Search

Keywords: accidental use; adrenaline; adverse effect; anaphylaxis; auto-injector; digital injection; side effect EN accidental use adrenaline adverse effect anaphylaxis auto-injector digital injection side effect 955 958 4 09/05/23 20230901 NES 230901 DATA AVAILABILITY STATEMENT The data that support the findings of this study are available on request from the corresponding author. In 3/6 cases, the ADRs occurred following a single adrenaline injection: chest tightness and paresthesia of the extremities ( I n i = 1), hypertension ( I n i = 1), and induration at the injection site ( I n i = 1). A US survey conducted with poison control centres (PCCs) (1994-2007) found 15,190 accidental injections related to AAIs, of which 0.2% were severe.[5] In our study, no side effects were observed related to accidental digital injections and no patient received vasodilators. [Extracted from the article]

Le traitement de l'allergie aux venins d'hyménoptère repose dans un premier temps sur le traitement symptomatique après une piqûre. La plupart des réactions cliniques sont légères à modérées, mais en cas d'anaphylaxie, la rapidité de la prise en charge avec l'utilisation adaptée de l'adrénaline est cruciale pour le pronostic. Au décours de la phase aiguë, le patient doit connaître les mesures de prévention des piqûres d'hyménoptères, avoir la prescription pour une trousse d'urgence à adapter en fonction de la clinique. Le traitement curatif est l'immunothérapie allergénique aux venins d'hyménoptère, qui permet la prévention à long terme des récidives allergiques graves. C'est le seul traitement qui modifie l'histoire naturelle de l'allergie. Actuellement, l'immunothérapie est disponible pour les venins de Vespula, de Poliste et d'abeille. Le choix du venin est fait au terme d'un bilan allergologique (tests cutanés et bilan biologique), parfois complexe en raison des réactions croisées, et pour lequel les outils actuels, notamment biologiques, sont d'une aide diagnostique. L'efficacité et la tolérance de l'immunothérapie allergénique aux venins, aussi bien chez l'adulte que chez l'enfant, ont été largement démontrées. De plus, elle améliore significativement la qualité de vie. Ses indications ont été réévaluées récemment. Cette prise en charge est nécessairement associée à une éducation thérapeutique régulière. L'allergie aux fourmis, pour lesquelles l'immunothérapie n'est pas encore disponible, ainsi qu'aux insectes non hyménoptères tels que les taons et les moustiques, sera également abordée. Treatment of hymenoptera venom allergy is based on immediate symptomatic treatment after a sting. Most reactions are mild and moderate, but in the case of severe anaphylactic reactions, prompt management and appropriate use of epinephrine are crucial to prognosis. After the acute phase, patient must known measures to prevent hymenoptera stings and have the prescription of an emergency kit according to the clinic. The curative treatment is allergenic immunotherapy to hymenoptera venom, which provides long-term prevention of severe allergic recurrences. It is the only treatment that modifies the natural history of the allergy. Currently, immunotherapy is available for Vespula wasp, Poliste wasp and honeybee. The choice of venom is made after an allergological assessment (skin tests and biological assessment), which is sometimes complex due to cross-reactions, and for which current tools, particularly biological, are of great diagnostic help. Efficacy and good tolerance of venom immunotherapy, in both adults and children, had been widely demonstrated. Moreover, it significantly improves quality of life. Its indications have recently been reassessed. This treatment is necessarily associated with regular therapeutic education. Allergy to ants, for which immunotherapy is not yet available, as well as to non-Hymenopteran insects such as horseflies and mosquitoes, will also be discussed. [ABSTRACT FROM AUTHOR]

Essential oils in air-spray form are being more and more used for several purposes, even by allergic and asthmatic patients. Available data on the potentially dangerous effects of volatile organic compounds and terpenes contained in essential oils are scarce, and sometimes difficult to compare. Through the present work, we evaluated the clinical tolerance of asthmatic patients exposed to compounds emitted by an essential oils spray, and compared previous and new data available in the scientific literature, focusing on the aspects that may influence clinical results. [ABSTRACT FROM AUTHOR]

