Characteristics of Severe Asthma Patients and Predictors of Asthma Control in the Swiss Severe Asthma Registry.

BACKGROUND: Asthma is a chronic airway disease, affecting over 300 million people worldwide. 5-10% of patients suffer from severe asthma and account for 50% of asthma-related financial burden. Availability of real-life data about the clinical course of severe asthma is insufficient. OBJECTIVES: The aims of this study were to characterize patients with severe asthma in Switzerland, enrolled in the Swiss Severe Asthma Registry (SSAR), and evaluate predictors for asthma control. METHOD: A descriptive characterisation of 278 patients was performed, who were prospectively enrolled in the registry until January 2022. Socio-demographic variables, comorbidities, diagnostic values, asthma treatment, and healthcare utilisation were evaluated. Groups of controlled and uncontrolled asthma according to the asthma control test were compared. RESULTS: Forty-eight percent of patients were female and the mean age was 55.8 years (range 13-87). The mean body mass index (BMI) was 27.4 kg/m2 (±6). 10.8% of patients were current smokers. Allergic comorbidities occurred in 54.3% of patients, followed by chronic rhinosinusitis (46.4%) and nasal polyps (34.1%). According to the ACT score, 54.7% had well controlled, 16.2% partly controlled and 25.9% uncontrolled asthma. The most common inhalation therapy was combined inhaled corticosteroids/long-acting ß2-agonists (78.8%). Biologics were administered to 81.7% of patients and 19.1% received oral steroids. The multivariable analysis indicated that treatment with biologics was positively associated with asthma control whereas higher BMI, oral steroids, exacerbations, and COPD were negative predictors for asthma control. CONCLUSION: Biologics are associated with improved control in severe asthma. Further studies are required to complete the picture of severe asthma in order to provide improved care for those patients.

Are blood cytokines reliable biomarkers of allergic disease diagnosis and treatment responses?

With the development of targeted therapies for allergic diseases, the need for biomarkers supporting disease diagnosis and management has increased. Recent research has elucidated the pattern of cytokines and their distinct roles in the pathogenesis of allergic diseases. This means that cytokines should be considered as biomarkers. In this review article, we summarize published findings and critically discuss the use of cytokine measurements in association with disease diagnosis and management. Among the variety of suggested cytokines, thymus and activation-regulated chemokine (TARC) stands out and can indeed serve as a biomarker of atopic dermatitis. Both biologic characteristics and technical issues determine the reliability and limit the use of blood cytokines as biomarkers.

[COPD : a still neglected condition]. / BPCO : une maladie encore négligée.

Chronic obstructive pulmonary disease (COPD) is a heterogeneous lung disorder with a complex clinical picture. The diagnosis may be difficult at times, as COPD may develop insidiously and remain unnoticed for a long time. Therefore, general practitioners play a central role in early detection of disease. Suspected COPD may be confirmed by further investigations in collaboration with a pulmonologist. The most recent GOLD guideline defines three COPD risk groups (A-B-E) which should guide the personalized treatment concept. General practitioners are crucial for implementing non-pharmacological measures such as smoking cessation, regular exercise, vaccinations, and patient self-management education. However, this also underlines the challenges to implement the GOLD recommendations in daily practice.

La BPCO est une maladie hétérogène avec un tableau clinique complexe. Le diagnostic n'est pas toujours facile à évoquer, car elle peut se développer insidieusement et passer longtemps inaperçue. Les médecins de premier recours (MPR) jouent donc un rôle central dans le diagnostic précoce. La suspicion de BPCO peut être confirmée en collaboration avec un pneumologue par des examens fonctionnels respiratoires avant l'instauration d'un traitement médicamenteux. Les nouvelles recommandations GOLD, publiées en 2022 définissent trois groupes de risques pour la BPCO (A-B-E). Les MPR sont importants pour la mise en œuvre de mesures accompagnant le traitement (arrêt du tabac, activité physique régulière, vaccinations, éducation thérapeutique). Mais cela souligne également les exigences élevées de la mise en œuvre des recommandations GOLD dans la pratique quotidienne.*.

Facilitating standardized COVID-19 suspicion prediction based on computed tomography radiomics in a multi-demographic setting.

