CRSwNP) And CRS Without Nasal Polyps Research Articles

Diverse Endotypes of Chronic Rhinosinusitis and Clinical Implications.

Chronic rhinosinusitis (CRS) is a highly heterogeneous disease characterized by inflammation in the nasal and sinus mucosa. The CRS phenotypes, based on the presence or absence of nasal polyps, are known as CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). However, this classification has limitations in fully capturing the mechanisms and clinical manifestations of CRS. To address the heterogeneity of CRS, there has been a growing focus on classifying the condition into distinct endotypes. Endotype classification involves grouping patients based on specific molecular, immunological, and clinical characteristics, allowing for more personalized and targeted treatment approaches.This review delves into the current state of endotype classifications for CRS. It explores the role of geographic factors, microbiome, and subphenotype in shaping different endotypes. Additionally, the review examines how various clinical features are associated with specific endotypes, providing valuable insights into tailoring treatment options for better outcomes and transitions between different endotypes.Overall, this review offers a comprehensive and up-to-date perspective on the intricate realm of CRS endotype classifications. By unraveling the molecular and clinical intricacies, this review lays the foundation for more precise, effective, and individualized treatment strategies in the management of CRS.

Biologics for Chronic Rhinosinusitis-A Modern Option for Therapy.

Chronic rhinosinusitis (CRS) is an important ENT pathology which affects about 5-12% of the general population. The treatment of CRS can be pharmacological (nasal sprays, douches, systemic antibiotics and steroids), surgical (endoscopic sinus surgery) or immunological according to established algorithms. CRS was divided for many years into CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). New ways of classifying CRS by endotypes (presence of neutrophilia, eosinophilia, fibrosis, glandular hypertrophy and epithelial dysmorphisms) appeared after the most recent understandings of the pathophysiology of the disease. Other classifications divide CRS into primary and secondary forms, localized/diffuse types and anatomical presentation. A new type of treatment has been administered in the last years, biologics. For the moment, biologics are indicated just in the cases of the patients who have undergone ESS or have contraindications for surgery and have bilateral polyps and meet a minimum of three of the following criteria: the necessity for systemic therapies with oral or parenteral corticosteroids or contraindications to systemic steroids, significant loss of smell or impaired QoL score, comorbid asthma and type 2 inflammation. This article aims to present the most relevant studies which used the three types of biologics (anti-IgE, anti-IL5 and anti-IL4/IL3) and wishes to increase the awareness of this new type of treatment that can be used in some CRS cases.

Is There a Correlation between Endoscopic Sinus Surgery and Improvement in Erectile Dysfunction?

In recent years, the focus on respiratory disorders has increased, notably on chronic rhinosinusitis (CRS), an inflammatory condition of the upper airway that can significantly impact one's quality of life. Interestingly, CRS has emerged as a potential comorbidity in erectile dysfunction (ED). This study aims to assess the impact of endoscopic sinus surgery for CRS on sexual function. The authors conducted a prospective study of patients who visited their clinics for chronic rhinosinusitis between June 2018 and June 2022. The study involved 53 patients aged between 40 and 70 years who were treated for CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). Preoperative and postoperative assessments were performed using the Nasal Obstruction Symptoms Evaluation Score (NOSE score) and the 5th International Index of Erectile Function Score (IIEF-5 score) to evaluate potential improvements in sexual function following endoscopic sinus surgery. Before surgery, the average NOSE score was 72.6, which decreased to 24.9 postoperatively. The average preoperative IIEF-5 score was 16.35, while the postoperative average increased to 19.52. Statistical analysis revealed a significant improvement in erectile function for penetration (p-value = 0.024) and overall satisfaction after intercourse (p-value < 0.001) regarding the degree of nasal obstruction. This study underscores the potential benefits of treating chronic obstructive upper airway diseases such as sinusitis in improving the sexual outcomes of patients clinically diagnosed with erectile dysfunction.