L'objectif est la comparaison des performances diagnostiques de deux puces IgE multi-allergéniques de composition et de principe différents. Vingt et un patients polysensibilisés ou ayant présenté une anaphylaxie inexpliquée ont été testés par deux puces : la puce ISAC® et la puce ALEX2®. La concordance globale des résultats entre les deux puces est très bonne (97,8 %) pour les allergènes communs. L'analyse par famille moléculaire montre une plus grande fréquence de positivité d'ALEX® pour les LTP (7,4 % versus 5,8 %), alors que c'est l'inverse pour les PR-10 (14,9 % en ISAC® versus 11,9 % en ALEX®). Cependant, les concentrations observées ne sont pas comparables et sont plus élevées en ALEX® pour les PR-10. Comme attendu, le prétraitement par un inhibiteur spécifique bloque l'interférence des IgE anti-CCD dans la puce ALEX®. L'analyse par patient a permis de mettre en évidence des sensibilisations à certains allergènes moléculaires spécifiques de chaque puce : viandes, poissons et pistache présents uniquement sur ALEX2® ou alpha-Gal sur ISAC®. Les résultats obtenus avec les deux puces sont globalement concordants pour les allergènes communs. Une puce plus complète associant des extraits comme des allergènes moléculaires non disponibles pour certains en unitaires devrait trouver sa place dans l'exploration d'anaphylaxie inexpliquée, mais le choix et le nombre d'allergènes testés devrait évoluer pour répondre au mieux aux besoins cliniques. The aim is to compare the diagnostic performances of two multi-allergenic IgE microarrays of different composition and principle. Twenty-one patients with polysensitivity or unexplained anaphylaxis were tested by two microarrays: the ISAC® biochip and the ALEX2® biochip. The overall agreement of results between the two biochips was very good (97.8%), Analysis by molecular protein family shows a higher frequency of ALEX® positivity for LTP (7.4% versus 5.8 %), while the opposite is true for PR-10 (14.9% for ISAC® versus 11.9% for ALEX®). However, the concentrations observed in ALEX® for PR-10 are higher. As expected, a pretreatment by a specific inhibitor blocked the interference of anti-CCD IgE in ALEX® biochip. The analysis by patient allowed to highlight sensitizations to some specific components of each biochip: meat, fish, and pistachio present only on ALEX2® or alpha-Gal on ISAC®. The results obtained with the 2 biochips are generally consistent for common allergens. A more complete chip combining extracts as molecular allergens not available in individual tests should find its place in the exploration of unexplained anaphylaxis but the choice and number of allergens tested should evolve to best meet clinical needs. [ABSTRACT FROM AUTHOR]

Novel diagnostic tools are needed to diagnose latent infection and to provide biologically meaningful surrogate markers to define cellular immune responses against Mycobacterium tuberculosis (MTB). Interferon gamma-based assays have recently been developed in addition to the more than 100-year-old tuberculin skin test (TST) for the immune diagnosis of MTB in blood. The advent of soluble MHC/peptide tetramer molecules allows to objectively enumerate antigen-specific T cells. We identified novel MHC class II-restricted MTB epitopes and used HLA-DR4 tetrameric complexes to visualize ex vivo CD4+ T cells directed against the antigens Ag85B and the 19-kDa lipoprotein, shared between MTB and other Mycobacterium species, and CD4+ T cells which recognize the MTB-associated ESAT-6 antigen. MTB-reactive CD4+ T cells reside predominantly in the CD45RA+ CD28+ and CD45− CD28+ T-cell subset and recognize naturally processed and presented MTB epitopes. HLA-DR4-restricted, Ag85B or ESAT-6-specific CD4+ T cells show similar dynamics over time in peripheral blood mononuclear cells (PBMC) when compared with CD8+ T cells directed against the corresponding HLA-A2-presented MTB epitopes in patients with pulmonary MTB infection and subsequent successful therapy. This was not found to be true for T-cell responses directed against the 19-kDa lipoprotein. The dissection of the cellular immune response in M. tuberculosis infection will enable novel strategies for monitoring MTB vaccine candidates and to gauge CD4+ T cells directed against MTB. [ABSTRACT FROM AUTHOR]

Background: Exposure to formaldehyde may lead to exacerbation of asthma.Objectives: Our aim in this study was to investigate whether exposure to a low level (500 microg/m[3]) of formaldehyde enhances inhaled allergen responses.Methods: Twelve subjects with intermittent asthma and allergy to pollen were exposed, at rest, in a double-blind crossover study to either formaldehyde or purified air for 60 min. The order of exposure to formaldehyde and air-only was randomized, and exposures were separated by 2 weeks. We also performed an allergen inhalation challenge after each exposure. Airway responsiveness to methacholine and lower airway inflammation (induced sputum) were assessed 8 hr after allergen challenge.Results: The median dose of allergen producing a 15% decrease in forced expiratory volume in 1 sec (PD[15]FEV[1]) was 0.80 IR (index of reactivity) after formaldehyde exposure compared with 0.25 IR after air-only exposure (p = 0.06). Formaldehyde exposure did not affect allergen-induced increase in responsiveness to methacholine (p = 0.42). We found no formaldehyde-associated effect on the airway inflammatory response, in particular the eosinophilic inflammatory response, induced by the allergen challenge 8 hr before.Conclusion: In this study, exposure to 500 microg/m[3] formaldehyde had no significant deleterious effect on airway allergen responsiveness of patients with intermittent asthma; we found a trend toward a protective effect. [ABSTRACT FROM AUTHOR]

