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Introduction Ameliorer le controle de l’asthme est un objectif essentiel de la prise en charge de l’asthme. L’effet du mepolizumab sur le controle de l’asthme evalue par l’Asthma Control Questionnaire-5(ACQ-5) a ete rapporte dans les essais cliniques, mais les donnees en vraie vie sont limitees. Methodes REALITI-A, etude prospective en vraie vie, multicentrique, internationale, a enrole des patients avec un asthme severe a eosinophiles (ASE), ayant initie un traitement par mepolizumab sur 51 centres dans 7 pays. Une periode de 12 mois de donnees precedant l’inclusion etait necessaire pour decrire les donnees demographiques des participants, le fardeau de l’ASE et les traitements. Le controle de l’asthme a ete evalue par l’ACQ-5. Les scores a l’initiation ont ete compares aux scores a 3,6,9 et 12 mois. Les changements du controle depuis l’initiation et le taux de participants ayant une difference minimale importante [DMI] depuis l’initiation de 0,5 unites ont ete evalues. Des modeles mixtes de mesures repetees ont ete utilises pour l’analyse. Resultats Les donnees initiales etaient disponibles pour 368 patients qui ont complete un suivi de 12 mois ( Fig. 1 ). Dix-neuf pour cent (n = 70/368) des patients ont arrete le mepolizumab dans l’annee suivant l’initiation ; les raisons les plus frequentes etaient : la decision du patient (7 % ; n = 27/368), la discretion de l’investigateur (4 % ; n = 14/368), le manque d’efficacite (4 % ; n = 13/368). A l’inclusion, les patients avaient un score moyen ACQ-5 en moindres carres (IC95 %) de 2,99 (2,85 ; 3,13). L’initiation du mepolizumab a ete associee a une amelioration du controle de l’asthme, avec des moyennes MC (IC95 %) du score ACQ-5 a 3,6,9 et 12 mois de 1,81 (1,66 ; 1,96), 1,73 (1,56 ; 1,89), 1,84 (1,62 ; 2,05), et 1,84 (1,63 ; 2,05). Dans les 3 mois, 65 % (152/234) des patients ont obtenu une DMI, passant a 71 % (84/119) apres 12 mois. Les ameliorations ont ete observees dans chaque tranche de taux d’eosinophiles sanguins a l’inclusion, avec 56 % (10/18), 60 % (9/15), et 75 % (62/83) des patients avec des taux d’eosinophiles sanguins Conclusion Cette etude prospective en vie reelle confirme l’efficacite du mepolizumab chez les patients avec un ASE en termes d’amelioration du controle de l’asthme a 3 mois, avec des ameliorations significatives du score ACQ-5. Ces resultats montrent un benefice rapide et significatif du controle de l’asthme avec le mepolizumab en vraie vie, coherent avec les resultats des essais cliniques controles.

