Steroids Inhibit Eosinophil Accumulation and Downregulate Hematopoietic Chemotaxic Prostaglandin D2 Receptor in Aspirin-Exacerbated Respiratory Disease.

BACKGROUND: Aspirin-exacerbated respiratory disease (AERD) is characterized by eosinophilic rhinosinusitis, nasal polyposis, aspirin sensitivity, and asthma. Aims/Objectives: This study aims to identify a mechanism to target for the future treatment of AERD via the elucidation of the effect of systemic steroids on the expression of hematopoietic prostaglandin D2 synthase (HPGDS) and chemotaxic prostaglandin D2 (DP2) receptor relative to eosinophil activation in the nasal polyps of patients with AERD. MATERIALS AND METHODS: Among 37 patients undergoing endoscopic sinus surgery, 28 received systemic steroids preoperatively. Nasal polyps were harvested from all 37 patients. After routine processing of paraffin sections, immunohistochemistry was performed using specific antibodies for HPGDS, eosinophil peroxidase (EPX), and DP2. RESULTS: Expression of HPGDS, DP2, and EPX by eosinophils was higher and more frequent in patients with non-preoperative steroid therapy. Likewise, HPGDS and DP2 were highly expressed in activated eosinophils in the nasal polyps, but not in normal eosinophils. CONCLUSION AND SIGNIFICANCE: This study provides clear evidence that systemic steroid therapy inhibits eosinophil activation and decreases HPGDS and DP2 expression in patients with AERD, indicating a reduction in prostaglandin D2 production and hence control hyperplasia of nasal polyps.

[Preoperative evaluation of surgery for intractable aspiration based on the prognostic nutritional index].

Because there is no absolute indicator of the nutritional status and prognosis in patients with severe aspiration problems, it is quite difficult to arrive at a true long-time prognosis. By performing surgery for intractable aspiration on such patients, both the prognosis and QOL of the patients could be expected to improve. In our department, we have experienced patients dying within 6 months after surgery. In these cases, the patient's preoperative nutritional status was not good. Therefore, we consider that, when we adopt this procedure, there should be some indicators we should use which could have an effect on the prognosis of such nutritionally-challenged patients. In patients who underwent surgery for intractable aspiration; we examined the relationship between their survival and the prognostic nutritional index (PNI) which is an indicator of the risk of complications such as post-operative events in the surgical field. We investigated the relationship between the prognosis and the postoperative indicators of each of the following: WBC, CRP, serum albumin level, and PNI. Out of a total of 31 cases, the average O-PNI of eight cases in which death occurred was 29.45, and the average of six cases in which death occurred within 6 months after surgery was 28.26. The average O-PNI of the survivors was 36.01. A significant association was noted between the early postoperative deaths and some of the four indicators namely that serum albumin level and O-PNI. Based on the ROC curve, the O-PNI offered higher precision than the albumin level. The cut-off value of the O-PNI value for early postoperative mortality rate was 32. The early postoperative mortality rate was 44.4% in patients with less than 32 O-PNI in the preoperative examination, but if it were O-PNI 32 or more, the early postoperative mortality rate was 9.1%, significantly lower. Therefore, O-PNI could be useful as one of the prognostic evaluation factors in the case of preoperative surgery for intractable aspiration. Based on the O-PNI score, it was possible to evaluate the survival benefit associated with this operative procedure. We showed a treatment algorithm based on the preoperative O-PNI value. We believe there is a necessity to develop preoperative effective nutritional therapy as a future issue.

Endolaryngeal extension of thyroglossal duct cyst.

Thyroglossal duct cysts are the most common congenital neck masses that develop during childhood, The masses develop from remnants of thyroglossal ducts, and typically appear as midline neck masses. Endolaryngeal extension of thyroglossal duct cysts has been reported mostly as midline neck swelling. We observed a case of extension of the thyroglossal duct cyst to the supraglottic area without neck swelling. A 50-year-old man presented with a 1-month history of foreign-body sensation in the throat. Fiberscopic and radiologic findings were similar to those associated with a saccular cyst, but its proximity to the hyoid bone raised the possibility of thyroglossal duct cyst. Operation was performed via an external incision to completely remove the cyst. Postoperative fiberscopy revealed that the aryepiglottic fold swelling had disappeared. Diagnosis of thyroglossal duct cyst was confirmed on the basis of pathological findings. In cases in which it is difficult to remove the cyst from the hyoid membrane, the hyoid bone midline portion should be dissected. Thyroglossal duct cysts should be considered in cases with a submucosal tumor in the supraglottic region, and radiological examinations should be performed.

