Dataset Information

IgA⁺ memory B-cells are significantly increased in patients with asthma and small airway dysfunction.

ABSTRACT:

Background

Comprehensive studies investigated the role of T-cells in asthma which led to personalised treatment options targeting severe eosinophilic asthma. However, little is known about the contribution of B-cells to this chronic inflammatory disease. In this study we investigated the contribution of various B-cell populations to specific clinical features in asthma.

Methods

In the All Age Asthma Cohort (ALLIANCE), a subgroup of 154 adult asthma patients and 28 healthy controls were included for B-cell characterisation by flow cytometry. Questionnaires, lung function measurements, blood differential counts and allergy testing of participants were analysed together with comprehensive data on B-cells using association studies and multivariate linear models.

Results

Patients with severe asthma showed decreased immature B-cell populations while memory B-cells were significantly increased compared with both mild-moderate asthma patients and healthy controls. Furthermore, increased frequencies of IgA⁺ memory B-cells were associated with impaired lung function and specifically with parameters indicative for augmented resistance in the peripheral airways. Accordingly, asthma patients with small airway dysfunction (SAD) defined by impulse oscillometry showed increased frequencies of IgA⁺ memory B-cells, particularly in patients with mild-moderate asthma. Additionally, IgA⁺ memory B-cells significantly correlated with clinical features of SAD such as exacerbations.

Conclusions

With this study we demonstrate for the first time a significant association of increased IgA⁺ memory B-cells with asthma and SAD, pointing towards future options for B-cell-directed strategies in preventing and treating asthma.

SUBMITTER: Habener A

PROVIDER: S-EPMC9630610 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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Publications

IgA<sup>+</sup> memory B-cells are significantly increased in patients with asthma and small airway dysfunction.

Habener Anika A Grychtol Ruth R Gaedcke Svenja S DeLuca David D Dittrich Anna-Maria AM Happle Christine C Abdo Mustafa M Watz Henrik H Pedersen Frauke F König Inke Regina IR Thiele Dominik D Kopp Matthias Volkmar MV von Mutius Erika E Bahmer Thomas T Rabe Klaus Friedrich KF Meyer-Bahlburg Almut A Hansen Gesine G Fuchs Oliver O Roesler Barbara B Welchering Nils N Kohistani-Greif Naschla N Kurz Johanna J Landgraf-Rauf Katja K Laubhahn Kristina K Maison Nicole N Liebl Claudia C Schaub Bianca B Ege Markus M Illi Sabina S Hose Alexander A Zeitlmann Esther E Berbig Mira M Marzi Carola C Schauberger Christina C Zissler Ulrich U Schmidt-Weber Carsten C Ricklefs Isabell I Diekmann Gesa G Liboschik Lena L Voigt Gesche G Sultansei Laila L Weckmann Markus M Nissen Gyde G Kirsten Anne-Marie AM Waschki Benjamin B Herzmann Christian C Biller Heike H Gaede Karoline I KI Bovermann Xenia X Steinmetz Alena A Husstedt Berrit Liselotte BL Nitsche Catharina C Veith Vera V Szewczyk Marlen M Brinkmann Folke F Malik Aydin A Schwerk Nicolaus N Dopfer Christian C Price Mareike M Jirmo Adan Chari AC Liu Bin B Calveron Mifflin-Rae MR Weber Stefanie S Foth Svenja S Skevaki Chrysanthi C Renz Harald H Meyer Meike M Schildberg Tom T Rietschel Ernst E van Koningsbruggen-Rietschel Silke S Alcazar Miguel M

The European respiratory journal 20221103 5

<h4>Background</h4>Comprehensive studies investigated the role of T-cells in asthma which led to personalised treatment options targeting severe eosinophilic asthma. However, little is known about the contribution of B-cells to this chronic inflammatory disease. In this study we investigated the contribution of various B-cell populations to specific clinical features in asthma.<h4>Methods</h4>In the All Age Asthma Cohort (ALLIANCE), a subgroup of 154 adult asthma patients and 28 healthy controls ...[more]