When caring for patients with respiratory diseases, always think of the heart! This is especially important for COPD patients, but also for a variety of other disorders of the respiratory system. At the workshop "Luftschlösser", held once more at Wiesbaden, Germany in February 2019 the many and important interactions of the lungs and the heart as well as the therapeutic implications were discussed. Based on pathophysiology, the psycho-social consequences of dyspnea, the leading symptom in patients with lung and heart disease became apparent. A particularly demanding diagnostic and therapeutic situation occurs in patients suffering simultaneously of lung and heart disease. It has been shown how frequently the diagnosis myocardial infarction is missed in COPD patients - and vice versa. Surprisingly, this is also the case in asthmatics with coronary heart disease or heart failure, a fact not readily known in clinical practice. In patients with emphysema and no apparent heart disease, hyperinflation leads to significantly restricted heart function. Reducing hyperinflation by inhaling broncholytics thus improves heart function. Biomarkers are increasingly being used for diagnostic purposes. Their role is being investigated in the large German COPD cohort COSYCONET. Lung patients suffering from more severe heart diseases pose a challenge for therapy in intensive care, especially when ventilated, and weaning from the ventilator is prolonged. Lung vessel diseases are "classic" examples of the intimate interaction of the lungs and the heart. In pulmonary arterial hypertension as well as in chronic thrombo-embolic pulmonary hypertension the lag time between the first symptoms and the definite diagnosis is often unacceptably long. For both diseases of the lung vessels therapeutic options have improved significantly over the last years. Pulmonologists should take care of this increasingly important patient group. Sleep-related breathing disorders and heart function are closely intertwined. Both conditions need special attention after the results of the SERVE-HF trial have been published. But there is no doubt that obstructive sleep apnea represents an independent and important risk factor for cardiovascular disease and needs to be treated according to existing guidelines.This workshop demonstrated impressively the multiple interactions of the respiratory system with cardiac function, resulting diagnostic and therapeutic problems, and means to overcome these problems. Guidelines for respiratory diseases should appropriately address cardiac comorbidity.Pneumologen sollten immer auch an das Herz denken, wenn sie Patienten mit pulmonalen Erkrankungen diagnostizieren und therapieren. Dies gilt besonders für die COPD, aber auch eine ganze Reihe anderer pneumologischer Krankheitsbilder. Auf dem Workshop „Luftschlösser“, der wieder im Februar 2019 in Wiesbaden abgehalten wurde, diskutierten die Teilnehmer die vielfältigen Interaktionen von Lunge und Herz und deren Bedeutung für die Therapie. Ausgehend von pathophysiologischen Überlegungen wurden die psychosozialen Auswirkungen des Kardinalsymptoms Dyspnoe für Patienten sowohl mit Lungen- als auch Herzerkrankungen deutlich. Eine besondere diagnostische und therapeutische Herausforderung liegt im simultanen Auftreten von pulmonalen und kardialen Krankheiten beim individuellen Patienten. So wurde gezeigt, wie häufig die Komorbidität Herzinfarkt bei COPD übersehen wird – und vice versa. Dass auch Asthmatiker häufiger eine koronare Herzerkrankung oder eine Herzinsuffizienz aufweisen, ist im klinischen Alltag nicht immer präsent. Die Überblähung der Lunge beim Emphysem beeinträchtigt die kardiale Funktion auch beim Herzgesunden. Die medikamentöse Verminderung der Überblähung verbessert so die kardiale Funktion. Biomarker helfen bei der Differenzialdiagnose. Ihre Rolle wird in der großen deutschen Kohorte COSYCONET untersucht. Der schwerergradig herzkranke Lungenpatient stellt therapeutisch eine große Herausforderung dar, insbesondere wenn er intensiv- und beatmungspflichtig wird und das Weaning prolongiert verläuft. Ein „klassisches“ Beispiel der Interaktion von Lunge und Herz stellen die Lungengefäßerkrankungen dar. Sowohl bei der pulmonal-arteriellen Hypertonie als auch der chronisch-thromboembolischen pulmonalen Hypertonie vergeht nicht selten eine zu lange Zeit bis zur Diagnosestellung. Die therapeutischen Möglichkeiten haben sich für beide Gruppen von Lungengefäßerkrankungen in den letzten Jahren erheblich verbessert und stellen eine wichtige Aufgabe für Pneumologen dar. Schlafbezogene Atmungsstörungen und die kardiale Funktion stehen in einer Wechselbeziehung, die nach der SERVE-HF-Studie einer besonderen Aufmerksamkeit bedarf. Unstrittig bleibt, dass die obstruktive Schlafapnoe ein unabhängiger Risikofaktor für kardiovaskuläre Erkrankungen ist und leitlinienkonform behandelt werden muss.Der Workshop zeigte eindrucksvoll die vielfältigen Wechselwirkungen von Herz und respiratorischem System, die zu Problemen in Diagnostik und Therapie führen können. Pneumologische Leitlinien sollten den Aspekt der kardialen Komorbidität stärker in den Fokus nehmen.

The recognition, correct diagnosis and adequate clinical management of infections caused by atypical mycobacteria are challenging tasks in clinical practice. Invasive infections caused byDie Erkennung, Diagnosestellung und Behandlung von Infektionen durch atypische Mykobakterien stellen eine besondere klinische Herausforderung dar. Über invasive Erkrankungen durch das zum

