Little is known regarding the epidemiology of chronic rhinosinusitis (CRS) in racial and ethnic minorities in the United States(US).
Comprehensively evaluate the current prevalence of chronic rhinosinusitis (CRS) across various treatment settings in order to identify possible disparities in health care access and utilization between racial and ethnic populations.
The NHIS, NAMCS, and NHAMCS database registries were extracted to identify the national prevalence of CRS in race/ethnic populations and resource utilization in ambulatory care settings. Systematic literature review identified studies reporting treatment outcomes in minority patients electing endoscopic sinus surgery(ESS). Data was supplemented using a multi-institutional cohort of patients undergoing surgical treatment.
National survey data suggests CRS is a significant health condition for all major race/ethnic groups in the US, accounting for a sizable portion of office, emergency, and outpatient visits. Differences in insurance status, work absenteeism, and resource utilization were found between race/ethnic groups. Despite its prevalence, few published studies include information regarding minority patients with CRS. Most(90%) cohort studies did not provide details of race/ethnicity for ESS outcomes. Prospective cohort analysis demonstrated that minority surgical patients accounted for only 18%, as compared to national census estimates(35%).
Chronic rhinosinusitis is an important health condition for all major race/ethnic groups in the US. Significant differences may exist across racial and ethnic categories with regard to CRS health status and healthcare utilization. Given current demographic shifts in the US, specific attention should be given to understanding CRS within the context of racial and ethnic populations.
Sinusitis; Continental Population Groups; Ethnology; Quality of Life; Outcomes Research; Registries; Database; Prevalence; Centers for Disease Control and Prevention; United States
Little is known regarding the epidemiology of chronic rhinosinusitis (CRS) in racial and ethnic minorities in the United States. This study was designed to comprehensively evaluate the current prevalence of CRS across various treatment settings to identify possible disparities in health care access and use between racial and ethnic populations.
The National Health Interview Survey (NHIS), National Ambulatory Medical Care Survey (NAMCS), and National Hospital Ambulatory Medical Care Survey (NHAMCS) database registries were extracted to identify the national prevalence of CRS in race/ethnic populations and resource use in ambulatory care settings. Systematic literature review identified studies reporting treatment outcomes in minority patients electing endoscopic sinus surgery (ESS). Data were supplemented using a multi-institutional cohort of patients undergoing surgical treatment.
National survey data suggest CRS is a significant health condition for all major race/ethnic groups in the United States, accounting for a sizable portion of office, emergency, and outpatient visits. Differences in insurance status, work absenteeism, and resource use were found between race/ethnic groups. Despite its prevalence, few published studies include information regarding minority patients with CRS. Most (90%) cohort studies did not provide details of race/ethnicity for ESS outcomes. Prospective cohort analysis indicated that minority surgical patients accounted for only 18%, when compared with national census estimates (35%).
CRS is an important health condition for all major race/ethnic groups in the United States. Significant differences may exist across racial and ethnic categories with regard to CRS health status and health care use. Given current demographic shifts in the United States, specific attention should be given to understanding CRS within the context of racial and ethnic populations. Public clinical trial registration (www.clinicaltrials.gov) I.D. No. NCT00799097.
Centers for Disease Control and Prevention; continental population groups; database; ethnology; outcomes research; prevalence; quality of life; registries; sinusitis; United States
Increasing epithelial chloride (Cl−) secretion in the upper airways represents a putative method for promoting MCC through augmentation of airway surface liquid depth. Several naturally occurring flavonoid compounds, including quercetin, have demonstrated the capacity to increase transepithelial Cl− transport. Quercetin exhibits well-known antioxidant and anti-inflammatory activity and is now recognized as a potent activator of the cystic fibrosis transmembrane conductance regulator (CFTR) anion channel activity in a fashion largely independent of cAMP signaling. The present study investigates whether this compound activates Cl− secretion and ciliary beat frequency (CBF) in well characterized culture models of sinonasal epithelium.
CF and non-CF primary human sinonasal (HSNE) and murine nasal septal epithelial (MNSE) cultures were studied for transepithelial ion transport in Ussing chambers under voltage clamp conditions and CBF was performed using pharmacologic manipulation.
