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The tracking of pathogen burden and host responses with minimal-invasive methods during respiratory infections is central for monitoring disease development and guiding treatment decisions. Utilizing a standardized murine model of respiratory Influenza A virus (IAV) infection, we developed and tested different supervised machine learning models to predict viral burden and immune response markers, i.e. cytokines and leukocytes in the lung, from hematological data. We performed independently in vivo infection experiments to acquire extensive data for training and testing purposes of the models. We show here that lung viral load, neutrophil counts, cytokines like IFN-γ and IL-6, and other lung infection markers can be predicted from hematological data. Furthermore, feature analysis of the models shows that blood granulocytes and platelets play a crucial role in prediction and are highly involved in the immune response against IAV. The proposed in silico tools pave the path towards improved tracking and monitoring of influenza infections and possibly other respiratory infections based on minimal-invasively obtained hematological parameters.

By the end of 2019 a global pandemic by the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV2) causing the coronavirus disease-19 (COVID-19) has emerged. Yet, COVID-19 represents a significant economic burden to healthcare systems, destabilizes global financial markets and has caused the death of almost 5 million people worldwide. In order to prevent severe disease courses of COVID-19 especially in elderly and to establish collective immunity on the long run, different vaccines have been developed, tested and were approved within a very short time period. In Germany, the first vaccines that have been approved by local authorities were AstraZeneca’s vector virus-based vaccine Vaxzevria and the mRNA vaccines Comirnaty and Spikevax, developed by BioNTech and Moderna, respectively. As it was reported that the novel coronavirus SARS-CoV2 can trigger autoimmunity, it is of significant interest to investigate whether anti-SARS-CoV2 vaccines evoke the formation of autoantibodies and subsequent autoimmunity. Here, we did set out to systematically analyze immune responses after homologous vaccinations with mRNA or vector virus-based vaccines or after heterologous Vector/mRNA vaccinations with respect to anti-COVID-19 immune responses and, in parallel, the development of autoantibodies. In our study, we obtained serum samples one day before and 14 as well as 28 days following booster vaccination and tested them for anti-SARS-CoV2 antibodies and for autoantibodies against Cardiolipin, Prothrombin, β2-Glycoprotein, cyclic citrullinated peptides (CCP), tissue-transglutaminase (TTG) and anti-nuclear antibodies (ANA). We find that compared to homologous mRNA and heterologous Vector/mRNA vaccination, anti-SARS-CoV2 antibody levels were 90% lower after homologous vector vaccination. Of note, heterologous Vector/mRNA vaccination was found to be more effective than homologous mRNA vaccination in terms of IgM and IgA responses against SARS-CoV2. However, in terms of autoantibody generation, we only detected increases after booster vaccination in participants with already pre-existing autoantibodies. In contrast, vaccinees showing no autoantibody formation before vaccination, did not respond with sustained autoantibody production upon vaccination. Taken together, our study suggests that all used SARS-CoV2 vaccines do not significantly foster autoantibody production over time but provide humoral immunity to SARS-CoV2.

Allergic asthma is a chronic inflammatory disease caused by immunoglobulin E (IgE)-mediated allergy. Omalizumab is a monoclonal anti-IgE antibody for the treatment of severe allergic asthma (SAA). The primary objective of the study was to assess asthma-related control in patients with SAA receiving omalizumab therapy. Secondary objectives included quality of life, treatment effectiveness, rate of severe exacerbations, and safety. This was a prospective, multi-centre, non-interventional study to assess patient-related long-term outcomes of omalizumab treatment in Germany. This 3-year study enrolled patients aged ≥ 18 years with SAA. Asthma control was assessed using the asthma control questionnaire (ACQ-6) and physician-assessed global evaluation of treatment effectiveness (GETE). Exacerbations were recorded, and quality of life was assessed using the mini-asthma quality of life questionnaire (mini-AQLQ). Of 161 patients screened, 153 participated in this study. Most patients (92.2%) had been receiving prior omalizumab therapy for mean (SD) 2.9 (2.3) years. Omalizumab slightly decreased mean ACQ-6 score from 2.0 (1.22) at baseline to 1.7 (1.23) at the end of the 3-year treatment period [difference: –0.18 (1.07), P = 0.340]. Post-hoc analyses of ACQ-6 for the small number of treatment-naive patients showed a decrease in mean (SD) ACQ-6 from 2.7 (1.08) at baseline to 1.4 (1.40) after 3 years of omalizumab treatment. Mini-AQLQ increased from 4.5 (1.26) at baseline to 4.7 (1.48) after 3 years [difference: 0.26 (1.35), P = 0.186]. GETE was reported as excellent or good for most patients (67.46–84.69%) and more than two-thirds had no severe exacerbation. There were no unexpected safety signals during the study period and no tachyphylaxis was observed. In conclusion, despite most patients receiving prior omalizumab treatment for approximately 3 years, there was no decrease in effectiveness or safety over the subsequent 3 years during this study. This supports the long-term use of omalizumab in maintaining asthma control and quality of life. Novartis Pharma GmbH, Germany.

