American Journal of Rhinology & Allergy最新文献

Background: Frontal sinus surgery remained a challenge of restenosis or obliteration of the drainage pathway caused by the scarring and neo-osteogenesis after mucosal stripping and bone drill-out. The pedicled or free nasal mucosal flap is typically used to repair the exposed bone surface to avoid or reduce recurrence.

Objective: This study aimed to explore the histopathological mechanism of mucosal flaps repairing bare bone after mucosal resection and bone drill-out in the rabbit model.

Methods: Thirty New Zealand white rabbits were used. Sixteen rabbits were selected as the experimental group, and Staphylococcus aureus was used to establish the CRS model (CRS group). Fourteen healthy rabbits were allocated to the control group (NCRS group). Each group was divided into two subgroups with or without mucosal flap repair (CRS-FLAP, CRS-NFLAP, NCRS-FLAP, and NCRS-NFLAP, respectively). The bony anterior and lateral walls of the maxillary sinus of each rabbit were abraded by the drill. The bare bone was then covered with a flap in FLAP subgroups. Bone remodeling and mucosal morphological changes were observed and compared by histopathological hematoxylin and eosin and Masson staining.

Results: In the CRS-NFLAP subgroup, the regenerated epithelium lacked typical structure, accompanied by numerous inflammatory cell infiltration and collagen deposition. Conversely, the inflammatory reaction was mild in the CRS-FLAP subgroup, and there was less collagen deposition. The restored mucosal structure was like the normal mucosa. The epithelium in the NCRS-NFLAP subgroup was partially exfoliated, with few cilia, goblet cells, and glandular structures. Compared with the NCRS-NFLAP subgroup, the CRS-NFLAP subgroup showed significant bone remodeling with enhanced activity of osteoblast and osteoclast cells.

Conclusions: Pedicled mucosal flap repair could significantly reduce local mucosal and bone remodeling in a rabbit model of CRS.

Background: Immune-related diseases can interact with each other, and growing evidence suggests that these diseases are associated with allergic rhinitis (AR). However, it is unclear whether previously observed associations reflect causal relationships.

Objective: This study estimated the genetic association between various immune-related diseases and AR using two-sample Mendelian randomization (MR).

Methods: Eight immune-related diseases were selected as exposure factors, and AR was selected as the outcome. The 8 immune-related disease categories included atopic dermatitis (AD), Graves' disease (GD), asthma, Crohn's disease (CD), multiple sclerosis (MS), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and ulcerative colitis (UC). Data from GWAS (Genome-Wide Association Studies) were selected to construct instrumental variables (IVs) for each disease, and multiple single-nucleotide polymorphisms (SNPs) were selected as IVs. Corresponding data were retrieved according to the selected SNPs, and all data were summarized and analyzed.

Results: A total of 416 SNPs were screened as IVs, and the results of IVW support a causal relationship between AR risk and AD (OR: 1.026, 95% CI: 1.014-1.038, P = 9.59 × 10^-6), asthma (OR: 1.057, 95% CI: 1.029-1.086, P = .0001), and CD (OR: 1.006, 95% CI: 1.002-1.011, P = .0085). Furthermore, GD (OR: 0.995, 95% CI: 0.991-0.999, P = .0213) and SLE (OR: 0.997, 95% CI: 0.995-1.000, P = .025) may be protective factors.

Conclusion: This MR study found that AD, asthma and CD increase the risk of AR in populations of European ancestry, GD and SLE may be protective factors. These results suggest that confounding factors may have influenced associations previously reported in observational studies.

Background: Chronic rhinosinusitis (CRS) is a heterogeneous condition characterized by differing inflammatory endotypes. The identification of suitable biomarkers could enable personalized approaches to treatment selection.

Objective: This study aimed to identify and summarize clinical studies of biomarkers in adults with CRS in order to inform future research into CRS endotypes.

Methods: We conducted systematic searches of MEDLINE and Web of Science from inception to January 30, 2022 and included all clinical studies of adult CRS patients and healthy controls measuring biomarkers using enzyme-linked immunosorbent assays or Luminex immunoassays. Outcomes included the name and tissue type of identified biomarkers and expression patterns within CRS phenotypes. Study quality was assessed using the National Institutes of Health quality assessment tool for observational cohort and cross-sectional studies. A narrative synthesis was performed.

Results: We identified 78 relevant studies involving up to 9394 patients, predominantly with CRS with nasal polyposis. Studies identified 80 biomarkers from nasal tissue, 25 from nasal secretions, 14 from nasal lavage fluid, 24 from serum, and one from urine. The majority of biomarkers found to distinguish CRS phenotypes were identified in nasal tissue, especially in nasal polyps. Serum biomarkers were more commonly found to differentiate CRS from controls. The most frequently measured biomarker was IL-5, followed by IL-13 and IL-4. Serum IgE, IL-17, pentraxin-3 and nasal phospho-janus kinase 2, IL-5, IL-6, IL-17A, granulocyte-colony stimulating factor, and interferon gamma were identified as correlated with disease severity.

