Bronchodilator Reversibility in the GAN Severe Asthma Cohort.

BACKGROUND AND OBJECTIVE: Positive bronchodilator reversibility (BDR) is a diagnostic criterion for asthma. However, patients with asthma may exhibit a negative BDR response. Aim: To describe the frequency of positive and Negative BDR response in patients with severe asthma and study associations with phenotypic characteristics. METHODS: A positive BDR response was defined as an increase in FEV1 >200 mL and >12% upon testing with a short-acting ß-agonist. RESULTS: BDR data were available for 793 of the 2013 patients included in the German Asthma Net (GAN) severe asthma registry. Of these, 250 (31.5%) had a positive BDR response and 543 (68.5%) a egative BDR response. Comorbidities significantly associated with a negative response were gastroesophageal reflux disease (GERD) (28.0% vs 40.0%, P<.01) and eosinophilic granulomatosis with polyangiitis (0.4% vs 3.0%; P<.05), while smoking history (active: 2.8% vs 2.2%; ex: 40.0% vs 41.7%) and comorbid chronic obstructive pulmonary disease (COPD) (5.2% vs 7.2%) were similar in both groups. Patients with a positive BDR response had worse asthma control (median Asthma Control Questionnaire 5 score, 3.4 vs 3.0, P<.05), more frequently reported dyspnea at rest (26.8% vs 16.4%, P<.001) and chest tightness (36.4% vs 26.2%, P<.001), and had more severe airway obstruction at baseline (FEV1% predicted, 56 vs 64, P<.001) and higher fractional exhaled nitric oxide (FeNO) levels (41 vs 33 ppb, P<0.05). There were no differences in diffusion capacity of the lung for carbon monoxide, single breath (% pred, 70% vs 71%). Multivariate linear regression analysis identified an association between positive BDR response and lower baseline FEV1% (P<.001) and chest tightness (P<.05) and a negative association between BDR and GERD (P<.05). CONCLUSION: In this real-life setting, most patients with severe asthma had a negative BDR response. Interestingly, this was not associated with smoking history or COPD, but with lower FeNO and presence of GERD.

[The Current Therapy of Asbestos-Associated Malignant Pleural Mesothelioma - An Expert Consensus Paper]. / Die aktuelle Therapie des asbestassoziierten malignen Pleuramesothelioms ­ Ein Experten-Konsensuspapier.

Asbestos-related mesotheliomas belong to the group of the most frequent occupational diseases in Germany, reaching about 1,000 new cases per year. The disease has a dismal prognosis because most tumors remain asymptomatic for a long time and therefore are diagnosed as incidental findings at later stages.During the last decade the German Social Accident Insurance (DGUV) has made considerable efforts to prepone the diagnosis in order to detect the disease at earliest possible stages. These efforts resulted in new findings showing that, in a high-risk group, a combination of the biomarkers calretinin and mesothelin was able to advance the diagnosis up to 12 months.Ideally, the diagnosis of a mesothelioma at an early stage has to be accompanied by the best possible individualized therapy. Standard therapeutic strategies are surgery and chemotherapy, added by radiotherapy and psycho-oncology. In recent years, several new therapeutic avenues are being explored. This review comprehensively presents both old and new therapeutic options in mesothelioma, based on international Leitlinien and new studies.

[Guideline for the Diagnosis and Treatment of Asthma - Addendum 2020 - Guideline of the German Respiratory Society and the German Atemwegsliga in Cooperation with the Paediatric Respiratory Society and the Austrian Society of Pneumology]. / S2k-Leitlinie zur Diagnostik und Therapie von Patienten mit Asthma ­ Addendum 2020.

The present addendum of the guideline for the diagnosis and treatment of asthma (2017) complements new insights into the diagnosis and management of asthma as well as for the newly approved drugs for the treatment of asthma. Current, evidence-based recommendations on diagnostic and therapeutic approaches are presented for children and adolescents as well as for adults with asthma.

[Congenital Pulmonary Artery Stenoses as a Rare Cause of Pulmonary Hypertension]. / Kongenitale Pulmonalarterienstenosen als seltene Ursache einer pulmonalen Hypertonie.

