American Journal of Rhinology & Allergy

Benzalkonium chloride (BKC) has been considered an innocuous preservative for prescription drugs.

We performed a double-blind, placebo-controlled, randomized, crossover, single-center trial with a 3-week washout period in 43 healthy volunteers comparing the effect of 3-week use of saline nasal spray containing BKC 0.01% to preservative-free saline t.i.d. on nasal mucociliary clearance rate. Evaluations were done at the beginning and the end of each period by γ-scintigraphy with technetium^99m-labeled strontium.

Nasal mucociliary clearance rate was significantly impaired by BKC with a difference of 1.23 mm·min^-1 (p < 0.01) between periods.

BKC in the concentration used in nasal preparations impaired mucociliary clearance in healthy individuals after 3 weeks of use. Presently, when preservative-free alternatives are available, BKC could be a risk without benefit.

In this study we aimed to investigate the effect of triamcinolone acetonide aqueous (TAA) intranasal spray that was used for 2 months to treat allergic rhinitis (AR) on the nasal carriage of Staphylococcus aureus (NCSA).

A total of 125 adult AR patients (study group) and 133 healthy individuals (control group) were enrolled for the study. The subjects were diagnosed with AR after a detailed history, physical examination, and prick testing. The AR subjects were administered TAA in a daily dosage of a 220-μg intranasal route. Nasal cultures were obtained on the 1st (baseline), 55th, and 60th days, and the subjects in the last two cultures of whom S. aureus was detected were accepted as NCSA.

After all exclusion criteria were used, 110 AR and 114 control group subjects were enrolled in the study. Based on the culture results that were obtained on the 55th and 60th days, 10 (%9.1) patients from the study group and 18 (%15.7) individuals from the control group were defined to be NCSA (p > 0.05).

We conclude that the use of TAA treatment for AR does not increase the prevalence of NCSA. However, additional studies with a larger series are required to explain the effects of steroids on nasal colonization of S. aureus.

To determine if gentamicin nasal irrigation is systemically absorbed, and to identify any ototoxic side effects related to its use.

Retrospective review of 12 patients treated with gentamicin nasal irrigations (30 cc of 80 mg/L solution used bilaterally twice daily).

Serum gentamicin levels were assayed after the course treatment. Pure tone audiometry (250–8000 Hz) and distortion product otoacoustic emissions (DP-OAEs) at 7280, 5133, 3640 and 2560 Hz were obtained before and after therapy.

Twelve patients (age 4 to 74, mean 43) with chronic rhinosinusitis were treated for 3–15 weeks (mean 7 weeks). All patients had undergone previous endoscopic sinus surgery. Ten patients had pretreatment cultures that grew organisms sensitive to gentamicin (Pseudomonas, Proteus, or methacillin resistant Staphylococcus aureus), and three patients had cystic fibrosis. Ten of 12 patients (83%) had detectable posttreatment levels of gentamicin, with a mean serum level of 0.42 mcg/mL (range 0.3 to 0.7 mcg/mL). Four of 12 patients (33%) had serum gentamicin levels within the normal range for gentamicin trough (0.5 to 2 mcg/mL). Comparison of pre- and posttreatment audiologic data revealed no significant change in PTA or DP-OAE, except for the right ear at 8000 Hz on PTA (p = 0.035) where a mean of 7 dB loss was observed. No patient reported hearing loss or vertigo during treatment.

Gentamicin nasal irrigation may be systemically absorbed. Although the otologic consequences of this finding are questionable, patients receiving gentamicin nasal irrigations should be counseled regarding this hypothetical possibility.

Despite the popularity of various nasal sprays and nebulizers, there are limited data regarding the anatomic distribution of particles generated by these devices. This pilot study sought to characterize distribution patterns of nebulized and sprayed saline particles in normal subjects and postsurgical sinus patients.

Fifteen subjects were studied in three trials: metered-dose nasal spray bottle versus vortex-propelled nebulizer in normal subjects, passive-diffusion nebulizer versus vortex nebulizer in normal subjects, and passive nebulizer versus vortex nebulizer in postsurgical sinus patients. Radiolabeled saline was administered, and nose, lungs, and stomach were imaged. Images were scored by four blinded reviewers for degree of penetration at nine anatomic subsites.