Specific (s)IgG antibodies against environmental and occupational antigens, especially from bacteria, moulds, yeasts, birds and chemicals play an important role for hypersensitivity pneumonitis (HP). An increased serum level of sIgG is one criterion in the diagnostic procedure of HP and crucial for the detection of the triggering antigen for successful avoidance of further exposure. In contrast to specific IgE, sIgG concentrations in healthy individuals vary greatly depending on the antigen, which makes it difficult to differentiate from patients with HP. The aim of this study is to update or establish sIgG-reference values for important HP antigens in a healthy blood donor group. Therefore a study including six clinical centres in Germany was conducted to collect sera from 121 subjects without any signs of HP and without obvious exposure to potential HP antigens. Specific IgG to 32 typical HP antigens were quantified by ImmunoCAP (ThermoFisher Scientific; Phadia, Uppsala, Sweden). For validation selected measurements were repeated, total IgG was determined, sera were tested for unspecific binding with the human serum albumin ImmunoCAP Ro401, and influence of potential confounders was analysed. Statistical distribution of the antigen-specific IgG values was evaluated and the nonparametric method of percentile calculation was applied. The levels of IgG antibodies to the different antigens varied considerably in the study group from < 0.02 to 726 mgA/L. Low sIgG levels were found against the chemicals and the highest levels to fungal antigens, especially to Aspergillus fumigatus and Botrytis cinerea. For three isocyanates, three acid anhydrides, Trichosporon pullulans and Acremonium kiliense reference values were proposed for the first time. For several avian antigens, moulds, and bacteria pre-existing reference values nearly could be confirmed without significant deviations, but already the 90 % quantile for sIgG against Penicillium chrysogenum, Aspergillus fumigatus and pigeon antigen (Ge91) clearly exceeded the pre-existing values. In contrast, the 97.5 % quantile value for Candida albicans was nearly half of the pre-existing cut-off value. In most cases specific IgG values were not significantly influenced by smoking and gender and most of them were unaffected by age. For implementation of these sIgG reference values into the routine diagnosis of HP, we provide an online available calculator to rank measured sIgG concentrations to the 32 different ImmunoCAP antigens.

ZusammenfassungBei der pulmonalen Hypertonie handelt es sich um eine Druckerhöhung in der Lungenstrombahn, dem sog. kleinen Kreislauf: Der pulmonalarterielle Mitteldruck (Messung im Rechtsherzkatheter) ist auf über 25 mmHg erhöht. Für die Prognose der meist stark beeinträchtigten Patienten ist eine frühe Diagnosestellung extrem wichtig. Der Beitrag widmet sich der Diagnostik, der klinischen Klassifikation und der gruppenspezifischen Therapie der pulmonalen Hypertonie.

Bronchial asthma is one of the most common chronic diseases worldwide and affects more than 300 million patients. Allergic asthma affects the majority of asthmatic children as well as approximately 50% of adult asthmatics. It is characterized by a Th2-mediated immune response against aeroallergens. Many aspects of the overall pathophysiology are known, while the underlying mechanisms and predisposing factors remain largely elusive today. Over the last decade, respiratory colonization with Staphylococcus aureus (S. aureus), a Gram-positive facultative bacterial pathogen, came into focus as a risk factor for the development of atopic respiratory diseases. More than 30% of the world’s population is constantly colonized with S. aureus in their nasopharynx. This colonization is mostly asymptomatic, but in immunocompromised patients, it can lead to serious complications including pneumonia, sepsis, or even death. S. aureus is known for its ability to produce a wide range of proteins including toxins, serine-protease-like proteins, and protein A. In this review, we provide an overview of the current knowledge about the pathophysiology of allergic asthma and to what extent it can be affected by different toxins produced by S. aureus. Intensifying this knowledge might lead to new preventive strategies for atopic respiratory diseases.

