Chronic Rhinosinusitis Without Nasal Polyps Patients Research Articles

Suppressor of Cytokine Signaling Proteins 3 and 5 Potentially Delineate Polarization of Th cells in Chronic Rhinosinusitis.

Background: Chronic rhinosinusitis (CRS) is an inflammatory condition classified into chronic rhinosinusitis with nasal polyps (CRSwNP) and chronic rhinosinusitis without nasal polyps (CRSsNP). Th cells manage inflammatory cells in CRS. Suppressor of Cytokine Signaling (SOCS) proteins regulate Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway in Th cells by polarizing toward Th1, Th2, and Th17 cells. This study evaluated the levels of SOCS1,3,5 in CRS patients to find associations with Th cells. Methods: In this cross-sectional study, 20 CRSwNP patients, 12 CRSsNP patients, and 12 controls participated. The infiltration of CD4+ T cells was determined using immunohistochemistry. The expression of specific transcription factors and SOCS proteins was assessed using real-time PCR. Cytokine levels were evaluated using ELISA. SOCS protein levels were investigated using western blot analysis. Results: The expression of SOCS3 increased in the CRSwNP group compared to CRSsNP and control groups (p <0.001). SOCS3 protein levels increased in the CRSwNP group compared to CRSsNP (p <0.05) and control (p <0.001) groups. Although there was a significant difference in SOCS5 expression between CRSsNP and control groups, SOCS5 protein levels were significantly different between CRSsNP and control (p <0.001) and CRSwNP (p <0.05) groups. Conclusions: Targeted therapies may be suggested for CRS by modulating SOCS3 and SOCS5 proteins that are responsible for polarization of Th cells toward Th2 or Th1 cells, respectively. JAK-STAT pathway targeting, which encompasses numerous cells, can be limited to SOCS proteins to more effectively orchestrate Th cell differentiation.

Individual SNOT-22 Items Aid in Differentiating Between Spontaneous Cerebrospinal Fluid Rhinorrhea and Chronic Rhinosinusitis Without Nasal Polyps.

Spontaneous cerebrospinal fluid (CSF) rhinorrhea is a diagnostic challenge due to its overlapping symptomatology with other sinonasal diseases. The objective of this study was to investigate whether items on the sinonasal outcome test (SNOT)-22 could suggest a diagnosis of spontaneous CSF rhinorrhea versus chronic rhinosinusitis without nasal polyps (CRSsNP). A multi-institutional retrospective chart review of patients with spontaneous CSF rhinorrhea and a control group of CRSsNP patients was performed. Individual SNOT-22 scores and domain scores were compared. One hundred fifteen patients were included in both cohorts. Of the patients in the CSF rhinorrhea group, 48% were misdiagnosed as chronic rhinosinusitis (CRS) prior to the correct identification of a CSF leak. On bivariate analysis, the CSF rhinorrhea group scored significantly higher on the SNOT-22 for runny nose (P < .001) and was more likely to designate this symptom as most important (P < .001). The CRSsNP group scored significantly higher in nasal blockage (P < .001), thick nasal discharge (P < .001), facial pain/pressure (P < .001), and in the ear/facial (P < .001) and rhinologic (P = .003) domains. Multivariable logistic regression revealed that runny nose (P < .001) was most predictive of spontaneous CSF rhinorrhea while nasal blockage (P < .001), thick nasal discharge (P < .001), and facial pain/pressure (P = .001) were predictive of CRSsNP after adjusting for relevant confounders. No significant difference was observed in total SNOT-22 scores between groups (P = .676). Spontaneous CSF rhinorrhea is commonly misdiagnosed as other sinonasal pathologies. However, individual SNOT-22 items can help aid in suggesting a CSF leak. Spontaneous CSF rhinorrhea should be suspected in patients who have high SNOT-22 scores for runny nose and report this symptom as most important, but have lower scores related to the other cardinal symptoms of CRS.

Short-term Oral Steroids Significantly Improves Chronic Rhinosinusitis Without Nasal Polyps.

