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Periostin: a novel biomarker for chronic rhinosinusitis., Objectives: Rhinosinusitis is characterized by inflammation of the sinuses, resulting in particular symptoms. This study aims to investigate the feasibility of periostin as a biomarker for chronic rhinosinusitis., Methodology: The mucosal tissues of the ethmoid sinus were sampled from 12 patients with chronic rhinosinusitis without nasal polyps (CRsNP) and 25 with chronic rhinosinusitis with nasal polyps (CRwNP). Inferior turbinate biopsy was performed in 15 patients with a deviation of the nasal septum (DNS). Immunohistochemical (IHC) staining was performed to assess the distribution of periostin. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) was conducted to detect the expression of periostin mRNA in nasal tissue specimens. The serum concentration of periostin was measured using enzyme-linked immunosorbent assay (ELISA). Correlation analysis among periostin mRNA in nasal mucosa, IHC staining score of periostin, serum concentration of periostin and proportion of blood eosinophils was performed., Results: The serum concentration of periostin and the IHC staining score of nasal mucosa from CRSsNP and CRSwNP patients were significantly higher than those in DNS counterparts (both P <0.01). The levels of periostin mRNA in CRSsNP and CRSwNP patients were slightly increased, but did not significantly differ from that in the DNS group (both P >0.05). The IHC staining score and serum concentration of periostin were correlated with the proportion of eosinophils in blood (P<0.05 and P <0.0 1)., Conclusion: Periostin can be used as a novel biomarker for chronic rhinosinusitis, which provides a potential target for individualized therapy of chronic rhinosinusitis.

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., (Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Objectives: We aim to provide useful evidence on the relationship between the albumin levels and chronic rhinosinusitis with nasal polyp (CRSwNP) and its potential use as an inexpensive, reliable, and independent prognostic marker of CRSwNP., Materials and Methods: Forty-five patients with CRSwNP and 45 healthy individuals were included in the study. Serum albumin levels were determined. The serum albumin levels of the study and control groups were compared to determine whether there is a statistically significant difference., Results: The mean albumin level of the study group was 4.65 ± 0.38, the median value was 4.70. The mean albumin level of the control group was 4.84 ± 0.39, the median value was 4.90. There was a statistically significant difference between the albumin levels of the study and control groups (P = 0.045, P < 0.05)., Conclusion: The albumin levels were found to be statistically significantly lower in patients with CRSwNP. This result may contribute to the diagnosis of CRSwNP and identifying its prognosis.

Although vitamin D status may be a modifiable risk factor for various respiratory ailments, limited data exists regarding its role in sinonasal infections. Our goal was to investigate the association of 25-hydroxyvitamin D (25OHD) levels with acute rhinosinusitis (ARS) in a large, nationally representative sample of non-institutionalized individuals from the United States. In this cross-sectional study of individuals ≥ 17 years from the National Health and Nutrition Examination Survey 2001-2006, we used multivariable regression analysis to investigate the association of 25OHD levels with ARS, while adjusting for season, demographics (age, sex, race, and poverty-to-income ratio), and clinical data (smoking, asthma, chronic obstructive pulmonary disease, diabetes mellitus, and neutropenia). A total of 3921 individuals were included in our analyses. Median 25OHD level was 22 (interquartile range 16-28) ng/mL. Overall, 15.8% (95% confidence interval [CI] 14.4-17.7) of participants reported ARS within the 24 hours leading up to their survey participation. After adjusting for season, demographics, and clinical data, 25OHD levels were associated with ARS (odds ratio 0.88, 95% CI 0.78-0.99 per 10 ng/mL). When vitamin D status was dichotomized, 25OHD levels < 20 ng/mL were associated with 33% higher odds of ARS (odds ratio 1.33, 95% CI 1.03-1.72) compared with levels ≥ 20 ng/mL. Our analyses suggest that 25OHD levels are inversely associated with ARS. Randomized, controlled trials are warranted to determine the effect of optimizing vitamin D status on the risk of sinonasal infections.

Background and Objectives: Chronic rhinosinusitis (CRS) is a commonly diagnosed disease that has a significant impact on a child's quality of life. However, no useful biomarker is available to identify antibiotic-responsive CRS. We determined the significance of eosinophil-related markers and total IgE levels in childhood CRS with regard to antibiotic response., Design and Setting: This was a case-control study of patients admitted to Uijeongbu St. Mary's Hospital between November 2010 and November 2011 and diagnosed with CRS., Patients and Methods: In this analytical cross-sectional study, we identified children whose symptoms and radiologic abnormalities did not resolve after 12 weeks despite appropriate antibiotics (non-responder CRS group), children whose symptoms and radiologic abnormalities resolved after 12 weeks with appropriate antibiotics (responder CRS group), and healthy controls selected from clinic patients. Skin prick tests were performed along with serum total IgE, total eosinophil count (TEC), serum eosinophil cationic protein (ECP) level, and ImmunoCAP analysis for common allergens., Results: This study included 36 responders, 22 nonresponders and 22 healthy controls. The prevalence of allergic diseases, atopy, and a family history of allergic diseases were significantly higher in the non-responder group than in the responder and control groups. TEC, ECP, and total IgE levels were significantly higher in the non-responder group than in the responder and control groups (all P < .05). Multiple linear regression analysis showed that no response to appropriate antibiotics and TEC was positively associated with ECP concentration., Conclusion: These findings suggest that there is a high prevalence of allergic diseases in the non-responder group, that the TEC and ECP levels in the non-responder group are significantly higher than those in the responder group and controls, and that no response to antibiotics may be due to eosinophilic inflammation. The measurement of serum ECP may be useful in monitoring the progress of childhood CRS with regard to antibiotic response.

Background: No standard study protocol or diagnostic criteria based on nasal provocation test (NPT) and acoustic rhinometry (AR) results are available for allergic rhinitis., Objective: We aimed to evaluate the usefulness of NPT plus AR for the differential diagnosis of local allergic rhinitis (LAR), allergic, and nonallergic rhinitis., Methods: The medical records and skin-prick test (SPT) and NPT results of 262 patients with symptoms of chronic rhinitis were reviewed. Patients were allocated to one of three groups, that is, group A [n = 110, negative SPT result for Dermatophagoides pteronyssinus (DP)], group B (n = 53, weakly positive result), or group C (n = 99, strongly positive result)., Results: Twelve patients had a negative SPT result and provoked response in NPT [≥29% decrease of minimal cross-sectional area (MCA) after DP challenge] were diagnosed to have LAR. After DP challenge, group C showed significant aggravation of nasal symptoms and a greater decrease in acoustic parameters than groups A and B (p < 0.01). In patients with a more than or equal to 2 visual analog scale (VAS) increase in nasal obstruction (NO) after DP challenge, the criterion "a change of total nasal symptom score (TNSS) of more than or equal to 6.5" had 90.6% sensitivity and 77.4% specificity for the diagnosis of allergic rhinitis, whereas the diagnostic criterion "a total nasal volume (TNV) change at 30 minutes after DP challenge of more than or equal to 27.6%" had 73.4% sensitivity and 58.1% specificity., Conclusion: NPT with AR could be a useful tool for the differential diagnosis of allergic, nonallergic, and local allergic rhinitis.