PurposeTransport of secretory immunoglobulin A (SIgA) through the airway epithelial cell barrier into the mucosal lumen by the polymeric immunoglobulin receptor (pIgR) is an important mechanism of respiratory mucosal host defense. Identification of immunomodulating substances that regulate secretory immunity might have therapeutic implications with regard to an improved immune exclusion.Thus, we sought to analyze secretory immunity under homeostatic and immunomodulating conditions in different compartments of the murine upper and lower respiratory tract (URT&LRT).MethodsPigrgene expression in lung, trachea, and nasal-associated lymphoid tissue (NALT) of germ-free mice, specific pathogen-free mice, mice with an undefined microbiome, as well as LPS- and IFN-γ-treated mice was determined by quantitative real-time PCR. IgA levels in bronchoalveolar lavage (BAL), nasal lavage (NAL), and serum were determined by ELISA. LPS- and IFN-γ-treated mice were colonized withStreptococcus pneumoniaeand bacterial CFUs were determined in URT and LRT.ResultsRespiratoryPigrexpression and IgA levels were dependent on the degree of exposure to environmental microbial stimuli. While immunostimulation with LPS and IFN-γ differentially impacts respiratoryPigrexpression and IgA in URTvs. LRT, only prophylactic IFN-γ treatment reduces nasal colonization withS. pneumoniae.ConclusionAirway-associated secretory immunity can be partly modulated by exposure to microbial ligands and proinflammatory stimuli. Prophylactic IFN-γ-treatment modestly improves antibacterial immunity in the URT, but this does not appear to be mediated by SIgA or pIgR.

Brain metastases frequently occur during the course of disease in patients suffering from lung cancer. Occasionally, neurological symptoms caused by brain metastases (BM) might represent the first sign of systemic tumor disease (so called precocious metastases), leading to the detection of the primary lung tumor. The biological basis of precocious BM is largely unknown, and treatment options are not well established for this subgroup of patients. Therefore, we retrospectively analyzed 33 patients (24 non-small cell lung cancer (NSCLC)), 9 small cell lung cancer (SCLC)) presenting with precocious BM focusing on molecular alterations potentially relevant for the tumor's biology and treatment. We found five FGFR1 amplifications (4 adenocarcinoma, 1 SCLC) among 31 analyzed patients (16.1%), eight MET amplifications among 30 analyzed tumors (7 NSCLC, 1 SCLC; 26.7%), three EGFR mutations within 33 patients (all adenocarcinomas, 9.1%), and five KRAS mutations among 32 patients (all adenocarcinomas; 15.6%). No ALK, ROS1 or RET gene rearrangements were detected. Our findings suggest that patients with precocious BM of lung cancer harbor EGFR mutations, MET amplifications or FGFR1 amplifications as potential targeted treatment options.

Chronic obstructive airway diseases are characterized by airflow obstruction and airflow limitation as well as chronic airway inflammation. Especially bronchial asthma and chronic obstructive pulmonary disease (COPD) cause considerable morbidity and mortality worldwide, can be difficult to treat, and ultimately lack cures. While there are substantial knowledge gaps with respect to disease pathophysiology, our awareness of the role of neurological and neuro-immunological processes in the development of symptoms, the progression, and the outcome of these chronic obstructive respiratory diseases, is growing. Likewise, the role of pathogenic and colonizing microorganisms of the respiratory tract in the development and manifestation of asthma and COPD is increasingly appreciated. However, their role remains poorly understood with respect to the underlying mechanisms. Common bacteria and viruses causing respiratory infections and exacerbations of chronic obstructive respiratory diseases have also been implicated to affect the local neuro-immune crosstalk. In this review, we provide an overview of previously described neuro-immune interactions in asthma, COPD, and respiratory infections that support the hypothesis of a neuro-immunological component in the interplay between chronic obstructive respiratory diseases, respiratory infections, and respiratory microbial colonization.