OBJECTIVE: To develop an automatic COVID-19 Reporting and Data System (CO-RADS)-based classification in a multi-demographic setting. METHODS: This multi-institutional review boards-approved retrospective study included 2720 chest CT scans (mean age, 58 years [range 18-100 years]) from Italian and Russian patients. Three board-certified radiologists from three countries assessed randomly selected subcohorts from each population and provided CO-RADS-based annotations. CT radiomic features were extracted from the selected subcohorts after preprocessing steps like lung lobe segmentation and automatic noise reduction. We compared three machine learning models, logistic regression (LR), multilayer perceptron (MLP), and random forest (RF) for the automated CO-RADS classification. Model evaluation was carried out in two scenarios, first, training on a mixed multi-demographic subcohort and testing on an independent hold-out dataset. In the second scenario, training was done on a single demography and externally validated on the other demography. RESULTS: The overall inter-observer agreement for the CO-RADS scoring between the radiologists was substantial (k = 0.80). Irrespective of the type of validation test scenario, suspected COVID-19 CT scans were identified with an accuracy of 84%. SHapley Additive exPlanations (SHAP) interpretation showed that the "wavelet_(LH)_GLCM_Imc1" feature had a positive impact on COVID prediction both with and without noise reduction. The application of noise reduction improved the overall performance between the classifiers for all types. CONCLUSION: Using an automated model based on the COVID-19 Reporting and Data System (CO-RADS), we achieved clinically acceptable performance in a multi-demographic setting. This approach can serve as a standardized tool for automated COVID-19 assessment. KEYPOINTS: • Automatic CO-RADS scoring of large-scale multi-demographic chest CTs with mean AUC of 0.93 ± 0.04. • Validation procedure resembles TRIPOD 2b and 3 categories, enhancing the quality of experimental design to test the cross-dataset domain shift between institutions aiding clinical integration. • Identification of COVID-19 pneumonia in the presence of community-acquired pneumonia and other comorbidities with an AUC of 0.92.

[Novelties in the Treatment of Asthma]. / Nouveautés dans la prise en charge de l'asthme.

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.

[Cough - an Interdisciplinary Condition: The Pneumologist's Perspective]. / Husten ­ eine interdisziplinäre Krankheit.

Cough - an Interdisciplinary Condition: The Pneumologist's Perspective Abstract. Cough is one of the most frequent reasons for a medical consultation. Patients mostly suffer from acute cough (< 2 weeks duration) and subacute cough (2 - 8 weeks) during consultation at primary care. Chronic cough (> 8 weeks) is mostly cared for by specialists. Acute and subacute cough is most frequently caused by infections with primarily viral pathogens. Chronic cough is commonly associated with obstructive airway disease (i. e. Asthma, COPD), gastroesophageal reflux and upper airway cough syndrome. Pulmonary causes are investigated by spirometry, bodyplethysmography, blood eosinophil count, exhaled nitric oxide, methacholine challenge test, chest x-rays and computed tomography. Treatment should target underlying diseases, causing cough. Trials of inhaled corticosteroids can be considered if an asthmatic cause is suspected. Secretolytics and cough-suppressing medications should be used only to reduce patient symptoms if there is no alternative causal treatment. Clinical trials show positive results for treatment of chronic refractory (no improvement of symptoms despite adequate treatment of the underlying condition) and chronic idiopathic cough with Gefapixant, a P2X3 purinergic receptor antagonist. If recent trial results are confirmed a first specific cough modulating substance might be available soon.

[COPD - An Underestimated Disease]. / COPD ­ eine unterschätzte Erkrankung.

COPD - An Underestimated Disease Abstract: Chronic obstructive pulmonary disease (COPD) is a heterogeneous lung condition with a complex clinical picture. The diagnosis is not easy to make because COPD can develop insidiously and remain unnoticed for a long time. Therefore, general practitioners play a central role in the early detection of the disease. Suspected COPD can be confirmed by special examinations in collaboration with pulmonologists. The new GOLD guideline defines three COPD risk groups (A-B-E) which should guide the personalized treatment concept. A short- or long-acting bronchodilator (SAMA/SABA or LAMA/LABA) is recommended for group A, and a dual long-acting bronchodilator therapy (LABA+LAMA) is recommended for group B and E. In case of blood eosinophilia (≥300 cells/µl) and/or recent hospitalization for COPD exacerbation, triple therapy (LABA+LAMA+ICS) is recommended. General practitioners are important in implementing non-pharmacological measures (smoking cessation, regular exercise, vaccinations, patient selfmanagement education). However, this also underlines the high demands of the implementation of the GOLD guideline in daily practice.

