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Zusammenfassung. Die Diagnose «Asthma bronchiale» überspannt schirmartig verschiedene Phänotypen dieses Krankheitsbildes. Die Differenzierung dieser Phänotypen und ihrer Overlaps wird immer wichtiger, da heute Phänotyp-spezifische Behandlungsansätze existieren, die nicht bei jeder Asthmaform Wirkung zeigen. Dazu gehören die Strategie der gezielten Allergenkarenz, die Allergen-Immuntherapie und vor allem auch die neu zur Verfügung stehenden Biologika für Asthma. Behandelbare Krankheitsmuster, sogenannte «Treatable Traits», erfordern eine gezielte Diagnostik. Das notwenige Wissen, um diese Merkmale identifizieren zu können, muss sich in der Praxis noch etablieren.

Spirometry in the Medical Practice - Part 1: Measuring Abstract. Today, every practitioner, as well as every hospital emergency, should be able to perform spirometry. However, the measurement requires solid basic knowledge as well as a certain amount of experience so that consistent and reproducible measurements are possible. Since the measurement depends heavily on the cooperation of the patient, typical errors must be recognised and corrected immediately. A rounded forced expiratory flow volume curve, or a sudden drop of the curve towards zero at the end of exhalation as well as clearly deviating curves or values in the minimum required three measurement manoeuvres are clear hints for an insufficiently forced expiration or an expiration that was stopped too early. Pulmonary function assistants need instructions as to when application of a rapid acting beta agonist with repeated spirometry to detect possible reversibility is necessary. This includes knowing how long therapeutic bronchodilators must be stopped prior to the test.

Zusammenfassung. Die Art und Weise, wie eine Spirometrie korrekt zu beurteilen ist, wurde 2005 international festgelegt. Im Vergleich zu vorher wurde neu definiert, dass der Quotient FEV1/VC als Parameter zur Erfassung einer Obstruktion herangezogen wird. Von einer signifikanten Obstruktion wird dann gesprochen, wenn dieser Messwert unterhalb der 5 %-Perzentile liegt, die üblicherweise als Z-Score von minus 1,645 im automatisch generierten Protokoll angegeben wird. Voraussetzung ist, dass die Software die modernen GLI-Normwerte enthält und die Patientendaten (Geschlecht, Alter, Grösse) eingegeben wurden. Eine nachgewiesene Obstruktion zeigt dann signifikante Reversibilität, wenn sich durch Bronchospasmolyse die FEV1 um mindestens 12 % und 200 ml absolut verbessert. Die Festlegung des Schweregrads einer Obstruktion basiert auf dem Ausmass der Minderung der FEV1 in Bezug auf den individuellen Normwert. Auch nach der Lektüre beider Teile dieser Publikation werden bei der Umsetzung in der klinischen Praxis in einzelnen Fällen noch Unklarheiten auftreten. Hier lohnt es sich, diese Befunde dem lokalen Pneumologen zur Mitbeurteilung vorzulegen. Daraus resultiert ein Lerneffekt, der die Expertise festigen wird.

[EN] While Casa de las Américas is recognized as one of the most influential cultural magazines in the Latin American intellectual field, its role in promoting literary translation has received little attention. This article focuses on how the magazine has translated and spread knowledge of literature written in the Anglophone Caribbean, one of the areas with the largest presence in the magazine during the 1970s. This interchange articulated a new dimension of the magazine’s discourse regarding Our America, which sought to establish unity among underdeveloped countries throughout the Americas as a means to assert regional and national identities amidst the onslaught of cultural imperialism. The enormous number of translations that Casa published in this period constitutes a milestone in the history of translation in the Caribbean and Latin America. The analysis in this article looks to dissect the exchanges, focusing on intersections of similarities and difference., [ES] Aunque Casa de las Américas es reconocida como una de las revistas culturales más influyentes en el campo intelectual latinoamericano, su papel de promotor de la traducción literaria ha sido poco estudiado. Este artículo se centra en cómo la revista traduce y difunde conocimiento sobre la producción literaria del Caribe anglófono, una de las zonas lingüísticas de la región que tuvo mayor presencia en la revista durante la década de los 70. Se plantea que, con este acercamiento, la revista articula una nueva dimensión de su discurso nuestroamericano, que busca establecer unidad entre los países subdesarrollados de América en pro de una afirmación identitaria que valora lo propio y resiste el colonialismo cultural. La gran cantidad de traducciones que puso en circulación la revista Casa en esta época constituye un hito en la historia de la traducción del Caribe y América Latina y su análisis en este artículo busca diseccionar los intercambios, enfocándose en los puntos de encuentro y desencuentro., Este artículo forma parte del proyecto “Connected Worlds: The Caribbean, Origin of Modern World” y ha recibido financiamiento del programa de investigación e innovación Horizon 2020, bajo el acuerdo de beca de Marie Sklodowska Curie, de la Unión Europea, por el Nº 823846 / This article forms part of the project “Connected Worlds: The Caribbean, Origin of Modern World” and has has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska Curie grant agreement Nº 823846.