The efficacy of short-term oral corticosteroids in chronic rhinosinusitis without nasal polyps (CRSsNP) is unknown. The aim of this controlled study was to assess the immediate and long-term outcomes from a short course of a commonly used oral corticosteroid, prednisolone, in well-defined CRSsNP patients. Prospective, observational controlled study. A prospective-controlled study of CRSsNP patients treated with prednisolone at 0.5 mg/kg tapered over 10 days and non-prednisolone treated CRSsNP patients (controls) and follow-up at 2, 6, and 12 months. Baseline and follow-up SinoNasal Outcome Test (SNOT)-22, nasal endoscopy (Lund-Kennedy), and sinus CT scan scores (Lund-Mackay) were compared. At 2 months, there was a significant improvement in the SNOT-22, nasal endoscopy, and sinus CT scan scores in the prednisolone group (P < .0001) compared with controls (p=ns, Mann-Whitney U test). 52.5% of prednisolone-treated CRSsNP patients had improved symptoms and did not require sinus surgery at 12 months compared with 14.3% of controls (P < .001). Side-effects were reported in 8.9% of prednisolone-treated patients. Patients who benefited from prednisolone had a median symptom duration of 7.25 (99% confidence, upper limit of 11) months compared with 18 months in those requiring surgery. Short-term oral prednisolone significantly improved all three clinical measures of disease in CRSsNP patients and avoided surgical intervention in 52.5% patients in the first 12 months. Patients with symptoms for less than 11 months were most likely to benefit. The side-effects of oral steroids require careful consideration and further studies are needed to ascertain appropriate dosage and treatment duration. 3 Laryngoscope, 131:E2618-E2626, 2021.

Long term outcomes of balloon sinuplasty for the treatment of chronic rhinosinusitis with and without nasal polyps

ObjectivesThe aim of this study was to evaluate the 4-year outcomes and effectiveness of balloon sinuplasty in the treatment of chronic rhinosinusitis (CRS). Material and methodsWe evaluated the long-term outcomes in terms of symptoms, nasal endoscopy and computed tomography of 110 patients with CRS submitted to balloon sinuplasty in Centro Hospitalar do Funchal retrospectively.Sinus symptoms were determined by the Sino-Nasal Outcome Test (SNOT-22), endoscopic examination determined by Modified Lund Kennedy score (MLK) and computerized tomography scan of paranasal sinuses (CT-PNS) was evaluated through Lund Mackay scores (LM).Data was collected from 82 patients with chronic rhinosinusitis without nasal polyps (CRSsNP) and from 28 patients with nasal polyps (CRSwNP). ResultsLocal anesthesia procedures were performed in 45.5% of the patients.First follow up was obtained at 2 years (median 22.45 ± 13.6 months) and at 4 years (median 44.45 ± 14 months) after balloon sinuplasty.The mean baseline SNOT-22 score was of 50.26 ± 15.33 for patients with CRSsNP and 52.25 ± 18.06 in CRSsNP patients. Both scores were reduced to 7.00 ± 13.5 and 10.00 ± 22.50 at 4 years follow-up respectively. Baseline MLK score was 4.90 ± 2.12 for patients in CRSsNP group and 10.00 ± 2.00 in the CRSwNP group Both scores were reduced to 1.65 ± 1.67 and 4.86 ± 2.16. The overall mean average LM CT-PNS score was 8.71 ± 4.728 preoperatively for the CRSsNP and 16.18 ± 3.9 in patients with CRSwNP and were reduced to 1.00 ± 1.75 and 8.69 ± 4.6 after BSP.SNOT 22, MLK and LM scores showed consistent improvement over baseline at all time points until the end of the study (median 44.45 ± 14 months).Significant improvements were recorded at all time points in the patient's symptom score, nasal endoscopy scores and imaging scores (P < 0.0001). ConclusionBalloon sinuplasty appears to be safe and effective for the treatment of CRS with great long-term outcomes.

Expression of long pentraxin 3 in human nasal mucosa fibroblasts, tissues, and secretions of chronic rhinosinusitis without nasal polyps.