Conclusion: We have identified numerous potential biomarkers to differentiate a range of CRS phenotypes. Future studies should focus on the prognostic role of nasal tissue biomarkers or expand on the more limited studies of nasal secretions and nasal lavage fluid.We registered this study in PROSPERO (CRD42022302787).

Background: Airway remodeling is demonstrated in Asian patients with allergic rhinitis (AR). The epithelial-mesenchymal transition (EMT) is one of the key mechanisms underlying airway remodeling. Thymic stromal lymphopoietin (TSLP) is an important contributor to airway remodeling. Although increased TSLP is found in AR, little is known about whether TSLP is involved in airway remodeling through induction of the EMT.

Objective: We investigated the effect of TSLP on the EMT in human nasal epithelial cells (HNECs) from AR patients.

Methods: Human nasal epithelial cells from AR patients were stimulated with TSLP in the absence or presence of the preincubation with a selective inhibitor of transforming growth factor beta 1 (TGF-β1) receptor (SB431542). The expression of TGF-β1 in the cells was evaluated by using real-time polymerase chain reaction, Western blotting, and immunocytochemistry. Western blotting and immunocytochemistry were used to assay EMT markers including vimentin, fibroblast-specific protein 1 (FSP1) and E-cadherin, small mothers against decapentaplegic homolog2/3 (Smad2/3), and phosphorylated Smad2/3 in the cells. The levels of extracellular matrix components such as collagens I and III in supernatants were measured by enzyme-linked immunoassay. Morphological changes of the cells were observed under inverted phase-contrast microscope.

Results: A concentration-dependent increase of TGF-β1 mRNA and protein was observed following stimulation with TSLP. Furthermore, TSLP decreased the expression of E-cadherin protein, but upregulated the production of FSP1 and vimentin proteins along with increased levels of collagens I and III, and the morphology of the cells was transformed into fibroblast-like shape. Additionally, a significant increase was found in phosphorylation of Smad2/3 protein. However, these effects were reversed by SB431542 preincubation.

Conclusion: TSLP-induced HNECs to undergo the EMT process via TGF-β1-mediated Smad2/3 activation. TSLP is an activator of the EMT in HNECs and might be a potential target for inhibiting EMT and reducing airway remodeling in AR.

Background: Evidence has shown that glucocorticoid-induced transcript 1 (GLCCI1) single nucleotide polymorphism (SNP) rs37937 is associated with asthma.

Objectives: The objective of this study was to investigate whether the GLCCI1 SNP rs37937 is a risk factor for allergic rhinitis (AR) in a Chinese Han population.

Methods: A total of 220 individuals including 109 AR patients and 111 healthy subjects were included. The genotyping of GLCCI1 rs37973 was performed by the SNaPshot method. The correlations of rs37973 polymorphism, AR risk, and clinical characteristics were further analyzed, as well as the treatment response to intranasal corticosteroids (INCS) in AR patients of different genotypes.

Results: Three GLCCI1 rs37973 SNP genotypes were identified in both AR patients and healthy subjects. Significant association between rs37973 polymorphism and AR under allele model, dominant model, heterozygote model, and homozygote model were shown. The A allele frequency of SNP rs37973 in AR was significantly higher than that in controls. The serum total immunoglobulin E (IgE) in AR patients of AA genotype was significantly higher than in patients of GA and GG genotype, and the serum total IgE in GA genotype was significantly higher than in GG genotype. Interestingly, after 4 weeks of INCS treatment for AR patients, the improvement of the nasal itching score, sneezing score, runny nose score, total nasal symptom score, and visual analog scale score of the GG genotype were worse than the AA or GA genotype.

Conclusion: The GLCCI1 rs37937 polymorphism is associated with the risk of developing AR and the response to INCS treatment in the Chinese Han population.

Background: Neurokinin-1 receptor (NK-1R) and normal T cell expressed and secreted (RANTES) have been shown to play important roles in allergic rhinitis (AR). However, whether the regulating effect of NK-1R in AR is achieved via RANTES remains unknown.

Methods: In the present study, Sprague-Dawley rats were sensitized and challenged with ovalbumin to make AR models. During the challenge period, the rats were treated intranasally with NK-1R-specific small interfering RNA (siRNA) for NKR group, negative siRNA for NCS group, rats in NSAR group and NS group were given saline. The amount of nasal secretion and the numbers of nose rubs and sneezes were measured in each rat. The levels of NK-1R and RANTES in the nasal mucosal tissues were determined through real-time fluorescence quantitative RT-PCR and immunohistochemical staining. The numbers of eosinophils in the collected nasal lavage fluid (NLF) were counted, and the concentration of RANTES in NLF was determined by enzyme-linked immunosorbent assay.

Results: Compared with that in the NS group, the expression of NK-1R and RANTES was significantly higher in the nasal mucosa of NSAR and NCS group rats. The sneezing and nose rubbing counts and the amount of nasal secretions were increased significantly in the NSAR and NCS groups. Rats in the NKR group experienced greater relief from AR symptoms than rats in the NSAR and NCS groups. Furthermore, knockdown of NK-1R expression also significantly eliminated RANTES expression and eosinophil infiltration in the nasal mucosa of NKR group rats.