For general practitioners there have been important novelties in the treatment of asthma due to recent modifications of the international guidelines from Global Initiative for Asthma (GINA). In Step 1, use of short-acting beta2-agonists (SABA) without concomitant inhaled corticosteroids (ICS) as controller is no longer recommended for lack of efficacy and safety reasons. Instead, low dose ICS-formoterol as needed is recommended. In Step 5, in patients with severe uncontrolled asthma GINA recommends targeted biologic therapies like interleukin antibodies. Asthma patients presenting simultaneously with symptoms of chronic obstructive pulmonary disease (COPD) should receive treatment containing ICS. Independent of the current corona pandemic, GINA recommendations stay in place.Les nouvelles recommandations GINA (Global Initiative for Asthma) modifient radicalement la prise en charge des patients asthmatiques pour le médecin de premier recours. Dans l’asthme léger (palier 1 GINA), les bêta2-agonistes à courte durée d’action (SABA) seuls comme traitement de secours ne sont plus recommandés au profit d’une association de corticostéroïdes inhalés (CSI) faiblement dosés avec un bronchodilatateur à longue durée d’action à début d’action rapide (formotérol). Dans l’asthme sévère non contrôlé (palier 5 GINA), l’objectif est d’éviter la corticothérapie orale au profit de thérapies biologiques ciblées (par exemple, anticorps anti-interleukine). Un traitement contenant des CSI doit être maintenu chez les asthmatiques même si une BPCO est associée. Les recommandations GINA ne sont pas modifiées par les conditions actuelles de pandémie.

Zusammenfassung. Inhalationen stellen die Grundlage der medikamentösen Behandlung von Atemwegserkrankungen dar. In den vergangenen Jahren ist die Therapie für die Patientinnen und Patienten, aber auch für medizinische Fachpersonen, komplexer geworden, da neue Systeme auf den Markt gekommen sind. Das dazu notwendige Wissen soll in diesem Artikel vermittelt werden.

Background Radiotherapy can induce cardiac injury in left-sided breast cancer cases. Cardiac-sparing irradiation using the deep inspiration breath-hold (DIBH) technique can achieve substantial dose reduction to vulnerable cardiac substructures compared with free breathing (FB). This study evaluated the dosimetric differences between both techniques at a single institution. Methods From 2017 to 2019, 130 patients with left-sided breast cancer underwent breast-conserving surgery (BCS; n = 121, 93.1%) or mastectomy (ME; n = 9, 6.9%) along with axillary lymph node staging (n = 105, 80.8%), followed by adjuvant irradiation in DIBH technique; adjuvant systemic therapy was included if applicable. 106 (81.5%) patients received conventional and 24 (18.5%) hypofractionated irradiation. Additionally, 12 patients received regional nodal irradiation. Computed tomography (CT) scans in FB and DIBH position were performed for all patients. Intrafractional 3D position monitoring of the patient surface in deep inspiration and breath gating was performed using Sentinel and Catalyst HD 3D surface scanning systems (C-RAD, Catalyst, C‑RAD AB, Uppsala, Sweden). Individual coaching and determination of breathing amplitude during the radiation planning CT was performed. Three-dimensional treatment planning was performed using standard tangential treatment portals (6 or 18 MV). The delineation of cardiac structures and both lungs was done in both the FB and the DIBH scan. Results All dosimetric parameters for cardiac structures were significantly reduced (p p p p p p Conclusion For all ascertained dosimetric parameters, a significant dose reduction could be achieved in DIBH technique.