Compared with spray bottle, the vortex nebulizer showed more focal intranasal distribution with reduced nasopharyngeal, pharyngeal, and gastric penetration in normal subjects. Three of five subjects showed probable frontal sinus penetration by vortex nebulizer, but no other sinus penetration was noted. No patients showed sinus penetration with the spray bottle. In a separate trial against the passive nebulizer, the vortex nebulizer again showed a greater tendency for sinus penetration in normal subjects, with three of five showing some degree of sphenoid penetration and one of five showing slight maxillary penetration. In contrast, no sinus penetration was observed with the passive nebulizer. In the postsurgical patient cohort, minimal sinus penetration was noted with either the vortex nebulizer or the passive nebulizer. Despite surgically patent sinuses, only one of five subjects showed any type of sinus penetration.

The nebulizer and nasal spray devices tested in general showed limited penetration of the sinuses in both normal and postoperative patients. The device showing greatest promise for sinus penetration in normal patients was the vortex nebulizer, with an overall penetration rate in normal patients of 30% in the frontal, 30% in the sphenoid, and 10% in the maxillary. Understanding delivery patterns of topical therapies may be important in evaluating the efficacy of various topical treatment modalities.

The most frequent causes of upper respiratory infections are human rhinoviruses. The nasopharyngeal area, which includes the respiratory epithelium, mucosa, and the olfactory neuroepithelium (ONe), is a first-line of defense against airborne viruses and allergens, some of which manage to penetrate the nasal mucosa and invade the tissues of the nasal respiratory epithelium. Biochemical evidence from several studies suggests that zinc is an effective cold treatment and that over-the-counter (OTC) zinc-gluconate compounds may provide the high pharmacologic doses of zinc needed to act as an effective means of treating and reducing the duration and severity of symptoms of the common cold.

A series of male Sprague-Dawley rats were fed an oral preparation of zinc-gluconate trihydrate or received the equivalent through drinking water to investigate the potential cytotoxic and/or neurotoxic insult to the olfactory receptor cells and other tissue in the ONe and afferent neuronal pathways.

Coronal sections of the rat ONe and corresponding olfactory bulbs showed consistent cellular and tissue damage of increasing severity that correlated with the duration of treatment with the zinc compound when compared with the control group animals.

The results of this analysis indicate that the repeated oral administration of such zinc-containing compounds have neurotoxic effects on the ONe and to the mitral cells in the olfactory bulbs of treated rats. These findings point toward the need for increased investigation into the potential deleterious effects of zinc-containing compounds to humans as well.

The nasal structures generate airflow resistance that can reach ∼50% of the total respiratory resistance. There are a series of factors that can alter the volume of these structures, among them physical exercise. The objective of this study was to determine the degree of changes in nasal volume at different levels of physical exercise, evaluating the influence of exercise intensity and duration, as well as the duration of the effect of exercise on the nasal mucosa.

Nineteen individuals were submitted to three distinct physical tests on a cycle ergometer: test 1, exercising for 5 minutes on a cycle ergometer at 50% the maximal load; test 2, exercising for 10 minutes on a cycle ergometer at 50% the maximal load; and test 3, exercising for 5 minutes on a cycle ergometer at 75% the maximal load. In each test, nasal volume was measured by acoustic rhinometry immediately after the end of exercise and 10 and 20 minutes thereafter.

The rhinometry results showed a significant increase (p < 0.001) in nasal volume after physical exercise for all tests performed. At 20 minutes, nasal volume had returned close to resting levels in all three tests. Comparison of the degree of improvement of nasal volume between the three physical tests showed a significant difference (p < 0.05) between T1 and T2 (T2 presented gain of 8.3% more in nasal volume than T1). Test 3 showed no significant difference (p > 0.05) compared with the other two tests, with 5.8% higher gain in nasal volume observed compared with T1, while the increase was 2.5% lower than in T2.

Physical exercise in general causes a significant increase in nasal volume, with the duration of exercise exerting a greater effect on the degree of improvement than intensity.

