Sinonasal Tissue Research Articles

Expression of Pendrin Periostin in Allergic Rhinitis Chronic Rhinosinusitis

Pendrin and periostin are newly identified mediators of the inflammatory process. The expression of these proteins in human sinonasal tissue and their roles in allergic rhinitis and chronic rhinosinusitis remain to be elucidated. This study investigated the expression of pendrin and periostin in sinonasal tissue of patients with allergic rhinitis, chronic rhinosinusitis, and aspirin-induced asthma. Prospective control study conducted at Yamagata University, Japan. Surgical samples were investigated by means of real-time reverse transcription-polymerase chain reaction to evaluate the expression of pendrin and periostin mRNA. The presence and location of pendrin and periostin were determined by immunohistochemistry and Western blotting. Pendrin and periostin production was significantly higher in patients with nasal disorders than in controls. Further significant increases in periostin expression were noted in patients with chronic rhinosinusitis with nasal polyps and in those with aspirin-induced asthma. Immunohistochemistry revealed positive staining for pendrin in epithelial cells and submucosal glands and for periostin in the basement membrane in all three disorders, and additionally for periostin in nasal polyp tissue in chronic rhinosinusitis and aspirin-induced asthma. Production of pendrin and periostin is upregulated in allergic rhinitis, chronic rhinosinusitis with nasal polyps, and aspirin-induced asthma. These findings suggest that pendrin can induce mucus production and that periostin can induce tissue fibrosis and remodeling in the nasal mucosa. Therefore, these mediators may be therapeutic target candidates for allergic rhinitis, chronic rhinosinusitis with nasal polyps, and aspirin-induced asthma.

Acute versus Chronic Invasive Fungal Rhinosinusitis: A Case-Control Study

Introduction Invasive fungal rhinosinusitis is a challenging condition that can be found mostly in immunocompromised patients. Failure to diagnose and treat this entity promptly usually results in rapid progression and death. The purpose of this study was to determine clinical presentation, complication and morbidity in patients with acute versus chronic invasive fungal rhinosinusitis. Setting and design Case-control study at Srinagarind Hospital, Khon Kaen University between January 1998 and May 2008. Methods The patient's data with the diagnosis of invasive fungal rhinosinusitis was included. Demographic data, underlying diseases, presenting symptoms, histologic sinonasal tissue evaluations, sinonasal tissue cultures, CT scan findings, surgical interventions, morbidity, and mortality were collected. Results Sixty-five patients were diagnosed as invasive fungal rhinosinusitis between January 1998 and May 2008. The data of six patients were unable to obtain. Fifty-nine patients were included in this study. Patients with immunocompromised status have significant greater risk for acute than chronic IFS, OR = 6.5 ( P = 0.004). Patients with mucosal necrosis have the significant higher risk for acute IFS, OR = 5.5 ( P = 0.01). There was no significant difference in orbital complications proportion between acute and chronic invasive fungal rhinosinusitis, OR = 2.42 ( P = 0.15). Sinus wall erosion have found significantly in chronic IFS group, OR = 0.24 ( P = 0.02). The average hospital stayed was 30.58 ± 26.43 days with no difference between groups ( P = 0.50). Fourteen patients in acute IFS group were dead (31.11%) while all patients in chronic IFS group were survived. Conclusions Invasive fungal rhinosinusitis continues to present a challenge to the otolaryngologist. Acute IFS was found most commonly in immunocompromised patients. The most consistent finding of acute IFS was mucosal necrosis and black crust/debris. The CT finding of sinus wall erosion may help in diagnosis of chronic IFS.

