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.

[Exercise Testing in Respiratory Medicine - DGP Recommendations]. / Belastungsuntersuchungen in der Pneumologie ­ Empfehlungen der Deutschen Gesellschaft für Pneumologie und Beatmungsmedizin e. V.

This document replaces the DGP recommendations published in 1998 and 2013. Based on recent studies and a consensus conference, the indications, choice and performance of the adequate exercise testing method and its necessary technical and staffing setting are discussed. Detailed recommendations are provided: for blood gas analysis and right heart catheterization during exercise, walk tests, spiroergometry, and stress echocardiography. The correct use of different exercise tests is discussed for specific situations in respiratory medicine: exercise induced asthma, obesity, monitoring of rehabilitation or therapeutical interventions, preoperative risk stratification, and evaluation in occupational medicine.

[Clinical classification and initial diagnosis of pulmonary hypertension: recommendations of the Cologne Consensus Conference 2016]. / Klinische Klassifikation der pulmonalen Hypertonie und initiale Diagnostik: Empfehlungen der Kölner Konsensus Konferenz 2016.

The 2015 European Guidelines on Diagnosis and Treatment of Pulmonary Hypertension are also valid for Germany. The guidelines contain detailed information about the clinical classification and diagnosis of pulmonary hypertension, and furthermore provide novel recommendations for risk stratification and follow-up assessments. However, the practical implementation of the European Guidelines in Germany requires the consideration of several country-specific issues and already existing novel data. This requires a detailed commentary to the guidelines, and in some aspects an update already appears necessary. In June 2016, a Consensus Conference organized by the PH working groups of the German Society of Cardiology (DGK), the German Society of Respiratory Medicine (DGP) and the German Society of Pediatric Cardiology (DGPK) was held in Cologne, Germany. This conference aimed to solve practical and controversial issues surrounding the implementation of the European Guidelines in Germany. To this end, a number of working groups was initiated, one of which was specifically dedicated to the clinical classification and initial diagnosis of PH. This article summarizes the results and recommendations of this working group.

[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.

[Prevalence of glaucoma in obstructive sleep apnea]. / Glaukomprävalenz bei obstruktiver Schlafapnoe.

BACKGROUND: A causal relationship between glaucoma and obstructive sleep apnea has been postulated in several clinical studies but also refuted by others. The aim of this study was to determine the prevalence of glaucoma in a cohort of patients with well-established obstructive sleep apnea in comparison to the published data on this topic. METHODS: A total of 100 consecutive patients (male:female 80:20, mean age 59 ± 11 years SD) with polysomnographically established obstructive sleep apnea underwent an ophthalmological examination including tonometry, static perimetry and dilated fundus photography. Visual fields and fundus photographs of the patients were classified as glaucomatous or non-glaucomatous by two independent examiners. RESULTS: The prevalence of glaucoma in the study patients was 2 % which corresponded to the published prevalence of glaucoma in the normal population. Intraocular pressure did not correlate with the respiratory index, body mass index or sex. CONCLUSION: The data from this study shed doubt on a causal relationship between obstructive sleep apnea and glaucoma.

Attenuated allergic airway inflammation in Cd39 null mice.

BACKGROUND: Extracellular Adenosine-5'-Triphosphate (ATP) is known to accumulate in the lung, following allergen challenge, and contributes via activation of purinergic receptors on dendritic cells (DC), to the development of allergic airway inflammation (AAI). Extracellular ATP levels in the airways are normally tightly regulated by CD39. This ectonucleotidase is highly expressed by DC purified from skin (Langerhans cells) and bone marrow, and has been shown to modulate DC adaptive/haptenic immune responses. In this study, we have evaluated the impact of Cd39 deletion and associated perturbation of purinergic signaling in AAI. METHODS: Standard ovalbumin (OVA)-alum and house dust mite (HDM) bone marrow-derived DC (BMDC)-dependent models of AAI were used to study effects of Cd39. Migration assays, time lapse microscopy, and T-cell priming assays were further used to determine functional relevance of Cd39 expression on BMDC in the setting of immune and Th2-mediated responses in these models. RESULTS: Cd39(-/-) mice exhibited marked increases in BALF ATP levels but paradoxically exhibited limited AAI in both OVA-alum and HDM models. These pathophysiological abnormalities were associated with decreased myeloid DC activation and chemotaxis toward ATP, and were linked to purinergic receptor desensitization responses. Further, Cd39(-/-) DCs exhibited limited capacity to both prime Th2 responses and form stable immune synaptic interactions with OVA-transgenic naïve T cells. CONCLUSIONS: Cd39-deficient DCs exhibit limited capacity to induce Th2 immunity in a DC-driven model of AAI in vivo. Our data demonstrate a role of CD39 and perturbed purinergic signaling in models of AAI.