Pulmonary diseases can occur across the entire disease spectrum of malignant hematologic systemic diseases. Although infectious processes of the lungs are common in these immunosuppressed patient collectives, noninfectious causes account for up to half of the pulmonary manifestations found in hematologic malignancies. Besides the frequent infections including opportunistic pathogens, a broad differential diagnosis including drug-induced lung injury by cytostatic substances, cytokines, and innovative immunotherapeutic agents, rarer transfusion of blood products and intrathoracic manifestations of the hematologic malignancy itself, have to be kept in mind. Finally, vascular complications can also lead to pulmonary reactions. Early and consistent diagnostics and treatment of the bronchopulmonary, intrathoracic and vascular complications within the framwework of hematologic systemic diseases can be essential for the patient's prognosis.

Purpose The aim of this study was to examine the perception and preference of geriatric patients for commonly used inhaler devices in Germany. Patients and Methods This was a prospective, open-label cross-sectional study with inpatient inhaler-naïve geriatric volunteers (age ≥ 70 years). All 106 participants were interviewed and subjected to a geriatric examination for cognitive, motor and fine motor skills before demonstrating the use of nine inhalers in random order. For each device, patients were asked to test the handling, to assess the device properties and to name the device that they would most or least prefer. Results The mean age of the patients was 80.8 years. From a selection of 7 predefined general inhaler attributes, ease of use, discrete handling and inhalation resistance were the most important for the geriatric participants. Across all inhaler devices, the volunteers needed an average of 2.47 attempts to error-free use. The device with the lowest mean number of attempts was the Nexthaler® (1.75; SD ± 0.903), followed by Spiromax® (1.96; SD ± 0.965) and Genuair® (2.05; SD ± 1.027). There was a weak to moderate correlation between the number of attempts required to ensure the correct use of these three inhalers and the patient’s cognitive and fine motor skills. Fifty-nine patients (56%) chose the Nexthaler as the inhalation device that they would most prefer (p

Zusammenfassung In der Therapie rheumatischer Erkrankungen kommen zahlreiche verschiedene Medikamente zum Einsatz, die potenziell pneumotoxisch sein können. Medikamentennebenwirkungen an den Atmungsorganen können vielfältige bronchopulmonale Erkrankungen induzieren. Sie können vital bedrohlich verlaufen. Selten liegt ein pathognomonisches Muster vor, sodass medikamenteninduzierte Erkrankungen eine Differenzialdiagnose von pulmonalen Manifestationen der rheumatischen Grunderkrankung, Infektionen und anderen genuinen pneumologischen Krankheiten darstellen. Die Diagnostik stützt sich vorwiegend auf den Nachweis eines kompatiblen Krankheitsbildes, den Ausschluss von Differenzialdiagnosen, die Bewertung des zeitlichen Zusammenhangs und der Effekte einer Medikamentenkarenz.

Eine Vermehrung der eosinophilen Granulozyten im peripheren Blut und in pulmonalen und extrapulmonalen Geweben kann bei verschiedenartigen bronchopulmonalen und extrapulmonalen Erkrankungen auftreten. Das differenzialdiagnostische Spektrum umfasst vor allem allergische Erkrankungen, Autoimmunerkrankungen, Infektionen, insbesondere Parasitosen, und exogene Noxen, wie z. B. Medikamente. Des Weiteren gibt es idiopathische Formen der eosinophilen Lungenerkrankungen. Es werden das differenzialdiagnostische Spektrum und das Vorgehen zur differenzialdiagnostischen Abklarung einer Eosinophilie dargestellt.

