Sputum cytology during late‐phase responses to inhalation challenge with different allergens

Revez, Joana A.; Killian, Kieran J.; O'Byrne, Paul M.; Boulet, Louis Philippe; Upham, John W.; Gauvreau, Gail M.; Ferreira, Manuel

doi:10.1111/all.13415

Cited by 9 publications

(7 citation statements)

References 42 publications

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“…The signature that we observed in sputum was enriched in proteins expressed by neutrophils, epithelial cells, and monocytes/macrophages. These cell types have been well described in sputum of asthmatics, with eosinophils, neutrophils, macrophages, and squamous epithelial cells elevated in sputum following allergen challenge . Recently, type 2 immune and epithelial‐associated gene networks, linked to mucociliary clearance, were characterized in sputum of HDM‐sensitized asthmatics with wheeze in response to natural allergen exposure, even in the absence of challenge .…”

Section: Discussionmentioning

confidence: 99%

Proteomic analysis of serum and sputum analytes distinguishes controlled and poorly controlled asthmatics

Kasaian

Lee

Brennan

et al. 2018

Clin Experimental Allergy

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Section: Discussionmentioning

confidence: 99%

Proteomic analysis of serum and sputum analytes distinguishes controlled and poorly controlled asthmatics

Kasaian

Lee

Brennan

et al. 2018

Clin Experimental Allergy

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“…In addition to the type of inhaled allergen, baseline airway responsiveness to methacholine could also be a determinant of late responses (13) (10,13). In our study, the decreased PC 20 -Mch after allergen bronchial challenge might be caused by the increased eosinophils in lower airways, as airway inflammation influence or determine AHR (25).…”

Section: Discussionmentioning

confidence: 62%

“…In this study, the percentage of eosinophils in PB and sputum were significantly increased after allergen bronchial challenge. Although airway responsiveness was different with various kind of allergen inhaled, airway inflammatory subtype in sputum is unlikely to be influenced by the type of inhaled allergen (13,25,26). The increased eosinophils in airways might be derived from bone marrow and PB after allergen challenge (9,(27)(28)(29), and airway inflammation changed over time, the eosinophilic inflammation may reach the peak level at different time points in different organs after allergen exposure.…”

Section: Discussionmentioning

confidence: 99%

Response of upper and lower airway inflammation to bronchial challenge with house dust mite in Chinese asthmatics: a pilot study

Zhu¹,

Wang²,

Xie³

et al. 2021

J Thorac Dis

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Background: Allergen nasal challenge can induce increase of eosinophils in sputum, but report about eosinophilic inflammation in upper airway after allergen bronchial challenge in Chinese asthmatics was rare. The article aims to evaluate response of upper and lower airways to house dust mite (HDM) allergen bronchial challenge. Methods: HDM allergen bronchial challenge was carried out in asthmatic patients with allergic rhinitis (AR). Bronchial methacholine challenge and blood test were performed before and at 24 hours after allergen challenge. Nasal lavage and induced sputum for differential cells count and fractional exhaled nitric oxide (FeNO) measurement were performed before, 7 and 24 hours after allergen challenge.Results: Eighteen asthmatic patients with AR underwent HDM allergen bronchial challenge with no serious adverse events reported. Fifteen patients showed dual asthmatic response (DAR), while 2 patients showed early (EAR) and 1 late asthmatic response (LAR) only. At 24 hours after allergen bronchial challenge testing, average PC 20 FEV 1 to methacholine significantly decreased (1.58 to 0.81 mg/mL, P=0.03), while both FeNO and the percentage of eosinophils in blood and sputum were significantly increased [52.0 (54.0) to 69.0 (56.0) ppb, P=0.01; 4.82% to 6.91%, P<0.001; 20.70% to 27.86%, P=0.03, respectively], but with no significant differences found in the percentage of eosinophils in nasal lavage (39.36% to 38.58%, P=0.89). However, at 7 hours after allergen challenge, the eosinophils in sputum were significant increased to 40.45% (P<0.001), but there was an increase (39.36% to 48.07%) with no statistical difference (P=0.167) found in nasal lavage. Conclusions: HDM allergen bronchial challenge induced different response of airway inflammation in upper and lower airways.

