Chronic Rhinosinusitis Subtypes Research Articles

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.

Increased exhaled nitric oxide and its oxidation metabolism in eosinophilic chronic rhinosinusitis

Monitoring of fractional concentrations of exhaled nitric oxide (FeNO) has become a reliable marker of inflammation in human nose and paranasal sinuses. However, it is still unknown to what extent nasal NO levels contribute to the pathology of chronic rhinosinusitis (CRS). In the present study, we aimed to examine FeNO levels and the underlying mechanism of NO production and metabolism in patients with eosinophilic chronic rhinosinusitis (ECRS) and non-ECRS. Thirty-three untreated ECRS patients, 16 non-ECRS patients, and 38 normal subjects were enrolled in this cross-sectional study of FeNO levels. Oral and nasal FeNO levels were measured before treatment using an electrochemical NO analyzer (NObreath(®)) with a nose adaptor. The mRNA expression of three nitric oxide synthase (NOS) isoforms, interleukin-5 (IL-5), and transforming growth factor-beta (TGF-β) in the ethmoid sinus mucosa and nasal polyps were analyzed by real-time PCR. Immunohistological localization of inducible NOS (iNOS) and nitrotyrosine (NT), a marker for oxidized NO metabolites, was also examined. ECRS patients showed significantly higher oral FeNO levels compared to non-ECRS patients and normal subjects (mean values, 47.6, 13.5, and 15.3ppb, respectively). Nasal FeNO levels of the non-ECRS patients (30.5ppb) were significantly lower than those of the ECRS patients (53.9ppb) and normal subjects (45.5ppb). Positive correlations existed between the blood eosinophil percentage and FeNO levels in ECRS patients. Histologically, ECRS patients showed higher eosinophil accumulation in the ethmoid mucosa than non-ECRS patients (103.1 vs. 16.3cells/HPF). Real-time PCR analysis showed significant upregulation of iNOS and IL-5 mRNA expression in the ethmoid mucosa of the ECRS patients compared to those of non-ECRS patients. Positive iNOS immunoreactivity was observed in ciliated epithelial cells, submucosal glands and associated inflammatory cells in both groups. NT immunoreactivity was detected in the epithelium and around inflammatory cells. Intense NT staining was co-localized with eosinophil accumulation and ECRS patients showed significantly higher rates of NT-positive cells than non-ECRS patients. A combination of oral and nasal FeNO measurement is a valid marker for the classification and definition of different CRS subtypes in Japan. Higher levels of oral and nasal FeNO in ECRS patients may reflect the persistence of eosinophilic inflammation in sinus mucosa with concomitant iNOS upregulation and accompanying deposition of oxidized NO metabolites.

Epithelial permeability alterations in an in vitro air–liquid interface model of allergic fungal rhinosinusitis

Chronic rhinosinusitis (CRS) is an inflammatory upper-airway disease with numerous etiologies. Patients with a characteristic subtype of CRS, allergic fungal rhinosinusitis (AFRS), display increased expression of T helper 2 (Th2) cytokines and antigen-specific immunoglobulin E (IgE). Various sinonasal inflammatory conditions are associated with alterations in epithelial barrier function. The aim of this study was to compare epithelial permeability and intercellular junctional protein expression among cultured primary sinonasal cells from AFRS patients vs noninflammatory controls. Epithelial cells isolated from paranasal sinus mucosa of AFRS and noninflammatory control patients were grown to confluence on permeable supports and transitioned to air-liquid interface (ALI). Transepithelial resistance (TER) was measured with a horizontal Ussing chamber to characterize the functional permeability of each cell type. After TER recordings were complete, a panel of intercellular junctional proteins was assessed by Western blot and immunofluorescence labeling followed by confocal microscopy. After 12 samples were measured from each group, we observed a 41% mean decrease in TER in AFRS cells (296 ± 89 ohms × cm(2) ) compared to control (503 ± 134 ohms × cm(2) , p = 0.006). TER deficits observed in AFRS were associated with decreased expression of the tight junction proteins occludin and junctional adhesion molecule-A (JAM-A), and increased expression of a leaky tight junction protein claudin-2. Cultured sinonasal epithelium from AFRS patients displayed increased epithelial permeability and altered expression of intercellular junctional proteins. Given that these cells were not incubated with inflammatory cytokines in vitro, the cultured AFRS epithelial alterations may represent a retained modification in protein expression from the in vivo phenotype.

