Protective Effects of Licochalcone A Improve Airway Hyper-Responsiveness and Oxidative Stress in a Mouse Model of Asthma.

Licochalcone A was isolated from Glycyrrhiza uralensis and previously reported to have antitumor and anti-inflammatory effects. Licochalcone A has also been found to inhibit the levels of Th2-associated cytokines in the bronchoalveolar lavage fluid (BALF) of asthmatic mice. However, the molecular mechanism underlying airway inflammation and how licochalcone A regulates oxidative stress in asthmatic mice are elusive. In this study, we investigated whether licochalcone A could attenuate inflammatory and oxidative responses in tracheal epithelial cells, and whether it could ameliorate oxidative stress and airway inflammation in asthmatic mice. Inflammatory human tracheal epithelial (BEAS-2B) cells were treated with licochalcone A to evaluate oxidative responses and inflammatory cytokine levels. In addition, BALB/c mice were sensitized with ovalbumin (OVA) and injected intraperitoneally with licochalcone A (5 or 10 mg/kg). Licochalcone A significantly inhibited reactive oxygen species, eotaxin, and proinflammatory cytokines in BEAS-2B cells. Licochalcone A also decreased intercellular adhesion molecule 1 levels in inflammatory BEAS-2B cells, blocking monocyte cell adherence. We also found that licochalcone A significantly decreased oxidative responses, reduced malondialdehyde levels, and increased glutathione levels in the lungs of OVA-sensitized mice. Furthermore, licochalcone A decreased airway hyper-responsiveness, eosinophil infiltration, and Th2 cytokine production in the BALF. These findings suggest that licochalcone A alleviates oxidative stress, inflammation, and pathological changes by inhibiting Th2-associated cytokines in asthmatic mice and human tracheal epithelial cells. Thus, licochalcone A demonstrated therapeutic potential for improving asthma.

Effects of Ligustrazine on Airway Inflammation in A Mouse Model of Neutrophilic Asthma.

OBJECTIVE: To investigate the effects of ligustrazine (LTZ) on airway inflammation in a mouse model of neutrophilic asthma (NA). METHODS: Forty healthy C57BL/6 female mice were randomly divided into 4 groups using a random number table, including the normal control, NA, LTZ and dexamethasone (DXM) groups, with 10 rats in each group. The NA mice model was established by the method of ovalbumin combined with lipopolysaccharide sensitization. At 0.5 h before each challenge, LTZ and DXM groups were intraperitoneally injected with LTZ (80 mg/kg) or DXM (0.5 mg/kg) for 14 d, respectively, while the other two groups were given the equal volume of normal saline. After last challenge for 24 h, the aerosol inhalation of methacholine was performed and the airway reactivity was measured. The bronchoalveolar lavage fluid (BALF) was collected. The Wright-Giemsa staining was used for total white blood cells and differential counts. The levels of cytokines interleukin (IL)-17 and IL-10 were detected by enzyme-linked immunosorbent assay. The pathological change of lung tissue was observed by hematoxylin eosin staining. RESULTS: The airway responsiveness of the NA group was signifificantly higher than the normal control group (P<0.05), while those in the LTZ and DXM groups were signifificantly lower than the NA group (P<0.05). The neutrophil and eosinophil counts in the LTZ and DXM groups were signifificantly lower than the NA group (P<0.05), and those in the LTZ group were signifificantly lower than the DXM group (P<0.05). There were a large number of peribronchiolar and perivascular inflammatory cells in fifiltration in the NA group. The airway inflflammation in the LTZ and DXM groups were signifificantly alleviated than the NA group. The infifiltration in the LTZ group was signifificantly reduced than the DXM group. Compared with the normal control group, the IL-17 level in BALF was signifificantly increased and the IL-10 level in BALF was signifificantly decreased in the NA group (P<0.05). LTZ and DXM treatment signifificantly decreased IL-17 levels and increased IL-10 levels compared with the NA group (P<0.05), and the changes in the above indices were more signifificant in the LTZ group (P<0.05). CONCLUSION: LTZ could alleviate the airway inflflammation in the NA mice model through increasing the IL-10 level and decreasing the IL-17 level.

Vitamin D Supplementation Reduces Induction of Epithelial-Mesenchymal Transition in Allergen Sensitized and Challenged Mice.