An association between impaired lower respiratory function and cardiovascular risk factors, such as hypertension, is often reported but it is unknown whether there is a relationship between upper airway disorders and cardiovascular risk factors, despite evidence that upper and lower respiratory tract disorders are closely linked. Our objective was to assess whether rhinitis is associated with arterial blood pressure and hypertension. In a population-based study of 330 adults aged 28-56 years, as part of the European Community Respiratory Health Survey, rhinitis was assessed by means of a questionnaire, and cardiovascular data were obtained using a questionnaire and by measuring blood pressure. Systolic blood pressure (SBP) was higher in men with rhinitis than in men without rhinitis (130.6 +/- 12.7 mm Hg versus 123.5 +/- 13.9 mm Hg; p = 0.002), and it was still the case after adjustment for cardiovascular and respiratory confounding factors. Hypertension was more frequent in men with rhinitis than in men without rhinitis, even after multivariate adjustment (odds ratio = 2.6, 95% confidence interval = [1.14-5.91]). The observation of SBP levels according to whether men have no rhinitis, seasonal rhinitis, or perennial rhinitis was compatible with a dose-response relationship (p for trend = 0.02). In conclusion, rhinitis is strongly associated with SBP and hypertension in men. Blood pressure should be regularly checked in men with rhinitis. [ABSTRACT FROM AUTHOR]

SUMMARY In response to antigenic stimulation, naive MHC-class I restricted and antigen-specific CD8+ CD45RA+ CD28+ T cells undergo clonal expansion, differentiate into CD8+ CD45RO+ memory T cells and convert to CD8+ CD45RA+ CD28- T cells displaying potent immune effector functions upon re-encounter with the nominal antigen. We show that the effector CD8+ CD45RA+ CD28- T cell subset is expanded in peripheral blood lymphocytes (PBL) from patients with human papilloma virus (HPV)+ cervical lesions as well as in PBL from patients with pulmonary tuberculosis. Flow-cytometric cell sorted CD8+ CD45RA+ CD28- and CD8+ CD45RA+ CD28- T cells were tested for recognition of HLA-A2 restricted peptides derived either from the human papillomavirus (HPV)16-E7 gene product, or from M. tuberculosis antigens. Mostly CD8+ CD45+ CD28- T cells define antigen/peptide-specific and MHC-restricted responses. These data were confirmed in PBL from patients with tuberculosis using HLA-A2 tetramer-complexes loaded with a peptide from the M. tuberculosis Ag85b antigen by flow cytometry. The sorting of this T cell subset enables to determine the fine specificity of CD8+ effector T cells without the need for in vitro manipulation. [ABSTRACT FROM AUTHOR]

Recent studies have suggested that vaccination induces alterations in the T cell receptor (TCR) repertoire. We investigate the diversity of the TCR repertoire after immunization with a recombinant hepatitis B surface vaccine in seven healthy subjects in CD8[sup +] T cells in peripheral blood lymphocytes. Cellular immune responses were monitored over time by sorting CD8 T cells followed by TCR-VA and -VB complementarity determining region 3 (CDR3) analysis. Frequency of individual VB families was determined by flow cytometry. TCR-VA/VB repertoires obtained from CD8[sup +] T cells drawn after vaccination were compared to the TCR repertoire determined prior to vaccination. Monoclonal TCR transcripts could be detected exclusively in CD8[sup +], but not in CD4[sup +] T cells. Such monoclonal TCR transcripts were either stable in some individuals, or could only be detected at certain time points after vaccination. Sorting of monoclonal TCR-VB3[sup +] T cells, which constituted up to 5% of the CD8[sup +] T cell population from one individual, revealed that this T cell clone recognizes an epitope provided by the recombinant hepatitis B vaccine presented by MHC-class I on autologous antigen-presenting cells. Examination of the structural anatomy, defined by the TCR, and the frequency of T cells responding to the immunizing antigen may be helpful to provide surrogate markers to monitor cellular immune responses induced by protein antigens utilized for vaccination. [ABSTRACT FROM AUTHOR]

Adrenaline is the first line treatment for anaphylaxis and adrenaline auto-injectors (AAI) allow reliable, safe and ergonomic administration in the community. However, AAIs have significant limitations and adrenaline is often not used in anaphylaxis. Innovations to administer adrenaline via alternative routes may potentially improve usage rates and treatment effectiveness. Here, we describe the known limitations and barriers to AAI use in anaphylaxis. We then summarise current data for adrenaline devices which use alternative routes of administration for treating anaphylaxis. Several novel devices are in development, which deliver adrenaline via nasal, sublingual or transcutaneous routes. Pharmacokinetic, pharmacodynamic and safety studies have compared these treatments with AAI or intramuscular adrenaline via needle and syringe. The first non-injectable adrenaline delivery device for emergency treatment of anaphylaxis was approved in Europe and the United States. Neffy, an adrenaline nasal spray, is licensed for use in adult and paediatric patients who weigh at least 30 kg. In the near future, multiple alternatives to injectable adrenaline may be available for managing anaphylaxis, overcoming some, but not all of the limitations of AAIs., (© 2024 The Author(s). Clinical & Experimental Allergy published by John Wiley & Sons Ltd.)