Patient's perception of recovery following surgical removal of mandibular third molars. A prospective european multi-center study.

This study evaluated patient's perception of recovery following surgical removal of mandibular third molars (SRM3s) including analyze of potential risk factors associated with impaired convalescent. Patient related parameters combined with preoperative questionnaires including Modified Dental Anxiety Scale, Oral Health Impact Profile-14, and Decayed, Missing, Filled Teeth index were correlated with questionnaires assessing pain, swelling, trismus, sick leave, social and working isolation, physical appearance, eating and speaking ability, diet variations, sleep impairment, impaired sensation of the lip, chin, and tongue, one month following SRM3s. Totally, 412 patients (223 females, 189 males) with mean age of 29.4 years were included. Treatment satisfaction and willingness to undergo similar surgery were reported by 92% and 95%, although 21% reported that the surgery and postoperative period had been worse than expected. Mean days with pain, sick leave, and swelling were 3.6, 2.1, and 3.6, respectively. Preoperative symptoms, dental anxiety level, and prolonged surgical time were associated with increased pain and swelling (P < 0.05). Pell and Gregory classification (I-IIIC) were associated with impaired sensation of the lower lip and chin (P < 0.05). Consequently, results from this study improve the surgeon's ability to predict parameters that predisposed to impaired recovery and neurosensory disturbances following SRM3s.

CD25 as a unique marker on human basophils in stable-mildly symptomatic allergic asthma.

Background: Basophils in acute asthma exacerbation are activated as evidenced by their increased expression levels of activation markers such as CD203c and CD63. However, whether basophils of allergic asthmatics who are in stable phase and have no asthma exacerbations display a specific and distinctive phenotype from those of healthy individuals has yet to be well characterized. Objective: We aimed to identify the phenotype of basophils from allergic asthmatics in the stable phase and investigate whether such a phenotype is affected by ex vivo allergen stimulation. Methods: We determined by flow cytometry, the expression of surface proteins such as CD25, CD32, CD63, CD69, CD203c, and CD300a and intracellular anti-apoptotic proteins BCL-2, BCL-xL, and MCL-1. We investigated these markers in blood basophils obtained from well-characterized patients with stable-mildly symptomatic form of allergic asthma with no asthma exacerbation and from healthy individuals. Moreover, we determined ex vivo CD63, CD69, and CD25 on blood basophils from stable-mildly symptomatic allergic asthmatics upon allergen stimulation. Results: In contrast to all tested markers, CD25 was significantly increased on circulating basophils in the patient cohort with stable-mildly symptomatic allergic asthma than in healthy controls. The expression levels of CD25 on blood basophils showed a tendency to positively correlate with FeNO levels. Notably, CD25 expression was not affected by ex vivo allergen stimulation of blood basophils from stable-mildly symptomatic allergic asthma patients. Conclusion: Our data identifies CD25 as a unique marker on blood basophils of the stable phase of allergic asthma but not of asthma exacerbation as mimicked by ex vivo allergen stimulation.

A New Albomycin-Producing Strain of Streptomyces globisporus subsp. globisporus May Provide Protection for Ants Messor structor.

There are several well-studied examples of protective symbiosis between insect host and symbiotic actinobacteria, producing antimicrobial metabolites to inhibit host pathogens. These mutualistic relationships are best described for some wasps and leaf-cutting ants, while a huge variety of insect species still remain poorly explored. For the first time, we isolated actinobacteria from the harvester ant Messor structor and evaluated the isolates' potential as antimicrobial producers. All isolates could be divided into two morphotypes of single and mycelial cells. We found that the most common mycelial morphotype was observed among soldiers and least common among larvae in the studied laboratory colony. The representative of this morphotype was identified as Streptomyces globisporus subsp. globisporus 4-3 by a polyphasic approach. It was established using a E. coli JW5503 pDualRep2 system that crude broths of mycelial isolates inhibited protein synthesis in reporter strains, but it did not disrupt the in vitro synthesis of proteins in cell-free extracts. An active compound was extracted, purified and identified as albomycin δ2. The pronounced ability of albomycin to inhibit the growth of entomopathogens suggests that Streptomyces globisporus subsp. globisporus may be involved in defensive symbiosis with the Messor structor ant against infections.

