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BACKGROUND: Vitamin D deficiency has been associated with chronic disorders including chronic obstructive pulmonary disease (COPD) but the relationships with inflammation, exacerbations and disease progression remain unclear. METHODS: In this monocentric cross-sectional observational study we analyzed the disease status, systemic inflammation, prior exacerbation frequency and loss in lung function in relation to serum 25-hydroxyvitamin D (25-OHD) levels in a cohort of 94 patients with COPD. Serum 25-OHD, C-reactive protein, interleukin-6 and tumor necrosis factor-α were quantified. Exacerbation frequencies and sunlight exposure were assessed. These parameters were analyzed in correlation to the current forced expiratory volume in 1 s (FEV(1)), the individual average 3-year FEV(1) decline and the Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage. RESULTS: We observed fair correlation between serum 25-OHD and the current FEV(1) (r=0.38, P

Zusammenfassung Hintergrund Eine Blockade von Immun-Escape-Mechanismen (z. B. PD1 /PD-L1) mit Immun-Checkpoint-Inhibition (ICI) kann das Überleben von Patienten mit fortgeschrittenem NSCLC wesentlich verlängern und ausgeprägte Remissionen induzieren. Eine neoadjuvante ICI bei Patienten mit resektablem (UICC-Stadium III) oder oligometastasiertem (UICC-Stadium IVA) NSCLC wurde bisher kaum untersucht. Patienten/Methoden Es wurden Biopsien von Patienten mit lokal fortgeschrittenem oder oligometastasiertem NSCLC untersucht. Es erfolgte bei einer PD-L1-Expression > 50 %, gutem ECOG-Status und zu erwartender Operabilität die ICI-Applikation und nach ca. 4 Wochen die thoraxchirurgische OP. Alle Patienten erhielten ein komplettes Staging einschließlich PET-CT, cMRT und endobronchialem Ultraschall. Es wurden die Verträglichkeit, das radiologische und histologische Tumoransprechen und das chirurgische Outcome analysiert. Ergebnisse 4 Patienten (2 männlich, 2 weiblich, Alter 56 – 78 Jahre, n = 3 Adenokarzinom, n = 1 Plattenepithelkarzinom) erhielten präoperativ einen ICI. Alle Patienten hatten lokal fortgeschrittene Tumore, und die mediastinalen Lymphknoten waren in 3 Fällen positiv. Bei einem Patienten lag eine isolierte Hirnmetastase vor, welche stereotaktisch radiotherapiert wurde. Alle Patienten erhielten präoperativ komplikationslos 2 – 6 Zyklen eines ICI (3 × Pembrolizumab; 1 × Atezolizumab). Dies führte nicht zu einer Verzögerung der OP. Nach iRECIST zeigten 3 Tumore eine partielle response (PR), und ein Patient wies ein stable disease (SD) auf. Alle Tumore wurden komplett reseziert, und die OP erwies sich trotz inflammatorischer Veränderungen als technisch unproblematisch. Es gab keine behandlungsbezogene Morbidität oder Mortalität und keine perioperativen Komplikationen. In den Resektaten waren jeweils 2-mal ein komplettes pathologisches Ansprechen (CPR), Regressionsgrad III nach Junker, und 2-mal ein Regressionsgrad IIa nach Junker nachweisbar. Das mittlere Follow-up betrug 12 (1 – 24) Monate. Die PPR-Patienten entwickelten entweder Fernmetastasen nach 6 Monaten oder ein Lokalrezidiv nach 4 Monaten. Die CPR-Patienten sind bisher rezidivfrei. Schlussfolgerungen Eine neoadjuvante Therapie mit ICI ist gut verträglich und kann bei ausgewählten Patienten eine komplette Tumorremission induzieren. Die Behandlung hat keinen negativen Einfluss auf den chirurgischen Eingriff. Die Prognose ist vielversprechend bei CPR und eingeschränkt bei PPR.

Not available.

