BACKGROUND: The situation in France is unique, having a legal framework for continuous and deep sedation (CDS). However, its use in intensive care units (ICU), combined with the withdrawal of life-sustaining therapies, still raises ethical issues, particularly its potential to hasten death. The legalization of assistance in dying, i.e., assisted suicide or euthanasia at the patient\'s request, is currently under discussion in France. The objectives of this national survey were first, to assess whether ICU professionals perceive CDS administered to ICU patients as a practice that hastens death, in addition to relieving unbearable suffering, and second, to assess ICU professionals\' perceptions of assistance in dying.
METHODS: A national survey with online questionnaires for ICU physicians and nursesaddressed through the French Society of Anesthesiology and Critical Care Medicine.
RESULTS: A total of 956 ICU professionals responded to the survey (38% physicians and 62% nurses). Of these, 22% of physicians and 12% of nurses (p < 0.001) felt that the purpose of CDS was to hasten death. For 20% of physicians, CDS combined with terminal extubation was considered an assistance in dying. For 52% of ICU professionals, the current framework did not sufficiently cover the range of situations that occur in the ICU. A favorable opinion on the potential legalization of assistance in dying was observed in 83% of nurses and 71% of physicians (p < 0.001), with no preference between assisted suicide and euthanasia.
CONCLUSIONS: Our findings highlight the tension between CDS and assisted suicide/euthanasia in the specific context of intensive care and suggest that ICU professionals would be supportive of a legislative evolution.

OBJECTIVE: Comparative assessment of the level of differentiating growth factor 15 (GDF 15 ) against the background of a 6-month course of respiratory support in the mode of automatic positive pressure in the airways therapy (aPAP therapy) in patients with obstructive sleep apnea syndrome (OSA).
METHODS: 59 men participated in the study, the average age was 51.9±2.4 years. The main group (MG1) consisted of 30 patients with a verified diagnosis of moderate OSA. 29 men of comparable age and body weight made up the control group (CG) without an objectively confirmed diagnosis of OSA. After the stage of introduction into the study, the type of respiratory support with individual pressure settings was selected for patients with MG1. After 6 months of aPAP therapy with high compliance (at least 85%), the same patients who made up MG2 after treatment underwent repeated polysomnography (PSG) and the GDF 15 content was evaluated. Methods: questionnaire, examination, polysomnography, enzyme immunoassay of blood serum to determine the content of GDF 15.
RESULTS: A 6-month course of aPAP therapy with a high degree of compliance significantly improved the sleep structure and breathing pattern: the representation of NREM 3 increased from 79.2±15.6 to 102.6±21.6 minutes and the REM phase from 56.9± 13.6 to 115.6±26.8. Episodes of apnea were eliminated - apnea-hypopnea index decreased from 21.1 [17.3; 39.1] to 2.5 [1.8; 4.6] and the average values of SaO2 increased from 85.9% to 91.5%. At the same time, a statistically significant excess of GDF 15 was revealed in MG1 - 20.4 [14.16; 31.71] and MG2 - 17.2 [13.63; 24.44]) in comparison with CG - 13.65 [10.7; 17.09]. Despite the lack of statistical significance, a change in the level of GDF 15 was revealed in the form of a decrease in its concentration after a 6-month course of aPAP therapy.
CONCLUSIONS: A 6-month course of aPAP therapy made it possible to eliminate intermittent nocturnal hypoxia and improve sleep structure in patients with OSA, as well as reduce the content of GDF 15 protein in blood serum in patients with OSA. However, the tendency to decrease the content of this protein, despite the lack of statistical reliability, confirms the effectiveness of OSA therapy and the possibility of preventing early and pathological aging from the standpoint of somnology and molecular biogerontology.
UNASSIGNED: Сравнительная оценка уровня дифференцировочного фактора роста 15 (GDF 15) на фоне 6-месячного курса респираторной поддержки в режиме автоматического создания положительного давления в дыхательных путях (automatic Positive Airway Pressure — aPAP-терапия) у пациентов с синдромом обструктивного апноэ сна (СОАС).
UNASSIGNED: В исследовании участвовали 59 мужчин, средний возраст 51,9±2,4 года. Основную группу (ОГ1) составили 30 пациентов с верифицированным диагнозом СОАС средней степени тяжести. Контрольную группу (КГ) составили 29 мужчин, сопоставимых по возрасту и массе тела, без объективно подтвержденного диагноза СОАС. После этапа введения в исследование пациентам ОГ1 был подобран тип респираторной поддержки с индивидуальными настройками давления. Через 6 мес aPAP-терапии с высоким комплаенсом (не менее 85%) этим же пациентам, которые составили после лечения ОГ2, была проведена повторная полисомнография (ПСГ) и оценено содержание GDF 15. Методы: анкетирование, осмотр, ПСГ, иммуноферментный анализ сыворотки крови для определения содержания GDF 15.
UNASSIGNED: Шестимесячный курс aPAP-терапии с высокой степенью комплаентности позволил значимо улучшить структуру сна и паттерн дыхания: увеличились представленность фазы медленного сна 3 (NREM 3) с 79,2±15,6 до 102,6±21,6 мин и фазы сна с быстрыми движениями глаз (REM) с 56,9±13,6 до 115,6±26,8. Устранены эпизоды апноэ — индекс апноэ-гипопноэ уменьшился с 21,1 [17,3; 39,1] до 2,5 [1,8; 4,6], увеличились средние значения сатурации крови кислородом (SaO2) с 85,9 до 91,5%. При этом выявлено статистически достоверное превышение GDF 15 в ОГ1 — 20,4 [14,16; 31,71] и ОГ2 — 17,2 [13,63; 24,44]) в сравнении с КГ — 13,65 [10,7; 17,09] пг/мл. Несмотря на отсутствие статистической значимости, выявлено изменение уровня GDF 15 в виде уменьшения его концентрации после 6-месячного курса aPAP-терапии.
UNASSIGNED: Шестимесячный курс aPAP-терапии позволил устранить интермиттирующую ночную гипоксию и улучшить структуру сна у пациентов с СОАС, а также снизить содержание белка GDF 15 в сыворотке крови у пациентов с СОАС. Однако тенденция к снижению содержания данного белка, несмотря на отсутствие статистической достоверности, является подтверждением эффективности терапии СОАС и возможности профилактики раннего и патологического старения с позиции сомнологии и молекулярной биогеронтологии.