Cytokine Profiles in Japanese Patients with Chronic Rhinosinusitis

Chronic rhinosinusitis (CRS) is classified in CRS without nasal polyp (CRSsNP) and CRS with nasal polyp (CRSwNP) in western countries, whereas this classification was not common so far in Japan. Studying inflammatory mediators in clearly defined disease subgroups may lead to a better differentiation of chronic sinus diseases. Homogenates of sinonasal mucosal tissue from 14 controls, 9 CRSsNP patients, and 19 CRSwNP patients were assayed for transforming growth factor (TGF)-β, interleukin (IL)-5, immunoglobulin E (IgE), Staphylococcus enterotoxin (SAE)-IgE, eosinophil-catioic protein (ECP), myeloperoxidase (MPO), IL-1β, IL-6, and IL-8 by enzyme-linked immunosorbent assay or UNICAP system. CRSwNP had significantly higher levels of IL-5, IgE, SAE-IgE, and ECP compared with CRSsNP and controls. CRSsNP was characterized by high levels of TGF-β, while CRSwNP showed a Th2 polarization and lower levels of TGF-β. Especially, in CRSwNP samples, 68.4% were eosinophilic (ECP/MPO ratio >1), and 52.6% were SAE-IgE positive. On the other hand, in 9 CRSsNP patients, eosinophilic or SAE-IgE positive sample was only one sample respectively. Additionally, 31.6% of CRSwNP were asthmatic patients, while none of CRSsNP patient was suffering from bronchial asthma. This study is thought to be the first one that showed the cytokine profiles in Japanese CRSs/wNP similar to those of European CRS. Based on mediator profiles, we suggest that CRSsNP and CRSwNP are distinct disease entities within the group of chronic sinus diseases.

RAGE Processing in Chronic Airway Conditions: Involvement of Staphylococcus Aureus and ECP

Background The receptor for advanced glycation end products (RAGE) is a multiligand receptor that exists as a membrane-bound (mRAGE) form and a soluble (sRAGE) form. RAGE is reported to play a role in diverse pathologies including lower airway conditions, but the exact mechanism of action remains poorly understood. In the upper airways, the involvement of RAGE remains completely unexplored. Objective To investigate the involvement of RAGE in the human upper airway conditions chronic rhinosinusitis without nasal polyps (CRSsNP) and chronic rhinosinusitis with nasal polyps (CRSwNP). Methods Protein levels of sRAGE, mRAGE, IL-5, and eosinophil cationic protein (ECP) were quantitatively assessed in inflamed tissue of CRSsNP and CRSwNP patients. Nasal tissue of subjects without disease served as control. Ex vivo human sinonasal tissue stimulation assays were used to assess the effect of Staphylococcus aureus and ECP on sRAGE processing. Results sRAGE protein levels were higher in CRSsNP tissue, whereas mRAGE protein levels were lower than in controls. In CRSwNP patients, both tissue sRAGE and mRAGE protein levels were reduced. Low tissue sRAGE protein concentrations were associated with high IL-5 and ECP protein levels. In vitro , S aureus induced the release of sRAGE from the tissue, while ECP was shown to be implicated in the breakdown of free sRAGE. Conclusions We demonstrate for the first time that RAGE protein is highly expressed in human upper airways under normal physiology and that it is subject to differential processing in CRSsNP and CRSwNP, identifying S aureus and ECP as novel and crucial players in this process.

Human sinonasal explant system for testing cytotoxicity of intranasal agents

Intranasal agents play a critical role in the management of sinonasal disorders. There are ongoing efforts to develop new intranasal medications to combat sinonasal disease. Some intranasal agents, however, can have cytotoxic effects on human sinonasal tissue. In order to facilitate safe drug discovery, we developed a simple and reliable in vitro screening assay using human sinonasal explants to measure the cytotoxic profiles of intranasal agents. We obtained sinonasal tissues from several regions of the nasal cavity from 12 patients undergoing endoscopic sinonasal surgery. These tissues were cultured on polytetrafluoroethylene membrane in serum-free growth medium. We determined the biochemical properties of these explants by measuring extracellular lactate dehydrogenase (LDH) levels and performing histological analyses over a period of 1 to 2 weeks. We then examined the cytotoxic profiles of 13 intranasal agents by measuring extracellular LDH levels using the human sinonasal explant system. Sinonasal explants exhibited a rapid reduction in extracellular LDH levels indicating stabilization in the culture environment within 2 days. Histological analysis showed maintenance of good cellular architecture for up to 2 weeks. The explants displayed intact epithelium and expressed βIII-tubulin and Ki-67. Of the 13 tested intranasal agents, 1% zinc sulfate (ZnSO(4) ), 5% ZnSO(4) , and Zicam application were cytotoxic. Based on the unique biochemical properties of the human nasal explant culture system, we developed a simple and reliable in vitro screening assay to determine the cytotoxic profiles of various intranasal agents by examining extracellular LDH levels and histopathology.

