Animals ; Asthma ; drug therapy ; immunology ; metabolism ; physiopathology ; Child, Preschool ; Humans ; Infant ; Leukotrienes ; immunology ; metabolism ; pharmacology ; Respiratory Sounds ; drug effects ; immunology ; physiopathology

OBJECTIVETo discuss the effect of integrated traditional Chinese and Western medicine on Th1/Th2 cytokines level in children with asthma.

METHODChildren with asthma were randomly divided into control group and treatment group. The control group was given Montelukast Sodium tablets for 4 mg (2-5 years old) or 5 mg (6-14 years old), once every night before sleeping. At the same time, the treatment group was given Pingchuan water decoction additionally for one tie per day, in four to six-divided doses for eight weeks. On the other hand, groups of health children were selected as blank control. Before and after treatment, the level of IL-4, IL-13 and IFN-gamma were detected by elisa from 3 mL of venous blood.

RESULTBefore treatment, IL-4 and IL-13 in two groups were obviously higher than healthy group, but IFN-gamma was lower (P < 0.01, P < 0.05). After eight weeks, IL-4 and IL-13 in treatment group went down, but IFN-gamma increased. And there were significant different compared with the control group (P < 0.05).

CONCLUSIONTreating children asthma by integrated traditional Chinese and western medicine can obviously reduce IL4 and IL-13, increase IFN-gamma, and therefore lighten the airway inflammation, prevent asthma attacks effectively.

Adolescent ; Asthma ; drug therapy ; immunology ; metabolism ; Child ; Cytokines ; metabolism ; Female ; Humans ; Male ; Medicine, Chinese Traditional ; methods ; Th1 Cells ; drug effects ; metabolism ; Th2 Cells ; drug effects ; metabolism ; Western World

OBJECTIVEInhaled glucocorticosteroids (ICS) remains the first line controller medication for chronic airway inflammation in asthma till now. If the impact of allergen could not be eliminated, how would the improvement of airway inflammation be achieved with inhaled glucocorticosteroids therapy? What was its effect on airway remodeling? In this study, an animal model of asthma was established and the effects of budesonide on airway allergic inflammation and extracellular matrix (ECM) deposition in sensitized guinea pigs with repeated exposure to allergen were investigated.

METHODSThirty-two male Hartley guinea pigs were randomly divided into four groups with 8 in each group: (A) Group of repeated exposure to ovalbumin (OVA), (B) Group of repeated exposure to OVA plus budesonide (BUD) intervention, (C) Group of stopping repeated exposure to OVA plus stopping BUD intervention, (D) Control group. At 24 h after the last OVA challenge (8 weeks after the first OVA challenge), bronchoalveolar lavage fluid (BALF) was collected from each animal. Total and differential leukocyte counts in BALF was performed on cell suspension smear stained with May-Grünwald-Giemsa (MGG) method. The upper lobe of right lung was removed and regularly fixed, then paraffin embedded lung tissues sections were prepared. The count of eosinophils infiltrated in the airway wall was performed on H&E stained lung tissue sections with LEICA Q500IW computerized image analysis system. Fibronectin and collagen type III (Col-III) deposited in the airway wall were detected by immunohistochemical staining on the paraffin embedded lung tissues sections. The intensity of positive reaction of fibronectin or Col-III deposited in the airway wall was analyzed with LEICA Q500IW computerized image analysis system.

RESULTSThe count of eosinophils in BALF (x 10(5)/ml) of group A and B were higher than that of group C and D (35.70 +/- 25.22, 11.49 +/- 5.51 vs. 1.00 +/- 0.90, 1.02 +/- 0.78, P < 0.01), the difference between group A and B, group B and C was significant. The count of eosinophils infiltrated at each level of airway wall in group A and B were higher than that of group C and D (large airway: 6.95 +/- 2.28, 1.54 +/- 1.09 vs. 0.76 +/- 0.45, 0.88 +/- 0.25; medial airway: 9.22 +/- 3.89, 3.99 +/- 2.3 vs. 1.25 +/- 1.20, 0.64 +/- 0.36; small airway: 11.56 +/- 4.02, 2.67 +/- 1.15 vs. 1.32 +/- 0.83, 0.43 +/- 0.24, P < 0.01), the difference between group A and B, group B and C was significant. The gray values of fibronectin deposited in medial and small airway of group A and B were lower than those of group C and D (medial airway 122 +/- 22, 174 +/- 23 vs. 219 +/- 34, 229 +/- 20; small airway 135 +/- 29, 165 +/- 41 vs. 236 +/- 20, 220 +/- 16, P < 0.05), the difference between group A and B, group B and C was significant. The gray values of Col-III deposited in medial and small airway of group A and B were lower than those of group C and D (medial airway 153 +/- 21, 174 +/- 22 vs. 189 +/- 14, 200 +/- 18; small airway 133 +/- 23, 176 +/- 20 vs. 191 +/- 14, 198 +/- 20, P < 0.05), the difference between group A and B was significant.