Background Residential greenness has been associated with health benefits, but its biological mechanism is largely unknown. Investigation of greenness-related DNA methylation profiles can contribute to mechanistic understanding of the health benefits of residential greenness. Objective To identify DNA methylation profiles associated with greenness in the immediate surroundings of the residence. Methods We analyzed genome-wide DNA methylation in 1938 blood samples (982 participants) from the Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults (SAPALDIA). We estimated residential greenness based on normalized difference vegetation index at 30 × 30 m cell (green30) and 500 m buffer (green500) around the residential address. We conducted epigenome-wide association study (EWAS) to identify differentially methylated CpGs and regions, and enrichment tests by comparing to the CpGs that previous EWAS identified as associated with allergy, physical activity, and allostatic load-relevant biomarkers. Results We identified no genome-wide significant CpGs, but 163 and 56 differentially methylated regions for green30 and green500, respectively. Green30-related DNA methylation profiles showed enrichments in allergy, physical activity, and allostatic load, while green500-related methylation was enriched in allergy and allostatic load. Conclusions Residential greenness may have health impacts through allergic sensitization, stress coping, or behavioral changes. Exposure to more proximal greenness may be more health-relevant.

Type-2 Asthma: Leaving Behind the Perspective of the Seventies

Spirometry in the Medical Practice - Part 2: Interpretation

Spirometry in the Medical Practice - Part 1: Measuring

Zusammenfassung. Zum Einsatz von ICS beim Asthma ist die Datenlage klar. Bei der COPD hingegen, bei der in den letzten Jahren das Pendel weg von ICS, hin zu einer dualen Therapie aus LABA / LAMA geschwungen war, ist die Diskussion durch neue Arbeiten wieder offen. Es wäre aber sicher falsch, zum jetzigen Zeitpunkt ICS als sinnvolle Therapie für alle COPD-Patienten zu empfehlen, da die Therapie mit ICS mit Nebenwirkungen behaftet ist, v. a. der Erhöhung des Risikos an einer Pneumonie bzw. einer Osteoporose zu erkranken. Keinen Zweifel gibt es aber daran, dass Patienten mit Asthma COPD Overlap einer ICS-Therapie bedürfen.

Background and PurposeWith improved life expectancy, preventing neurocognitive decline after cerebral radiotherapy is gaining more importance. Hippocampal damage has been considered the main culprit for cognitive deficits following conventional whole-brain radiation therapy (WBRT). Here, we aimed to determine to which extent hippocampus-avoidance WBRT (HA-WBRT) can prevent hippocampal atrophy compared to conventional WBRT.Methods and MaterialsThirty-five HA-WBRT and 48 WBRT patients were retrospectively selected, comprising a total of 544 contrast-enhanced T1-weighted magnetic resonance imaging studies, longitudinally acquired within 24 months before and 48 months after radiotherapy. HA-WBRT patients were treated analogously to the ongoing HIPPORAD-trial (DRKS00004598) protocol with 30 Gy in 12 fractions and dose to 98% of the hippocampus ≤ 9 Gy and to 2% ≤ 17 Gy. WBRT was mainly performed with 35 Gy in 14 fractions or 30 Gy in 10 fractions. Anatomical images were segmented and the hippocampal volume was quantified using the Computational Anatomy Toolbox (CAT), including neuroradiological expert review of the segmentations.ResultsAfter statistically controlling for confounding variables such as age, gender, and total intracranial volume, hippocampal atrophy was found after both WBRT and HA-WBRT (p < 10−6). However, hippocampal decline across time following HA-WBRT was approximately three times lower than following conventional WBRT (p < 10−6), with an average atrophy of 3.1% versus 8.5% in the first 2 years after radiation therapy, respectively.ConclusionHA-WBRT is a therapeutic option for patients with multiple brain metastases, which can effectively and durably minimize hippocampal atrophy compared to conventional WBRT.

