergen and lactose. In a monocenter, placebo-controlled, single-blind, dose-escalation pilot study, 18 subjects with perennial allergic rhinitis and sensitization to HDM were exposed to HDM allergen for 4 h at either 250, 500, 1000 SQE/m3 or lactose alone (0 SQE/m3 ) 7 days apart. The dose of 500 SQE/m³ was repeated to investigate reproducibility. Total nasal symptom score (TNSS) was the primary endpoint. RESULTS: Exposure to HDM increased TNSS (mean ± SD) to 3.4 ± 1.8, 3.3 ± 2.1, and 3.6 ± 2.0 at 250, 500 and 1000 SQE/m3 , respectively, while lactose alone did not change TNSS (0.7 ± 0.6). The results were reproducible at 500 SQE/m3 . Pulmonary function and adverse event frequency did not change with escalation of allergen dose. CONCLUSION: This HDM allergen particle generation is safe, specific and reproducible and can therefore be used for efficacy testing of immunotherapy and for basic clinical research.

Measurement of exhaled volatile organic compounds from patients with chronic obstructive pulmonary disease (COPD) using closed gas loop GC-IMS and GC-APCI-MS.

Due to its high sensitivity, compact size and low cost ion mobility spectrometry (IMS) has the potential to become a point-of-care breath analyzer. Therefore, we developed a prototype of a compact, closed gas loop IMS with gas chromatographic (GC) pre-separation and high resolving power of R = 90. In this study, we evaluated the performance of this GC-IMS under clinical conditions in a COPD study to find correlations between VOCs (10 ppbv to 1 ppmv) and COPD. Furthermore, in order to investigate possible correlations between ultra-low concentrated breath VOCs (0.1 pptv to 1 ppbv) and COPD, a modified mass spectrometer (MS) with atmospheric pressure chemical ionization (APCI) and GC pre-separation (GC-APCI-MS) was used. The GC-IMS has been used in 58 subjects (21 smokers with moderate COPD, 12 ex-smokers with COPD, 16 healthy smokers and 9 non-smokers). GC-APCI-MS data were available for 94 subjects (21 smokers with moderate COPD, 25 ex-smokers with COPD, 25 healthy smokers and 23 non-smokers). For 44 subjects, a comparison between GC-IMS and GC-APCI-MS data could be performed. Due to service intervals, subject availability and corrupt data, patient numbers were different for GC-APCI-MS and GC-IMS measurements. Using GC-IMS, three VOCs have been found showing a significant difference between healthy controls and patients with COPD. In the GC-APCI-MS data, we only observed one distinctive VOC, which has been identified as 2-pentanone. This proof-of-principle study shows the potential of our high-resolution GC-IMS in the clinical environment. Due to different linear dynamic response ranges, the data of GC-IMS and GC-APCI-MS were only comparable to a limited extent.

A dual center study to compare breath volatile organic compounds from smokers and non-smokers with and without COPD.

There is increasing evidence that breath volatile organic compounds (VOC) have the potential to support the diagnosis and management of inflammatory diseases such as COPD. In this study we used a novel breath sampling device to search for COPD related VOCs. We included a large number of healthy controls and patients with mild to moderate COPD, recruited subjects at two different sites and carefully controlled for smoking. 222 subjects were recruited in Hannover and Marburg, and inhaled cleaned room air before exhaling into a stainless steel reservoir under exhalation flow control. Breath samples (2.5 l) were continuously drawn onto two Tenax(®) TA adsorption tubes and analyzed in Hannover using thermal desorption-gas chromatography-mass spectrometry (TD-GC-MS). Data of 134 identified VOCs from 190 subjects (52 healthy non-smokers, 52 COPD ex-smokers, 49 healthy smokers, 37 smokers with COPD) were included into the analysis. Active smokers could be clearly discriminated by higher values for combustion products and smoking related VOCs correlated with exhaled carbon monoxide (CO), indicating the validity of our data. Subjects from the study sites could be discriminated even after exclusion of cleaning related VOCs. Linear discriminant analysis correctly classified 89.4% of COPD patients in the non/ex-smoking group (cross validation (CV): 85.6%), and 82.6% of COPD patients in the actively smoking group (CV: 77.9%). We extensively characterized 134 breath VOCs and provide evidence for 14 COPD related VOCs of which 10 have not been reported before. Our results show that, for the utilization of breath VOCs for diagnosis and disease management of COPD, not only the known effects of smoking but also site specific differences need to be considered. We detected novel COPD related breath VOCs that now need to be tested in longitudinal studies for reproducibility, response to treatment and changes in disease severity.