Zusammenfassung Hintergrund Bei niedrigen Influenza-Impfraten unter chronisch Kranken sollen Ansätze zu deren Steigerung unter Risikopatienten mit chronisch obstruktiver Lungenerkrankung (COPD) aufgedeckt werden. Methoden 120 COPD-Patienten aus Magdeburg füllten einen Fragebogen mit selbst erstellten Fragen und etablierten Skalen aus und wurden bez. des Influenza-Impfstatus 2015/2016 bzw. 2016/2017 analysiert. Geimpfte und Ungeimpfte wurden in sozioepidemiologischen Faktoren, Komponenten des Modells gesundheitlicher Überzeugungen, Selbstwirksamkeit (GESIS-ASKU), Angst/Depressionen (HADS-D) und Krankheitsverarbeitung (FKV-LIS) verglichen. Ergebnisse 62.5 % (n = 75) waren geimpft, 31.7 % (n = 38) ungeimpft, 5.8 % (n = 7) machten keine Angabe. Bei über/gleich 60-Jährigen waren 76 %, bei unter 60-Jährigen 42 % geimpft. 60 % (n = 72) zählten sich zur Risikogruppe. Ungeimpfte gaben stärker Sorgen vor Nebenwirkungen der Impfung an (p = .004) und zogen eine schlechtere Nutzen-Aufwand-Bilanz (p = .001). Ungeimpfte zeigten sich häufiger unsicher bez. des Impfschutzes und der Erkrankungsschwere der Influenza (p ≤ .001). Geimpfte hatten eine hohe Motivation, selbst an die Impfung zu denken, und häufiger eine positive Impfhistorie (p = .001). Die Impfempfehlung erfolgte häufiger durch Hausärzte als durch Pneumologen. Bei COPD-Patienten zeigte sich eine niedrigere Selbstwirksamkeit als in der Referenzgruppe der deutschen Allgemeinbevölkerung (p = .000), Geimpfte und Ungeimpfte unterschieden sich nicht (p = .418). Kein Unterschied zwischen Geimpften und Ungeimpften zeigte sich in der Krankheitsverarbeitung und in Depressivität und Angst, Ungeimpfte gaben jedoch tendenziell höhere Angstwerte an. Schlussfolgerung Maßnahmen sollten insbesondere auf unter 60-jährige COPD-Patienten mit negativer Impfhistorie abzielen und diese als Risikopatienten sensibilisieren. Verbreitete Unsicherheiten zur Erkrankungsschwere der Influenza sowie zum Impf-Schutz sollten angegangen werden. Es sollte vermittelt werden, dass die Influenzaimpfung nicht zur Exazerbation führt. Die Impfempfehlung sollte verstärkt durch Pneumologen erfolgen.

A wide variety of drugs and substances have the potential to damage the respiratory system by different mechanisms. Clofazimine is an anti-leprosy drug that is normally only prescribed for a few years. It has a very long half-life, and crystalline deposition of the drug in various tissues has been documented. But up to now, no fatalities due to pulmonary damage have been described. We report the case of a patient who took clofazimine for almost 27 years as off-label treatment for Melkersson-Rosenthal syndrome. He suffered from progressive dyspnea, productive cough, and occasional hemoptysis. X-ray and CT of the thoracic organs revealed extensive multilocular, compact, tumor-like infiltrates with central necrosis in both lungs. Pulmonary function tests showed restrictive impairment and manifest hypoxemia. Histology of lung biopsies revealed intense interstitial accumulation of histiocytes and marked deposition of crystalline foreign material. The patient died from progressive respiratory failure. Autopsy revealed crystalline deposition and a histiocytic reaction in many other parenchymal organs. Conclusion: Pulmonary parenchymal deposition of drug crystals is a rare mechanism of drug-induced pulmonary diseases. Long-standing, off-label use of clofazimine may cause severe destruction of the lungs and can be fatal.

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.

Severe influenza infection has no effective treatment available. One of the key barriers to developing host-directed therapy is a lack of reliable prognostic factors needed to guide such therapy. Here, we use a network analysis approach to identify host factors associated with severe influenza and fatal outcome. In influenza patients with moderate-to-severe diseases, we uncover a complex landscape of immunological pathways, with the main changes occurring in pathways related to circulating neutrophils. Patients with severe disease display excessive neutrophil extracellular traps formation, neutrophil-inflammation and delayed apoptosis, all of which have been associated with fatal outcome in animal models. Excessive neutrophil activation correlates with worsening oxygenation impairment and predicted fatal outcome (AUROC 0.817–0.898). These findings provide new evidence that neutrophil-dominated host response is associated with poor outcomes. Measuring neutrophil-related changes may improve risk stratification and patient selection, a critical first step in developing host-directed immune therapy., Identification of host factors associated with severe influenza infection could provide insights into treatment options. Here, the authors provide transcriptomic analyses of blood from >100 influenza infected patients and show that changes in circulating neutrophils are associated with severe influenza infection.