Change in short circuit current (ΔISC -expressed as μA/cm2) in response to quercetin were significantly greater than controls in both MNSE (23.23+/−5.44 vs. 2.47 +/− 1.62, p<0.0001) and HSNE (−8.72+/−1.88 vs. −1.88+/−0.66, p<0.01) cultures. CBF was significantly increased in quercetin-treated cells (expressed as fold-change over baseline) in w.t. [1.65+/−0.13 vs. 1.23+/−0.05 (control), p<0.01), but not CFTR−/− (1.65+/−0.29 vs. 1.48+/−0.38, p = 0.23).
Quercetin significantly increased transepithelial Cl− transport and CBF in MNSE and HSNE cultures. Future studies investigating quercetin as a means to promote mucociliary transport in individuals with rhinosinusitis are warranted.
There is a clinical association between asthma and chronic rhinosinusitis (CRS). This study was designed to determine whether severity of coexistent asthma affects the clinical presentation of CRS.
Cross-sectional analysis was performed of prospectively collected data in 187 patients with CRS who were evaluated in a large, tertiary academic nasal and sinus center. Patients were stratified into three groups based on asthma status using National Institutes of Health criteria: (1) nonasthmatic, (2) intermittent/mild asthma, (3) or moderate/severe asthma.
Mean Lund-Mackay scores were 9.7, 11.6, and 15.6, respectively. ANOVA testing with post-hoc Tukey analysis revealed that Lund-MacKay scores were significantly greater in group 3 than either group 1 (p < 0.05) or group 2 (p < 0.01). The prevalence of allergic sensitization was 72.4, 82.8, and 100% in groups 1, 2, and 3, respectively (p < 0.03). The prevalence of nasal polyposis was 31.4% in group 1, 48.3% in group 2, and 94.4% in group 3 (p < 0.0001). No differences were observed regarding demographic factors or the incidence of the triad of aspirin sensitivity, asthma, and nasal polyposis among those with different severities of asthma.
Increasing severity of asthma is associated with advancing radiological severity of CRS and a greater prevalence of allergic sensitization and nasal polyposis. This large adult series shows that asthma severity may have a significant correlation with the presentation of CRS. This study adds to the growing support for the unified airway theory.
Specific antibody deficiency may predispose patients to recurrent respiratory tract infections. There is limited literature assessing specific antibody deficiency in chronic rhinosinusitis (CRS). This study evaluated the role of specific antibody deficiency in patients with CRS who have failed medical therapy.
We performed a retrospective chart review of patients with CRS who underwent functional endoscopic sinus surgery and had prior assessment for humoral immunodeficiency. Each patient’s record was reviewed for serum quantitative immunoglobulin G (IgG) and IgA and anti–Streptococcus pneumoniae antibody titers measured at baseline and 6 weeks postvaccination with the 23-valent unconjugated pneumococcal vaccine. Clinical characteristics, including asthma, atopy, and nasal polyps, were recorded.
Of the 129 CRS patients who met inclusion criteria, 93 (72%) had low baseline antipneumococcal titers. Fifteen (11.6%) patients were diagnosed with specific antibody deficiency based on an inadequate response to the pneumococcal polysaccharide vaccine. The group of patients with specific antibody deficiency had significantly lower serum IgA levels when compared with those patients with normal preimmunization titers (138 ± 67.3 versus 330 ± 356; p < 0.05). Patients with specific antibody deficiency had a significantly lower number of preimmunization protective antipneumococcal titers when compared with vaccine responders (1.41 versus 2.72; p < 0.0005).
This retrospective study indicates that patients with medically refractory CRS may have a high prevalence of low preimmunization antipneumococcal titers and specific antibody deficiency. Furthermore, lower serum IgA levels identified in these specific antibody deficiency patients suggests that a prospective study to further characterize this relationship is warranted.
Nasal airway obstruction (NAO) is a common health condition impacting mood, energy, recreation, sleep, and overall quality of life. Nasal surgery often addresses NAO but the results are sometimes unsatisfactory. Evaluating surgical treatment efficacy could be improved if objective tests were available that correlated with patient-reported measures of symptoms. The goal of this study was to develop methods for comparing nasal resistance computed by computational fluid dynamics (CFD) models with patient-reported symptoms of NAO using early data from a 4-year prospective study.