Evidence for intranasal antinuclear autoantibodies in patients with chronic rhinosinusitis with nasal polyps

Chronic rhinosinusitis (CRS) with nasal polyps is an inflammatory condition of the nasal passage and paranasal sinuses characterized by T(H)2-biased inflammation with increased levels of B-cell activating factor of the TNF family (BAFF), B lymphocytes, and immunoglobulins. Because high levels of BAFF are associated with autoimmune diseases, we assessed for evidence of autoimmunity in patients with CRS. The objective of this study was to investigate the presence of autoantibodies in sinonasal tissue from patients with CRS. Standardized nasal tissue specimens were collected from patients with CRS and control subjects and assayed for immunoglobulin production, autoantibody levels, tissue distribution of immunoglobulins, and binding potential of antibodies in nasal tissue with a multiplexed autoantibody microarray, ELISA, and immunofluorescence. Increased levels of several specific autoantibodies were found in nasal polyp tissue in comparison with levels seen in control tissue and inflamed tissue from patients with CRS without nasal polyps (P< .05). In particular, nuclear-targeted autoantibodies, such as anti-dsDNA IgG and IgA antibodies, were found at increased levels in nasal polyps (P< .05) and particularly in nasal polyps from patients requiring revision surgery for recurrence. Direct immunofluorescence staining demonstrated diffuse epithelial and subepithelial deposition of IgG and increased numbers of IgA-secreting plasma cells not seen in control nasal tissue. Autoantibodies, particularly those against nuclear antigens, are present at locally increased levels in nasal polyps. The presence of autoantibodies suggests that the microenvironment of a nasal polyp promotes the expansion of self-reactive B-cell clones. Although the pathogenicity of these antibodies remains to be elucidated, the presence of increased anti-dsDNA antibody levels is associated with a clinically more aggressive form of CRS with nasal polyps requiring repeated surgery.

La maladie de Rosai – Dorfman : enjeux thérapeutiques à propos de 2 observations

Rosai-Dorfman disease (RDD) is a benign lymphoproliferative disorder characterized by cervical lymph node enlargement with a consistent risk of airway compression and esthetic damage. Extranodal localizations are also described. There is no therapeutic consensus for pediatric forms of RDD. Through 2pediatric cases with nodal involvement in 1patient and a sinonasal and soft tissue localization in the other, we focus on the management problems of both nodal and extranodal RDD.

Staphylococcus aureus biofilms

Chronic rhinosinusitis (CRS) patients with biofilms have persistent postoperative symptoms, ongoing mucosal inflammation, and recurrent infections. Recent evidence suggests that biofilms of differing species confer varying disease profiles in CRS patients. We aimed to prospectively investigate the effects of Staphylococcus aureus, Pseudomonas aeruginosa, Haemophilus influenzae, and fungal biofilms on outcomes following endoscopic sinus surgery (ESS). Prospective blinded study. In this prospective blinded study, 39 patients undergoing ESS for CRS assessed their symptoms preoperatively using internationally accepted standardized symptom scoring systems and quality-of-life measures (10-point visual analog scale, Sino-Nasal Outcome Test-20, global severity of CRS). Their sinonasal mucosa was graded (Lund-Kennedy scale) and extent of radiologic disease on computed tomography scans scored (Lund-McKay scale). Random sinonasal tissue samples were assessed for different bacterial species forming biofilms by using fluorescent in-situ hybridization and confocal laser microscopy. For 12 months after surgery, CRS symptoms, quality of life, and objective evidence of persisting disease were assessed by using the preoperative tools. Different bacterial species combinations were found in 30 of 39 patients; 60% of these 30 biofilms were polymicrobial biofilms and 70% had S aureus biofilms. Preoperative nasendoscopy and radiologic disease severity were significantly worse in patients with multiple biofilms (P = .02 and P = .01, respectively), and they had worse postsurgery mucosal outcomes on endoscopy (P = .01) requiring significantly more postoperative visits (P = .04). Those with S aureus biofilms progressed poorly with their symptom scores and quality-of-life outcomes, with significant differences in nasendoscopy scores (P = .007). S. aureus biofilms play a dominant role in negatively affecting outcomes of ESS with persisting postoperative symptoms, ongoing mucosal inflammation, and infections.