Nasal obstruction is thought to be a risk factor in obstructive sleep apnea (OSA). However, the relationship between nasal patency and sleep-disordered breathing remains controversial. The aim of this study was to examine the association between acoustic rhinometry findings and results of overnight polysomnography.

From February to October 2003, patients who underwent overnight polysomnography assessment were enrolled in the study. We excluded patients who were under 20 years old, had severe deviated nasal septum, had previously received nasal or palatal surgery, or could not complete sleep test or acoustic rhinometry examination. Participants’ basic data including age, gender, neck circumference, and body mass index (BMI) were collected. All participants received acoustic rhinometry before overnight polysomnography. The results along with sleep-test outcomes were recorded and analyzed.

A total of 87 patients were included in this study. Patients with respiratory disturbance index (RDI) less than 5/h (n = 26) or with RDI of 5–30/h (n = 28) tended to have larger minimal cross-sectional area (MCA) compared with those of patients whose RDI was more than 30/h (n = 33) (P = 0.001). A stepwise multiple regression analysis showed that BMI, male gender, and MCA were contributing factors in RDI. The R² value of the multiple regression analysis was 0.406.

Patients with severe OSA tended to have smaller MCA when compared with patients with RDI less than 30/h. However, it was hard to predict whether patients had OSA from acoustic rhinometry examination.

The pathogenesis of chronic rhinosinusitis (CRS) has been found to be multifactorial, with environmental, general host, and local anatomic factors all contributing to its development. Recent studies have indicated that local osteitis of the underlying bone also may play a critical role in the elaboration of CRS by inducing persistent inflammatory changes in the surrounding mucosa. The purpose of this study was to determine the clinical incidence rate of osteitis in patients with CRS undergoing functional endoscopic sinus surgery.

From January to July 2003, a prospective study was performed on 121 patients undergoing functional endoscopic sinus surgery for CRS. Age, number of previous surgeries, radiographic bony characteristics, and pathological findings were all documented. The presence of concurrent osteitis was assessed using both radiographic (neoosteogenesis) and pathological (bony remodeling) criteria.

The mean age of the patients was 44.3 years. Fifty-eight percent of the cases were revision surgeries, with each patient having an average of 2.2 operative procedures in the past. Computed tomography (CT) showed neoosteogenesis in 36% of patients, and 53% showed pathological evidence of osteitis on histological analysis of surgical specimens.

Concurrent osteitis can be found in 36–53% of patients with CRS, using both radiographic and pathological criteria, respectively. Although a causal relationship between osteitis and CRS can not be inferred from this data, these clinical findings correlate well with previous evidence of bone involvement in CRS found in animal models, further reaffirming the association between underlying osteitis and the pathogenesis of CRS.

Patients often report postnasal drip (PND), but objective rhinosinusitis and allergy findings are frequently absent. In this study, we evaluate the association between PND and pharyngeal reflux.

Sixty-eight participants underwent 24-hour pH testing, including chronic rhinosinusitis (CRS) patients persistently symptomatic after endoscopic sinus surgery, CRS patients successfully treated by endoscopic sinus surgery, and volunteers without a CRS history. The pH probes contained nasopharyngeal (NP), laryngopharyngeal (LP), and distal esophageal sensors. Participants completed the Sinonasal Outcome Test-20 (SNOT-20) and Modified Reflux Symptom Index (MRSI) questionnaires. Survey items addressing PND symptomatology were compared with NP reflux (NPR) below pH 4 and pH 5 (defined as ≥1 event), and LP reflux (LPR; defined as ≥7 events or reflux area index <6.3).

Pearson analyses revealed a positive correlation of r = 0.87 between SNOT-20 and MRSI PND items. For NPR < pH 4, no significant difference existed between participants with and without reflux on the SNOT-20 or MRSI (p < 0.05). However, for NPR < pH 5, reflux-positive participants exhibited significantly more PND symptoms on the SNOT-20 (p = 0.030) and the MRSI (p = 0.018) compared with participants without reflux. Finally, participants with LPR had significantly more PND symptomatology on the SNOT-20 (p = 0.010) versus those without LPR. A borderline significant difference existed on the MRSI PND item between participants positive and negative for LPR (p = 0.055).

Objective evidence of NPR and LPR exists in patients reporting PND. Reflux treatment may reduce PND complaints.