Conculsion: For the first time, we show that intranasal treatment with NK-1R-specific siRNA can significantly decrease RANTES expression, AR-related symptoms, and eosinophil inflammation, suggesting that the regulating effect of NK-1R in the development of AR occurs via alteration of RANTES expression.

Background: Extensive data suggest that exposure to cigarette smoke can induce pulmonary epithelial barrier dysfunction. However, the effects of cigarette smoke on the nasal epithelial barrier are still unclear. Here, we investigated the consequence and mechanism of cigarette smoke on the nasal epithelial barrier.

Methods: Sprague Dawley rats were exposed to cigarette smoke for 3 or 6 months, and changes in inflammatory markers and nasal barrier function were evaluated. Moreover, underlying mechanisms were explored. Finally, normal human bronchial epithelial cells were cultured with or without tumor necrosis factor-alpha (TNF-α) in vitro, and the levels of continuity and tight junction-associated proteins were measured.

Results: In vivo experiments showed that the nasal mucosal barrier function of rats exposed to cigarette smoke was disturbed. Indeed, proteins associated with tight junctions were decreased, and the levels of inflammatory factors, such as IL-8, IL-6, and TNF-α, were dramatically increased in comparison to those of control animals. In vitro, TNF-α was shown to disrupt the continuity of proteins associated with tight junctions and to downregulate the expression of these proteins in bronchial epithelial cells.

Conclusions: We found that cigarette smoke disrupted the nasal mucosal barrier, and the extent of the damage was correlated with the duration of cigarette smoke exposure. We showed that TNF-α can disrupt the continuity and attenuate the expression of tight junction proteins in human bronchial epithelial cells. Therefore, cigarette smoke may induce nasal epithelial barrier dysfunction through TNF-α.

Background: Eosinophilic chronic rhinosinusitis with nasal polyps (Eos-CRSwNP) remains a recalcitrant disease with a high recurrence rate.

Objective: This study aimed to identify a predictor of long-term recurrence in patients with Eos-CRSwNP.

Methods: A total of 39 Eos-CRSwNP patients who had their initial and recurrent nasal polyps surgically removed were retrospectively included in this study, with 49 Eos-CRSwNP patients without recurrence and 32 patients with non-Eos-CRSwNP matched by randomly chosen. Clinical characteristics were compared among or between groups. Spearman correlation analyses and a backward stepwise multivariate logistic regression analysis were performed to find factors associated with the recurrence and recurrence time of Eos-CRSwNP. Furthermore, a receiver operating characteristic (ROC) curve was used to determine the predictor of long-term Eos-CRSwNP recurrence.

Results: The number and ratio of tissue eosinophils were highest in Eos-CRSwNP with recurrence and lowest in non-Eos-CRSwNP. The ratio of tissue lymphocytes was highest in non-Eos-CRSwNP and lowest in Eos-CRSwNP with recurrence, with the number of tissue lymphocytes higher in Eos-CRSwNP without recurrence than the other two groups. The numbers of tissue lymphocytes in the initial nasal polyps were lower and the numbers of tissue eosinophils were higher in the group of recurrent nasal polyps that recurred at >5 years after surgery than in the nasal polyps that recurred at <5 years after surgery. The tissue lymphocyte-to-eosinophil ratio (LER) showed a significant negative correlation with the recurrence and the recurrence time of Eos-CRSwNP. A ROC curve revealed that a tissue LER value < 0.67 predicted long-term Eos-CRSwNP recurrence with 72.73% sensitivity and 82.35% specificity (area under the curve  =  0.789).

Conclusion: Tissue LER is strongly associated with Eos-CRSwNP recurrence and may play a key role in predicting long-term Eos-CRSwNP recurrence.

Background: Positron emission tomography (PET) scan is a valuable imaging modality widely used in the management of cancers. Its usage is well defined for most head and neck malignancies. However, there is a lack of consensus regarding the utility of PET scan for sinonasal malignancies. This is highlighted by the latest international consensus statement on endoscopic skull base surgery.

Objective: This systematic review aims to clarify the role of PET scan in the management of sinonasal malignancies.

Methods: We conducted a comprehensive literature search using PubMed, MEDLINE, EMBASE, Web of Science, CINAHL, and Cochrane databases for research studies of interest. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) updated statement was used to guide the review.

Results: In total, 1807 articles were assessed for eligibility. Thirty-nine original papers, published between 2004 and 2021, met inclusion criteria. Seven articles focused on the role of PET scan for inverted papilloma, 23 for sinonasal carcinoma, 4 for melanoma, and 3 for lymphoma, and finally, 3 articles focused on the use of specific PET scan tracers for sinonasal malignancies. Qualitative summaries for each potential role of PET scans were provided. In general, included studies were retrospective in nature with low level of evidence.

Conclusions: In general, and across all types of sinonasal malignancies, PET scan yielded positive results regarding detection and initial staging. It was also considered as the modality of choice for detection of distant metastases, except in the case of sinonasal lymphoma. PET scan's main limit resides in its inability to detect lesions in or close to the metabolic activity of the brain.