Functional burden and limitations in children with chronic sinusitis.
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ABSTRACT:
SUBMITTER: Cheng BT
PROVIDER: S-EPMC7444026 | biostudies-literature | 2020 Jan
REPOSITORIES: biostudies-literature
Publications
Functional burden and limitations in children with chronic sinusitis.
Cheng Brian T BT Smith Stephanie S SS Fishbein Anna B AB
Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology 20191009 1
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| PRJEB29467 | ENA
Project description:ObjectiveThe association between autoimmune diseases and chronic rhinosinusitis in observational studies remains unclear. This study aimed to explore the genetic correlation between chronic rhinosinusitis and autoimmune diseases.MethodsWe employed Mendelian randomization (MR) analysis and linkage disequilibrium score regression (LDSC) to investigate causal relationships and genetic correlations between autoimmune phenotypes and chronic rhinosinusitis. Additionally, transcriptome-wide association (TWAS) analysis was conducted to identify the shared genes between the two conditions to demonstrate their relationship. The CRS GWAS (genome-wide association study) data and other autoimmune diseases were retrieved from ieuOpenGWAS (https://gwas.mrcieu.ac.uk/), the FinnGen alliance (https://r8.finngen.fi/), the UK Biobank (https://www.ukbiobank.ac.uk/), and the EBI database (https://www.ebi.ac.uk/).ResultsUtilizing a bivariate two-sample Mendelian randomization approach, our findings suggest a significant association of chronic rhinosinusitis with various autoimmune diseases, including allergic rhinitis (p = 9.55E-10, Odds Ratio [OR] = 2,711.019, 95% confidence interval [CI] = 261.83391-28,069.8), asthma (p = 1.81E-23, OR = 33.99643, 95%CI = 17.52439-65.95137), rheumatoid arthritis (p = 9.55E-10, OR = 1.115526, 95%CI = 1.0799484-1.1522758), hypothyroidism (p = 2.08828E-2, OR = 4.849254, 95%CI = 1.7154455-13.707962), and type 1 diabetes (p = 2.08828E-2, OR = 01.04849, 95%CI = 1.0162932-1.0817062). LDSC analysis revealed a genetic correlation between the positive autoimmune phenotypes mentioned above and chronic rhinosinusitis: AR (rg = 0.344724754, p = 3.94E-8), asthma (rg = 0.43703672, p = 1.86E-10), rheumatoid arthritis (rg = 0.27834931, p = 3.5376E-2), and hypothyroidism (rg = -0.213201473, p = 3.83093E-4). Utilizing the Transcriptome-Wide Association Studies (TWAS) approach, we identified several genes commonly associated with both chronic rhinosinusitis and autoimmune diseases. Genes such as TSLP/WDR36 (Chromosome 5, top SNP: rs1837253), ORMDL3 (Chromosome 13, top SNP: rs11557467), and IL1RL1/IL18R1 (Chromosome 2, top SNP: rs12905) exhibited a higher degree of consistency in their shared involvement across atopic dermatitis (AT), allergic rhinitis (AR), and chronic rhinosinusitis (CRS).ConclusionCurrent evidence suggests a genetic correlation between chronic rhinosinusitis and autoimmune diseases like allergic rhinitis, asthma, rheumatoid arthritis, hypothyroidism, and type 1 diabetes. Further research is required to elucidate the mechanisms underlying these associations.
| S-EPMC11458559 | biostudies-literature
Project description:Objectives/hypothesisAlthough many proinflammatory cytokines have been identified in nasal polyp tissue, the initial trigger that causes this inflammation characterized by edema, lymphocytosis, and eosinophilia, is still unknown. The purpose of the present study is to identify the presence of genetic polymorphisms in proinflammatory, anti-inflammatory, and chemokine genes that might contribute to genetic susceptibility to chronic hyperplastic sinusitis with nasal polyposis (CHSwNP).Study designCase control study.MethodsBuccal swabs were taken from the left and right oral mucosal surfaces from 179 patients with CHSwNP and 153 nonpolyposis controls with the Purgene DNA purification protocol (Gentra). Genotyping assays for cytokine gene loci were performed on 14 cytokine genes using the iPlex Gold and the Mass Array Compact system (Sequenom, San Diego, CA). Tests of Hardy-Weinberg equilibrium proportions were performed separately in the cases and controls. Tests for evidence of association between alleles at each single-nucleotide polymorphism (SNP) and case-control status were performed using unconditional logistic regression.ResultsThe frequency of the A allele in a SNP located in tumor necrosis factor (TNF)-alpha (rs1800629) is significantly different in patients with nasal polyposis versus controls without nasal polyposis, 18.6% and 11.5%, respectively with an individuals' odds of susceptibility to nasal polyps increasing almost two-fold (odds ratio, 1.86; confidence interval, 1.4-3.09) given at least one copy of the A allele at this SNP. All other cytokine gene polymorphisms of both inflammatory, anti-inflammatory, and chemokine genes were not statistically different between the two groups.ConclusionsTNF-alpha-308, a SNP in the promoter region of this cytokine gene is associated with increased odds of developing nasal polyposis. TNF-alpha is a potent immuno-mediator and proinflammatory cytokine that has been implicated in the pathogenesis of a large number of human diseases. The location of this gene on the short arm of chromosome 6, with the major histocompatibility complex genes and complement, has raised the probability that polymorphism within this locus may contribute to a genetic association of this region of the genome with a wide variety of infectious and autoimmune diseases.
