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Following the European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA) treatment algorithm for chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP), patients suffering from severe uncontrolled CRSwNP are recommended to receive oral corticosteroids, (revision) sinus surgery, systemic biologicals and/or aspirin treatment after desensitization (ATAD). Given the major differences in indications, outcomes, practical considerations, risks and costs of these key pillars of treatment, there is a growing need to define criteria for each treatment option and list the clinically relevant and major considerations for them. This EUFOREA document therefore provides an expert panel overview of the expected outcomes, specific considerations and (contra)indications of the five major treatment arms of severe uncontrolled CRSwNP: oral corticosteroids, primary and revision sinus surgery, biological treatment and ATAD. This overview of treatment considerations is needed to allow physicians and patients to consider the different options in the context of providing optimal and personalized care for severe uncontrolled CRSwNP. In conclusion, the five major treatment options for severe uncontrolled CRSwNP have intrinsic advantages, specific indications and considerations that are of importance to the patient, the physician and the society. This EUFOREA statement supports the unmet need to define criteria for the indication of every treatment pillar of CRSwNP. [ABSTRACT FROM AUTHOR]

Background: In the 52‐week Phase III SYNAPSE study, mepolizumab given every 4 weeks (100 mg subcutaneously) reduced nasal polyp (NP) size, improved symptoms and quality of life (QoL), and reduced corticosteroid use and number of sinus surgeries in patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP), versus placebo. Because the durability of mepolizumab's efficacy after discontinuation is poorly understood in CRSwNP, the efficacy of mepolizumab after discontinuation was analyzed in severe CRSwNP, over a 24‐week follow‐up. Methods: Changes from SYNAPSE baseline to end of treatment (week 52) and end of follow‐up (week 76) were assessed for total endoscopic NP score, nasal obstruction and overall symptoms visual analog scale scores, and 22‐item Sino‐Nasal Outcome Test score. Time to first sinus surgery, time to first corticosteroid use, and geometric mean blood eosinophil counts (BECs) were also assessed. Results: Among 134 follow‐up patients, clinical improvements observed with mepolizumab versus placebo were partially evident 24 weeks after discontinuation despite BEC returning to baseline. The mean (95% confidence interval [CI]) change from baseline in NP score (week 52: −1.3 [1.8 to −0.9] vs. −0.3 [−0.6 to 0.1]; week 76: −1.2 [−1.6 to −0.7] vs. −0.1 [−0.5 to 0.3]) and the proportion of patients having sinus surgery (week 52: 4% vs. 25%; week 76: 9% vs. 31%) remained substantially improved with mepolizumab versus placebo. Mepolizumab‐associated improvements in overall symptoms, quality of life, and corticosteroid use versus placebo were partially sustained at week 76. Conclusion: Fifty‐two weeks of mepolizumab treatment is associated with sustained clinical benefits up to 24 weeks after discontinuation in patients with severe CRSwNP, which should be considered by physicians when making treatment decisions. [ABSTRACT FROM AUTHOR]

Over the past years, eosinophils have become a focus of scientific interest, especially in the context of their recently uncovered functions (e.g. antiviral, anti‐inflammatory, regulatory). These versatile cells display both beneficial and detrimental activities under various physiological and pathological conditions. Eosinophils are involved in the pathogenesis of many diseases which can be classified into primary (clonal) and secondary (reactive) disorders and idiopathic (hyper)eosinophilic syndromes. Depending on the biological specimen, the eosinophil count in different body compartments may serve as a biomarker reflecting the underlying pathophysiology and/or activity of distinct diseases and as a therapy‐driving (predictive) and monitoring tool. Personalized selection of an appropriate therapeutic strategy directly or indirectly targeting the increased number and/or activity of eosinophils should be based on the understanding of eosinophil homeostasis including their interactions with other immune and non‐immune cells within different body compartments. Hence, restoring as well as maintaining homeostasis within an individual's eosinophil pool is a goal of both specific and non‐specific eosinophil‐targeting therapies. Despite the overall favourable safety profile of the currently available anti‐eosinophil biologics, the effect of eosinophil depletion should be monitored from the perspective of possible unwanted consequences. [ABSTRACT FROM AUTHOR]

