Near-Road Exposure and Impact of Air Pollution on Allergic Diseases in Elementary School Children: A Cross-Sectional Study.

PURPOSE: The study aims to classify schools based on traffic pollutants and their complex sources, to assess the environment, to determine the state of allergic diseases among students using the International Study of Asthma and Allergies in children (ISAAC) questionnaire, and to assess their connection to air pollutants. MATERIALS AND METHODS: A total of seven schools were divided into three categories according to the characteristics of their surrounding environments: three schools in traffic-related zones, two schools in complex source zones I (urban), and two schools in complex source zones II (industrial complex). ISAAC questionnaires were administered and the 4404 completed questionnaires were analyzed. RESULTS: The frequency of asthma treatment during the past 12 months showed a significant increase (p<0.05) with exposure to NO2 [1.67, 95% confidence intervals (CIs) 1.03-2.71] in the complex source zones. The frequency of allergic rhinitis treatment during the past 12 months increased significantly with exposure to Black Carbon (1.60, 95% CIs 1.36-1.90) (p<0.001), SO2 (1.09, 95% CIs 1.01-1.17) (p<0.05), NO2 (1.18, 95% CIs 1.07-1.30) (p<0.01) for all subjects. CONCLUSION: In terms of supporting children's health, care, and prevention related to major spaces for children, such as school zones, spaces used in coming to and leaving school, playgrounds, and classrooms are essential to ensuring not only the safety of children from traffic accidents but also their protection from local traffic pollutants and various hazardous environmental factors.

[Some features of development and course of bronchial asthma in children in azerbaijan].

According to the international "ISAAC" program, we studied the peculiarities of bronchial asthma in children at the age of 13-14 years, in various climatic and geographic regions of Azerbaijan. At the first stage of investigation, 14693 eighth class pupils of high school from the four various regions were surveyed: the I region (n=4979) - an industrial city, placed in a semi-desert area; the II region (n=3010) - rural areas, located in a semi-desert climatic zone; the III region (n=3133) - areas, located in a subtropical climatic zone; the IV region (n=3571) - an ecologically clean mountainous region, located along southern slopes of the Greater Caucasian ridge. At the second stage of the investigation allergological, clinical-functional examinations were carried out in children with symptoms of allergic diseases. It was established that prevalence of BA was reliably more frequent in the industrial city (4,6%) than in other three, especially rural areas. In subtropical climatic area 2,8%, in rural semi-desert area - 2,5%, in mountainous region - 1,8% of examined children were suffering from BA. Study of the clinical course of diseases in children with allergic diseases and their allergic status revealed that structure and expressiveness of sensitization to domestic, pollen, fungous and food allergens depends on residing area.

Weighted road density and allergic disease in children at high risk of developing asthma.

BACKGROUND: Evidence for an association between traffic-related air pollution and allergic disease is inconsistent, possibly because the adverse effects may be limited to susceptible subgroups and these have not been identified. This study examined children in the Childhood Asthma Prevention Study (CAPS), potentially susceptible to air pollution effects because of a family history of asthma. METHODS: We examined cross-sectional associations at age eight years between road density within 75 m and 50 m of home address weighted by road type (traffic density), as a proxy for traffic-related air pollution, on the following allergic and respiratory outcomes: skin prick tests (SPTs), total and specific serum IgE, pre- and post-bronchodilator lung function, airway hyperresponsiveness, exhaled NO, and reported asthma and rhinitis. RESULTS: Weighted road density was positively associated with allergic sensitisation and allergic rhinitis. Adjusted relative risk (RR) for house dust mite (HDM) positive SPT was 1.25 (95% CI: 1.06-1.48), for detectable house dust mite-specific IgE was 1.19 (95% CI: 1.01-1.41) and for allergic rhinitis was 1.30 (95% CI: 1.03-1.63) per 100 m local road or 33.3 m motorway within 50 m of home. Associations were also seen with small decrements of peak and mid-expiratory flows and increased risk of asthma, current wheeze and rhinitis in atopic children. CONCLUSION: Associations between road density and allergic disease were found in a potentially susceptible subgroup of children at high risk of developing atopy and asthma.

Stress and anxiety effects on positive skin test responses in young adults with allergic rhinitis.