Asthma is a chronic disease of the lung associated with airway hyperresponsiveness (AHR), airway obstruction and airway remodeling. Airway remodeling involves differentiation of airway epithelial cells into myofibroblasts via epithelial-mesenchymal transition (EMT) to intensify the degree of subepithelial fibrosis. EMT involves loss in E-cadherin with an increase in mesenchymal markers, including vimentin and N-cadherin. There is growing evidence that vitamin D has immunomodulatory and anti-inflammatory properties. However, the underlying molecular mechanisms of these effects are still unclear. In this study, we examined the contribution of vitamin D on the AHR, airway inflammation and expression of EMT markers in the airways of mice sensitized and challenged with a combination of clinically relevant allergens, house dust mite, ragweed, and Alternaria (HRA). Female Balb/c mice were fed with vitamin D-sufficient (2000 IU/kg) or vitamin D-supplemented (10,000 IU/kg) diet followed by sensitization with HRA. The density of inflammatory cells in the bronchoalveolar lavage fluid (BALF), lung histology, and expression of EMT markers by immunofluorescence were examined. Vitamin D-supplementation decreased AHR, airway inflammation in the BALF and the features of airway remodeling compared to vitamin D-sufficiency in HRA-sensitized and -challenged mice. This was accompanied with increased expression of E-cadherin and decreased vimentin and N-cadherin expression in the airways. These results indicate that vitamin D may be a beneficial adjunct in the treatment regime in allergic asthma.

The MIF Antagonist ISO-1 Attenuates Corticosteroid-Insensitive Inflammation and Airways Hyperresponsiveness in an Ozone-Induced Model of COPD.

INTRODUCTION: Macrophage migration inhibitory factor (MIF) is an inflammatory cytokine associated with acute and chronic inflammatory disorders and corticosteroid insensitivity. Its expression in the airways of patients with chronic obstructive pulmonary disease (COPD), a relatively steroid insensitive inflammatory disease is unclear, however. METHODS: Sputum, bronchoalveolar lavage (BAL) macrophages and serum were obtained from non-smokers, smokers and COPD patients. To mimic oxidative stress-induced COPD, mice were exposed to ozone for six-weeks and treated with ISO-1, a MIF inhibitor, and/or dexamethasone before each exposure. BAL fluid and lung tissue were collected after the final exposure. Airway hyperresponsiveness (AHR) and lung function were measured using whole body plethysmography. HIF-1α binding to the Mif promoter was determined by Chromatin Immunoprecipitation assays. RESULTS: MIF levels in sputum and BAL macrophages from COPD patients were higher than those from non-smokers, with healthy smokers having intermediate levels. MIF expression correlated with that of HIF-1α in all patients groups and in ozone-exposed mice. BAL cell counts, cytokine mRNA and protein expression in lungs and BAL, including MIF, were elevated in ozone-exposed mice and had increased AHR. Dexamethasone had no effect on these parameters in the mouse but ISO-1 attenuated cell recruitment, cytokine release and AHR. CONCLUSION: MIF and HIF-1α levels are elevated in COPD BAL macrophages and inhibition of MIF function blocks corticosteroid-insensitive lung inflammation and AHR. Inhibition of MIF may provide a novel anti-inflammatory approach in COPD.

Low Level Laser Therapy Reduces the Development of Lung Inflammation Induced by Formaldehyde Exposure.

Lung diseases constitute an important public health problem and its growing level of concern has led to efforts for the development of new therapies, particularly for the control of lung inflammation. Low Level Laser Therapy (LLLT) has been highlighted as a non-invasive therapy with few side effects, but its mechanisms need to be better understood and explored. Considering that pollution causes several harmful effects on human health, including lung inflammation, in this study, we have used formaldehyde (FA), an environmental and occupational pollutant, for the induction of neutrophilic lung inflammation. Our objective was to investigate the local and systemic effects of LLLT after FA exposure. Male Wistar rats were exposed to FA (1%) or vehicle (distillated water) during 3 consecutive days and treated or not with LLLT (1 and 5 hours after each FA exposure). Non-manipulated rats were used as control. 24 h after the last FA exposure, we analyzed the local and systemic effects of LLLT. The treatment with LLLT reduced the development of neutrophilic lung inflammation induced by FA, as observed by the reduced number of leukocytes, mast cells degranulated, and a decreased myeloperoxidase activity in the lung. Moreover, LLLT also reduced the microvascular lung permeability in the parenchyma and the intrapulmonary bronchi. Alterations on the profile of inflammatory cytokines were evidenced by the reduced levels of IL-6 and TNF-α and the elevated levels of IL-10 in the lung. Together, our results showed that LLLT abolishes FA-induced neutrophilic lung inflammation by a reduction of the inflammatory cytokines and mast cell degranulation. This study may provide important information about the mechanisms of LLLT in lung inflammation induced by a pollutant.