Background: Drug challenge is the gold standard for identifying causative agents of drug allergies. Although clinical guidelines have recently been published, they do not recommend neuromuscular blocking agent (NMBA) drug challenges. NMBA challenges are rendered difficult by the lack of homogeneity of routine allergy work-ups and the necessity of a specialised setting. Several scenarios support NMBA challenges, such as an ambiguous allergy work-up, a high suspicion of a false-positive skin test or identification of a well tolerated alternative NMBA strategy. Furthermore, routine allergy work-ups may not recognise non-IgE mechanisms, such as IgG or MRGPRX2, whereas drug challenges may reveal them. Finally, if the culprit NMBA is not identified, subsequent anaesthesia regimens will be challenging to implement, resulting in increased risk., Objectives: This literature review discusses the indications, strategies, doses, monitoring methods, limitations, and unresolved issues related to drug challenges for NMBAs., Design: The literature review included randomised controlled trials, observational studies, reviews, case reports, series, and comments on humans., Data Sources: Studies were retrieved from databases (PubMed) and electronic libraries (OVID, EMBASE, Scopus, etc.)., Eligibility Criteria: All studies that referred to the NMBA challenge were included without publication date limitations., Results: NMBA challenge may be considered in NMBA anaphylaxis patients with inconclusive or ambivalent IgE diagnostic work-up under controlled conditions (presence of anaesthetists and allergists with continuous monitoring in a secured environment). To illustrate its utility, a case report of a double NMBA challenge in a patient with NMBA cross-reactivity is presented, along with biological explorations to detect subclinical cellular activation, a novel aspect of this procedure., Conclusion: Drug challenges could be implemented during the NMBA allergy work-up under strict safety conditions at specialised centres with close collaboration between anaesthetists and allergists. This could decrease uncertainty and contribute to defining a safer strategy for subsequent anaesthetic drug regimens., (Copyright © 2024 European Society of Anaesthesiology and Intensive Care. Unauthorized reproduction of this article is prohibited.)

Background: The first line of prevention of surgical site infection relies on the timely administration of antibiotic prophylaxis. First- and second-generation cephalosporins are the most recommended antibiotics in elective surgery. The incidence of cefazolin allergy has increased worldwide over the years. The sensitization mechanism of cefazolin is currently unknown, and data supporting cross-reactivity between penicillins and cephalosporins are lacking. Sensitization could occur through previous exposure either to cefazolin or to structurally related chemical agents. The objective of this study was to evaluate sensitization agents towards cefazolin., Methods: The OpenBabel chemoinformatics toolbox was used to search for similarities between cefazolin and other molecules in an extensive drug database. Using the pholcodine-rocuronium similarity score as a threshold, we selected drugs with the most similar structure to that of cefazolin. Exposure to those drugs and cefazolin was assessed in a cohort of patients with skin test-proven cefazolin allergy at a specialized allergy centre via a self-administered anonymous questionnaire., Results: Using the pholcodine-rocuronium similarity score as a threshold (score≥0.7), 42 molecules were found to be similar to cefazolin (all cephalosporins). Only 8 were marketed in France. None of the 14 cefazolin-allergic patients who answered the questionnaire (65% female, median age 56 years) reported exposure to any identified antibiotics. In contrast, 11 (78%) had at least one previous surgery requiring cefazolin before the index case., Conclusion: Direct previous cefazolin exposure was identified in 78% of cefazolin-allergic patients. Cefazolin started to take a central place in antibiotic prophylaxis after 2010, when cefamandole usage decreased drastically. Changes in antibiotic prophylaxis over the past 14 years in France could have been the turning point for the increased incidence of cefazolin allergy., (Copyright © 2024 Société française d'anesthésie et de réanimation (Sfar). Published by Elsevier Masson SAS. All rights reserved.)

Competing Interests: Declaration of Competing Interest Authors declare no conflict of interest.

Background/objectives: Food hypersensitivity (FHS) is common, but little is known about the factors associated with severe reactions, age of onset and whether sensitization persists. This study examines the factors associated with self-reported severe food reactions, onset age and the changes in prevalence of sensitization to foods over time in an adult sample., Subjects/methods: We used data from adults taking part in the European Community Respiratory Health Survey (ECRHS) III (2010-2014) who provided information on food hypersensitivity, including symptoms, suspected culprit food and onset age (n = 4865). A subsample from six countries had serum food-specific IgE tested for 25 core foods and also in 10 years earlier (ECRHS II). We applied logistic regression and McNemar's test for analyses., Results: The prevalence of self-reported FHS was 13.5% at ECRHS III. Of those providing information on symptoms (n = 611), 26.4% reported severe reactions. About 80% of 1033 reported food-specific reactions (reported by 596 participants) began after age 15. History of asthma (odds ratio OR 2.12 95% confidence interval CI 1.13-3.44) and a younger age of onset of FHS (OR 1.02, 95% CI 1.01-1.03, per year) were associated with higher risks of a lifetime experience of severe food reactions. In the subsample with IgE tested in both surveys (n = 1612), the overall prevalence of sensitization to foods did not change over 10 years., Conclusion: Our findings support previous observations of more severe food reactions in people with asthma and that most FHS reported by this sample started after age 15. We found no evidence of changes in the prevalence of sensitization to food in adults followed for 10 years., (© 2023. The Author(s).)