OBJECTIVE: Analysis of factors affecting adherence to continuous positive airway pressure (CPAP) therapy in patients with obstructive sleep apnea (OSA).
METHODS: The literature search was carried out using the databases PubMED, Google Scholar, E-library, Cyberleninka for the period 2013-2023 and included reviews and original articles.
RESULTS: The main groups of factors affecting adherence to CPAP therapy in patients with OSA have been established. These include sociodemographic and socioeconomic factors, the severity of OSA and the severity of clinical symptoms, and psychosocial factors. Strategies that can improve adherence were identified (educational technologies for patients, telemedicine technologies, behavioral therapy, modern technical interventions).
CONCLUSIONS: Factors that improve adherence to CPAP therapy are high levels of education and income, more severe OSA forms accompanied by daytime sleepiness, support from the patient\'s spouse and social support. Factors such as low levels of education and income, smoking, symptoms of depression and hypochondria, as well as side-effects worsen adherence to CPAP therapy, including refusal to continue treatment. It should be noted that all the identified factors are very closely associated with each other, so it is necessary to evaluate them comprehensively in each patient with OSA.
UNASSIGNED: Анализ факторов, оказывающих влияние на приверженность неинвазивной вентиляции постоянным положительным давлением воздушного потока во время сна (CPAP-терапия) пациентов с СОАС.
UNASSIGNED: Поиск литературы проводился с помощью поисковых систем PubMed, Google Scholar, eLIBRARY, Киберленинка за период 2013—2023 гг. и включал обзорные и оригинальные статьи.
UNASSIGNED: Установлены основные группы факторов, оказывающих влияние на приверженность CPAP-терапии пациентов с СОАС. К ним относятся социально-демографические и социально-экономические факторы, степень тяжести СОАС и выраженность клинических симптомов, психосоциальные факторы. Выявлены мероприятия, направленные на улучшение приверженности (обучающие технологии для пациентов, телемедицинские технологии, поведенческая терапия, современные технические решения).
UNASSIGNED: Исходя из вышеизложенного, факторами, улучшающими приверженность CPAP-терапии, являются высокие уровни образованности и доходов пациентов, более тяжелые формы СОАС, сопровождающиеся дневной сонливостью, поддержка супруга пациента и социальная поддержка. А такие факторы, как низкие уровни образования и доходов, курение, наличие симптомов депрессии и ипохондрии, а также возникающие побочные эффекты, ухудшают приверженность CPAP-терапии вплоть до отказа от продолжения лечения. Следует отметить, что все выявленные факторы очень тесно взаимосвязаны друг с другом, поэтому необходимо оценивать их комплексно у каждого пациента с СОАС.