[Exercise testing in respiratory medicine]. / Belastungsuntersuchungen in der Pneumologie.

This document replaces the DGP recommendations published in 1998. Based on recent studies and a consensus conference, the indications, choice and performance of the adequate exercise testing method in its necessary technical and staffing setting are discussed. Detailed recommendations are provided: for arterial blood gas analysis and right heart catherterization during exercise, 6-minute walk test, spiroergometry, and stress echocardiography. The correct use of different exercise tests is discussed for specific situations in respiratory medicine: exercise induced asthma, monitoring of physical training or therapeutical interventions, preoperative risk stratification, and evaluation in occupational medicine.

Body plethysmography--its principles and clinical use.

Body plethysmography allows to assess functional residual capacity (FRC(pleth)) and specific airway resistance (sRaw) as primary measures. In combination with deep expirations and inspirations, total lung capacity (TLC) and residual volume (RV) can be determined. Airway resistance (Raw) is calculated as the ratio of sRaw to FRC(pleth). Raw is a measure of airway obstruction and indicates the alveolar pressure needed to establish a flow rate of 1 L s(-1). In contrast, sRaw can be interpreted as the work to be performed by volume displacement to establish this flow rate. These measures represent different functional aspects and should both be considered. The measurement relies on the fact that generation of airflow needs generation of pressure. Pressure generation means that a mass of air is compressed or decompressed relative to its equilibrium volume. This difference is called "shift volume". As the body box is sealed and has rigid walls, its free volume experiences the same, mirror image-like shift volume as the lung. This shift volume can be measured via the variation of box pressure. The relationship between shift volume and alveolar pressure is assessed in a shutter maneuver, by identifying mouth and alveolar pressure under zero-flow conditions. These variables are combined to obtain FRC(pleth), sRaw and Raw. This presentation aims at providing the reader with a thorough and precise but non-technical understanding of the working principle of body plethysmography. It also aims at showing that this method yields significant additional information compared to spirometry and even bears a potential for further development.

[Non-invasive diagnosis of pulmonary hypertension: ESC/ERS Guidelines with commentary of the Cologne Consensus Conference 2010]. / Nicht-invasive Diagnostik der pulmonalen Hypertonie: ESC/ERS-Leitlinien mit Kommentierung der Kölner Konsensus-Konferenz 2010.

The 2009 European Guidelines on Diagnosis and Treatment of Pulmonary Hypertension have been adopted for Germany. The guidelines contain detailed recommendations for the diagnosis of pulmonary hypertension. However, the practical implementation of the European Guidelines in Germany requires the consideration of several country-specific issues and already existing novel data. This requires a detailed commentary to the guidelines, and in some aspects an update y appears necessary. In June 2010, a Consensus Conference organized by the PH working groups of the German Society of Cardiology (DGK), the German Society of Respiratory Medicine (DGP) and the German Society of Pediatric Cardiology (DGPK) was held in Cologne, Germany. This conference aimed to solve practical and controversial issues surrounding the implementation of the European Guidelines in Germany. To this end, a number of working groups was initiated, one of which was specifically dedicated to non-invasive diagnosis of PH. This commentary summarizes the results and recommendations of the working group on treatment of PAH.

Iloprost has potent anti-inflammatory properties on human monocyte-derived dendritic cells.