PMID: 35595320

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Project description:RationaleSmall airway dysfunction (SAD) is a frequent feature of asthma that has been linked to disease severity and poor symptom control. However, little is known about the role of SAD in nocturnal asthma.ObjectiveTo study the association between the severity of SAD and frequency of nocturnal symptoms compared to conventional lung function testing.MethodsWe assessed the frequency of self-reported nocturnal symptoms through the asthma control test. We studied the impact of nocturnal asthma using the Asthma Quality of Life Questionnaire (AQLQ) and the Multidimensional Fatigue Inventory (MFI-20). We assessed the lung function using spirometry, body plethysmography, impulse oscillometry, single and multiple inert gas washout and measured markers of T2-inflammation (blood and sputum eosinophils; fractional exhaled nitric oxide (FeNo)). We stratified the patients according to the presence and frequency of nocturnal asthma.ResultsA total of 166 asthma patients were enrolled in the analysis. Eighty-seven patients (52%) reported to have nocturnal symptoms at least once in the last four weeks. The odds ratio of nocturnal asthma correlated with the severity of all non-spirometric measures of SAD, yet neither with airflow obstruction (FEV1 and FEV/FVC) nor with large airway resistance (R20). Patients with frequent nocturnal asthma (n = 29) had a numerical increase of T2 markers and more severe SAD, as indicated by all non-spirometric measures of SAD (all p-values < 0.05), worse overall asthma control, increased fatigue and reduced quality of life (all p-values < 0.01) compared to patients with infrequent nocturnal asthma (n = 58) or patients without nocturnal asthma (n = 79). We identified 63 patients without airflow obstruction, nearly 43% of them (n = 27) had nocturnal asthma. In this subgroup, only markers of air trapping and ventilation heterogeneity were significantly elevated and correlated with the frequency of nocturnal symptoms: LCI (Spearman's coefficient = -0.42, p < 0.001), RV% (-0.32, p = 0.02).ConclusionSAD is closely associated to asthma with nocturnal symptoms. Spirometry might underestimate the broad spectrum of distal lung function impairments in this population of patients.

Project description:BackgroundSmall airway dysfunction not only affects asthma control, but also has adverse effects on the psychological and/or social activities of asthma patients. However, few long-term observational studies have explored the complex relationship between small airway dysfunction and asthma control and health-related quality of life in patients with asthma exacerbations.MethodsThe study recruited 223 patients with exacerbations of asthma (i.e. those with at least one asthma attack over the past year) and 228 patients without exacerbations of asthma (i.e. those without asthma attacks over the past year). We evaluated SAD in patients with asthma exacerbations using impulse oscillometry method. At each evaluation time point within one year of follow-up, the attending physician conducts a case investigation of the patients. We analyzed the correlation between SAD and general characteristics (age, obesity, smoking history), type 2 inflammation (blood eosinophils, exhaled nitric oxide), FEV1, as well as asthma control (ACT) and health-related quality of life (mini-AQLQ) in patients with asthma exacerbations, and constructed a structural equation model to evaluate the causality of these clinical variables.ResultsThe SAD prevalence in patients with asthma exacerbation is as high as 75%. SAD is connected with poor asthma control and poor health-related quality of life. The structural equation model indicates that age, obesity, FeNO, and FEV1 are independent predictive factors of SAD. SAD is the main determinant factor of asthma control, which in turn affected health-related quality of life. FEV1 and age directly affect asthma control and affect health-related quality of life through asthma control. In addition, there is a bidirectional relationship between FEV1 and small airway dysfunction and between asthma control and health-related quality of life.ConclusionsSmall airways are involved from an early stage in asthma. Abnormal function of the small airways can significantly increase airway resistance in asthma patients, while worsening their clinical symptoms. In addition, aging is also a key risk factor for asthma control. Especially, small airway dysfunction links asthma control with health-related quality of life.