BACKGROUND: Anxiety and psychological stress affect allergy-related immune function. How these relations influence the evaluations of patients with allergic rhinitis is unknown. OBJECTIVE: To examine whether anxiety and stress exposure affect skin prick test (SPT) responses to common allergens for which patients with atopy showed no prior positive SPT response. METHODS: Patients with allergic rhinitis, evidenced by clinical history and SPT results, were admitted twice to a hospital research unit for 4 hours. In a crossover design, SPT wheals were assessed before and after the Trier Social Stress Test and then the following morning; for comparison, SPT wheals were assessed before and after a laboratory session without a stressor. Analyses focused on wheal responses for common allergens that tested negative (wheal size <3 mm larger than saline) from SPTs performed at multiple baseline assessments. RESULTS: After the Trier Social Stress Test, more anxious patients with atopy had a higher incidence of positive SPT reactions to antigens that previously tested negative. Anxiety was unrelated to positive SPT incidence under nonstressful conditions. Based on clinical symptom reports, newly positive SPT reactions after the stressor were apparently corrections of previously false-negative SPT reactions. The SPT wheal responses for allergens previously testing negative were enhanced after a stressor. Histamine (positive control) or saline (negative control) SPT responses were not affected. CONCLUSION: A laboratory stressor affected allergen SPT responses in more anxious patients with allergic rhinitis. In addition to clinical history, assessment of anxiety and current stress at the time of the SPT may provide valuable information about a patient's allergic status and aid in clinical decision making.

Work-related airway symptoms, nasal reactivity and health-related quality of life in female hairdressers: a follow-up study during exposure.

OBJECTIVES: Hairdressers often complain of work-related rhinitis (WR). They are infrequently sensitized to persulphates. The cause and mechanism of the symptoms and the effects on their health-related quality of life (HRQoL) remains unclear. The objectives were to follow female hairdressers with WR mainly from bleaching powder regarding nasal reactivity to persulphate and to evaluate symptoms, HRQoL and inflammatory markers in nasal lavage during a working period after vacation and compared with hairdressers without symptoms and pollen allergic women. METHODS: Skin prick tests to persulphate were performed in the hairdressers. Participants kept a diary of symptoms and of work tasks (hairdressers only). They completed HRQoL questionnaires. Eosinophil cationic protein (ECP) in nasal lavage fluid was examined. The symptomatic hairdressers performed nasal challenges with persulphate before and after the exposure. RESULTS: Skin prick tests were negative. Although the nasal reactivity to persulphate did not change a steady increase in nasal symptoms, especially blockage, and in ECP was noticed in the symptomatic hairdressers. The HRQoL deteriorated in the symptomatic hairdressers indicating an effect on their working situation and daily life. The atopics had more, but varying symptoms (itching, sneezing and secretion). CONCLUSIONS: The difference in the clinical picture between the symptomatic hairdressers and the pollen allergic women, the increase in symptoms and ECP in the nasal lavage support the view that a sensitization to hairdresser chemicals by a mechanism not yet understood is operating. The deterioration of the HRQoL in the symptomatic hairdressers indicates a considerable effect on their life.

[Anti-allergic effects of xuebijing and potential role of heme oxygenase-1 against ovalbumin-induced murine allergic rhinitis model].

OBJECTIVE: In this study, we investigated the anti-inflammation effects of Xuebijing in OVA-induced murine allergic rhinitis model. Furthermore, we determined whether heme oxygenase (HO)-1 is required for the protective activity of Xuebijing. METHOD: Airways of OVA-sensitized mice exposed to OVA challenge developed eosinophilia, mucus hypersecretion and increased cytokine levels. Levels of interleukin IL-4, IL-5, IL-13, and tumor necrosis factor (TNF)-alpha in nasal lavage fluid were measured using enzyme-linked immunosorbent assays (ELISAs). Lung tissue and nasal mucosa sections were stained with Mayer's hematoxylin and eosin for assessment of cell infiltration and mucus production, Immunohistochemistry, Real-time PCR and Western Blot analyses for HO-1 protein expression. RESULT: Orally administered Xuebijing significantly inhibited the number of OVA-induced inflammatory cells and IgE production, along with reduced T-helper (Th) 2 cytokine levels, such as IL-4, IL-5 and IL-13, improved the level of IFN-gamma, in nasal lavage fluid. In addition, Xuebijing induced a marked decrease in OVA-induced inflammatory cell infiltration and mucus production in nasal and lung tissues. These effects were correlated with HO-1 mRNA and protein induction. CONCLUSION: Our results indicate that Xuebijing protects against OVA-induced airway inflammation, at least in part, via HO-1 upregulation.