Rationale Alterations of acid-base metabolism are an important outcome predictor in acute exacerbations of COPD, whereas sufficient metabolic compensation and adequate renal function are associated with decreased mortality. In stable COPD there is, however, only limited information on the combined role of acid-base balance, blood gases, renal and respiratory function on exacerbation risk grading. Methods We used baseline data of the COPD cohort COSYCONET, applying linear and logistic regression analyses, the results of which were implemented into a comprehensive structural equation model. As most informative parameters it comprised the estimated glomerular filtration rate (eGFR), lung function defined via forced expiratory volume in 1 s (FEV1), intrathoracic gas volume (ITGV) and (diffusing capacity for carbon monoxide (DLCO), moreover arterial oxygen content (CaO2), partial pressure of oxygen (PaCO2), base exess (BE) and exacerbation risk according to GOLD criteria. All measures were adjusted for age, gender, body-mass index, the current smoking status and pack years. Results 1506 patients with stable COPD (GOLD grade 1–4; mean age 64.5 ± 8.1 y; mean FEV1 54 ± 18 %predicted, mean eGFR 82.3 ± 16.9 mL/min/1.73 m2) were included. BE was linked to eGFR, lung function and PaCO2 and played a role as indirect predictor of exacerbation risk via these measures; moreover, eGFR was directly linked to exacerbation risk. These associations remained significant after taking into account medication (diuretics, oral and inhaled corticosteroids), whereby corticosteroids had effects on exacerbation risk and lung function, diuretics on eGFR, BE and lung function. Conclusion Even in stable COPD acid-base metabolism plays a key integrative role in COPD risk assessment despite rather small deviations from normality. It partially mediates the effects of impairments in kidney function, which are also directly linked to exacerbation risk.

The COPD is a very common, chronic, non-contagious disease causing high mortality as well as high socio-economical costs worldwide. Its clinical assessment progressively becomes more comprehensive including the lung function, the rate of exacerbations, the physical capacity, the sensation of dyspnoea, and comorbidities. On the other hand, our therapeutic options are very limited: Although there are several well-tolerated and effective combinable bronchodilators of the group of long-acting beta2-mimetics and anticholinergics, drugs causally affecting pathophysiology are barely available. As anti-inflammatory principles only inhaled glucocorticoids as well as one orally available inhibitor of phosphodiesterase 4 are approved, each improving the course of disease in a subgroup of patients. This lack of effective causative therapeutic principles on the one hand and of biomarkers clearly stratifying patients on the other hand to a large extend are caused by our limited understanding of the pathophysiology. Therefore, this review presents the current progress in clinical and experimental research on COPD with regard to clinical practice.

Despite considerable progress concerning pharmaceutical therapeutic options, many COPD patients show a markedly reduced quality of life and increased mortality risk. This workshop aimed to identify COPD-specific factors impeding an improved mode of care for patients with COPD. Such factors are: the generally lower social and educational status of the majority of COPD patients; the stigma of COPD as a self-inflicted disease ("smoker's lung"); the strict sectoral separation within the German health care system. In the second part the workshop tried to identify ways to improve the care of COPD patients. Use of health information technology, improved communication between care givers and patients as well as between the health care sectors, integrating rehabilitation and establishing self-management education are factors within an integrated patient-centered approach. In summary, an integrated management of the individual patient with COPD including multi-professional teams should contribute to optimizing the quality of COPD care.Die Lebensqualität und Prognose der COPD-Patienten lässt trotz erheblich verbesserter medikamentöser Therapieoptionen weiterhin zu wünschen übrig. Ziel des Workshops war es, COPD-spezifische Hindernisse auf dem Weg zur verbesserten Betreuung der Patienten zu beschreiben. Dazu zählen der Sozial- und Bildungsstatus der COPD-Patienten sowie die gesellschaftliche Stigmatisierung der Erkrankung als selbstverschuldete „Raucherkrankheit“. Die strenge sektorale Trennung trägt zu Defiziten in der Betreuung bei. Im zweiten Teil des Workshops wurden Möglichkeiten der Verbesserung dargestellt. Die Nutzung IT-basierter Hilfsmittel, verbesserte Kommunikation zwischen Patienten und Therapeuten und zwischen den Sektoren des Gesundheitswesens, verbesserte Integration von Rehabilitation sowie durch Strategien des Selbstmanagements, sind solche Möglichkeiten. Als Schlussfolgerung konnte festgehalten werden, dass ein integriertes Patientenmanagement mit Einbeziehung multiprofessioneller Teams die Betreuungsqualität nachhaltig verbessern könnte.