Zusammenfassung. Für die Allgemeinpraktikerin und den Allgemeinpraktiker gibt es wichtige Neuerungen in der Asthmabehandlung, da sich die internationalen Empfehlungen auf Basis der Global Initiative for Asthma (GINA) geändert haben. Für die Stufe 1 wird der alleinige Einsatz kurzwirksamer β2-Agonisten (SABA) ohne inhalatives Kortikosteroid (ICS) aufgrund der mangelnden Wirksamkeit und Sicherheit nicht mehr empfohlen, sondern stattdessen niedrig dosiertes ICS-Formoterol bei Bedarf. Bei schwerem, unkontrolliertem Asthma der Stufe 5 wird der Einsatz von biologischen Therapien, wie z.B. Interleukin-Antikörpern, empfohlen. Weisen Asthma-Kranke gleichzeitig auch Symptome einer chronisch-obstruktiven Lungenkrankheit (COPD) auf, sollten sie mit einer ICS-enthaltenden Therapie behandelt werden. Die Empfehlungen der GINA bleiben auch während der Corona-Pandemie unverändert gültig. Aktuelle Verschreibungsdaten der Schweiz belegen, dass sowohl SABA als auch orale Kortikosteroide (OCS) noch eine grosse Rolle in der Asthmabehandlung spielen und die GINA-Empfehlungen noch nicht ausreichend umgesetzt wurden.

Physical and Clinical Aspects of Inhalation Therapy for Asthma and COPD

Background and aims Alpha-1 antitrypsin (A1AT) is the most abundant serine protease inhibitor in human blood and exerts important anti-inflammatory and immune-modulatory effects. In combination with smoking or other long-term noxious exposures such as occupational dust and fumes, genetic A1AT deficiency can cause chronic obstructive pulmonary disease, a condition with elevated cardiovascular risk. The effects of A1AT deficiency on cardiovascular risk have hardly been studied today. Methods Using data from 2614 adults from the population-based SAPALDIA cohort, we tested associations of serum A1AT and SERPINA1 mutations with carotid intima-media thickness (CIMT, measured by B-mode ultrasonography) or self-reported arterial hypertension or cardiovascular disease in multiple regression models using a Mendelian Randomization like analysis design. Mutations Pi-S and Pi-Z were coded as ordinal genotype score (MM, MS, MZ/SS, SZ and ZZ), according to their progressive biological impact. Results Serum A1AT concentration presented a u-shaped association with CIMT. At the lower end of the A1AT distribution, an analogous, linear association between SERPINA1 score and higher CIMT was observed, resulting in an estimated 1.2% (95%-confidence interval -0.1-2.5) increase in CIMT per unit (p = 0.060). Genotype score was significantly associated with arterial hypertension with an odds ratio (OR) of 1.2 (1.0–1.5) per unit (p = 0.028). The association with cardiovascular disease was not significant (OR 1.3 (0.9–1.9)). Conclusions Our results support a possible causal relationship between genetic A1AT deficiency and increased cardiovascular risk, which needs to be better taken into account for the management of affected patients and first-degree relatives.

Erworben im Rahmen der Schweizer Nationallizenzen (http://www.nationallizenzen.ch), Respiratory diseases are associated with increased cardiovascular risk in adults, but little is known on the early impact on the vasculature in youth. The SAPALDIA Youth study, the offspring study of the Swiss Study on Air Pollution and Lung and Heart Disease In Adults (SAPALDIA), investigated the association between physician-diagnosed asthma status and common carotid artery intima media thickness (CIMT). Offspring underwent standardized clinical protocols and provided information on early life factors, health, and lifestyle. The association between per subject averages of CIMT and asthma was estimated using mixed linear regression analyses adjusting for main confounders, testing for interaction with gender and age. Of 257 offspring (mean age 15 years, 53% female), 11.5% reported doctor-diagnosed asthma (male 17%, female 7%). Mean CIMT was significantly different by gender (male 0.53 mm (± 0.045), female 0.50 mm (± 0.048); p