Type III interferon signaling contributes to the pathogenesis of the important human pathogen Staphylococcus aureus in the airway. Little is known of the cellular factors important in this response. Using Ifnl2-green fluorescent protein reporter mice combined with flow cytometry and cellular depletion strategies, we demonstrate that the alveolar macrophage is the primary producer of interferon lambda (IFN-λ) in response to S. aureus in the airway. Bone marrow chimeras showed reduced bacterial burden in IFN-λ receptor (IFNLR1)-deficient recipient mice, indicative that non-hematopoietic cells were important for pathogenesis, in addition to significant reductions in pulmonary inflammation. These observations were confirmed through the use of an airway epithelial-specific IFNLR knockout mouse. Our data suggest that upon entry to the airway, S. aureus activates alveolar macrophages to produce type III IFN that is subsequently sensed by the airway epithelium. Future steps will determine how signaling from the epithelium then exerts its influence on bacterial clearance. These results highlight the important, yet sometimes detrimental, role of type III IFN signaling during infection and the impact the airway epithelium plays during host-pathogen interactions.IMPORTANCEThe contribution of type III interferon signaling to the control of bacterial infections is largely unknown. We have previously demonstrated that it contributes to the pathogenesis of acute Staphylococcus aureus respiratory infection. In this report, we document the importance of two cell types that underpin this pathogenesis. We demonstrate that the alveolar macrophage is the cell that is responsible for the production of type III interferon and that this molecule is sensed by airway epithelial cells, which impacts both bacterial clearance and induction of inflammation. This work sheds light on the first two aspects of this important pathogenic cascade.

Airway microbiota are known to contribute to lung diseases, such as cystic fibrosis (CF), but their contributions to pathogenesis are still unclear. To improve our understanding of host-microbe interactions, we have developed an integrated analytical and bioinformatic mass spectrometry (MS)-based metaproteomics workflow to analyze clinical bronchoalveolar lavage (BAL) samples from people with airway disease. Proteins from BAL cellular pellets were processed and pooled together in groups categorized by disease status (CF vs. non-CF) and bacterial diversity, based on previously performed small subunit rRNA sequencing data. Proteins from each pooled sample group were digested and subjected to liquid chromatography tandem mass spectrometry (MS/MS). MS/MS spectra were matched to human and bacterial peptide sequences leveraging a bioinformatic workflow using a metagenomics-guided protein sequence database and rigorous evaluation. Label-free quantification revealed differentially abundant human peptides from proteins with known roles in CF, like neutrophil elastase and collagenase, and proteins with lesser-known roles in CF, including apolipoproteins. Differentially abundant bacterial peptides were identified from known CF pathogens (e.g., Pseudomonas), as well as other taxa with potentially novel roles in CF. We used this host-microbe peptide panel for targeted parallel-reaction monitoring validation, demonstrating for the first time an MS-based assay effective for quantifying host-microbe protein dynamics within BAL cells from individual CF patients. Our integrated bioinformatic and analytical workflow combining discovery, verification, and validation should prove useful for diverse studies to characterize microbial contributors in airway diseases. Furthermore, we describe a promising preliminary panel of differentially abundant microbe and host peptide sequences for further study as potential markers of host-microbe relationships in CF disease pathogenesis.IMPORTANCEIdentifying microbial pathogenic contributors and dysregulated human responses in airway disease, such as CF, is critical to understanding disease progression and developing more effective treatments. To this end, characterizing the proteins expressed from bacterial microbes and human host cells during disease progression can provide valuable new insights. We describe here a new method to confidently detect and monitor abundance changes of both microbe and host proteins from challenging BAL samples commonly collected from CF patients. Our method uses both state-of-the art mass spectrometry-based instrumentation to detect proteins present in these samples and customized bioinformatic software tools to analyze the data and characterize detected proteins and their association with CF. We demonstrate the use of this method to characterize microbe and host proteins from individual BAL samples, paving the way for a new approach to understand molecular contributors to CF and other diseases of the airway.