CONCLUSIONInhaled budesonide could partially inhibit allergic inflammation and ECM deposition in airway wall in guinea pig chronic asthma model with repeated exposure to allergen. Early inhaled budesonide combined with avoidance of OVA exposure could completely inhibit allergic inflammation and ECM deposition. These results suggest that the inhibitory effect on airway allergic inflammation and airway remodeling of inhaled glucocorticosteroids would be limited when the allergen factor could not be avoided.

Administration, Inhalation ; Airway Remodeling ; drug effects ; immunology ; Allergens ; administration & dosage ; immunology ; Animals ; Asthma ; chemically induced ; drug therapy ; immunology ; Bronchitis, Chronic ; chemically induced ; drug therapy ; immunology ; Bronchoalveolar Lavage Fluid ; immunology ; Budesonide ; administration & dosage ; pharmacology ; Collagen Type III ; metabolism ; Disease Models, Animal ; Eosinophils ; immunology ; Extracellular Matrix ; immunology ; Fibronectins ; metabolism ; Glucocorticoids ; administration & dosage ; pharmacology ; Guinea Pigs ; Immunohistochemistry ; Lung ; drug effects ; immunology ; Male ; Ovalbumin ; administration & dosage ; immunology

OBJECTIVETo evaluate the effect of Shen-reinforcing and qi-supplementing (SRQS) drugs on some ingredients of neuro-endocrine-immune (NEI) network in asthma rat model.

METHODSAsthma model was established by ovalbumin sensitization and long-term excitation. Forty healthy Brown Norway rats of clean grade were randomly divided into 4 groups by randomized digital table, the normal control group and the three treated groups treated by low, moderate and high dose of SRQS drugs respectively. Blood content of adrenocorticotrophic hormone (ACTH) was detected by RIA; interleukin-6 (IL-6) and corticosterone were determined by ELISA; and the mRNA expresion of corticosteroid release hormone (CRH) in hypothalamus was tested by Realtime-PCR.

RESULTSEosinophile inflammation was shown in the pathology of asthma model rats, and also shown a multiple level hypothalamic-pituitary-adrenal axis (HPA axis) disorder at the repeated attack of asthma. After treatment, levels of ACTH and CRH mRNA expression in the treated groups were significantly higher than those in the control group (P <0.05), but the corticosterone only showed a rising tendency. Level of IL-6 increased during the episode, showing a significant negative correlation with ACTH (r = - 0.325, P = 0.043), and had somewhat reduction after SRQS treatment.

CONCLUSIONSRQS drugs could improve the function of HPH axis independent of IL-6, suggesting that the action is possibly targeted on the neuro-endocrine axis, which might be the hypothalamus.

Animals ; Asthma ; drug therapy ; genetics ; immunology ; physiopathology ; Disease Models, Animal ; Drugs, Chinese Herbal ; Humans ; Hypothalamus ; drug effects ; immunology ; metabolism ; Interleukin-6 ; genetics ; immunology ; Kidney ; drug effects ; physiopathology ; Male ; Pituitary-Adrenal System ; drug effects ; immunology ; Qi ; Random Allocation ; Rats