Background: Chronic obstructive pulmonary disease (COPD) is not restricted to smokers. Dietary habits may contribute to the disease occurrence. Epidemiological studies point to a protective effect of fruit and vegetable intake against COPD. Objective: To investigate the associations between dietary patterns and parameters of lung function related to COPD in the Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults (SAPALDIA). Methods: Data were included from the second follow-up assessment of the SAPALDIA cohort in 2010–2011 using a food frequency questionnaire. Principal component factor analysis was used to derive dietary patterns, whose association with FEV1, FEV1/FVC, FEF2575, and COPD was investigated by applying multivariate regression analyses. Results: After adjustment for potential confounders, the “prudent dietary pattern” characterised by the predominant food groups vegetables, fruits, water, tea and coffee, fish, and nuts was positively associated with FEV1 (increase of 40 mL per SD, p < 0.001). Also for factor 3 (“high-carbohydrate diet”), we found a significant positive association with FEV1 (with an increase per SD of 36 mL, p = 0.006). Conclusions: The main results are consistent with a protective effect of a diet rich in fruits, vegetables, fish, and nuts against age-related chronic respiratory disease. If confirmed in prospective cohorts, our results may guide nutritional counselling towards respiratory health promotion.

The Global Initiative for Asthma (GINA) is a network of individuals, organizations, and public health officials that was established to disseminate information about the care of patients with asthma and to improve asthma care. The GINA (“Global Strategy for Asthma Management and Prevention”) report has been updated annually since 2002. Due to new knowledge and therapeutic development in the field, the Swiss Respiratory Society felt the need to provide a new document that is based on both the available literature and the recommendations of the 2016 GINA report. Key new features of the 2016 GINA report include a “new” definition of asthma, underscoring its heterogeneous nature, and the core elements of variable symptoms and variable expiratory airflow limitation; the importance of confirming the diagnosis of asthma in order to minimize both under- and overtreatment; practical tools for the assessment of symptom control and risk factors for adverse outcomes; a comprehensive approach to asthma management that acknowledges the foundational role of inhaled corticosteroid therapy, but also provides a framework for individualizing patient care; an emphasis on maximizing the benefit of available medications by addressing common problems such as incorrect inhaler technique and poor adherence; a continuum of care for worsening asthma, starting with early self-management and progressing to primary care or acute care management; and diagnosis of the asthma/chronic obstructive pulmonary disease overlap syndrome. This document is meant to advice the key stakeholders on the diagnosis and management of asthma and highlights the need to individualize the care of each and every asthmatic patient.

Background - The current study was aimed at investigating the feasibility of hippocampus‐avoidance whole‐brain radiation therapy with a simultaneous integrated boost (HA‐WBRT+SIB) for metastases and at assessing tumor control in comparison with conventional whole‐brain radiation therapy (WBRT) in patients with multiple brain metastases. Methods - Between August 2012 and December 2016, 66 patients were treated within a monocentric feasibility trial with HA‐WBRT+SIB: hippocampus‐avoidance WBRT (30 Gy in 12 fractions, dose to 98% of the hippocampal volume ≤ 9 Gy) and a simultaneous integrated boost (51 or 42 Gy in 12 fractions) for metastases/resection cavities. Intracranial tumor control, hippocampal failure, and survival were subsequently compared with a retrospective cohort treated with WBRT via propensity score matching analysis. Results - After 1:1 propensity score matching, there were 62 HA‐WBRT+SIB patients and 62 WBRT patients. Local tumor control (LTC) of existing metastases was significantly higher after HA‐WBRT+SIB (98% vs 82% at 1 year; P = .007), whereas distant intracranial tumor control was significantly higher after WBRT (82% vs 69% at 1 year; P = .016); this corresponded to higher biologically effective doses. Intracranial progression‐free survival (PFS; 13.5 vs 6.4 months; P = .03) and overall survival (9.9 vs 6.2 months; P = .001) were significantly better in the HA‐WBRT+SIB cohort. Four patients (6.5%) developed hippocampal metastases after hippocampus avoidance. The neurologic death rate after HA‐WBRT+SIB was 27.4%. Conclusions - HA‐WBRT+SIB can be an efficient therapeutic option for patients with multiple brain metastases and is associated with improved LTC of existing metastases, higher intracranial PFS, a reduction of the neurologic death rate, and an acceptable risk of radiation necrosis. The therapy has the potential to prevent neurocognitive adverse effects, which will be further evaluated in the multicenter, phase 2 HIPPORAD trial.