Inter- and intrasubject variability of the inflammatory response to segmental endotoxin challenge in healthy volunteers.

Segmental endotoxin challenge with lipopolysaccharide (LPS) can be used as a pharmacodynamic model to safely induce a transient airway inflammation in the peripheral lung of healthy subjects and to test the anti-inflammatory efficacy of investigational new drugs. In contrast to whole lung LPS challenge only a fraction of the dose is required that can be precisely administered to a specific lung region and a vehicle challenged segment as an intra-subject control can be included. The aim of this study was to assess the intra- and inter-individual variability of the response to segmental LPS challenge for the appropriate design and power calculation of future clinical trials. Two cohorts with 10 subjects each underwent two segmental LPS challenges within five weeks. The inflammatory response was evaluated in bronchoalveolar lavage (BAL) fluid at 6 (cohort 1) and 24 h (cohort 2) both in the LPS and in a vehicle challenged segment, as well as in plasma for up to 26 h post LPS challenge. While the cytokine response was more pronounced at 6 h, the influx of neutrophils and monocytes dominated at 24 h; e.g. neutrophils increased from a median (inter-quartile range, IQR) of 0.14 (0.16) and 0.09 (0.08)x10(4) cells/mL BAL fluid at baseline to 10.2 (17.1) and 19.3 (15.9)x10(4) cells/mL 24 h after the two separate challenges. The within-subject variability was higher than the between-subject variability for most of the markers. However, sample size estimations based on the variability of outcome variables found lower or equal numbers with cross-over designs compared to parallel group designs for cellular markers at 24 h and cytokine variables at 6 h. The segmental LPS challenge model was safe. Future study designs have to balance between burden to the study subjects (4 versus 2 bronchoscopies), variability (within-versus between-subject), and the desired outcome variable (cells versus chemo/cytokine).

Efficacy and safety of inhaled calcium lactate PUR118 in the ozone challenge model--a clinical trial.

BACKGROUND: The ozone challenge model can be used to assess the efficacy of anti-inflammatory compounds in early phases of clinical drug development. PUR118, a calcium salt based formulation engineered in the iSPERSE(TM) dry powder delivery technology, is a novel anti-inflammatory drug for COPD. Here we evaluated the efficacy and safety of three doses of PUR118 in attenuating ozone-induced airway inflammation in healthy volunteers. METHODS: In a single-blind, phase 1B proof of concept study, 24 subjects were enrolled to sequentially receive three doses of PUR118 (5.5 mg, n = 18; 11.0 mg, n = 18; 2.8 mg, n = 16). Each dose was inhaled 3 times (1, 13, 25 h, preceded by 2 puffs salbutamol) before the ozone exposure (250 ppb, 3 h intermittent exercise). Sputum was induced 3 h after the end of exposure. RESULTS: Sputum neutrophils, sputum CD14+ cells, as well as concentrations of IL1B, IL6, IL8, MMP9, and TNFA in sputum supernatant significantly increased after ozone exposure (n = 24). The percentage of sputum neutrophils (n = 12 who completed all treatments) did not change following treatment with different doses of PUR118. The high dose treatment group (n = 16) showed a decrease in the percentage and number of sputum macrophages (p ≤ 0.05) as well as a decrease in blood neutrophils (p = 0.04), and an increase in blood CD14 + cells (p = 0.04) compared to baseline. All dosages of PUR118 were safe and well tolerated. CONCLUSION: Ozone challenge resulted in the expected and significant increase of sputum inflammatory parameters. Treatment with multiple rising doses of PUR118 was safe and three applications within 25 h prior to the ozone challenge had small effects on ozone-induced airway inflammation. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01690949. Registered 12 September 2012.

Childhood asthma is associated with mutations and gene expression differences of ORMDL genes that can interact.