Blood eosinophil count in the diagnosis of allergic-like rhinitis with chronic rhinosinusitis.

Allergic rhinitis (AR) and nonallergic rhinitis (NAR) often are comorbid with chronic rhinosinusitis (CRS). Finding a convenient test that distinguishes these complex conditions is helpful for effective treatment. We aimed to analyse blood parameter differences between AR and NAR patients with/without CRS. Eight hundred thirteen patients, including AR and NAR with different conditions [CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP)] were analysed in this retrospective study. Patients with a nasal deviation alone were included as healthy controls (HC). Receiver operating characteristic analysis was used to assess the value of blood parameters for diagnosing AR or NAR with/without CRS. Compared to nonallergic-like rhinitis (HC, CRSwNP and CRSsNP), the blood eosinophil count was significantly increased in the allergic-like rhinitis groups, except for NAR-CRSsNP (AR, AR-CRSwNP, AR-CRSsNP, NAR and NAR-CRSwNP). The NAR-CRSsNP group had a higher level of eosinophils than the HC and CRSsNP groups. Among allergic-like rhinitis patients, eosinophils were higher in allergic-like rhinitis patients with CRSwNP (AR-CRSwNP and NAR-CRSwNP) than in allergic-like rhinitis patients without CRSwNP (AR, AR-CRSsNP, NAR and NAR-CRSsNP). However, no difference in blood eosinophils was observed between AR and NAR. There was also no difference among nonallergic-like rhinitis patients. Similar findings were found for the blood eosinophil proportion. Furthermore, the blood eosinophil count was a good predictor of allergic-like rhinitis, especially allergic-like rhinitis with CRSwNP. The blood eosinophil count and proportion may be good diagnostic predictors of allergic-like rhinitis but cannot differentiate between AR and NAR. This indicator may be much better in predicting allergic-like rhinitis with CRSwNP.

Endotypes of Asian chronic rhinosinusitis with nasal polyps: A narrative review

Chronic rhinosinusitis (CRS) is classified as CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). CRSwNP is a distinct phenotype with heterogeneous endotypes and complex pathophysiological mechanisms. Inflammation of the sinonasal mucosa that forms NPs causes symptoms such as nasal obstruction, rhinorrhea, and smell loss, and lowers patients’ quality of life. In recent years, researchers have attempted to elucidate the inflammatory endotypes of CRSwNP, and the inflammatory pattern of Asian CRSwNP was found to be different from that of Western CRSwNP. The main endotype of CRSwNP is type 2 inflammation, in which interleukin (IL)-4, IL-5, and IL-13 are key cytokines. In contrast, type 1 inflammation (interferon-γ) and type 3 inflammation (IL-17 or IL-22) play essential roles in Asian CRSwNP. Biological agents, which have recently been highlighted for the treatment of CRSwNP, are very effective in suppressing the type 2 inflammatory response and recovering smell loss. However, little information is available on the efficacy of these biologics in Asian patients with CRSwNP. Herein, we reviewed the endotypes of Asian CRSwNP and compared them to those of Western CRSwNP. We identified changes in the inflammatory patterns and summarized the therapeutic options for Asian CRSwNP.

Novel involvement of PLD-PKCδ-CREB axis in regulating FGF-2-mediated pentraxin 3 production in human nasal fibroblast cells.

