Capnovolumetry in combination with clinical history for the diagnosis of asthma and COPD.

Capnovolumetry performed during resting ventilation is an easily applicable diagnostic tool sensitive to airway obstruction. In the present analysis, we investigated in which way capnovolumetric parameters can be combined with basic anamnestic information to support the diagnosis of asthma and COPD. Among 1400 patients of a previous diagnostic study, we selected 1057 patients with a diagnosis of asthma (n = 433), COPD (n = 260), or without respiratory disease (n = 364). Besides performing capnovolumetry, patients answered questions on symptoms and smoking status. Logistic regression analysis, single decision trees (CHAID), and ensembles of trees (random forest) were used to identify diagnostic patterns of asthma and COPD. In the random forest approach, area/volume of phase 3, dyspnea upon strong exertion, s3/s2, and current smoking were identified as relevant parameters for COPD vs control. For asthma vs control, they were wheezing, volume of phase 2, current smoking, and dyspnea at strong exertion. For COPD vs asthma, s3/s2 was the primary criterion, followed by current smoking and smoking history. These parameters were also identified as relevant in single decision trees. Regarding the diagnosis of asthma vs control, COPD vs control, and COPD vs asthma, the area under the curve was 0.623, 0.875, and 0.880, respectively, in the random forest approach. Our results indicate that for the diagnosis of asthma and COPD capnovolumetry can be combined with basic anamnestic information in a simple, intuitive, and efficient manner. As capnovolumetry requires less cooperation from the patient than spirometry, this approach might be helpful for clinical practice.

[Standardization of spirometry: 2015 update. Published by German Atemwegsliga, German Respiratory Society and German Society of Occupational and Environmental Medicine]. / Leitlinie zur Spirometrie. Leitlinie der Deutschen Atemwegsliga, der Deutschen Gesellschaft für Pneumologie und Beatmungsmedizin und der Deutschen Gesellschaft für Arbeitsmedizin und Umweltmedizin zur Spirometrie.

Spirometry is a simple test and considered the gold standard in lung function. An obstructive ventilatory defect is a disproportionate reduction of maximal airflow from the lung in relation to the maximal volume that can be displaced from the lung. It implies airway narrowing and is defined by a reduced FEV1/FVC ratio below the 5th percentile of the predicted value (lower limit of normal, LLN). A restrictive disorder may be suspected when vital capacity (FVC) is reduced and FEV1/FVC is normal. It is definitely proven, however, only by a decrease in TLC below the 5th percentile of predicted value (LLN). The measurement of TLC by body plethysmography is necessary to confirm or exclude a restrictive defect or hyperinflation of the lung when FVC is below the LLN. 2012 a task force of the ERS published new reference values based on 74,187 records from healthy non-smoking males and females from 26 countries. The new reference equations for the 3-95 age range are now available that include appropriate age-dependent mean values and lower limits of normal (LLN). This presentation aims at providing the reader with recommendations dealing with standardization and interpretation of spirometry.

[Lung function diagnostics for the small airways]. / Lungenfunktionsdiagnostik der kleinen Atemwege.

In the recent years growing interest has focused on the involvement of the distal airways (internal diameter < 2 mm) in obstructive lung diseases and other pulmonary conditions. Inflammation in the small airways seems to play a major role in severe and uncontrolled asthma as a major determinant of airflow obstruction. Thus, small airways represent an important target for inhalation therapy. Currently there is no accepted single lung function parameter to detect small airway dysfunction. Various invasive and non-invasive techniques have been described. In future, non-invasive lung function testing will gain more importance. Using spirometry or body plethysmography, lung function parameters such as the ratio of forced vital capacity to slow vital capacity (FVC/SVC) and the residual volume (RV) can provide information about air trapping in small airway disease. Recent data show that techniques such as impulse oscillometry, nitrogen washout testing and analysis of exhaled nitric oxide are promising tools to assess involvement of the small airways. Impulse oscillometry is a sensitive method to calculate peripheral airway resistance, nitrogen washout allows one to detect air trapping and inhomogeneous ventilation in the distal lung, and the alveolar nitric oxide concentration represents a marker of peripheral inflammation. Further studies are needed to validate these functional tests or their combination for diagnosis and assessment of treatment response in pulmonary diseases involving small airways.

Identification of two distinct deleted regions on the short arm of chromosome 1 and rare mutation of the CDKN2C gene from 1p32 in oligodendroglial tumors.

Oligodendroglial tumors frequently show allelic losses on the short arm of chromosome 1. To narrow down the putative tumor suppressor gene site(s) on 1p, we have investigated 35 oligodendrogliomas and 10 mixed gliomas (oligoastrocytomas) for loss of heterozygosity (LOH) at 21 highly polymorphic loci on chromosome 1 (19 loci on 1p and 2 loci on 1q). LOH at loci on 1p was found in 30 of the 45 tumors (67%). Two distinct regions of common allelic loss were identified: a distal region between D1S76 and D1S253 at 1p36.3, and a proximal region between D1S482 and D1S2743 at 1p34-p35. We also analyzed our tumor series for genetic alterations and expression of the cyclin dependent kinase inhibitor gene CDKN2C (p18INK4c) from 1p32. We found 1 recurrent anaplastic oligodendroglioma that carried a somatic CDKN2C mutation at codon 113 (GAA ==> TAA: Glu ==> Stop). The remaining 44 tumors of our series showed neither coding sequence mutations nor homozygous deletions of CDKN2C. Investigation of 35 tumors by differential reverse transcription-PCR revealed expression of CDKN2C transcripts in all instances. Our data thus provide evidence for more than a single oligodendroglioma-associated tumor suppressor gene on 1p and implicate CDKN2C as a candidate tumor suppressor gene altered in a low fraction of oligodendroglial tumors.

Spatially Resolved Observation of Static Magnetic Flux States in YBa2Cu3O7-dgr Grain Boundary Josephson Junctions.

With low-temperature scanning electron microscopy, the magnetic flux states in high critical temperature Josephson junctions have been imaged. The experiments were performed with YBa(2)Cu(3)O(7-delta) thin-film grain boundary Josephson junctions fabricated on [001] tilt SrTiO(3) bicrystals. For applied magnetic fields parallel to the grain boundary plane, which correspond to local maxima of the magnetic field dependence of the critical current, the images clearly show the corresponding magnetic flux states in the grain boundary junction. The spatial modulation of the Josephson current density by the external magnetic field is imaged directly with a spatial resolution of about 1 micrometer.