| S-EPMC2952427 | biostudies-literature
Project description:BackgroundAcute bacterial sinusitis is a frequent complication of viral upper respiratory infection (URI). We describe the clinical and virologic features of URIs that remain uncomplicated and those that precede an episode of sinusitis. We hypothesize that certain viruses are more likely to lead to acute sinusitis, and we compare viruses identified at the time of diagnosis of sinusitis with those identified early in the URI.MethodsChildren aged 48-96 months were followed longitudinally for 1 year. Nasal samples were obtained at surveillance visits, on Day 3-4 of the URI, and on Day 10, when sinusitis was diagnosed. Molecular diagnostic testing was performed on nasal washes for common respiratory viruses and pathogenic bacteria. A standardized score was used to quantify symptom severity.ResultsWe evaluated 519 URIs, and 37 illnesses in 31 patients met the criteria for sinusitis. Respiratory syncytial virus was detected more frequently in URI visits that led to sinusitis, compared to in uncomplicated URIs (10.8% vs 3.4%; P = .05). New viruses were detected in 29% of sinusitis episodes, and their pattern was different than those patterns observed at surveillance. The median number of URIs per subject per year was 1 (range 0-9) in uncomplicated URI subjects and 3 (range 1-9) in sinusitis subjects (P < .001).ConclusionsChildren who developed sinusitis experienced more frequent URIs, compared to children whose URIs remained uncomplicated. When nasal samples were obtained on the day of diagnosis of acute sinusitis, nearly 30% of children had a new virus identified, suggesting that some children deemed to have sinusitis were experiencing sequential viral infections.
| S-EPMC7108184 | biostudies-literature
Project description:ObjectiveTo perform a comprehensive molecular pathways analysis of genes identified through genome-wide expression profiling and the published literature for chronic sinusitis with polyps.Study designMolecular pathways analysis.SettingAcademic medical center.MethodsA molecular pathways analysis of gene biomarkers discovered through hypothesis-driven and high-throughput molecular studies was performed. Genes identified with a PubMed literature search were analyzed with Ingenuity Pathways Analysis software to identify central molecules implicated in the pathogenesis of chronic sinusitis with polyps. The central pathways were then compared with those identified through genome-wide expression profiling of ethmoid polyps.ResultsA total of 97 molecules were investigated with Ingenuity Pathways Analysis based on 55 studies that evaluated differences in gene expression (39), genetic variation (12), or proteomics (4). The analysis revealed 9 statistically significant molecular networks containing central nodes that included transcription factors, protein kinases, cytokines, and growth factors/receptors. The highest scoring networks implicated nuclear factor kappa-B, tumor necrosis factor, and mitogen-activated protein kinases. The majority of pathways in the literature review analysis overlapped with those identified through a single genome-wide expression study.ConclusionsChronic sinusitis with polyps is a complex disease with suspected contribution of multiple genetic and environmental factors. The search for causative genes has led to the discovery of numerous candidates. Pathways analysis applied to these candidate genes identified common central molecules that are likely to be key mediators of the disease process. Novel therapies targeting these molecules may be applicable for the treatment of chronic sinusitis with polyps.
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Project description:BackgroundThe strategic framework on multiple chronic conditions released by the US Department of Health and Human Services calls for identifying homogeneous subgroups of older adults to effectively target interventions aimed at improving their health.ObjectiveWe aimed to identify combinations of chronic conditions, functional limitations, and geriatric syndromes that predict poor health outcomes. DESIGN, SETTING AND PARTICIPANTS Data from the 2010-2012 Health and Retirement Study provided a representative sample of U.S. adults 50 years of age or older (n = 16,640).Main measuresOutcomes were: Self-reported fair/poor health, self-rated worse health at 2 years, and 2-year mortality. The main independent variables included self-reported chronic conditions, functional limitations, and geriatric syndromes. We conducted tree-based classification and regression analysis to identify the most salient combinations of variables to predict outcomes.Key resultsTwenty-nine percent and 23 % of respondents reported fair/poor health and self-rated worse health at 2 years, respectively, and 5 % died in 2 years. The top combinations of conditions identified through our tree analysis for the three different outcome measures (and percent respondents with the outcome) were: a) for fair/poor health status: difficulty walking several blocks, depressive symptoms, and severe pain (> 80 %); b) for self-rated worse health at 2 years: 68.5 years of age or older, difficulty walking several blocks and being in fair/poor health (60 %); and c) for 2-year mortality: 80.5 years of age or older, and presenting with limitations in both ADLs and IADLs (> 40 %).ConclusionsRather than chronic conditions, functional limitations and/or geriatric syndromes were the most prominent conditions in predicting health outcomes. These findings imply that accounting for chronic conditions alone may be less informative than also accounting for the co-occurrence of functional limitations and geriatric syndromes, as the latter conditions appear to drive health outcomes in older individuals.