Background: A written action plan (WAP) for managing asthma exacerbations is recommended., Objective: We aimed to compare the effect on unscheduled medical contacts (UMCs) of a digital action plan (DAP) accessed via a smartphone web app combined with a WAP on paper versus that of the same WAP alone., Methods: This randomized, unblinded, multicenter (offline recruitment in private offices and public hospitals), and parallel-group trial included children (aged 6-12 years) or adults (aged 18-60 years) with asthma who had experienced at least 1 severe exacerbation in the previous year. They were randomized to a WAP or DAP+WAP group in a 1:1 ratio. The DAP (fully automated) provided treatment advice according to the severity and previous pharmacotherapy of the exacerbation. The DAP was an algorithm that recorded 3 to 9 clinical descriptors. In the app, the participant first assessed the severity of their current symptoms on a 10-point scale and then entered the symptom descriptors. Before the trial, the wordings and ordering of these descriptors were validated by 50 parents of children with asthma and 50 adults with asthma; the app was not modified during the trial. Participants were interviewed at 3, 6, 9, and 12 months to record exacerbations, UMCs, and WAP and DAP use, including the subjective evaluation (availability and usefulness) of the action plans, by a research nurse., Results: Overall, 280 participants were randomized, of whom 33 (11.8%) were excluded because of the absence of follow-up data after randomization, leaving 247 (88.2%) participants (children: n=93, 37.7%; adults: n=154, 62.3%). The WAP group had 49.8% (123/247) of participants (children: n=45, 36.6%; mean age 8.3, SD 2.0 years; adults: n=78, 63.4%; mean age 36.3, SD 12.7 years), and the DAP+WAP group had 50.2% (124/247) of participants (children: n=48, 38.7%; mean age 9.0, SD 1.9 years; adults: n=76, 61.3%; mean age 34.5, SD 11.3 years). Overall, the annual severe exacerbation rate was 0.53 and not different between the 2 groups of participants. The mean number of UMCs per year was 0.31 (SD 0.62) in the WAP group and 0.37 (SD 0.82) in the DAP+WAP group (mean difference 0.06, 95% CI -0.12 to 0.24; P=.82). Use per patient with at least 1 moderate or severe exacerbation was higher for the WAP (33/65, 51% vs 15/63, 24% for the DAP; P=.002). Thus, participants were more likely to use the WAP than the DAP despite the nonsignificant difference between the action plans in the subjective evaluation. Median symptom severity of the self-evaluated exacerbation was 4 out of 10 and not significantly different from the symptom severity assessed by the app., Conclusions: The DAP was used less often than the WAP and did not decrease the number of UMCs compared with the WAP alone., Trial Registration: ClinicalTrials.gov NCT02869958; https://clinicaltrials.gov/ct2/show/NCT02869958., (©Nicole Beydon, Camille Taillé, Harriet Corvol, Judith Valcke, Jean-Jacques Portal, Laurent Plantier, Gilles Mangiapan, Caroline Perisson, Guillaume Aubertin, Alice Hadchouel, Guillaume Briend, Laurent Guilleminault, Catherine Neukirch, Pierrick Cros, Corinne Appere de Vecchi, Bruno Mahut, Eric Vicaut, Christophe Delclaux. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 29.06.2023.)

Competing Interests: The authors declare that they do not have conflict of interests related to the contents of this article.

Increased blood fibrocytes are associated with a poor prognosis in fibrotic lung diseases. We aimed to determine whether the percentage of circulating fibrocytes could be predictive of severity and prognosis during coronavirus disease 2019 (COVID-19) pneumonia. Blood fibrocytes were quantified by flow cytometry as CD45 + /CD15 - /CD34 + /collagen-1 + cells in patients hospitalized for COVID-19 pneumonia. In a subgroup of patients admitted in an intensive care unit (ICU), fibrocytes were quantified in blood and bronchoalveolar lavage (BAL). Serum amyloid P (SAP), transforming growth factor-β1 (TGF-β1), CXCL12, CCL2, and FGF2 concentrations were measured. We included 57 patients in the hospitalized group (median age = 59 yr [23-87]) and 16 individuals as healthy controls. The median percentage of circulating fibrocytes was higher in the patients compared with the controls (3.6% [0.2-9.2] vs. 2.1% [0.9-5.1], P = 0.04). Blood fibrocyte count was lower in the six patients who died compared with the survivors (1.6% [0.2-4.4] vs. 3.7% [0.6-9.2], P = 0.02). Initial fibrocyte count was higher in patients showing a complete lung computed tomography (CT) resolution at 3 mo. Circulating fibrocyte count was decreased in the ICU group (0.8% [0.1-2.0]), whereas BAL fibrocyte count was 6.7% (2.2-15.4). Serum SAP and TGF-β1 concentrations were increased in hospitalized patients. SAP was also increased in ICU patients. CXCL12 and CCL2 were increased in ICU patients and negatively correlated with circulating fibrocyte count. We conclude that circulating fibrocytes were increased in patients hospitalized for COVID-19 pneumonia, and a lower fibrocyte count was associated with an increased risk of death and a slower resolution of lung CT opacities.