Increased expression of the chemokine CCL23 in eosinophilic chronic rhinosinusitis with nasal polyps

Chronic rhinosinusitis (CRS) is a heterogeneous chronic disease characterized by local inflammation of the sinonasal tissues. The pathogenesis of CRS remains controversial, but it has been associated with the accumulation of various immune and inflammatory cells in sinus tissue. The objective of this study was to investigate the expression of the chemokine CCL23, which is known to bind to CCR1 and recruit monocytes, macrophages, and dendritic cells, in patients with CRS. We collected nasal tissue from patients with CRS and control subjects. We assayed mRNA for CCL23 by using real-time PCR and measured CCL23 protein by means of ELISA, immunohistochemistry, and immunofluorescence. CCL23 mRNA levels were significantly increased in nasal polyps (NPs) from patients with CRS with nasal polyps (CRSwNP; P< .05) compared with inferior turbinate and uncinate tissue from patients with CRS or control subjects. CCL23 protein levels were also increased in NPs, although these levels were not statistically significant. Immunohistochemical analysis revealed CCL23 expression in mucosal epithelial cells and inflammatory cells, but accumulation of CCL23(+) inflammatory cells occurred only in NPs. Immunofluorescence data showed CCL23 colocalization with eosinophil cationic protein-positive eosinophils. The concentration of CCL23 in NPs positively correlated with the concentration of eosinophil cationic protein, suggesting that eosinophils are major CCL23-producing cells in NPs. Finally, we found that CCL23 protein levels were significantly increased in NPs from patients with CRSwNP with aspirin sensitivity. Overproduction of CCL23 in NPs might contribute to the pathogenesis of eosinophilic CRSwNP through the recruitment of CCR1(+) inflammatory cells, including monocytes and macrophages, and the amplification of local inflammation.

Measurement of Mycotoxins in Patients with Chronic Rhinosinusitis

Mycotoxins are toxic secondary metabolites produced by a variety of fungi including Aspergillus, Alternaria, and Penicillium species. The presence of mycotoxins in sinonasal tissue and secretions and any possible link to chronic rhinosinusitis (CRS) or other diseases of the head and neck have not been reported. The authors performed an exploratory study to determine the presence and levels of mycotoxins in the sinonasal tissue and secretions of 18 subjects undergoing endoscopic sinus surgery for CRS. Using commercial enzyme-linked immunosorbent assay kits, samples were analyzed for the following mycotoxins: aflatoxin, deoxynivalenol, zearalenone, ochratoxin, and fumonisin. All specimens were negative for aflatoxin, deoxynivalenol, zearalenone, and fumonisin. Four (22%) of 18 specimens were positive for ochratoxin. The clinical significance of this finding remains to be determined.

Topographic gene expression in the sinonasal cavity of patients with chronic sinusitis with polyps.