Reactive oxygen species (ROS) play an important role in the pathogenesis of airway inflammation and hyperresponsiveness. Recent studies have demonstrated that antioxidants are able to reduce airway inflammation and hyperreactivity in animal models of allergic airway disease. A newly developed antioxidant, small molecular weight thiol compound, N-acetylcysteine amide (AD4) has been shown to increase cellular levels of glutathione and to attenuate oxidative stress related disorders such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis. However, the effects of AD4 on allergic airway disease such as asthma are unknown. We used ovalbumin (OVA)-inhaled mice to evaluate the role of AD4 in allergic airway disease. In this study with OVA-inhaled mice, the increased ROS generation, the increased levels of Th2 cytokines and VEGF, the increased vascular permeability, the increased mucus production, and the increased airway resistance in the lungs were significantly reduced by the administration of AD4. We also found that the administration of AD4 decreased the increases of the NF-kappaB and hypoxia-inducible factor-1alpha (HIF-1alpha) levels in nuclear protein extracts of lung tissues after OVA inhalation. These results suggest that AD4 attenuates airway inflammation and hyperresponsiveness by regulating activation of NF-kappaB and HIF-1alpha as well as reducing ROS generation in allergic airway disease.
Acetylcysteine/*analogs & derivatives/therapeutic use ; Animals ; Asthma/drug therapy/*immunology/pathology ; Bronchial Hyperreactivity/*drug therapy/metabolism ; Hypoxia-Inducible Factor 1, alpha Subunit/*metabolism ; Mice ; NF-kappa B/*metabolism ; Ovalbumin/immunology ; Reactive Oxygen Species/*metabolism ; Vascular Endothelial Growth Factor A/metabolism

Corticosteroids are considered to be one of the most effective medicine for asthma by suppressing airway inflammation. This study was carried out to investigate the effects of prednisolone in the sputum of exacerbated asthmatics. Clinical severity, cell differentials, levels of interleukin (IL)-5, eosinophil cationic protein (ECP), EG2+ eosinophils, and nitric oxide (NO) metabolites were measured. Sputum was examined 2 weeks apart in 13 exacerbated asthmatics before and after prednisolone treatment, and once in 12 stable asthmatics. We used a sandwich ELISA for IL-5, fluoroimmunoassay for ECP, immunohistochemical staining for EG2+ eosinophils, a NO metabolites assay using modified Griess reaction. Exacerbated asthmatics, in comparison with stable asthmatics, had significantly higher proportion of eosinophils, higher level of ECP, higher percentage of EG2+ eosinophils, and NO metabolites. Exacerbated asthmatics after treatment with prednisolone had reduced the proportions of eosinophils, reduced level of IL-5, ECP and percentage of EG2+ eosinophils. FEV1 was correlated with the proportion of eosinophils, ECP, and IL-5 respectively. These findings suggest that prednisolone is considered to be effective medicine for asthma by suppressing eosinophil activation through IL-5.
Administration, Oral ; Adolescence ; Adrenal Cortex/metabolism ; Adult ; Aged ; Anti-Inflammatory Agents, Steroidal/administration & dosage* ; Asthma/metabolism ; Asthma/immunology* ; Asthma/drug therapy* ; Biological Markers ; Blood Proteins/metabolism* ; Eosinophils/metabolism ; Eosinophils/immunology ; Eosinophils/drug effects* ; Female ; Human ; Interleukin-5/metabolism* ; Leukocyte Count ; Male ; Middle Age ; Nitric Oxide/metabolism ; Prednisolone/administration & dosage* ; Sputum/immunology ; Sputum/cytology

Aspirin intolerant asthma (AIA) is frequently characterized as an aspirin (ASA)-exacerbated respiratory disease (AERD). It is a clinical syndrome associated with chronic severe inflammation in the upper and lower airways resulting in chronic rhinitis, sinusitis, recurrent polyposis, and asthma. AERD generally develops secondary to abnormalities in inflammatory mediators and arachidonic acid biosynthesis expression. Upper and lower airway eosinophil infiltration is a key feature of AERD; however, the exact mechanisms of such chronic eosinophilic inflammation are not fully understood. Cysteinyl leukotriene over-production may be a key factor in the induction of eosinophilic activation. Genetic studies have suggested a role for variability of genes in disease susceptibility and response to medication. Potential genetic biomarkers contributing to the AERD phenotype include HLA-DPB1* 301, LTC4S, ALOX5, CYSLT, PGE2, TBXA2R, TBX21, MS4A2, IL10 -1082A > G, ACE -262A > T, and CRTH2 -466T > C; the four-locus SNP set was composed of B2ADR 46A > G, CCR3 -520T > G, CysLTR1 -634C > T, and FCER1B -109T > C. Management of AERD is an important issue. Aspirin ingestion may result in significant morbidity and mortality, and patients must be advised regarding aspirin risk. Leukotriene receptor antagonists (LTRA) that inhibit leukotriene pathways have an established role in long-term AERD management and rhinosinusitis. Aspirin desensitization may be required for the relief of upper and lower airway symptoms in AERD patients. Future research should focus on identification of biomarkers for a comprehensive diagnostic approach.
Animals ; Asthma, Aspirin-Induced/drug therapy/*genetics/*immunology ; Eosinophils/metabolism ; Genetic Predisposition to Disease/genetics ; Humans ; Leukotriene Antagonists/therapeutic use ; Leukotrienes/metabolism ; Models, Biological ; Polymorphism, Genetic/genetics/physiology