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.Die vorliegende Leitlinie ist eine Neufassung und Aktualisierung der Leitlinie zur Diagnostik und Therapie von Patienten mit Asthma, welche die bisher für den deutschen Sprachraum gültige Version aus dem Jahr 2006 ablöst. Die Fülle an neuen Erkenntnissen zur Pathophysiologie und zu den Phänotypen von Asthma und das erweiterte Spektrum an diagnostischen und therapeutischen Möglichkeiten bei dieser Erkrankung machte eine Neufassung und Aktualisierung notwendig. Es werden sowohl für Kinder und Jugendliche als auch für Erwachsene mit Asthma die aktuellen, Evidenz-basierten diagnostischen und therapeutischen Empfehlungen dargelegt.

Insufficient cerebral blood flow regulation to meet increasing metabolic demand during physical exertion could be associated with cognitive impairment. We compared cerebral oxygen availability during exercise in cognitively impaired (CI) to cognitively normal (CN) COPD patients. Fifty-two patients (FEV1: 51 ± 16%) were classified as CN or CI according to the Montreal Cognitive Assessment. Patients performed cycle-ergometry at 75% peak capacity with continuous measurement of Near-Infrared Spectroscopy frontal-cortex Tissue oxygen Saturation Index (TSI), cerebral haemoglobin indices (oxy/deoxy/total- Hb), transcutaneous carbon-dioxide partial pressure (TcPCO2), and arterial oxygen saturation (SpO2). Twenty-one patients (40%) presented evidences of CI. During exercise, CN and CI patients exhibited mild to moderate SpO2decline (nadir[Δ]≥ −3 ± 2% and −5 ± 3%, respectively) but preserved baseline frontal-cortex TSI levels, whilst presenting small TcPCO2 perturbations and increased cerebral total-Hb (post [Δ]≥ 2.0 ± 3 μM sec−1). CI patients preserve the capacity to adequately maintain cerebral oxygen availability during submaximal exercise. Therefore, rehabilitative exercise training in CI patients with COPD exhibiting mild to moderate exercise-induced SpO2 decline does not appear to lead to reduced cerebral oxygen availability. © 2018 Elsevier B.V.

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.

Chronic obstructive pulmonary disease (COPD) is considered to be a complex and heterogeneous disease comprising multiple components. Its clinical presentation, pattern of functional disturbance, disease presentation and pathology varies tremendously between individuals despite the common feature of incompletely reversible airflow obstruction. It is therefore widely accepted that COPD is characterized by discriminable phenotypes that represent specific patterns of these disease features. COPD phenotypes are believed to correlate with outcome parameters such as severity of symptoms, exacerbations, functional loss or death and to require different treatment algorithms.This survey is the result of presentations that were given during an expert conference. It highlights the significance of major comorbidities, genetic, morphologic and inflammatory COPD-phenotypes and their impact on disease progression and treatment modalities.

Objectives: We aimed to identify clinical characteristics and to assess effectiveness of different initial antibiotic regimens in adult patients with community-acquired pneumonia (CAP) caused by Haemophilus influenzae. Methods: Characteristics were compared between patients with H. influenzae monoinfection versus CAP of other and unknown aetiology enrolled by the German prospective cohort study CAPNETZ. Impact of initial antibiotic treatment on "early clinical response" according to FDA criteria and overall clinical cure were analysed. Results: H. influenzae was found in 176 out of 2790 patients with pathogen detection (6.3%). Characteristics significantly associated with a H. influenzae CAP (p

The COPD is a very common, chronic, non-contagious disease causing high mortality as well as high socio-economical costs worldwide. Its clinical assessment progressively becomes more comprehensive including the lung function, the rate of exacerbations, the physical capacity, the sensation of dyspnoea, and comorbidities. On the other hand, our therapeutic options are very limited: Although there are several well-tolerated and effective combinable bronchodilators of the group of long-acting beta2-mimetics and anticholinergics, drugs causally affecting pathophysiology are barely available. As anti-inflammatory principles only inhaled glucocorticoids as well as one orally available inhibitor of phosphodiesterase 4 are approved, each improving the course of disease in a subgroup of patients. This lack of effective causative therapeutic principles on the one hand and of biomarkers clearly stratifying patients on the other hand to a large extend are caused by our limited understanding of the pathophysiology. Therefore, this review presents the current progress in clinical and experimental research on COPD with regard to clinical practice.

