Role of Vitamin D and Its Receptors in the Pathophysiology of Chronic Rhinosinusitis.

OBJECTIVES: Chronic rhinosinusitis (CRS) is a disease that represents a challenging therapeutic problem. Vitamin D and its receptors (VDR) are involved in the regulation of the immune system and may play role in CRS. Objectives of this study were to assess the relationships between the total concentration of vitamin D (25VD3) in sera, vitamin D receptor (VDR) expression, 1α-hydroxylase expression, and clinical data, including age, gender, Sino-Nasal Outcome Test (SNOT-22), computerized tomography (CT) scan, allergy status, and vitamin D supplementation in CRS patients with (CRSwNP) and without nasal polyps (CRSsNP), and in a control group. METHODS: The studied group comprised 52 patients with CRS without nasal polyps (sNP), 55 with CRS with nasal polyps (wNP), and 59 in the control group. The endpoints were determined by appropriate methods. We conducted immunohistochemical staining of gathered tissue from the ostiomeatal complex for determination of VDR and 1α-hydroxylase. Analytical results were compared with clinical data as already noted. RESULTS: A decrease in VDR nuclear staining occurred in CRS patients as compared to controls. Insignificant differences were observed in 1α-hydroxylase, expression in all studied groups, while VDR and cytochrome CYP27B1 protein expression (1α-hydroxylase) correlated with clinical data. CONCLUSIONS: The data provide evidence that indicates that vitamin D and its receptor and enzymes may play a role in CRS.

Allergic sensitization is age-dependently associated with rhinitis, but less so with asthma.

BACKGROUND: Epidemiologic data describing the association between allergic sensitization and asthma and allergic rhinitis in adults are scarce. OBJECTIVE: To determine the prevalence and impact of specific sensitization to airborne allergens on asthma and allergic rhinitis among adults in relation to age. METHODS: A random population sample (age 21-86 years) was examined with structured interview and analysis of specific IgE to 9 common airborne allergens. Of those invited, 692 (68%) subjects participated in blood sampling. IgE level of 0.35 U/mL or more to the specific allergen was defined as a positive test result. RESULTS: Allergic sensitization decreased with increasing age, both in the population sample and among subjects with asthma and allergic rhinitis. In a multivariate model, sensitization to animal was significantly positively associated with asthma (odds ratio [OR], 4.80; 95% CI, 2.68-8.60), whereas sensitization to both animal (OR, 3.90; 95% CI, 2.31-6.58) and pollen (OR, 4.25; 95% CI, 2.55-7.06) was significantly associated with allergic rhinitis. The association between allergic sensitization and rhinitis was consistently strongest among the youngest age group, whereas this pattern was not found for asthma. The prevalence of allergic sensitization among patients with asthma decreased by increasing age of asthma onset, 86% with asthma onset at age 6 y or less, 56% at age 7 to 19 years, and 26% with asthma onset at age 20 years or more. CONCLUSIONS: Sensitization to animal was associated with asthma across all age groups; allergic rhinitis was associated with sensitization to both pollen and animal and consistently stronger among younger than among older adults. Early onset of asthma was associated with allergic sensitization among adults with asthma.

Comparative pharmacokinetics of a marker compound, baicalin in KOB extract after oral administration to normal and allergic-induced rats.

KOB extracts are a polyherbal medicine had been prescribed for the treatment of hyperhydrosis and allergic diseases such as allergic asthma and rhinitis in oriental clinics. Therefore, the pharmacokinetic studies of the KOB extract administered orally to normal rats and rhinitis-induced rats to understand the correlation of the efficacy and plasma concentration of KOB in patients of allergic rhinitis in future were performed. The study was conducted according to administration for pure baicalin in normal rats, baicalin in KOB extract in normal rats and rhinitis-induced rats. Baicalin in rat plasma was analyzed and validated by HPLC analysis. The interday precision based on the standard deviation of replicates of quality control samples ranged from 3.6% to 7.9% with accuracy ranging from 92.9% to 101.2% for baicalin. Based on validated analysis, pharmacokinetic study was carried out. Pure baicalin in normal rats and baicalin in KOB extract in normal rats showed bimodal curves due to direct absorption and glucuronidation. The Tmax, Cmax and AUC of pure baicalin in normal rats or baicalin in KOB extract in normal rats were 12 h, 0.68 µg/ml and 9.85 µg h/ml, respectively, or 12 h, 0.46 µg/ml and 6.36 µg h/ml, respectively. The analytical method showed excellent sensitivity, precision and accuracy, being successfully employed in a pharmacokinetic study of polyherbal medicine, KOB extract. Allergic-induced condition did not affect the pharmacokinetics of KOB extracts, suggesting KOB extracts did not require dosage adjustment in subjects with allergic-induced diseases.

