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Chronic rhinosinusitis in elderly patients is associated with an exaggerated neutrophilic proinflammatory response to pathogenic bacteria.

ABSTRACT: BACKGROUND:Potential effects of aging on chronic rhinosinusitis (CRS) pathophysiology have not been well defined but might have important ramifications given a rapidly aging US and world population. OBJECTIVE:The goal of the current study was to determine whether advanced age is associated with specific inflammatory CRS endotypes or immune signatures. METHODS:Levels of 17 mucus cytokines and inflammatory mediators were measured in 147 patients with CRS. Hierarchical cluster analysis was used to identify and characterize inflammatory CRS endotypes, as well as to determine whether age was associated with specific immune signatures. RESULTS:A CRS endotype with a proinflammatory neutrophilic immune signature was enriched in older patients. In the overall cohort patients 60 years and older had increased mucus levels of IL-1?, IL-6, IL-8, and TNF-? when compared with their younger counterparts. Increases in levels of proinflammatory cytokines were associated with both tissue neutrophilia and symptomatic bacterial infection/colonization in aged patients. CONCLUSIONS:Aged patients with CRS have a unique inflammatory signature that corresponds to a neutrophilic proinflammatory response. Neutrophil-driven inflammation in aged patients with CRS might be less likely to respond to corticosteroids and might be closely linked to chronic microbial infection or colonization.

SUBMITTER: Morse JC

PROVIDER: S-EPMC6408962 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Chronic rhinosinusitis in elderly patients is associated with an exaggerated neutrophilic proinflammatory response to pathogenic bacteria.

Morse Justin C JC Li Ping P Ely Kim A KA Shilts Meghan H MH Wannemuehler Todd J TJ Huang Li-Ching LC Sheng Quanhu Q Chowdhury Naweed I NI Chandra Rakesh K RK Das Suman R SR Turner Justin H JH

The Journal of allergy and clinical immunology 20181122 3

<h4>Background</h4>Potential effects of aging on chronic rhinosinusitis (CRS) pathophysiology have not been well defined but might have important ramifications given a rapidly aging US and world population.<h4>Objective</h4>The goal of the current study was to determine whether advanced age is associated with specific inflammatory CRS endotypes or immune signatures.<h4>Methods</h4>Levels of 17 mucus cytokines and inflammatory mediators were measured in 147 patients with CRS. Hierarchical cluster ...[more]

PMID: 30468775

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Project description:Chronic rhinosinusitis (CRS) is marked by an inflamed mucosa of sinuses and is accompanied by a significantly reduced quality of live. Since no guidelines for the treatment of CRS are available, long lasting clinical histories with health care costs adding up to dozens of billion $ annually are caused by CRS. The progression of CRS is often induced by bacterial infections and/or a shift in microbiome as well as biofilm formation. The exact microbiome alterations are still unclear and the impenetrable biofilm renders the treatment with common antibiotics ineffective. This study focuses on characterizing the microbiome changes in CRS and investigating the inhibition of biofilm growth by 1,8-Cineol, a small, non-polar and hence biofilm penetrating molecule with known antimicrobial potential. We performed MALDI-TOF MS based characterization of the microbiomes of healthy individuals and CRS patients (n = 50). The microbiome in our test group was shifted to pathogens (Staphylococcus aureus, Escherichia coli, and Moraxella catarrhalis). In contrast to published studies, solely based on cell culture techniques, we could not verify the abundance of Pseudomonas aeruginosa in CRS. The inhibition of bacterial proliferation and biofilm growth by 1,8-Cineol was measured for these three pathogens. Interestingly, S. aureus, the most prominent germ in CRS, showed a biofilm inhibition not simply correlated to its inhibition of proliferation. RT-qPCR confirmed that this was due to the downregulations of major key players in biofilm generation (agrA, SarA and σB) by 1,8-Cineol. Furthermore we verified this high biofilm inhibition potential in a model host system consisting out of S. aureus biofilm grown on mature respiratory epithelium. A second host model, comprising organotypic slices, was utilized to investigate the reaction of the innate immune system present in the nasal mucosa upon biofilm formation and treatment with 1,8-Cineol. Interestingly Staphylococcus epidermidis, the cause of very common catheter infections, possesses a biofilm generation pathway very similar to S. aureus and might be treatable in a similar fashion. The two presented in vitro model systems might be transferred to combinations of every biofilm forming bacterial with most kind of epithelium and mucosa.

Project description:BackgroundMolecular microbiological analysis of airway samples in asthma has demonstrated an altered microbiome in comparison to healthy controls. Such changes may have relevance to treatment-resistant severe asthma, particularly those with neutrophilic airway inflammation, as bacteria might be anticipated to activate the innate immune response, a process that is poorly steroid responsive. An understanding of the relationship between airway bacterial presence and dominance in severe asthma may help direct alternative treatment approaches.ObjectiveWe aimed to use a culture independent analysis strategy to describe the presence, dominance and abundance of bacterial taxa in induced sputum from treatment resistant severe asthmatics and correlate findings with clinical characteristics and airway inflammatory markers.MethodsInduced sputum was obtained from 28 stable treatment-resistant severe asthmatics. The samples were divided for supernatant IL-8 measurement, cytospin preparation for differential cell count and Terminal Restriction Fragment Length Polymorphism (T-RFLP) profiling for bacterial community analysis.ResultsIn 17/28 patients, the dominant species within the airway bacterial community was Moraxella catarrhalis or a member of the Haemophilus or Streptococcus genera. Colonisation with these species was associated with longer asthma disease duration (mean (SD) 31.8 years (16.7) vs 15.6 years (8.0), p = 0.008), worse post-bronchodilator percent predicted FEV1 (68.0% (24.0) vs 85.5% (19.7), p = 0.025) and higher sputum neutrophil differential cell counts (median (IQR) 80% (67-83) vs 43% (29-67), p = 0.001). Total abundance of these organisms significantly and positively correlated with sputum IL-8 concentration and neutrophil count.ConclusionsAirway colonisation with potentially pathogenic micro-organisms in asthma is associated with more severe airways obstruction and neutrophilic airway inflammation. This altered colonisation may have a role in the development of an asthma phenotype that responds less well to current asthma therapies.

Dataset Information

Chronic rhinosinusitis in elderly patients is associated with an exaggerated neutrophilic proinflammatory response to pathogenic bacteria.

Publications

Chronic rhinosinusitis in elderly patients is associated with an exaggerated neutrophilic proinflammatory response to pathogenic bacteria.

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