To determine whether variations in gene expression exist at multiple subsites along the sinonasal tract in patients with chronic sinusitis with polyps and in healthy controls. Prospective, controlled study. Academic medical center. Tissue expression levels of 5 genes, previously found to be characteristic of ethmoid polyps, were measured using real-time quantitative polymerase chain reaction in 100 sinonasal tissue samples. Specimens harvested from 5 regions--the ethmoid sinus, septum, inferior turbinate, middle turbinate, and lateral nasal wall--in 10 patients with chronic sinusitis and ethmoid polyps were compared to tissue from similar regions in 10 control patients without sinusitis. Western blot analysis was performed to validate differential gene expression at the protein level. Gene expression levels of ethmoid polyps differed significantly from those of healthy ethmoid mucosa, as well as tissue from 4 surrounding anatomical sites in both patients with chronic sinusitis and controls. Alterations specific to the polyp tissue included downregulated genes, prolactin-induced protein (fold change 377.2 ± 169.0, P < .0001), and zinc α2-glycoprotein (fold change 72.1 ± 26.5, P < .0001), as well as upregulated genes, met proto-oncogene (fold change 2.5 ± 0.7, P = .029), and periostin (fold change 7.5 ± 3.4, P = .003). No significant differences in gene expression was found for neurabin 2 (fold change 1.0, P = .99). The transcriptional pattern of ethmoid polyps appears to be unique compared with other subsites in the sinonasal cavity of patients with chronic sinusitis. Care must be taken when collecting specimens for molecular studies of the sinonasal tract to differentiate polyp from nonpolyp tissue in chronic sinusitis.

Oral corticosteroid therapy in chronic rhinosinusitis without polyposis: a systematic review

Recognition of inflammation in the pathophysiology of chronic rhinosinusitis (CRS) has caused corticosteroid therapy in CRS to gain favor. A systematic evaluation of oral steroid use in CRS without nasal polyps (CRSsNP) has not been previously conducted. The objective of the study was to assess evidence on oral steroid therapy in CRSsNP, via a systematic literature review. Ovid and PubMed databases were searched for studies on oral steroid therapy in CRSsNP. Manuscripts were reviewed and graded by evidence-based medicine (EBM) level. A total of 33 studies met inclusion criteria; 30 on CRSsNP and 3 on allergic fungal sinusitis (AFS). CRSsNP studies did not include any randomized controlled trial (RCT) or any clinical study employing systemic corticosteroids alone. They included 20 reviews/expert opinions (Level 5) with differing recommendations, and 4 treatment guidelines (Level 4) with weak recommendations on use. Three studies, 2 retrospective (Level 4) and 1 prospective study (Level 3), used oral steroids in combination with antibiotics and nasal steroids. The multidrug regimen improved symptoms, radiologic findings, short-term relapses, nasal endoscopy, and cytokine pattern expression. An experimental study (Level 5) found oral steroids to reverse sinonasal tissue inflammation. Two studies in animal models (Level 5) found no benefit of adding systemic steroids to antibiotics. Three clinical AFS studies, 1 RCT (Level 1) and 2 prospective (Level 3), found oral steroids to benefit postoperative recurrence, endoscopy or computed tomography (CT). No study has employed systemic corticosteroids alone in treating CRSsNP. Evidence supporting oral steroid therapy in CRSsNP is mostly Level 4 or 5; there is lack of any RCT to support use.

The Role of IgE Production in the Pathophysiology of Rhinitis and Rhinosinusitis

A multitude of potential etiologies exist for rhinitis and rhinosinusitis. These sinonasal disorders are heterogeneous entities that are best understood by evaluating the causative factors in each individual patient. More precise diagnosis permits accurate and effective treatment. The association of allergy with sinonasal symptoms has been described for decades; however, the specific relationship between allergy, rhinitis, and rhinosinusitis is complex. Considering allergy in terms of a systemic atopic disorder, along with a local inflammatory process mediated by IgE production in sinonasal tissues, is helpful in unveiling the complex connection between allergy, rhinitis, and rhinosinusitis. This article reviews recent literature regarding local IgE and sinonasal inflammatory conditions.