[A case of Schneiderian middle-ear and sinonasal papilloma with intracranial complications].

Unlike Schneiderian papilloma, a widespread benign epithelial neoplasm arising in the sinonasal tract mucosa of the nasal cavity, paranasal sinus, trachea, and larynx, middle-ear Schneiderian papilloma is extremely rare. We report a case of recurrent Schneiderian papilloma spreading to the bilateral middle ear and right paranasal sinus, and eventually causing cerebellar complications. A-52-year old woman seen for episodes of inarticulateness was first, found to have middle right ear and right ethmoid papilloma, that occurred thereafter is the middle left ear. This bilateral middle-ear papilloma is, to our knowledge, the only case reported thus far, and fell into a low-risk malignant formation group based on HPV-DNA testing. Given previous cases, we concluded that ours warranted meticulous follow-up because recurrence and malignancy are more common in multiple-site middle-ear papilloma as in our case rather than papilloma of the middle ear alone.

Quercetin stimulates Na+/K+/2Cl- cotransport via PTK-dependent mechanisms in human airway epithelium.

We investigated regulatory mechanisms of Cl(-) secretion playing an essential role in the maintenance of surface fluid in human airway epithelial Calu-3 cells. The present study reports that quercetin (a flavonoid) stimulated bumetanide-sensitive Cl(-) secretion with reduction of apical Cl(-) conductance, suggesting that quercetin stimulates Cl(-) secretion by activating an entry step of Cl(-) across the basolateral membrane through Na(+)/K(+)/2Cl(-) cotransporter (NKCC1). To clarify the mechanism stimulating NKCC1 by quercetin, we verified involvement of protein kinase (PK)A, PKC, protein tyrosine kinase (PTK), and cytosolic Ca(2+)-dependent pathways. A PKA inhibitor (PKI-14-22 amide), a PKC inhibitor (Gö 6983) or a Ca(2+) chelating agent did not affect the quercetin-stimulated Cl(-) secretion. On the other hand, a PTK inhibitor (AG18) significantly diminished the stimulatory action of quercetin on Cl(-) secretion without inhibitory effects on apical Cl(-) conductance, suggesting that a PTK-mediated pathway is involved in the stimulatory action of quercetin. The quercetin action on Cl(-) secretion was suppressed with brefeldin A (BFA, an inhibitor of vesicular transport from ER to Golgi), and the BFA-sensitive Cl(-) secretion was not observed in the presence of an epidermal growth factor receptor (EGFR) kinase inhibitor (AG1478), suggesting that quercetin stimulates Cl(-) secretion by causing the EGFR kinase-mediated translocation of NKCC1 or an NKC1-activating factor to the basolateral membrane in human airway epithelial Calu-3 cells. However, the surface density of NKCC1 was not increased by quercetin, but quercetin elevated the activity of NKCC1. These observations indicate that quercetin stimulates Cl(-) secretion by activating NKCC1 via translocation of an NKCC1-activating factor through an EGFR kinase-dependent pathway.

A 13-year study of Japanese cedar pollinosis in Japanese schoolchildren.

BACKGROUND: Japanese cedar pollen (JCP) sensitization and Japanese cedar pollinosis (JCPS) appear to be increasingly prevalent in younger children. The present study investigated factors affecting JCP sensitization and JCPS development in school children. METHODS: In May or June each year from 1994 to 2006, 275-510 children were assessed for serum JCP-IgE and house dust mite (HDM)-IgE levels, and surveyed regarding rhinoconjunctival symptoms. RESULTS: Strong JCP sensitization (IgE > or = 17.5 U(A)/ml) was associated with age (odds ratio (OR) = 2.65), the amount of dispersed pollen in the observed year (OR = 2.03) and in the year following birth (OR = 1.51), the month of birth (OR = 2.18), and the recent birth cohort (OR = 1.96). Symptoms were negatively correlated with the recent birth cohort (OR = 0.69) after adjusting for JCP-IgE levels. Strong HDM sensitization was associated with gender (OR = 0.65 for girls) and the recent birth cohort (OR = 1.76). CONCLUSIONS: JCP sensitization appeared to be associated with the recent birth cohort and to increases in dispersed pollen just after birth and in the observed season. Although the recent birth cohort was more easily sensitized, they were not more likely to develop symptoms. In contrast to JCP sensitization, strong HDM sensitization appeared to develop prior to commencement of primary school and was more likely to affect boys.

