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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]