Clinical, functional and inflammatory characteristics in patients with paucigranulocytic stable asthma: Comparison with different sputum phenotypes

Ntontsi, Polyxeni; Loukides, Stelios; Bakakos, Petros; Κostikas, Κonstantinos; Papatheodorou, Georgios; Papathanassiou, Evgenia; Hillas, Georgios; Koulouris, Nikolaos; Papiris, Spyros; Papaioannou, Andriana Ι.

doi:10.1111/all.13184

Cited by 73 publications

(100 citation statements)

References 26 publications

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“…Our second finding relating to heterogeneity of type 2 inflammation in asthma was that a subset of participants with paucigranulocytic airway inflammation had elevated sputum MCs. These participants could represent a “treated” type 2 asthma phenotype where ongoing ICS therapy has suppressed sputum eosinophilia, 41 but not MCs. Contrary to this hypothesis are observations that both ICS and OCS treatment result in suppression of sputum MC‐related gene expression, suggesting that MCs are often lowered by corticosteroid treatment 36,42 .…”

Section: Discussionsupporting

confidence: 88%

Relationship of sputum mast cells with clinical and inflammatory characteristics of asthma

Fricker

Qin

Niessen

et al. 2020

Clin Experimental Allergy

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Background: Mast cells (MCs) are innate immune cells that regulate atopic and nonatopic inflammation in the airways. MCs play a critical role in the pathogenesis of asthma, yet their relationship to airway and systemic inflammation and clinical characteristics of asthma is poorly understood. Objective: To quantify MCs in induced sputum samples and understand their relationship to airway and circulatory immune cells, and clinical variables in asthma. Methods: We employed flow cytometry of sputum samples to quantify MCs, basophils and other immune cells in 51 participants (45 asthma and 6 non-asthma controls). Relationship of MCs to airway (n = 45) and blood (n = 19) immune cells, participant demographics, asthma history, spirometry and airways hyperresponsiveness (AHR) to hypertonic saline was determined by correlation and comparison of cut-off-based sputum MC high vs low participants. Results: Mast cells, basophils and eosinophils were increased in asthma vs non-asthma control sputum. In asthma sputum, MCs, basophils and eosinophils were significantly intercorrelated, and MCs and basophils were elevated in participants with eosinophilic asthma. MCs and basophils, but not eosinophils, correlated with AHR. Sputum MC high asthma was characterized by an increased proportion of participants with uncontrolled asthma and reduced FEV 1 and FVC. Trends towards similar clinical associations with elevated MCs were observed in a paucigranulocytic subpopulation (n = 15) lacking airway eosinophilia or neutrophilia. Receiver operator characteristic (ROC) analysis showed peripheral blood eosinophil (PBE) count predicted elevated sputum eosinophils and basophils, but not MCs. Conclusions and Clinical Relevance: Sputum MCs are elevated in asthma, and their measurement may be useful as they relate to key clinical features of asthma (spirometry, asthma control, AHR). PBE count did not predict airway MC status, suggesting direct measurement of airway MCs by sensitive methods such as flow cytometry should be further developed. | 697 FRICKER Et al.

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Section: Discussionsupporting

confidence: 88%

Relationship of sputum mast cells with clinical and inflammatory characteristics of asthma

Fricker

Qin

Niessen

et al. 2020

Clin Experimental Allergy

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“…However, other type-2 response markers such as total IgE and ECP levels did not differ significantly among the four different groups. Lung function tests revealed that G2 tended toward lower FEV 1 % and PC 20 methacholine levels compared to the other three groups, finding that are in agreement with other studies reporting lower FEV 1 %/PC 20 methacholine levels or poor asthma controls in G2 [7,18,24]. Previous research has shown a significant association between asthma severity and mixed granulocytic asthma [25].…”

Section: Discussionsupporting

confidence: 90%

Serum potential biomarkers according to sputum inflammatory cell profiles in adult asthmatics

Hur

Yang

et al. 2020

Korean J Intern Med

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Background/Aims: Asthma is not a single disease but, rather, a heterogeneous inf lammatory disorder with various pathogenic mechanisms. We analyzed the associations between the cellular profile of sputum and the serum levels of inflammatory mediators/cytokines in a cohort of adult asthmatics. Methods: We recruited 421 adult asthmatic patients. All subjects were classified into four groups according to their sputum cellular profiles: G1, eosinophilic; G2, mixed granulocytic; G3, neutrophilic; and G4, paucigranulocytic. Serum levels of cytokines and mediators including periostin, eosinophil-derived neurotoxin (EDN), S100A9, and folliculin were quantified. Results: Among 421 patients, G1 accounted for 149 (35.4%), G2 for 71 (16.9%), G3 for 155 (36.8%), and G4 for 46 (10.9%). Serum periostin and EDN levels were significantly higher in G1 (p = 0.004, and p = 0.031) than in the others. Serum S100A9 levels were elevated in G2 and G3 (p = 0.008). Serum folliculin levels differed significantly among the four groups, with the highest level in G4 (p = 0.042). To identify G1 from G1 plus G2 groups, the optimal serum cutoff levels were 1.71 ng/mL for periostin, and 1.61 ng/mL for EDN. When these two parameters were combined, the sensitivity was 76.0% and the specificity was 64.3% (area under the curve, 0.701; p = 0.004). Conclusions: The serum periostin and EDN levels may be used as predictors to discriminate the eosinophilic asthma group from patients having eosinophilic or mixed granulocytic asthma, and the serum folliculin level is significantly elevated in patients with paucigranulocytic asthma compared to those with different inflammatory cell profile.

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“…Measuring sputum biomarkers, in particular, cytokines, have emerged as promising tools for defining airway disease phenotypes (Westerhof et al, 2015; Robinson et al, 2017), development of targeted monoclonal antibody therapies (Hambly and Nair, 2014), evaluating and optimising treatment response (Chakir et al, 2010; Nair et al, 2013; Mukherjee and Nair, 2015). For assessing expression levels of ‘target’ antigen in the airways, enzyme-linked immunosorbent assays (ELISA) with a peroxidase-based colour development using either horseradish peroxidase (HRP)-conjugated or biotin-conjugated secondary antibodies remain the method of choice in sputum research (Pizzichini et al, 1996b; Keatings et al, 2002; Jee et al, 2010; Ntontsi et al, 2017). Indeed, adapting biotinylated secondary antibodies into an HRP-based system, otherwise conventionally followed by an alkaline phosphatase (AP) based colour development (Figure 1), has stemmed from the fact that the peroxidase-based protocol is often preferred over AP substrates.…”

Section: Introductionmentioning

confidence: 99%

Endogenous peroxidases in sputum interfere with horse-radish peroxidase-based ELISAs

Kim

Plaza

Thomas

et al. 2018

Journal of Immunological Methods

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Clinical, functional and inflammatory characteristics in patients with paucigranulocytic stable asthma: Comparison with different sputum phenotypes

Cited by 73 publications

References 26 publications

Relationship of sputum mast cells with clinical and inflammatory characteristics of asthma

Relationship of sputum mast cells with clinical and inflammatory characteristics of asthma

Serum potential biomarkers according to sputum inflammatory cell profiles in adult asthmatics

Endogenous peroxidases in sputum interfere with horse-radish peroxidase-based ELISAs

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