Inhibition of granulocyte migration by tiotropium bromide

<p>Abstract</p> <p>Study objectives</p> <p>Neutrophil influx into the airways is an important mechanism in the pathophysiology of the inflammatory process in the airways of patients with chronic obstructive pulmonary disease (COPD). Previously it was shown that anticholinergic drugs reduce the release of non-neuronal paracrine mediators, which modulate inflammation in the airways. On this basis, we investigated the ability of the long-acting anticholinergic tiotropium bromide to inhibit a) alveolar macrophage (AM)-mediated chemotaxis of neutrophils, and b) cellular release of reactive oxygen species (ROS).</p> <p>Method</p> <p>AM and neutrophils were collected from 71 COPD patients. Nanomolar concentrations of tiotropium bromide were tested in AM cultured up to 20 h with LPS (1 μg/ml). AM supernatant was tested for TNFα, IL8, IL6, LTB4, GM-CSF, MIPα/β and ROS. It was further used in a 96-well chemotaxis chamber to stimulate the migration of fluorescence labelled neutrophils. Control stimulants consisted of acetylcholine (ACh), carbachol, muscarine or oxotremorine and in part PMA (phorbol myristate acetate, 0.1 μg/ml). Potential contribution of M_1-3-receptors was ascertained by a) analysis of mRNA transcription by RT-PCR, and b) co-incubation with selective M-receptor inhibitors.</p> <p>Results</p> <p>Supernatant from AM stimulated with LPS induced neutrophilic migration which could be reduced by tiotropium in a dose dependent manner: 22.1 ± 10.2 (3 nM), 26.5 ± 18,4 (30 nM), and 37.8 ± 24.0 (300 nM, p < 0.001 compared to non-LPS activated AM). Concomitantly TNFα release of stimulated AM dropped by 19.2 ± 7.2% of control (p = 0.001). Tiotropium bromide did not affect cellular IL8, IL6, LTB4, GM-CSF and MIPα/β release in this setting. Tiotropium (30 nM) reduced ROS release of LPS stimulated AM by 36.1 ± 15.2% (p = 0.002) and in carbachol stimulated AM by 46.2 ± 30.2 (p < 0.001). M3R gene expression dominated over M2R and M1R. Chemotaxis inhibitory effect of tiotropium bromide was mainly driven by M3R inhibition.</p> <p>Conclusion</p> <p>Our data confirm that inhibiting muscarinic cholinergic receptors with tiotropium bromide reduces TNFα mediated chemotactic properties and ROS release of human AM, and thus may contribute to lessen cellular inflammation.</p

The treatment of mild upper respiratory tract infections – a position paper with recommendations for best practice

Following the waning severity of COVID-19 due to vaccination and the development of immunity, the current variants of SARS-CoV-2 often lead to mild upper respiratory tract infections (MURTIs), suggesting it is an appropriate time to review the pathogenesis and treatment of such illnesses. The present article reviews the diverse causes of MURTIs and the mechanisms leading to symptomatic illness. Different symptoms of MURTIs develop in a staggered manner and require targeted symptomatic treatment. A wide variety of remedies for home treatment is available, including over-the-counter drugs and plant-derived substances. Recent pharmacological research has increased the understanding of molecular effects, and clinical studies have shown the efficacy of certain herbal remedies. However, the use of subjective endpoints in these clinical studies may suggest limited validity of the results. In this position paper, the importance of patient-centric outcomes, including a subjective perception of improved well-being, is emphasized. A best practice approach for the management of MURTIs, in which pharmacists and physicians create an improved multi-professional healthcare setting and provide healthcare education to patients, is proposed. Pharmacists act as first-line consultants and provide patients with remedies, considering the individual patient's preferences towards chemical or plant-derived drugs and providing advice for self-monitoring. Physicians act as second-line consultants if symptoms worsen and subsequently initiate appropriate therapies. In conclusion , general awareness of MURTIs should be increased amongst medical professionals and patients, thus improving their management

Investigation and management of residual sleepiness in CPAP-treated patients with obstructive sleep apnoea: the European view

Excessive daytime sleepiness (EDS) is a major symptom of obstructive sleep apnoea (OSA), defined as the inability to stay awake during the day. Its clinical descriptors remain elusive, and the pathogenesis is complex, with disorders such as insufficient sleep and depression commonly associated. Subjective EDS can be evaluated using the Epworth Sleepiness Scale, in which the patient reports the probability of dozing in certain situations; however, its reliability has been challenged. Objective tests such as the multiple sleep latency test or the maintenance of wakefulness test are not commonly used in patients with OSA, since they require nocturnal polysomnography, daytime testing and are expensive. Drugs for EDS are available in the United States but were discontinued in Europe some time ago. For European respiratory physicians, treatment of EDS with medication is new and they may lack experience in pharmacological treatment of EDS, while novel wake-promoting drugs have been recently developed and approved for clinical use in OSA patients in the USA and Europe. This review will discuss 1) the potential prognostic significance of EDS in OSA patients at diagnosis, 2) the prevalence and predictors of residual EDS in treated OSA patients, and 3) the evolution of therapy for EDS specifically for Europe

Sleep and Breathing Conference highlights 2023: a summary by ERS Assembly 4

During the SBC 2023, the latest research and clinical topics in sleep disordered breathing were presented. The sessions provided novel insights into sleep apnoea pathophysiology and treatment approaches, as well as in e-health and big data management. There were several opportunities for early career delegates to discover the latest scientific insights to different topics, as well as to benefit from networking opportunities, as presented in a previous Early Career Forum article [1]. This paper summarises some of the most relevant sessions and topics presented at the SBC, written by early career members from ERS Assembly 4info:eu-repo/semantics/publishedVersio