Over the past 20 years, many patients have benefited from endoscopic sinus surgery and its ability to relieve sinus obstruction. However, problems still occur with surgery, thereby leaving room for innovation. Recently, catheter-based technology has provided new options for treating cardiac, vascular, and urologic diseases. We speculated that catheter technology also might offer new treatment options for sinusitis patients. The purpose of this investigation was to explore the feasibility and safety of catheter-based technology to relieve sinus ostial obstruction.

Anatomic models and human cadaver specimens were used initially to design and iterate catheters to open sinus ostial drainage pathways. Thereafter, the safety of balloon-catheter dilation was evaluated in six human cadaver heads. CT scan obtained before and after catheter ostial dilation was analyzed for evidence of catheter-induced trauma. Dilated ostia also were examined by endoscopy and gross anatomic dissection for unwanted catheter-induced trauma.

Catheters successfully dilated 31 of 31 ostia, including 9 maxillary, 11 sphenoid, and 11 frontal ostia/recesses. CT scan, endoscopy, and gross anatomic dissection revealed that such dilation did not cause trauma to surrounding structures such as the orbit or skull base. Mucosal trauma imparted by catheter dilation appeared to be less than that normally seen with standard endoscopic instruments.

This initial study suggests that catheter technology can be used to dilate sinus ostia safely. Mucosal preservation and ease of use make catheters an attractive minimally invasive treatment strategy. Additional testing in patients is indicated to gain additional safety information and to explore the usefulness of catheter-based technology.

Postoperative scarring in the frontal recess is the most common cause of iatrogenic frontal sinusitis. Topical mitomycin-C (MMC) is an antifibroblastic agent that has been shown to reduce clinical scarring. This is a preliminary report of a double-blind, randomized, placebo-controlled trial using MMC to determine its effectiveness in reducing frontal recess stenosis after frontal sinusotomy.

All patients with chronic rhinosinusitis undergoing primary or revision bilateral image-guided endoscopic sinus surgery were enrolled. Patients requiring frontal sinus stents and those with allergic fungal sinusitis were excluded. After completion of the frontal sinusotomy, dimensions of the frontal recess were measured using curved Frazer suction diameters. A neuropattie soaked in 0.5 mg/mL of MMC was then placed into one frontal recess for 4 minutes in a randomized manner. A saline control was used for the other side. The primary surgeon was blinded to the medicated side intraoperatively and throughout the follow-up period. Measurements of the frontal recess were repeated at 1, 3, and 6 months.

There was no difference in the degree of frontal recess stenosis between the MMC and control sides at 1, 3, and 6 months postoperatively for both primary and revision cases.

One-time intraoperative topical MMC is not effective in reducing postoperative frontal recess stenosis in both primary and revision cases.

The aim of this study was to determine the effects of radiofrequency-induced thermotherapy (RFITT) in patients with nasal polyps.

A retrospective analysis was performed of prospectively collected data from 17 consecutive patients (11 men and 6 women; mean age, 51.7 ± 16.9 years) treated with RFITT from 2002 to 2003. The postoperative outcome was assessed using active anterior rhinomanometry, “sniffin’ stick” test, and endoscopic nasal examination preoperatively and 4 weeks postoperatively. Subjective complaints were assessed with Likert scales.

Transnasal airflow increased by 40.3% 4 weeks postoperatively (p = 0.029). Endoscopic appearance of nasal polyps indicated a nonsignificant reduction of 37.1%. Subjective complaints such as impaired nasal ventilation (p = 0.014), nasal discharge (p = 0.0007), postnasal drip (p = 0.0002), and hyposmia (p = 0.048) improved significantly 4 weeks after surgery.

RFITT is well tolerated as a day case procedure under local anesthesia and might be a procedure for treating recurrence of NP after sinus surgery. It remains unclear at this point whether RFITT for nasal polyps results in a permanent reduction.

The aim of this study was to show the effect of endoscopic sinus surgery on subjective headache scores in patients diagnosed with chronic rhinosinusitis (CRS) with or without nasal polyps.