Polysensitization to aeroallergens and food in eosinophilic esophagitis in a pediatric population.

There are few studies on eosinophilic esophagitis (EE) in the pediatric population in Europe. We present our data and emphasize the following findings: a) all patients had symptoms of allergic respiratory disease prior to receiving a diagnosis of EE with polysensitization (aeroallergens, food allergens); and b) in contrast with the results of earlier studies, food sensitization in our series most often corresponded to legumes.

Polysensitization to aeroallergens and food in eosinophilic esophagitis in a pediatric population / Polisensibilización a aeroalergenos y alimentos en la esofagitis eosinofílica en una población pediátrica

There are few studies on eosinophilic esophagitis (EE) in the pediatric population in Europe. We present our data and emphasize the following findings: a) all patients had symptoms of allergic respiratory disease prior to receiving a diagnosis of EE with polysensitization (aeroallergens, food allergens); and b) in contrast with the results of earlier studies, food sensitization in our series most often corresponded to legumes

Hay pocos estudios sobre esofagitis eosinofílica (EE) en la población pediátrica en Europa. Presentamos nuestros datos, destacando los siguientes hallazgos: a) presencia de enfermedad alérgica respiratoria en todos los pacientes previamente diagnosticados de EE, polisensibiizados (aeroalergenos, alimentos); b) sensibilización a alimentos en nuestra serie, la mayoría a legumbres, en contraste con el resultado de estudios anteriores

[Clinical manifestations of cross-allergic reactions to food among children].

Scientists have recently studied the frequency and possible forms of clinical manifestations of cross-reactivity to food among 239 of Abakan at the age from 6 month to 15 years with skin, respiratory and combined manifestation of atopy It was proved that risk factors of development of cross-reactivity to food occur among 80% of children who have various forms of allergic diseases moreover the cross allergic reactions between the foodstuffs most frequently occur with the gastrointestinal and with skin forms of food allergy and the cross allergic reactions between the pollen and food allergens more frequently occut with the respiratory forms of atopy and dermorespiratory syndrome. Considerably more rarely this type of reactions is discovered between the epidermal and food allergens, which most frequently were revealed with the dermatorespiratory syndrome.

No effects of high-dose omeprazole in patients with severe airway hyperresponsiveness and (a)symptomatic gastro-oesophageal reflux.

Acid gastro-oesophageal reflux may aggravate respiratory symptoms in patients with asthma and chronic obstructive pulmonary disease (COPD) by increasing airway hyperresponsiveness through vagally-mediated pathways. We wanted to determine whether elimination of acid reflux could improve symptoms in such patients. In a randomized, double-blind, placebo-controlled study, 36 allergic and nonallergic subjects (17 males and 19 females, mean age 52 yrs), with airway obstruction and severe airway hyperresponsiveness despite maintenance treatment with an inhaled corticosteroid and with increased acid gastro-oesophageal reflux, were treated either with omeprazole, 40 mg b.i.d., or placebo for 3 months. Primary endpoints were: airway hyperresponsiveness, as determined by the provocative concentration of methacholine producing a 20% fall in forced expiratory volume in one second (PC20); and airway obstruction. Secondary endpoints were: peak expiratory flow variability; reversibility to inhaled ipratropium bromide as a parameter of vagal activity; asthma symptoms scores; and medication used. Reflux was measured by 24 h ambulatory intraoesophageal pH measurement. Omeprazole, 40 mg b.i.d., for 3 months had no beneficial effect on any of the pulmonary parameters, despite its profound effect on acid reflux and improvement of reflux symptoms scores, compared to placebo. The results of this study do not support a role for intensive antireflux therapy to improve pulmonary symptoms and function in patients with asthma and chronic obstructive pulmonary disease, who have severe airway hyperresponsiveness despite maintenance treatment with inhaled corticosteroids.

[Immuno-biological diagnosis of food allergy]. / Diagnostic immuno-biologique de l'allergie alimentaire.

Food allergy is becoming more frequent, with 6% of asthmatics reporting an isolated food allergy, and 5 to 6% of atopic dermatitis patients also have either a single or multiple true food allergy. There is value in immuno-biological diagnosis by: Measurement of total serum IgE. Measurement of mono-allergen-specific IgE, following a measurement by a multi-allergen of the Trophatope type. A study of elimination of foods for 2 or 3 months followed by their re-introduction. Oral provocation tests in a hospital environment under clinical control and subsequent measurement of the mediators:-Plasma histamine, tryptase, and urinary methylhistamine to give proof of responsibility of the food allergen. Nowadays, it is perfectly possible to include in diagnosis the new technologies of the test of activation of basophils/or lymphocytes by means of flow cytometry.