BACKGROUND: Genomewide association studies identified ORMDL3 as a plausible asthma candidate gene. ORMDL proteins regulate sphingolipid metabolism and ceramide homeostasis and participate in lymphocyte activation and eosinophil recruitment. Strong sequence homology between the three ORMDL genes and ORMDL protein conservation among different species suggest that they may have shared functions. We hypothesized that if single nucleotide polymorphisms (SNPs) in ORMDL3 alter its gene expression and play a role in asthma, variants in ORMDL1 and ORMDL2 might also be associated with asthma. METHODS: Asthma associations of 44 genotyped SNPs were determined in at least 1303 subjects (651 asthmatics). ORMDL expression was evaluated in peripheral blood mononuclear cells (PBMC) from 55 subjects (eight asthmatics) before and after allergen stimulation, and in blood (n = 60, 5 asthmatics). Allele-specific cis-effects on ORMDL expression were assessed. Interactions between human ORMDL proteins were determined in living cells. RESULTS: Sixteen SNPs in all three ORMDLs were associated with asthma (14 in ORMDL3). Baseline expression of ORMDL1 (P = 1.7 × 10(-6) ) and ORMDL2 (P = 4.9 × 10(-5) ) was significantly higher in PBMC from asthmatics, while induction of ORMDLs upon stimulation was stronger in nonasthmatics. Disease-associated alleles (rs8079416, rs4795405, rs3902920) alter ORMDL3 expression. ORMDL proteins formed homo- and heterooligomers and displayed similar patterns of interaction with SERCA2 and SPT1. CONCLUSIONS: Polymorphisms in ORMDL genes are associated with asthma. Asthmatics exhibit increased ORMDL levels, suggesting that ORMDLs contribute to asthma. Formation of heterooligomers and similar interaction patterns with proteins involved in calcium homeostasis and sphingolipid metabolism could indicate shared biological roles of ORMDLs, influencing airway remodeling and hyperresponsiveness.

Cardiac safety of tiotropium in patients with COPD: a combined analysis of Holter-ECG data from four randomised clinical trials.

BACKGROUND: Tiotropium is generally well tolerated; however, there has been debate whether antimuscarinics, particularly tiotropium administered via Respimat(®) Soft Mist(™) Inhaler, may induce cardiac arrhythmias in a vulnerable subpopulation with cardiovascular comorbidity. The aim of this study was to provide evidence of the cardiac safety of tiotropium maintenance therapy. METHODS: Combined analysis of Holter electrocardiogram (ECG) data from clinical trials of tiotropium in chronic obstructive pulmonary disease (COPD). Trials in the Boehringer Ingelheim clinical trials database conducted between 2003 and 2012, involving tiotropium HandiHaler(®) 18 µg and/or tiotropium Respimat(®) (1.25-, 2.5-, 5.0- and 10-µg doses) were reviewed. All trials involving Holter-ECG monitoring during this period were included in the analysis. Men and women aged ≥ 40 years with a smoking history of ≥ 10 pack-years, and a clinical diagnosis of COPD were included. Holter ECGs were evaluated for heart rate (HR), supraventricular premature beats (SVPBs), ventricular premature beats (VPBs) and pauses. Quantitative and categorical end-points were derived for each of the Holter monitoring days. RESULTS: Four trials (n = 727) were included in the analysis. Respimat(®) (1.25-10 µg) or HandiHaler(®) (18 µg) was not associated with changes in HR, SVPBs, VPBs and pauses compared with placebo or the pretreatment baseline period. In terms of cardiac arrhythmia end-points, there was no evidence for an exposure-effect relationship. CONCLUSIONS: In this analysis, tiotropium maintenance therapy administered using Respimat(®) (1.25-10 µg) or HandiHaler(®) (18 µg) once daily for periods of up to 48 weeks was well tolerated with no increased risk of cardiac arrhythmia in patients with COPD.

Pharmacokinetics and pharmacodynamics of tiotropium solution and tiotropium powder in chronic obstructive pulmonary disease.

The aim of the study was to characterize pharmacokinetics of tiotropium solution 5 µg compared to powder 18 µg and assess dose-dependency of tiotropium solution pharmacodynamics in comparison to placebo. In total 154 patients with chronic obstructive pulmonary disease (COPD) were included in this multicenter, randomized, double-blind within-solution (1.25, 2.5, 5 µg, and placebo), and open-label powder 18 µg, crossover study, including 4-week treatment periods. Primary end points were peak plasma concentration (Cmax,ss ), and area under the plasma concentration-time profile (AUC0-6h,ss ), both at steady state. The pharmacodynamic response was assessed by serial spirometry (forced expiratory volume in 1 second/forced vital capacity). Safety was evaluated as adverse events and by electrocardiogram/Holter. Tiotropium was rapidly absorbed with a median tmax,ss of 5-7 minutes postdosing for both devices. The gMean ratio of solution 5 µg over powder 18 µg was 81% (90% confidence interval, 73-89%) for Cmax,ss and 76% (70-82%) for AUC0-6h,ss , indicating that bioequivalence was not established. Dose ordering for bronchodilation was observed. Powder 18 µg and solution 5 µg were most effective, providing comparable bronchodilation. All treatments were well tolerated with no apparent relation to dose or device. Comparable bronchodilator efficacy to powder18 µg at lower systemic exposure supports tiotropium solution 5 µg for maintenance treatment of COPD.

[Pediatrics]. / Pédiatrie.

