Potentially Pathogenic Airway Bacteria and Neutrophilic Inflammation in Treatment Resistant Severe Asthma

Green, Ben; Wiriyachaiporn, Surasa; Grainge, Christopher; Rogers, Geraint B.; Kehagia, Valia; Lau, Laurie; Carroll, Mary; Bruce, Kenneth D.; Howarth, Peter H.

doi:10.1371/journal.pone.0100645

Cited by 258 publications

(281 citation statements)

References 33 publications

Supporting

Mentioning

268

Contrasting

Order By: Relevance

“…One possibility is the colonisation by Gram-negative bacteria of the lower airways, as LPS is found in the outer membrane of Gram-negative bacteria. Recently, the relationship between bacterial colonisation in the airways and the development or severity of asthma has been highlighted [11,12,[34][35][36]. For example, BISGAARD et al [34] reported that bacterial colonisation in the airway increased the risk for the development of asthma.…”

Section: Discussionmentioning

confidence: 99%

“…HUANG et al [35] reported that airway microbiota composition and diversity were significantly correlated with AHR in asthma. Among these reports, several have emphasised the significance of Gram-negative bacteria [11,12]. For example, GOLEVA et al [11] reported the airway expansion of specific Gram-negative bacteria such as Haemophilus parainfluenzae in severe asthma.…”

Section: Discussionmentioning

confidence: 99%

“…For example, GOLEVA et al [11] reported the airway expansion of specific Gram-negative bacteria such as Haemophilus parainfluenzae in severe asthma. Moreover, GREEN et al [12] reported that bacterial colonisation was associated with low forced expiratory volume in 1 s (FEV1), sputum neutrophil counts and disease duration, and that Moraxella catarrhalis was the bacterial species most associated with sputum neutrophilia and IL-8. Therefore, colonisation by Gram-negative bacteria may play a role in the pathogenesis of severe asthma through the upregulation of LPS and neutrophils in the airway.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, GOLEVA et al [10] reported that LPS and genes associated with activation of LPS signalling are higher in BAL fluid of corticosteroid-resistant asthma than in corticosteroid-sensitive asthma, and IL-8 mRNA expression by BAL cells positively correlates with the amount of LPS in BAL fluid. Although the reason why LPS is upregulated in the airway of severe asthma is unknown, several studies suggested the role of Gram-negative bacteria or of house dust in the upregulation of LPS in severe asthma [11][12][13][14]. For example, a relationship between Gram-negative bacterial colonisation in the airways and the severity of asthma has been reported [11,12].…”

Section: Introductionmentioning

confidence: 99%

“…Although the reason why LPS is upregulated in the airway of severe asthma is unknown, several studies suggested the role of Gram-negative bacteria or of house dust in the upregulation of LPS in severe asthma [11][12][13][14]. For example, a relationship between Gram-negative bacterial colonisation in the airways and the severity of asthma has been reported [11,12]. Furthermore, the frequency and severity of asthma correlated with LPS concentrations, not with house dust mite (HDM) concentrations, in house dust [13,14].…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Trans-Basement Membrane Migration of Eosinophils Induced By LPS-Stimulated Neutrophils from Human Peripheral Blood in Vitro

Nakagome

Nishihara

Kobayashi

et al. 2016

Journal of Allergy and Clinical Immunology

View full text Add to dashboard Cite

In the airways of severe asthmatics, an increase of neutrophils and eosinophils is often observed despite high-dose corticosteroid therapy. We previously reported that interleukin-8-stimulated neutrophils induced trans-basement membrane migration (TBM) of eosinophils, suggesting the link between neutrophils and eosinophils. Concentrations of lipopolysaccharide (LPS) in the airway increase in severe asthma. As neutrophils express Toll-like receptor (TLR)4 and can release chemoattractants for eosinophils, we investigated whether LPS-stimulated neutrophils modify eosinophil TBM.Neutrophils and eosinophils were isolated from peripheral blood of healthy volunteers and severe asthmatics. Eosinophil TBM was examined using a modified Boyden's chamber technique. Eosinophils were added to the upper compartment, and neutrophils and LPS were added to the lower compartment. Migrated eosinophils were measured by eosinophil peroxidase assays.LPS-stimulated neutrophils induced eosinophil TBM (about 10-fold increase), although LPS or neutrophils alone did not. A leukotriene B 4 receptor antagonist, a platelet-activating factor receptor antagonist or an anti-TLR4 antibody decreased eosinophil TBM enhanced by LPS-stimulated neutrophils by almost half. Neutrophils from severe asthmatics induced eosinophil TBM and lower concentrations of LPS augmented neutrophil-induced eosinophil TBM.These results suggest that the combination of neutrophils and LPS leads eosinophils to accumulate in the airways, possibly involved the pathogenesis of severe asthma. @ERSpublications LPS-stimulated neutrophils induced eosinophil TBM, which may be involved in the pathogenesis of severe asthma

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Trans-Basement Membrane Migration of Eosinophils Induced By LPS-Stimulated Neutrophils from Human Peripheral Blood in Vitro

Nakagome

Nishihara

Kobayashi

et al. 2016

Journal of Allergy and Clinical Immunology

View full text Add to dashboard Cite

show abstract

Relative abundance of nasal microbiota in chronic rhinosinusitis by structured histopathology