A higher expression level of mitogenic fibroblast growth factor-2 (FGF-2) has been reported in human nasal mucus of both chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). Meanwhile, we have shown that long pentraxin 3 (PTX3), an essential component of humoral innate immunity that is produced at sites of infection and inflammation, was overproduced in human nasal mucosae and secretions of CRSsNP. Therefore, this study was aimed to investigate how FGF-2 regulates PTX3 expression in human CRSsNP nasal mucosa-derived fibroblast cells (hNMDFs). The FGF-2 treatment caused ptx3 mRNA expression and PTX3 protein induction and secretion. In parallel, a differential expression of FGF receptor (FGFR)-1 to FGFR-4 was observed in hNMDFs and human nasal tissues. While conventionally known PI3K/Akt/mTOR and AP-1 pathways following FGFR activation were shown to be involved, the protein kinase Cδ (PKCδ) and cAMP response element-binding protein (CREB) were also found to be as critical signaling molecules in FGF-2-induced PTX3 induction. The PKCδ and CREB activation could be detected in total cells and in the cell nucleus. Accordingly, a novel CREB binding sequence was detected in the human ptx3 promoter region and could interact with activated CREB in cells challenged with FGF-2. Surprisingly, the phospholipase D (PLD), but not phosphoinositide- and phosphatidylcholine-phospholipase C, was necessarily required for PKCδ and CREB activation. Therefore, we demonstrated here for the first time that FGF-2 mediates PTX3 production not only through PI-3K/Akt/mTOR and AP-1 activation, but also through a novel FGFR-PLD-PKCδ-CREB cellular signaling pathway.

Multidisciplinary consensus on a stepwise treatment algorithm for management of chronic rhinosinusitis with nasal polyps.

Multidisciplinary consensus on a stepwise treatment algorithm for management of chronic rhinosinusitis with nasal polyps.

Biologics: A New Option in Treatment of Severe Chronic Rhinosinusits with Nasal Polyps

Chronic rhinosinusitis (CRS) is defined as an inflammation of the nose and paranasal sinuses with prevalence of 10.9 % and by the presents of 2 or more symptoms, which last more than 12 weeks. The symptoms are nasal obstruction, nasal discharge (anterior/post nasal drip), facial pain or pressure and/or olfactory disorder. CRS has a high negative impact on an individual's quality of life. The pathogenesis is multifactorial and complex. CRS has been subclassified into 2 groups: CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). Regarding further knowledge of the inflammatory pathway the primary CRS is considered by endotype dominance, either type 2 or non-type 2. 80 % of the CRSwNP reveals a type 2 inflammation. The proteins, interleukin (IL)-4, IL-5, IL-13, and IgE were previously identified as key mediators in nasal polyp tissues pattern. CRSwNP is often refractory to medical and surgical management, especially in patients with asthma and aspirin intolerance. In most cases the control of the disease is a challenge. Patients with asthma but especially with Samter's triad are significantly more likely to have a recurrence of nasal polyps and undergo a second surgery following recurrence. In patients with severe CRSwNP, in whom the current standard of care including topical and oral corticosteroids, antibiotics and surgical procedures fail to control the disease, biologics can open new perspectives in treatment. They allow avoiding the possible adverse events resulting from repeated use of systemic corticosteroids and surgery. These biologics have a high impact on type 2 immune reaction and lead to a reduction of IgE as well as of local mucosal eosinophil migration and activation, resulting in a significant effect on nasal polyps, smell, quality of life and asthma comorbidity.

The Olfactory Cleft Endoscopy Scale: a multi-institutional validation study in chronic rhinosinusitis.

Olfactory dysfunction (OD) associated with chronic rhinosinusitis (CRS) remains quite challenging. Instruments to precisely assess olfactory cleft anatomy and their association with olfaction are needed. The olfactory cleft endoscopy scale (OCES) was used to assess the olfactory cleft in healthy control subjects and a cohort of patients with CRS. Psychophysical and psychosocial olfactory function were assessed and correlations with OCES scores were measured. Control subjects and subjects with CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP) were enrol- led. OCES correlated with both psychophysical and psychosocial olfaction, as measured by threshold, discrimination and identi- fication (TDI) scores and Questionnaire on Olfactory Disorders (QOD-NS) scores for all case and control subjects combined. OCES improved in both CRS groups postoperatively with the highest correlation seen in postoperative olfaction in CRSwNP patients. CRS patients who achieve near perfect OCES and sinus endoscopy scores after surgery have olfactory metrics that are indistin- guishable from controls regardless of polyp status. The OCES is a valid olfactory-specific measure that demonstrates strong validity and provides complimentary infor- mation to traditional sinus endoscopy to aid in our understanding of OD associated with CRS.