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.

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.

COPD and asthma are two distinct but sometimes overlapping diseases exhibiting varying degrees and types of inflammation on different stages of the disease. Although several biomarkers are defined to estimate the inflammatory endotype and stages in these diseases, there is still a need for new markers and potential therapeutic targets. We investigated the levels of a phytohormone, abscisic acid (ABA) and its receptor, LANCL2, in COPD patients and asthmatics. In addition, PPAR-γ that is activated by ABA in a ligand-binding domain-independent manner was also included in the study. In this study, we correlated ABA with COPD-propagating factors to define the possible role of ABA, in terms of immune regulation, inflammation, and disease stages. We collected blood from 101 COPD patients, 52 asthmatics, and 57 controls. Bronchoscopy was performed on five COPD patients and 29 controls. We employed (i) liquid chromatography–tandem mass spectrometry and HPLC to determine the ABA and indoleamine 2,3-dioxygenase levels, respectively; (ii) real-time PCR to quantify the gene expression of LANCL2 and PPAR-γ; (iii) Flow cytometry to quantify adipocytokines; and (iv) immunoturbidimetry and ELISA to measure CRP and cytokines, respectively. Finally, a multinomial regression model was used to predict the probability of using ABA as a biomarker. Blood ABA levels were significantly reduced in COPD patients and asthmatics compared to age- and gender-matched normal controls. However, PPAR-γ was elevated in COPD patients. Intriguingly, ABA was positively correlated with immune-regulatory factors and was negatively correlated with inflammatory markers, in COPD. Of note, ABA was increased in advanced COPD stages. We thereby conclude that ABA might be involved in regulation of COPD pathogenesis and might be regarded as a potential biomarker for COPD stages.

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.

Multi-task learning (mtl) provides state-of-the-art results in many applications of computer vision and natural language processing. In contrast to single-task learning (stl), mtl allows for leveraging knowledge between related tasks improving prediction results on the main task (in contrast to an auxiliary task) or all tasks. However, there is a limited number of comparative studies on applying mtl architectures for regression and time series problems taking recent advances of mtl into account. An interesting, non-linear problem is the forecast of the expected power generation for renewable power plants. Therefore, this article provides a comparative study of the following recent and important mtl architectures: Hard parameter sharing, cross-stitch network, sluice network (sn). They are compared to a multi-layer perceptron model of similar size in an stl setting. Additionally, we provide a simple, yet effective approach to model task specific information through an embedding layer in an multi-layer perceptron, referred to as task embedding. Further, we introduce a new mtl architecture named emerging relation network (ern), which can be considered as an extension of the sluice network. For a solar power dataset, the task embedding achieves the best mean improvement with 14.9%. The mean improvement of the ern and the sn on the solar dataset is of similar magnitude with 14.7% and 14.8%. On a wind power dataset, only the ern achieves a significant improvement of up to 7.7%. Results suggest that the ern is beneficial when tasks are only loosely related and the prediction problem is more non-linear. Contrary, the proposed task embedding is advantageous when tasks are strongly correlated. Further, the task embedding provides an effective approach with reduced computational effort compared to other mtl architectures., Comment: 8 pages;2 tables;5 figures

Task embeddings in multi-layer perceptrons (MLP) for multi-task learning and inductive transfer learning in renewable power forecasts is an exciting new technique. In many cases, this approach improves the forecast error and reduces the required training data. However, it does not take the periodic influences in power forecasts within a day into account, i.e., the diurnal cycle. Therefore, we extended this idea to temporal convolutional networks to consider those in tasks of day-ahead power forecasts for renewables. We propose transforming the embedding space, which contains the latent similarities between tasks, through convolution and providing these results to the network’s residual block. The proposed architecture significantly improves the forecast accuracy up to \(25\%\) for multi-task learning for power forecasts on the open EuropeWindFarm and GermanSolarFarm datasets compared to the MLP approach. Based on the same data, we achieve a ten percent improvement for the wind datasets and more than \(20\%\) in most cases for the solar dataset for inductive transfer learning without catastrophic forgetting. Finally, we are the first to propose zero-shot learning for renewable power forecasts. The proposed architecture achieves an error as good as the task embedding MLP with a full year of training data in the respective experiments.