ZusammenfassungBei symptomatischen malignen Pleuraergüssen sollte ein therapeutisches Verfahren gewählt werden, welches die Dyspnoe und die konsekutive Einschränkung der Lebensqualität in der meist palliativen Situation verbessert. Ein dauerhaft implantierter Pleurakatheter (indwelling pleural catheter – IPC) ist eine der aktuell zur Verfügung stehenden Methoden, deren Bedeutung in den letzten Jahren zugenommen hat. Effektivität und Sicherheit dieser Methode sind unter realen klinischen Bedingungen außerhalb von Studien noch unzureichend geklärt. Es wurden die Daten von 94 Patienten, die aus klinischer Indikation mit einem IPC versorgt wurden, retrospektiv analysiert. Ausgewertet wurden neben Sicherheit und Effektivität die Patientencharakteristika, peri- und postinterventionelle Komplikationen, wie Infektionen oder das Auftreten eines Pneumothorax, und der längerfristige Verlauf mit dem Schwerpunkt der Frage, ob eine Pleurodese eingetreten ist. Insgesamt 89,5% (n = 85) der Patienten erhielten den IPC aufgrund eines rezidivierenden Pleuraergusses bei maligner Grunderkrankung. Die mittlere Krankenhausverweildauer nach Implantation lag für diejenigen Patienten, die nicht noch im Krankenhaus an ihrer infausten Erkrankung verstorben sind, bei 3,29 Tagen. Bei 21,2% (n = 20) der Patienten kam es zu einer Pleurodese. Methodenbedingte Komplikationen traten bei 33,7% (n = 32) der Patienten auf, lediglich bei 8 Patienten gab es jedoch weiteren Handlungsbedarf. Spätkomplikationen sind bei 9 Patienten aufgetreten. Die mittlere Überlebenszeit nach Implantation lag bei durchschnittlich 88,72 Tagen. Zusammenfassend zeigen die Daten, dass der IPC eine technisch einfach durchführbare, minimalinvasive Alternative zu rezidivierenden Punktionen oder anderen Pleurodeseverfahren ist. Ein wesentlicher Vorteil ist die ambulante Versorgungsmöglichkeit.

Eosinophils are circulating and tissue-resident leukocytes that have potent proinflammatory effects in a number of diseases. Recently, eosinophils have been shown to have various other functions, including immunoregulation and antiviral activity. Eosinophil levels vary dramatically in a number of clinical settings, especially following eosinophil-targeted therapy, which is now available to selectively deplete these cells. There are key coronavirus disease 2019 (COVID-19)-related questions concerning eosinophils whose answers affect recommended prevention and care. First, do patients with eosinophilia-associated diseases have an altered course of COVID-19? Second, do patients with eosinopenia (now intentionally induced by biological drugs) have unique COVID-19 susceptibility and/or disease course? This is a particularly relevant question because eosinopenia is associated with acute respiratory deterioration during infection with the severe acute respiratory syndrome coronavirus 2, the causative agent of COVID-19. Third, do eosinophils contribute to the lung pathology induced during COVID-19 and will they contribute to immunopotentiation potentially associated with emerging COVID-19 vaccines? Herein, we address these timely questions and project considerations during the emerging COVID-19 pandemic.

Das Asthma bronchiale ist eine heterogene Erkrankung mit einer komplexen molekularen und zellularen Pathophysiologie. Gezielte Eingriffe mit monoklonalen Antikorpern (Biologika) in diese Kaskade aus zahlreichen Zellen, Mediatoren und Zytokinen haben die Behandlung des schweren Asthmas deutlich verbessert. Aktuell stehen Antikorper zur Verfugung, die gegen Immunglobulin E (IgE) und gegen Interleukin-5 (IL-5) gerichtet sind. IgE ist ein zentrales Molekul in der Genese des allergischen Asthmas, es gibt jedoch eine zunehmende Evidenz, dass auch Patienten mit nichtallergischem Asthma von einer Anti-IgE-Therapie profitieren konnen. IL-5 ist essenziell fur die eosinophile Inflammation beim Asthma und eine Anti-IL-5-Therapie ist wirksam bei Patienten mit einem refraktaren eosinophilen Asthma bronchiale. Weitere Biologika werden gegenwartig in klinischen Studien getestet. Nach den aktuellen Therapieempfehlungen und klinischen Standards werden Biologika (aktuell Anti-IgE oder Anti-IL-5) in der Dauertherapie des schweren Asthmas vor einer eventuellen Therapie mit systemischen Glukokortikosteroiden eingesetzt. Der Artikel gibt eine Ubersicht uber den aktuellen Stand der individualisierten Therapie des schweren Asthmas mit Biologika.