Denatonium benzoate bitter taste perception in chronic rhinosinusitis subgroups.

Chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP), and aspirin-exacerbated respiratory disease (AERD) have varying levels of inflammation and disease severity. Solitary chemosensory cells (SCCs) are enriched in nasal polyps, are the primary source of interleukin 25 (IL-25) in upper airways, leading to type 2 inflammation, and are activated by bitter-tasting denatonium benzoate (DB). Thus, we sought to evaluate DB taste perception at a range of concentrations in order to identify 1 that most differentiates CRS subgroups from controls. CRSsNP (n = 25), CRSwNP (n = 26), and AERD (n = 27) patients as well as controls (n = 25) tasted 6 DB concentrations in a fixed, random order, rating on a category scale of 0 (no intensity) to 12 (extremely intense). Sinonasal epithelial cultures were treated with and without denatonium and analyzed for IL-25 via flow cytometry. CRSsNP patients rated DB as significantly less intense than did controls at all concentrations: 5.62 × 10-9 M, 1.00 × 10-8 M, 1.78 × 10-8 M, 3.16 × 10-8 M, 5.62 × 10-8 M, and 1.00 × 10-7 M (all p < 0.0083). CRSwNP patients did not show significant differences from controls. AERD patients rated DB as significantly more intense than did controls at concentrations of 1.00 × 10-8 M and 3.16 × 10-8 M (p < 0.0083). In vitro data demonstrated significant increase in IL-25-positive cells after denatonium stimulation (n = 5), compared to control (n = 5) (p = 0.012). Our findings link in vitro DB stimulation of sinonasal tissue with increased IL-25 and show differential DB taste perception in CRS subgroups relative to the control group, with CRSsNP being hyposensitive and AERD being hypersensitive. We propose a concentration of 3.16 × 10-8 M for future study of clinical utility.

Phenotypes in Chronic Rhinosinusitis.

Chronic rhinosinusitis (CRS) is a heterogenous disease process affecting a significant proportion of the population and impacting quality of life and productivity. Historically, CRS has been classified broadly into CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). Increased understanding regarding unique presentations of CRS subsets and their underlying inflammatory profiles has led to a new system for classifying CRS phenotypes. Consideration of CRS phenotypes has traditionally been a key factor in determining treatment paradigms. Under a new phenotype classification system, physical findings will continue to drive treatment decisions, but with more precision. Recent rapidly accumulated knowledge indicates that the broad categorization of CRSwNP or CRSsNP is no longer clinically useful. Reorganization of CRS phenotypes and their underlying endotypes will lead to more targeted and efficacious therapy.

Correlations between symptoms, nasal endoscopy and computed tomography findings in patients with chronic rhinosinusitis without nasal polyps

Background/Aim. Chronic rhinosinusitis (CRS) is one of the most common chronic conditions that is diagnosed on the basis of the condition symptoms, nasal endoscopy and computed tomograhpy (CT) of the nose and paranasal sinuses. There are two forms of CRS: CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). The aim of this paper was to determine if there is a correlation between the symptoms, nasal endoscopy and CT in patients with CRSsNP. Methods. The study included 110 patients with CRSsNP. The intensity of the symptoms assessed on the visual analogue scale (VAS) and the condition of nasal mucosa and the presence of nasal secretion was estimated by endoscopic examination of the nose while CT was used to determine the Lund-Mackay (LM) score values. Pearson?s coefficient of correlation was used for statistic data processing. Results. The severity of the disease as a whole (r = 0.509) and nasal discharge (r = 0.562) moderately correlated with CT. Nasal congestion (r = 0.354) and the reduction of loss of smell (r = 0.324) mildly correlated with CT, while facial pain/pressure (r = 0.218) had a very weak correlation with CT. The severity of the disease as a whole (r = 0.717) and nasal discharge (r = 0.821) strongly correlated with nasal endoscopy. Nasal congestion (r = 0.525) had a moderate correlation with nasal endoscopy while facial pain/pressure (r = 0.345) and the reduction of the loss of smell (r= 0.394) had a mild correlation with nasal endoscopy. A moderate correlation was found between nasal endoscopy and CT (r = 0.630). Conclusion. The severity of the disease as a whole and nasal discharge have more significant correlations both with nasal endoscopy and CT in relation to the correlations between other symptoms and nasal endoscopy, as well as CT. More significant correlations between the symptoms and nasal endoscopy in relation to the correlations between the symptoms and CT and the existence of a moderate correlation between nasal endoscopy and CT, enable a lesser use of CT diagnostics and only in precisely defined situatiations.