OBJECTIVEAllergic asthma is thought to be mediated by CD4+ T lymphocytes producing the Th2-associated cytokines, which play a critical role in the development of the airway hyper-responsiveness and the eosinophilic inflammatory response. The costimulatory pathway CD28/B7 has been shown to play an important role in CD4+ T cell activation in allergic asthma. This study was conducted to evaluate the role of another costimulatory pathway OX40/OX40 ligand (L) in the pathogenesis of allergic asthma in BALB/c mice.

METHODSAn allergic asthma model in BALB/c mice was established. Thirty-six BALB/c mice were randomly divided into three groups with 12 in each. Mice in treatment group (group B) were treated with neutralizing anti-OX40L monoclonal antibody (mAb, 300 microg per mouse) during the sensitization period. Mice in two control groups, asthma model group (group A) and IgG antibody group (group C) were treated with normal saline (NS) and control IgG respectively instead of anti-OX40L mAb. Bronchoalveolar lavage fluid (BALF) was collected from the mice of each group for counting the total number of white blood cells (including neutrophil granulocyte, lymphocyte, monocyte and eosinophil granulocyte) and the proportions of these cells. The levels of IL-4 and INF-gamma in BALF were measured by ELISA. Lungs were removed for morphological examination after HE and PAS staining, and expression of OX40 in lungs was evaluated by immunohistochemical method.

RESULTS(1) The count of total number of white blood cells in BALF (x10(6)/ml) was lower in group B than that of group A and group C (26.6 +/- 4.6 vs. 36.8 +/- 5.2 and 34.3 +/- 6.9, respectively), the difference between the treatment group (group B) and two control groups (groups A and C) was significant; The proportions of eosinophils and lymphocytes in the BALF (%) were lower in group B than those in group A and group C (eosinophils 15.1 +/- 2.6 vs. 20.0 +/- 4.1 and 19.9 +/- 3.9, respectively; lymphocytes 7.0 +/- 0.9 vs. 8.9 +/- 1.6 and 8.6 +/- 1.8, respectively), the difference between the treatment group and two control groups was significant. (2) The IL-4 level in BALF (pg/ml) was lower in group B than that in group A and group C (672 +/- 58 vs. 809.57 +/- 106.00 and 784 +/- 58, respectively), but the INF-gamma levels in BALF (pg/ml) were higher than those in group A and group C (0.86 +/- 0.09 vs. 0.69 +/- 0.15 and 0.67 +/- 0.13 respectively), and all the differences were statistically significant. (3) The expression of OX40 in the lungs of mice in group B were at a lower level than that of group A and group C, and the morphological changes of asthma were ameliorated in the mice of the treatment group. The signs of mice in treatment group were obviously ameliorated as compared to the two control groups.

CONCLUSIONBlocking the costimulatory pathway by administering the neutralizing anti-OX40L mAb during the sensitization period of allergic asthma model could balance the Th1/Th2 responses, inhibit lung inflammation and ameliorate the signs of mice model of asthma.

Animals ; Antibodies, Monoclonal ; administration & dosage ; immunology ; pharmacology ; Antigens, Differentiation ; immunology ; metabolism ; Asthma ; immunology ; metabolism ; pathology ; therapy ; Bronchoalveolar Lavage Fluid ; cytology ; immunology ; Disease Models, Animal ; Enzyme-Linked Immunosorbent Assay ; Eosinophils ; immunology ; Female ; Immunoglobulin G ; administration & dosage ; immunology ; pharmacology ; Immunohistochemistry ; Interferon-gamma ; analysis ; immunology ; Interleukin-4 ; analysis ; immunology ; Leukocyte Count ; Leukocytes ; immunology ; Lung ; drug effects ; immunology ; pathology ; Lymphocytes ; immunology ; Membrane Glycoproteins ; immunology ; Mice ; Mice, Inbred BALB C ; Ovalbumin ; toxicity ; Tumor Necrosis Factors ; immunology

OBJECTIVETo understand the mechanism of effect of conditioned immune response in curing bronchial asthma.