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.

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.

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.

For the integration of renewable energy sources, power grid operators need realistic information about the effects of energy production and consumption to assess grid stability. Recently, research in scenario planning benefits from utilizing generative adversarial networks (GANs) as generative models for operational scenario planning. In these scenarios, operators examine temporal as well as spatial influences of different energy sources on the grid. The analysis of how renewable energy resources affect the grid enables the operators to evaluate the stability and to identify potential weak points such as a limiting transformer. However, due to their novelty, there are limited studies on how well GANs model the underlying power distribution. This analysis is essential because, e.g., especially extreme situations with low or high power generation are required to evaluate grid stability. We conduct a comparative study of the Wasserstein distance, binary-cross-entropy loss, and a Gaussian copula as the baseline applied on two wind and two solar datasets with limited data compared to previous studies. Both GANs achieve good results considering the limited amount of data, but the Wasserstein GAN is superior in modeling temporal and spatial relations, and the power distribution. Besides evaluating the generated power distribution over all farms, it is essential to assess terrain specific distributions for wind scenarios. These terrain specific power distributions affect the grid by their differences in their generating power magnitude. Therefore, in a second study, we show that even when simultaneously learning distributions from wind parks with terrain specific patterns, GANs are capable of modeling these individualities also when faced with limited data. These results motivate a further usage of GANs as generative models in scenario planning as well as other areas of renewable energy.

An overt pro-inflammatory immune response is a key factor contributing to lethal pneumococcal infection in an influenza pre-infected host and represents a potential target for therapeutic intervention. However, there is a paucity of knowledge about the level of contribution of individual cytokines. Based on the predictions of our previous mathematical modeling approach, the potential benefit of IFN-γ- and/or IL-6-specific antibody-mediated cytokine neutralization was explored in C57BL/6 mice infected with the influenza A/PR/8/34 strain, which were subsequently infected with the Streptococcus pneumoniae strain TIGR4 on day 7 post influenza. While single IL-6 neutralization had no effect on respiratory bacterial clearance, single IFN-γ neutralization enhanced local bacterial clearance in the lungs. Concomitant neutralization of IFN-γ and IL-6 significantly reduced the degree of pneumonia as well as bacteremia compared to the control group, indicating a positive effect for the host during secondary bacterial infection. The results of our model-driven experimental study reveal that the predicted therapeutic value of IFN-γ and IL-6 neutralization in secondary pneumococcal infection following influenza infection is tightly dependent on the experimental protocol while at the same time paving the way toward the development of effective immune therapies.

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

To analyze the diagnostic performance of dual time point imaging (DTPI) for pre-therapeutic lymph node (LN) staging in non-small cell lung cancer (NSCLC). This was a retrospective analysis of 47 patients with NSCLC who had undergone DTPI by PET (early + delayed) using F18-fluorodeoxyglucose (FDG). PET raw data were reconstructed iteratively (point spread function + time-of-flight). LN uptake in PET was assessed visually (four-step score) and semi-quantitatively (SUVmax, SUVmean, ratios LN/primary, LN/liver, and LN/mediastinal blood pool). DTPI analyses included retention indices (RIs), Δ-ratios and changes in visual score. Histology or cytology served as standards of reference. Accuracy was determined based on ROC analyses. Thirty-six of 155 LNs were malignant. DTPI accuracy was low for all measures (visual assessment, 24.5%; RI SUVmax, 68.4%; RI SUVmean, 65.8%; Δ-ratios, 63.9-76.1%) and significantly inferior to early PET. Accuracies of early (range, 86.5–92.9%) and delayed PET (range, 85.2–92.9%) were comparable. At early PET, accuracy of the visual score (92.9%) was similar or superior to semi-quantitative analyses (range, 86.5–92.3%). Using a modern PET/CT device and novel image reconstruction, neither additional delayed PET nor DTPI analyses improved the accuracy of PET-based LN staging. Dedicated visual assessment criteria performed very well. • DTPI did not improve accuracy of PET-based LN staging in NSCLC. • Analyzed SUV ratios were not superior to LN SUVmax or SUVmean. • A four-step visual score may allow highly accurate, standardized LN assessment.