Numerous studies have shown that microbiomes play an important role in the pathogenesis of chronic rhinosinusitis (CRS). In addition to a known short pentraxin, C-reactive protein, long pentraxin 3 (PTX3) belongs to pentraxin family which detects conserved microbial pentraxin motifs and mobilizes early defense against foreign invaders, but its participation in CRS remains unclear. In the present study, through an intensive screening, peptidoglycan (PGN) was selected as a main material to investigate the action mechanism of a cell wall component on CRS without nasal polyps (CRSsNP) nasal mucosa-derived fibroblasts and the PTX3 expression in human nasal mucosa tissue and discharge. The PGN not only enhanced PTX3 mRNA and protein production in cells but also caused marked PTX3 secretion into extracellular space. The pharmacological interventions indicated that the PTX3 induction was mediated mainly through toll-like receptor 2 (TLR2), phosphoinositide-phospholipase C (PI-PLC), protein kinase C (PKC), NF-κB, and cAMP response element binding protein (CREB), which was further confirmed by the observations that a direct PKC activator (phorbol ester) had a similar inductory effect on PTX3 expression/production and the siRNA interference knockdown of PKCμ/δ, NF-κB, and CREB compromised PTX3 production. Meanwhile, PTX3 was found to be overexpressed/produced in nasal mucosa and discharge/secretion of the CRSsNP patients. Collectively, we first demonstrated here that PGN enhances PTX3 expression and release in nasal fibroblasts through TLR2, PI-PLC, PKCμ/δ, NF-κB, and CREB signaling pathways. The PTX3 is overexpressed in nasal mucosa and discharge/secretion of CRSsNP patients, revealing its possible importance in CRSsNP development and progression. KEY MESSAGES: Long pentraxin 3 (PTX3) is highly expressed in nasal mucosa and discharge/secretion of patients of chronic rhinosinusitis without nasal polyps (CRSsNP). The bacteria cell wall component-peptidoglycan (PGN) causes PTX3 expression in CRSsNP nasal mucosa-derived fibroblasts, contributing to the PTX3 increase in tissues. PGN induces PTX3 expression through a previously known IκB/NF-κB and a novel PKCμ/δ and CREB signaling pathway. The PTX3 may be used as a biomarker for CRS.

"In-Office Balloon Sinus Ostial Dilation with Concurrent Antiplatelet and Anticoagulant Therapy for Chronic Rhinosinusitis without Nasal Polyps".

Functional endoscopic sinus surgery (FESS) and balloon sinus ostial dilation (BSD) are well-recognized minimally invasive surgical treatments for chronic rhinosinusitis without nasal polyps (CRSsNP) refractory symptoms to medical therapy. Patients on antiplatelet and anticoagulant therapies (AAT) usually are recommended to discontinue their medications around the period of endoscopic sinus surgery. The goal of this study is to assess the clinical experience of BSD in CRSsNP patients with concurrent anticoagulant or antiplatelet therapy. A review of prospectively-collected clinical data from October 2012 to March 2017 were used to perform a cohort study of subjects with CRSsNP who met criteria for surgical intervention while on antiplatelet and anticoagulant therapy. Data were collected on demographics, details of the procedures, type of AAT used, pre- and postoperative 22-item Sino-Nasal Outcome Test (SNOT-22) scores, and complications. Thirty-five patients underwent in-office BSD while on antiplatelet and/or anticoagulant therapy. The mean difference in pre- and postoperative SNOT-22 scores of 9.9 (SD 14.4, P < .001) was both statistically significant and exceeded the minimal clinically important difference of 8.9. Absorbable nasal packing was used for persistent bleeding immediately post-procedure in two patients. Intraoperative bleeding was associated with aspirin 325 mg and warfarin. FESS was required for further management of chronic sinusitis in four patients after anticoagulant/antiplatelet therapy could be discontinued. There were no systemic complications. None of the patients experienced significant bleeding events postoperatively after leaving the office. In-office BSD appears to be a safe alternative to endoscopic sinus surgery in select patients who cannot discontinue antiplatelet and anticoagulant therapy. IV.

Transcription factors gene expression in chronic rhinosinusitis with and without nasal polyps.

BackgroundChronic rhinosinusitis (CRS) current therapeutic approaches still fail in some patients with severe persistent symptoms and recurrences after surgery. We aimed to evaluate the master transcription factors gene expression levels of T cell subtypes in chronic rhinosinusitis with nasal polyps (CRSwNP) and chronic rhinosinusitis without nasal polyps (CRSsNP) that could represent new, up-stream targets for topical DNAzyme treatment.Patients and methodsTwenty-two newly diagnosed CRS patients (14 CRSwNP and 8 CRSsNP) were prospectively biopsied and examined histopathologically. Gene expression levels of T-box transcription factor (T-bet, TBX21), GATA binding protein 3 (GATA3), Retinoic acid-related orphan receptor C (RORC) and Forkhead box P3 (FOXP3) were analyzed by real-time quantitative polymerase chain reaction (RT-qPCR).ResultsEosinophilic CRSwNP was characterized by higher level of GATA3 gene expression compared to noneosinophilic CRSwNP, whereas there was no difference in T-bet, RORC and FOXP3 between eosinophilic and noneosinophilic CRSwNP. In CRSsNP, we found simultaneous upregulation of T-bet, GATA3 and RORC gene expression levels in comparison to CRSwNP; meanwhile, there was no difference in FOXP3 gene expression between CRSwNP and CRSsNP.ConclusionsIn eosinophilic CRSwNP, we confirmed the type 2 inflammation by elevated GATA3 gene expression level. In CRSsNP, we unexpectedly found simultaneous upregulation of T-bet and GATA3 that is currently unexplained; however, it might originate from activated CD8+ cells, abundant in nasal mucosa of CRSsNP patients. The elevated RORC in CRSsNP could be part of homeostatic nasal immune response that might be better preserved in CRSsNP patients compared to CRSwNP patients. Further data on transcription factors expression rates in CRS phenotypes are needed.