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Project description:A Capnocytophaga sp. was inadvertently isolated from a cat with chronic sinusitis and rhinitis when cytopathic effects were observed in Crandall-Reese feline kidney cells that had been inoculated with oropharyngeal swab samples. Although Capnocytophaga spp. are of considerable zoonotic importance, their clinical relevance for dogs or cats has not been established. However, failure to do so may be attributed to the infrequent use of specialized isolation techniques that are required to grow Capnocytophaga spp. To our knowledge, successful isolation of these organisms from a cat with nasopharyngeal disease has not been reported.
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Project description:Allergic rhinitis (AR) is a common allergic inflammatory disease that affects the upper respiratory tract. Although previous research suggests a potential association between gut microbiota alterations and AR, the causal relationship remains unclear. This study employs Mendelian randomization (MR) to reduce confounding factors and reverse causality. By using genetic variants as instrumental variables, the MR approach aims to provide more reliable causal evidence of the relationship between gut microbiota, immune-related antibodies, and AR. This study utilized large-scale genome-wide association study data from the FINRISK 2002 cohort and the UK Biobank to systematically investigate the causal relationships between gut microbiota, antibody immune responses, and AR through a 2-sample MR approach. We applied the inverse variance weighting method to assess the potential mediating role of antibody immune responses in the interaction between gut microbiota and AR. MR analysis identified 17 gut microbiomes significantly associated with chronic rhinosinusitis (CRS) risk. Specifically, increased abundances of the CAG-884 and UBA1407 species were linked to a higher CRS risk, while greater levels of Atopobiaceae and Bacteroides thetaiotaomicron were associated with a reduced risk. In addition, of the 29 immune cell types correlated with CRS, 12 were found to increase risk, while 17 reduced it. Notably, CAG-884 indirectly influenced CRS risk by affecting the proportion of TD double negative (CD4-CD8-) % T cells, with a mediating effect ratio of 36.4%. Our findings confirm a causal relationship between gut microbiota and immune cells in relation to CRS, underscoring the mediating role of immune cells in this interaction.
| S-EPMC11749507 | biostudies-literature
Project description:BackgroundIn medically refractory chronic frontal sinusitis, ethmoidectomy without instrumentation of the frontal ostium may resolve frontal disease. Our aim was to determine the efficacy of ethmoidectomy alone for the treatment of chronic frontal sinusitis.MethodsAdults with chronic rhinosinusitis prospectively enrolled in a multicenter study who demonstrated frontal sinusitis on computed tomography were divided into 2 groups: (1) endoscopic sinus surgery (ESS) incorporating ethmoidectomy, but excluding frontal sinusotomy; and (2) ESS incorporating frontal sinusotomy. The primary outcome was improvement in 22-item Sino-Nasal Outcome Test (SNOT-22) scores. Secondary outcomes included endoscopic scores and use of corticosteroids and antibiotics.ResultsA total of 196 cases undergoing frontal sinusotomy and 30 cases treated with ethmoidectomy without frontal sinusotomy were analyzed and were comparable demographically. The prevalence of nasal polyps, previous ESS, asthma, and aspirin intolerance was more common in the frontal sinusotomy group (p < 0.050). Preoperative endoscopy and computed tomography scores were higher in the frontal sinusotomy group (p ≤ 0.001). Postoperatively, both groups showed comparable SNOT-22 scores with worse endoscopy scores in the frontal sinusotomy group (p = 0.038). Postoperative improvement in SNOT-22 total and subdomain scores was comparable between groups. Nasal endoscopy scores improved to a greater degree in the frontal sinusotomy group (p = 0.023). Duration of postoperative topical steroid use was higher in the frontal sinusotomy group (p = 0.007). Revision surgery was needed in 2.6% of frontal sinusotomy patients and 0% of patients without frontal sinusotomy.ConclusionThe treatment of chronic frontal sinusitis through ethmoidectomy is a potential alternative to frontal sinusotomy achieving similar quality of life (QOL) improvements in patients manifesting less severe sinus disease.
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Project description:The investigators will investigate the efficacy of dupilumab in patients with severe eosinophilic CRSsNP who are resistant to the conventional treatment with intranasal corticosteroids and have significantly extensive disease involving more than 2 sinuses bilaterally in sinus CT scan and Lund-Mackay sinus (LMK) CT score >=10 at baseline.
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