We performed a retrospective analysis of prospectively collected data from 201 patients over a 2-year period. Headache and Sino-Nasal Outcomes Test (SNOT-20) mean scores were compared preoperatively and 2 years postoperatively on patients diagnosed with CRS with or without nasal polyps.

Two hundred one patients underwent surgical management of CRS with or without nasal polyps over a 3-year period. One hundred four patients were men and 97 were women, with a mean age of 49 (range, 18–80 years) years. Polyps were present in 78 patients with CRS. The mean subjective headache score based on a 0–10 visual analog scale improved from 4.7 preoperatively to 0.8 2 years postoperatively (p < 0.0001). The mean headache score of 123 patients without polyps was larger compared with 78 patients with polyps (5.1 versus 4.1, respectively; p < 0.05). As previously reported, the mean overall preoperative and postoperative SNOT-20 scores were 28.7 and 6.7, respectively (p < 0.0001).

Headache is a common symptom with CRS, present in 73.6% of our patients undergoing functional endoscopic sinus surgery for CRS with or without nasal polyps. An overall decrease in mean headache scores was noted at 2-year follow-up.

Mechanical obstruction of odorant flow to the olfactory neuroepithelium may be a primary cause of olfactory loss in nasal-sinus disease patients. Surgical removal of nasal obstruction may facilitate the recovery of olfactory ability. Unfortunately, quantifying the functional impact of nasal obstruction and subsequent surgical outcomes using acoustic rhinometry, rhinomanometry, or CT scans is inadequate.

Using computational fluid dynamics (CFD) techniques, we can convert patient CT scans into anatomically accurate 3D numerical nasal models that can be used to predict nasal airflow and odorant delivery rates. These models also can be rapidly modified to reflect anatomic changes, e.g., surgical removal of polyps.

CFD modeling of one patient's nose pre- and postsurgery showed significant improvement in postsurgical ortho- and retronasal airflow and odorant delivery rate to olfactory neuroepithelium (<1000 times), which correlated well with olfactory recovery.

This study has introduced a novel technique (CFD) to calculate nasal airflow dynamics and its effects on olfaction, nasal obstruction, and sinus disease. In the future, such techniques may provide a quantitative evaluation of surgical outcome and an important preoperative guide to optimize nasal airflow and odorant delivery.

Recently, modified endoscopic medial maxillectomy (MEMM) has been described as an alternative technique to open maxillectomy for benign sinonasal neoplasms. However, few reports discuss the efficacy of MEMM for treatment of inflammatory disease of the maxillary sinus. We evaluate the efficacy of MEMM in treating chronic maxillary sinusitis.

A retrospective review of patients who underwent MEMM for refractory inflammatory disease between December 2002 and September 2004 was performed. All patients were treated with MEMM alone or as part of an endoscopic sinus surgery procedure. Standard demographic data, operative technique, and postoperative follow-up times were collected.

Nineteen patients (average age, 57 years) underwent 24 EMMs for chronic maxillary sinusitis refractory to middle meatal antrostomy. All patients failed prior sinus surgery, including 14 Caldwell-Luc procedures. Average follow-up was 19.5 months (range, 10–27 months). One patient has persistent hyperplastic sinusitis that currently requires monthly follow-up and medical treatment. Our only complication was one nasolacrimal duct injury.

MEMM is both a safe and an effective treatment for chronic maxillary sinusitis refractory to standard medical and endoscopic surgical management.

The aim of this study was to review the presentation and management of children admitted for intracranial complications arising from frontal rhinosinusitis. We performed a retrospective case series review at two academic tertiary care children's hospitals.

This study consisted of children <18 years old who presented with intracranial complications from frontal rhinosinusitis between January 1, 1990 and December 31, 2002. Relevant literature was reviewed with the assistance of Medline. Presentation, type of intracranial complication, radiographic evaluations, response to treatment, and prognosis were evaluated.

Sixteen patients were identified with intracranial complications due to frontal rhinosinusitis. Patients were usually older (mean age, 14 years and 3 months), of male gender (M/F, 4.3:1.0), and African American (AA/W, 3.0:1.0). Headache, nasal congestion, and visual changes were the most common early symptoms and neurological findings indicated advanced disease. Subdural (56%), epidural (44%), and cerebral abscesses (19%) were the most common complications. Meningitis alone was identified in 13% and was associated with another intracranial complication in 6%. Multiple intracranial complications were noted in 31%. Polymicrobial cultures were obtained in 50% of patients. Although CT was excellent in identifying orbital pathology, MRI was superior for characterization of intracranial disease.