Computed tomography (CT) scans and patient-reported scores from the Nasal Obstruction Symptom Evaluation (NOSE) scale and a visual analog scale (VAS) measuring unilateral airflow sensation were obtained pre- and postoperatively in two NAO patients showing no significant mucosal asymmetry who were successfully treated with functional nasal surgery, including septoplasty. Pre- and postsurgery CFD models were created from the CT scans. Numerical simulation of steady-state inspiratory airflow was used to calculate bilateral and unilateral CFD-derived nasal resistance (CFD-NR).
In both subjects, NOSE and VAS scores improved after surgery, bilateral CFD-NR decreased, and unilateral CFD-NR decreased on the affected side. In addition, NOSE and VAS scores tracked with unilateral CFD-NR on the affected side.
These preliminary results suggest a possible correlation between unilateral NR and patient-reported symptoms and imply that analysis of unilateral obstruction should focus on the affected side. A formal investigation of unilateral CFD-NR and patient-reported symptoms in a series of NAO patients is needed to determine if these variables are correlated.
Computational fluid dynamics; nasal resistance; nasal surgery; NOSE scale; numerical simulation; patient-reported measures; patient-reported symptoms; septoplasty; unilateral nasal resistance; VAS scale
B-cell responses may play a role in the pathogenesis of nasal polyposis via local IgA and IgE production and activation of eosinophils and mast cells. B-cell attracting chemokines may therefore have relevance in the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNPs)
Polyp and inferior turbinate tissues were obtained from CRSwNPs, CRS without NPs (CRSsNPs), and control patients; ELISA and reverse-transcription polymerase chain reaction were used to detect levels of protein and mRNA for selected B-cell chemokines (B-cell attracting chemokine 1 [CXCL13/BCA-1/BLC]), thymus expressed chemokine (CCL25/TECK), mucosae-associated epithelial chemokine (CCL28/MEC), stromal cell–derived factor-1alpha (CXCL12/SDF-1alpha), and selected chemokine receptor genes (CXCR4, CXCR5, and CXCR7).
BCA-1 and SDF-1alpha protein levels were significantly increased in polyp tissue compared with turbinate tissue from CRSsNP patients and controls (p < 0.05 and p < 0.01, respectively). Differences in TECK and MEC were not significant. For mRNA, expression of BCA-1 was significantly up-regulated in polyp tissue and levels correlated with CD20 mRNA expression. Additionally, significant up-regulation of mRNA for the SDF-1alpha receptors CXCR7 and CXCR4 was detected in polyps, while there was a trend for up-regulation of the BCA-1 receptor CXCR5.
Elevated levels of the BCA-1 and SDF-1alpha and their receptors may account for an increased presence of B cells and their products, contributing to eosinophilic inflammation in patients with CRSwNP.
B-cell recruitment; CCL25/TECK; CCL28/MEC; chemokines; chronic rhinosinusitis; CXCL12/SDF-1alpha; CXCL13/BCA-1; nasal polyposis
Chronic rhinosinusitis (CRS) occurs at high frequency in patients with cystic fibrosis, suggesting that the cystic fibrosis transmembrane conductance regulator (CFTR) chloride (Cl) ion channel might be involved in the development of chronic sinusitis in the general population. CFTR Cl ion transport controls the hydration of mucosal surfaces and promotes effective mucociliary clearance. Altered ion transport, and hence disrupted mucociliary function, could play a role in the pathogenesis of sinus disease. L-ascorbate is a metabolically active component of the nasal and tracheobronchial airway lining fluids and appears to serve as an important biological effector of CFTR-mediated chloride secretion. The purpose of this study was to determine the effects of L-ascorbate on Cl ion transport in freshly excised sinonasal epithelia from normal controls and patients with CRS.
Four different types of sinonasal tissue (normal sinus mucosa, sinus mucosa from CRS, normal nasal mucosa, nasal mucosa from CRS) were obtained during endoscopic sinus surgery and mounted on sliders with open areas of 0.03 to 0.71cm2 between Ussing hemichambers. Short-circuit current (Isc) was continuously recorded, and a serosa-to-mucosa-directed Cl gradient was applied to increase the electrochemical driving force.