Acute hypersensitivity reactions to drugs occur infrequently during anaesthesia and the peri-operative period. When clinical presentation includes the classical triad, erythema, cardiovascular abnormalities and increased airway pressure, the diagnosis is evident and the challenge is to prescribe a therapeutic regimen according to guidelines and to manage refractory signs in a timely manner. In many situations, however, the initial clinical signs are isolated, such as increased airway pressure or arterial hypotension. Rendering a differential diagnosis with causes and mechanisms other than acute hypersensitivity reactions (AHRs) is difficult, delaying treatment with possible worsening of the clinical signs, and even death, in previously healthy individuals. In these difficult diagnostic situations, clinical reasoning is mandatory, and guidelines do not explicitly explain the elements on which clinical reasoning can be built. In this article, based on clinical evidence whenever available, experimental data and pathophysiology, we propose algorithms that have been evaluated by experts. The goal of these algorithms is to provide explicit elements on which the differential diagnosis of AHRs can be made, accelerating the implementation of adequate therapy., (Copyright © 2021 European Society of Anaesthesiology and Intensive Care. Unauthorized reproduction of this article is prohibited.)

Introduction: Among allergic rhinitis (AR) symptoms, nasal obstruction particularly affects the quality of life. Antihistamines and intranasal corticosteroids are the most frequently prescribed symptomatic drugs, but their efficacy is often incomplete. Essential oils (EO) have shown an anti-inflammatory effect and potential in treating patients with AR. The aim of this study was to evaluate the effectiveness of a hypertonic EO-based nasal spray on perennial AR (PAR) symptoms., Methods: This prospective, open-label, non-randomized, multicentric trial included 43 patients with PAR sensitized to mites, not controlled for more than a year. All were treated with Puressentiel® Respiratory-Decongestant Nasal Spray for 30 days. Their usual treatment remained unchanged during the study period. Before and after treatment, each participant filled out a rhinitis questionnaire, the Allergic Rhinitis Control Test (ARCT). A nasal inspiratory peak flow (NIPF) was performed., Results: The mean ARCT was 16.4 and 20.5 at D0 and D30, respectively (p < 0.001); the mean increase between D0 and D30 was 4.1 (p < 0.001). The proportion of patients with controlled rhinitis after 30 days of treatment was 69.8 versus 14% before treatment (p < 0.001). The mean NIPF was 86.5 L/min and 105.1 L/min at D0 and D30, respectively (p < 0.001); the mean increase between D0 and D30 was 18.5 L/min., Conclusion: A hypertonic EO-based nasal spray could be a new and natural option in the management of PAR. It could also be used as an add-on therapy when nasal symptoms are not fully controlled., (The Author(s). Published by S. Karger AG, Basel.)