Measurement of Mycotoxins in Patients with Chronic Rhinosinusitis

Mycotoxins are toxic secondary metabolites produced by a variety of fungi including Aspergillus, Alternaria, and Penicillium species. The presence of mycotoxins in sinonasal tissue and secretions and any possible link to chronic rhinosinusitis (CRS) or other diseases of the head and neck have not been reported. The authors performed an exploratory study to determine the presence and levels of mycotoxins in the sinonasal tissue and secretions of 18 subjects undergoing endoscopic sinus surgery for CRS. Using commercial enzymelinked immunosorbent assay kits, samples were analyzed for the following mycotoxins: aflatoxin, deoxynivalenol, zearalenone, ochratoxin, and fumonisin. All specimens were negative for aflatoxin, deoxynivalenol, zearalenone, and fumonisin. Four (22%) of 18 specimens were positive for ochratoxin. The clinical significance of this finding remains to be determined.

A New Method For Cell Isolation Reveals Elevated Numbers of T and B Lymphocytes In Sinonasal Tissue From Patients With Chronic Rhinosinusitis

A New Method For Cell Isolation Reveals Elevated Numbers of T and B Lymphocytes In Sinonasal Tissue From Patients With Chronic Rhinosinusitis

Down-regulation of annexin A1 and A2 protein expression in intestinal-type sinonasal adenocarcinomas

Annexins are a structurally related family of calcium- and phospholipid-binding proteins that have been implicated in a broad range of molecular and cellular processes. The altered expression of individual annexins has been implicated in tumor development and progression. In this study the expression of annexin A1 and annexin A2 was studied by immunohistochemistry in intestinal-type sinonasal adenocarcinoma using a study set of 57 intestinal-type sinonasal adenocarcinomas represented on an intestinal-type sinonasal adenocarcinoma tissue microarray to assess its potential role in the pathogenesis of these tumors. Our results showed that annexin A1 expression was consistently lost in 52 (91%) intestinal-type sinonasal adenocarcinomas, as compared with the normal epithelium. The expression of annexin A2 was more heterogeneous, and only 19 (33%) cases showed annexin A2 negative expression. Annexin A2 expression was correlated with the histopathological type, being lower in the mucinous type (P = .022). The loss of annexin A2 expression correlated with a reduced survival in univariate analysis (P = .004). However, the impact of annexin A2 expression on patient survival could be an indirect consequence of its association with the histopathological type, since annexin A2 expression was not found to be an independent predictor in multivariate analyses. These results suggest that annexin A1 expression is frequently and commonly lost in intestinal-type sinonasal adenocarcinoma development. Annexin A2 expression is also reduced in intestinal-type sinonasal adenocarcinoma, and this loss of expression is associated to the more aggressive histopathological types.

“How Much Is Enough?” Endonasal Surgery for Olfactory Neuroblastoma

“How Much Is Enough?” Endonasal Surgery for Olfactory Neuroblastoma

The Impact of Biofilms on Outcomes after Endoscopic Sinus Surgery

Although biofilms have been implicated in the pathogenesis of chronic rhinosinusitis (CRS), there is little evidence that their presence or absence has any effect on the outcomes of endoscopic sinus surgery (ESS). The aim of this study was to investigate the effect of biofilms on postsurgical outcomes after ESS. A prospective, blinded study of 51 consecutive patients undergoing ESS for CRS was conducted. Preoperatively, patients assessed their symptoms using internationally accepted standardized symptom scoring systems and quality-of-life (QOL) measures, i.e., the 10-point Visual Analog Scale (VAS), Sino-Nasal-Outcome-Test 20, and global severity of CRS. Their sinonasal mucosa was graded using the Lund-Kennedy scale and the extent of radiological disease on computed tomography scans was scored using the Lund-McKay scale. Random sinonasal tissue samples were assessed for biofilm presence using confocal laser microscopy. At each postoperative visit, patients reassessed their sinus symptoms and completed QOL measures. Postsurgical state of their sinonasal mucosa was graded endoscopically. Bacterial biofilms were found in 36 of 51 (71%) CRS patients. Patients with biofilms presented with significantly worse preoperative radiology and nasendoscopy scores (p = 0.003 and 0.01, respectively). After a median follow-up period of 16 months postsurgery, biofilm-positive patients had statistically worse sinus symptoms (VAS, p = 0.002) and worse nasendoscopy scores (p = 0.026). They also required extra postoperative visits and multiple antibiotic treatments deviating from the standard postoperative care required by biofilm-negative patients. This study has shown that patients with biofilms have more severe disease preoperatively and persistence of postoperative symptoms, ongoing mucosal inflammation, and infections. This study strengthens the evidence for the role that biofilms may play in recalcitrant CRS.