Intracranial complications of frontal rhinosinusitis are rare in children. Early symptoms often are nonspecific, with neurological findings more commonly seen in advanced disease. Adolescent African American male patients were found to be at highest risk for intracranial complications from frontal rhinosinusitis. Headache and orbital complaints associated with rhinosinusitis in older children failing to respond to initial therapy should prompt an aggressive evaluation including MRI.

Although multiple etiologies contribute to the development of rhinosinusitis, a common pathophysiological sequelae is ineffective sinonasal mucociliary clearance, resulting in stasis of sinonasal secretions, with subsequent infection, and persistent inflammation. The respiratory cilia beat continually at a basal rate, while during times of stress, such as exercise or infection, ciliary beat frequency (CBF) increases, accelerating mucus clearance. Previous investigations have led to conflicting results with some authors reporting decreased CBF while others have found normal values of CBF in patients with chronic rhinosinusitis (CRS). Additionally, these studies have only analyzed basal CBF. The goal of this study was to compare the basal as well as the stimulated sinonasal CBF in patients with CRS versus controls.

A dual temperature controlled perfusion chamber, differential interference contrast microscopy, and high-speed digital video were used to analyze both basal and adenosine triphosphate (100 μM)–stimulated CBF in human sinonasal mucosal explants.

Although no difference in basal CBF was detected between control and CRS patients, a marked difference in stimulated CBF was noted. Exogenously applied adenosine triphosphate resulted in a 50–70% increase of CBF in control tissue with a minimally observed CBF increase in explants from CRS patients.

Dynamic regulation of respiratory ciliary activity is critical for the respiratory epithelium to adapt to varying environmental situations. Thus, diminished or absent adaptation could predispose the sinonasal cavity to accumulation of inhaled infectious and noxious particulate matter resulting in infection/inflammation. Our findings suggest that CRS patients have decreased sinonasal ciliary adaptation to environmental stimuli.

Chitin is an abundant polysaccharide found in fungi, insects, and parasitic nematodes. Innate immune host defense against chitin-containing pathogens include production of chitinases. In human lower airways, acidic mammalian chitinase (AMCase) is produced in epithelial cells via a Th2-specific, IL-13–dependent pathway, and may act as an inflammatory mediator in asthma. The role of AMCase in chronic rhinosinusitis (CRS) has not been studied previously.

Eleven controls and 22 subjects with medically recalcitrant CRS were prospectively enrolled before undergoing endoscopic sinus surgery. RNA was extracted from surgically obtained ethmoid mucosa, and real-time PCR was used to determine expression of AMCase, eotaxin, and IL-13. Subjects were followed for at least 6 months postoperatively to assess for polyp recurrence. Based on the presence or absence of polyps, the subjects were classified as either recalcitrant or responsive to therapy.

AMCase mRNA was detected in the sinus mucosa of 72% of control subjects and in 72% of patients with eosinophilic CRS with nasal polyps (CRSwNP). The expression of AMCase was significantly greater in recalcitrant CRSwNP than it was in treatment-responsive CRSwNP. There was no significant difference in IL-13 expression between these two groups.

AMCase may be an important mediator in the pathogenesis of Th2 inflammatory diseases of the respiratory tract. Failure of medical and surgical therapy in CRSwNP is associated with significantly increased expression of AMCase, but not the Th2 cytokines IL-13 and eotaxin. Additional studies are needed to determine the potential of AMCase as a therapeutic target in CRSwNP.

Nitric oxide (NO) is produced by the action of NO synthase (NOS) isoforms and is considered an important mediator of inflammatory response including airways. In this study, the changes in the expression levels of NOS isoforms in nasal mucosae were determined in a guinea pig model of allergic rhinitis.