Background: The optimal treatment for patients with severe coronavirus-19 disease (COVID-19) and hyper-inflammation remains debated., Material and Methods: A cohort study was designed to evaluate whether a therapeutic algorithm using steroids with or without interleukin-1 antagonist (anakinra) could prevent death/invasive ventilation. Patients with a ≥5-day evolution since symptoms onset, with hyper-inflammation (CRP≥50mg/L), requiring 3-5 L/min oxygen, received methylprednisolone alone. Patients needing ≥6 L/min received methylprednisolone + subcutaneous anakinra daily either frontline or in case clinical deterioration upon corticosteroids alone. Death rate and death or intensive care unit (ICU) invasive ventilation rate at Day 15, with Odds Ratio (OR) and 95% CIs, were determined according to logistic regression and propensity scores. A Bayesian analysis estimated the treatment effects., Results: Of 108 consecutive patients, 70 patients received glucocorticoids alone. The control group comprised 63 patients receiving standard of care. In the corticosteroid±stanakinra group (n = 108), death rate was 20.4%, versus 30.2% in the controls, indicating a 30% relative decrease in death risk and a number of 10 patients to treat to avoid a death (p = 0.15). Using propensity scores a per-protocol analysis showed an OR for COVID-19-related death of 0.9 (95%CI [0.80-1.01], p = 0.067). On Bayesian analysis, the posterior probability of any mortality benefit with corticosteroids+/-anakinra was 87.5%, with a 7.8% probability of treatment-related harm. Pre-existing diabetes exacerbation occurred in 29 of 108 patients (26.9%)., Conclusion: In COVID-19 non-ICU inpatients at the cytokine release phase, corticosteroids with or without anakinra were associated with a 30% decrease of death risk on Day 15., Competing Interests: Raphael Borie, Laurent Savalle, Antoine Dossier, Camille Taillé, Benoit Visseaux, Kamel Jebreen, Sébastien Ottaviani, Chloe Tesmoingt, Lise Morer, Tiphaine Goletto, Nathalie Faucher, Linda Hajouji, Catherine Neukirch, Mathilde Phillips, Sandrine Stelianides, Solenn Brosseau, Johan Pluvy, Marie Pierre Debray, Raynaud-Simon Agathe, Antoine Khalil, Vincent Descamps, Thomas Papo, Marc Humbert, Bruno Crestani, Eric Vicaut, Gérard Zalcman have nothing to disclose. Jean Francois Timsit reported participation to an advisory board from Gilead. Is the principal investigator of PHRC-N 'Covidicus' (Dexamethasone vs. Placebo on Covid-19 pneumonia in ICUs) granted by the French Ministry of Health. Jade Ghosn reported receiving Jade Ghosn reported receiving travel grants and fundings from Gilead Sciences, ViiV Healthcare and MSD. Benoit Visseaux reported grants from QIAGEN outside the scope of the current work Xavier Lescure reported travel grants and fundings from from Gilead, MSD, Astellas, Eumedica. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Interpretation of genetic variants detected by sequencing of genomic DNA, which may cause splicing defects, regularly requires mRNA analysis. Usually, only bioinformatic testing is provided, because simple and non-invasive assay protocols are lacking. Furthermore, the detection of mis-splicing is often hampered by nonsense mediated mRNA decay (NMD)., Methods: Starting from a case of Pompe disease with two potential splicing variants an assay for the analysis of splice defects in general was developed. We analyzed the transcripts from the gene of interest by standard methods after short-term culture of the patient's lymphocytes in the presence and absence of a NMD inhibitor. Variant and wild type transcript expression were quantified by allele specific PCR in the patient and both parents and the expression ratio with/without NMD inhibition was calculated for each transcript., Results: NMD detection in lymphocytes was optimized and evaluated by analyzing a naturally occurring NMD transcript. Several compounds inhibited NMD successfully, including potential therapeutic agents. Sample storage for up to 4 days at room temperature prior to lymphocyte isolation did not affect results. In a proof of concept we identified two candidate variants as severe splicing variants in a patient with Pompe disease, but the strategy can also be used to screen for any mis-spliced transcripts prone to NMD., Conclusions: We developed a simple, non-invasive assay for the detection and characterization of potential splicing variants. This is essential, because early and near-term diagnosis and disease classification is required to facilitate therapy in many genetic diseases., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

The small β-pore-forming α-toxin, also termed α-hemolysin or Hla is considered to be an important virulence factor of Staphylococcus aureus. Perforation of the plasma membrane (PM) by Hla leads to uncontrolled flux of ions and water. Already a small number of toxin pores seems to be sufficient to induce complex cellular responses, many of which depend on the efflux of potassium. In this article, we discuss the implications of secondary membrane lesions, for example, by endogenous channels, for Hla-mediated toxicity, for calcium-influx and membrane repair. Activation of purinergic receptors has been proposed to be a major contributor to the lytic effects of various pore forming proteins, but new findings raise doubts that this holds true for Hla. However, the recently discovered cellular pore forming proteins gasdermin D and Mixed lineage kinase domain-like pseudokinase (MLKL) which perforate the PM from the cytosolic side might contribute to both calcium-influx-dependent damage and membrane repair. Activation of endogenous pore forming proteins by Hla above a threshold concentration could explain the apparent dependence of pore characteristics on toxin concentrations. If secondary membrane damage in the aftermath of Hla-attack contributes significantly to overall PM permeability, it might be an interesting target for new therapeutic approaches.