Introduction: In allergic asthma patients, one of the more common phenotypes might benefit from allergen immunotherapy (AIT) as add‐on intervention to pharmacological treatment. AIT is a treatment with disease‐modifying modalities, the evidence for efficacy is based on controlled clinical trials following standardized endpoint measures. However, so far there is a lack of a consensus for asthma endpoints in AIT trials. The aim of a task force (TF) of the European Academy of Allergy and Clinical Immunology (EAACI) is evaluating several outcome measures for AIT in allergic asthma. Methods: The following domains of outcome measures in asthmatic patients have been evaluated for this position paper (PP): (i) exacerbation rate, (ii) lung function, (iii) ICS withdrawal, (iv) symptoms and rescue medication use, (v) questionnaires (PROMS), (vi) bronchial/nasal provocation, (vii) allergen exposure chambers (AEC) and (viii) biomarkers. Results: Exacerbation rate can be used as a reliable objective primary outcome; however, there is limited evidence due to different definitions of exacerbation. The time after ICS withdrawal to first exacerbation is considered a primary outcome measure. Besides, the advantages and disadvantages and clinical implications of further domains of asthma endpoints in AIT trials are elaborated in this PP. Conclusion: This EAACI‐PP aims to highlight important aspects of current asthma measures by critically evaluating their applicability for controlled trials of AIT. [ABSTRACT FROM AUTHOR]

To the Editor, Asthma is a heterogeneous disease, as reflected by differences in age of onset, severity, treatment response and inflammatory profile. In all, FP-025 in a dose-dependent manner significantly attenuated AHR, BAL inflammatory cell numbers and lung pathohistology in a mouse model of persistent HDM-allergic asthma. FP-025 markedly reduced MMP-12 expression in airway epithelial cells and levels of MMP-12 in lung parenchyma and airways, indicating that the enhanced expression in allergic asthma depends on an autocrine process. [Extracted from the article]

Introduction: Allergic asthmatics with both an early (EAR) and a late allergic reaction (LAR) following allergen exposure are termed 'dual responders' (DR), while 'single responders' (SR) only have an EAR. Mechanisms that differentiate DR from SR are largely unknown, particularly regarding the role and phenotypes of neutrophils. Therefore, we aimed to study neutrophils in DR and SR asthmatics. Methods: Thirty‐four allergic asthmatics underwent an inhaled allergen challenge, samples were collected before and up to 24 h post‐challenge. Cell differentials were counted from bronchial lavage, alveolar lavage and blood; and tissue neutrophils were quantified in immune‐stained bronchial biopsies. Lavage neutrophil nuclei lobe segmentation was used to classify active (1–4 lobes) from suppressive neutrophils (≥5 lobes). Levels of transmigration markers: soluble (s)CD62L and interleukin‐1Ra, and activity markers: neutrophil elastase (NE), DNA‐histone complex and dsDNA were measured in lavage fluid and plasma. Results: Compared with SR at baseline, DR had more neutrophils in their bronchial airways at baseline, both in the lavage (p =.0031) and biopsies (p =.026) and elevated bronchial neutrophils correlated with less antitransmigratory IL‐1Ra levels (r = −0.64). DR airways had less suppressive neutrophils and more 3‐lobed (active) neutrophils (p =.029) that correlated with more bronchial lavage histone (p =.020) and more plasma NE (p =.0016). Post‐challenge, DR released neutrophil extracellular trap factors in the blood earlier and had less pro‐transmigratory sCD62L during the late phase (p =.0076) than in SR. Conclusion: DR have a more active airway neutrophil phenotype at baseline and a distinct neutrophil response to allergen challenge that may contribute to the development of an LAR. Therefore, neutrophil activity should be considered during targeted diagnosis and bio‐therapeutic development for DR. [ABSTRACT FROM AUTHOR]