Association Between Endoscopic, Radiologic and Patient-reported Chronic Rhinosinusitis with Nasal Polyps

Objectives: Chronic Rhinosinusitis without Nasal Polyps (CRSsNP) and with Nasal Polyps (CRSwNP) affect 10% and 1-4% of the general population respectively. Early detection and treatment of CRSwNP might prevent recalcitrant disease forms. The aim of this prospective controlled study was to evaluate association between endoscopic, radiologic, and self-reported CRSwNP, and a family history in defining CRSwNP. Methods: This study involved 73 CRS patients aged 18 years or over undergoing CRS-surgical consultation at the Tampere University Hospital. Data of sinus Computed Tomography (CT) scans and nasal endoscopy was obtained from patient records. Sixty controls ±allergic rhinitis underwent clinical examination. All subjects filled a questionnaire. Associations were analyzed by Chi square and adjusted regression models. The predictive performance of various parameters was assessed using the Area Under the Receiver Operating Characteristic curve (AUROC). Results: A total of 33% of CRSwNP patients reported not having Nasal Polyps (NPs), while 18% of CRSsNP patients reported having NPs (p &lt; 0.001). Radiologic Nasal Polyp (NP) score differentiated CRSwNP from CRSsNP with an AUROC of 0.95 (95% CI 0.91-1.00). The AUROC value for Lund-Mackay (LM) score was 0.84 (0.75-0.94). Positive family history of NP did not differ significantly between CRS and control groups. Family history of allergy or asthma was given with certainty, whereas CRS patients had uncertainty of reporting NPs in family compared to controls (adjusted OR=6.02, 95% CI 1.98-18.30, p = 0.002). Conclusion: Our findings suggest that in situations where nasal endoscopy cannot be performed, early detection of CRSwNP could result from information obtained from sinus CT scans and patients, in comparison to family history which has lower predictive value. However validation studies with larger sample sizes are still needed.

Exhalation Delivery System with Fluticasone (EDS-FLU) Improves Outcomes in Chronic Rhinosinusitis without Nasal Polyps (CRSsNP) in Patients With or Without Recent Intranasal Steroid Use

Systemic steroids significantly reduce inflammation and symptoms in CRSsNP, but have a poor safety profile. Multiple guidelines recommend topical intranasal steroids (INS), but efficacy is frequently unsatisfactory with currently available steroid nasal sprays (regardless of steroid molecule). EDS-FLU is different because it delivers steroid to sites high/deep in the nose, including where sinus ostia drain/ventilate. We report EDS-FLU treatment outcomes for CRSsNP patients with and without a recent INS. We analyzed CRSsNP data from two, multicenter, single-arm studies (n=898), EXHANCE-3 (12 weeks) and EXHANCE-12 (52 weeks) where patients received EDS-FLU 372μg BID. Multiple objective, subjective, quality of life and safety outcomes were examined. Sinonasal Outcomes Test (SNOT-22), Lund-Kennedy endoscopic edema assessment and Patient Global Impression of Change (PGIC) are reported by prior INS use (+INS=use ≤30 days before randomization or -INS=no use within 30 days). At study end, SNOT-22 improved by 22.1 and 19.5 (+INS) and 28.4 and 18.8 (-INS) in EXHANCE- 3 and -12, respectively. Among patients with nasal edema at baseline, 53% and 58.6% (+INS) and 50% and 41.2% (-INS) achieved resolution of edema by end-of-study in EXHANCE-3 and -12, respectively. In EXHANCE-3/12, 68.1%/74.5% +INS compared with 70.7%/66.7% -INS, respectively, reported being ‘much’ or very much improved on PGIC. EDS-FLU improved objective and subjective measures of disease and quality-of-life similarly in CRSsNP who had or had not recently used currently available INS. These data suggest EDS-FLU could play an important role in patients who do not adequately respond to currently available INS.