Oral corticosteroids in the management of adult chronic rhinosinusitis with and without nasal polyps: an evidence‐based review with recommendations

Oral steroids are commonly used in the management of chronic rhinosinusitis (CRS) with and without nasal polyps (CRSwNP and CRSsNP, respectively). Past reports have included evaluation of the evidence for the use of oral steroids in CRS subtypes. However, a review with evidence-based recommendations for all CRS subtypes has never been performed. The purpose of this article is to provide a comprehensive, evidence-based approach for the utilization of oral steroids in the management of CRS. A systematic review of the literature was performed following recommendations of the Clinical Practice Guideline Manual, Conference on Guideline Standardization, and Appraisal of Guidelines and Research Evaluation. Inclusion criteria were: adult population ≥ 18 years old; CRS; oral steroids as the treatment group; and clearly defined primary clinical end-point. This review identified and evaluated the literature on the use of oral steroids for CRSwNP, CRSsNP, allergic fungal sinusitis (AFS), and the use of oral steroids in the perioperative period in these patients. Recommendations based on evidence, benefit/harm assessment, and value judgments are made. Oral steroids are strongly recommended for short-term management of CRSwNP. Oral steroids are also recommended for management of AFS. Oral steroid use in CRSsNP is optional due to insufficient strong evidence. Oral steroids are also strongly recommended in the perioperative period for CRSwNP and AFS. There is no recommendation for oral steroids use in the perioperative period in patients with CRSsNP. The risks of oral steroids are rare, but significant adverse effects must be considered.

Macrophage Quantification in Chronic Rhinosinusitis

Objective: Macrophages are major producers of inflammatory cytokines; however, their role in chronic rhinosinusitis (CRS) has not been clearly defined. The aim of this study was to quantify monocytes and macrophages in sinonasal tissue of patients with various subtypes of CRS. Method: Human sinonasal tissue was taken from patients with CRS with nasal polyposis (CRSwNP), CRS without nasal polyposis (CRSsNP), and allergic fungal rhinosinusitis (AFRS). Control tissue was taken from patients without evidence of inflammatory sinus disease. Samples were immunhisotychemically stained for macrophage/monocyte markers Mac387, CD68, and PM-2K. Results: AFRS patients had approximately 4 times as many Mac387 and CD68 staining cells as CRSsNP and control patients ( P < .05). CRSwNP patients had approximately 2.5 times as many Mac387 cells and 3 times as many CD68 cells as CRSsNP and control patients ( P < .05). There were trends toward increased numbers of cells staining positively for PM-2K in tissue samples of AFRS and CRSwNP, and increased staining of CD68 and PM-2K in atopic CRWwNP patients; however, this did not reach statistical significance. Conclusion: Macrophages are increased in CSRwNP and AFRS patients and may contribute to the immunopathology of CRS.

Age-related differences in the pathogenesis of chronic rhinosinusitis

Age-related differences in the pathogenesis of chronic rhinosinusitis

Chronic Rhinosinusitis with Nasal Polyps: A Proteomic Analysis

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a severe subtype of chronic rhinosinusitis that can affect patients despite medical and surgical interventions. The purpose of this study was to utilize the techniques of proteomics to investigate differences in protein abundance within the sinonasal mucosa of patients with CRSwNP compared to healthy controls. In a case-control study at a tertiary-care academic medical center, sinonasal mucosa was harvested from 3 patients with CRSwNP and 3 control patients undergoing transsphenoidal excision of pituitary tumors. Two-dimensional gel electrophoresis was used to identify proteins with elevated or reduced abundance in CRSwNP patients compared to controls. The proteins showing the greatest abundance differences were characterized by mass spectrometry. More than 300 differentially abundant proteins (p < or = 0.05) were identified. Many of these protein species were involved in the host inflammatory response. Proteins up-regulated in CRSwNP patients included eosinophil lysophospholipase by a ratio (R) of 18.13, RHO-GDP dissociation inhibitor 2 (R = 2.80), and apolipoprotein A-1 (R = 1.73). Down-regulated proteins in CRSwNP patients included catalase (R = -5.87), annexin A1 (R = -6.27), and keratin II-8 (R = -6.73). A detailed analysis of additional protein species is outlined. The proteomic approach allows detection of significant differences in protein abundance in CRSwNP and provides unique insight into the pathophysiology of this common disease.