Lactoferrin administration into the nostril alleviates murine allergic rhinitis and its mechanisms.

Lactoferrin (LF) can downregulate allergic airway inflammation in asthma. However, the in vivo effect of exogenous LF on allergic rhinitis (AR), a disease attributed to airway inflammation, has yet to be determined. We investigated the effect of intranasal administration recombinant human (rh) LF and its underlying mechanisms on AR in BALB/c mice. Multiple parameters of allergic responses were evaluated to determine the effect of rhLF. We found that the number of eosinophils and goblet cells, as well as mRNA and protein expression of type 2 helper T (Th2), Th17 and regulatory T (Treg) cells in the nasal cavity, was significantly upregulated in AR mice compared with the controls, Conversely, administration of rhLF prior to or after intranasal ovalbumin challenge markedly downregulated these same parameters. Th1-specific mRNA and protein expression in the nasal cavity of the controls was not different from that in AR mice, but expression significantly increased with rhLF treatment. The mRNA and protein expression of endogenous LF in the nasal cavity was significantly downregulated in AR mice compared with the controls. However, after rhLF treatment, endogenous LF mRNA and protein expression was significantly upregulated. Exogenous rhLF inhibited allergic inflammation in AR mice, most likely by promoting the endogenous LF expression and skewing T cells to a Th1, but not a Th2 and Th17 phenotype in the nasal mucosa. Our findings suggest that rhLF treatment may be a novel therapeutic approach for prevention and treatment AR.

Acetaminophen and/or antibiotic use in early life and the development of childhood allergic diseases.

BACKGROUND: Our understanding of whether the use of acetaminophen and/or antibiotics in early life can cause allergic diseases in later childhood remains inconclusive. The objective of this study was to investigate the temporal relationship between exposure to acetaminophen and/or antibiotics in early life and the development of allergic diseases in later childhood, using two independent birth cohorts derived from the National Health Insurance Research Database (NHIRD) in Taiwan. METHODS: The authors conducted a prospective birth cohort study of 263 620 children born in 1998 and 9910 children born in 2003, separately, from the NHIRD. Exposure status of acetaminophen and/or antibiotics and potential confounding factors were included in the analyses. Cox proportional hazards models were applied to determine the temporal relationship between acetaminophen and/or antibiotic exposure and the development of allergic diseases. RESULTS: We observed a positive relationship between acetaminophen and/or antibiotic exposure during the 1st year of life and the subsequent development of the three examined allergic diseases (atopic dermatitis, asthma and allergic rhinitis) in the 1998 birth cohort, but the observed relationship of drug exposure in the 2003 cohort, especially for atopic dermatitis and asthma, was lower than for those in the 1998 cohort and was not statistically significant. CONCLUSIONS: Our findings provide suggestive evidence that the temporal effect of exposure to acetaminophen and/or antibiotics influences the development of common allergic diseases in later childhood. Further functional studies and/or animal studies are needed to better understand the underlying regulatory mechanisms driving this important clinical and public health issue.

[Development of allergic airway disease model in mice].