BACKGROUND: Particulate β-glucans (WGP) are natural compounds with regulatory roles in various biological processes, including tumorigenesis and inflammatory diseases such as allergic asthma. However, their impact on mast cells (MCs), contributors to airway hyperresponsiveness (AHR) and inflammation in asthma mice, remains unknown.
METHODS: C57BL/6 mice underwent repeated OVA sensitization without alum, followed by Ovalbumin (OVA) challenge. Mice received daily oral administration of WGP (OAW) at doses of 50 or 150 mg/kg before sensitization and challenge. We assessed airway function, lung histopathology, and pulmonary inflammatory cell composition in the airways, as well as proinflammatory cytokines and chemokines in the bronchoalveolar lavage fluid (BALF).
RESULTS: The 150 mg/kg OAW treatment mitigated OVA-induced AHR and airway inflammation, evidenced by reduced airway reactivity to aerosolized methacholine (Mch), diminished inflammatory cell infiltration, and goblet cell hyperplasia in lung tissues. Additionally, OAW hindered the recruitment of inflammatory cells, including MCs and eosinophils, in lung tissues and BALF. OAW treatment attenuated proinflammatory tumor necrosis factor (TNF)-α and IL-6 levels in BALF. Notably, OAW significantly downregulated the expression of chemokines CCL3, CCL5, CCL20, CCL22, CXCL9, and CXCL10 in BALF.
CONCLUSIONS: These results highlight OAW\'s robust anti-inflammatory properties, suggesting potential benefits in treating MC-dependent AHR and allergic inflammation by influencing inflammatory cell infiltration and regulating proinflammatory cytokines and chemokines in the airways.

Cough is a powerful, protective expulsive behavior that assists in maintaining respiratory health by clearing foreign material, pathogens, and mucus from the airways. Therefore, cough is critical to survival in both health and disease. Importantly, cough protects the airways and lungs from both antegrade (e.g., food, liquid, saliva) and retrograde (e.g., bile, gastric acid) aspirate contents. Aspiration is often the result of impaired swallowing (dysphagia), which allows oral and/or gastric contents to enter the lung, especially in individuals who also have cough dysfunction (dystussia). Cough hyposensitivity, downregulation, or desensitization- collectively referred to as hypotussia- is common in individuals with dysphagia, and increases the likelihood that aspirated material will reach the lung. The consequence of hypotussia with reduced airway clearance can include respiratory tract infection, chronic inflammation, and long-term damage to the lung parenchyma. Despite the clear implications for health, the problem of managing hypotussia in individuals with dysphagia is frequently overlooked. Here, we provide an overview of the current interventions and treatment approaches for hypotussic cough. We synthesize the available literature to summarize research findings that advance our understanding of these interventions, as well as current gaps in knowledge. Further, we highlight pragmatic resources to increase awareness of hypotussic cough interventions and provide support for the clinical implementation of evidence-based treatments. In culmination, we discuss potential innovations and future directions for hypotussic cough research.