Differential expression of miR-4492 and IL-10 is involved in chronic rhinosinusitis with nasal polyps.

Chronic rhinosinusitis (CRS) is one of the most common types of respiratory disease and affects a large proportion of the population worldwide. The clinical differences between CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP) facilitate studies on the development of polyps. In the present study, next-generation sequencing was performed to identify differentially expressed microRNAs (miRNAs/miRs) in CRSwNP vs. CRSsNP tissues and subsequently validated the expression of selected genes using reverse transcription-quantitative polymerase chain reaction analysis. In total, 6 miRNAs were identified to be downregulated in the CRSwNP samples compared with those in the CRSsNP samples. The predicted targets of these miRNAs were determined to be enriched in a number of signaling pathways, including the ErbB, Ras, cyclic adenosine monophosphate and Janus kinase (Jak)/signal transducer and activator of transcription (STAT) pathways. The expression of miR-4492 and that if its targets predicted by a bioinformatics analysis, tumor necrosis factor α (TNF-α) and interleukin (IL)-10, was validated in 96 clinical specimens. miR-4492 was downregulated and IL-10 was upregulated in CRSwNP vs. CRSsNP tissues, and an inverse correlation between miR-4492 and IL-10 was determined in CRS tissues; however no difference was identified in the expression of TNF-α between the different groups. The present results indicate that the miR-4492/IL-10 interaction in the Jak/STAT signaling pathway may be one of the key mechanisms in CRSwNP.

Inflammation and Endotyping in Chronic Rhinosinusitis-A Paradigm Shift.

Chronic rhinosinusitis (CRS) is a heterogeneous chronic inflammatory condition of the paranasal sinuses and nasal passage. It is characterized as inflammation of the sinonasal passage, presenting with two or more symptoms (nasal blockage, secretions, facial pain and headaches) for more than 12 weeks consecutively. The disease is phenotypically differentiated based on the presence of nasal polyps; CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). Traditionally, CRSwNP has been associated with a type 2 inflammatory profile, while CRSsNP has been associated with a type 1 inflammatory profile. Extensive work in characterizing the inflammatory profiles of CRS patients has challenged this dichotomy, with great variation both between and within populations described. Recent efforts of endotyping CRS based on underlying pathophysiology have further highlighted the heterogeneity of the disease, revealing mixed inflammatory profiles coordinated by a number of inflammatory cell types. This review will highlight the current understanding of inflammation in CRS, and discuss the importance and impact of refining this understanding in the development of appropriate treatment options for CRS sufferers.