Distinct mucosal immunopathologic profiles in atopic and nonatopic chronic rhinosinusitis without nasal polyps in Central China.

The role of atopy to aeroallergens in chronic rhinosinusitis without nasal polyps (CRSsNP) remains unclear. This study aimed to investigate the mucosal immunopathologic characteristics of CRSsNP with and without atopy to inhalant allergens. Thirteen nonatopic CRSsNP patients, 9 atopic CRSsNP patients, and 11 nonatopic control subjects were enrolled in this study. The expression of type 1, 2, and 17 cytokines, growth factors, and chemokines for T cell subsets and granulocytes in sinonasal mucosa was detected using Bio-Plex suspension chip technology or enzyme-linked immunosorbent assay (ELISA). Subjective symptoms were scored on a visual analogue scale (VAS), while disease severity on computed tomography (CT) was graded by the Lund-Mackay CT scoring system. There was no significant difference in VAS and CT scores between atopic and nonatopic CRSsNP. Compared with control, both atopic and nonatopic CRSsNP demonstrated increased interferon γ (IFN-γ) levels in sinonasal mucosa. In contrast, although no difference in interleukin 5 (IL-5), IL-13 and eotaxin-1 expression, or mucosal eosinophil infiltration, was found between the control and whole CRSsNP group, atopic CRSsNP manifested an increased expression of IL-5, IL-13 and eotaxin-1, as well as an enhanced infiltration of mucosal eosinophils in comparison with control and nonatopic CRSsNP. Mucosal eosinophil infiltration correlated with IL-5 and eotaxin-1 expression. No difference in IL-12, IL-4, IL-6, IL-17A, IL-8, myeloperoxidase, "regulated upon activation normal T cell expressed and presumably secreted" (RANTES), or chemokine (C-X-C motif) ligand 10 (CXCL10) protein expression was found among control, atopic CRSsNP, and nonatopic CRSsNP. Atopic and nonatopic CRSsNP have distinct mucosal immunopathologic profiles. CRSsNP is a heterogeneous disorder consisting of multiple groups of biological subtypes, or "endotypes," which may argue for different therapeutic strategies.

Characterization of immunoglobulin E plasma cells that are elevated in the upper airway mucosa of nonatopic patients with chronic rhinosinusitis without nasal polyps.

The immunologic mechanisms driving inflammation in the upper airways of patients with chronic rhinosinusitis (CRS) are poorly understood. Previous studies have shown that B cells and immunoglobulin E (IgE) levels are elevated in the nasal tissue of patients with atopic chronic rhinosinusitis without nasal polyps (CRSsNP). However, less is known regarding B cell subsets and IgE-producing plasmablasts in nonatopic CRSsNP patients. Human blood and ethmoid sinus mucosa samples were analyzed from control (n = 6) and nonatopic CRSsNP (n = 11) patients. Tissue samples were evaluated using high-dimensional flow cytometry. A population of IgE antibody secreting cells is significantly increased in situ within inflamed nasal tissue of nonatopic CRSsNP subjects when compared to control nasal tissue and the circulating peripheral blood (p < 0.05). This IgE plasma cell population displays ∼90% cell surface Ig lambda light chain, is mitotically active (Ki-67(+)), and displays intracellular IgE expression. The predominant B cell population expressing IgE are plasmablasts (CD38(high), CD138(-)) not typically found in the blood or peripheral tissue of these patients. The nasal mucosa from nonatopic CRSsNP patients demonstrate a significant regional spike in resident in situ IgE plasmablast cells not seen in control nasal tissue or peripheral blood from the same patient. The restricted expression of Ig lambda light chain in this mitotically active IgE plasmablast population supports the hypothesis of aberrant B cell proliferation in the context of CRS. These findings suggest the presence of a unique regional immune microenvironment for B cell priming and/or selection within chronically inflamed airway tissues.