Background: Medical treatment of chronic rhinosinusitis with nasal polyposis (CRSwNP) centers on the administration of steroids. High-dose topical nasal steroids (HDTNS) have shown promising results with less systemic effects than oral steroids. One promising HDTNS is 0.132% dexamethasone nasal spray. We investigated whether intranasal dexamethasone was associated with changes in serum cortisol and/or intraocular pressure (IOP)., Methods: Patients with CRSwNP were treated with dexamethasone sodium phosphate 0.132% nasal spray twice daily. Morning serum cortisol and IOP were checked after at least 6 weeks of therapy., Results: Twenty-eight patients met study criteria. The average serum cortisol level after at least 6 weeks of therapy (average duration of 38.3 weeks) was 9.8 μg/dL (normal range, 4 to 22 μg/dL). Ten patients had suppressed cortisol levels (average, 2.5 μg/dL). Ten patients underwent IOP measurements and none revealed ocular hypertension on tonometry., Conclusion: High-dose dexamethasone nasal spray given for a period of at least 6 weeks does appear to have the potential to cause a decrease in serum cortisol levels; however, future studies with greater power are necessary to support this claim. Additionally, similar administration of high-dose dexamethasone nasal spray did not reveal IOP diagnostic of ocular hypertension on single-measurement tonometry readings., (© 2015 ARS-AAOA, LLC.)

Objective: To investigate the effect of IL-17 and IL-23 in the pathogenesis of allergic rhinitis(AR) and non. allergic rhinitis(NAR)., Method: Selected 156 cases of patients with allergic rhinitis (AR group) and 59 cases of patients with non-allergic rhinitis (NAR group), 60 cases of healthy people (control group). All cases in AR group and NAR groups were evaluated by a visual analog scale (VAS) score of nasal symptoms. Collected peripheral blood and nasal secretions in all cases and then detected IL-17 and IL-23 expression levels., Result: There was no significant difference in VAS score of AR group and NAR group (P>0. 05). IL-17 and IL-23 levels of serum and nasal secretions in AR group and NAR group were both higher than control group, with a highly significant difference (P <0. 05). The research showed a clear correlation between expression of IL-17 and IL-23 both in serum and nasal secretions of AR group and NAR(P<0. 05)., Conclusion: IL-17 and IL-23 may be important cytokines and IL-23/IL-17 pathway may play a significant role in the pathogenesis of allergic rhinitis and non-allergic rhinitis.

Background: The mechanisms and immune pathways associated with chronic rhinosinusitis (CRS) are not fully understood. Immunological changes during acute exacerbation of CRS may provide valuable clues to the pathogenesis and perpetuation of the disease., Objective: To characterize local and systemic immune responses associated with acute worsening of sinonasal symptoms during exacerbation in CRS with nasal polyps (CRSwNP) compared to controls., Methods: This was a non-interventional prospective study of individuals with CRSwNP and normal controls. Subjects underwent a baseline visit with collection of nasal secretions, nasal washes, and serum specimens. Within 3 days of acute worsening of sinonasal symptoms, subjects underwent a study visit, followed by a post-visit 2 weeks later. The sinonasal outcome test-22 (SNOT-22) scores and immunological parameters in the specimens were analysed using a novel, unsupervised learning method and by conventional univariate analysis., Results: Both CRSwNP patients and control subjects showed a significant increase in SNOT-22 scores during acute exacerbation. Increased nasal levels of IL-6, IL-5, and eosinophil major basic protein were observed in CRSwNP patients. A network analysis of serum specimens revealed changes in a set of immunological parameters, which are distinctly associated with CRSwNP but not with controls. In particular, systemic increases in VEGF and GM-CSF levels were notable and were validated by a conventional analysis., Conclusions: CRSwNP patients demonstrate distinct immunological changes locally and systemically during acute exacerbation. Growth factors VEGF and GM-CSF may be involved in the immunopathogenesis of subjects with CRS and nasal polyps experiencing exacerbation., (© 2014 John Wiley & Sons Ltd.)

Background: Asthma is a heterogeneous disease composed of various phenotypes. Periostin, a molecule inducible with interleukin (IL)-4 or IL-13 in bronchial epithelial cells, is a biomarker of "TH2-high" asthma. The objective of this study is to examine whether the serum periostin concentrations are correlated with the severity, specific phenotype(s), or comorbidity of asthma., Methods: Serum concentrations of periostin were measured in 190 Japanese asthmatic patients and 11 healthy controls. The protocol was registered under UMIN 000002980 in the clinical trial registry., Results: The serum concentrations of periostin were significantly higher (P = 0.014) in asthmatics [70.0 (54.0-93.5) ng/ml] than in healthy subjects [57.0 (39.0-63.0) ng/ml], though we found no correlation between serum periostin concentrations and treatment steps required to control asthma. To characterize "high-periostin" phenotype(s), the patients with asthma were divided among tertiles based on the serum concentrations of periostin. The high-periostin group was older at onset of asthma (P = 0.04), had a higher prevalence of aspirin intolerance (P = 0.04) or concomitant nasal disorders (P = 0.03-0.001), higher peripheral eosinophil counts (P < 0.001), and lower pulmonary function (P = 0.02-0.07). The serum concentrations of periostin were particularly high in asthmatic patients complicated by chronic rhinosinusitis with nasal polyps and olfactory dysfunction. In contrast, neither atopic status, control status of asthma, nor quality of life were related with the "high-periostin" phenotype., Conclusion: Elevated periostin concentrations in serum were correlated with a specific phenotype of eosinophilic asthma, late-onset and often complicated by obstructive pulmonary dysfunction and nasal disorders., (Copyright © 2014 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.)

Background: The immunopathogenesis of chronic rhinosinusitis (CRS) is largely unknown, but it is thought that different inflammatory profiles are responsible for the different CRS subtypes. 25-Hydroxyvitamin-D (25-VD3) has been shown to alter inflammatory mediators in other disease processes and 25-VD3 deficiency is associated with CRS with nasal polyps (CRSwNP), but it is unknown if 25-VD3 levels impact local inflammation in CRS. This study investigated the correlation between plasma 25-VD3 and sinonasal mucus monocyte chemoattractant protein-1 (MCP-1), regulated upon activation normal T cell expressed and secreted (RANTES), and basic fibroblast growth factor (bFGF) levels in patients with CRS., Methods: Study subjects undergoing endoscopic sinus surgery (ESS) for CRS were prospectively enrolled from January 2012 to August 2014. Control subjects included patients undergoing ESS for noninflammatory pathology. Blood and sinonasal mucus were collected at the time of ESS. Plasma 25-VD3 was measured by enzyme-linked immunosorbent assay (ELISA) and mucus levels of MCP-1, RANTES, and bFGF by cytometric bead array (CBA)., Results: A total of 57 patients were enrolled and categorized as CRS without nasal polyps (CRSsNP) (n = 31), CRSwNP (n = 14), and controls (n = 12). No significant correlation was found between MCP-1 and 25-VD3. There was a significant negative correlation between 25-VD3 and RANTES (r = -0.612; p = 0.026) and bFGF (r = -0.578; p = 0.039) in CRSwNP patients; however, there was no significant correlation in CRSsNP patients., Conclusion: This data suggests that 25-VD3 may play a role in regulation of RANTES and bFGF expression in CRSwNP. This may occur through regulation of NP fibroblasts or other immune cells. Further investigation is warranted to better elucidate the role of RANTES, bFGF, and 25-VD3 in CRSwNP., (© 2015 ARS-AAOA, LLC.)

