Millimeter-wave gas spectroscopy for breath analysis of COPD patients in comparison to GC-MS

The analysis of human breath is a very active area of research, driven by the vision of a fast, easy, and non-invasive tool for medical diagnoses at the point of care. Millimeter-wave gas spectroscopy (MMWGS) is a novel, well-suited technique for this application as it provides high sensitivity, specificity and selectivity. Most of all, it offers the perspective of compact low-cost systems to be used in doctors' offices or hospitals. In this work, we demonstrate the analysis of breath samples acquired in a medical environment using MMWGS and evaluate validity, reliability, as well as limitations and perspectives of the method. To this end, we investigated 28 duplicate samples from chronic obstructive lung disease patients and compared the results to gas chromatography-mass spectrometry (GC-MS). The quantification of the data was conducted using a calibration-free fit model, which describes the data precisely and delivers absolute quantities. For ethanol, acetone, and acetonitrile, the results agree well with the GC-MS measurements and are as reliable as GC-MS. The duplicate samples deviate from the mean values by only 6% to 18%. Detection limits of MMWGS depend strongly on the molecular species. For example, acetonitrile can be traced down to 1.8 × 10−12 mol by the MMWGS system, which is comparable to the GC-MS system. We observed correlations of abundances between formaldehyde and acetaldehyde as well as between acetonitrile and acetaldehyde, which demonstrates the potential of MMWGS for breath research.Deutsche Forschungsgemeinschafthttp://dx.doi.org/10.13039/501100001659Deutsches Zentrum für Lungenforschunghttp://dx.doi.org/10.13039/501100010564Peer Reviewe

DNA methylation-based classification of sinonasal tumors

The diagnosis of sinonasal tumors is challenging due to a heterogeneous spectrum of various differential diagnoses as well as poorly defined, disputed entities such as sinonasal undifferentiated carcinomas (SNUCs). In this study, we apply a machine learning algorithm based on DNA methylation patterns to classify sinonasal tumors with clinical-grade reliability. We further show that sinonasal tumors with SNUC morphology are not as undifferentiated as their current terminology suggests but rather reassigned to four distinct molecular classes defined by epigenetic, mutational and proteomic profiles. This includes two classes with neuroendocrine differentiation, characterized by IDH2 or SMARCA4/ARID1A mutations with an overall favorable clinical course, one class composed of highly aggressive SMARCB1-deficient carcinomas and another class with tumors that represent potentially previously misclassified adenoid cystic carcinomas. Our findings can aid in improving the diagnostic classification of sinonasal tumors and could help to change the current perception of SNUCs

DNA methylation-based classification of sinonasal tumors

The diagnosis of sinonasal tumors is challenging due to a heterogeneous spectrum of various differential diagnoses as well as poorly defined, disputed entities such as sinonasal undifferentiated carcinomas (SNUCs). In this study, we apply a machine learning algorithm based on DNA methylation patterns to classify sinonasal tumors with clinical-grade reliability. We further show that sinonasal tumors with SNUC morphology are not as undifferentiated as their current terminology suggests but rather reassigned to four distinct molecular classes defined by epigenetic, mutational and proteomic profiles. This includes two classes with neuroendocrine differentiation, characterized by IDH2 or SMARCA4/ARID1A mutations with an overall favorable clinical course, one class composed of highly aggressive SMARCB1-deficient carcinomas and another class with tumors that represent potentially previously misclassified adenoid cystic carcinomas. Our findings can aid in improving the diagnostic classification of sinonasal tumors and could help to change the current perception of SNUCs

A randomized cross-over trial on the direct effects of oxygen supplementation therapy using different devices on cycle endurance in hypoxemic patients with Interstitial Lung Disease.

BackgroundIn patients with interstitial lung disease (ILD) a cardinal feature is exercise intolerance, often associated with significant dyspnea and severe hypoxemia. Supplemental oxygen therapy may be offered during exercise. The Oxymizer is a nasal cannula with an incorporated reservoir with the potential to deliver higher oxygen doses to the patient.ObjectiveThe primary aim was to investigate the effect of supplemental oxygen delivered via Oxymizer compared to a conventional nasal cannula (CNC) in patients with ILD during constant work rate tests (CWRT). Secondary aim was to evaluate effects on oxygen saturation (SpO2), dyspnea and heart rate at isotime.MethodsIn this randomized crossover study 24 ILD patients established on long-term oxygen treatment were included. Patients performed four cycling CWRT at 70% of their peak work rate; twice with the Oxymizer and twice with the CNC.ResultsTwenty-one patients finished all CWRTs (age 60 ± 10.9 years, VC 55.4 ± 23.0%predicted). Cycle endurance time was significantly higher while using the Oxymizer compared to CNC (718 ± 485 vs. 680 ± 579 seconds, p = 0.02), and SpO2 at isotime was significantly higher while using the Oxymizer (85.5 ± 6.7 vs. 82.8± 7.2, p = 0.01). Fifteen of the 21 (71%) patients cycled longer with the Oxymizer. There were no significant differences for dyspnea and heart rate.ConclusionsSupplemental oxygen provided by the Oxymizer significantly, but modestly, improved cycle endurance time and SpO2 at isotime in ILD patients compared to CNC

Whole-body vibration training versus conventional balance training in patients with severe COPD—a randomized, controlled trial