An allergic rhinitis model was prepared in guinea pigs by repeated challenge with aerosolized dinitrophenylated ovalbumin antigen. Twenty-four hours after the last antigen challenge, the expression levels of NOS isoforms in nasal mucosae were determined by immunoblottings. Changes in the isometrical tension of isolated mucosal tissues of nasal septa induced by histamine were measured also.

Although the expression levels of endothelial NOS (eNOS) and neuronal NOS (nNOS) in nasal mucosae were not affected by the repeated antigen exposure, the inducible NOS (iNOS) level was markedly and significantly increased in the challenged animals. In isolated nasal mucosal tissues, histamine induced a concentration-dependent relaxation, which was sensitive to an H₁-receptor antagonist, mepyramine, and an NOS inhibitor, l-NMMA. No significant change in the histamine responsiveness was observed between the sensitized control and repeatedly antigen-challenged groups.

The expression of three isoforms of NOS, including eNOS, nNOS, and iNOS, was presented in guinea pig nasal mucosa. A marked increase in iNOS expression in the repeatedly antigen-challenged animals suggests an important role of iNOS in the pathogenesis of allergic rhinitis. However, the pathophysiological role(s) of NO generated by iNOS in nasal allergy is still unclear.

Prostaglandin D2 (PGD2) is the major prostanoid produced in the acute phase of allergic reactions. However, its pathophysiological role in addition to the pathway of production in allergic rhinitis remains unclear. We sought to determine the expression of synthases and receptors for PGD2 in human nasal mucosa. These expressions were compared between allergic and nonallergic patients.

The expression and localization of hematopoietic-type (h)-PGD2 synthase (PGDS) and lipocalin-type (l)-PGDS were detected by immunohistochemistry. The expression of D prostanoid (DP) receptor and chemoattractant receptor–homologous molecule expressed on Th2 cells (CRTH2) was determined by quantitative real-time PCR.

The h-PGDS but not l-PGDS was clearly expressed in nasal mucosa. The expression of h-PGDS in allergic patients was significantly higher than in control patients without mucosal hypertrophy. A variety of infiltrating cells including mast cells, eosinophils, macrophages, and lymphocytes as well as constitutive cells such as epithelial cells and fibroblasts expressed h-PGDS. The expression of both DP and CRTH2 was confirmed also. Although either the amount of DP or the amount of CRTH2 was not correlated with serum levels of IgE, the amount of CRTH2 but not DP was highly and significantly correlated with the number of eosinophils infiltrating into nasal musosa.

These results suggest that PGD2 is released via the action of h-PGDS from various cells, and the expression of h-PGDS may be associated with the hypertrophic inflammation in the nose. In addition, ligation of PGD2 to CRTH2 appears to be selectively involved in eosinophil recruitment into the nose regardless of atopic status.

The vascular responsiveness of nasal mucosa has been determined frequently by using isolated mucosal tissues although it is not clear whether the response of the whole tissue truly reflects the response of the vasculature (especially veins) in mucosa. In this study, the in vivo responsiveness of mucosal veins was compared with in vitro responsiveness of isolated mucosal tissue in guinea pig nasal septa.

The in vivo venous responsiveness to norepinephrine (NE) of guinea pig nasal septal mucosa was measured by changes in the diameters of mucosal veins, stereomicroscopically. The in vitro responsiveness to NE of isolated nasal septal mucosae from guinea pigs also was determined by standard organ-bath technique.

Application of NE induced concentration-dependent contractile responses both in vivo and in vitro with the pD₂ (negative logarithm for 50% effective concentration [M] of NE) values of 5.23 ± 0.29 and 5.00 ± 0.17, respectively.

The equal potencies obtained by the in vivo and in vitro experiments suggest that an increase in tension of isolated nasal mucosal tissue might be caused by the contraction of mucosal veins. Both the in vivo and the in vitro methods used in this study might be useful for determining vasoreactivity of nasal mucosa in experimental animals.

Eosinophils are a characteristic inflammatory cell infiltrate in both chronic rhinosinusitis (CRS) and sinonasal polyposis (SNP). The posttranslational modifications, 3-bromo-tyrosine (Br-Tyr) and 3-chloro-tyrosine (Cl-Tyr), serve as specific molecular markers for production of brominating and chlorinating oxidants, respectively, by the eosinophil peroxidase and myeloperoxidase systems of leukocytes. The aim of this study was to identify mechanisms of oxidative protein modifications in sinonasal mucosa of CRS and SNP patients by measuring Br-Tyr, Cl-Tyr, and alternative molecular markers of distinct oxidative pathways.