S2k-Leitlinie der Deutschen Gesellschaft fur Allergologie und klinische Immunologie (DGAKI) in Zusammenarbeit mit dem Arzteverband Deutscher Allergologen (AeDA), dem Berufsverband der Kinder- und Jugendarzte (BVKJ), dem Deutschen Allergie- und Asthmabund (DAAB), der Deutschen Dermatologischen Gesellschaft (DDG), der Deutschen Gesellschaft fur Ernahrung (DGE), der Deutschen Gesellschaft fur Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS), der Deutschen Gesellschaft fur Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie, der Deutschen Gesellschaft fur Kinder- und Jugendmedizin (DGKJ), der Gesellschaft fur Padiatrische Allergologie und Umweltmedizin (GPA), der Deutschen Gesellschaft fur Pneumologie und Beatmungsmedizin (DGP), der Deutschen Gesellschaft fur Gastroenterologie und Ernahrung (GPGE), der Deutschen KontaktallergieGruppe (DKG), der Osterreichischen Gesellschaft fur Allergologie und Immunologie (OGAI), dem BerufsVerband Oecotrophologie e.V. (VDOE) und der Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften (AWMF)

Zusammenfassung Hintergrund Interstitielle Lungenerkrankungen (ILD) umfassen verschiedenste heterogene, zumeist chronische Erkrankungen des Interstitiums und/oder der Alveolen mit bekannten und unbekannten Ursachen. Die Diagnostik der ILD ist sehr komplex und sollte interdisziplinär erfolgen. Eine der wesentlichen Basisuntersuchungen ist eine umfangreiche Anamnese. Hierzu kam im deutschsprachigen Raum bisher der Frankfurter Bogen von 1985 zur Anwendung, der mittlerweile jedoch sprachlich und inhaltlich einer Überarbeitung bedurfte. Methode Unter Schirmherrschaft der klinischen Sektion der DGP erfolgte die Erstellung eines neuen Patientenfragebogens zur Diagnostik interstitieller und seltener Lungenerkrankungen. Der Fragebogen entstand unter Mitarbeit von Pneumologen mit ILD-Expertise, Arbeitsmedizinern und Psychologen sowie der Unterstützung von Selbsthilfegruppen. Abschließend wurde der Fragebogen mithilfe von Patienten sprachlich optimiert. Ergebnisse Der neu erstellte Patientenfragebogen zur Diagnostik interstitieller und seltener Lungenerkrankungen umfasst mehrere Bereiche: Initiale und aktuelle Symptome, Fragen zur Vorgeschichte inklusive Medikation, pulmonale und extrapulmonale Vorerkrankungen, mögliche Expositionen im häuslichen, privatem und beruflichem Umfeld sowie Familienanamnese und Reisetätigkeiten. Schlussfolgerung Der neu erstellte Fragebogen kann in der klinischen Routine die Diagnostik bei Patienten mit Verdacht auf eine interstitielle Lungenerkrankung wesentlich erleichtern.

Real-world studies include a broader patient population for a longer duration than randomised controlled trials (RCTs) and can provide relevant insights for clinical practice. PASSPORT was a multicentre, prospective, post-authorisation study of patients who were newly prescribed pirfenidone and followed for 2 years after initiating treatment. Physicians collected data on adverse drug reactions (ADRs), serious ADRs (SADRs) and ADRs of special interest (ADRSI) at baseline and then every 3 months. Post hoc stepwise logistic regression models were used to identify baseline characteristics associated with discontinuing treatment due to an ADR. Patients (n=1009, 99.7% with idiopathic pulmonary fibrosis) had a median pirfenidone exposure of 442.0 days. Overall, 741 (73.4%) patients experienced ADRs, most commonly nausea (20.6%) and fatigue (18.5%). ADRs led to treatment discontinuation in 290 (28.7%) patients after a median of 99.5 days. Overall, 55 (5.5%) patients experienced SADRs, with a fatal outcome in six patients. ADRSI were reported in 693 patients, most commonly gastrointestinal symptoms (38.3%) and photosensitivity reactions/skin rashes (29.0%). Older age and female sex were associated with early treatment discontinuation due to an ADR. Findings were consistent with the known safety profile of pirfenidone, based on RCT data and other post-marketing experience, with no new safety signals observed., Real-world safety results from 1009 patients in PASSPORT were consistent with the known pirfenidone safety profile http://ow.ly/oXjv30lrzAf