Analysis of transforming growth factor β signaling in chronic rhinosinusitis

Background It has been reported that there is a significant difference in the local tissue concentration of transforming growth factor (TGF)-β1 between chronic rhinosinusitis without nasal polyps (CRSsNP) and chronic rhinosinusitis without nasal polyps (CRSwNP) patients. TGF-β has been reported to play an important role in regulating epithelial cell repair in lower airway remodeling and may be a critical factor involved in the remodeling process of chronic rhinosinusitis (CRS). Methods Ethmoidal mucosal samples collected from CRS and healthy control patients were analyzed for TGF-β1, TGF-β receptor I, TGF-β receptor II, Smad3, phospho-Smad3, Smad7, and Smad anchor for receptor activation by Western blotting analysis. The proliferation of sinonasal epithelial cells at baseline and after TGF-β1 and/or EGF stimulation was evaluated by the MTT assay. Results In CRSsNP, TGF-β1, TGF-β receptor I, TGF-β receptor II, and Smad3 protein levels were significantly higher than controls. In CRSwNP, TGF-β1, Smad3, and pSmad3 protein levels were significantly lower than controls. Smad7 protein was significantly higher in CRS than controls. In vitro experiments demonstrated that the baseline proliferation levels of sinonasal epithelial cells were lower in CRS than controls. Conclusions CRSwNP is characterized by a lower level of TGF-signaling compared with the control. In CRSsNP, although the upstream signaling of TGF-β was enhanced, the high Smad7 protein expression may restrain the downstream signaling components (e.g., pSmad3) and the TGF-β antiproliferative effect on sinonasal epithelium. The difference in the local tissue concentration of TGF-β1 between CRSsNP and CRSwNP patients did not result in significant differences in epithelial proliferation.

A prospective multicenter clinical trial of medical and surgical treatment for chronic rhinosinusitis

To demonstrate the clinical outcomes of maximal medical therapy(MMT) and functional endoscopic sinus surgery+ maximal medical therapy (FESS+MMT) for moderate to severe chronic rhinosinusitis without nasal polyps (CRSsNP) in China, to provide clinical evidence for treatment recommendation. A prospective multicenter case control study consisting of 90 strictly selected CRSsNP patients were carried out by ENT Hospital of SUN Yet-sen university and 7 other university affiliated hospitals across China from March 2011 to October 2012. All patients were selected to MMT group or FESS+MMT group followed by 3 months treatment and 6 months follow up. Treatment efficacy evaluation indicators included improvement of visual analogue scale (VAS) score, quality of life, CT score and post-operative nasal endoscopic evaluations. SPSS16.0 software was used to analyze the data. All patients enrolled complied with moderate to severe CRSsNP evaluation criteria. There were no significant differences found in the baseline data between two groups (P > 0.05). (1) At the 3 time points (pre-treatment, 3 months and 6 mongths after treatment) , VAS overall symptom score in MMT group were 6.52 ± 2.61, 2.66 ± 2.10, 2.40 ± 1.56, significant differences were found among them (t value were 2.083 and 2.295, both P < 0.05); in FESS+MMT group the values were 6.99 ± 2.70, 0.95 ± 0.84, 0.60 ± 0.81, significant differences were found among them (t value were 3.582 and 5.196, both P < 0.05); SNOT-20 score in MMT group were 38.61 ± 17.36, 18.59 ± 14.04, 18.40 ± 8.91, significant differences were found among them (t value were 2.737 and 2.657, both P < 0.05); in FESS+MMT group the values were 38.21 ± 19.61, 5.94 ± 5.01, 2.65 ± 2.31, significant differences were found among them (t value were 3.247, 3.319, both P < 0.05). (2) FESS+MMT group relative to the MMT group in VAS overall symptom score and quality of life improvements appeared earlier and were more pronounced. (3) Overall treatment efficacy showed that in MMT group: complete control 14 cases (30.4%), partially control 31 cases (67.4%), uncontrolled 1 cases (2.2%); In FESS+MMT group: complete control 17 cases (38.6%), partially control 26 cases (59.1%), uncontrolled 1 cases (2.3%). (4) Patients' satisfaction survey showed that the number of the patients who were very satisfied with the efficacy in the FESS+MMT group were 2 times higher than the MMT group. (1) For moderate to severe CRSsNP, both MMT and FESS+MMT treatment can effectively control the overall symptoms and classified symptoms, reduce CT scores and significantly improve the quality of life, the ineffective rate is less than 5%. (2) FESS+MMT group in terms of improving symptoms and the onset time are better than MMT group, especially in improving the stuffy nose, head and face fullness, and mental and physical symptoms are better than MMT group. (3) FESS+MMT group showed better results in patient satisfaction survey compared to the MMT group. Therefore for moderate to severe CRSsNP patients, FESS+MMT therapy could be recommended as the preferred treatment.