Das Asthma-COPD-Overlap ist ein wichtiger COPD-Phanotyp. Es lasst sich klinisch nicht erkennen, sondern muss aktiv gesucht werden.

Benralizumab: Targeting the IL-5 Receptor in Severe Eosinophilic Asthma

Zusammenfassung. Für Patienten mit schwierig kontrollierbarem, schwerem Asthma bronchiale stehen heute neben der inhalativen Medikation hochwirksame, gezielte Behandlungsmöglichkeiten zur Verfügung. Bei Vorliegen einer deutlichen Eosinophilie verspricht die Hemmung der Interleukin-5-Achse (IL-5) mit spezifischen, monoklonalen Antikörpern eine wirksame und nebenwirkungsarme Alternative zur dauerhaften systemischen Steroidtherapie. In diesem Übersichtsartikel werden die Daten zu Benralizumab, einem spezifischen Antikörper gegen den IL-5-Rezeptor Alpha, zusammengefasst. Dieser Angriffspunkt verhindert die Rezeptorstimulation durch IL-5 und aktiviert eine NK-zellvermittelte zytotoxische Reaktion, die zur Apoptose der eosinophilen Granulozyten führt. Die s.c.-Applikation von Benralizumab führt innerhalb von Tagen zur nahezu vollständigen Depletion der Eosinophilen im Blut mit konsekutiver Verbesserung der Lungenfunktion und Stabilisierung des Asthmas. Für ausgewählte Patienten mit schwerem Asthma eröffnet sich hier eine vielversprechende Therapie-Option.

Zusammenfassung. Für Patienten mit schwierig kontrollierbarem, schwerem Asthma bronchiale stehen heute neben der inhalativen Medikation hochwirksame, gezielte Behandlungsmöglichkeiten zur Verfügung. Bei Vorliegen einer deutlichen Eosinophilie verspricht die Hemmung der Interleukin-5-Achse (IL‑5) mit spezifischen, monoklonalen Antikörpern eine wirksame und nebenwirkungsarme Alternative zur dauerhaften systemischen Steroidtherapie. In diesem Übersichtsartikel werden die Daten zu Benralizumab, einem spezifischen Antikörper gegen den IL-5-Rezeptor Alpha, zusammengefasst. Dieser Angriffspunkt verhindert die Rezeptorstimulation durch IL-5 und aktiviert eine NK-zellvermittelte zytotoxische Reaktion, die zur Apoptose der eosinophilen Granulozyten führt. Die s.c.-Applikation von Benralizumab führt innerhalb von Tagen zur nahezu vollständigen Depletion der Eosinophilen im Blut mit konsekutiver Verbesserung der Lungenfunktion und Stabilisierung des Asthmas. Für ausgewählte Patienten mit schwerem Asthma eröffnet sich hier eine vielversprechende Therapie-Option.

Zusammenfassung. Dauert Husten länger als 8 Wochen an, wird er als chronisch bezeichnet. Patienten mit Husten sind stark in ihrer Lebensqualität eingeschränkt. Der Besuch eines Konzerts kann verunmöglicht werden, Mitmenschen vermuten teilweise eine infektiöse Ursache und ziehen sich zurück. Bei massivem Husten kann es zu Urininkontinenz, Hustensynkopen und zur Entwicklung von Abdominal- bzw. Leistenhernien kommen. Einem chronischen Husten liegen meist mehrere kausale Faktoren zugrunde. Nach Identifizierung und Elimination sistiert der Hustenreiz oft. Allerdings fällt auf, dass die gleichen Faktoren im selben Masse bei einer anderen Person vorhanden sein können, ohne dass chronischer Husten auftritt. Es muss davon ausgegangen werden, dass Menschen mit chronischem Husten an einem Hypersensitivitäts-Syndrom leiden, das zu diesem Phänotyp führt. Therapieversuche mit Gabapentin wurden unternommen. Noch wirksamere Substanzen sind in der Erprobung.