The relation between physician-diagnosed sinusitis, asthma, and skin test reactivity to allergens in 8-year-old children.

The purpose of this study was to assess the prevalence of sinusitis in a nonselected sample of children, and the relation of sinusitis to allergic rhinitis (AR), atopy, asthma, and cough in the same population sample. Of 1246 children enrolled at birth in the Tucson Children's Respiratory Study, 835 were studied at a mean age +/-SD of 8.6 +/- 0.7 years. Questionnaires asking about MD-Sinusitis, MD-AR, MD-Asthma, and cough were completed by parents. Skin tests for seven common aeroallergens in the Tucson area had been performed in 630 of the participating children at the mean age +/-SD of 6.3 +/- 0.9 years. Prevalence of MD-Sinusitis was 13.1%; 78% of subjects with MD-Sinusitis also had MD-AR. Detailed analysis of the relation between MD-Sinusitis and individual environmental allergens tested for showed that only a response to Bermuda grass pollen was significantly associated with MD-Sinusitis after controlling for MD-AR [adjusted odds ratio 2.3 (95% CI 1.2-4.3)]. Having MD-Sinusitis was also significantly associated with MD-Asthma and cough [odds ratios 3.0 (95% CI 1.8-5.2)] and 2.5 (95% CI 1.6-3.8), respectively]. However, logistic regression demonstrated that, after controlling for MD-AR and skin test reactivity, MD-Sinusitis was no longer significantly associated with MD-Asthma or cough. We conclude that MD-Sinusitis is a common condition in childhood. The main independent risk factors in our community for MD-Sinusitis were grass pollen and current MD-AR. MD-Sinusitis was not associated with MD-Asthma or with cough after controlling for skin test reactivity and for MD-AR.

Contact allergy to aeroallergens in children with atopic dermatitis: comparison with allergic contact dermatitis.

Immediate and delayed cutaneous hypersensitivity are believed to be implicated in the physiopathology atopic dermatitis (AD). The purpose of this study was to evaluate Type I and Type IV allergy to aeroallergens in children with AD. 59 children (mean age 5.2 years), presenting with AD according to Hanifin and Rajka's criteria, were skin tested (patch and corresponding prick tests) with common environmental aeroallergens and a restricted panel of the European standard series over a 1-year period. History and clinical data were carefully recorded using a standardized evaluation sheet; total and specific IgE serum levels were evaluated. 17 of 59 patients (28.8%) had at least 1 positive patch test, 32 of 59 patients (54.2%) had at least 1 positive prick test. Corresponding patch and prick tests were observed in 8 out of 17 patients. 5 children with positive patch tests had negative prick tests. Irritant pustular reactions (2/59, i.e. 3%), "angry back" reactions (6/59, i.e. 10%) and doubtful reactions (3/59, i.e. 5%) were excluded from the positive group. Positive patch tests observed included, in decreasing order: D. pteronyssinus and D. farinae (26.8%), garden trees (12.2%), plantain (9.8%), timothy grass, mugwort and damp area trees (4.9% each), and orchard grass (2.44%). 6 children with positive aeroallergen patch tests and 11 children with negative aeroallergen patch tests had at least 1 positive patch test to standard allergens. All children with an irritant reaction to aeroallergens had no reaction to standard patch tests. The relevance of aeroallergens in upgrading the severity of AD lesions has still to be explored by challenge studies and by long-term follow-up.

Adverse food reactions in patients with grass pollen allergic respiratory disease.

The purpose of this study was to assess the frequency of reported food-induced symptoms, and of food allergy or intolerance in 169 allergic patients monosensitized to grass pollen and in a control group of 50 patients who were monosensitized to Dermatophagoides. This study clearly demonstrates that patients with grass pollen-allergic respiratory disease report adverse food reactions more frequently than patients allergic to Dermatophagoides. This increased incidence is due to a high percentage of adverse reactions to some vegetable foods, especially peanut, garlic, tomato, onion; and fruits, such as peach; and animal foods, such as egg (white) and pork. By separating the food-allergic patients from the food-intolerant patients, the number of subjects with food intolerance was higher than that of the patients with food allergy. Crossreactivity between pollen allergens and fruits and vegetable allergens may explain the association between pollen allergy and food allergy, but not the higher incidence of food intolerance. An increased intestinal permeability to macromolecules may be hypothesized as part of a primary defect in permeability in "atopic (pollen allergic?) constitution."

Allergies, upper respiratory tract infections, and asthma.