Reactive Oxygen Species in Chronic Rhinosinusitis and Secondhand Smoke Exposure

Reactive oxygen species (ROS) can potentiate cellular injury and inflammation. This study aimed to (1) assess the presence of reactive oxygen species in the sinus tissue of patients with chronic rhinosinusitis (CRS) and (2) assess the impact of secondhand smoke (SHS) exposure on reactive oxygen species (ROS) production. Retrospective cohort study. Academic medical center. Sinus tissue samples from patients undergoing sinus surgery were analyzed using diaminobenzidine (DAB) staining to assess for ROS. Stained specimens were photographed at random by a blinded photographer and then quantified by 3 blinded graders. The patient's SHS exposure was determined by hair nicotine levels. were compared between non-smoke exposed cohorts and those exposed to secondhand smoke and by diagnosis. Sixty-nine adults undergoing sinus surgery were included in the study. For the non-SHS-exposed cohorts, chronic rhinosinusitis with nasal polyps (CRSwNP) had the highest number of DAB+ cells/high-powered field (hpf) followed by chronic rhinosinusitis without nasal polyps (CRSsNP) and controls. When comparing the control patients to their SHS-exposed counterparts, SHS exposure yielded statistically significantly higher levels of DAB-positive cells/hpf. SHS exposure did not affect DAB staining in CRSsNP or CRSwNP patients. ROS are differentially expressed in various subtypes of CRS. SHS exposure increases ROS in sinus tissue of control patients, but the clinical significance of this is unclear.

Differential expression of Toll-like receptor pathway genes in chronic rhinosinusitis with or without nasal polyps

Conclusions: Our results indicate that chronic rhinosinusitis without nasal polyps (CRSsNP) is characterized by the down-regulation of a Toll-like receptor (TLR)-mediated signaling pathway and such a deficiency within the innate immune system may contribute to the inflammatory process of CRSsNP. In contrast, the inflammatory process found in CRS with nasal polyps (CRSwNP) is characterized by an excessively activated TLR-mediated signaling pathway, which may contribute to the formation of nasal polyps. This study suggests that the pathophysiologic mechanism of CRSsNP and CRSwNP is different. Objective: The nasal mucosa expresses a variety of TLRs that serve in recognizing microorganisms. We investigated the gene expression of a TLR-mediated signaling pathway within two distinctive patient subgroups: CRSwNP and CRSsNP. Methods: Nasal mucosal tissue was obtained from 78 subjects with CRS and 23 control subjects. qRT-PCR and immunohistochemistry were used to investigate tissues for the expression of TLR2, TLR4, TLR7, their downstream signaling components, MyD88 and TRIF, and associated cytokines, interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-4, and IL-10. Results: TLR2, TLR4, TLR7, and IL-4 were significantly increased in CRSwNP patients when compared with either CRSsNP patients or control subjects, whereas TLR4 and TLR7, and downstream MyD88 were significantly decreased in CRSsNP patients versus patients from CRSwNP and control subjects.

Comparison of Efficacy of Mometasone Furoate versus Clarithromycin in the Treatment of Chronic Rhinosinusitis without Nasal Polyps in Chinese Adults

Although both nasal steroids and macrolide antibiotics have been recommended for the treatment of chronic rhinosinusitis without nasal polyps (CRSsNPs), whether there is any difference in their clinical efficacy remains unexplored. In addition, few studies have investigated their clinical efficacy in a Chinese population living in China, who present distinct inflammatory patterns compared with white patients in western countries. This study compares the efficacy of mometasone furoate and clarithromycin treatment in CRSsNP in Chinese adults in a preliminary prospective, open-label, randomized trial. Forty-three CRSsNP patients were randomized to receive mometasone furoate nasal spray at 200 μg (n = 21) or clarithromycin tablet at 250 mg (n = 22) once daily for 12 weeks. Patients were assessed before the treatment and after 4, 8, and 12 weeks after treatment. Subjective symptoms were scored on a visual analog scale. Endoscopy physical findings were scored according to Lanza-Kennedy scoring system. Moreover, smoking and atopic status and coexistence of allergic rhinitis (AR) and asthma were recorded. Before the treatment, no significant difference in symptoms and nasal endoscopic physical findings were found between mometasone furoate and clarithromycin group. As early as 4 weeks after dosing, a significant reduction of total symptom scores, nasal obstruction, headache, rhinorrhea and overall burden scores, and mucosal swelling and nasal discharge scores were observed in both groups. No significant difference in symptom or endoscopic scores was observed between these two groups at any posttreatment observation time point. The coexistence of AR was correlated with lower scores of mucosal edema and nasal secretion in the mometasone furoate group after 12-week treatment. Mometasone furoate and clarithromycin show a comparable clinical effect for CRSsNPs in Chinese adults. Mometasone furoate is more effective in improving edema and secretion for CRSsNP patients with concomitant AR.