Kongenitale Pulmonalarterienstenosen sind eine seltene Ursache der pulmonalen Hypertonie (PH). Die Erkrankung wird in ihrer Häufigkeit vermutlich unterschätzt, und sie sollte in der Abklärung einer PH bedacht werden.Die Vorstellung einer 43-jährigen Patientin erfolgte zur Therapieoptimierung und Evaluation einer möglichen Lungentransplantation mit der Arbeitsdiagnose kongenitale Pulmonalarterienstenosen.Die Patientin beklagte eine seit der frühen Kindheit bestehende Belastungsdyspnoe aktuell entsprechend WHO-FC-Klasse II-III.Die Krankengeschichte zeigte die Erstdiagnose einer primären pulmonalarteriellen Hypertonie (IPAH) vor 17 Jahren. Es erfolgte eine PH-spezifische Medikation in wechselnden Kombinationen. Im Rahmen eines Zentrumswechsels erfolgte eine Reevaluation, und bei Nachweis eines typischen Mismatch mit normaler Ventilation, jedoch keilförmig gestörter Perfusion in der Lungenszintigrafie wurde eine chronisch thromboembolische pulmonale Hypertonie (CTEPH) vermutet. Die Pulmonalis-Angiografie zeigte ausschließlich subsegmental gelegene Stenosierungen sowie Gefäßabbrüche mit korrespondierenden Minderperfusionen, passend zu einer CTEPH. Im Rahmen der ersten Intervention erfolgte aufgrund der ungewöhnlichen Morphologie der pulmonalarteriellen Läsionen eine Erweiterung der Diagnostik mittels optischer Kohärenztomografie (OCT). Bei der Patientin fand sich kein endoluminales Material, jedoch eine kräftige Gefäßwand. Damit wurde die Diagnose einer pumonalen Hypertonie bei kongenitalen Pulmonalarterienstenosen mit In-situ-Thrombosierung gestellt.

[COVID-19 Vaccination in Asthma Patients Treated with Biologicals - Statement of the Austrian Society of Pneumology and German Respiratory Society]. / COVID-19-Impfungen bei Biologika-Therapie von Asthma bronchiale.

Patients with asthma should be vaccinated against COVID-19. This includes patients with severe asthma. Treatment with a biological for asthma is no contra-indication for vaccination against COVID-19.

Case delay in the OR morning start in hospitals of different size and academic status : Results from a German multicenter study to identify incidence and causes of delayed anesthesia ready time.

BACKGROUND: Delays in the start of morning operations cause a loss of expensive OR capacity as well as frustration and potential conflicts among the different professions involved. There are a lot of reasons which can lead to delayed anesthesia ready time (ART). This is the first large multicenter study to identify incidence, extent and reasons of delay in ART. METHODS: First case delays in ART were studied in all regular ORs in 36 hospitals of different sizes (smaller community hospitals, larger community hospitals and university hospitals) over a period of 2 weeks. We analyzed the results comparing the 3 hospital types regarding incidence, extent and reasons for delay. RESULTS: A total of 3628 first of day cases were included in the study. Incidences of delayed ART (delay >5 min) ranged from 26.5% in university hospitals to 40.8% in larger community hospitals. However, university hospitals had higher incidences than smaller community hospitals of delays greater than 15 and 30 min. The main reasons for delays were prolonged induction of anesthesia, patient in-hospital logistics and delayed patient arrival at the hospitals. The highest mean delay of delayed cases was found in university hospitals with 21.7 min ± 14.7 min (SD). CONCLUSIONS: Delays in anesthesia ready time have a high prevalence in most hospitals, however the reasons for delay are manifold, making interventions to reduce delay complex.

[A Rarely Differential Diagnosis of Exertional Dyspnea]. / Seltene Differenzialdiagnose einer Belastungsdyspnoe.

The determination of exercise-induced dyspnea is an important multifaceted task for a differential diagnosis of the pulmonologist. We are reporting the case of a 70-year old female patient at the time of the first presentation with a tumor filling almost the entire left hemithorax. Histologically a solitary pleural fibroma could be diagnosed.

Modulating local airway immune responses to treat allergic asthma: lessons from experimental models and human studies.

With asthma affecting over 300 million individuals world-wide and estimated to affect 400 million by 2025, developing effective, long-lasting therapeutics is essential. Allergic asthma, where Th2-type immunity plays a central role, represents 90% of child and 50% of adult asthma cases. Research based largely on animal models of allergic disease have led to the generation of a novel class of drugs, so-called biologicals, that target essential components of Th2-type inflammation. Although highly efficient in subclasses of patients, these biologicals and other existing medication only target the symptomatic stage of asthma and when therapy is ceased, a flare-up of the disease is often observed. Therefore, it is suggested to target earlier stages in the inflammatory cascade underlying allergic airway inflammation and to focus on changing and redirecting the initiation of type 2 inflammatory responses against allergens and certain viral agents. This focus on upstream aspects of innate immunity that drive development of Th2-type immunity is expected to have longer-lasting and disease-modifying effects, and may potentially lead to a cure for asthma. This review highlights the current understanding of the contribution of local innate immune elements in the development and maintenance of inflammatory airway responses and discusses available leads for successful targeting of those pathways for future therapeutics.