L-ascorbate (500µM) stimulated Cl currents (ΔICl, µA/cm2) across sinonasal epithelia from normal and CRS patients. The Cl secretory response to L-ascorbate was effectively blocked by the Cl ion transport inhibitors glibenclamide and bumetanide. A maximal dose of L-ascorbate (at 1 mM) stimulated 53–70% of Cl currents elicited by the cAMP agonist forskolin. CRS sinonasal tissue was characterized by impaired Cl secretory responses to L-ascorbate that were reduced by 33% in sinus epithelial tissue and by 70% in nasal epithelial tissue when compared to normal subjects. In nasal epithelial tissue from normal subjects, Cl secretion was approximately 2-fold increased when compared to sinus epithelial tissue. In contrast, nasal versus sinus epithelial tissue from CRS patients showed no differences.
Topical administration of L-ascorbate to freshly excised sinus and nasal mucosa enhances chloride secretion. Given that decreased CFTR-mediated Cl secretion may contribute to the development of CRS, L-ascorbate may offer potential as a therapeutic agent for the improvement of mucociliary clearance.
ascorbate; vitamin C; chloride channel; CFTR; ion transport; chronic rhinosinusitis; Ussing chamber; epithelium
Histologic inflammation correlates with the degree of baseline olfactory dysfunction in patients with chronic rhinosinusitis (CRS), however factors associated with improvement in olfactory status after endoscopic sinus surgery (ESS) remain elusive.
Our purpose was to compare histopathologic findings in CRS patients with olfactory loss and evaluate whether inflammatory markers can predict long-term olfactory improvement after ESS.
Adult (≥18 years) patients with CRS were prospectively enrolled after electing ESS due to failed medical management. Mucosal tissue specimens were collected at the time of surgery and underwent pathlogic review in a blinded fashion. Subjects completed the 40-item Smell Identification Test (SIT) preoperatively and at least 6 months postoperatively. Multivariate logistic regression was used to identify histologic factors associated with postoperative improvement in SIT score.
The final cohort was comprised of 101 patients with a mean follow-up of 16.7 ± 6.0 months. Mean mucosal eosinophil count was higher in patients with hyposmia and anosmia (p<0.001). Patients with preoperative anosmia were more likely to have greater severity of BM thickening compared to subjects with hyposmia or normosmia (p=0.021). In patients with olfactory dysfunction, 54.7% reported olfactory improvement of at least 4 points on postoperative SIT scores. After controlling for nasal polyposis, histologic variables were not associated with postoperative improvement in olfaction.
Patients with severe olfactory dysfunction were more likely to have mucosal eosinophilia and basement membrane thickening on ethmoid histopathologic examination compared to normosmics. The presence of specific histologic inflammatory findings did not however predict olfactory improvement after surgery.
Chronic rhinosinusitis; olfaction; histology; eosinophils; eosinophilia; pathology; sinusitis; endoscopic sinus surgery; inflammation
Previous outcomes studies of patients with chronic rhinosinusitis (CRS) have mostly excluded subjects with immunodeficiency or autoimmune disease. While expert opinion suggests these patients are often refractory to therapy, outcomes following endoscopic sinus surgery (ESS) are not well delineated.
We evaluated improvement in objective and quality of life (QoL) measures following endoscopic sinus surgery in adult patients treated in the ambulatory setting with immune dysfunction including immunodeficiency and autoimmune diseases.
Patients with CRS associated with immune dysfunction (n=22) were evaluated and matched 1:1 with control subjects from a prospective cohort in a nested case-control design. Preoperative computed tomography (CT) and pre/postoperative endoscopic findings were recorded. Disease-specific QoL instruments (Rhinosinusitis Disability Index (RSDI) and Chronic Sinusitis Survey (CSS)) were administered pre- and postoperatively.