Introduction: Due to functional and cognitive impairments of older patients effective inhalation therapy is often limited. The frequency of inhaler technique errors, the association between device type, the patient’s health condition and preferences of 9 inhaler devices were investigated in a geriatric patient population. Methods: Within this industry-independent study of 106 geriatric patients (40 male, 66 female, mean age 80,75 y.) a complete geriatric assessment was performed, including cognitive functioning, visual acuity and motoric skills, since these functions are essential for the correct use of a device. The following devices were tested in randomized order:BreezhalerTM, DiskusTM, MDI, ElpenhalerTM, GenuairTM, NexthalerTM, RespimatTM, SpiromaxTM and TurbohalerTM. We assessed the number of attempts necessary for correct use, its duration, the type of errors, the influence of motoric and cognitive impairment as well as patient preferences. Results: Nexthaler was found to be superior to most of the devices in terms of the frequency of inhaler technique errors (p Conclusion: Nexthaler, Spiromax and Genuair displayed better usability and favoritism in geriatric patients. The preferred devices were associated with less inhaler technique errors. The preference seem to depend on the condition and the properties of the devices.

Purpose Remote ischemic preconditioning (RIP) may protect remote organs from ischemia-reperfusion-injury (IRI) in surgical and non-surgical patients. There are few data available on RIP and lung function, especially not in healthy volunteers. The null-hypothesis was tested that RIP does not have an effect on pulmonary function when applied on healthy volunteers that were breathing spontaneously and did not experience any intervention. After approval of the Ethics Committee and informed consent of the study subjects, 28 healthy non-smoking volunteers were included and randomized in either the RIP group (n = 13) or the control group (n = 15). In the RIP group, lower limb ischemia was induced by inflation of a blood pressure cuff to a pressure 20 mmHg above the systolic blood pressure. After five minutes the blood pressure cuff was released for five minutes rest. The procedure was repeated three times resulting in 40 min ischemia and reperfusion. Capillary blood samples were taken, and lung function tests were performed at baseline (T1) and 60 min (T2) and 24 h (T3) after RIP. The control group was treated in the same fashion, but the RIP procedure was replaced by a sham protocol. Results 60 min after RIP capillary pO2 decreased significantly and returned to baseline level after 24 h in the RIP group. This did not occur in the control group. Capillary pCO2, variables of lung function tests and pulmonary capillary blood volume remained unchanged throughout the experiment in both groups. Conclusion Oxygenation is impaired early after RIP which is possibly induced by transient ventilation-perfusion inequality. No late effects of RIP were observed. The null hypothesis has to be rejected that RIP has no effect on respiratory variables in healthy volunteers.

Pulmonary hypertension is a chronic, incurable disease with poor prognosis. The therapeutic aim is a stabilization of patients showing signs of right heart failure as well as disease progression. A pulmonary hypertension is diagnosed in patients displaying a mean pulmonary arterial pressure of 25 mmHg in resting state. Invasively measured hemodynamics evaluated by right heart catheterization (mean pulmonary arterial pressure [mPAP], pulmonary arterial wedge pressure [PAWP], diastolic pressure gradient [DPG] and pulmonary vascular resistance [PVR]) allows to differentiate between pre-capillary, post-capillary and combined pulmonary hypertension, which constitutes the basis for classification. Diagnostics and therapy shall occur within a center of expertise. Currently, 10 medications belonging to 5 substance classes are approved. Combination therapy should be introduced early. In accordance with risk stratification, therapy is oriented towards estimated 1-year survival as opposed to single target values. If pulmonary hypertension is associated with left heart disease (group 2) or lung disease (group 3), optimal care of the primary disease should be paramount. These associations make up for a greater proportion of patients than idiopathic pulmonary arterial hypertension (PAH). In isolated cases, patients of group 2 may be treated in centers of expertise within the scope of medical studies. Patients with PAH may be categorized into typical versus atypical PAH. For patients with atypical PAH, an initial monotherapy is to be introduced. In case of chronic thromboembolic pulmonary hypertension, the possibility of an operative pulmonary endarterectomy should be evaluated. To date, the only approved drug is Riociguat, a stimulator of the soluble guanylate cyclase.Bei der pulmonalen Hypertonie handelt es sich um eine Druckerhöhung in der Lungenstrombahn, dem sog. kleinen Kreislauf: Der pulmonalarterielle Mitteldruck (Messung im Rechtsherzkatheter) ist auf über 25 mmHg erhöht. Für die Prognose der meist stark beeinträchtigten Patienten ist eine frühe Diagnosestellung extrem wichtig. Der Beitrag widmet sich der Diagnostik, der klinischen Klassifikation und der gruppenspezifischen Therapie der pulmonalen Hypertonie.