OBJECTIVE: To investigate the method of development of allergic airway disease model in mice. METHODS: Ten BALB/c mice were devided into the model group and the control group. Each group contained 5 mice. Ovalbumin (OVA) was used as allergen. OVA was emulsified with aluminum hydroxide and injected intraperitoneally for sensitization. Afterwards the mice from model group were challenged with aerosolized 5% OVA and subsequently instilled with OVA intranasally. For the blank control group the mice were sensitized and challenged with phosphate buffer saline (PBS). After final challenge, the nasal symptoms were scored, and mice were sacrificed for evaluation of eosinophilia of nasal septum, peribronchial inflammation and goblet cell hyperplasia. Mice serum was collected for measurement of OVA-specific IgE concentration, and levels of IL-4 and IL-5 from bronchoalveolar fluids were also tested. RESULTS: Compared with blank control mice, mice from model group displayed typical sneezing and nasal scratching symptoms. The histopathological changes, such as eosinophilia of nasal septum mucosa, infiltration of peribronchial inflammatory cells and hyperplasia of goblet cells were successfully induced by OVA sensitization and challenge. Moreover, mice in model group showed higher level of OVA-specific IgE in serum and IL-4 and IL-5 cytokines in bronchoalveolar fluids[mice from model group: IgE (1237.00 ± 153.20) pg/ml, IL-4 (46.50 ± 10.15) pg/ml, IL-5 (50.81 ± 11.41) pg/ml; mice from control group: IgE (191.90 ± 43.20) pg/ml, IL-4 (7.96 ± 1.80) pg/ml, IL-5 (7.53 ± 2.23) pg/ml;t value were 6.569, 3.738 and 3.724, respectively, all P < 0.05]. CONCLUSION: The method using OVA as allergen could effectively develop a mouse model of allergic airway disease which could be used for pathogenesis study and drug effect evaluation.

Therapeutic potential of curcumin in experimentally induced allergic rhinitis in guinea pigs.

In the present experiments, the possible role of curcumin in ovalbumin induced allergic rhinitis in guinea pig model was investigated. Various allergic rhinitis symptoms viz sneezing, rubbing frequencies, lacrimation and nasal congestion at various humidity conditions as well as on repeated sensitization were studied. The biochemical changes like serum IgE, IL-4 and nitric oxide (NO) in nasal lavage and eosinophil peroxidase activity in nasal homogenates were determined in allergic rhinitis. Curcumin treatment significantly reduced the symptoms (sneezing, rubbing frequencies, lacrimation and nasal congestion) and improved the histopathological alterations (reduction in inflammatory cells infiltration) of nasal mucosa in allergic rhinitis. Furthermore, curcumin treatment prevented significantly elevation of serum IgE, IL-4, NO in nasal lavage and eosinophil peroxidase in nasal homogenate. In the present experimental findings, we suggest that curcumin is a promising anti-allergic agent that may be useful in the clinical management of allergic rhinitis.

Effects of airway exposure to di-(2-ethylhexyl) phthalate on allergic rhinitis.

Recent epidemiological studies have suggested a positive link between atopy morbidity and exposure to phthalate esters, which are environmental chemicals mainly involved in house dust. Nevertheless, experimental studies applying several allergic in vivo models (in addition to epidemiological studies) are needed to prove the precise correlation between phthalates and facilitation of the allergic response/pathophysiology. Among the phthalate esters, di-(2-ethylhexyl) phthalate (DEHP) has been widely used in flexible polyvinyl chloride products, including vinyl flooring and wall covering, and has been widely suggested to have immunomodulating potential. In the present study, we examined the effects of airway exposure to DEHP on allergen (ovalbumin: OVA)-induced rhinitis in mice. The repeated administration of OVA via an intranasal route induced nasal inflammation characterized by the infiltration of granulocytes (neutrophils and eosinophils) into the nasal cavity. In this experimental setting, DEHP did not exaggerate OVA-related inflammatory pathology. However, local (nasal) IL-13 levels were significantly higher in mice treated with allergen plus DEHP than with allergen alone. Taken together, phthalate esters including DEHP have the potential to exacerbate the allergic milieu in the nasal system, as well as dermal and respiratory systems.

Genomic and non-genomic effects of glucocorticoids on allergic rhinitis model in mice.