Interleukin -19 Up-Regulates Mucin 5AC Production in Patients with Chronic Rhinosinusitis via STAT3 Pathway

Background: The mucin gene MUC5AC is highly expressed both in chronic respiratory inflammatory diseases and in inflammatory bowel disease where mucin secretion is regulated by members of the interleukin IL-20 subfamily. This study was conducted to determine the roles and mechanisms of IL-19, a member of the IL-20 subfamily, in regulating MUC5AC production in chronic rhinosinusitis (CRS). Methods: We analyzed the expression of mucin and MUC5AC in the nasal mucosa of patients with CRS by periodic acid Schiff (PAS) staining and immunohistochemical examination. Real-time quantitative PCR, ELISA, confocal microscopy and western blotting were used to measure MUC5AC expression in primary human nasal epithelium cells (PHNECs) stimulated with recombinant human IL-19 (rhIL-19), IL-19 receptor siRNA transfection or control. The involvement of the STAT3 signaling pathways was examined by the use of cryptotanshinone (CRY, an inhibitor of signal transducer and activator of transcription [STAT]3). Findings: Mucin and MUC5AC were significantly increased in mucosa of CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP) compared to mucosa isolated from control who had no CRS, but there were no significant differences between these two groups. Pretreatment with rhIL-19 up-regulated the expression of MUC5AC in both mRNA and protein levels in PHNECs. Knockdown of IL-20R2 and pretreatment with CRY attenuated MUC5AC production induced by rhIL-19. Interpretation: We propose that mucin, MUC5AC and IL-19 are highly expressed in CRS and IL-19 up-regulates MUC5AC-induced mucin production via the STAT3 pathway, highlighting the important role IL-19 may play in mucin production in chronic respiratory diseases. Funding Statement: TThis study was supported by grants from the National Natural Science Foundation of China (No. 81371073, No. 81670913, No. 81500769, No. 81671611) and the Guangdong Introducing Innovative and Entrepreneurial Teams (2016ZT06S252). Declaration of Interests: The authors have no conflicts of interest to declare. Ethics Approval Statement: The protocol was approved by the ethics committee for clinical medical research at Third Affiliated Hospital of Sun Yat-sen University (No∙ [2016]2-26). All enrolled subjects had been given their written informed consent.

Role of Exhaled Nasal Nitric Oxide in Distinguishing between Chronic Rhinosinusitis with and without Nasal Polyps

Chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP) nasal polyps is a global health concern. Several clinical biomarkers, such as inhaled carbon monoxide and exhaled nitric oxide (NO), have been studied to assess the presence and degree of inflammation in the airway mucosa. To evaluate the clinical application of exhaled nasal NO (nNO) in distinguishing between CRSwNP and CRSsNP in consideration of the atopic status of patients. Eighty-eight patients with CRS and 20 healthy volunteers were recruited for this study. The exhaled nNO level was measured by using a hand-held device. Nasal endoscopy (with Lund-Mackay scoring of CRS) and sinus computed tomographies (CT) were used to evaluate the nasal cavity and sinuses of the subjects. Atopic status was confirmed by using skin prick tests (SPTs). The mean ± standard deviation (SD) levels of nNO in patients with CRSsNP were significantly higher than those in patients with CRSwNP (591 ± 153 ppb versus 360 ± 181 ppb, p < 0.001), whereas patients with CRS exhibited lower levels of nNO compared with the control subjects (449 ± 204 ppb versus 881 ± 161 ppb, p < 0.001). Patients with atopy and with and without nasal polyps exhibited significantly higher levels of nNO compared with patients without atopy (atopic CRSsNP versus nonatopic CRSsNP, 734 ± 120 ppb versus 503 ± 92 ppb [p < 0.001]; atopic CRSwNP versus nonatopic CRSwNP, 518 ± 161 ppb versus 299 ± 150 ppb [p < 0.001]). The levels of nNO were negatively correlated with the Lund-Mackay scores in both atopic (r = -0.45; p = 0.016) and nonatopic (r = -0.600; p < 0.001) patients with CRS. Receiver operating characteristic curves differentiated patients as CRSwNP, CRSsNP, and healthy controls, and in atopic and nonatopic subgroups, with acceptable sensitivity and specificity (>70 to 90%). Exhaled nNO levels can be used to distinguish between patients with CRSwNP and patients with CRSsNP. However, the atopic status of the patient influenced the use of nNO as a diagnostic or monitoring biomarker in CRS.

