American Journal of Rhinology & Allergy最新文献

Background: The Epistaxis Severity Score (ESS) is the gold-standard patient-reported outcome measure for evaluating nosebleed severity in patients with hereditary hemorrhagic telangiectasia (HHT). To date, the ESS has been assessed only for content validity and concurrent validity.

Objective: We evaluate the internal consistency and test-retest reliability of the ESS.

Materials and methods: After receiving institutional review board approval, we sent an online survey battery, including the ESS survey, to 305 (39% male) English-speaking HHT patients ≥18 years old at a single center. Of those, 140 (46%) patients completed the battery, and 110/140 (79%) reported epistaxis. Cronbach's alpha and correlation analyses were used to evaluate internal consistency. For the test-retest reliability evaluation, we recruited 69 HHT patients during HHT clinic to complete 2 self-administered ESS surveys 2 weeks apart. Participants also completed a modified Clinical Global Impression-Improvement scale with readministration of the ESS survey. We calculated the intraclass correlation coefficient in a 2-way mixed model with absolute agreement.

Results: The ESS survey demonstrated low internal consistency (Cronbach's alpha = 0.495), suggesting that it measured multiple unrelated concepts. Factor analysis revealed 3 latent factors with moderate intercorrelation, suggesting the presence of 3 related but distinct constructs underlying the ESS. However, the ESS demonstrated excellent test-retest reliability (intraclass correlation coefficient = 0.955; 95% CI, 0.91-0.98).

Conclusion: Although the ESS demonstrates high test-retest reliability, it may not adequately assess different dimensions of nosebleed severity. Additional correlated survey questions and sub-scores may be needed to increase internal consistency to accurately measure each component of epistaxis severity. It is necessary to acknowledge epistaxis severity from different dimensions and to consider evaluating individual ESS items separately for a comprehensive understanding.

Background: Studies evaluating health-related quality of life (HRQOL) in patients with hereditary hemorrhagic telangiectasia (HHT) have expanded rapidly in the past decade. These studies have evaluated QOL aspects ranging from the general QOL for patients living with HHT to intervention-specific outcomes. However, few tools have been fully validated across the spectrum of disease manifestations and interventions in HHT.

Objective: In this scoping review, we aim to map the literature on HHT-QOL metrics, identify gaps, inform future QOL research, and facilitate future metric development.

Methods: We analyzed articles in English that assessed at least 1 measure of general HRQOL, including physical health, mental health, social health, or intervention-specific QOL in patients with HHT. Searches across 2 bibliographic databases (PubMed and Scopus) yielded 186 articles after duplicates were removed. Sixty-three studies met eligibility criteria: 22 prospective studies (34.9%), 20 retrospective studies (31.7%), 12 cross-sectional studies (17.5%), 6 randomized controlled trials or secondary analyses of a randomized controlled trials (9.5%), 2 qualitative studies (3.2%), and 1 case-control study (1.6%). Two additional studies-1 prospective and 1 cross-sectional study-were identified at the October 2022 14th International HHT Conference and included, making a total of 65 studies.

Results: The 65 eligible studies used 30 QOL instruments. Twenty studies characterized baseline HRQOL, and 45 studies evaluated QOL before and after treatment. Of those 45 studies, 37 evaluated HRQOL before and after therapies targeting epistaxis and nasal symptoms, 4 targeted therapies for liver arteriovenous malformations and high-output heart failure, 3 evaluated therapies for both epistaxis and gastrointestinal bleeding, and 1 evaluated treatment targeting gastrointestinal bleeding alone.

Conclusions: Comparison of results across studies remains challenging given the heterogeneity in outcomes measures. Further development of HHT-specific patient-reported outcomes instruments that capture the global illness experience of HHT is needed.

Background: Eosinophilic chronic rhinosinusitis (eCRS) is a type 2 inflammatory disease that frequently recurs after surgery. In recent years, dupilumab has been available for the treatment of refractory chronic rhinosinusitis since 2020 in Japan. Although there are some reports of its usefulness, there are not enough reports of its clinical efficacy for longer than 1 year, especially for olfactory recovery.