Background: Specific antibody deficiency (SAD) involves a deficient response to a polysaccharide vaccine in the setting of normal immunoglobulin G (IgG) levels and chronic infections. Patients with chronic rhinosinusitis (CRS) are often evaluated for SAD. There are limited data that describe patients with CRS and SAD., Objective: The objective of this study was to better characterize the role of SAD in CRS., Methods: We reviewed electronic records of adults with CRS who were evaluated for immunodeficiency with quantitative Ig levels and pre- and postantibody titers to a pneumococcal polysaccharide vaccine (PPV)., Results: Fourteen pneumococcal serotypes were determined in 239 subjects from 2002 to 2009. Of these subjects, 64 had adequate protective titers of 1.3 μg/mL or higher in 7 or more serotypes of the 14 serotypes checked; 56 (23%) had less than 7 protective titers post-PPV and were diagnosed with SAD; and 119 had an adequate response to the vaccine with 7 or more serotypes being higher than 1.3 μg/mL (>50% response) and were characterized as "responders." Subjects with SAD received more antibiotic courses relative to responders in the 2 years after immunization (3.19 ± 2.64 vs 2.19 ± 2.24, P < .05). Of 56 subjects with SAD, 10 (17.9%) received Ig replacement therapy. Subjects who received Ig had fewer numbers of protective pneumococcal titers post-PPV and had more pneumonia (40.0%) versus subjects with SAD who did not receive Ig (10.9%)., Conclusions: Of the 239 patients with CRS with normal IgG levels evaluated for immunodeficiency, 56 (23.4%) had SAD. A majority of patients with SAD may not need Ig replacement; however, a subset of patients with SAD benefit from Ig replacement., (Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Objective: Newly discovered cytokines TSLP and IL33 are being studied as important indicators of Th2 inflammation and their effect on Treg cells is likely to modulate immune response. We attempted to study TSLP and IL-33 and then correlated with Tregs in order to find possible biomarker in these patients., Methods: Sixty-five children (37 with asthma only and 28 with asthma and rhinitis) aged 6.4 ± 3.2 years (patient group) and 15 healthy children aged 8.0 ± 2.6 years (control group) were recruited in this study. In vitro analysis of TSLP and IL-33 was done in serum samples of 65 newly diagnosed children for allergic asthma and 15 healthy children using the sandwich ELISA method. The expression of Treg cells (CD4 + CD25 + FOXP3+) was analyzed by flow cytometry., Results: The mean TSLP in the patient group (592 ± 68 pg/ml) was significantly higher than controls (215 ± 45 pg/ml) (p < 0.05). Alternatively, the expression of FOXP3 + T reg cells was significantly lower in the patient group (52 ± 36) compared with the controls (95.9 ± 3.6) (p = 0.003). IL-33 was also significantly higher (4044 ± 413 pg/ml) in the patient group compared with the controls (3282 ± 331.5 pg/ml) (p = 0.0001). The expression of Treg cells was negatively correlated with the TSLP (r = -0.23, p = 0.07). Asthma control test (ACT) was also negatively correlated with TSLP in the patient group (r = -0.14, p > 0.05)., Conclusion: Children with asthma show elevated serum levels of TSLP, which correlated negatively with asthma control test and Treg cells. TSLP may be used as a biomarker for inflammation in pediatric asthma patients.

Aims: The aim of this study was to analyze the relationship between allergy and different subtypes of chronic rhinosinusitis with nasal polyps (CRSwNP)., Methods: A total of 83 patients with CRSwNP and 20 patients with nasal septum deviation (NSD) as controls were enrolled in our study. Nasal tissue was obtained from all subjects during surgery. Hematoxylin and eosin staining was performed and the CRSwNP cases were classified into eosinophilic nasal polyps (ENP) and noneosinophilic nasal polyps (nENP) cases according to the percent of eosinophils. The Allergy Screen test was used to detect total and specific immunoglobulin E (IgE) against 5 kinds of common inhalant allergens., Results: There were 28 (33.73%) patients with ENP and 55 with nENP. Total IgE levels were significantly increased in ENP compared with nENP patients. The IgE level was significantly correlated with the eosinophil count. According to the 5 kinds of common inhalant allergens, only ENP patients exhibited higher sensitivity to dust mites., Conclusion: Patients with ENP showed significantly higher IgE levels when compared with patients with nENP based on allergy., (© 2015 S. Karger AG, Basel.)

Introduction: We evaluated associations between three a-cellular measures of the oxidative potential (OP) of particulate matter (PM) and acute health effects., Methods: We exposed 31 volunteers for 5 h to ambient air pollution at five locations: an underground train station, two traffic sites, a farm and an urban background site. Each volunteer visited at least three sites. We conducted health measurements before exposure, 2 h after exposure and the next morning. We measured air pollution on site and characterised the OP of PM2.5 and PM10 using three a-cellular assays; dithiotreitol (OP(DTT)), electron spin resonance (OP(ESR)) and ascorbic acid depletion (OP(AA))., Results: In single-pollutant models, all measures of OP were significantly associated with increases in fractional exhaled nitric oxide and increases in interleukin-6 in nasal lavage 2 h after exposure. These OP associations remained significant after adjustment for co-pollutants when only the four outdoor sites were included, but lost significance when measurements at the underground site were included. Other health end points including lung function and vascular inflammatory and coagulation parameters in blood were not consistently associated with OP., Conclusions: We found significant associations between three a-cellular measures of OP of PM and markers of airway and nasal inflammation. However, consistency of these effects in two-pollutant models depended on how measurements at the underground site were considered. Lung function and vascular inflammatory and coagulation parameters in blood were not consistently associated with OP. Our study, therefore, provides limited support for a role of OP in predicting acute health effects of PM in healthy young adults., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: Rhinitis affects many young adults and often shows comorbidity with asthma., Objective: We hypothesized that young adult rhinitis, like asthma, exhibits clinical heterogeneity identifiable by means of cluster analysis., Methods: Participants in the Isle of Wight birth cohort (n = 1456) were assessed at 1, 2, 4, 10, and 18 years of age. Cluster analysis was performed on those with rhinitis at age 18 years (n = 468) by using 13 variables defining clinical characteristics., Results: Four clusters were identified. Patients in cluster 1 (n = 128 [27.4%]; ie, moderate childhood-onset rhinitis) had high atopy and eczema prevalence and high total IgE levels but low asthma prevalence. They showed the best lung function at 18 years of age, with normal fraction of exhaled nitric oxide (Feno), low bronchial hyperresponsiveness (BHR), and low bronchodilator reversibility (BDR) but high rhinitis symptoms and treatment. Patients in cluster 2 (n = 199 [42.5%]; ie, mild-adolescence-onset female rhinitis) had the lowest prevalence of comorbid atopy, asthma, and eczema. They had normal lung function and low BHR, BDR, Feno values, and total IgE levels plus low rhinitis symptoms, severity, and treatment. Patients in cluster 3 (n = 59 [12.6%]; ie, severe earliest-onset rhinitis with asthma) had the youngest rhinitis onset plus the highest comorbid asthma (of simultaneous onset) and atopy. They showed the most obstructed lung function with high BHR, BDR, and Feno values plus high rhinitis symptoms, severity, and treatment. Patient 4 in cluster 4 (n = 82 [17.5%]; ie, moderate childhood-onset male rhinitis with asthma) had high atopy, intermediate asthma, and low eczema. They had impaired lung function with high Feno values and total IgE levels but intermediate BHR and BDR. They had moderate rhinitis symptoms., Conclusion: Clinically distinctive adolescent rhinitis clusters are apparent with varying sex and asthma associations plus differing rhinitis severity and treatment needs., (Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Objective: To explore the expression of interleukin-25 (IL-25) in chronic rhinosinusitis with nasal polyps (CRSwNP) and its potential significance in pathogenesis., Method: IL-25 expression in blood was detected by enzyme-linked immunosorbent assay (ELISA). IL-25 expression in tissue was detected by immunohistochemistry (LSAB method) from polyps (68 CRSwNP patients) and 55 inferior turbinate mucosa from patients with deviation of nasal septum served as control. Complete blood count and HE staining of blood and tissue eosinophil infiltration degree., Result: IL-25 expression in CRSwNP group were significantly higher than the control group, the difference was statistically significant (P < 0.01). IL-25 expression in local organizations was positively correlated with the number of eosinophil infiltration in CRSwNP group (r = 0.679, P < 0.01)., Conclusion: The expression of IL-25 in CRSwNP patients mutually reinforcing and might increase eosinophil infiltration and play an important role in the development of CRSwNP.