Glucocorticoids (GCs) are well known for their anti-inflammatory effects, which are elicited through a transcriptional mechanism via a cytosolic glucocorticoid receptor (cGR)-mediated genomic effect. However, recent in vitro studies report that GCs can act as a membrane glucocorticoid receptor (mGR). This study aimed to examine whether mometasone furoate (MF) influences the nasal symptoms induced by histamine, substance P, ATP. Furthermore, the influences of various compounds on MF action were studied in vivo. The mice were intranasally administered with nasal symptom-inciting agents, and the occurrences of sneezing and nasal rubbing were counted. MF repressed the nasal symptoms caused when it was administered 10, 30 and 60min before the induction of nasal symptoms. The repressive effect observed 10min after the administration of MF was inhibited by RU486, a GR antagonist, but not by actinomycin D, a transcriptional inhibitor. In contrast, the repressive effect observed 60min after the administration of MF was inhibited by RU486 and actinomycin D. Therefore, the effects observed 10 and 60min after the MF administration were classified as non-genomic and genomic effects, respectively. The non-genomic effect suppressed the nasal symptoms induced by m-3M3FBS, a phospholipase C (PLC) activator, and was inhibited by U-73122, a PLC inhibitor. The genomic effect was inhibited by N-(p-amylcinnamoyl) anthranilic acid, a phospholipase A2 (PLA2) inhibitor. These results indicate that MF has a non-genomic effect through repression of the activation of PLC via the mGR, and MF has also a genomic effect that was influenced by the inhibition of PLA2 through transcriptional regulation via cGR.

Consumption of artificially-sweetened soft drinks in pregnancy and risk of child asthma and allergic rhinitis.

BACKGROUND: Past evidence has suggested a role of artificial sweeteners in allergic disease; yet, the evidence has been inconsistent and unclear. OBJECTIVE: To examine relation of intake of artificially-sweetened beverages during pregnancy with child asthma and allergic rhinitis at 18 months and 7 years. METHODS: We analyzed data from 60,466 women enrolled during pregnancy in the prospective longitudinal Danish National Birth Cohort between 1996 and 2003. At the 25th week of gestation we administered a validated Food Frequency Questionnaire which asked in detail about intake of artificially-sweetened soft drinks. At 18 months, we evaluated child asthma using interview data. We also assessed asthma and allergic rhinitis through a questionnaire at age 7 and by using national registries. Current asthma was defined as self-reported asthma diagnosis and wheeze in the past 12 months. We examined the relation between intake of artificially-sweetened soft drinks and child allergic disease outcomes and present here odds ratios with 95% CI comparing daily vs. no intake. RESULTS: At 18 months, we found that mothers who consumed more artificially-sweetened non-carbonated soft drinks were 1.23 (95% CI: 1.13, 1.33) times more likely to report a child asthma diagnosis compared to non-consumers. Similar results were found for child wheeze. Consumers of artificially-sweetened carbonated drinks were more likely to have a child asthma diagnosis in the patient (1.30, 95% CI: 1.01, 1.66) and medication (1.13, 95% CI: 0.98, 1.29) registry, as well as self-reported allergic rhinitis (1.31, 95% CI: 0.98, 1.74) during the first 7 years of follow-up. We found no associations for sugar-sweetened soft drinks. CONCLUSION: Carbonated artificially-sweetened soft drinks were associated with registry-based asthma and self-reported allergic rhinitis, while early childhood outcomes were related to non-carbonated soft drinks. These results suggest that consumption of artificially-sweetened soft drinks during pregnancy may play a role in offspring allergic disease development.

Airway inflammatory responses to diesel exhaust in allergic rhinitics.

CONTEXT: Proximity to traffic, particularly to diesel-powered vehicles, has been associated with inducing and enhancing allergies. To investigate the basis for this association, we performed controlled exposures of allergic rhinitics to diesel exhaust (DE) at a dose known to be pro-inflammatory in healthy individuals. OBJECTIVE: We hypothesized that diesel-exhaust exposure would augment lower airway inflammation in allergic rhinitics. MATERIALS AND METHODS: Fourteen allergic rhinitics were exposed in a double-blinded, randomized trial to DE (100 µg/m³ PM10) and filtered air for 2 h on separate occasions. Bronchoscopy with endobronchial mucosal biopsies and airway lavage was performed 18 h post-exposure, and inflammatory markers were assessed. RESULTS: No evidence of neutrophilic airway inflammation was observed post-diesel, however, a small increase in myeloperoxidase was found in bronchoalveolar lavage (p = 0.032). We found no increases in allergic inflammatory cells. Reduced mast cell immunoreactivity for tryptase was observed in the epithelium (p = 0.013) parallel to a small decrease in bronchial wash stem cell factor (p = 0.033). DISCUSSION AND CONCLUSION: DE, at a dose previously shown to cause neutrophilic inflammation in healthy individuals, induced no neutrophilic inflammation in the lower airways of allergic rhinitics, consistent with previous reports in asthmatics. Although there was no increase in allergic inflammatory cell numbers, the reduction in tryptase in the epithelium may indicate mast cell degranulation. However, this occurred in the absence of allergic symptoms. These data do not provide a simplistic explanation of the sensitivity in rhinitics to traffic-related air pollution. The role of mast cells requires further investigation.