[Outcomes of endoscopic sinus surgery in chronic sinusitis cases complicated/ not complicated by bronchial asthma and eosinophilic infiltration of the sinus mucosa].

BACKGROUND: Intractable sinusitis is, in most cases, complicated by bronchial asthma and severe eosinophilic infiltration of the sinus mucosa. Our aim here was to study the postoperative outcomes of chronic sinusitis complicated/not complicated by bronchial asthma and of cases with eosinophilic sinusitis/non-eosinophilic sinusitis. METHODS: We conducted a prospective analysis of the outcome of 180 patients with or without bronchial asthma and eosinophilic infiltration who underwent endoscopic sinus surgery (ESS) for chronic sinusitis. The patients were divided into four groups by the presence/absence of asthma and presence/absence of eosinophilic infiltration of the sinus mucosa. One surgeon performed the ESS, and all the groups received the same postoperative treatment. RESULTS: The outcomes of ESS were significantly worse in the cases complicated by eosinophilic sinusitis and asthma, especially in relation to the incidence of smell disturbances and the endonasal findings. Patients suffering from chronic sinusitis without asthma showed good improvement following ESS. There was no significant differences in the outcome after ESS between cases of eosinophilic sinusitis and those with non-eosinophilic sinusitis among the patients without asthma. CONCLUSIONS: We contend that eosinophilic sinusitis without asthma may not represent intractable sinusitis. We wish to emphasize that complication by

Effects of polysaccharide derived from black currant on relieving clinical symptoms of Japanese cedar pollinosis: a randomized double-blind, placebo-controlled trial.

We investigated the efficacy of the polysaccharide derived from black currant, named cassis polysaccharide (CAPS), for inhibiting Japanese cedar pollinosis symptoms and improving quality of life by a randomized double-blind, placebo-controlled trial in 2006. A total of 28 subjects were enrolled in the study, and 10 subjects in each group completed the trial. Although there was no significant difference between the CAPS and placebo group in the weekly mean value of any symptom in the daily symptom diary at any time, a smaller degree of final symptom aggravation was found in the CAPS group. Significant aggravation of the score was finally observed in the placebo group with inferior conch swelling and with sneezing, itchy nose, itchy eye and watery eye in the Japan rhino-conjunctivitis quality of life questionnaire assessment, while the changes observed in the CAPS group were not significant. In conclusion, our findings clearly indicate that CAPS would be useful as a food supplement in assisting the treatment of Japanese cedar pollinosis.

Epithelial Na+ channel and ion transport in human nasal polyp and paranasal sinus mucosa.

The purpose of the present study is to characterize the ENaC-mediated Na+ absorption in human upper airway epithelia, nasal cavity, and paranasal sinus. To perform the purpose, we obtained epithelial cells from human nasal polyp (NP) and paranasal sinus mucosa (PSM) by endoscopic surgery. We measured the short-circuit current (I(sc)) sensitive to benzamil (a specific ENaC blocker). The benzamil-sensitive I(sc) (Na+ absorption) in NP was larger than that in PSM. The mRNA expression of three subunits of ENaC was as follows: alpha>beta>gamma in both tissue, NP and MS. The mRNA expression of gamma subunit of ENaC in NP was larger than that in PSM, but no difference of mRNA expression of alpha or beta ENaC subunit between NP and PSM was detected. We found correlation of the Na+ absorption to mRNA expression of gamma ENaC in NP and PSM. Forskolin diminished the Na+ absorption associated with an increase in Cl- secretion. These observations suggest that: (1) human NP absorbs more ENaC-mediated Na+ than PSM, (2) expression of gamma ENaC in plays a key role in the ENaC-mediated Na+ absorption in NP and PSM, and (3) cAMP diminishes the ENaC-mediated Na+ absorption by stimulating Cl- secretion (diminution of driving force for Na+ absorption) in NP and PSM.

Epithelial ion transport of human nasal polyp and paranasal sinus mucosa.

