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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]

"Epidemiology of comorbidities and their association with asthma control" (Tomisa, G., Horváth, A., Sánta, B. et al. Epidemiology of comorbidities and their association with asthma control. Allergy Asthma Clin Immunol 17, 95 (2021). https://doi.org/10.1186/s13223-021-00598-3) is an interesting paper reflecting data collection from more than 12,000 asthmatic patients in Hungary regarding their condition and associated comorbidities. We found it valuable that the paper provides an overview of asthma comorbidities not usually considered in similar reports. Nevertheless, we believe that chronic rhinosinusitis (CRS) with or without nasal polyps (CRSwNP or CRSsNP) should have been listed due to its high incidence and prevalence, its association with asthma which is also endorsed in both GINA and EPOS, as well as in several peer-reviewed scientific papers, and to reflect the role of this comorbidity in poor control and a most severe presentation of asthma for the patient. Consequently, several targeted therapies (especially monoclonal antibodies) used for several years in severe forms of asthma are now indicated also for the effective treatment of nasal polyps. [ABSTRACT FROM AUTHOR]

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]

Background: A subset of individuals with allergic asthma develops a late phase response (LPR) to inhaled allergens, which is characterized by a prolonged airway obstruction, airway inflammation and airway hyperresponsiveness. The aim of this study was to identify changes in the plasma proteome and circulating hematopoietic progenitor cells associated with the LPR following inhaled allergen challenge.Methods: Serial plasma samples from asthmatics undergoing inhaled allergen challenge were analyzed by mass spectrometry and immunosorbent assays. Peripheral blood mononuclear cells were analyzed by flow cytometry. Mass spectrometry data were analyzed using a linear regression to model the relationship between airway obstruction during the LPR and plasma proteome changes. Data from immunosorbent assays were analyzed using linear mixed models.Results: Out of 396 proteins quantified in plasma, 150 showed a statistically significant change 23 h post allergen challenge. Among the most upregulated proteins were three protease inhibitors: alpha-1-antitrypsin, alpha-1-antichymotrypsin and plasma serine protease inhibitor. Altered levels of 13 proteins were associated with the LPR, including increased factor XIII A and decreased von Willebrand factor. No relationship was found between the LPR and changes in the proportions of classical, intermediate, and non-classical monocytes.Conclusions: Allergic reactions to inhaled allergens in asthmatic subjects were associated with changes in a large proportion of the measured plasma proteome, whereof protease inhibitors showed the largest changes, likely to influence the inflammatory response. Many of the proteins altered in relation to the LPR are associated with coagulation, highlighting potential mechanistic targets for future treatments of type-2 asthma. [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]