Toward understanding the communication in sperm whales.

Machine learning has been advancing dramatically over the past decade. Most strides are human-based applications due to the availability of large-scale datasets; however, opportunities are ripe to apply this technology to more deeply understand non-human communication. We detail a scientific roadmap for advancing the understanding of communication of whales that can be built further upon as a template to decipher other forms of animal and non-human communication. Sperm whales, with their highly developed neuroanatomical features, cognitive abilities, social structures, and discrete click-based encoding make for an excellent model for advanced tools that can be applied to other animals in the future. We outline the key elements required for the collection and processing of massive datasets, detecting basic communication units and language-like higher-level structures, and validating models through interactive playback experiments. The technological capabilities developed by such an undertaking hold potential for cross-applications in broader communities investigating non-human communication and behavioral research.

The effect of the COVID-19 pandemic on severe asthma care in Europe: will care change for good?

Background: The coronavirus disease 2019 (COVID-19) pandemic has put pressure on healthcare services, forcing the reorganisation of traditional care pathways. We investigated how physicians taking care of severe asthma patients in Europe reorganised care, and how these changes affected patient satisfaction, asthma control and future care. Methods: In this European-wide cross-sectional study, patient surveys were sent to patients with a physician-diagnosis of severe asthma, and physician surveys to severe asthma specialists between November 2020 and May 2021. Results: 1101 patients and 268 physicians from 16 European countries contributed to the study. Common physician-reported changes in severe asthma care included use of video/phone consultations (46%), reduced availability of physicians (43%) and change to home-administered biologics (38%). Change to phone/video consultations was reported in 45% of patients, of whom 79% were satisfied or very satisfied with this change. Of 709 patients on biologics, 24% experienced changes in biologic care, of whom 92% were changed to home-administered biologics and of these 62% were satisfied or very satisfied with this change. Only 2% reported worsening asthma symptoms associated with changes in biologic care. Many physicians expect continued implementation of video/phone consultations (41%) and home administration of biologics (52%). Conclusions: Change to video/phone consultations and home administration of biologics was common in severe asthma care during the COVID-19 pandemic and was associated with high satisfaction levels in most but not all cases. Many physicians expect these changes to continue in future severe asthma care, though satisfaction levels may change after the pandemic.

Influence of ventilation inhomogeneity on diffusing capacity of carbon monoxide in smokers without COPD.

In smokers with preserved spirometry, D LCO is associated with ventilation inhomogeneity arising from peripheral airways. Measurement of D LCO to screen for early lung function abnormalities in smokers may be suboptimal and could be replaced by MBW. https://bit.ly/3nLmgg1.

[Novelties in the Treatment of Asthma]. / Neues in der Asthma-Grundversorgung.

Novelties in the Treatment of Asthma Abstract. 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). Step 1 no longer recommends the use of short-acting ß2-agonists (SABA) without concomitant inhaled corticosteroids (ICS) as a controller because of the lack of efficacy and for safety reasons. Instead, low dose ICS-formoterol as needed is recommended. GINA step 5 recommends targeted biologic therapies like interleukin antibodies in patients with severe uncontrolled asthma. 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. Recent data on prescriptions of SABA and oral corticosteroids (OCS) in Switzerland indicate that they still play an important role in asthma management and that GINA recommendations have not yet been sufficiently implemented into practice.

Synthesis and Application of Arylaminophosphazene as a Flame Retardant and Catalyst for the Polymerization of Benzoxazines.

A novel type of phosphazene containing an additive that acts both as a catalyst and as a flame retardant for benzoxazine binders is presented in this study. The synthesis of a derivative of hexachlorocyclotriphosphazene (HCP) and meta-toluidine was carried out in the medium of the latter, which made it possible to achieve the complete substitution of chlorine atoms in the initial HCP. Thermal and flammability characteristics of modified compositions were investigated. The modifier catalyzes the process of curing and shifts the beginning of reaction from 222.0 °C for pure benzoxazine to 205.9 °C for composition with 10 phr of modifier. The additive decreases the glass transition temperature of compositions. Achievement of the highest category of flame resistance (V-0 in accordance with UL-94) is ensured both by increasing the content of phenyl residues in the composition and by the synergistic effect of phosphorus and nitrogen. A brief study of the curing kinetics disclosed the complex nature of the reaction. An accurate two-step model is obtained using the extended Prout-Tompkins equation for both steps.

