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The complex pathophysiology of allergic rhinitis: scientific rationale for the development of an alternative treatment option.

ABSTRACT: Allergic rhinitis (AR) poses a global health problem and can be challenging to treat. Many of the current symptomatic treatments for AR have been available for decades, yet there has been little improvement in patient quality of life or symptom burden over the years. In this review, we ask why this might be and explore the pathophysiological gaps that exist within the various AR treatment classes. We focus on the benefits and drawbacks of different treatment options and delivery routes for AR treatments and consider how, given what is known about AR pathophysiology and symptomatology, patients may be offered more effective treatment options for rapid, effective, and sustained AR control. In particular, we consider how a new AR preparation, MP-AzeFlu (Dymista®, Meda, Sweden), comprising a formulation of an intranasal antihistamine (azelastine hydrochloride), an intranasal corticosteroid (fluticasone propionate), and excipients delivered in a single spray, may offer benefits over and above single and multiple AR therapy options. We review the evidence in support of this treatment across the spectrum of AR disease. The concept of AR control is also reviewed within the context of new European Union and Contre les Maladies Chroniques pour un VIeillissement Actif-Allergic Rhinitis and its Impact on Asthma initiatives.

SUBMITTER: Bjermer L

PROVIDER: S-EPMC6469109 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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The complex pathophysiology of allergic rhinitis: scientific rationale for the development of an alternative treatment option.

Bjermer Leif L Westman Marit M Holmström Mats M Wickman Magnus C MC

Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology 20190416

Allergic rhinitis (AR) poses a global health problem and can be challenging to treat. Many of the current symptomatic treatments for AR have been available for decades, yet there has been little improvement in patient quality of life or symptom burden over the years. In this review, we ask why this might be and explore the pathophysiological gaps that exist within the various AR treatment classes. We focus on the benefits and drawbacks of different treatment options and delivery routes for AR tr ...[more]

PMID: 31015846

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Project description:BackgroundAllergen-specific immunotherapy (AIT) is a causative treatment in allergic rhinitis (AR), comprising long-term allergen administration and over three years of treatment. This study is carried out for revealing the mechanisms and key genes of AIT in AR.MethodsThe present study utilized online Gene Expression Omnibus (GEO) microarray expression profiling dataset GSE37157 and GSE29521 to analyze the hub genes changes related to AIT in AR. Based on limma package, differential expression analysis for the two groups (samples of allergic patients prior to AIT and samples of allergic patients undergoing AIT) was performed to obtain differentially expressed genes (DEGs). Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of DEGs were conducted using DAVID database. A Protein-Protein Interaction network (PPI) was built and a significant network module was acquired by using Cytoscape software (Cytoscape, 3.7.2). Utilizing the miRWalk database, we identified potential gene biomarkers, constructed interaction networks of target genes and microRNAs (miRNAs) using Cytoscape software, and explore the cell type-specific expression patterns of these genes in peripheral blood using publicly available single-cell RNA sequencing data (GSE200107). Finally, we are using PCR to detect changes in the hub genes that are screened using the above method in peripheral blood before and after AIT treatment.ResultsGSE37157 and GSE29521 included 28 and 13 samples, respectively. A total of 119 significantly co-upregulated DEGs and 33 co-downregulated DEGs were obtained from two datasets. The GO and KEGG analyses demonstrated that protein transport, positive regulation of apoptotic process, Natural killer cell mediated cytotoxicity, T cell receptor signaling pathway, TNF signaling pathway, B cell receptor signaling pathway and Apoptosis may be potential candidate therapeutic targets for AIT of AR. From the PPI network, 20 hub genes were obtained. Among them, the PPI sub-networks of CASP3, FOXO3, PIK3R1, PIK3R3, ATF4, and POLD3 screened out from our study have been identified as reliable predictors of AIT in AR, especially the PIK3R1.ConclusionOur analysis has identified novel gene signatures, thereby contributing to a more comprehensive understanding of the molecular mechanisms underlying AIT in the treatment of AR.