[Does hospital volume correlate with surgical process time? : Retrospective analysis of the five most common procedures for visceral surgery, trauma and orthopedic surgery and gynecology/obstetrics from the benchmarking program of the Berufsverband Deutscher Anästhesisten (BDA), Berufsverband Deutscher Chirurgen (BDC) and Verband für OP-Management (VOPM)]. / Korreliert die Leistungsmenge eines Krankenhauses mit der chirurgischen Prozesszeit? : Retrospektive Analyse der jeweils fünf häufigsten Prozeduren aus den Bereichen Viszeralchirurgie, Unfall­/orthopädische Chirurgie und Gynäkologie/Geburtshilfe aus dem Benchmarking-Programm von BDA, BDC und VOPM.

BACKGROUND: Minimum volume thresholds for specific surgical procedures in German hospitals were established in 2004 but remain controversial. For the first time, this study investigated the relationship between hospital performance volume and surgical procedure duration in a multicenter approach. The question here was whether a concentration on frequently performed procedures leads to a reduction in surgical process times. METHODS: In a retrospective analysis, the 5 most common procedures from visceral, trauma/orthopedic and gynecological/obstetrics surgery were examined in hospitals participating in a benchmarking program. For each procedure performed between 2013 and 2015, hospitals were divided into 4 groups depending on the hospital volume provided. The average surgical duration of incision to suture time was calculated between the group with "very low" hospital volume and the other three groups ("low", "high" and "very high"). RESULTS: OR cases from 75 hospitals were analyzed. The number of included cases per procedure ranged from 31,940 to 2705. The average number of operations performed in a specific procedure was 3-4 times higher in high-volume hospitals compared to very low-volume hospitals. A linear relationship between hospital volume and surgical process time only appeared to be clearly seen in laparoscopic cholecystectomy, appendectomy and arthroscopic meniscus surgery: a higher case load led to a reduction in incision to suture time. For the other procedures, the surgical process times were inconsistent between the hospital groups. CONCLUSION: The case volume only appeared to have a direct but limited influence on incision to suture times in laparoscopic and arthroscopic procedures. Overall, the hospital performance volume appeared to be of subordinate importance in terms of OR-economics.

Changes in serum KL-6 levels are associated with the development of chronic lung allograft dysfunction in lung transplant recipients.

Chronic lung allograft dysfunction (CLAD) remains a leading cause of death after lung transplantation. KL-6 is a reliable biomarker for various interstitial lung diseases and levels are increased in lung transplant recipients with versus without bronchiolitis obliterans syndrome. This study investigated whether changes in serum KL-6 levels over time were associated with CLAD. Twenty-one lung transplant recipients had serum KL-6 measured (NANOPIA®) at baseline and after 7 years. Changes in serum KL-6 levels from baseline were determined. Receiver operating characteristic curves and Kaplan-Meier analysis were used to test the predictive value of changes in serum KL-6 over time. The average increase in KL-6 in patients with CLAD was 15% versus a 28% decrease in non-CLAD patients (p = .042). An 11% decrease in serum KL-6 level was determined as the best cut-off value to be associated with the development of CLAD (86% sensitivity, 78% specificity). Kaplan-Meier analysis confirmed the association between this cut-off and the development of CLAD (log rank p = .013). In this small cohort, changes in serum KL-6 over time were associated with the development of CLAD after lung transplantation.

[Guideline for the Diagnosis and Treatment of Asthma - Guideline of the German Respiratory Society and the German Atemwegsliga in Cooperation with the Paediatric Respiratory Society and the Austrian Society of Pneumology]. / S2k-Leitlinie zur Diagnostik und Therapie von Patienten mit Asthma.

The present guideline is a new version and an update of the guideline for the diagnosis and treatment of asthma, which replaces the previous version for german speaking countries from the year 2006. The wealth of new data on the pathophysiology and the phenotypes of asthma, and the expanded spectrum of diagnostic and therapeutic options necessitated a new version and an update. This guideline presents the current, evidence-based recommendations for the diagnosis and treatment of asthma, for children and adolescents as well as for adults with asthma.

High intensity training in obesity: a Meta-analysis.