Background : Essential oils are volatile compounds of plant origin increasingly used by allergic and/or asthmatic subjects to purify indoor air. The active compounds of essential oils belong to terpenes, the most widespread biogenic volatile organic compounds (VOC). Although there is substantial literature showing associations between exposure to chemical VOCs and asthmatic symptoms and impaired respiratory function, the impact of essential oils in patients with asthma has never been studied. Objectives : To evaluate the safety of a purifying air spray containing 41 essential oils (PPAS) in patients with mild or moderate allergic asthma. Methods : This was a prospective open study in which 25 mild (19) and moderate (6) asthmatics were exposed to PPAS, one spray twice a day at 8 am and 8 pm in two different corners of a given subjects bedroom for 4 weeks. Before and after 4 weeks of exposure, fractional exhaled nitric oxide (FeNO), lung function and methacholine challenge (PD 20 ) were performed and asthma control was assessed by the 5 questions of the Asthma Control Test (ACT). The spray was weighed after the 4-week exposure to assess compliance. Results : FeNO was the primary endpoint and was thus analyzed in all ( N  = 25) subjects irrespective of the level of airflow obstruction. The results apply to all ( N  = 25) subjects in which FeNO could be measured at D1 and D30 (17 subjects). Mean (SD) FeNO amounted to 37.4 (16.6) and to 33.1 (18.7) ppm before and after PPAS exposure, respectively ( p  = 0.09). No significant change in lung function and methacholine responsiveness was noted after PPAS exposure, the mean PD 20 amounting to 1179 (1124.42) μg (range 100-3200) before and to 1226 (1189.8) μg ( p  = 0.06) after. The mean ACT before and after PPAS exposure amounted to 20.9 (4.2) and 21 (5.15), respectively ( p  = 0.80). The mean weight of the PPAS bottles was 211.4 g (DS:0) before the first use and 171.41 g (DS: 29.8) at the end of the study. The average amount of PPAS used was 40.0 g (29.8). In the subgroup of subjects who used the highest quantities of essential oils (>40 g), as assessed by the mean weight of the bottle at the end of the study, FeNO after 30 days of exposure decreased more than in the entire group: 7.9 ppm vs 4.2 ppm ( p  = 0.07). Conclusion : No difference was noted on airway inflammation, lung function or asthma control in mild and moderate allergic asthmatics after exposure twice a day for one month, to a spray containing a mixture of 41 essential oils.

Anaphylaxis is a systemic acute hypersensitivity reaction that is considered to depend on allergen-specific immunoglobulin E (IgE) antibodies and histamine release by mast cells and basophils. Nevertheless, allergen-specific IgG antibodies have been proposed to contribute when the allergen is an abundant circulating large molecule, e.g., after infusions of therapeutic antibodies or dextran. Data from animal models demonstrate a pathway involving platelet-activating factor (PAF) release by monocytes/macrophages and neutrophils activated via their Fc gamma receptors (FcγRs). We hypothesized that such a pathway may also apply to small drugs and could be responsible for non-IgE-mediated anaphylaxis and influence anaphylaxis severity in humans. We prospectively conducted a multicentric study of 86 patients with suspected anaphylaxis to neuromuscular-blocking agents (NMBAs) during general anesthesia and 86 matched controls. We found that concentrations of anti-NMBA IgG and markers of FcγR activation, PAF release, and neutrophil activation correlated with anaphylaxis severity. Neutrophils underwent degranulation and NETosis early after anaphylaxis onset, and plasma-purified anti-NMBA IgG triggered neutrophil activation ex vivo in the presence of NMBA. Neutrophil activation could also be observed in patients lacking evidence of classical IgE-dependent anaphylaxis. This study supports the existence of an IgG-neutrophil pathway in human NMBA-induced anaphylaxis, which may aggravate anaphylaxis in combination with the IgE pathway or underlie anaphylaxis in the absence of specific IgE. These results reconcile clinical and experimental data on the role of antibody classes in anaphylaxis and could inform diagnostic approaches to NMBA-induced acute hypersensitivity reactions., (Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Background: We previously showed that patients with severe allergic asthma have high numbers of circulating ILC2s expressing CCR10., Method: Herein, CCR10 + ILC2s were further analyzed in the blood of healthy individuals or patients with allergic and non-allergic asthma. Characteristics of human CCR10 + and CCR10 - ILC2s were assessed by flow cytometry as well as single-cell multiplex RT-qPCR. The role of CCR10 + ILC2s in asthma pathophysiology was studied in allergen-treated mice., Results: When compared to healthy controls, CCR10 + ILC2s are enriched in the blood of both allergic and non-allergic severe asthmatic patients, and these cells are recruited to the lungs. Plasma concentrations of the CCR10 ligand CCL27 are significantly increased in severe asthmatics when compared to non-asthmatic patients. CCR10 + ILC2s secrete little T H 2 cytokines, but exhibit ILC1-like properties, including a capacity to produce IFN-γ. Also, single-cell analysis reveals that the CCR10 + ILC2 subset is enriched in cells expressing amphiregulin. CCR10 + ILC2 depletion, as well as blocking of IFN-γ activity, exacerbates airway hyperreactivity in allergen-challenged mice, providing evidence for a protective role of these cells in allergic inflammation., Conclusions: Frequencies of circulating CCR10 + ILC2s and CCL27 plasma concentrations represent candidate markers of asthma severity. The characterization of CCR10 + ILC2s in human samples and in mouse asthma models suggests that these cells downregulate allergic inflammation through IFN-γ production., (© 2018 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)