This review presents state‐of‐the‐art knowledge and identifies knowledge gaps for future research in the area of exercise‐associated modifications of infection susceptibility. Regular moderate‐intensity exercise is believed to have beneficial effects on immune health through lowering inflammation intensity and reducing susceptibility to respiratory infections. However, strenuous exercise, as performed by professional athletes, may promote infection: in about half of athletes presenting respiratory symptoms, no causative pathogen can be identified. Acute bouts of exercise enhance the release of pro‐inflammatory mediators, which may induce infection‐like respiratory symptoms. Relatively few studies have assessed the influence of regularly repeated exercise on the immune response and systemic inflammation compared to the effects of acute exercise. Additionally, ambient and environmental conditions may modify the systemic inflammatory response and infection susceptibility, particularly in outdoor athletes. Both acute and chronic regular exercise influence humoral and cellular immune response mechanisms, resulting in decreased specific and non‐specific response in competitive athletes. The most promising areas of further research in exercise immunology include detailed immunological characterization of infection‐prone and infection‐resistant athletes, examining the efficacy of nutritional and pharmaceutical interventions as countermeasures to infection symptoms, and determining the influence of various exercise loads on susceptibility to infections with respiratory viruses, including SARS‐CoV‐2. By establishing a uniform definition of an "elite athlete," it will be possible to make a comparable and straightforward interpretation of data from different studies and settings. [ABSTRACT FROM AUTHOR]

Non‐steroidal anti‐inflammatory drugs (NSAIDs) and other eicosanoid pathway modifiers are among the most ubiquitously used medications in the general population. Their broad anti‐inflammatory, antipyretic, and analgesic effects are applied against symptoms of respiratory infections, including SARS‐CoV‐2, as well as in other acute and chronic inflammatory diseases that often coexist with allergy and asthma. However, the current pandemic of COVID‐19 also revealed the gaps in our understanding of their mechanism of action, selectivity, and interactions not only during viral infections and inflammation, but also in asthma exacerbations, uncontrolled allergic inflammation, and NSAIDs‐exacerbated respiratory disease (NERD). In this context, the consensus report summarizes currently available knowledge, novel discoveries, and controversies regarding the use of NSAIDs in COVID‐19, and the role of NSAIDs in asthma and viral asthma exacerbations. We also describe here novel mechanisms of action of leukotriene receptor antagonists (LTRAs), outline how to predict responses to LTRA therapy and discuss a potential role of LTRA therapy in COVID‐19 treatment. Moreover, we discuss interactions of novel T2 biologicals and other eicosanoid pathway modifiers on the horizon, such as prostaglandin D2 antagonists and cannabinoids, with eicosanoid pathways, in context of viral infections and exacerbations of asthma and allergic diseases. Finally, we identify and summarize the major knowledge gaps and unmet needs in current eicosanoid research. [ABSTRACT FROM AUTHOR]

Bronchial lavage, cysteinyl-leukotriene pathway, allergen bronchoprovocation test, asthma, prostaglandin pathway Keywords: Bronchial lavage; cysteinyl-leukotriene pathway; prostaglandin pathway; allergen bronchoprovocation test; asthma EN Bronchial lavage cysteinyl-leukotriene pathway prostaglandin pathway allergen bronchoprovocation test asthma 2549 2551 3 08/09/22 20220801 NES 220801 ACKNOWLEDGMENTS This work was supported by independent grants from the Swedish Asthma and Allergy Association's Research Foundation, Crafoord Foundation, Swedish Heart and Lung Foundation and Alfred Österlund Foundation. The levels of cysteinyl-leukotriene metabolites, Cys-LT, and prostaglandin metabolites, prostaglandin E metabolites (PGEM), were measured in the lavage fluids by the respective ELISA from Cayman Chemical (Ann Arbor, MI). [Extracted from the article]

Rescue ICS/SABA (under development as a single inhaler8 with favourable results of the pivotal studies just announced)9 would address many of these limitations as it could be used to overcome the current barriers to the ICQ generalizability at all treatment steps, irrespective of the type of background maintenance asthma therapy (if any). Anti-inflammatory treatment is the pharmacological cornerstone of asthma management. [Extracted from the article]