Background: This study was performed to investigate the serum level of interleukin (IL)-13, IL-4, and interferon (IFN)-γ in chronic rhinosinusitis with nasal polyps (CRSwNP) and subsequent inflammation pattern and comorbidities including asthma and aspirin intolerance., Methods: A case-control study was conducted on 60 adult patients with CRSwNP with mean age of 37.7±12.7 (ranging from 18 to 70) years, and on 20 healthy controls. Serum levels of IL-13, IL-4, and IFN-γ were assessed, using enzyme-linked immunosorbent assay to be compared between case and control groups. Serum level of total immunoglobulin (Ig) E was also assessed in the patients with CRSwNP., Results: Serum level of IL-13 in the patients with CRSwNP was significantly higher than the controls (0.98±1.56 vs. 0.34±0.16 pg/ml, respectively, p=0.002). IL-4 and IFN-γ did not differ significantly between the two groups. Total IgE level was significantly increased in the patients with CRSwNP, compared to the normal values (301.43±516.54 IU/ml, p=0.033). Among the patients with CRSwNP, 12/60 (20%) had aspirin intolerance and 44/60 (73.3%) had asthma. IgE was also higher in asthmatics than non-asthmatics patients (364.9±586.6 vs. 126.7±135.7, respectively, p=0.015). Patients with aspirin intolerance had higher levels of IFN-γ (4.7±1.4 vs. 4.1±0.6, respectively, p=0.022)., Conclusions: IL-13 with high level of total IgE was observed in the patients with CRSwNP, which predisposes them to have concomitant asthma. IFN-γ seems to be down-regulated in the patients with CRSwNP, but could be over-expressed in the presence of aspirin intolerance., (Copyright © 2013 SEICAP. Published by Elsevier Espana. All rights reserved.)

The surrogate markers for subclassifying eosinophilic chronic rhinosinusitis (ECRS) and non-ECRS remain elusive. We herein performed a cross-sectional study to assess the clinical implication of clinical symptoms, CT findings, blood eosinophil (EOS) examination based on histological examination of tissue eosinophilia in 105 adult CRS patients (including 72 with nasal polyps and 33 without nasal polyps) in southern China. We found the mean score of smell loss was significantly higher in ECRS subgroup than those in non-ECRS subgroup (p < 0.05), whereas the average ethmoid osteitis index in non-ECRS subgroup was significantly higher than that in ECRS subgroup (p < 0.05). Moreover, we found both the mean blood EOS number and ratio were significantly higher in ECRS subgroup than those in non-ECRS subgroup (p < 0.05). By applying receiver operating characteristic (ROC) curve analysis, we found blood EOS number had a sensitivity of 84.9 % and specificity of 84.4 % [area under the curve (AUC): 0.873] at the cutoff level of 0.16 × 10(9)/L, and blood EOS ratio had a sensitivity of 89.0 % and specificity of 84.4 % (AUC: 0.863) at the cutoff level of 2.05 % in this cohort. Our findings indicated that smell loss score, ethmoid osteitis index and blood EOS number and ratio may be used for the differential diagnosis of ECRS as the surrogate markers.

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.

Objectives: Immunoglobulin G4-related disease (IgG4-RD) is characterized by elevation in serum IgG4 levels, typical multiorgan involvement and dramatic response to steroid therapy. We determined the predictive value of an elevated serum IgG4 for the diagnosis of IgG4-RD. We also sought to identify novel conditions, which have characteristic features of IgG4-RD., Methods: We identified all Mayo Clinic Rochester patients with serum IgG4 levels measured between January 2008 and December 2011 (n = 6014). Those with elevated serum IgG4 levels (reference range, 121-140 mg/dL) were included in the analysis and were classified as "definite," "probable," or "no" IgG4-RD., Results: Serum IgG4 levels were elevated in 390 subjects (6.5%) of whom only 39 (10%) had IgG4-RD (29 "definite," 10 "probable"). The positive predictive value of an elevated serum IgG4 for IgG4-RD was poor (10%). Subjects with IgG4-RD differed from those without IgG4-RD in mean age (59.6 ± 15.2 vs 54.4 ± 18.3 years, P < 0.05), % males (90% vs 58%, P < 0.05), mean serum IgG4 level (437 ± 471 vs 223 ± 194 mg/dL, P < 0.05), and presence of chronic rhinosinusitis (7/39 vs 29/351, P = 0.05)., Conclusions: Elevated serum IgG4 levels are not specific for IgG4-RD and are likely to be a false-positive. Chronic rhinosinusitis is likely an as yet underrecognized manifestation of IgG4-RD.

Background: This study investigates the prevalence of local, antigen-specific immunoglobulin E (IgE) from mucosal brush biopsy (MBB) of the inferior turbinates in people diagnosed with chronic, idiopathic, nonallergic rhinitis (NAR) based on negative skin and/or in vitro testing., Methods: A standard cytology brush was used to harvest epithelial cells from the inferior turbinates of 20 adults. These cells were then processed and tested for the presence of total and antigen-specific IgE to 9 common aeroallergens using immunofluorescence. The relationships between detectable IgE and quality of life (QOL), self-reported seasonal symptoms and season of specimen collection were determined., Results: Antigen-specific IgE for at least 1 antigen was detected on MBB in all of 20 (100%) study participants with a mean of approximately 3 sensitizations per participant. IgE to cockroach was present in 18 of 20 (90%) participants. There was no significant association noted between QOL scores or self-reported seasonal symptoms and the presence of specific IgE to any of the study antigens, although the presence of white oak and ragweed IgE was significantly higher in patients tested during the pollen season., Conclusion: This study demonstrated that, using MBB of the inferior turbinates, antigen-specific IgE to at least 1 airborne allergen is detectable in 100% of the idiopathic, NAR study population. This rate of sensitization is notably higher than previous reports, suggesting that the prevalence of atopic disease in the general population may be higher than current estimates. Testing for local sensitization should be considered as part of the complete evaluation for atopic disease., (© 2014 The Authors. International Forum of Allergy & Rhinology published by Wiley Periodicals, Inc., on behalf of ARS-AAOA, LLC.)

Rationale: Most virus-induced attacks of asthma are caused by rhinoviruses (RVs)., Objectives: To determine whether people with asthma are susceptible to an increased viral load during RV infection., Methods: Seventy-four children (4-18 yr old) were enrolled; 28 with wheezing, 32 with acute rhinitis, and 14 without respiratory tract symptoms. Nasal washes were evaluated using quantitative polymerase chain reaction for RV to judge viral load along with gene sequencing to identify strains of RV. Soluble intercellular adhesion molecule-1, IFN-λ1, and eosinophil cationic protein in nasal washes, along with blood eosinophil counts and total and allergen-specific IgE in sera, were also evaluated. Similar assessments were done in 24 young adults (16 with asthma, 8 without) who participated in an experimental challenge with RV (serotype 16)., Measurements and Main Results: Fifty-seven percent of wheezing children and 56% with acute rhinitis had nasal washes testing positive for RV. The geometric mean of viral loads by quantitative polymerase chain reaction in washes from wheezing children was 2.8-fold lower, but did not differ significantly from children with rhinitis (7,718 and 21,612 copies of viral RNA per microliter nasal wash, respectively; P = 0.48). The odds for wheezing were increased if children who tested positive for RV were sensitized to one or more allergens (odds ratio, 3.9; P = 0.02). Similarly, neither peak nor cumulative viral loads differed significantly in washes from adults with asthma compared with those without asthma during the experimental RV challenge., Conclusions: During acute symptoms, children infected with RV enrolled for wheezing or acute rhinitis had similar viral loads in their nasal washes, as did adults with and without asthma infected with RV-16 experimentally.