Methods: Twenty patients with eCRS who had recurrence after surgery and had been receiving dupilumab were enrolled retrospectively. The nasal polyp score (NPS), computed tomography (CT) score, T&T olfactometer, and olfactory cleft opacification on CT were evaluated at baseline, at an average of 5.1 months later (short term), and at an average of 18.3 months later (long term).

Results: At the short-term evaluation, there were significant improvements in the NPS and CT scores (P < .001, P = .008, respectively). The CT score was further improved at the long-term evaluation compared to the short-term evaluation (P = .018) and baseline (P = .008). T&T detection/recognition thresholds and olfactory cleft opacification showed significant improvements only at the long-term evaluation compared to baseline (P = .002, P = .006, and, P = .006, respectively).

Conclusion: The NPS remained improved, and the CT score showed further improvement with long-term treatment, whereas olfactory function and olfactory cleft opacification showed significant improvement only after long-term treatment. There was a dissociation between the time to improve in the NPS and CT scores and the time to improve in olfactory function and olfactory cleft opacification. Based on these results, dupilumab should be administered for longer than 1 year, especially for olfactory function.

Objective: The purpose of this study is to characterize the presentation, outcomes, and barriers to care for White and non-White patients undergoing endoscopic sinus surgery (ESS).

Background: ESS is often successful in providing long-term relief for patients suffering from chronic rhinosinusitis (CRS). Literature that uses robust measures of socioeconomic status (SES) and barriers to care to assess ESS outcomes is limited.

Methods: A retrospective matched cohort study of patients who underwent ESS for CRS between 1/1/2015 and 6/1/2021 at a single tertiary care academic center was conducted. White and non-White patients were matched 1-to-1 by sex and age (± 5 years). SES was evaluated using the area of deprivation index (ADI).

Results: Of the 298 patients included in the study, 149 are White and 149 are non-White, 111 (37.2%) have CRS with nasal polyposis (CRSwNP), 141 (47.3%) had allergic rhinitis, 90 (30.2%) had asthma and 22 (7.4%) required revision ESS. Non-White patients were 3.62 times more likely to present with CRSwNP (95% confidence interval [CI] 2.2-5.96) and had 2.87 times increased odds for requiring revision ESS than age and sex-matched White patients (95% CI 1.090-7.545). The median ADI for non-White (6.00) patients was higher than for White patients (3.00) (P < .001) and 21.5% more non-White patients presented with Medicaid (P < .001).

Conclusion: Non-White patients undergoing ESS for CRS are more likely to present from areas with fewer resources and be underinsured. Using robust measures of SES, such as ADI, may allow for care to be tailored to patients with barriers to care.

Background: Over the last few decades, reflux diseases, such as laryngopharyngeal reflux (LPR) and gastroesophageal reflux disease (GERD), have been identified as significant contributors to inflammatory upper aerodigestive tract diseases. Establishing a direct relationship between reflux disease and chronic rhinosinusitis (CRS) is challenging due to the high prevalence of both diseases and their potential for independent coexistence.

Objective: The purpose of this study is to review the existing literature and evaluate the evidence of an association between reflux diseases and CRS.

Methods: A comprehensive electronic search was conducted across multiple databases to identify all studies that investigated the relationship between LPR, GERD, and CRS from January 1, 1950, to June 16, 2022. Only studies with English manuscripts involving adult populations were included, while case series, case reports, and in vitro studies were excluded. The risk of bias was evaluated using The Newcastle-Ottawa Scale for case-control studies and the NIH quality assessment tool for observational cohort and cross-sectional studies.

Results: The search strategy yielded a total of 427 articles, out of which 25 studies examined the correlation between reflux diseases and CRS. The meta-analysis indicated a significant association between the presence of GERD and CRS compared to control groups (P < .001; CI 3.56 [2.25, 5.65]), as well as significantly higher pH values and pepsin detection in CRS patients when compared to healthy individuals (P = .003). Furthermore, all studies that evaluated proton pump inhibitor (PPI) therapy in CRS patients reported positive outcomes, with 93% of CRS patients showing improvement on PPIs.

Conclusion: The existing literature provides suggestive evidence of an association between reflux diseases and CRS, with regards to both prevalence and treatment. Nonetheless, further studies are required to confirm this relationship.

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.