Benzoxazine Monomers and Polymers Based on 3,3'-Dichloro-4,4'-Diaminodiphenylmethane: Synthesis and Characterization.

To reveal the effect of chlorine substituents in the ring of aromatic amine on the synthesis process of benzoxazine monomer and on its polymerization ability, as well as to develop a fire-resistant material, a previously unreported benzoxazine monomer based on 3,3'-dichloro-4,4'-diaminodiphenylmethane was obtained in toluene and mixture toluene/isopropanol. The resulting benzoxazine monomers were thermally cured for 2 h at 180 °C, 4 h at 200 °C, 2 h at 220 °C. A comparison between the rheological, thermal and fire-resistant properties of the benzoxazines based on 3,3'-dichloro-4,4'-diaminodiphenylmethane and, for reference, 4,4'-diaminodimethylmethane was made. The effect of the reaction medium on the structure of the oligomeric fraction and the overall yield of the main product were studied and the toluene/ethanol mixture was found to provide the best conditions; however, in contrast to most known diamine-based benzoxazines, synthesis in the pure toluene is also possible. The synthesized monomers can be used as thermo- and fire-resistant binders for polymer composite materials, as well as hardeners for epoxy resins. Chlorine-containing polybenzoxazines require more severe conditions for polymerization but have better fire resistance.

Combining HF rTMS over the Left DLPFC with Concurrent Cognitive Activity for the Offline Modulation of Working Memory in Healthy Volunteers: A Proof-of-Concept Study.

It has been proposed that the effectiveness of non-invasive brain stimulation (NIBS) as a cognitive enhancement technique may be enhanced by combining the stimulation with concurrent cognitive activity. However, the benefits of such a combination in comparison to protocols without ongoing cognitive activity have not yet been studied. In the present study, we investigate the effects of fMRI-guided high-frequency repetitive transcranial magnetic stimulation (HF rTMS) over the left dorsolateral prefrontal cortex (DLPFC) on working memory (WM) in healthy volunteers, using an n-back task with spatial and verbal stimuli and a spatial span task. In two combined protocols (TMS + WM + (maintenance) and TMS + WM + (rest)) trains of stimuli were applied in the maintenance and rest periods of the modified Sternberg task, respectively. We compared them to HF rTMS without a cognitive load (TMS + WM-) and control stimulation (TMS - WM + (maintenance)). No serious adverse effects appeared in this study. Among all protocols, significant effects on WM were shown only for the TMS + WM- with oppositely directed influences of this protocol on storage and manipulation in spatial WM. Moreover, there was a significant difference between the effects of TMS + WM- and TMS + WM + (maintenance), suggesting that simultaneous cognitive activity does not necessarily lead to an increase in TMS effects.

Author Correction: Electrically pumped photonic integrated soliton microcomb.

The original version of this Article contained an error in the first sentence of the Acknowledgements, which incorrectly read 'This publication was supported by Contract HR0011-15-C-0055 (DODOS) from the Defense Advanced Research Projects Agency (DARPA), Defense Sciences Office (DSO).' The correct version states 'Microsystems Technology Office (MTO)' in place of 'Defense Sciences Office (DSO)'. This has been corrected in both the PDF and HTML versions of the Article.

Electrically pumped photonic integrated soliton microcomb.

Microcombs provide a path to broad-bandwidth integrated frequency combs with low power consumption, which are compatible with wafer-scale fabrication. Yet, electrically-driven, photonic chip-based microcombs are inhibited by the required high threshold power and the frequency agility of the laser for soliton initiation. Here we demonstrate an electrically-driven soliton microcomb by coupling a III-V-material-based (indium phosphide) multiple-longitudinal-mode laser diode chip to a high-Q silicon nitride microresonator fabricated using the photonic Damascene process. The laser diode is self-injection locked to the microresonator, which is accompanied by the narrowing of the laser linewidth, and the simultaneous formation of dissipative Kerr solitons. By tuning the laser diode current, we observe transitions from modulation instability, breather solitons, to single-soliton states. The system operating at an electronically-detectable sub-100-GHz mode spacing requires less than 1 Watt of electrical power, can fit in a volume of ca. 1 cm3, and does not require on-chip filters and heaters, thus simplifying the integrated microcomb.