Project description:PurposeNasal cytology is important in the diagnosis and treatment of nasal inflammatory diseases. Treatment of allergic rhinitis (AR) according to nasal cytology has not been fully studied. We plan to explore the individualized treatment of AR according to nasal cytology.MethodsNasal cytology from 468 AR patients was examined for inflammatory cell quantity (grade 0-5) and the percentage of neutrophils and eosinophils. Results were subdivided into the following categories: AR(Eos), eosinophil ≥50% of the whole inflammatory cells; AR(Neu), neutrophils ≥90%; AR(Eos/Neu), 10%≤ eosinophil <50%; AR(Low), grade 0/1 inflammatory cell quantity. Nasal cytology-guided treatment was implemented: all AR(Eos) patients (n=22) and half of the AR(Neu) patients (AR[Neu1], n=22) were treated with mometasone furoate spray and oral loratadine. Another half of the AR(Neu) patients (AR[Neu2], n=22) were treated with oral clarithromycin. Visual analog scale (VAS), symptom scores, and nasal cytology were evaluated 2 weeks before and after treatment.ResultsThere were 224/468 (47.86%) AR(Eos), 67/468 (14.32%) AR(Neu), 112/468 (23.93%) AR(Eos/Neu), and 65/468 (13.89%) AR(Low) of the AR patients studied. There were no significant differences in clinical characteristics among these subgroups, except that the nasal blockage score was higher in AR(Eos) patients than in AR(Neu) patients (1.99 vs 1.50, P=0.02). Comparing AR(Eos) patients with AR(Neu1) patients 2 weeks after treatment, nasal symptoms and VAS were significantly lower in AR(Eos) patients, except for nasal blockage symptoms (P<0.05 of nasal itching and sneezing; P<0.01 for nasal secretion, total scores, and VAS). Comparing AR(Neu1) with AR(Neu2) patients, nasal symptoms, and VAS were significantly lower in AR(Neu2), except for nasal blockage and nasal itching symptoms (P<0.05 for nasal secretions, sneezing, total score, and VAS).ConclusionsNasal cytology may have important value in subtyping AR and optimizing AR treatment. Treating neutrophils is very important in AR patients with locally predominant neutrophils.

Project description:IntroductionAlthough recent studies have shown that the human microbiome is involved in the pathogenesis of allergic diseases, the impact of microbiota on allergic rhinitis (AR) and non-allergic rhinitis (nAR) has not been elucidated. The aim of this study was to investigate the differences in the composition of the nasal flora in patients with AR and nAR and their role in the pathogenesis.MethodFrom February to September 2022, 35 AR patients and 35 nAR patients admitted to Harbin Medical University's Second Affiliated Hospital, as well as 20 healthy subjects who underwent physical examination during the same period, were subjected to 16SrDNA and metagenomic sequencing of nasal flora.ResultsThe microbiota composition of the three groups of study subjects differs significantly. The relative abundance of Vibrio vulnificus and Acinetobacter baumanni in the nasal cavity of AR patients was significantly higher when compared to nAR patients, while the relative abundance of Lactobacillus murinus, Lactobacillus iners, Proteobacteria, Pseudomonadales, and Escherichia coli was lower. In addition, Lactobacillus murinus and Lacttobacillus kunkeei were also negatively correlated with IgE, while Lacttobacillus kunkeei was positively correlated with age. The relative distribution of Faecalibacterium was higher in moderate than in severe AR patients. According to KEGG functional enrichment annotation, ICMT(protein-S-isoprenylcysteine O-methyltransferase,ICMT) is an AR microbiota-specific enzyme that plays a role, while glycan biosynthesis and metabolism are more active in AR microbiota. For AR, the model containing Parabacteroides goldstemii, Sutterella-SP-6FBBBBH3, Pseudoalteromonas luteoviolacea, Lachnospiraceae bacterium-615, and Bacteroides coprocola had the highest the area under the curve (AUC), which was 0.9733(95%CI:0.926-1.000) in the constructed random forest prediction model. The largest AUC for nAR is 0.984(95%CI:0.949-1.000) for the model containing Pseudomonas-SP-LTJR-52, Lachnospiraceae bacterium-615, Prevotella corporis, Anaerococcus vaginalis, and Roseburia inulinivorans.ConclusionIn conclusion, patients with AR and nAR had significantly different microbiota profiles compared to healthy controls. The results suggest that the nasal microbiota may play a key role in the pathogenesis and symptoms of AR and nAR, providing us with new ideas for the treatment of AR and nAR.

Dataset Information

The complex pathophysiology of allergic rhinitis: scientific rationale for the development of an alternative treatment option.

Publications

The complex pathophysiology of allergic rhinitis: scientific rationale for the development of an alternative treatment option.

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