Tsogyal Daniela Latshang

Background: Severe asthma is a complex chronic airway disease. Biologic therapies are targeted monoclonal antibody treatments used in patients with uncontrolled, severe asthma, but real-world data from long-term registries and on patients who remain biologic-naïve are limited. This study compared severe asthma patients with and without biologic therapy and identified predictors of key clinical remission components. Methods: In this cross-sectional analysis of adult patients from the Swiss Severe Asthma Registry (SSAR), we compared patients treated with a biologic for ≥6 months to biologic-naïve patients (never exposed to biologics). Baseline characteristics were summarized descriptively. Multivariable logistic regression was used to identify predictors of four remission components: good asthma control (ACT ≥ 20), absence of exacerbations, no maintenance oral corticosteroid (OCS) use, and preserved lung function (FEV₁ > 80% predicted). Results: Of 394 patients, 298 (75.6%) were biologic-treated and 96 (24.4%) were biologic-naïve. Biologic-treated patients more often had allergic asthma and type-2–related comorbidities, and showed better outcomes, including fewer exacerbations (0.49 vs. 1.09/year; p < 0.001) and higher ACT scores (20.0 vs. 17.2; p < 0.001). Biologic therapy was independently associated with higher odds of asthma control (OR 3.96; p = 0.006), no exacerbations (OR 5.11; p = 0.001), no OCS use (OR 6.27; p = 0.002), and FEV₁ > 80% predicted (OR 4.42; p = 0.011). Overall, 24.2% of biologic-treated patients and 6.2% of biologic-naïve patients fulfilled all four remission components. Conclusions: In this real-world registry cohort, biologic-treated patients were more likely to meet individual and composite remission criteria than biologic-naïve patients. The relatively low proportion of patients achieving all four stringent criteria highlights the need to revisit current remission definitions and to adopt individualized, multidimensional treatment goals in severe asthma.

Background: Limited data exist on the reliability, efficacy and safety of ultrasound-guided transbronchial cryobiopsy for suspicious mediastinal and hilar lesions. This study shares findings from implementing this method and compares the results with those of the standard endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). Methods: Patients undergoing diagnostic bronchoscopy for mediastinal or hilar lesions in four Swiss centres were included. The study aims to assess the diagnostic yield and safety of EBUS-guided cryobiopsy compared with EBUS-TBNA. Tunnelling to the target lesion was performed using an electric needle knife (70.8%), a 19 G- (12.4%) or a 22 G needle (16.8%). Cryobiopsies were obtained with a freezing time of 4–7 s (18.2% with a 1.7 mm probe) or 6–10 s (81.8% with a 1.1 mm probe). Results: Altogether, 137 patients were enrolled with a median follow-up of 89 days. The overall diagnostic yield was 56.2% for EBUS-TBNA and 91.2% for cryobiopsies (p<0.001). Cryobiopsies increased the diagnostic yield for benign disorders (+28.5%), uncommon tumours (+5.9%) and other metastatic cancer (+0.6%), but not for lung cancer (+0%). For lung cancer (n=27), immunohistochemistry was obtainable in 40.7% of EBUS-TBNA (median of 3 probes [IQR 3 to 3]), significantly lower than cryobiopsy’s 88.9% yield (median of 4 probes [IQR 3 to 5]) (p<0.001). Adverse events were found in 23.4% of participants; 10.2% had mild to moderate bleeding, 0.7% had pneumonia, and 0.7% (one) of patients had pneumothorax following pneumomediastinum. No deaths or mediastinum infections were observed. Conclusion: Cryobiopsy of mediastinal and hilar lesions improves the diagnostic yield compared with EBUS-TBNA while maintaining a favourable safety profile.

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.