Background!#!Whole-body vibration training (WBV) performed on a vibration platform can significantly improve physical performance in patients with chronic obstructive pulmonary disease. It has been suggested that an important mechanism of this improvement is based on an improvement in balance. Therefore, the aim of this study was to investigate the effects of WBV compared to conventional balance training.!##!Methods!#!48 patients with severe COPD (FEV!##!Results!#!Static balance performance improved significantly more (p = 0.032) in favor of WBV (path length during semi-tandem stand: - 168 ± 231 mm vs. + 1 ± 234 mm). Muscular power also increased significantly more (p = 0.001) in the WBV group (+ 2.3 ± 2.5 W/kg vs. - 0.1 ± 2.0 W/kg). 6MWD improved to a similar extent in both groups (WBV: 48 ± 46 m, p < 0.001 vs. BAL: 38 ± 32 m; p < 0.001) whereas the 4MGST increased significantly only in the WBV-group (0.08 ± 0.14 m/s!##!Conclusions!#!WBV can improve balance performance and muscular power significantly more compared to conventional balance training.!##!Trial registration!#!Clinical-Trials registration number: NCT03157986; date of registration: May 17, 2017. https://clinicaltrials.gov/ct2/results?cond=&term=NCT03157986&cntry=&state=&city=&dist  = 

Transcutaneous carbon-dioxide partial pressure trends during six-minute walk test in patients with very severe COPD

Background: Transcutaneous carbon-dioxide partial-pressure (TCPCO2) can be reliably measured and may be of clinical relevance in COPD. Changes in TCPCO2 and exercise-induced hypercapnia (EIH) during six-minute walk test (6MWT) need further investigation. We aimed (1) to define patterns of TCPCO2 trends during 6MWT and (2) to study determinants of CO2-retention and EIH. Methods: Sixty-two COPD patients (age: 63 +/- 8years, FEV1: 33 +/- 10%pred.) were recruited and T(C)PCO2 was recorded by SenTec digital-monitoring-system during 6MWT. Results: Half of patients (50%) exhibited CO2-retention (TCPCO2 [Delta] >4 mmHg); 26% preserved and 24% reduced TCPCO2. Nineteen (31%) patients presented EIH (TCPCO2 >45 mmHg). EIH was associated to higher baseline-PCCO2, worse FEV1, lower inspiratory-pressures, underweight/normal BMI, and pre-walk dyspnea. Stronger determinants of CO2-retention were FEV1 and pre-walk dyspnea, whereas baseline-PCCO2 and pre-walk dyspnea better predict EIH. Conclusions: PCO2 response to 6MWT is highly heterogeneous; however, very low FEV1 and elevated baseline-PCCO2 together with pre-walk dyspnea increase the risk for CO2-retention and EIH. Overweight-BMI seems to carry a protective effect against EIH in very severe COPD

High-intensity non-invasive ventilation during exercise-training versus without in people with very severe COPD and chronic hypercapnic respiratory failure: a randomised controlled trial

Background People with very severe chronic obstructive pulmonary disease (COPD) using nocturnal non-invasive ventilation (NIV) for chronic hypercapnic respiratory failure (CHRF) experience reduced exercise capacity and severe dyspnoea during exercise training (ET). The use of NIV during ET can personalise training during pulmonary rehabilitation (PR) but whether high-intensity NIV (HI-NIV) during exercise is accepted and improves outcomes in these extremely physically limited patients is unknown. The aim of this trial was to determine if ET with HI-NIV during PR was more effective than without at improving exercise capacity and reducing dyspnoea during exercise.Methods Patients with COPD, CHRF and nocturnal-NIV were randomised to supervised cycle-ET as part of PR with HI-NIV or without (control). Primary outcome was change in cycle endurance time (ΔCETtime), while secondary outcomes were dyspnoea at isotime during the cycle endurance test and during ET-sessions and for the HI-NIV group, post-trial preferred exercising method.Results Twenty-six participants (forced expiratory volume in 1 s 22±7%pred, PaCO251±7 mm Hg) completed the trial (HI-NIV: n=13, ET: IPAP 26±3/EPAP 6±1 cm H2O; control n=13). At completion of a 3 week ET-programme, no significant between-group differences in ΔCETtime were seen (HI-NIV-control: Δ105 s 95% CI (−92 to 302), p=0.608). Within-group ΔCETtime was significant (HI-NIV: +246 s 95% CI (61 to 432); control: +141 s 95% CI (60 to 222); all p<0.05). The number of responders (Δ>minimal important difference (MID)101 s: n=53.8%) was the same in both groups for absolute ΔCETtime and 69.2% of control and 76.9% of the HI-NIV group had a %change>MID33%.Compared with control, the HI-NIV group reported less isotime dyspnoea (Δ−2.0 pts. 95% CI (−3.2 to −0.8), p=0.005) and during ET (Δ−3.2 pts. 95% CI (−4.6 to −1.9), p<0.001). Most of the HI-NIV group (n=12/13) preferred exercising with NIV.Conclusion In this small group of patients with very severe COPD requiring nocturnal NIV, participation in an ET-programme during PR significantly improved exercise capacity irrespective of HI-NIV use. Reported dyspnoea was in favour of HI-NIV.Trial registration number NCT03803358