Introduction: About 10% of all asthmatics suffer from severe allergic asthma, which is frequently caused by IgE hypersensitivity against perennial and/or seasonal allergens. However, allergy testing is often limited to the most frequent allergens. Purpose: The aim of this ongoing project is to gain data on sensitizations towards aeroallergens in severe asthmatic patients, in which no allergen could be detected in previous testings and who are therefore considered non-atopic. Methods: 35 local perennial aeroallergens (mites, fungi, animal epithelia and insects) are measured by specific IgE assessment in 600 severe asthmatic patients in Germany who had negative results in previous allergen tests by either Skin Prick Test or analyses of specific IgE. Furthermore, total IgE levels are determined and a general anamnesis is documented. Results: In an interim analysis of 362 patients (62.4 % females, mean age 53.4 y), 51.4 % demonstrated at least one sensitization towards a perennial aeroallergen despite them being considered non-atopic before. According to GINA classification 84.2 % of the patients were (partly) uncontrolled and 50.8 % had ≥2 exacerbations in the past 12 months. The most common sensitizations were found towards Staph. aureus Enterotoxin B and A (20.7% and 11.5%), R. nigricans (14.9 %), A. fumigatus (14.4 %), D. farinae and cat dander (11 % each). Conclusion: These results indicate a lack of diagnostics of sensitization towards aeroallergens in severe asthmatic patients. This suggests that the percentage of non-allergic asthmatics might be overestimated. These data might help to identify the most frequent, as well as infrequent aeroallergens in asthma.

Rationale Pre-operative lobar function is estimated by scintigraphy in patients with pulmonary malignancies and compromised function. This study compared the lobar perfusion determined by scintigraphy (PS) with data from SPECT/low-dose-CT (SPECT/ldCT) analyzed manually and semi-automatic. Methods Retrospective analysis on 39 patients (m/f = 25/14; age: 72.5 [22–89] years) with indication for pulmonary perfusion scintigraphy. Imaging was performed using SPECT/ldCT. Data was analyzed manually and by semi-automatic software. Readers’ confidence in 3D-segmentation was scored by two independent readers. Interrater agreement was calculated. In addition, Spearman’s rank correlation and Wilcoxon’s test were used. Results Results from PS differed significantly from SPECT/ldCT processed manually or semi-automatically in 4/5 lobes (total difference ≤21.6%; rho ≥0.44) and in 3/5 (total difference 21.6%; rho ≥0.37), respectively. Readers’ confidence in 3D-segmentation showed a perfect interrater agreement (κ = 0.98). Conclusion Quantification of lobar perfusion by SPECT/ldCT differs significantly from planar scintigraphy (e.g., with potential influence on therapy). The semi-automatic software analysis provides an applicable methodology.

Hintergrund und Methodik: Omalizumab ist ein monoklonaler Anti-IgE-Antikorper zur Behandlung des schweren allergischen Asthma bronchiale. Ziel dieser Arbeit war die Bewertung der vorhandenen Evidenz durch ein Expertengremium und die Formulierung daraus resultierender Empfehlungen zu moglichen krankheitsmodifizierenden Effekten und der Dauer der Behandlung mit Omalizumab. Ergebnisse: Eine direkte oder indirekte Interaktion zwischen Omalizumab und der IgE-Produktion ist wahrscheinlich. Die aufgrund eines pharmakokinetisch-pharmakodynamischen Modells erwarteten IgE-modulierenden Eigenschaften von Omalizumab werden derzeit in der klinischen Anwendung uberpruft. Therapieentscheidungen auf Grundlage dieses Modells zu treffen kann allerdings nicht empfohlen werden. Anhand der verfugbaren Evidenz wird ein abschwachender Einfluss von Omalizumab auf Faktoren der strukturellen Veranderungen in den Atemwegen (Airway Remodeling) angenommen. Daten, um eine Empfehlung zur Dosisreduktion oder zum Absetzen von Omalizumab nach Langzeittherapie auszusprechen, fehlen derzeit. Schlussfolgerungen: Aktuell kann bei Patienten mit schwergradigem allergischen Asthma unter langfristiger Omalizumab-Behandlung aufgrund der vorliegenden klinischen Daten weder eine Dosisreduktion noch ein Absetzen der Therapie empfohlen werden. Fur eine klare Beurteilung mussen die Ergebnisse laufender klinischer Studien abgewartet werden.