Project description:Background: Type 2 (T2)-low asthma can be severe and corticosteroid-resistant. Airway epithelial cells play a pivotal role in the development of asthma, and mitochondria dysfunction is involved in the pathogenesis of asthma. However, the role of epithelial mitochondria dysfunction in T2-low asthma remains unknown. Methods: Differentially expressed genes (DEGs) were identified using gene expression omnibus (GEO) dataset GSE4302, which is originated from airway epithelial brushings from T2-high (n = 22) and T2-low asthma patients (n = 20). Gene set enrichment analysis (GSEA) was implemented to analyze the potential biological pathway involved between T2-low and T2-high asthma. T2-low asthma related genes were identified using weighted gene co-expression network analysis (WGCNA). The mitochondria-related genes (Mito-RGs) were referred to the Molecular Signatures Database (MSigDB). T2-low asthma related mitochondria (T2-low-Mito) DEGs were obtained by intersecting the DEGs, T2-low asthma related genes, and Mito-RGs. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) was performed to further explore the potential function of the T2-low-Mito DEGs. In addition, the hub genes were further identified by protein-protein interaction (PPI), and the expressions of hub genes were verified in another GEO dataset GSE67472 and bronchial brushings from patients recruited at Tongji Hospital. Results: Six hundred and ninety-two DEGs, including 107 downregulated genes and 585 upregulated genes were identified in airway epithelial brushings from T2-high and T2-low asthma patients included in GSE4302 dataset. GSEA showed that mitochondrial ATP synthesis coupled electron transport is involved in T2-low asthma. Nine hundred and four T2-low asthma related genes were identified using WGCNA. Twenty-two T2-low-Mito DEGs were obtained by intersecting the DEGs, T2-low asthma and Mito-RGs. The GO enrichment analysis of the T2-low-Mito DEGs showed significant enrichment of mitochondrial respiratory chain complex assembly, and respiratory electron transport chain. PPI network was constructed using 22 T2-low-Mito DEGs, and five hub genes, ATP5G1, UQCR10, NDUFA3, TIMM10, and NDUFAB1, were identified. Moreover, the expression of these hub genes was validated in another GEO dataset, and our cohort of asthma patients. Conclusion: This study suggests that mitochondria dysfunction contributes to T2-low asthma.

Project description:BackgroundThe purpose of this study was to investigate physiological phenotypes of asthma in obesity.Research questionDo physiological responses during bronchoconstriction distinguish different groups of asthma in people with obesity, and also differentiate from responses simply related to obesity?Study design and methodsCross-sectional study of people with obesity (31 with asthma and 22 without lung disease). Participants underwent methacholine challenge testing with measurement of spirometry and respiratory system impedance by oscillometry.ResultsParticipants had class III obesity (BMI, 46.7 ± 6.6 kg/m2 in control subjects and 47.2 ± 8.2 kg/m2 in people with asthma). Most participants had significant changes in peripheral airway impedance in response to methacholine: in control subjects, resistance at 5 Hz measured by oscillometry increased by 45% ± 27% and area under the reactance curve (AX) by 268% ± 236% in response to 16 mg/mL methacholine; in people with asthma, resistance at 5 Hz measured by oscillometry increased by 52% ± 38% and AX by 361% ± 295% in response to provocation concentration producing a 20% fall in FEV1 dose of methacholine. These responses suggest that obesity predisposes to peripheral airway reactivity. Two distinct groups of asthma emerged based on respiratory system impedance: one with lower reactance (baseline AX, 11.8; interquartile range, 9.9-23.4 cm H2O/L) and more concordant bronchoconstriction in central and peripheral airways; the other with high reactance (baseline AX, 46.7; interquartile range, 23.2-53.7 cm H2O/L) and discordant bronchoconstriction responses in central and peripheral airways. The high reactance asthma group included only women, and reported significantly more gastroesophageal reflux disease, worse chest tightness, more wheeze, and more asthma exacerbations than the low reactance group.InterpretationPeripheral airway reactivity detected by oscillometry is common in obese control subjects and obese people with asthma. There is a subgroup of obese asthma characterized by significant peripheral airway dysfunction by oscillometry out of proportion to spirometric airway dysfunction. This peripheral dysfunction represents clinically significant respiratory disease not readily assessed by spirometry.

Dataset Information

IgA⁺ memory B-cells are significantly increased in patients with asthma and small airway dysfunction.

Background

Methods

Results

Conclusions

Publications

IgA<sup>+</sup> memory B-cells are significantly increased in patients with asthma and small airway dysfunction.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

IgA+ memory B-cells are significantly increased in patients with asthma and small airway dysfunction.

Background

Methods

Results

Conclusions

Publications

IgA<sup>+</sup> memory B-cells are significantly increased in patients with asthma and small airway dysfunction.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

IgA⁺ memory B-cells are significantly increased in patients with asthma and small airway dysfunction.