Aim: Study some immunological indexes in children with allergic diseases depending on bodyweight and clinical manifestations of allergy., Materials and Methods: A correlation analysis of relationship of indexes of natural resistance (phagocytosis, complement), immunoglobulin level and main lymphocyte populations with body weight in 214 children aged 12 - 17 years with various allergic diseases (rhinitis/ rhinoconjunctivitis, atopic dermatitis, bronchial asthma) was carried out. The children were divided into groups based on body mass index (BMI): 73 (34%) children with normal weight, 74 (35%) overweight and 67 (31%) obese., Results: The analysis has shown that the frequency of detection of children with obesity is the highest for age 12 - 14 years. With the increase of age the number of obese children decreases (OR - 9.0; 95% CI: 1.56 - 51.87; p = 0.008 and OR - 0.27; 95% CI: 0.08 - 0.94; p = 0.04, respectively). An interrelation of BMI with clinical exacerbations of allergy was detected. Out of 166 patients with allergic diseases combined with bronchial asthma excessive weight was detected in 62 (37%), obesit--in 57 (34%) and normal weigh--in 47 (28%). In a group of 48 children with allergy without asthma excessive weight was noted in 12 (25%), obesit--in 10 (21%) and normal weigh--in 26 (54%) of patients. In children with bronchial asthma excessive weight occurs almost 3 times more frequently than in children with allergy and without asthma. Differences could not be detected in 3 groups of children when immune status indexes were compared, except total IgE and NK cell levels. Total IgE level was the highest in obese children (2.7 log), differed significantly from the level in obese (2.46 log) and normal weight (2.37 log, r = 0.32, p < 0.05) children. The relative content of NK cells in blood of obese children was significantly higher than in children withnoormal and excessive weight (r = 0.41). The analysis of significant correlation coefficient indexes detected correlative associations of some immunological indexes with BMI. In overweight children a negative relation between the level of complement and BMI (r = -0.61) and positive relation with phagocytosis index (r = 0.58) were detected., Conclusion: Obesity in children with allergic diseases is associated with an increase of conjugation of immunological indexes manifesting in an increase of number of natural killers (NK), phagocytosis indexes, increased total IgE level against the background of negative interrelation with the main populations of lymphocytes, that in general influences aggravation of allergopathology in the form of a higher frequency of detection of atopic bronchial asthma.

Background: A close relationship between upper and lower respiratory tract diseases has been reported. However, little is known about pulmonary function in patients with upper respiratory tract diseases., Methods: Pulmonary function was measured in: 68 patients with chronic rhinosinusitis without nasal polyps, 135 patients with chronic rhinosinusitis with nasal polyps, 89 patients with allergic rhinitis and 100 normal control subjects. The relationships between pulmonary function and clinical parameters were assessed. These parameters included radiographic severity of chronic rhinosinusitis, serum total immunoglobulin E levels, concentrations of cytokines in nasal secretions and exhaled nitric oxide levels., Results: The pulmonary function of patients with chronic rhinosinusitis was significantly affected. The level of interleukin-5 in nasal secretions was significantly correlated with pulmonary function in patients with chronic rhinosinusitis., Conclusion: The findings indicated latent obstructive lung function changes in chronic rhinosinusitis patients. The cytokines in nasal secretions might be related to obstructive lung function changes in chronic rhinosinusitis.

Background: Vitamin D deficiency is reported to be associated with increased incidence of allergic airway diseases and is correlated with the severity of asthma. This study was designed to determine if serum Vitamin D level is lower in chronic rhinosinusitis with nasal polyposis (CRSwNP) patients and if low serum Vitamin D level is correlated with the severity of CRSwNP., Methods: New CRSwNP patients undergoing elective endoscopic sinus surgery were recruited. Patients with malignancies or asthma were excluded. Twenty chronic rhinosinusitis without nasal polyposis (CRSsNP) patients were used as control. Demographic characteristic information was collected. The severity of CRSwNP was assessed with the Lund-Mackay (LM) score and polyp grading system. Vitamin D status was assessed by measuring circulating 25-hydroxyvitamin D (25OHD) by using commercial chemiluminescence immunoassay. Data were stratified by factors known to affect serum 25OHD, including sex, race, and body mass index., Results: Serum 25OHD levels (ng/mL ± SD) were significantly lower in patients with CRSwNP (21.4 ± 5.7) than in those with CRSsNP (28.8 ± 6.2; p < 0.001). The incidences of vitamin D deficiency (<20 ng/mL) in CRSwNP and CRSsNP patients were 45.5 and 6.3%; however, the incidences of vitamin D insufficiency (20-30 ng/mL) in these patients were 50.0 and 62.5%, respectively. A significantly negative relationship was found between serum 25OHD level and polyp grade (r = -0.63; p = 0.001), indicating lower serum 25OHD was associated with higher polyp grade. Serum 25OHD was inversely related to both LM score and total IgE level as well; however, statistical significance was not found., Conclusion: A significantly lower vitamin D level was found in a group of Taiwanese CRSwNP patients, which revealed an association with greater nasal polyp size. Serum vitamin D levels could be added to the routine workup of patients suffering from CRS and these data could be used to potentially help determine the disease severity.

Background: Mast cells are involved in a number of diseases, including inflammatory diseases such as asthma. Tryptase is a known marker of mast cell burden and activity. However, little is known about the genetic influence on serum tryptase variation. Also, only few and conflicting data exist on serum tryptase in asthma., Objective: To estimate the overall contribution of genetic and environmental factors to the variation in serum tryptase and to examine the correlation between serum tryptase and asthma, rhinitis, markers of allergy, airway inflammation, and airway hyperresponsiveness (AHR) in a sample of Danish twins., Methods: A total of 575 twins underwent a skin prick test and had lung function, AHR to methacholine, exhaled nitric oxide and serum tryptase measured. Multiple regression and variance components models (using the statistical package SOLAR) were computed., Results: Serum tryptase values were available in 569 subjects. Intraclass correlations of serum tryptase in monozygotic and dizygotic twin pairs were 0.84 and 0.42 (P < .001). Variance decomposition showed that genetic factors accounted for 82% (95% confidence interval 74-90, P < .001) of the variation in serum tryptase. Body mass index and sex, but not asthma, rhinitis, or AHR, were correlated to serum tryptase., Conclusion: As much as 82% of the variation in serum tryptase is due to genetic factors. Body mass index and sex, but not asthma or AHR to methacholine, correlate to serum tryptase. A genetic overlap may exist between serum tryptase and body mass index., (Copyright © 2013 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Objectives: To investigate the aetiology of rhinitis occurring in pregnancy, by (1) describing the relationship between pregnancy rhinitis and serum oestrogen, progesterone, placental growth hormone and insulin-like growth factor, and (2) assessing the prevalence of pregnancy rhinitis among Malaysian women., Methods: Prospective study involving 30 pregnant women followed at an ante-natal clinic for 14 months. Hormone levels were analysed during pregnancy and the post-partum period., Results: Levels of all four hormones were elevated in the third trimester, compared with first trimester and postpartum values. Rhinitis patients had higher levels of oestrogen and insulin-like growth factor 1 in the third trimester than non-rhinitis patients, although these differences were not statistically significant. The prevalence of rhinitis was 53.3 per cent, with most cases occurring in the third trimester. Patients with pregnancy rhinitis had a higher prevalence of female babies, compared with non-rhinitis patients (p = 0.003)., Conclusions: Pregnancy rhinitis was significantly more common in women giving birth to female babies. Women with pregnancy rhinitis had a non-significant elevation in oestrogen and insulin-like growth factor 1 levels, compared with those without rhinitis.