Pathophysiology of Chronic Rhinosinusitis with Nasal Polyp

Chronic rhinosinusitis (CRS) is a common inflammatory condition of the paranasal sinuses and nasal passages. CRS with nasal polyp (CRSwNP) is a subtype of CRS, and the pathogenesis of CRSwNP remains largely unclear. This article reviews the literature regarding the pathophysiology of CRSwNP. Evidence suggests that altered innate immunity, adaptive immunity, tissue remodeling, and/or effects of microorganisms may play a role in the development of CRSwNP. Aberrant arachidonic acid metabolism may also contribute to the pathogenesis of CRSwNP in patients with aspirin-exacerbated respiratory disease. There have been significant advances in the understanding pathophysiology of CRSwNP. Additional research is needed to elucidate these mechanisms and to determine their relative importance in the pathogenesis of CRSwNP.

Increased presence of dendritic cells and dendritic cell chemokines in the sinus mucosa of chronic rhinosinusitis with nasal polyps and allergic fungal rhinosinusitis

The aim of this study was to determine if there is a link between local dendritic cells (DCs) and various subtypes of chronic rhinosinusitis (CRS): CRS with nasal polyposis (CRSwNP), CRS without nasal polyposis (CRSsNP), and allergic fungal rhinosinusitis (AFRS). Once DC presence was established we considered possible mechanisms for DC recruitment to the sinuses. Biopsy specimens were taken from the osteomeatal complex during endoscopic sinus surgery in patients with AFRS (n ≥ 5), CRSsNP (n ≥ 6), and CRSwNP (n ≥ 6). Control patients (n ≥ 5) were undergoing either tumor resection or repair of cerebrospinal fluid leak and had no radiographic or endoscopic evidence of inflammatory sinus disease. Tissue samples were immunohistochemically stained for DC marker, CD209, costimulatory molecules, CD80 and CD86, and chemokine receptors, CCR2 and CCR6. Sinus tissue lysates were examined for levels of the DC chemoattractants, chemokine ligand 2 (CCL2) and CCL20. Analysis of sinus tissue from AFRS and CRSwNP revealed elevated numbers of cells staining positive for CD209, CD80, CD86, CCR2, and CCR6 compared to controls. CCL2 and CCL20 levels were elevated in AFRS and CRSwNP compared to controls, similar to increases in their receptors, CCR2 and CCR6, respectively. While there were trends toward increases in all markers in CRSsNP, none was statistically significant compared to control. AFRS and CRSwNP have increased numbers of DCs displaying costimulatory molecules, DC chemoattractants, and their corresponding receptors in the sinus mucosa compared to controls. These differences represent a possible mechanism for increased numbers of DCs with a T helper 2 (Th2)-skewed profile seen in CRSwNP and AFRS.

Proteomics Blood Testing to Distinguish Chronic Rhinosinusitis Subtypes

To evaluate the potential of surface enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) proteomic profiling of serum samples to distinguish chronic rhinosinusitis subtypes. Translational study of serum samples from prospectively enrolled patients undergoing sinus surgery. Patients undergoing endoscopic sinus surgery for chronic rhinosinusitis with nasal polyposis were prospectively enrolled in an ongoing, institutional review board approved proteomics study. SELDI-TOF-MS was performed on 42 serum samples in patients with chronic rhinosinusitis with nasal polyposis (15 patients diagnosed with allergic fungal rhinosinusitis, 10 patients with Samter's triad, and 17 with chronic rhinosinusitis with nasal polyposis). Classification tree analysis on protein spectra developed from peaks detected in the 0 to 100 kD range was performed to identify disease subtypes. SELDI-TOF-MS correctly identified patients with allergic fungal rhinosinusitis from serum samples with 84% sensitivity and 90% specificity, and correctly identified patients with Samter's triad with 88% sensitivity and 88% specificity in two subtype comparison groups. SELDI-TOF-MS correctly identified patients with allergic fungal rhinosinusitis with 76% sensitivity and 82% specificity, and correctly identified patients with Samter's triad with 80% sensitivity and 90% specificity in three subtype comparison groups. The study provides molecular evidence that allergic fungal rhinosinusitis is a discrete subtype of chronic rhinosinusitis. SELDI-TOF-MS is a promising technology that could lead to the development of a rapid blood test, to identify severe chronic rhinosinusitis subtypes. Further investigation into the utility of this technology is warranted.