Inflammatory infiltrate and mucosal remodeling in chronic rhinosinusitis with and without polyps: structured histopathologic analysis.

Chronic rhinosinusitis (CRS) is commonly classified into CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). Structured histopathologic reporting has the potential to identify salient histologic markers to differentiate subtypes and provide insights into pathophysiologic mechanisms in CRS. A structured histopathology report of 13 variables was prospectively employed to analyze ethmoid sinus tissue removed during endoscopic sinus surgery for 99 patients, including 43 CRSsNP and 56 CRSwNP. These variables were compared in association with presence of nasal polyps, radiographic computed tomography scores (Lund-Mackay Score [LMS]), subjective symptoms scores (SNOT-22), duration of CRS, comorbid asthma, and atopy. Overall inflammation did not differentiate between CRSsNP and CRSwNP (p < 0.26). Compared to CRSsNP, CRSwNP had statistically significant increase in basement membrane thickening (76.8% vs 48.8%, p < 0.004), subepithelial edema (19.6% vs 2.3%, p < 0.01), fibrosis (58.9% vs 27.9%, p < 0.002), hyperplastic/papillary changes (12.5% vs 0.0%, p < 0.016), eosinophilia (41.1% vs 18.6%, p < 0.047), and eosinophilic aggregates (30.4% vs 11.6%, p < 0.022). Higher LMS was associated with increased eosinophilia (p < 0.001), eosinophil aggregates (p < 0.000), inflammation (p < 0.023), basement membrane thickening (p < 0.037), hyperplastic/papillary changes (p < 0.040) and fibrosis (p < 0.000). SNOT-22 scores were not associated with any histologic parameters. Significant histopathologic differences were evident in patients with CRSwNP and CRSsNP. No single feature reliably differentiated between the 2 subtypes, underscoring the heterogeneity of CRS and limitation of this phenotypic classification system. Eosinophilic aggregates were associated with significantly worse disease, possibly signifying a unique subtype. Further studies are needed to understand the relationship of histopathologic features to disease outcome.

Peripheral blood T-helper cells and eosinophil populations in patients with atopic and nonatopic chronic rhinosinusitis.

Analysis of recent research indicated that T-helper cells may play an important role in the pathogenesis of chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). The purpose of this study was to investigate the peripheral blood Th1 and Th2 cells and eosinophil population in patients with CRS. Peripheral blood samples were obtained from nine nonatopic controls, 37 patients with CRSsNP, and 66 patients with CRSwNP. The samples were then analyzed by flow cytometry analysis (Th1 cell [CD4+, interleukin 4-, interferon γ+]; and Th2 cell [CD4+, interleukin 4+, interferon γ-]). The patients were stratified into four groups based on their allergic status by using skin-prick test results and immunoglobulin E level measurements as the following: (1) nonatopic CRSsNP, (2) nonatopic CRSwNP, (3) atopic CRSsNP, and (4) atopic CRSwNP. Eosinophil counts were also compared. The severity of nasal diseases in these patients was assessed via the Lund-Mackay score. No significant differences in peripheral blood Th1 and Th2 cells were found among all the atopic, nonatopic CRS groups, and the nonatopic control groups. Peripheral blood eosinophil levels in atopic CRSwNP were significantly elevated compared with the nonatopic controls (p < 0.05), but no significant difference was found among all atopic and nonatopic CRS groups. Analysis of our data demonstrated that a proportion of systemic Th1- and Th2-skewed lymphocytes in all CRS groups were similar to that in healthy subjects, irrespective of atopic status. The patients with CRSwNP and with atopy but not the patients with CRSsNP and with atopy demonstrated systemic eosinophilic inflammation. Further studies are needed to investigate underlying pathophysiologic mechanism or endotypes.

Prevalence and Risk Factors of Chronic Rhinosinusitus, Allergic Rhinitis, and Nasal Septal Deviation: Results of the Korean National Health and Nutrition Survey 2008-2012.