Levels of Br-Tyr; Cl-Tyr; di-Tyrosine (di-Tyr), a specific oxidative cross-link; ortho-tyrosine (o-Tyr) and meta-tyrosine (m-Tyr), markers for protein modification by hydroxyl radical-like oxidants; and nitro-tyrosine (NO₂-Tyr), a stable product of nitric oxide (NO)–derived oxidants, were measured in anterior ethmoid mucosa tissue from CRS and SNP patients, as well as in middle turbinate mucosa from normal volunteers, using tandem mass spectrometry.

Tissue levels of Br-Tyr were significantly higher in the CRS group compared with the control group (797 μmol/mol versus 515 μmol/mol tyrosine, p < 0.015), but no differences were detected for Cl-Tyr, di-Tyr, m-Tyr, o-Tyr, and NO₂-Tyr. Tissue levels of both Br-Tyr and di-Tyr were significantly higher in the SNP group compared with the control group (879 μmol/mol versus 515 μmol/mol, p < 0.005; 5090 μmol/mol versus 1700 μmol/mol, p < 0.024, respectively), but no differences were detected for Cl-Tyr, m-Tyr, o-Tyr, and NO₂-Tyr.

Br-Tyr, a molecular footprint predominantly formed by eosinophil peroxidase–catalyzed tissue damage, may serve as an objective index of CRS and SNP disease activity.

In nasal inverted papilloma (IP) and its malignant transformation process, abnormal cell growth has been regarded as an altered proliferation of the epithelial cells, while the role of programmed cell death in this process remains to be determined.

An apoptotic index was calculated, and the proliferation ability by using Ki67 as a marker was evaluated in the study subjects, which consisted of 15 cases of nasal chronic sinusitis, 23 cases of nasal IP, 9 cases of nasal IP with dysplasia, 8 cases of nasal IP with squamous cell carcinoma (SCC), and 21 cases of primary SCC. In addition, expressions of apoptosis-related molecules p53, Bcl-2, Bax, and Fas were investigated also.

The result showed that the Ki67 index increased in IP and IP with dysplasia. The Ki67 value was further enhanced in SCC within IP and primary SCC. The apoptotic index was low in IP with dysplasia, IP with SCC, and primary SCC. Concerning the expression of apoptosis-related proteins, p53 protein accumulated in IP with dysplasia, IP with SCC, and primary SCC. The p53 overexpression was directly correlated with the Ki67 index in IP and primary SCC diseases. No remarkable differences were found regarding expression of Bcl-2 and Fas productions among these diseases, and Bax protein was decreased only in primary SCC.

We concluded that inhibition of apoptosis could be an early sign of IP undergoing malignant transformation. A high proliferative rate was a characteristic of IP-associated malignant diseases.

The sensitivity of the human nasal cavity mucosa to touch is not well understood. The site of receptors and mode of action responsible for the sensation of the nasal airflow is a topic of controversy. Previous studies have suggested that the skin-lined nasal vestibule is more sensitive to airflow than the mucosa of the nasal cavity. A possible decline in nasal sensitivity to airflow in older subjects has not been studied.

The threshold of the mucosal sensitivity to jets of air was assessed in 76 subjects with healthy nasal cavities. A total of 141 nostrils were tested, 67 in younger patients and 74 in older patients.

Statistically significant (p < 0.001) increases in thresholds were found for all points tested for older patients compared with the younger patients. In general, the more sensitive locations were in the nasal vestibule. The nasal cavity mucosa in the inferior meatus was slightly more sensitive than the middle meatus.

We have measured the threshold to touch (air jet sensitivity) in nine places in each of 141 nasal cavities and determined that the variability and sensitivity of these measurements among people varies by age and the distance from the nostril. Older subjects were found to have a higher threshold for the sensation of air flow, and the nasal vestibule was found to be more sensitive than the rest of the nasal cavity mucosa with the inferior meatus slightly more sensitive then the middle meatus.