Nasal cavity and paranasal sinus have various functions. However, little information is available on ion transport in these upper airway epithelia. In the present study, we measured the anion secretion and the anion channel activity to characterize the ion transport in epithelial cells prepared from human paranasal sinus mucosa (PSM) and nasal polyp (NP). To estimate the anion secretion and the anion channel activity, we measured the short-circuit current (Isc) and the transepithelial conductance (Gt) sensitive to NPPB (a Cl(-) channel blocker). The NPPB-sensitive Isc in PSM was larger than that in NP, correlating to the NPPB-sensitive Gt (Cl(-) channel activity). Forskolin stably elevated the NPPB-sensitive Isc associated with an increase in the NPPB-sensitive Gt in PSM and NP. UTP transiently stimulated the Isc associated with an elevation of Gt in PSM and NP. The stimulatory action of UTP on Isc and Gt was diminished by application of NPPB but not benzamil in PSM and NP, suggesting that UTP induced the NPPB-sensitive Isc (Cl(-) secretion) and Gt (Cl(-) channel activity). These observations suggest that in human PSM and NP, cAMP stably stimulates anion secretion by activating the Cl(-) (anion) channels, and that UTP just transiently elevates anion secretion via activation of some Cl(-) (anion) channels.

Potential role of abnormal ion transport in the pathogenesis of chronic sinusitis.

OBJECTIVES: To create well-differentiated cultures of normal and chronic sinusitis paranasal sinus epithelial cells and to compare their electrophysiologic properties. DESIGN: In vitro investigation using primary sinus epithelial cells, initially cultured on plastic tissue culture dishes. Cells were characterized by means of immunocytochemical analysis and then passaged to air-liquid interface culture conditions. The morphologic features of air-liquid interface cultures were assessed using light and electron microscopy. Epithelial Na(+) channel, Na(+)-K(+)-2Cl(-) cotransporter, cystic fibrosis transmembrane conductance regulator, and Ca(2+)-activated Cl(-) channel function were investigated in Ussing chambers. SUBJECTS: Specimens were obtained from 15 patients undergoing transsphenoidal pituitary procedures, tumor removal, or trauma repair and from 9 patients with chronic sinusitis. RESULTS: After culture at an air-liquid interface for 21 days, the epithelium was pseudostratified and contained basal, mucous secretory, and ciliated cells. There were no detectable morphologic differences between normal and chronic sinusitis cells. In cultures of normal cells, median basal short circuit current was 4.7 microA/cm(2), and Na(+) transport, defined as the amiloride hydrochloride-sensitive component, was approximately 20% of the total. Basal and amiloride-sensitive short circuit currents were greater in cultures of chronic sinusitis cells. Basal short circuit currents in both types of cultures were insensitive to the Cl(-) transport inhibitor bumetanide, but all responded to forskolin or uridine triphosphate. After amiloride pretreatment, forskolin and uridine triphosphate responses were greater in chronic sinusitis cells. CONCLUSIONS: We established methods for well-differentiated sinus epithelial cultures. The cells exhibited Na(+) absorption and Cl(-) secretion, and elevated rates of ion transport may be pathophysiologically relevant in chronic sinusitis.

A clinical study of endoscopic sinus surgery for sinusitis in patients with bronchial asthma.

BACKGROUND: An association between bronchial asthma and sinusitis has long been suspected. Our aim is to study the clinical features of chronic sinusitis associated with bronchial asthma as two manifestations of one airway disease. METHODS: We conducted a prospective analysis of the outcome of 88 patients, with or without bronchial asthma, who underwent endoscopic sinus surgery (ESS) for chronic sinusitis. Patients were divided into two groups by the presence or absence of asthma and were evaluated. One surgeon performed the ESS, and the same postoperative treatment was given to both groups. The postoperative outcomes of symptoms and objective findings related to sinusitis were evaluated numerically, with a maximum score of 2 points for each examination item. Twenty-eight patients with asthma symptoms were assessed before and after surgery, using peak flow (liter/second) and medication scores (according to US Food and Drug Administration) to determine whether bronchial asthma was improved by first-time ESS. RESULTS: The outcomes of ESS were significantly worse in the asthma group, especially the endonasal findings. Patients suffering from chronic sinusitis and bronchial asthma showed improvement following ESS in terms of their asthma symptoms, peak flow and medication score. Patients with a good ESS result tended to have the greatest improvement in their asthma. CONCLUSIONS: We conclude that sinusitis and asthma are closely related to each other, acting as two manifestations of one airway disease. We recommend treating cases of sinusitis complicated by asthma as a single disease of the entire respiratory tract.