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“…Second, the provoked model of asthma that we used might not be the most effective approach to assess the efficacy of therapies that target non‐type 2 inflammatory pathways. Based on historical data, we expected that ~40% of patients tested using this model would develop airway inflammation during the LAR that was rich in both eosinophils and neutrophils, the inflammatory subtype that we and others have suggested is more likely to respond to TCZ treatment. However, at 7 h postchallenge, only one of the 11 patients was found to have mixed‐granulocytic sputum, with an additional two patients having this subtype at 24 h postchallenge.…”

Section: Discussionmentioning

confidence: 99%

“…This was determined using the approach described by Borm et al., and assuming that (1) the standard deviation (SD) of the LAR max%fall was 10% and (2) the correlation between the LAR max%fall measured in the same individuals at two time points was 0.6. These statistics were estimated based on results from allergen challenges performed in previous clinical trials, specifically pretreatment data for the LAR max%fall (mean = 23%) measured in 24 individuals tested with the same allergen twice in a 12‐month period. An absolute between‐group difference of 11.5% corresponds to a relative attenuation in LAR max%fall of 50% (i.e.…”

Section: Methodsmentioning

confidence: 99%

Effects of interleukin‐6 receptor blockade on allergen‐induced airway responses in mild asthmatics

et al. 2019

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Background Interleukin (IL)‐6 signalling has been implicated in allergic asthma by animal, genetic association and clinical studies. In this study, we tested the hypothesis that tocilizumab (TCZ), a human monoclonal antibody that blocks IL‐6 signalling, can prevent the development of allergen‐induced bronchoconstriction in humans. Methods We performed a randomised, double‐blind, placebo‐controlled study, with eligible participants completing two allergen inhalation challenge tests, conducted before and after treatment with a single dose of TCZ or placebo. The primary efficacy endpoint was the magnitude of the late asthmatic response recorded between 3 and 7 after allergen challenge. The secondary efficacy endpoint was the early asthmatic response, measured 20 min to 2 h after allergen challenge. Results A total of 66 patients enrolled between September 2014 and August 2017, when the trial was stopped for futility based on results from an interim analysis. Eleven patients fulfilled all eligibility criteria assessed at baseline and were subsequently randomised to the TCZ ( n = 6) or placebo ( n = 5) groups. Both the primary and secondary efficacy endpoints were not significantly different between the two groups. Five patients reported adverse events (AEs), three in the TCZ group (11 AEs) and two in the placebo group (four AEs). Only one AE was TCZ‐related (mild neutropenia), and there were no serious AEs. Significant treatment effects were observed for serum levels of C‐reactive protein, IL‐6 and soluble IL‐6R levels. Conclusion In a small proof‐of‐concept clinical trial, we found no evidence that a single dose of tocilizumab was able to prevent allergen‐induced bronchoconstriction. (Trial registered in the Australian New Zealand Clinical Trials Registry, number ACTRN12614000123640).

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Sputum cytology during late‐phase responses to inhalation challenge with different allergens

Abstract: Unlike reported in mice, in humans the sputum inflammatory subtype observed after an allergen-induced asthma exacerbation is unlikely to be influenced by the type of allergen used.

Cited by 9 publications

References 42 publications

Proteomic analysis of serum and sputum analytes distinguishes controlled and poorly controlled asthmatics

Proteomic analysis of serum and sputum analytes distinguishes controlled and poorly controlled asthmatics

Response of upper and lower airway inflammation to bronchial challenge with house dust mite in Chinese asthmatics: a pilot study

Effects of interleukin‐6 receptor blockade on allergen‐induced airway responses in mild asthmatics

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