Das Churg-Strauss-Syndrom (CSS; Synonym fur eosinophile granulomatose Polyangiitis) ist durch ein meist schweres Asthma bronchiale, eine Eosinophilie und eine systemische Gefasentzundung, die zahlreiche unterschiedliche Organmanifestationen aufweisen kann, gekennzeichnet. Es stellt eine wichtige und therapierelevante Differenzialdiagnose des schweren Asthmas dar. Typisch ist ein phasenhafter Verlauf mit einer Prodromalphase, einer Phase der eosinophilen Gewebsinfiltration und einer vaskulitischen Phase. In Abhangigkeit von der klinischen Prasentation und dem Nachweis von antizytoplasmatischen Antikorpern (ANCA) werden zwei Phanotypen unterschieden. Das Asthma bronchiale beim CSS wird entsprechend der Standards der Asthmatherapie behandelt, in der vaskulitischen Phase ist in Abhangigkeit von der Schwere der Erkrankung und den Organmanifestationen oft eine kombinierte Therapie mit systemischen Kortikosteroiden und Immunsuppressiva erforderlich. Aktuelle Daten sprechen fur einen positiven Effekt von Biologicals. Auf Grundlage einer aktuellen Literaturrecherche wird eine Ubersicht uber die Pathogenese, Klinik, Diagnostik und Therapie des CSS gegeben.

Background: In July 2005, omalizumab was approved as add-on therapy in Germany to improve asthma control in patients with severe allergic asthma (SAA). X-Tab, a German non-interventional study was designed to address real-life outcomes, including measures of asthma control and health-related quality of life (QoL), in patients treated with omalizumab. Methods: 161 patients at 35 centers were included into the ongoing study with a follow-up of 3 years. At baseline, allergic history, lung function and Asthma control questionnaire (ACQ) and Mini-Asthma Quality of Life Questionnaire (MiniAQLQ) were documented. Results: At baseline, mean age was 48.8±12.2 years (60.9% female). The mean duration of SAA was 16.2±12.6 years. The mean level of IgE prior to therapy with omalizumab was 437 IU/mL (median 260.5). Frequencies of specific IgE were as follows: 60.9% (mites), 46.6% (animal epithel) and 51.6% (molds) of patients. Additionally, 51.6% of patients had allergic rhinitis and 20.5% had food allergy. 74.5% had a lung function of FEV1 Conclusion: The baseline characteristics of this SAA cohort indicate that most patients that initiate treatment with omalizumab in Germany have evidence of atopy and relatively high levels of serum IgE, compromised lung function and a lack of asthma control. Clinical data that will emerge from this cohort will provide information that is important for patients, providers and payers, including asthma control and health-related QoL.

Ein 45-jahriger Patient stellte sich mit zunehmender Dyspnoe vor. Rontgenologisch war ein diffuser Lungenparenchymprozess nachweisbar, der CT-morphologisch als Crazy-paving-Muster imponierte. Funktionell lagen eine manifeste respiratorische Insuffizienz und schwere Einschrankung der pulmonalen Diffusionskapazitat vor. Mit einer bronchoalveolaren Lavage und histologischen Untersuchungen von transbronchialen Lungenbiopsien wurde eine Alveolarproteinose nachgewiesen. Diese wurde aufgrund des positiven serologischen Nachweises von Autoantikorpern gegen den „granulocyte-macrophage colony-stimulating factor“ (GM-CSF) als primare Form eingestuft. Durch 2-malige therapeutische Ganzlungenlavage wurde eine anhaltende Remission erreicht.