Several preliminary studies suggest that prophylactic administration of probiotics reduces the incidence of necrotizing enterocolitis (NEC) in preterm infants, and several neonatology units have introduced this treatment under strict surveillance. Nonetheless, breast milk feeding remains the mainstay of NEC prevention. The beta-blocker propranolol, known for its effectiveness on cutaneous hemangiomas, is also proving useful for the treatment of subglottic or visceral hemangiomas. Following the decrease in severe bacterial infections thanks to widespread vaccinations, the McCarthy clinical score has regained importance in the prediction of the risk of bacterial infection in febrile infants. It is easy to use, economical, and has a diagnostic value comparable to laboratory tests. The new WHO growth charts have been introduced in Switzerland in 2011 to take into account the increasing regional and ethnic variations in our country. Any significant change in growth velocity should prompt an evaluation of the need of further investigations.

The NKT cell ligand αgalactosylceramide suppresses allergic airway inflammation by induction of a Th1 response.

One experimental approach for the treatment of allergic reactions is the stimulation of immunoregulatory NKT cells with the synthetic glycolipid αgalactosylceramide. For a first evaluation of the immunomodulatory potential of αGalCerMPEG a human in vitro allergy model was exploited. Acting as an adjuvant, the glycolipid induced an enhanced Th1-biased allergen-specific immune response of autologous lymphocytes. In a mouse model of allergic airway inflammation, αGalCerMPEG-activated NKT cells promoted a cytokine environment in the spleen, leading to priming of Th1 cells. The shift towards a Th1-dominated allergen-specific immune response thus might mediate the abrogation of allergic airway inflammation and thereby might provide a valid option for therapeutic intervention.

[Comparison of four identical electronic noses and three measurement set-ups]. / Vergleich von vier baugleichen elektronischen Nasen und drei Messaufbauten.

BACKGROUND: Volatile organic compounds (VOCs) can be used as biomarkers in exhaled air. VOC profiles can be detected by an array of nanosensors of an electronic nose. These profiles can be analysed using bioinformatics. It is, however, not known whether different devices of the same model measure identically and to which extent different set-ups and the humidity of the inhaled air influence the VOC profile. METHODS: Three different measuring set-ups were designed and three healthy control subjects were measured with each of them, using four devices of the same model (Cyranose 320™, Smiths Detection). The exhaled air was collected in a plastic bag. Either ambient air was used as reference (set-up Leipzig), or the reference air was humidified (100% relative humidity) (set-up Marburg and set-up Munich). In the set-up Marburg the subjects inhaled standardised medical air (Aer medicinalis Linde, AGA AB) out of a compressed air bottle through a demand valve; this air (after humidification) was also used as reference. In the set-up Leipzig the subjects inhaled VOC-filtered ambient air, in the set-up Munich unfiltered room air. The data were evaluated using either the real-time data or the changes in resistance as calculated by the device. RESULTS: The results were clearly dependent on the set-up. Apparently, humidification of the reference air could reduce the variance between devices, but this result was also dependent on the evaluation method used. When comparing the three subjects, the set-ups Munich and Marburg mapped these in a similar way, whereas not only the signals but also the variance of the set-up Leipzig were larger. CONCLUSION: Measuring VOCs with an electronic nose has not yet been standardised and the set-up significantly affects the results. As other researchers use further methods, it is currently not possible to draw generally accepted conclusions. More systematic tests are required to find the most sensitive and reliable but still feasible set-up so that comparability is improved.

[Smelling diseases? A short review on electronic noses]. / Krankheiten erriechen? Eine kurze Übersicht über elektronische Nasen.

Non-invasive pulmonary diagnostics is a promising and interesting field in respiratory medicine. Beside exhaled breath condensate, there is an increasing interest in alternative and faster techniques such as electronic noses (EN). EN aim to mimic or improve the sense of smelling. Different types of EN have been employed in research so far. In addition to ion mobility spectrometry and mass spectrometry, ENs that consist of various biopolymer sensors for the sensing of volatile organic compounds (VOCs) have been tested. VOCs bind to the sensors depending on size, structure, hydrogen binding and polarity. This leads to physical alterations, e. g., swelling resulting in a change of resistance. The smell print represents composite patterns in contrast to single compounds, and the distinction between different categories is achieved by pattern recognition algorithms. Other types of EN like mass spectrometry and ion mobility spectrometry are capable of identifying even single analyte fractions provided that their characteristics have been saved in data repositories. The non-invasive nature, onsite availability and relatively cheap sampling are advantages of ENs that underly the increasing interest in their use for medical purposes. Some promising results have already been published. This review aims to describe the state of the art in brief form.