Kuhar

Tajudeen

Mahdavinia

et al. 2018

Int Forum Allergy Rhinol

View full text Add to dashboard Cite

Background: Chronic rhinosinusitis (CRS) is an inflammatory disease process with several different phenotypes. Recent data has shown that CRS phenotypes maintain distinct nasal microbiota that may predict surgical outcomes. Nasal microbiota and structured histopathologic reporting have the potential to further differentiate subtypes and provide additional insight into the pathophysiology of CRS. Methods:Sinus swabs collected during functional endoscopic sinus surgery (FESS) were studied by polymerase chain reaction analysis of 16S ribosomal RNA. A structured histopathology report of 13 variables was utilized to analyze sinus tissue removed during FESS. Histopathology variables and relative abundance of nasal microbiota were compared among CRS patients. Results: A total of 51 CRS patients who underwent FESS were included. Relative abundance of the Firmicutes phylum in nasal microbiota of CRS patients was associated with presence of neutrophilic infiltrate (27.47 ± 44.75 vs 9.21 ± 11.84, p < 0.029), presence of mucosal ulceration (47.67 ± 45.52 vs 13.27 ± 26.48, p < 0.041), presence of squamous metaplasia (5562.70 ± 2715.66 vs 3563.73 ± 2580.84, p < 0.035), and absence of Charcot-Leyden crystals (5423.00 ± 3320.57 vs 679.94 ± 1653.66, p < 0.001).Relative abundance of the Bacteroidetes phylum in nasal microbiota of CRS patients was associated with increased severity of inflammatory degree (p < 0.004) and presence of mucosal ulceration (p < 0.004). Conclusion: Distinct histopathologic features of CRS are associated with relative abundance of nasal microbiota phyla, specifically Firmicutes and Bacteroidetes. These findings contribute to the growing body of literature on microbiota in sinonasal disease and may have important implications for understanding pathophysiologic mechanisms of CRS subtypes and disease management. C 2018 ARS-AAOA, LLC. How to Cite this Article: Kuhar HN, Tajudeen BA, Mahdavinia M, et al. Relative abundance of nasal microbiota in chronic rhinosinusitis by structured histopathology. Int Forum Allergy Rhinol. 2018;8:1430-1437.

show abstract

Six gene and TH2 signature expression in endobronchial biopsies of participants with asthma

Sánchez-Ovando

Baines

Barker

et al. 2020

Immunity Inflam & Disease

View full text Add to dashboard Cite

Background Both the six gene signature (6GS: CPA3, DNASE1L3, CLC, IL1B, ALPL, and CXCR2) and T‐helper 2 signature (TH2S: CLCA1, SERPINB2, and POSTN) are proposed as biomarkers in the identification of inflammatory phenotypes of asthma in induced sputum and epithelial brushings, respectively. The aim of this study was to explore patterns of gene expression of known signatures, 6GS and TH2S in endobronchial biopsies. Methods This was an exploratory cross‐sectional study of gene expression in endobronchial biopsies of 55 adults with asthma and 9 healthy controls (HC). The expression of the 6GS and TH2S was determined by quantitative polymerase chain reaction. Correlations with clinical and cellular characteristics were performed, and receiver operating characteristic was utilized to assess signatures' ability to predict asthma from HC and inflammatory phenotypes. Results Gene expression of DNASE1L3 (P = .045) was upregulated in asthma compared with HC, and IL1B (P = .017) was upregulated in neutrophilic asthma compared with non‐neutrophilic asthma. In asthma, the expression of CPA3 was negatively associated with ICS daily dose (r = −.339; P = .011), IL1B expression was positively associated with bronchial lavage fluid (BLF) total cell count (r = .340; P = .013) and both CLC and POSTN expression were associated with lymphocytes percentage in BLF (r = −.355, P = .009; r = −.300, P = .025, respectively). Both 6GS (area under curve [AUC] = 86.3%; P = .017) and TH2S (AUC = 72.7%; P = .037) could significantly predict asthma from HC. In addition, 6GS can identify neutrophilic (AUC = 93.2%; P = .005) and TH2S identifies eosinophilic (AUC = 62.7%; P = .033) asthma. Conclusions and Clinical Relevance There was increased expression of DNASE1L3 in asthma and IL1B in neutrophilic asthma. These results show similar upregulated patterns of expression in two genes of the 6GS in endobronchial biopsies, previously identified in sputum. The upregulation of DNASE1L3 and IL1B suggests that common mechanisms may be at play throughout the airway.

show abstract

Potentially Pathogenic Airway Bacteria and Neutrophilic Inflammation in Treatment Resistant Severe Asthma

Cited by 258 publications

References 33 publications

Trans-Basement Membrane Migration of Eosinophils Induced By LPS-Stimulated Neutrophils from Human Peripheral Blood in Vitro

Trans-Basement Membrane Migration of Eosinophils Induced By LPS-Stimulated Neutrophils from Human Peripheral Blood in Vitro

Relative abundance of nasal microbiota in chronic rhinosinusitis by structured histopathology

Six gene and TH2 signature expression in endobronchial biopsies of participants with asthma

Contact Info

Product

Resources

About