BACKGROUND: The stable prostaglandin I2 analogue (iloprost) iloprost has been shown to inhibit allergic airway inflammation in mice by modulating the function of myeloid dendritic cells (DCs). OBJECTIVE: The aim of the current study was to investigate the biological activity of iloprost on human monocyte-derived DCs. METHODS: I prostanoid (IP) receptor expression was analysed by RT-PCR. Cytokine secretion by DCs and CD4+ T cells was measured by ELISA. The expression of the transcription factor FoxP3 after co-culture of DCs with CD4+ CD45RA+ T cells was analysed by flow cytometry. RESULTS: Human monocyte-derived DCs were found to express mRNA specific for the PGI2 receptor IP, and stimulation with iloprost resulted in increased cyclic AMP levels in both immature DCs (iDCs) and mature DCs (mDCs). Moreover, iloprost dose dependently inhibited the secretion of TNF-alpha, IL-6, IL-8 and IL-12p70 in mDCs, while it enhanced IL-10 production. Changes in cytokine secretion were paralleled by an altered T-cell priming capacity of DCs: in co-culture experiments of iloprost-treated mDC and naïve CD45RA+ T cells, an induction of regulatory T cells could be observed, as demonstrated by increased intracellular FoxP3 expression and IL-10 production. Additionally, iloprost inhibited the MIP-3beta-induced migration of mDCs. CONCLUSION: In summary, our results provide evidence that iloprost profoundly affects the function of human myeloid DCs. Therefore, iloprost might also be a new therapeutical option for the treatment of asthma in humans.

Local administration of uridine suppresses the cardinal features of asthmatic airway inflammation.

BACKGROUND: The immuno-modulatory properties of nucleotides such as adenosine or inosine, have been described extensively. Recently, the nucleoside uridine and its analogue 4-thiouridine have gained attention for their protective role in acute lung inflammation. OBJECTIVE: In this study, we investigated the influence of uridine on asthmatic airway inflammation. METHODS: We used the classical ovalbumin (OVA)-alum model, as well as a model of house dust mite-(HDM)-induced airway inflammation. The degree of inflammation was determined by bronchoalveolar lavage (BAL), histology, and measurement of bronchial hyperresponsiveness. RESULTS: Intratracheal treatment of OVA-sensitized animals with uridine before allergen challenge resulted in a reduction in total BAL cells and BAL eosinophils. This was accompanied by reduced tissue infiltration and diminished production of T helper type 2-cytokines by mediastinal lymph node cells. Additionally, mice treated with uridine developed less bronchial hyperresponsiveness. Uridine was also effective in reducing airway inflammation in HDM-induced asthma. The protective effects of uridine were independent of myeloid dendritic cell (mDC) function, because in vitro pre-treatment of allergen-pulsed DCs with uridine did not alter the degree of inflammation. However, uridine inhibited the release of pro-inflammatory mediators in vivo and by cultured lung epithelial cells, suggesting an effect on lung structural cells. CONCLUSION: In summary, we were able to show that uridine inhibits the classical features of asthmatic airway inflammation. As uridine supplementation is well tolerated in humans, it might be a new therapeutic approach for the treatment of bronchial asthma.

[Lung function]. / Lungenfunktion.

The term lung function is often restricted to the assessment of volume time curves measured at the mouth. Spirometry includes the assessment of lung volumes which can be mobilised with the corresponding flow-volume curves. In addition, lung volumes that can not be mobilised, such as the residual volume, or only partially as FRC and TLC can be measured by body plethysmography combined with the determination of the airway resistance. Body plethysmography allows the correct positioning of forced breathing manoeuvres on the volume-axis, e.g. before and after pharmacotherapy. Adding the CO single breath transfer factor (T(LCO)), which includes the measurement of the ventilated lung volume using He, enables a clear diagnosis of different obstructive, restrictive or mixed ventilatory defects with and without trapped air. Tests of reversibility and provocation, as well as the assessment of inspiratory mouth pressures (PI(max), P(0.1)) help to classify the underlying disorder and to clarify treatment strategies. For further information and to complete the diagnostic of disturbances of the ventilation, diffusion and/or perfusion (capillar-)arterial bloodgases at rest and under physical strain sometimes amended by ergospirometry are recommended. Ideally, lung function measurements are amended by radiological and nuclear medicine techniques.

Compliance in sleep apnoea therapy: influence of home care support and pressure mode.