Objectives/hypothesis: Chronic Rhinosinusitis (CRS) is accompanied by evidence of a vigorous adaptive immune response, and emerging studies demonstrate that some nasal polyps manifest a polyclonal autoantibody response. We previously found that antibodies against BP180, a component of the hemidesmosome complex and the dominant epitope in autoimmune bullous pemphigoid, were found at elevated levels in nasal polyp tissue. Given the critical role of hemidesmosomes in maintaining epithelial integrity, we sought to investigate the distribution of BP180 in nasal tissue and evaluate for evidence of systemic autoimmunity against this antigen in CRS., Study Design: Case-control experimental study., Methods: The expression and distribution of BP180 in cultured nasal epithelial cells and normal nasal tissue were confirmed using real-time polymerase chain reaction (PCR), Western immunoblotting, immunofluorescence and immunohistochemistry. Sera were collected from three groups: control, CRSsNP, and CRSwNP. A commercially available ELISA was utilized to compare anti-BP180 autoantibody levels in sera., Results: BP180 is expressed in nasal epithelium, but is not confined to the basement membrane as it is in human skin. In cultured nasal epithelial cells, confocal immunofluorescence showed a punctate distribution of BP180 along the basal surface, consistent with its distribution in epithelial keratinocytes. There are significantly higher levels of circulating nonpathologic anti-BP180 autoantibodies in CRS patients compared with normal controls (P <0.05)., Conclusions: BP180 is more widely expressed in nasal epithelium versus skin, although it appears to play a similar role in the formation of hemidesmosomes along the basement membrane. Further investigations are ongoing to characterize the pathogenicity of the anti-epithelial antibody response in CRS.

Background: Eosinophil cationic protein (ECP) is a major granule-derived protein with cytotoxic activity found in eosinophils and has been known as a useful marker of allergic inflammation. In this study, we assessed the clinical significance of ECP in chronic inflammation of the nasal mucosa by evaluating the relationship between eosinophil activity and serum ECP concentration in a cohort of subjects with or without chronic rhinosinusitis (CRS) and allergic rhinitis (AR)., Methods: We retrospectively reviewed the medical records of 492 subjects and analyzed eosinophil percentage in nasal smears, serum eosinophil counts, serum ECP concentrations, symptom scores, CT scores, the size of nasal polyp, and recurrence of CRS at follow-up., Results: Elevated serum ECP concentration was closely related with higher eosinophil expression in all subject's nasal smears and sera. CRS subjects without AR had a higher percentage of immune cells that were eosinophils compared with control subjects and it was similar to subjects' with AR only or with both CRS and AR. CRS subjects without AR also had significantly higher serum ECP concentrations and eosinophil counts compared with control subjects. Additionally, serum ECP concentration was significantly correlated with CT scores, symptom scores, polyp size, and recurrence rate in CRS subjects without AR., Conclusion: Serum ECP concentration can be used as a marker of local and systemic eosinophil expression. We conjecture that although serum ECP elevation may not be specific in AR, analysis of serum ECP concentration could be particularly useful in estimating the progression and prognosis of CRS.

Objectives: To investigate which air pollution characteristics are associated with biomarkers for acute nasal airway inflammation in healthy subjects. We hypothesised that associations would be strongest for oxidative potential (OP) of particles., Methods: 31 volunteers were exposed to ambient air pollution at five sites in The Netherlands: two traffic sites, an underground train station, a farm and an urban background site. Each subject visited at least three sites between March and October 2009 and was exposed for 5 h per visit including exercise for 20 min every hour (h). Air pollution measurements during this 5-h-period included particulate matter (PM) mass concentration, elemental composition, elemental and organic carbon (OC), particle number concentration, OP, endotoxins, O3 and NO2. Pro-inflammatory biomarkers were measured before, 2 and 18 h postexposure, including cytokine IL-6 and IL-8, protein and lactoferrin in nasal lavage (NAL) as well as IL-6 in blood. One- and two-pollutant mixed models were used to analyse associations between exposure and changes in biomarkers., Results: In two-pollutant models, cytokines in NAL were positively associated with OC, endotoxin and NO2; protein was associated with NO2; and lactoferrin was associated with all PM characteristics that were high at the underground site. In blood, associations with OC and endotoxin were negative., Conclusions: We observed no consistent effects in two-pollutant models for PM mass concentration and OP. Instead, we found consistent associations with nasal inflammatory markers for other PM characteristics, specifically OC, endotoxin and NO2.

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.

Background: Nonallergic rhinitis (NAR) is a common disease, and local allergic rhinitis (LAR) is a newly described entity that is called "entopy" in recent years. However, the etiology and incidence of NAR and LAR are uncertain. This study evaluates the incidence of LAR in Chinese subjects and serum eosinophil cationic protein (ECP) levels in patients with NAR and LAR and its relationship with symptom scores., Methods: Positive skin-prick tests (SPT), nasal allergen provocation testing (NAPT) to Dermatophagoides farinae (DF), serum Phadiatop tests, and symptom score evaluations were performed in 147 patients with nonatopic persistent rhinitis. LAR was diagnosed by positive NAPT to DF results. The serum ECP level was measured using the UniCAP100 automated system by enzyme-linked immunosorbent assay (Pharmacia Diagnostics, Uppsala, Sweden)., Results: Twelve patients were diagnosed with LAR, and 135 patients were diagnosed with NAR. There was no statistical difference of the visual analog scale scores between the two groups. Serum ECP was significantly increased in the patients with NAR. Serum ECP in the LAR group showed no difference compared with the NAR group or the controls. In the NAR group, nasal obstruction, rhinorrhea, and total scores had close and statistically significant relationships with serum ECP level., Conclusion: The present study provides the first evidence that LAR exists in Chinese subjects. This study also suggests that eosinophils and ECP take part in the pathogenesis of NAR. A local examination for ECP and specific IgE in nasal lavage fluid or secretions in patients with LAR should be performed in a future study.

Background: Obeche wood dust is a known cause of occupational asthma where an IgE-mediated mechanism has been demonstrated., Objective: To characterize the allergenic profile of obeche wood dust and evaluate the reactivity of the proteins by in vitro, ex vivo and in vivo assays in carpenters with confirmed rhinitis and/or asthma, Materials and Methods: An in-house obeche extract was obtained, and two IgE binding bands were purified (24 and 12 kDa) and sequenced by N-terminal identity. Specific IgE and IgG, basophil activation tests and skin prick tests (SPTs) were performed with whole extract and purified proteins. CCD binding was analyzed by ELISA inhibition studies., Results: Sixty-two subjects participated: 12 with confirmed occupational asthma/rhinitis (ORA+), 40 asymptomatic exposed (ORA-), and 10 controls. Of the confirmed subjects, 83% had a positive SPT to obeche. There was a 100% recognition by ELISA in symptomatic subjects vs. 30% and 10% in asymptomatic exposed subjects and controls respectively (p<0.05). Two new proteins were purified, a 24 kDa protein identified as a putative thaumatin-like protein and a 12 kDa gamma-expansin. Both showed allergenic activity in vitro, with the putative thaumatin being the most active, with 92% recognition by ELISA and 100% by basophil activation test in ORA+ subjects. Cross-reactivity due to CCD was ruled out in 82% of cases., Conclusions: Two proteins of obeche wood were identified and were recognized by a high percentage of symptomatic subjects and by a small proportion of asymptomatic exposed subjects. Further studies are required to evaluate cross reactivity with other plant allergens.

Eosinophilia occurs in up to 75-90% of nasal polyps in Caucasians. The chemokines eotaxin and RANTES increase eosinophil recruitment, activation, and survival, and these chemokines are significantly expressed in nasal polyps. We hypothesized that eotaxin and RANTES plasma levels might be correlated with disease severity. We compared the eotaxin and RANTES plasma levels in 20 Taiwanese patients with chronic rhinosinusitis and nasal polyps and 20 Taiwanese healthy controls. Eotaxin and RANTES plasma levels were measured by ELISA and disease severity was scored by CT scans. Compared to controls, patients with nasal polyps had significantly elevated plasma levels of eotaxin and RANTES and increased peripheral blood eosinophils (p < 0.001). Eotaxin plasma levels were significantly correlated with disease severity in patients with chronic rhinosinusitis to a greater extent than were RANTES levels. RANTES and eotaxin levels were also positively correlated with the percentages of peripheral blood eosinophils. Eotaxin plasma levels are significantly correlated with disease severity in Taiwanese patients with nasal polyposis to a greater degree than are RANTES levels. Additional studies are needed to assess whether eotaxin plasma levels can be used to monitor disease progression and attenuation.