Effects of various physical treatment methods on arteriolar vasomotion and microhemodynamic functional characteristics in case of deficient regulation of organ blood flow. Results of a placebo-controlled, double-blind study.

As part of a placebo-controlled study, high-resolution measurement methods were used to examine, on the basis of representative functional characteristics of microcirculation, whether and to what extent six different, commercially available, physical treatment devices were suitable for influencing, through complementary therapy, deficient blood-flow regulation. Of the six commercially available devices tested, two proved to be ineffective and three not effective enough to be therapeutically relevant. Only in one device was it possible to show a complementary-therapeutic effect: the device uses a specific, biorhythmically defined stimulus for vasomotion.

Bronchial hyperresponsiveness in seasonal allergic rhinitis patients is associated with increased IL-18 during natural pollen exposure.

BACKGROUND: The mechanism of bronchial hyperresponsiveness (BHR) is not certain in seasonal allergic rhinitis (SAR) patients. OBJECTIVE: We aimed to investigate the effects of natural pollen exposure on IL-18 and its relationship with BHR. METHODS: Thirty-two SAR patients with grass pollen sensitivity, 14 nonallergic rhinitis (NAR) patients and 17 normal-controls were included. Sixteen SAR patients had BHR during pollen season and off-season. Serum IL-18 levels were measured in SAR patients during pollen season between May-August and off-season between November-February. IL-18 levels were measured in NAR patients and normal controls once. RESULTS: During pollen season, SAR patients with BHR had significantly increased levels of IL-18 than those without BHR (279.2 ± 161.1 versus 145.3 ± 101.0 pg/ml, p=0.012). Serum IL-18 levels were not different between SAR patients with and without BHR during off-season (233.8 ± 139.7 versus 183.2 ± 162.9 pg/ml, p=0.16). Serum IL-18 levels in SAR patients during pollen season (212.3 ± 148.8 pg/ml) and off-season (208.5 ± 151.5 pg/ml) were not different than those NAR patients (224.8 ± 180.1 pg/ml, p=0.98 and p=1.0, respectively) and normal controls (174.8 ± 76.0 pg/ml, p=0.60 and p=0.76, respectively). CONCLUSION: The results suggested us that BHR in SAR patients is associated with increased IL-18 during natural pollen exposure.

Effect of a Chinese herbal formula, Shi-Bi-Lin, on an experimental model of allergic rhinitis.

BACKGROUND: Jia Wei Cang Er Zi San, a traditional Chinese herbal formula, has been used to treat allergic rhinitis (AR) for several centuries. However, its effect on experimental animal models and its therapeutic mechanism remain unclear. OBJECTIVE: To study the effect of Shu-Bi-Lin, a modified Jia Wei Cang Er Zi San, on an animal model of AR. METHODS: Shu-Bi-Lin was administered to the guinea pig model of AR. Meanwhile, an antihistamine-treated group for the treatment control, an ovalbumin-sensitized and untreated group for the positive control, and a sham-sensitized, sham-challenged group for the sham control were studied in parallel. Symptomatic and some pathophysiologic variables were evaluated. RESULTS: Sneezing and nasal scratching after challenges were significantly ameliorated in the Shu-Bi-Lin-treated group compared with the ovalbumin-sensitized and untreated group, but rhinorrhea volume was not reduced. Shu-Bi-Lin significantly suppressed the production of IgG1 in the passive cutaneous anaphylaxis test. The thromboxane B2 level in nasal lavage fluid was significantly deceased in the Shu-Bi-Lin-treated group; however, the reduction in histamine and peptide leukotriene levels did not reach statistical significance. In addition, eosinophil infiltration and endothelial nitric oxide synthase immunoreactivity in the nasal tissues were reduced in the Shu-Bi-Lin-treated group. CONCLUSIONS: Shu-Bi-Lin could alleviate the nasal symptoms of AR, and its mechanism might be related to its inhibitory effect on type I anaphylaxis reactions and eosinophil infiltration in the nasal tissues, as well as the inhibition of some mediators related to AR.