Continuous positive airway pressure (CPAP) is an effective treatment for obstructive sleep apnoea syndrome (OSAS) but therapy adherence is often low. The hypothesis that CPAP-adherence and clinical outcomes can be improved by either using an autoadjusting-CPAP (APAP) device or an intensive support was tested. A controlled parallel group study was performed with 100 newly diagnosed OSAS patients, randomised into 4 groups (n = 25 each): standard or intensive support plus either APAP or CPAP. Intensive support included education and monthly home visits for 6 months. Clinical outcome was monitored by polysomnography at CPAP initiation and, after 3 and 9 months, compliance data were downloaded from the CPAP devices. After 9 months, intensively supported patients returned for follow-up in 88 versus 68% in the standard-support-group. Daily usage (mean+/-sem 5.7+/-0.2 for intensive support versus 4.6+/-0.4 h for standard support), percentage of days used (80.4+/-2.8 versus 57.0+/-5.9%) and proportion of individual sleep time (80.6+/-3.2 versus 64.9+/-6.2%) were also higher. There was no significant difference between APAP or CPAP, (daily usage 5.2+/-0.4 versus 5.1+/-0.3 h, percentage of days 67.9+/-5.0 versus 69.2+/-4.9%, proportion of sleep time 72.5+/-5.0% versus 72.1+/-5.2%, for APAP and CPAP) but retention rate was higher with CPAP. In summary, intensive support after continuous positive airway pressure initiation, rather than the application of autoadjusting-continuous positive airway pressure, increased therapy adherence.

Lung hyperinflation: foe or friend?

Breath-hold divers employ glossopharyngeal insufflation (GI) in order to prevent the lungs from compressing at great depth and to increase intrapulmonary oxygen stores, thus increasing breath-hold time. The presented case study shows the physiological data and dynamic magnetic resonance imaging (dMRI) findings of acute hyperinflation, deliberately induced by GI, in a breath-hold diver and discusses the current state of knowledge regarding the associated hazards of this unique competitive sport. Static and dynamic lung volumes and expiratory flows were within the normal range, with vital capacity and peak expiratory flow being higher than the predicted values. Airway resistance and diffusing capacity of the lung for carbon monoxide were normal. Static compliance was normal and increased five-fold with hyperinflation. dMRI revealed a preserved shape of the thorax and diaphragm with hyperinflation. A herniation of the lung beneath the sternum and enlargement of the costodiaphragmatic angle were additional findings during the GI manoeuvre. After expiration, complete resolution to baseline was demonstrated. Hyperinflation can be physiological and even protective under abnormal physical conditions in the sense of acute adaptation to deep breath-hold diving. Dynamic magnetic resonance imaging is adequate for visualisation of the sequence of the glossopharyngeal insufflation manoeuvre and the complete reversibility of deliberate hyperinflation.

Gas exchange measurements with high temporal resolution: the breath-by-breath approach.

Respiratory gas analysis as an indicator for metabolic strain during exercise has a long history. First introduced in the 18th century, huge gas collectors served for the determination of oxidative energy delivery. While still being accepted as accurate, this particular method delivers data of low temporal resolution only. Further developments of gas analysis techniques therefore focused on a higher density of data. When algorithms became available for indispensable calculations, the so-called "breath-by-breath" (BBB) method was established some decades ago. Thereby, the term BBB in the narrower sense means that a particular physiologic value is determined for each of a subject's single respiratory cycles. Reliable application of this approach depends on the performance of available computer systems, the quality of the analyzing software routines, and the responsiveness of the gas analyzers. Thus, it appears that even nowadays technical progress is continuing in this area. This review describes technical aspects and prerequisites of the BBB approach and its specific areas of application.

Peak or plateau maximal inspiratory mouth pressure: which is best?

There is no clear evidence as to how maximal inspiratory mouth pressure (PI,max) should be measured, although plateau pressures sustained for 1 s and measured at residual volume (RV) are usually recommended. Peak and plateau PI,max were measured at RV and at functional residual capacity (FRC) in 533 healthy subjects (aged 10-90 yrs) in order to comparably test all PI,max measurements for their predictors, reproducibility and normal values. Plateau pressures accounted for 82.0-86.3%, of peak pressures. Peak and plateau pressures measured at FRC accounted for 84.3-90.5% of pressures at RV, and were highly correlated. Age was negatively predictive and weight and body mass index positively predictive of PI,max, but regression parameters were low. All PI,max measurements were comparable when calculating regression parameters, between-subject variability and reproducibility. In conclusion, peak and plateau maximal inspiratory mouth pressure are comparably useful for the assessment of inspiratory muscle strength and can be reliably measured at functional residual capacity and at residual volume. Regression equations are of low impact in predicting normal values due to the weak influence of demographic and anthropometric factors and to the high unexplained between-subject-variability. Age-related 5th percentiles can indicate the lower limit of the normal range.