Mean postoperative follow-up was similar for both cases (18.6±6.6 months) and controls (18.4±8.7 months). Preoperative CT and endoscopy scores (i.e. disease severity) were similar in both cases and controls. Post-operative endoscopy scores were significantly improved for both cases (p<0.001) and controls (p=0.012). Both groups had similar preoperative and postoperative scores on the CSS, however control subjects reported significantly worse RSDI baseline scores. Immunodeficiency and autoimmune cases and CRS controls experienced significant improvement in QoL after surgery (p≤0.041).
Immunodeficiency and autoimmune cases, in the ambulatory setting, present with similar severity of disease as compared to controls with CRS. We found similar improvements in both objective and QoL outcomes for case subjects and control subjects, suggesting that patients with immune dysfunction may experience similar benefit from ESS.
immunodeficiency; autoimmune; chronic rhinosinusitis; quality-of-life; outcomes; sinusitis; endoscopic surgery; ambulatory; endoscopy
The greater palatine canal (GPC) local injection is used to limit posterior bleeding during sinus surgery in adults. Given the potential for causing iatrogenic damage to the intraorbital contents, this procedure is not commonly used in the pediatric population. No studies have described the anatomic development of the GPC during facial growth. By using age-stratified radioanatomic analysis, the dimensions of the GPC and the clinical implications are described for pediatric patients. An age-stratified radioanatomic study was performed.
High-resolution computed tomography measurements included the thickness of the mucosal plane overlying the GPC, the length of the GPC, and the distance between the base of the pterygopalatine fossa (PPF) and the orbital floor. Mean distance and standard deviation were calculated for each age cohort and compared using the one-way ANOVA test.
The GPC length correlated directly with patient age. It varied from 9.14 ± 0.11 mm in the youngest age group (<2 years) to 19.36 ± 2.76 mm in adults (18–64 years). The height of the orbit relative to the hard palate approximated the adult dimensions described in the literature by 12–13 years (49.58 ± 1.72 mm).
These radioanatomic results suggest that the GPC injection described for adult patients may be safely administered to selected pediatric patients. For patients >12 years old, we recommend bending the needle 45° and inserting it 25 mm. For patients 6–12 years old, the needle should be inserted 20 mm to enter into the PPF. In patients <6 years old, the needle may safely be placed 12 mm into the GPC. Each of these descriptions is based on the minimal distance required to effectively access the PPF but with maximal safety in regard to the orbit. Further clinical correlation of these findings is necessary through future investigation.
One major function of the airways is to inactivate and remove pathogens from inhaled air and thereby prevent infection. The secretion of protons by the airway epithelium presents an integral part of the innate host defense mechanism and involves the proton channel (hydrogen voltage-gated channel 1, HVCN1). The purpose of this study was to measure the effect of airway inflammation on acid secretion in asthmatic and non-asthmatic patients with chronic rhinosinusitis by using freshly excised human sinonasal tissue.
Nasal or sinus mucosa from subjects with three different conditions (normal, chronic rhinosinusitis (CRS), CRS with asthma) was harvested during sinus surgery. The rate of proton (H+) secretion by each tissue was measured using the pH-stat titration technique in an Ussing type chamber. The contribution of the HVCN1 proton channel to acid secretion was identified using ZnCl2 as a blocker.
Nasal epithelia isolated from subjects with a diagnosis of both chronic rhinosinusitis (CRS) and asthma had a mucosal equilibrium pH = 6.95 (n = 5), which was significantly lower than the equilibrium pH found in nasal epithelia from normal (n = 5, 7.35 ± 0.21) or from subjects with CRS without asthma (n = 5, 7.33 ± 0.15). When alkalinizing the mucosal pH to 8.0, nasal epithelia from CRS with asthma (n = 5) secreted H+ at a rate of 135.1±46.2 nmol·min−1·cm−2. This rate was significantly higher compared to normal (73.3±39.3 nmol·min−1·cm−2, n = 8) or CRS without asthma (51.4±27.7 nmol·min−1·cm−2, n = 7). Mucosal addition of ZnCl2 blocked H+ secretion by 70% in normal, 52.6% in CRS without asthma, and by 50.8% in CRS with asthma.