Objective: To test the immunoglobulin free light chain (FLC) from nasal secretion(s) and serum of patients with allergic rhinitis and non-allergic rhinitis for the purpose of exploring the possible immunological mechanism., Methods: Sixty consecutive patients were selected between September and December in 2009, involving 30 patients with allergic rhinitis and 30 patients with non-allergic rhinitis, diagnosed by symptoms, signs, SPT and sIgE. Thirty volunteers was chosen as health control (HC). ELISA was used to detect the total IgE, eosinophil cationic protein (ECP), mast cell tryptase (MCT), κFLC, λFLC in nasal secretion and serum. The data was statistically analyzed by SPSS 17.0 software., Results: According to the VAS scores, the nasal symptoms of AR and NAR, including sneeze, nasal discharge, nasal obstruction and nasal itching were compared. There was no statistical difference (t value was 1.189, 0.741, 0.758, 0.797, respectively, P < 0.5); In serum, κFLC, λFLC, IgE, ECP & MCT were increased in NAR compared to HC (P < 0.05); λFLC was increased in NAR compared to AR group (P < 0.05), κFLC and ECP were increased in AR. There was no significant difference between AR and NAR (P < 0.05); In nasal secretion, κFLC, λFLC, IgE, ECP and MCT were increased in AR and NAR compared to HC, and the ECP and IgE were significantly increased in AR compared to NAR (P < 0.05). ; In nasal secretion, the FLCs revealed a significantly higher correlation with MCT (r value was 0.518 and 0.484, P < 0.01), and in serum revealed a significant correlation with ECP (r value was 0.343 and 0.342, P < 0.01)., Conclusions: Immunoglobulin free light chain takes part in the path of physiological process of allergic rhinitis and non-allergic rhinitis with the immunological mechanism.

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., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: The pathogenesis of chronic rhinosinusitis (CRS) has not been fully elucidated. Increased inflammatory cell infiltration and decreased numbers and/or impaired function of T regulatory cells (Tregs) have been reported. This study aimed to determine the role of Tregs in CRS in peripheral blood (PB) and sinus tissue., Methods: Sinus tissue was obtained from 16 CRS subjects and 5 controls. PB from additional 16 CRS subjects and total 20 controls was obtained. Immunohistochemical analysis (CD3(+), CD4(+), CD8(+), and Treg [CD4(+)-FoxP3(+) and CD25(+)-FoxP3(+)] cells) of sinus tissue was performed. Percentage of PB Tregs (CD4(+)-CD25(+)-FoxP3(+) cells) was analyzed by flow cytometry. Spontaneous and phytohemagglutinin (PHA)-induced release of cytokines (IL-6, IL-4, IL-10, interferon gamma, transforming growth factor [TGF] beta1, and TNF-alpha) from PB mononuclear cells (PBMCs) was determined., Results: PB flow cytometric analysis revealed a lower percentage of Tregs in subjects with CRS compared with healthy controls (p = 0.0003). Although no differences in the PB Treg counts were observed between the CRS subjects with nasal polyposis (CRSwNP) and without nasal polyposis (CRSsNP), immunohistochemical analysis performed on sinus tissue revealed a higher proportion of Tregs in CRSwNP subjects compared with CRSsNP (p < 0.05). Additionally, we failed to detect any Tregs from control sphenoid sinus tissue. Lower levels of regulatory cytokines (IL-10 and TGF-β1) and higher levels of proinflammatory cytokines (TNF-α and IL-6) were found from PBMCs from CRS subjects compared with controls (p < 0.05)., Conclusion: Our findings suggest that CRS subjects exhibit a decreased percentage of PB Tregs compared with normal controls. PBMCs from CRS subjects show a more proinflammatory and less regulatory phenotype.

Background: Causes of osteitis in chronic rhinosinusitis (CRS) other than previous surgery are poorly defined. Patients with eosinophilic CRS (ECRS) have more severe disease and poorer outcomes despite repeated surgery. Associations between osteitis and markers of ECRS are not well described., Methods: A cross-sectional study of CRS patients undergoing sinus surgery was conducted. Osteitis was scored radiologically using previously published measures. Associations between osteitis and histopathology, symptoms, endoscopy, CT mucosal score and seromarkers were analyzed., Results: Eighty-eight patients were assessed of whom forty-five had osteitis. Patients undergoing revision surgery recorded higher osteitis scores. Patients with mucosal eosinophilia had higher osteitis score than those without. Patients with osteitis had higher serum eosinophil. Similar relationships were also found in primary surgery. Osteitis was associated with endoscopic and radiologic, but not symptomatic disease severity., Conclusions: Osteitis is associated with tissue and serum eosinophilia in both patients with and without prior surgery. Patients with these features may benefit from post-operative corticosteroid therapy to prevent osteitis.

Background: The association between undetectable serum total IgE level and chronic upper and lower respiratory tract inflammatory diseases is uncertain. We sought to determine whether chronic sinopulmonary inflammatory diseases are present in adult patients with undetectable serum total IgE who reside in inner-city Chicago, IL, USA., Methods: Medical records of patients aged ≥18 years with reported serum total IgE levels <2 and ≥2,000 kU/L who were diagnosed with rhinitis, chronic rhinosinusitis, asthma, and COPD at the University of Illinois Medical Center and Jesse Brown VA Medical Center, Chicago, IL, between 2005 and 2009 were reviewed., Results: Seventeen patients with serum total IgE <2 kU/L and 17 patients with serum total IgE ≥2,000 kU/L, were identified. Ten of 17 patients (59%) with serum total IgE <2 kU/L were diagnosed with chronic sinopulmonary inflammatory diseases, three with chronic rhinosinusitis, four with asthma, one with asthma/COPD, and two with COPD. Twelve of 17 patients (71%) with serum total IgE ≥2,000 kU/L were diagnosed with chronic sinopulmonary inflammatory diseases, three with allergic rhinitis, four with asthma, four with asthma/COPD, and one with COPD. None of the patients reported recurrent sinopulmonary infections. The difference in the number of patients with chronic sinopulmonary inflammatory diseases between both groups was not statistically significant (p = 0.48)., Conclusions: Chronic rhinosinusitis and asthma are present in adult patients with undetectable serum total IgE who reside in inner-city Chicago. Whether this represents a biomarker of distinct chronic rhinosinusitis and asthma phenotypes in this population remains to be determined.

European (Dermatophagoides pteronyssinus) and American (Dermatophagoides farinae) house dust mite species are considered the most common causes of asthma and allergic symptoms worldwide. Der p 1 protein, one of the main allergens of D. pteronyssinus, is found in high concentration in mites faecal pellets, which can became easily airborne and, when inhaled, can cause perennial rhinitis and bronchial asthma. Here we report the isolation of the Der p 1 gene from an Italian strain of D. pteronyssinus and the PVX-mediated expression of its mature form (I-rDer p 1) in Nicotiana benthamiana plants. Human sera from characterized allergic patients were used for IgE binding inhibition assays to test the immunological reactivity of I-rDer p 1 produced in N. benthamiana plants. The binding properties of in planta produced I-rDer p 1 versus the IgE of patients sera were comparable to those obtained on Der p 1 preparation immobilized on a microarray. In this paper we provide a proof of concept for the production of an immunologically active form of Der p 1 using a plant viral vector. These results pave the way for the development of diagnostic allergy tests based on in planta produced allergens.