Osteomeatal Complex Obstruction is not Associated with Adjacent Sinus Disease in Chronic Rhinosinusitis with Polyps

It is universally accepted that osteomeatal complex (OMC) disease is linked to the subsequent development of chronic rhinosinusitis without nasal polyps (CRSsNPs) via postobstructive mechanisms. The role of OMC obstruction in the pathogenesis of CRSwNPs is less clear. This study was designed to identify if there is an association between OMC obstruction and inflammation of the adjacent sinuses, when patients are stratified by polyp status. This is a follow-up and expanded series of a previous pilot study from our group. CT scans of 144 patients with CRSsNPs and 123 patients with CRS with nasal polyps (CRSwNPs) were evaluated for each sinus and OMC. Patients had no previous surgeries for NPs. CT scans were obtained after a trial of maximal medical therapy. Increasing OMC involvement was associated with increasing Lund-Mackay score for both CRSsNPs and CRSwNPs. In CRSsNP patients, OMC status significantly correlated with adjacent sinus status (p << 0.0001). Meanwhile in CRSwNPs, OMC status does not correlate with adjacent sinus status (p = 0.328). OMC obstruction in the setting of CRSwNP may be a barometer of the overall disease process, but in this scenario, paranasal sinus inflammation can not be classified as a postobstructive phenomenon. These findings question the role of minimally invasive procedures in the management of CRSwNPs.

Evaluation of Long-Term Clarithromycin Treatment in Adult Chinese Patients with Chronic Rhinosinusitis without Nasal Polyps

Objective: To evaluate the efficacy of long-term clarithromycin (CAM) treatment in adult Chinese patients suffering from chronic rhinosinusitis without nasal polyps (CRSnNP). Methods: Thirty-three CRSnNP patients were enrolled and subjected to CAM treatment for 12 weeks (250 mg daily). The total nasal symptom scores (TNSS), nasal resistance and inflammatory mediators including interleukin (IL)-8 and myeloperoxidase (MPO) were evaluated at weeks 0 and 12. Quality of life (QoL) was assessed in all patients by using the Sinonasal Outcome Test 20 and Short Form 36 questionnaires. Results: CAM treatment significantly improved TNSS, nasal resistance and QoL, and it inhibited IL-8 and MPO production in CRSnNP patients (p < 0.05). CAM treatment was more effective for IL-8^high CRSnNP patients than for IL-8^low CRSnNP patients (p < 0.05). Conclusion: Long-term, low-dose CAM treatment is effective and safe for the treatment of CRSnNP in Chinese patients.

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Local IgE production in nonatopic nasal polyposis.

Chronic rhinosinusitis with nasal polyposis (CRSwNP) represents an eosinophilic T-helper 2 inflammatory response. Local production of IgE within nasal polyps (NPs) has been demonstrated, suggesting a role for local IgE in the pathogenesis of NP in atopic CRS patients. We hypothesized that local IgE specific to inhalant allergens may also play a role in the genesis of NP in nonatopic CRS patients. Sinus and inferior turbinate tissue was obtained from nonatopic CRSwNP patients (n = 7), chronic rhinosinusitis without nasal polyps (CRSsNP) patients (n = 15), and healthy controls (n = 9) at the time of surgery. ImmunoCAP analysis (Phadia AB, Portage, MI) for 14 common inhalant antigens was performed on tissue homogenates to determine the antigen-specific response. Total IgE levels did not differ in sinus or turbinate tissue between CRSwNP, CRSsNP, or control patients. CRSwNP sinus tissue had higher levels of specific IgE for cockroach and plantain (p = .03) than other groups and elevated Alternaria IgE levels when compared with CRSsNP sinus tissue (p < .05). No significant differences were found for any of the other antigen-specific IgE levels. Fifty-seven percent of CRSwNP polyps demonstrated a polyclonal IgE response, whereas the other 43% had no demonstrable antigen-specific IgE. In contrast, only 17% of CRSsNP patients demonstrated a polyclonal response within sinus tissue, whereas 67% had no detectable antigen-specific IgE. There was no significant difference in levels of IgE in inferior turbinate tissue between the groups (p > .05). Localized mucosal IgE specific to common inhalant allergens appears to play a role in a subset of CRSwNP patients without evidence of systemic atopy.