Freshly excised human nasal and sinus epithelia secrete acid across the apical cell membrane. Sinonasal tissue isolated from asthmatic CRS patients showed lower mucosal pH values and higher rates of H+ secretion than CRS and normal subjects, and ~50–70% of acid secretion was mediated by the HVCN1 H+ channel in all groups. Excessive acid secretion might contribute to epithelial injury in CRS patients with asthma.
proton secretion; pH stat; Ussing chamber; mucosa; asthma; sinusitis; airway surface liquid (ASL); acid
Airway secretions possess intrinsic antimicrobial properties that contribute to the innate host defense of the respiratory tract. These microbicidal capabilities have largely been attributed to the presence of antibacterial polypeptides. However, recent investigation has demonstrated that host-derived lipids including cholesteryl esters also exhibit antimicrobial properties. The purpose of this study was to determine whether sinus secretions contain such antimicrobial lipids and to compare the lipid composition in patients with and without chronic rhinosinusitis (CRS).
Maxillary sinus fluid was obtained via antral lavage from subjects with (7) and without (9) a history of CRS. Following specimen collection, total lipid was extracted according to Bligh & Dyer and lipid profiles were obtained by reverse phase HPLC on an amide-embedded C18 column. In addition, the neutrophil specific antimicrobial peptides HNP1-3 were quantified by immunoblotting.
Lipids were identified in the maxillary sinus secretions of patients with and without CRS including cholesteryl esters. However, levels of lipid composition differed between the two groups with CRS patients exhibiting greater amounts of all classes of lipids; reaching over 10-fold higher concentration when compared to nonCRS patients. This increase was independent of HNP1-3 content.
Sinus secretions of patients with CRS appear to demonstrate elevated levels of antimicrobial lipids compared to controls independent from neutrophil influx. This upregulation suggests that host-derived lipids act as mediators of mucosal immunity in CRS. Further study is necessary to determine if such antimicrobial lipids function alone or synergistically with antibacterial peptides in conferring such inherent microbicidal properties.
Chronic rhinosinusitis (CRS) is among the most common causes of olfactory loss. The loss of the sense of smell is thought to result from structural and functional changes occurring in the olfactory epithelium caused by inflammation. However, the cellular mechanisms underlying CRS-associated olfactory loss remain incompletely understood.
Transgenic mice expressing TNF-alpha specifically within the olfactory epithelium were used as a model for CRS-associated olfactory loss. TNF-alpha expression was induced over different time intervals, and olfactory epithelial tissue was assessed for the expression of neuronal markers by laser scanning confocal microscopy and Western blot.
TNF-alpha expression results in an inflammatory infiltrate in the olfactory epithelium, thinning of the olfactory neuron layer, and a progressive loss of olfactory function. Reduced expression of markers for neurons and mature olfactory neurons (neural cell adhesion molecule [NCAM] and olfactory marker protein [OMP], respectively) was observed in the neuroepithelium and in the subepithelial axon bundles. Expression of growth-associated protein (GAP) 43, a marker for immature neurons, was also reduced. These alterations were reversed when TNF-alpha expression was discontinued.
TNF-alpha expression in a transgenic model of CRS-associated olfactory loss results in progressive loss of olfactory neurons. Decreased GAP-43 expression suggests that TNF-alpha–associated inflammation inhibits differentiation of progenitor cells into immature olfactory neurons. Therefore, reduced regeneration of olfactory neurons may be an important mechanism underlying olfactory loss in CRS, in addition to neuronal loss or apoptosis. This mouse model represents a potential tool in the development of novel therapeutic strategies for the prevention of olfactory neuron loss in CRS.
GAP-43; inflammation; markers; NCAM; olfaction; OMP; rhinosinusitis; TNF; transgenic
Olfactory loss is a debilitating symptom of chronic rhinosinusitis (CRS). Although olfactory sensory neurons (OSNs) are normally regenerated constantly in the olfactory epithelium (OE), a transgenic model of CRS-associated olfactory loss (inducible olfactory inflammation [IOI] mouse) shows that inflammation causes widespread OSN loss without progenitor cell proliferation. In this study, we further examine whether the inflammatory cytokine tumor necrosis factor alpha (TNF-alpha) inhibits olfactory regeneration.