UNASSIGNED: Sleep has important effects on breathing and gas exchange that may have negative consequences in patients with chronic obstructive pulmonary disease (COPD). COPD and obstructive sleep apnea (OSA) are highly prevalent and may coexist, which is referred to as the overlap syndrome.
UNASSIGNED: The probability of OSA-COPD overlap represents the balance of protective and promoting factors such as hyperinflation and fluid retention; thus, different clinical COPD phenotypes influence the likelihood of comorbid OSA. The clinical presentation of OSA-COPD overlap is nonspecific, and the diagnosis requires clinical awareness to identify patients needing overnight studies. Both COPD and OSA are associated with a range of overlapping physiological and biological disturbances including hypoxia and inflammation that contribute to cardiovascular comorbidities. The management of OSA-COPD overlap patients differs from those with COPD alone and the survival of overlap patients treated with positive airway pressure (PAP) is superior to those untreated.
UNASSIGNED: The recognition of OSA-COPD overlap has important clinical relevance because of its impact on outcomes and management. Management of the overlap should address both sleep quality and disordered gas exchange. PAP therapy has demonstrated reductions in COPD exacerbations, hospitalizations, healthcare costs and mortality in overlap patients.

Adenosine triphosphate (ATP) can be released into the extracellular milieu from various types of cells in response to a wide range of physical or chemical stresses. In the respiratory tract, extracellular ATP is recognized as an important signal molecule and trigger of airway inflammation. Chlorine (Cl2), sulfur dioxide (SO2), and ammonia (NH3) are potent irritant gases and common industrial air pollutants due to their widespread uses as chemical agents. This study was carried out to determine if acute inhalation challenges of these irritant gases, at the concentration and duration simulating the accidental exposures to these chemical gases in industrial operations, triggered the release of ATP in the rat respiratory tract; and if so, whether the level of ATP in bronchoalveolar lavage fluid (BALF) evoked by inhalation challenge of a given irritant gas was elevated by chronic allergic airway inflammation. Our results showed: 1) Inhalation of these irritant gases caused significant increases in the ATP level in BALF, and the magnitude of evoked ATP release was in the order of Cl2 > SO2 > NH3. 2) Chronic airway inflammation induced by ovalbumin-sensitization markedly elevated the ATP level in BALF during baseline (breathing room air) but did not potentiate the release of ATP in the lung triggered by inhalation challenges of these irritant gases. These findings suggested a possible involvement of the ATP release in the lung in the regulation of overall airway responses to acute inhalation of irritant gases and the pathogenesis of chronic allergic airway inflammation.

Pulmonary function testing is critical to the diagnosis of equine asthma (EA), an important cause of respiratory disease in the horse, but its clinical use has remained elusive, unfortunately, due to the complexity of reference methods, esophageal balloon/pneumotachography (EBP) and forced oscillatory mechanics (FOM), so we sought a non-invasive, portable method for use in horses through rapid interruption of airflow for equilibration of alveolar pressure with proximal airway pressure, termed flow interruption (FI). Resistance (RINT) was computed as the relationship between the change in pressure at the nose before and immediately after interruption and flow immediately before interruption. A pilot study in 5 healthy university-owned animals using EBP and FI showed good correspondence between the two methods: RINT (0.33 +/- 0.05 cm H2O/l/s) and RL (0.31 +/- 0.06 cm H2O/l/s). In 2 separate populations of client-owned horses, with random assignment of methods to FI v EBP (n = 8), RINT showed good correlation with RL in horses, (rs =.995, p = .0002) and accords with RL, with no significant difference between RINT and RL. Using FOM (n = 12), RINT (0.67 +/- 0.31 cmH2O/l/s) has good correlation with RRS measured with FOM (r =.834, p = .0001), but is consistently smaller than RRS (0.74 +/- 0.33 cmH2O/l/s) . Histamine bronchoprovocation (HBP) was performed in a subset of these horses: FI classified one horse in 6 as less reactive than did EBP, and FI classified one horse in 7 as less reactive than did FOM.