Anaphylaxis to Cyphomandra betacea Sendth (tamarillo) in an obeche wood (Triplochiton scleroxylon)--allergic patient.

BACKGROUND: Anaphylaxis after the first exposure to a food allergen is uncommon unless a cross-reaction is present. OBJECTIVE: To investigate a possible relationship between the fruit Cyphomandra betacea Sendth (commonly known as tamarillo) and the wood of Triplochiton scleroxylon (obeche) in a patient with allergic occupational bronchial asthma due to obeche wood who began to experience anaphylaxis episodes after eating tamarillo. METHODS: A 33-year-old carpenter exposed to obeche wood in his occupation was initially seen with rhinitis and bronchial asthma. The causal relationship of these symptoms to obeche wood exposure was investigated by means of peak flow monitoring and bronchial inhalation testing. Furthermore, the patient had 2 acute episodes of anaphylaxis a few minutes after eating salad containing tamarillo. He had never tasted tamarillo before. The allergologic study included skin prick tests, serum specific IgE determinations, bronchial challenges, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and immunoblotting. RESULTS: Results of skin prick tests with common aeroallergens were negative. Strong skin prick test responses were obtained with obeche and tamarillo. Results of bronchial challenge testing with obeche extract were positive. In tamarillo extract, a 28-kDa band appeared as the most relevant IgE-binding antigen. A similar band of 28 kDa happens to be frequently detected in obeche-allergic patients. CONCLUSION: To our knowledge, this is the first reported case of anaphylaxis to tamarillo presented in a patient allergic to obeche, which raises the question of a new cross-reactivity antigen.

[Efficacy of noninvasive hemolaserotherapy in patients with bronchial asthma and concomitant rhinosinusitis]. / Effektivnost' neinvazivnoi gemolazeroterapii u bol'nykh bronkhial'noi astmoi s soputstvuiushchim rinosinusitom.

AIM: To study efficacy of low-intensive infrared laser radiation impact on the tympanic membrane in patients with bronchial asthma (BA) and concomitant rhinosinusitis (RS). MATERIAL AND METHODS: 78 patients with moderate BA of a mixed type and concomitant chronic RS were divided into 3 groups: group 1 patients received medication plus infrared laser radiation of the tympanic membrane and paranasal sinuses; group 2 patients were exposed to supravenous laser radiation (0.63 mcm); group 3 received pharmacotherapy alone. The effect of the treatment was assessed by spirometry, peakflowmetry and paranasal sinuses findings. RESULTS: The highest response was achieved in group 1 which manifested with positive changes in clinical, device and spirometric data on BA and x-ray data on RS courses. The least effective treatment was observed in group 3. CONCLUSION: Use of infrared laser radiation of the tympanic membrane and paranasal sinuses projection in the treatment of BA patients with RS is effective, nontoxic and easy to use both in hospitals and outpatient departments.

Association of skin test reactivity, specific IgE, total IgE, and eosinophils with nasal symptoms in a community-based population study. The Dutch ECRHS Group.