Asphericity (ASP) is a tumour shape descriptor based on the PET image. It quantitates the deviation from spherical of the shape of the metabolic tumour volume (MTV). In order to identify its biological correlates, we investigated the relationship between ASP and clinically relevant histopathological and molecular signatures in non-small-cell lung cancer (NSCLC).The study included 83 consecutive patients (18 women, aged 66.4 ± 8.9 years) with newly diagnosed NSCLC in whom PET/CT withSUVmax, MTV and ASP were associated with pathological T stage (Kruskal-Wallis, p = 0.001, p 0.0005 and p 0.0005, respectively) and N stage (p = 0.017, p = 0.003 and p = 0.002, respectively). Only ASP was associated with M stage (p = 0.026). SUVmax, MTV and ASP were correlated with Ki-67 index (Spearman's rho = 0.326/p = 0.003, rho = 0.302/p = 0.006 and rho = 0.271/p = 0.015, respectively). The latter correlations were considerably stronger in adenocarcinomas than in squamous cell carcinomas. ASP, but not SUVmax or MTV, showed a tendency for a significant association with the extent of VEGF expression (p = 0.058). In multivariate Cox regression analysis, ASP (p 0.0005) and the presence of distant metastases (p = 0.023) were significantly associated with progression-free survival. ASP (p = 0.006), the presence of distant metastases (p = 0.010), and Ki-67 index (p = 0.062) were significantly associated with overall survival.The ASP of primary NSCLCs on FDG PET images is associated with tumour dimensions and molecular markers of proliferation and angiogenesis.

Bronchial asthma is one of the most common chronic diseases. Its pathogenesis is still not fully understood and its progression is still not predictable. There are individual differences in frequency, severity and duration of symptoms and progression as well as in the response to therapy. The diagnosis is based on a detailed medical history and physical examination, on lung function tests and allergy tests. In recent years great improvements in medical treatment and patient care have been achieved. This article summarizes the pathogenesis, clinical picture, diagnosis and treatment of bronchial asthma.

Eine 72-jahrige Patientin stellte sich mit unklarer und zunehmender Dyspnoe vor (New-York-Heart-Association-Stadium III). In der Echokardiographie wurde ein persistierendes Foramen ovale mit Rechtsherzbelastung diagnostiziert. Die Rechtsherzkatheteruntersuchung ergab einen grosen Links-rechts-Shunt aufgrund einer arteriovenosen Malformation in der Leber. Bei zusatzlichen Teleangiektasien der Lippen lautete die Verdachtsdiagnose: Morbus Osler (Rendu-Osler-Weber-Syndrom). Da das Nasenbluten als Leitsymptom dieser Erkrankung bei der Patientin fehlte und nur 2 von 4 Curacao-Kriterien positiv waren, wurde eine genetische Untersuchung durchgefuhrt, die die Verdachtsdiagnose sicherte. Es erfolgte ein Off-label-Therapieversuch mit dem Angiogenesehemmer Bevacizumab, unter dem es zu einer Besserung der Dyspnoe kam.

The first line treatment for obstructive sleep apnea (OSA) is nasal continuous positive airway pressure (nCPAP), for which a variety of masks are available. While nasal masks (NM) are the first choice; oronasal masks (ONM) are also frequently used to prevent mouth dryness resulting from mouth opening. Our cross-sectional, prospective, randomized, un-blinded study addressed the efficacy of wearing an oral shield in addition to NM in preventing mouth leakage METHODS: Patients with OSA and established therapy using NM and complaining about mouth dryness (n = 29) underwent three polysomnographies (PSGs) using NM, ONM or a nose mask in combination with an oral shield (NMS). Mask leakage was continuously documented and objective sleep quality was assessed.There were significant differences in the apnea-hypopnea-index (AHI) between ONM (8.5/h; SD 6,7) and NM/nasal mask combined with oral shield device (NMS) (2.6/h; SD 2,3; 2.7/h; SD 2,6) (p 0,05) as well as in leakage [ONM (39.7 l/min SD 12,4); NM (34.6 l/min SD 9,4); NMS (33.1 l/min SD 9,6)] (p = 0.011). Furthermore, analysis of sleep quality (NREM3) favored NM and NMS over ONM (p = 0.02). There were no significant differences between NM and NMS in any objective outcome.Our data consistently confirmed the NM as the first choice for continuous positive airway pressure (CPAP) therapy of OSA. Notably, we demonstrated a high potential of the oral shield for patients with mouth opening to achieve additional comfort and thereby possibly compliance, without affecting nCPAP therapy effectiveness.