The aims of this study were (1) to quantify the prevalence of aeroallergen hypersensitivity in presentations for emergency treatment of asthma and (2) to determine the strength of association between viral upper respiratory tract infections (URTIs) and admission for treatment of asthma. A series of 209 asthmatic patients presenting to the Emergency Department (ED) of the Alfred Hospital over 6 months underwent skin prick testing and venipuncture for serum IgE and rye grass pollen (RGP) RAST. A case-control study of 38 asthmatic inpatients and 90 controls admitted for road trauma or endoscopy underwent nasopharyngeal aspiration for viral culture and immunofluorescence (IF). Eighty-four percent of ED asthmatic patients had one or more positive skin tests to common aeroallergens, 57% had a positive skin test, and 45% had a positive RAST to RGP. Viral cultures or IF studies were positive in 8 asthmatic patients and 2 controls. Asthmatic inpatients were 6 times more likely to have a viral URTI than were controls. It is concluded that aeroallergen hypersensitivity is present in most asthmatic patients presenting to the ED, and that there is a strong association between viral URTIs and admission for asthma.

Allergy to honey: relation to pollen and honey bee allergy.

To identify the allergenic components of honey we studied 22 patients with a history of systemic allergic symptoms following honey ingestion. The group of honey-allergic patients was compared with three control groups: 10 subjects sensitized to artemisia, 10 with honey bee venom allergy and 10 without a history of atopy or bee sting reactions. The allergological tests included skin tests and RAST with three different kinds of Swiss honey (dandelion, forest and rape), pollen of compositae species, celery tuber, extract of bee pharyngeal glands, honey bee venom and bee whole body extract. The results show that 3/4 of honey-allergics are sensitive to dandelion honey and 13 of 22 also to compositae pollen. Nine of the honey allergic patients were sensitized to honey bee venom, 3 also to bee pharyngeal glands and to bee whole body extract. Analysis of diagnostic tests and RAST inhibition studies suggest that besides compositae pollen other allergens, most likely of bee origin are important. In honey allergics primary sensitization may be due either to the honey itself, to airborne compositae pollen or even to cross-reacting bee venom components.

[The assessment of the incidence of food allergy or intolerance in patients with respiratory allergy]. / Valutazione della frequenza di allergia o intolleranza alimentare in pazienti affetti da allergia respiratoria.

In this study we have evaluated the possible relationship between food allergens and hypersensitivity to grass pollens. One hundred-thirty patients with grass pollen pollinosis and symptoms probably related to adverse reaction to foods were selected. Skin prick test for food allergens was positive in 79 patients (60.7%) Statistical analysis using chi-square test showed a high significant relationship between grass pollen and nuts, peanuts, beans and peas (p less than 0.0001). Elimination diet and challenge test allowed us to identify the responsible foods in 61 out 79 patients (77.2%). Twelve patients were affected by food allergy (challenge test, skin prick test and RAST positive and concordant); 49 patients suffered from intolerance. Possible causes of this high relationship are discussed.

Effect of pollen immunotherapy on food hypersensitivity in children with birch pollinosis.

Of 72 children with severe rhinoconjunctivitis due to birch pollinosis, 67 (93%) reported sensitivity against nuts, apples, etc. The hayfever symptoms improved by immunotherapy but neither subcutaneous (n = 42) nor oral (n = 14) immunotherapy with birch pollen allergen preparations made the food sensitivity decrease significantly more than the placebo oral immunotherapy (n = 16).

Sensitivity to tomato and peanut allergens in children monosensitized to grass pollen.

Possible associations between allergy to grass pollen and positive skin tests to food allergens were studied in 102 children monosensitized (as to inhalant allergens) to grass pollen, and in 117 children monosensitized (as to inhalant allergens) to Dermatophagoides. Thirty-two foods were tested by an epicutaneous method. Positive skin tests to food allergens were more frequent in children with allergy to grass pollen (59.8%) than in children with allergy to Dermatophagoides (9.4%). A considerably high frequency of positive reactions to tomato (39.2%), peanut (22,5%), green pea (13.7%), and wheat (11.7%) was observed in children with allergy to grass pollen. Positive skin tests to peanut closely correlated with positive RAST results and nasal provocation tests, whereas in children with skin test positivity to tomato a close correlation with nasal provocation tests but a 45% correlation with a positive RAST result were observed. RAST inhibition experiments were carried out, and the results may suggest the presence of cross-reacting IgE to grass pollen, tomato, and peanut antigens. Clinical implications of these findings are discussed in the light of histories of food hypersensitivity, urticaria-angioedema, and atopic dermatitis in children with allergy to grass pollen.