The parameters of peroxidation of lipids in blood and saliva were analyzed on sampling of 60 patients with recurrent diseases of upper respiratory tracts during period of remission. It is established that the content of primary and secondary products of peroxidation of neutral lipids in blood plasma is lower as compared with healthy persons. The content of end products of peroxidation of neutral lipids and products of oxidation of phospholipids in blood plasma is higher as compared with healthy persons. The characteristics of alterations of intermediates of peroxidation of lipids in various biologic samples depend on the localization of inflammatory process.

The examination was applied to 81 children aged 5-15 years, including 64 children with diagnosis of rhinosinusitis. The control group consisted of 17 healthy children. The set of laboratory clinical diagnostic techniques was applied to detect the causes of pathology. It is established that children with rhinosinusitis suffered from concurrent bacterial and virus infections. The morphologic presentation of mucous membrane of nasal cavity reflects the etiologic factor and the stage of inflammatory process. The detection of concentration of IL-4, IL-6 and IL-8 of blood serum gives a possibility to diagnose children with combined mechanisms of development of rhinosinusitis.

Background: Not much data are available from large, unselected, birth cohort studies on the natural course and comorbidities of rhinitis in children., Objective: To study phenotypes of rhinitis in relation to the natural course and comorbidities of allergic diseases in preschool-age and early school-age children., Methods: We analyzed data from a birth cohort of 2024 children, for whom information on IgEs against 8 common inhaled allergens was available, collected at age 4 and 8 years. The children were assigned to groups of allergic rhinitis (rhinitis with sensitization to allergens), nonallergic rhinitis (rhinitis without sensitization), allergic sensitization but no rhinitis, or neither rhinitis nor sensitization., Results: The proportion of children with allergic rhinitis increased from 5% to 14% from age 4 to 8 years, whereas the proportion of children with nonallergic rhinitis decreased slightly over the same period of development, from 8% to 6%. Of the children with allergic rhinitis when they were 4 years old, 12% underwent remission by the time they were 8 years old; of the children with nonallergic rhinitis, 73% underwent remission during this period of development. Among 4-year-olds without rhinitis who were sensitized to allergen, 56% had allergic rhinitis when they were 8 years old. Among 4- and 8-year-olds, allergic rhinitis and nonallergic rhinitis were associated with asthma, eczema, and food hypersensitivity. Twenty-five percent of 8-year-olds with allergic rhinitis also had oral allergy syndrome., Conclusions: Fewer preschool-age children with allergic rhinitis undergo remission than do those with nonallergic rhinitis. Sensitization to inhaled allergens at an early age (4 years) precedes the development of allergic rhinitis, whereas symptoms of rhinitis do not. Oral allergy syndrome is common among 8-year-olds with allergic rhinitis., (Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)

Vitamin D has been linked in some studies with atopy- and asthma-associated phenotypes in children with established disease, but its role in disease inception at the community level is less clear. The aim of the present study was to investigate associations between vitamin D status and biological signatures indicative of allergy and asthma development in children aged 6 and 14 years in Perth, WA, Australia (latitude 32° S). Serum vitamin D was assayed in 989 6-yr-olds and 1,380 14-yr-olds from an unselected community birth cohort; 689 subjects were assessed at both ages. Vitamin D levels were assessed as a risk modifier for respiratory and allergic outcomes at both ages, using previously ascertained phenotypic data. The predictive value of vitamin D levels at age 6 yrs for development of clinical phenotypes at age 14 yrs was also examined. Serum vitamin D levels in children of both ages were negatively associated with concurrent allergic phenotypes; sex stratification revealed that this association was restricted mainly to males. Furthermore, vitamin D levels at age 6 yrs were significant predictors of subsequent atopy/asthma-associated phenotypes at age 14 yrs. In an unselected community setting, children (particularly males) with inadequate vitamin D are at increased risk of developing atopy, and subsequently bronchial hyperresponsiveness (BHR) and asthma. In a large unselected cohort, males with inadequate vitamin D at 6 and 14 yrs of age had increased atopy and BHR. Low vitamin D at age 6 yrs was a predictor of atopy and asthma at 14 yrs of age.

Objective: Chronic rhinosinusitis is a heterogeneous disease. Most cases of chronic rhinosinusitis with nasal polyp(s) (CRSwNP) in Western countries show a strong tendency for recurrence after surgery and pronounced eosinophil infiltration in the nasal polyps. The prevalence of CRSwNP with pronounced eosinophilic inflammation is steadily increasing and is classified as eosinophilic chronic rhinosinusitis (ECRS) in Japan. However, less than 50% of CRSwNP patients in Japan and East Asia show such features. Since the treatment strategy of ECRS differs from that of non-ECRS, clinical diagnostic criteria that distinguish ECRS from non-ECRS are needed., Methods: A total of 124 patients with CRSwNP patients who underwent endonasal sinus surgery were classified as ECRS or non-ECRS according to their clinical characteristics and the clinical features of the two groups were compared. Computed tomography (CT) images of the sinuses were graded according to the Lund-Mackay system. We also graded CT images of the olfactory cleft. Blood examination findings, sinus CT images and asthma complications were analyzed by multivariate logistic regression. Clinical findings that were significantly different between ECRS and non-ECRS were analyzed by receiver operating characteristic curves to determine optimal predictors of ECRS., Results: Blood eosinophilia, asthma complications and CT image scores were significantly different between ECRS and non-ECRS. In particular, increased blood eosinophil percentage and CT image scores for the posterior ethmoid and the olfactory cleft showed good accuracy as predictors of ECRS. A combination of the cut-off values for three predictors (increased blood eosinophil percentage above the normal range, olfactory cleft score ≥1 and posterior ethmoid score ≥1) indicated high accurate diagnostic ability (sensitivity, 84.6%; specificity, 92.3%)., Conclusion: A set of three clinical findings can differentiate ECRS from non-ECRS with high accuracy, even when these findings are assessed in regular outpatient clinics., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Background: 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., Methods: 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., Results: 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)., Conclusion: 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.

Vitamin D(3) (VD(3) ) is a steroid hormone that regulates bone health and numerous aspects of immune function and may play a role in respiratory health. We hypothesized that T helper type 2 (Th2) disorders, chronic rhinosinusitis with nasal polyps (CRSwNP) and allergic fungal rhinosinusitis (AFRS) would have VD(3) deficiencies, resulting in increased mature dendritic cells (DCs) and bone erosion. We conducted a retrospective study examining VD(3) levels in patients with AFRS (n = 14), CRSwNP (n = 9), chronic rhinosinusitis without nasal polyps (CRSsNP) (n = 20) and cerebrospinal fluid leak repair (non-diseased controls) (n = 14) at time of surgery. Circulating immune cell levels were determined by immunostaining and flow cytometric analysis. Plasma VD(3) and immune regulatory factors (granulocyte-macrophage colony-stimulating factor and prostaglandin E(2) ) were measured by enzyme-linked immunosorbent assay. It was observed that CRSwNP and AFRS demonstrated increased circulating DCs, while chronic rhinosinusitis without nasal polyps displayed increased circulating macrophages. CRSwNP and AFRS were to found to have insufficient levels of VD(3) which correlated inversely with circulating numbers of mature DCs, DC regulatory factors and bone erosion. CRSsNP displayed no change in circulating DC numbers or VD(3) status compared to control, but did display increased numbers of circulating macrophages that was independent of VD(3) status. Lastly, VD(3) deficiency was associated with more severe bone erosion. Taken together, these results suggest support a role for VD(3) as a key player in the immunopathology of CRSwNP and AFRS., (© 2011 The Authors. Clinical and Experimental Immunology © 2011 British Society for Immunology.)