Analysis of the association between air pollution and allergic diseases exposure from nearby sources of ambient air pollution within elementary school zones in four Korean cities.

The objectives of this study were to survey elementary school students regarding the environmental conditions of their elementary schools and to assess the relationship between air pollution and allergic disease using the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire. Therefore, this study was designed as a cross-sectional study. In this study, seven elementary schools were selected and they were classified into three categories. The selection included one school with no traffic-related or other pollutants, three with traffic-related pollutants, and three with traffic-related and other pollutants from industrial and filling station sources. The ISAAC questionnaire survey was given to all of the students except to those in the 1st grade who were presumed to be less likely to be exposed to the school environment than the remainder of the students attending those seven schools. The assessment of allergic disease was conducted on a total of 4,545 students. Three school zones with critical exposure were selected within each school and they were evaluated based on the levels of black carbon (BC), PM10, SO2, NO2, and O3. There was a significant increase in the risks based on the odds ratios of treatment experiences (within 1 year) for allergy-related diseases such as asthma and allergic rhinitis (a) in the school group with traffic-related pollutants and the school group with complex pollutants were 2.12 (1.41-3.19) and 1.59 (1.06-2.37), respectively, in comparison to the school groups with no exposure to pollutants. This was determined based on the odds ratio of symptoms and treatment experiences for allergy-related diseases by group based on the home town zone as a reference. Also, in the case of atopic dermatitis, the odds ratio of treatment experiences (within 1 year) was 1.42 (1.02-1.97), which indicated elevated risks compared to the students in the S1 school. A regression analysis was used to assess the relationship between the substances and the symptomatic experiences within the last year. There were significant increases in the odds ratio of the symptoms associated with allergic rhinitis and the BC and SO2 in the complex pollution areas. The results of the assessment of the relationship between atopic dermatitis-associated symptoms and O3 showed that the odds ratio increased with statistical significance.

Clara cell 10-kDa protein inhibits T(H)17 responses through modulating dendritic cells in the setting of allergic rhinitis.

BACKGROUND: T(H)17 responses have recently been implicated to play a role in allergic airway diseases, but their local expression in the setting of allergic rhinitis (AR) and their regulation in allergic airway diseases remain unclear. OBJECTIVE: We sought to investigate the regulatory role of Clara cell 10-kDa protein (CC10), an endogenous regulator of airway inflammation, on T(H)17 responses in the setting of AR. METHODS: Wild-type and homozygous CC10-null mice were used to establish an ovalbumin (OVA)-induced AR model. Human recombinant CC10 was given during sensitization or challenge. T(H)17 responses in human subjects and mice were examined by using flow cytometry, quantitative RT-PCR assay, immunohistochemistry, and ELISA. The direct effect of CC10 on T(H)17 cells and CD11c(+) dendritic cells (DCs) was studied by means of cell culture. Adoptive transfer was used to examine the influence of CC10-conditioned DCs on airway inflammation. The regulatory effect of CC10 on the expression of the CCL20 gene was tested by using the BEAS-2B cell line. RESULTS: Compared with those of control subjects, T(H)17 responses were enhanced in the nasal mucosa of patients with AR. CC10-null mice with AR showed enhanced T(H)17 responses, and CC10 treatment significantly decreased T(H)17 responses. CC10 had no direct effect on in vitro T(H)17 cell differentiation. CC10 could significantly decrease the expression of OX40 ligand, IL-23, and IL-6 but enhance CD86 and TGF-ß expression in DCs. Importantly, CC10 was able to inhibit T(H)17 cell polarization in the presence of OVA-pulsed DCs. CC10 pretreatment inhibited T(H)17 responses elicited by adoptive transfer of OVA-pulsed DCs. Furthermore, CC10 decreased the expression of CCL20 in BEAS-2B cells induced by inflammatory cytokines. CONCLUSION: T(H)17 responses are enhanced in patients with AR, and CC10 inhibits T(H)17 responses through modulation of the function of DCs.