IOI mice underwent either unilateral bulbectomy or sham surgery and then were induced to express TNF-alpha in the OE for 1 week. After death, the mice were assessed histologically and with bromodeoxyuridine staining to determine the effect of TNF-alpha on olfactory regeneration.
In the absence of TNF-alpha, bulbectomy was associated with death of OSNs, followed by robust proliferation of neural progenitors and regrowth of the OE. At 12 days postbulbectomy, OE thickness on the operated side had recovered to >80% of the unoperated side. In mice in which TNF-alpha expression was induced, significantly reduced proliferation was observed, associated with failure of normal reconstitution of OE thickness.
The mechanism of olfactory dysfunction in CRS remains incompletely understood. Previous studies with a transgenic mouse model suggested that inflammation inhibits progenitor cell proliferation and olfactory regeneration. Here, the role of the CRS-associated cytokine TNF-alpha was investigated using surgical ablation of the olfactory bulb to stimulate synchronous OSN turnover. We find that TNF-alpha expression prevents normal OE recovery, supporting the role of suppressed olfactory regeneration in the pathophysiology of CRS-associated olfactory loss.
Sinonasal epithelial cells participate in host defense by initiating innate immune mechanisms against potential pathogens. Antimicrobial innate mechanisms have been shown to involve Th1-like inflammatory responses. Although epithelial cells can also be induced by Th2 cytokines to express proeosinophilic mediators, no environmental agents have been identified that promote this effect.
Human sinonasal epithelial cells from patients with chronic rhinosinusitis with nasal polyps (CRSwNPs) and controls were harvested and grown in primary culture. Cell cultures were exposed to a range of concentrations of chitin for 24 hours, and mRNA for acidic mammalian chitinase (AMCase), eotaxin-3, and thymic stromal-derived lymphopoietin (TSLP) were assessed. Other cultures were exposed to interleukin 4 (IL- 4) alone and in combination with dust-mite antigen (DMA) for 36 hours. Extracted mRNA and cell culture supernatant were analyzed for expression of AMCase and eotaxin-3.
Chitin induced a dose-dependent expression of AMCase and eotaxin-3 mRNA but not TSLP. Patients with recalcitrant CRSwNPs showed lower baseline expression of AMCase when compared with treatment-responsive CRSwNP and less induction of AMCase expression by chitin. DMA did not directly induce expression of AMCase or eotaxin-3. Expression of eotaxin-3 was stimulated by IL-4 and further enhanced with the addition of DMA. Levels of AMCase were not significantly affected by either IL-4 or DMA exposure. In some cases, the combination of IL-4 and DMA was able to induce AMCase expression in cell cultures not producing AMCase at baseline.
The abundant biopolymer chitin appears to be recognized by a yet uncharacterized receptor on sinonasal epithelial cells. Chitin stimulates production of AMCase and eotaxin-3, two pro-Th2 effector proteins. This finding suggests the existence of a novel innate immune pathway for local defense against chitin-containing organisms in the sinonasal tract. Dysregulation of this function could precipitate or exacerbate Th2 inflammation, potentially acting as an underlying factor in recalcitrant CRSwNP.
Acidic mammalian chitinase; cell culture; chitin; eosinophils; epithelial cell; rhinitis; rhinosinusitis; sinonasal; Th2
Abnormalities in host mucosal immunity exist in chronic rhinosinusitis with nasal polyps (CRSwNPs), but it is unclear whether this is a cause or an effect of the eosinophilic inflammation and frequent microbial colonization that characterizes the disease. Sinonasal epithelial cells (SNECs) are critical participants in healthy antimicrobial innate immune defense. They also can promote Th2 inflammation with various mediators, including interleukin (IL)-33, which induces T helper cells to produce Th2 cytokines.
CRSwNP SNECs were obtained during sinus surgery and stored. Patients were subsequently classified as either treatment responsive or treatment recalcitrant, based on long-term outcomes of medical and surgical therapy. Epithelial cells from these patients were grown in air–liquid interface (ALI) culture and treated with IL-13, as well as the bacteria-associated molecule, CpG. Expression of IL-33 mRNA was determined by real-time polymerase chain reaction.