BACKGROUND: Skin prick tests and measurement of specific IgE are important markers of the possible causes of disorders of the upper respiratory tract. OBJECTIVE: In this study we investigated the association of skin test reactivity and specific IgE positivity to five common aeroallergens separately and of total serum IgE and eosinophil count with nasal allergy symptoms in a random sample of the adult population in the Netherlands. METHODS: A cross-sectional study was carried out in a sample of 2167 subjects, aged 20 to 70 years, stratified by age and gender. Nasal allergy symptoms were differentiated into three categories: symptoms after exposure to indoor allergens only, symptoms after exposure to outdoor allergens only, and symptoms after exposure to both indoor and outdoor allergens. Associations were investigated by multiple logistic regression analyses with adjustment for area of residence, gender, age, and smoking status. RESULTS: Skin test and specific IgE reactivity to indoor and outdoor allergens were significantly related to their corresponding nasal symptom groups. Odd ratios increased with increasing number of positive skin test results or increasing levels of specific IgE to allergens in all three nasal symptom groups. For each allergen, a positive skin test result together with a positive specific IgE measurement were the strongest predictors of nasal symptoms. Sensitization to house dust mite was the most prevalent in our study population, whereas the association of skin test reactivity and specific IgE positivity with nasal symptoms was strongest for cat allergen. Skin test and specific IgE reactivity to Cladosporium species were not significantly related to the prevalence of nasal symptoms. Total serum IgE was related to nasal symptoms only in subjects who reported symptoms in response to both indoor and outdoor allergens and only at high levels of IgE. Eosinophil count was associated with nasal symptoms in all nasal symptom groups. CONCLUSION: Our findings confirm the close relationship of skin test positivity with reported symptoms of nasal allergy in a general population. Specific IgE positivity also shows a close relationship with nasal symptoms in response to allergen exposure in a general population. Skin testing and specific IgE measurement may be considered complementary to one another in diagnosing allergic rhinitis. Total IgE may be considered an indicator of greater dysregulation of the immune system in atopic allergy. Eosinophil count is associated with nasal symptoms, regardless of type and extent of nasal symptoms.

Major basic protein and topical administration of ketotifen in pollinosis under natural allergen provocation.

In this study we investigated the potential relation among subjective symptoms, blood eosinophil counts and the levels of major basic protein (MBP) in serum throughout the pre- to postpollen season. In addition, we compared the effects of topical administration of ketotifen on these parameters between the prophylactic treatment group (n = 10) and the postsymptomatic treatment group (n = 10). We found that (1) the levels of MBP in serum during the season were significantly higher than those before the season and (2) the levels of the above three parameters in the prophylactic treatment group were significantly lower than those in the postsymptomatic treatment group during the season. It was concluded from these results that the action of MBP may be involved in the pathogenesis of allergic rhinitis. Furthermore, for the first time we provided evidence that topical ketotifen administration could suppress the systemic upregulation of the blood eosinophil count and MBP level in subjects with pollinosis.

Podocarpus gracilior and Callitris verrucosa--newly identified allergens that crossreact with Cupressus sempervirens.

Thirty-six symptomatic patients, with positive skin reactions to Cupressus sempervirens pollen extract were skin-tested with pollen extracts of Podocarpus gracilior and Callitris verrucosa, of these 17 (47%) had positive responses to P. gracilior, nine (25%) to C. verrucosa, and six (17%) to both. None of the non-atopic healthy controls had positive reactions to either of the extracts. Radioallergosorbent test (RAST)-inhibition studies were performed with pooled sera from three patients. Fifty per cent inhibition was obtained with 11 micrograms protein of C. sempervirens, 54 micrograms of P. gracilior, and 71 micrograms of C. verrucosa; however, when pollen extract of Olea europaea, an unrelated allergen, was tested, 265 micrograms protein were needed to obtain 50% inhibition. One-dimension sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) analysis of pollen extracts from the three species revealed that they had several very similar protein bands. Using Western blot analysis, several closely related IgE binding proteins were identified in the three species. It was concluded that the pollen grains of P. gracilior and of C. verrucosa are potentially allergenic. The presence of common allergenic proteins indicate partial crossreactivity with C. sempervirens.

cDNA cloning and expression of Cry j II the second major allergen of Japanese cedar pollen.

We have isolated and sequenced a cDNA clone coding for Cry j II, the second major allergen of Japanese cedar (Cryptomeria japonica) pollen. A 1.7-kilobase cDNA clone contained an open reading frame coding for a 514-amino acid protein, including a putative signal peptide of 54 amino acid and three potential glycosylation sites. The deduced amino acid sequence of the Cry j II shows significant identities to those of the polygalacturonases associated with fruit-ripening in tomato (40%) and avocado (43%) and found in pollen of maize (34%). Cry j II cDNA product expressed in E. coli was recognized by human IgE from patients suffering from cedar pollinosis, suggesting that recombinant Cry j II might be used as an allergen for the clinical diagnosis of cedar pollinosis.