Die chronisch-obstruktive Lungenerkrankung (COPD) ist charakterisiert durch eine nichtreversible und typischerweise progrediente Atemwegsobstruktion und tritt uberwiegend bei alteren Personen auf. Rauchen ist wichtigster Risikofaktor. Bis zu 25% der Patienten entwickeln jedoch ungewohnlich fruh eine COPD oder haben nie geraucht; hier bestehen oft diagnostische und therapeutische Unsicherheiten. In dieser Ubersicht werden Umweltfaktoren, genetische Dispositionen und Vorerkrankungen diskutiert, die in eine COPD munden konnen. Die Genetik der COPD ist komplex. Einzige gesicherte genetische Pradisposition ist der α1-Antitrypsin-Mangel (AATM): Mutationen des kodierenden Gens SERPINA1 bedingen Konformationsanderungen des Proteins, die zur Akkumulation von AAT in Leberzellen und zu einem Mangel im Organismus fuhren, der in der Lunge in einer fruhen COPD resultieren kann. Rechtzeitige Identifikation des AATM und subsequente Lebensstilanderung konnen helfen, den Ausbruch der COPD hinauszuzogern.

In industrialized countries respiratory tract infections are one of the most common reasons for medical consultations. It is assumed that almost one third of these infections include the lower respiratory tract (LRTI), e. g. acute bronchitis, acute exacerbation of chronic obstructive pulmonary disease (COPD), community- or hospital-acquired pneumonia and influenza. Due to a lack of sufficient and valid investigations to prove the presence of respiratory viruses their impact in the pathogenesis of lower respiratory tract infection has probably been underestimated for a long time. Therefore, there might have been many cases of unnecessary antibiotic treatment, especially in cases of acute bronchitis or acute exacerbations of COPD, because of an assumed bacteriological cause. With the introduction of more sensitive investigational procedures, such as polymerase chain reaction, it is possible to sufficiently prove respiratory viruses and therefore illuminate their role in the pathogenesis of lower respiratory tract infections of the adult. We have reviewed the current literature on the impact of viruses in lower respiratory tract infections to elucidate the role of viruses in the pathogenesis of lower respiratory tract infections. The preceding parts of this series provided an introduction to the frequently found viruses, pathogenesis, and diagnostic procedures (part I) as well as common viral infections of the lower respiratory tract (part II). The present 3 (rd) part deals with therapy for and prevention of viral LRTI.

Eine akute respiratorische Insuffizienz und das „acute respiratory distress syndrome“ (ARDS) sind haufige Krankheitsbilder der internistischen Intensivmedizin und treten als Folge verschiedener Ausloser auf. Hier werden die Krankengeschichten von 2 Patientinnen vorgestellt, bei denen eine maligne Erkrankung der Ausbildung einer akuten respiratorischen Insuffizienz zugrunde lag. Bei der ersten Patientin bestand eine akute myeloische Leukamie M5 nach FAB. Die zweite Patientin war an einem weit fortgeschrittenen Bronchialkarzinom erkrankt, welches bereits ausgedehnt metastasiert hatte. Diese Fallberichte zeigen, dass sich neben den klassischen Ursachen eines ARDS im klinischen Alltag auch Krankheitsbilder finden, die ein ARDS imitieren. Neben den soliden Tumoren und Lymphomen sind dies insbesondere akute Verlaufsformen entzundlicher, parenchymatoser Lungenerkrankungen wie z. B. die akute interstitielle Pneumonie, die akute eosinophile Pneumonie, die diffuse alveolare Hamorrhagie und die akute Form einer exogen allergischen Alveolitis. Bei unklaren Krankheitsbildern mit respiratorischer Insuffizienz empfiehlt sich eine dahingehende diagnostische Abklarung.

Augmentation therapy in Alpha-1 Antitrypsin Deficiency aims to reduce the progression of lung emphysema, to reduce exacerbation frequency, and to improve quality of life. This expert statement briefly summarizes the most important treatment studies performed in patients with Alpha-1 Antitrypsin Deficiency and severe lung emphysema. Indications and contraindications for long-term intravenous augmentation therapy with human Alpha-1 Antitrypsin are derived from the available study results. Safety issues and the controversies of this topic are discussed in detail.