Two-photon microscopic analysis of acetylcholine-induced mucus secretion in guinea pig nasal glands.

The spatiotemporal changes in intracellular free Ca(2+) concentration ([Ca(2+)](i)) as well as fluid secretion and exocytosis induced by acetylcholine (ACh) in intact acini of guinea pig nasal glands were investigated by two-photon excitation imaging. Cross-sectional images of acini loaded with the fluorescent Ca(2+) indicator fura-2 revealed that the ACh-evoked increase in [Ca(2+)](i) was immediate and spread from the apical region (the secretory pole) of acinar cells to the basal region. Immersion of acini in a solution containing a fluorescent polar tracer, sulforhodamine B (SRB), revealed that fluid secretion, detected as a rapid disappearance of SRB fluorescence from the extracellular space, occurred exclusively in the luminal region and was accompanied by a reduction in acinar cell volume. Individual exocytic events were also visualized with SRB as the formation of Omega-shaped profiles at the apical membrane. In contrast to the rapidity of fluid secretion, exocytosis of secretory granules occurred with a delay of approximately 70s relative to the increase in [Ca(2+)](i). Exocytic events also occurred deep within the cytoplasm in a sequential manner with the latency of secondary exocytosis being greatly reduced compared with that of primary exocytosis. The delay in sequential compound exocytosis relative to fluid secretion may be important for release of the viscous contents of secretory granules into the nasal cavity.

[Clinical study of the paranasal sinuses of patients with Japanese Cedar pollinosis].

To clarify paranasal sinus change in patients with Japanese cedar pollinosis, we studied reactions to medical treatment via X-ray images of patients during the 2000 cedar pollen season. Medication was administered to 577 patients consulting facilities in 3 regions--Kyoto, Fukui and Osaka--having different pollen counts i.e., 4555/cm2 in Fukui, 801/cm2 in Kyoto and 531/cm2 in Osaka. The paranasal sinus was X-rayed by Water's method, and the degree of positivity was classified by Katagiri'shadow classification. Patients were grouped into 334 suffering extensive Fukui pollen dispersion and 243 suffering relatively limited Kyoto and Osaka pollen dispersion. At 3-4 weeks after pollen dispersion, contrast shadow positivity was 22.2%, with no difference before pollen dispersion (22.2%) in Kyoto and Osaka. In Fukui, positivity was 39.7%, a clear increase over pre pollen dispersion (19.2%). In the initial treatment group, positivity was 25.8% in Fukui and 28.6% in Kyoto and Osaka. Our results suggest that the incidence of sinusitis in patients with Japanese cedar pollinosis tended to increase with exposure to extensive pollen dispersion and to be suppressed by initial treatment.

Prevalence of Japanese cedar pollinosis among schoolchildren in Japan.

BACKGROUND: Japanese cedar pollinosis is an important allergic rhinoconjunctivitis in Japan in spring. We investigated the relationship between the amount of pollen in the air and the prevalence of the disease and sensitization to Japanese cedar pollen in this ecological study. METHODS: The IgE antibody to Japanese cedar pollen (JCP-IgE) was determined in human serum and rhinoconjunctival symptoms were surveyed in 407-510 children in May or June every year from 1995 to 2001. Japanese cedar pollinosis was defined as being JCP-IgE >or=1.5 IU/ml and having any rhinoconjunctival symptom lasting 3 weeks or longer in March or April. RESULTS: Prevalence rates of Japanese cedar pollinosis were 13.8-22.9%. Prevalence rates of being JCP-IgE >or=1.5 IU/ml were 39.0-50.1%, and those of being JCP-IgE >or=15.01 IU/ml were 11.4-23.2%. All prevalence rates were significantly related to the amount of pollen in the air. The proportion of subjects with rhinoconjunctival symptoms was relatively constant in each stratum of low JCP-IgE levels (<0.35, 1.50-2.99, 3.0-14.9 IU/ml). CONCLUSION: High exposure to Japanese cedar pollen was associated with higher levels of JCP-IgE antibody and a high prevalence of Japanese cedar pollinosis. The relationship between the level of JCP-IgE and the proportion of subjects with symptoms was relatively constant.