Chronic rhinosinusitis (CRS), allergic rhinitis (AR), and nasal septal deviation (NSD) are frequent rhinologic diseases that consume considerable health care resources. To determine the prevalence and risk factors of CRS, AR, and NSD in Korea. This study analyzed 5-year cross-sectional data from the Korean National Health and Nutrition Examination Survey (KNHANES) 2008-2012. A total of 35 511 participants, who underwent an interview regarding nasal symptoms and a nasal examination, were enrolled and subsequently divided into 3 groups: children (aged 7-12 years), adolescents (aged 13-19 years), and adults (aged ≥20 years). Adult CRS was classified into CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). Diagnosis of AR was based on symptoms and serum levels of specific IgE for 3 allergens, including Dermatophagoides farinae. The precise prevalence of AR was reestimated by multiplying the reciprocal of D farinae frequency based on a conventional skin prick test. Nasal septal deviation was diagnosed via nasal endoscopy after nasal decongestion. This study estimated the association of the 3 diseases with demographic data, including sex, age, obesity, level of education, socioeconomic status, residence, smoking, and alcohol. The prevalence of CRSwNP and CRSsNP in 28 912 adults was 2.6% and 5.8%, respectively. An association was found between CRSwNP and age (odds ratio [OR], 1.03; 95% CI, 1.02-1.04; P < .001), lower level of education (OR, 1.40; 95% CI, 1.02-1.92; P = .04), and obesity (OR, 1.46; 95% CI, 1.16-1.84; P = .001). Symptom-based and allergy test result-based AR had a prevalence of 27.5% (n = 35 511) and 16.1% (n = 2298), respectively. The reestimated prevalence of AR was 18.5% for all ages. Urban residence increased the risk of AR (OR, 1.21; 95% CI, 1.06-1.38; P = .005), but age was associated with a decreased risk (OR, 0.99; 95% CI, 0.98-0.99; P < .001). The prevalence of NSD was 48.0% and increased with age. In addition, NSD was a risk factor for CRSsNP (adjusted OR, 1.16; 95% CI, 1.02-1.32; P = .03) but not for CRSwNP. In KNHANES 2008-2012, older age was associated with increased risk for CRSwNP and NSD but associated with a decreased risk for AR. Obesity was another risk factor for CRSwNP.

Biomarker assessment in chronic rhinitis and chronic rhinosinusitis: Endothelin-1, TARC/CCL17, neopterin, and α-defensins.

Chronic rhinitis (CR) is characteristically divided into several major clinical phenotypes: allergic rhinitis (AR); nonallergic, noninfectious rhinopathy (NAR); and chronic rhinosinusitis (CRS). CRS has two phenotypic variants: CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). An area of growing interest is to identify biologic markers that could assess different aspects of CR phenotypes. The aim of the study was to evaluate four CR biomarkers: endothelin-1 (ET-1), thymus and activation-regulated chemokine (CCL17), neopterin, and α-defensins in subjects with AR, NAR, and CRS. Fifty-one patients with AR, 43 patients with NAR, 46 patients with CRSsNP, 54 patients with CRSwNP, and 40 healthy controls were included. ET-1, TARC/CCL17, neopterin, and α-defensins levels in subjects' serum and nasal secretions (NS) were measured by the enzyme-linked immunosorbent assay. High NS levels of ET-1, TARC/CCL17, and α-defensins were characteristic for CRSwNP, although only high NS levels of neopterin were found in the CRSsNP phenotype. AR phenotype was characterized by high NS levels of ET-1 and TARC/CCL17. In the subjects with NAR, none of these biomarker levels in serum and NS differed from those of healthy controls. CR can be categorized by ET-1, TARC/CCL17, neopterin, and α-defensins into several disease phenotypes. Further studies are needed to better investigate pathophysiologic roles of these biomarkers in CRS.