Right ventricular (RV) dysfunction is recognized as a cardinal prognostic marker in systolic heart failure patients. Conflicting data exist on the interaction of RV function and left ventricular (LV) reverse remodeling after cardiac resynchronization therapy (CRT). This prospective monocentric trial was set up to assess the predictive value of baseline RV function and corresponding RV-pulmonary artery (PA) coupling on LV reverse remodeling after CRT.110 patients with a CRT indication were prospectively enrolled. RV function and RV-PA interaction were analyzed at baseline using echocardiographic and invasive pressure-volume loop catheter approach. The primary endpoint was reverse LV remodeling (CRT-responder) defined as a reduction in LV end-systolic volume of ≥15% at 6 months.Responders had higher RV-PA coupling ratios (single-beat end-systolic elastance/PA elastance: Ees/Ea) at baseline, which corresponded to smaller RVs with better ejection fraction and lower afterload. After multivariate adjustment, the baseline Ees/Ea remained an independent predictor for LV response (OR 14.0 [1.5-130.8], p = 0.021). Normal coupling (Ees/Ea ≥ 1) was associated with higher responder rates (RR) (86%). Progressive uncoupling was associated with lower LV-RR (Ees/Ea ≤ 1-0.5: 57%, and Ees/Ea 0.5: 32%, p 0.001), corresponded with higher degrees of LV impairment and severity of mitral regurgitation, and was independently associated with an adverse outcome.A higher baseline RV-PA coupling, reflecting a lower degree of LV-induced pulmonary hypertension and secondary RV-dysfunction, is associated with an improved LV-reverse remodeling and is independently associated with better prognosis. The value of RV-PA ratio as potential guide for CRT patient selection warrants further investigation. Clinical Trial Registration - URL: http://www.drks.de. Unique Identifier: DRKS00011133.

In this article, we propose the Coopetititve Soft Gating Ensemble or CSGE for general machine learning tasks and interwoven systems. The goal of machine learning is to create models that generalize well for unknown datasets. Often, however, the problems are too complex to be solved with a single model, so several models are combined. Similar, Autonomic Computing requires the integration of different systems. Here, especially, the local, temporal online evaluation and the resulting (re-)weighting scheme of the CSGE makes the approach highly applicable for self-improving system integrations. To achieve the best potential performance the CSGE can be optimized according to arbitrary loss functions making it accessible for a broader range of problems. We introduce a novel training procedure including a hyper-parameter initialisation at its heart. We show that the CSGE approach reaches state-of-the-art performance for both classification and regression tasks. Further on, the CSGE provides a human-readable quantification on the influence of all base estimators employing the three weighting aspects. Moreover, we provide a scikit-learn compatible implementation., 8 pages, 10 figures, 4 tables, submitted (accepted for publication) - SISSY 2018 - Workshop on Self-Improving System Integration at IEEE ICAC/ SASO 2018

Bronchoconstriction is a hallmark of asthma and impairs gas exchange. We hypothesized that pharmacokinetics of volatile anesthetics would be affected by bronchoconstriction. Ventilation/perfusion (VA/Q) ratios and pharmacokinetics of desflurane in both healthy state and during inhalational administration of methacholine (MCh) to double peak airway pressure were studied in a piglet model. In piglets, MCh administration by inhalation (100 μg/ml, n=6) increased respiratory resistance, impaired VA/Q distribution, increased shunt, and decreased paO2 in all animals. The uptake and elimination of desflurane in arterial blood was delayed by nebulization of MCh, as determined by Micropore Membrane Inlet Mass Spectrometry (wash-in time to P50, healthy vs. inhalation: 0.5 min vs. 1.1 min, to P90: 4.0 min vs. 14.8 min). Volatile elimination was accordingly delayed. Inhaled methacholine induced severe bronchoconstriction and marked inhomogeneous VA/Q distribution in pigs, which is similar to findings in human asthma exacerbation. Furthermore, MCh-induced bronchoconstriction delayed both uptake and elimination of desflurane. These findings might be considered when administering inhalational anesthesia to asthmatic patients.