Allergic asthma caused by exposure to bacterial alpha-amylase Termamyl®.

BACKGROUND: Airborne enzymes behave as potent respiratory allergens. Till date, allergic disorders caused by genetically engineered enzymes widely used in the industry, have not been reported. RESULTS AND CONCLUSIONS: We describe a worker employed in the detergent industry who developed asthma and rhinitis from IgE-mediated sensitization to the thermostable endo-alpha-amylase Termamyl® and to the protease Savinase®. This is the first report showing that Termamyl® elicits allergic respiratory disorders in humans.

Design and synthesis of a series of pyrido[2,3-d]pyrimidine derivatives as CCR4 antagonists.

A series of pyrido[2,3-d]pyrimidine derivatives were designed and synthesized based on known CC chemokine receptor 4 (CCR4) antagonists. The activities of all the newly synthesized compounds were evaluated using a chemotaxis inhibition assay. Compound 6b was proven to be a potent CCR4 antagonist that can block cell chemotaxis induced by macrophage-derived chemokine (MDC), thymus and activation regulated chemokine (TARC), and CKLF1, the natural ligands of CCR4. In addition, compound 6b is more effective than budesonide in the murine rhinitis model. The intravenous injection LD50 of compound 6b is 175 mg/kg and the oral LD50 is greater than 2,000 mg/kg.

Bamboo salt reduces allergic responses by modulating the caspase-1 activation in an OVA-induced allergic rhinitis mouse model.

Bamboo salt (BS) is a specially processed salt according to the traditional recipe using sun-dried salt (SDS) and bamboo in Korea. The present study investigated the effects and mechanism of BS, SDS, NaCl, or mineral mixture (containing zinc, magnesium, and potassium) on ovalbumin (OVA)-induced allergic rhinitis (AR) animal model. The increased number of rubs was inhibited by the oral administration of BS, SDS, NaCl, mineral mixture, or nose inhalation of BS. The increased levels of IgE, histamine, and interleukin (IL)-1ß in serum were reduced by BS. The level of interferon-γ was increased, whereas the level of IL-4 was reduced on the spleen tissue of BS-treated mice. In the BS-treated mice, the number of eosinophils and mast cells infiltration increased by OVA-sensitization were also decreased. Protein levels of inflammatory cytokines were reduced by BS or NaCl administration in the nasal mucosa of the AR mice. In addition, BS inhibited caspase-1 activity in the nasal mucosa tissue. In activated human mast cells, BS significantly inhibited the production of IL-1ß and thymic stromal lymphopoietin and activation of caspase-1. Our data indicate that BS has anti-allergic and anti-inflammatory effects by regulating of caspase-1 activation in AR mice and in vitro models.

An antagonist for CCR4 alleviates murine allergic rhinitis by intranasal administration.

BACKGROUND: CCR4 is highly expressed on Th2 cells. These cells play an important role in acute inflammatory responses, including those involved in allergic rhinitis. We determined whether disrupting the CCR4 ligand interaction with CCR4 antagonist could alleviate allergic rhinitis in a mouse model. METHODS: BALB/c mice were sensitized with ovalbumin and alum by intraperitoneal injection and challenged with intranasally administered ovalbumin. Compound 22, which has been reported as a novel small-molecule antagonist of CCR4, was also administered intranasally. In addition, budesonide, an efficient glucocorticoid, was used as a positive control. The effects of compound 22 were quantified by multiple parameters of allergic responses in both nasal and pulmonary tissues. RESULTS: Compound 22 significantly improved symptoms of allergic rhinitis and suppressed levels of total IgE of serum. It dramatically reduced the levels of IL-4 in bronchoalveolar lavage fluid and also decreased the number of inflammatory cells in the fluid. The infiltration of inflammatory cells, especially eosinophils, was markedly reduced in the nasal and pulmonary tissues. The number of IL-4+ cells was also significantly reduced in these tissues. Moreover, the numbers of Foxp3+ cells and IL-17+ cells were reduced, though not to a statistically significant degree. CONCLUSIONS: In our research, CCR4 antagonists such as compound 22 were proven for the first time to alleviate murine allergic rhinitis when administered nasally. CCR4 antagonists may have therapeutic potential for the treatment of allergic rhinitis.