Real time geotechnical field data acquistion using a distributed approach

A distributed geotechnical remote analysis of data system (Distributed G-RAD) can benefit both owners and contractors in providing better quality control and assurance on geotechnical projects. The Distributed G-RAD approach involves efficient data acquisition using PDAs with GPS capability, radio frequency identification (RFID) tags for labeling soil samples, laser scanning for measuring lift thickness and volumes of stockpiles and borrow pits. Spatial data storage is provided using a geographic information system (GIS). Portions of this system are already developed while other parts are still being considered. This paper also describes how RFID and laser scanning technologies can be used in the larger Distributed G-RAD system

‘Triangular’ Konsep Transformasi Geometri dalam Komposisi Musik

Kajian sumber yang digunakan sebagai pijakan dalam penelitian penciptaan ini adalah kumpulan literatur berupa buku-buku, jurnal-jurnal, dan karya-karya yang dianggap berkaitan dengan musik dan matematika. Metode penelitian yang digunakan adalah penelitian kualitatif dengan pendekatan studiliteratur. Hasil penelitian penciptaan ini adalah, ditemukan konsep baru dalam merancang komposisi menggunakan transformasi geometri. Hal ini diperoleh dari hasil eksperimen yang didasarkan pada cara kerja yang ditentukan pada tahap eksplorasi. Kesimpulan dari penelitian penciptaan ini adalah, transformasi geometri bisa digunakan sebagai konsep merancang musik, yaitu translasi dengan menggunakan vektor. Untuk menggunakannya dalam rancangan komposisi musik adalah dalam bentuk deret nada yang dijadikan subjek dan kontra subjek, melodi dan kontra melodi yang diterapkan pada komposisi sesuai dengan kaidah-kaidah komposisi musik

Consensus statement on the orofacial myofunctional assessment and therapy in patients with OSA: proposal of an international Delphi Method process

La rééducation myofonctionnelle orofaciale a été montrée efficace dans la prise en charge multidisciplinaire du syndrome d’apnées obstructives du sommeil chez l’enfant, l’adolescent et l’adulte, et elle est prescrite à plusieurs étapes de ces prises en charge. Cependant, compte tenu du manque d’homogénéité des protocoles de traitement et de mesures des résultats, du manque de recherches sur le type, la fréquence et la durée des exercices myofonctionnels et sur les phénotypes spécifiques qui peuvent en bénéficier, il apparait nécessaire de définir des recommandations de bonne pratique. Un consensus de recommandations Delphi consacré à l’évaluation et au traitement myofonctionnel orofacial pour les patients atteints de SAOS, a été mis en oeuvre à l’initiative de Marc Richard Moeller. Les deux premières étapes du consensus de recommandations Delphi sont achevées. La troisième étape, consacrée à l’élaboration du questionnaire aura lieu lors de la réunion conjointe de la World Sleep Society et de l’Academy of Applied Myofunctional Sciences, en mars 2022 à Rome. Les conclusions du consensus de recommandations Delphi seront publiées l’année suivante et largement diffusées.info:eu-repo/semantics/publishedVersio

Management of obstructive sleep apnea in Europe – A 10-year follow-up

Funding Information: Sleep medicine has been further established and recognized in the past 10 years. This is also shown by the fact that sleep-related diseases may receive a separate chapter in the new ICD-11 (International Classification of Diseases 11th Revision) [11]. However, the initial expansion in sleep laboratories and sleep centers seems to be over, at least in Europe, which stands in contradiction to the growing need. While sleep medical care still seems to be secured by the established structures, the gap between the increasing need and existing structures is still widening [ 12–14]. There is a lack of sleep medicine specialists, new outpatient structures, and new billing models with the sponsoring institutions. Approaches to solve these problems include the establishment and expansion of home sleep apnea testing (HSAT) [15] and telemedicine-based technologies in the diagnosis and treatment of OSA [16,17]. Telemedicine found its way into sleep medicine around 10 years ago [ 18–20]. One of the very first approaches as early as 1994 used a telephone circuit and a computer-controlled support system to improve OSA treatment by improving lifestyle through tele-guidance on nutrition and exercise [21]. Publisher Copyright: © 2022 The Authors Copyright © 2022 Elsevier B.V. All rights reserved.Objective: In 2010, a questionnaire-based study on obstructive sleep apnea (OSA) management in Europe identified differences regarding reimbursement, sleep specialist qualification, and titration procedures. Now, 10 years later, a follow-up study was conducted as part of the ESADA (European Sleep Apnea Database) network to explore the development of OSA management over time. Methods: The 2010 questionnaire including questions on sleep diagnostic, reimbursement, treatment, and certification was updated with questions on telemedicine and distributed to European Sleep Centers to reflect European OSA management practice. Results: 26 countries (36 sleep centers) participated, representing 20 ESADA and 6 non-ESADA countries. All 21 countries from the 2010 survey participated. In 2010, OSA diagnostic procedures were performed mainly by specialized physicians (86%), whereas now mainly by certified sleep specialists and specialized physicians (69%). Treatment and titration procedures are currently quite homogenous, with a strong trend towards more Autotitrating Positive Airway Pressure treatment (in hospital 73%, at home 62%). From 2010 to 2020, home sleep apnea testing use increased (76%–89%) and polysomnography as sole diagnostic procedure decreased (24%–12%). Availability of a sleep specialist qualification increased (52%–65%) as well as the number of certified polysomnography scorers (certified physicians: 36%–79%; certified technicians: 20%–62%). Telemedicine, not surveyed in 2010, is now in 2020 used in diagnostics (8%), treatment (50%), and follow-up (73%). Conclusion: In the past decade, formal qualification of sleep center personnel increased, OSA diagnostic and treatment procedures shifted towards a more automatic approach, and telemedicine became more prominent.Peer reviewe