Recalcitrant CRSwNP epithelial cells had increased baseline expression of IL-33 compared with responsive CRSwNPs, which was further increased by 24-hour exposure to CpG. Treatment-responsive epithelial cells were not induced by CpG to express IL-33. Prolonged treatment with IL-13 during differentiation at the ALI diminished the baseline expression of IL-33 and prevented the subsequent induction of IL-33 by CpG.
Mucosal innate immunity likely plays an important role in CRSwNP pathogenesis. A definitive link between infectious triggers and the development of Th2 inflammation has been elusive. We have found constitutive IL-33 expression by SNECs in recalcitrant CRSwNPs, which can be further induced by a bacteria-associated molecular pattern. Dysregulated epithelial cell immune interactions between host and environment may contribute to Th2 inflammation in CRSwNPs.
Chronic; cytokines; IL-33; nasal polyps; polyps; rhinosinusitis; Th2
Impaired olfactory function leads to a decrease in the quality of life for many patients. Surgical treatment options are limited, especially for those suffering from hyposmia or anosmia following post-traumatic injury to the olfactory nerves. Stem cells located in the olfactory epithelium have the capacity to grow new neurons, making the olfactory epithelium an ideal candidate for restorative tissue grafting.
To determine if strips of olfactory epithelium survive transplantation directly to the olfactory bulb.
Transgenic mice, expressing a green fluorescent protein (GFP), were used to obtain the donor graft tissue. Strips of olfactory epithelium from GFP donor mice were transplanted directly to sites in the olfactory bulb and cerebral cortex (control sites) of wild type mice. Graft survival rates at 30 days were determined for transplant sites in the olfactory bulb and cerebral cortex.
Strips of olfactory epithelium from transgenic mice survived transplantation to the olfactory bulb and continued to express the GFP marker protein. The 30 day survival rate in the olfactory bulb (83%, 5 out of 6 grafts) was the same as in the cerebral cortex (10 out of 12 grafts). The morphology of the graft revealed characteristics found in normal olfactory epithelium
We demonstrated that strips of olfactory epithelium can be successfully grafted to both the olfactory bulb and cerebral cortex. Grafts of the olfactory epithelium, if strategically positioned on the ventral surface of the bulb and given access to the nasal cavity, could provide the basis for new surgical treatments to restore olfactory function.
Olfactory epithelium; Grafts; Anosmia; Hyposmia; Olfactory bulb; GFP; Stem cells; Olfactory impairment; Surgical treatment
Olfactory dysfunction is deemed to be a significant contributor to poor quality of life (QOL). However, little is known about the relationship of olfactory testing to other measures of disease burden in patients with chronic rhinosinusitis (CRS).
In this study, we examine the relationship of olfactory function to computed tomography (CT) scores, endoscopy scores, and QOL measures in patients with CRS.
A multi-institutional, cross-sectional analysis of 367 patients was performed. Several objective measures were collected: the Smell Identification Test, Lund-MacKay CT score, Lund-Kennedy endoscopy score, two validated disease-specific QOL instruments, the Rhinosinusitis Disability Index and the Chronic Sinusitis Survey, and a general health-related QOL instrument, the Medical Short Form-36. Analysis of variance was performed. Correlation coefficients were calculated.
Patients with olfactory dysfunction had significantly worse mean endoscopy scores (normosmics: 4.16 (± 3.97); hyposmics: 6.26 (± 4.21); anosmics: 9.61 (± 4.48); p<0.001) and significantly worse CT scores (normosmics: 9.11 (± 5.40); hyposmics: 11.16 (± 5.96); anosmics: 17.62 (± 5.37); p<0.001). Endoscopy scores were moderately correlated with olfactory scores (r= -0.46, 95% CI -0.38, -0.54; p<0.001). CT scores were moderately correlated with olfactory scores (r= -0.53, 95% CI -0.45, -0.60; p<0.001). Olfactory function was not correlated with disease-specific or general health-related QOL measures.
Although previous studies have suggested that olfactory impairment is associated with poor QOL, this study found no such correlation. In contrast, olfaction scores correlated well with other objective measures of CRS, namely endoscopy and CT scores.
chronic rhinosinusitis; olfaction disorders; sinusitis; smell; computed tomography; endoscopy; quality of life; anosmia