Ex vivo lung perfusion (EVLP) has been implemented to increase the number of donor lungs available for transplantation. The use of K(ATP) channel modulators during EVLP experiments may protect against lung ischemia-reperfusion injury and may inhibit the formation of reactive oxygen species. In a rat model of donation after circulatory death with 2 h warm ischemic time, we evaluated rat lungs for a 4-hour time in EVLP containing either mitochondrial-specific or plasma membrane and/or sarcolemmal-specific forms of K(ATP) channel modulators. Lung physiological data were recorded, and metabolic parameters were assessed. When compared to the control group, in the EVLP performed with diazoxide or 5-hydroxydecanoic acid (5-HD) we recorded significantly lower pulmonary vascular resistance and only in the diazoxide group recorded significant lung weight loss. In the perfusate of the 5-HD group, interleukin-1β and interleukin-1α were significantly lower when compared to the control group. Perfusate levels of calcium ions were significantly higher in both 5-HD and cromakalim groups, whereas the levels of calcium, potassium, chlorine and lactate were reduced in the diazoxide group, although not significantly when compared to the control. The use of a diazoxide mitochondrial-specific K(ATP) channel opener during EVLP improved lung physiological and metabolic parameters and reduced edema.

Zusammenfassung. Der Gesundheitszustand von Patienten mit einer vorbestehenden Lungenkrankheit wird auf unterschiedlichste Art durch die hypobare Hypoxie während eines Höhenaufenthaltes beeinflusst. Nicht alle Patienten mit vorbestehender Lungenkrankheit müssen auf das Höhenbergsteigen verzichten. Die Reise sollte aber mit grosser Sorgfalt geplant werden und insbesondere vorgängig eine ärztliche Beurteilung des Krankheitszustandes beinhalten. Es müssen genügend Medikamente, auch für den Notfall, mitgeführt werden. Alle bekannten Vorsichtsmassnahmen, die das Risiko für eine höhenassoziierte Erkrankung vermindern können, müssen bedacht und allenfalls Routenplanung und Medikation angepasst respektive ergänzt werden. In den letzten Jahren wurden grössere, randomisiert – kontrollierte Studien an Patienten mit Schlafapnoe und COPD auf moderater Höhe (1630 – 3200 m) durchgeführt, mit dem Ziel, die pathophysiologischen Auswirkungen der hypobaren Hypoxie und die optimale Therapieoption zu finden. Bei anderen Lungenerkrankungen wie Asthma bronchiale, pulmonaler Hypertonie oder diffusen parenchymatösen Lungenerkrankungen findet sich nur eine begrenzte Anzahl an Studien mit kleinen Patientenzahlen, es kann aber dennoch, unter Beachtung pathophysiologischer Überlegungen, eine Einschätzung des Gesundheitsrisikos mit Therapieempfehlungen während eines Höhenaufenthaltes abgegeben werden.

Latshang, Tsogyal Daniela, Daniela Juliana Mueller, Christian Maurizio Lo Cascio, Anne-Christin Stöwhas, Katrin Stadelmann, Noemi Tesler, Peter Achermann, Reto Huber, Malcolm Kohler, and Konrad Ernst Bloch. Actigraphy of wrist and ankle for measuring sleep duration in altitude travelers. High Alt Med Biol. 17:194–202, 2016—Aims: Actigraphy might be convenient to assess sleep disturbances in altitude field studies. Therefore, we evaluated whether actigraphy accurately measures sleep duration in healthy subjects traveling to altitude. Methods: Fifty-one healthy men, aged mean ± standard deviation (SD) 27 ± 9 years, were studied during one night at Zurich (490 m), two nights at Davos Wolfgang (1630 m), and two nights at Jakobshorn (2590 m), in randomized order. Sleep duration measured by actigraphy, using a one-axis device at the wrist (n = 51), a three-axis device at the other wrist, and a three-axis device at the ankle (n = 22), was compared with corresponding total sleep time (TST) measured by polysomnography. Results: During 255 polysomnographic overnight studies, 449 paired actigraphic recordings were obtained. The median polysomnographic-derived TST ranged from 397 to 408 minutes. Actigraphic mean TST from wrists with one-axis and three-axis devices, and from ankle agreed well with polysomnographic values with a bias of +1, −7, +6 minutes, respectively. Corresponding limits of agreement (±2 SD of bias) were ±51, ±60, and ±59 minutes. Limits of agreement of mean TST over five nights by actigraphy and polysomnography were similar to the coefficient of repeatability (2 SD of mean) of polysomnographic TST, that is, ±31, ±38, and ±36 minutes versus ±34 minutes. Conclusions: Actigraphy of the wrist or ankle by a one-axis or a three-axis device accurately estimates mean TST in groups of subjects and mean TST over several nights in individuals traveling to altitude. Therefore, actigraphy is valuable for assessing effects of altitude and other environmental influences on sleep duration during field studies over extended periods.