INTRODUCTION: High Intensity training (HIT) is a time-effective alternative to traditional exercise programs in adults with obesity, but the superiority in terms of improving cardiopulmonary fitness and weight loss has not been demonstrated. OBJECTIVE: to determine the effectiveness of HIT on cardiopulmonary fitness and body composition in adults with obesity compared to traditional (high volume continuous) exercise. METHODS: A systematic search of the main health science databases was conducted for randomized controlled trials comparing HIT with traditional forms of exercise in people with obesity. Eighteen studies were included in the meta-analysis. The (unstandardized) mean difference of each outcome parameters was calculated and pooled with the random effects model. RESULTS: HIT resulted in greater improvement of cardiopulmonary fitness (VO2max) (MD 1.83, 95% CI 0.70, 2.96, p<0.005; I2=31%) and a greater reduction of %body fat (MD -1.69, 95% CI -3.10, -0.27, p=0.02, I2=30%) compared to traditional exercise. Overall effect for BMI was not different between HIT and traditional exercise. CONCLUSION: Training at high intensity is superior to improve cardiopulmonary fitness and to reduce %body fat in adults with obesity compared to traditional exercise. Future studies are needed to design specific HIT programs for the obese with regard to optimal effect and long-term adherence.

[Biologicals in the Treatment of Bronchial Asthma]. / Biologika in der Behandlung des Asthma bronchiale.

Biologicals are a therapeutic option for patients with severe asthma. Difficult asthma in patients with untreated comorbidities or persistent trigger factors is much more common than severe refractory asthma. Optimized medical treatment, adherence to medication, elimination of trigger factors and treatment of comorbidities are essential before escalating the therapy with a biological. A careful phenotyping of patient with severe asthma is necessary because all available biological are only effective in certain phenotypes of the disease. For patients with severe allergic asthma an antibody against IgE (Omalizumab) is available. For patients with severe asthma and eosinophilic inflammation the Interleukin (IL)-5 Antibodies Mepolizumab and Reslizumab have recently been approved. The most prominent effect of biological treatment is the reduction of acute exacerbations in these patients. Further antibodies against IL-5 receptor (Benralizumab) or against the IL-4 receptor alpha chain (Dupilumab) are in advanced clinical development.

[Exacerbation of COPD]. / Expertentreffen COPD: Exazerbation der COPD.

Acute worsenings of chronic obstructive pulmonary disease (COPD) were for a long time regarded as transient deteriorations, although occasionally life-threatening. No connection to disease progression was recognized. Data emerging during the last decade showed that patients had a considerably worse survival outcome after severe exacerbations. This insight was consolidated in 2012 by a large population-based cohort analysis. At present, severe exacerbations are regarded as key risk factors for COPD disease progression. The present article summarises the current knowledge on exacerbations of COPD, as delineated during an expert workshop in February 2017. It comprises pathogenic mechanisms, exacerbation triggers, the characteristics of frequent exacerbators, and the predictors of worse survival outcome. The role of comorbidities is considered more closely. The presentation of the pharmacotherapy of acute exacerbation is supplemented by an overview of ventilatory support. Finally, pharmacological and nonpharmacological preventive measures are summarised.

GARP inhibits allergic airway inflammation in a humanized mouse model.

BACKGROUND: Regulatory T cells (Treg) represent a promising target for novel treatment strategies in patients with inflammatory/allergic diseases. A soluble derivate of the Treg surface molecule glycoprotein A repetitions predominant (sGARP) has strong anti-inflammatory and regulatory effects on human cells in vitro as well as in vivo through de novo induction of peripheral Treg. The aim of this study was to investigate the immunomodulatory function of sGARP and its possible role as a new therapeutic option in allergic diseases using a humanized mouse model. METHODS: To analyze the therapeutic effects of sGARP, adult NOD/Scidγc(-/-) (NSG) mice received peripheral blood mononuclear cells (PBMC) derived from allergic patients with sensitization against birch allergen. Subsequently, allergic inflammation was induced in the presence of Treg alone or in combination with sGARP. RESULTS: In comparison with mice that received Treg alone, additional treatment with sGARP reduced airway hyperresponsiveness (AHR), influx of neutrophils and macrophages into the bronchoalveolar lavage (BAL), and human CD45(+) cells in the lungs. Furthermore, the numbers of mucus-producing goblet cells and inflammatory cell infiltrates were reduced. To elucidate whether the mechanism of action of sGARP involves the TGF-ß receptor pathway, mice additionally received anti-TGF-ß receptor II (TGF-ßRII) antibodies. Blocking the signaling of TGF-ß through TGF-ßRII abrogated the anti-inflammatory effects of sGARP, confirming its essential role in inhibiting the allergic inflammation. CONCLUSION: Induction of peripheral tolerance via sGARP is a promising potential approach to treat allergic airway diseases.