Involvement of HIF1α in mediating VEGF-dependent epithelial cell growth and overexpression in chronic rhinosinusitis with nasal polyposis (91.4)

Abstract We recently reported that VEGF is overexpressed in chronic rhinosinusitis (CRSwNP) and functions to promote nasal epithelial cell hyperplasia, a key feature of sinus polyposis, by regulating autocrine epithelial cell growth. However, the upstream signals regulating this process remain unclear. Hypoxia-inducible factor-1α (HIF1α) is a known regulator of VEGF. Therefore we examined whether HIF1α may regulate VEGF dependent cell growth in nasal epithelial cells. Immunohistochemical analysis of sinonasal surgical tissue showed significantly increased staining for HIF1α in epithelium in polyps of CRSwNP subjects as compared to normal control sinus tissue (p&amp;lt; 0.001, n=5). Culture of human primary nasal epithelial cells (PNEC) from CRSwNP subjects demonstrated abundant expression of HIF1α by realtime PCR (Ct=19+/-2, n=5). To implicate a role of HIF1α in regulation of VEGF in CRSwNP, we performed siRNA knockdown of HIF1α in PNEC from CRSwNP subjects. This resulted in specific inhibition of VEGF mRNA by 77% (p&amp;lt;0.01, n=3). ELISA of PNEC cell supernatants confirmed inhibition of soluble VEGF expression by 47% (p&amp;lt;0.01, n=3). In addition, silencing of HIF1α resulted in 56% reduction of cell growth rate comparable to that of PNECs from normal control subjects, as measured by DNA binding growth assay (p&amp;lt;0.01, n=3). These data suggest that HIF1α regulates VEGF in perpetuating hyperplastic epithelial cell growth observed in CRSwNP.

Evidence for diminished levels of epithelial psoriasin and calprotectin in chronic rhinosinusitis

Decreased epithelial expression of mRNA for S100A7 (psoriasin) and S100A8/A9 (calprotectin) has been reported in patients with chronic rhinosinusitis (CRS). We sought to assess whether the expression of S100 proteins is also altered in the sinonasal cavity of patients with CRS. We determined levels of S100 proteins in nasal lavage fluid and sinonasal tissue extracts from patients with CRS using ELISA and immunohistochemical analysis of nasal polyp tissue from patients with CRS with nasal polyps and uncinate tissue from healthy control subjects, patients with CRSsNP, and patients with CRSwNP. Expression levels of S100 proteins were decreased compared with those seen in control subjects in nasal lavage fluid from both CRS groups (P < .05). Similarly, tissue expression of these proteins assessed by means of immunohistochemistry demonstrated clear reductions, primarily in the epithelial lining. Interestingly, levels of calprotectin were increased in nasal polyp tissue despite lower levels in lavage fluid. Levels of calprotectin in nasal tissues were correlated with levels of neutrophils, as assessed by means of quantification of neutrophil elastase. Several S100 proteins are in the epidermal differentiation complex of genes and have been demonstrated to play a role in maintenance of barrier function and formation of an antimicrobial shield. We demonstrate significantly decreased levels of expression of S100 proteins in the epithelium of patients with CRS, which might lead to diminished innate immune responses and barrier function. Increased levels of calprotectin in nasal polyp tissue might reflect neutrophil recruitment and a compensatory mechanism. Future studies will be important to determine whether reduced levels of S100 proteins lead to decreased antimicrobial responses in the upper airways and sinuses and whether this reduction plays a causative role in CRS pathogenesis and susceptibility to infectious disease.