METHODSAn experimental asthma modal was produced on healthy BALB/C mice (female, 4 - 6 weeks old) by sensitization and stimulation with ovalbumin (OV A). Totally 105 mice were divided into 7 groups randomly with 15 in each and treated differently: in group CIR(1), noise was used as conditioned stimulus (CS) and budesonide and salbutamol as unconditioned stimulus (UCS) respectively, a conditioned immune response model of mice with asthma was established by the combination of CS and UCS 7 times (7 days), then the mice were given CS only, and the combination were given once a week for 20 weeks. In group CIR(2) saccharin (SAC) was taken as CS, and the other treatments were the same as the group CIR(1). In the group of conventional therapy, the mice were given inhalation of nebulized budesonide and salbutamol only for 20 weeks. In the group of lower dose conventional therapy, the mice were given nebulized inhalation of budesonide and salbutamol for the first 7 days, then once a week for 20 weeks. In the noise group the mice were given noise only everyday for 20 weeks. In SAC group the mice were treated with SAC only everyday for 20 weeks. In the blank control group the mice were treated with placebo for 20 weeks. The mice in all the groups were stimulated with OVA once a day. The mice in the healthy control group were given PBS inhalation for 20 weeks. After 20 weeks therapy, the bronchoalveolar lavage fluid (BALF) was taken for eosinophils (EOS) counting. The spleens were taken to obtain CD4(+)T lymphocytes and the expression of neuronal acetylcholine receptor alpha 7 (nAChRalpha7), IL-4, IFN-gamma and IL-17 were detected by flow cytometry.

RESULTS(1) The percent of EOS of groups CIR(1), CIR(2), conventional therapy and healthy control was much lower than that of blank control (P < 0.01), and there was no significant difference among groups CIR(1), CIR(2) and conventional therapy (P > 0.05). (2) The expression of nAChRalpha7, IL-4 and IL-17 of groups CIR(1), CIR(2), conventional therapy and healthy control was much lower than that in blank control group, IFN-gamma was much higher (P < 0.01), and no significant difference was found among groups CIR(1), CIR(2) and conventional therapy (P > 0.05). There was a positive correlation between nAChRalpha7 and IL-4 (r = 0.76, P < 0.01), nAChRalpha7 and IL-17 (r = 0.46, P < 0.01). There was a negative correlation between nAChRalpha7 and IFN-gamma (r = 0.69, P < 0.01). (3) In the groups treated with lower dose of conventional therapy, noise, SAC and blank control, the epithelial tissue of airway were much thicker, the lumens were much narrower, and inflammatory cells and collagen fibers were much more than in the healthy control group, and after therapy, the inflammation in groups CIR(1), CIR(2) and conventional therapy was significantly improved.

CONCLUSIONThe conditioned immune response models established by both noise and SAC as CS and budesonide and salbutamol as UCS can downregulate nAChRalpha7 on CD4(+)T lymphocytes, regulate the function of CD4(+)T lymphocytes, and achieve the same therapeutic efficacy in treatment of asthma.

Administration, Inhalation ; Animals ; Asthma ; drug therapy ; immunology ; Budesonide ; therapeutic use ; CD4-Positive T-Lymphocytes ; immunology ; metabolism ; Female ; Gene Expression Regulation ; Mice ; Mice, Inbred BALB C ; Receptors, Nicotinic ; metabolism ; alpha7 Nicotinic Acetylcholine Receptor

The safety of accelerated schedules of allergen immunotherapy (ASAI) in patients with bronchial asthma (BA) has been reported but there are little data on the safety of ASAI for patients with atopic dermatitis (AD). In this study, we investigated the safety of ASAI in patients with AD. Sixty patients with AD and 18 patients with BA sensitized to house dust mites (HDM) were studied. A maximum maintenance dose of HDM extract, adsorbed to aluminum hydroxide, was administered to patients by subcutaneous injection with either a 3-day protocol (rush immunotherapy) or 1-day protocol (ultra-rush immunotherapy). Systemic reactions were observed 4 of 15 patients (26.7%) with AD during rush immunotherapy, 13 of 45 patients (28.9%) with AD during ultra-rush immunotherapy, and 4 of 18 patients (22.2%) with BA during rush immunotherapy (P > 0.05). No severe or near fatal systemic reactions occurred in 78 subjects of this study. Systemic reactions developed within 4 hr after administration of the maximum allergen dose in 20 of 21 patients (95.2%) with AD and BA who showed systemic reactions during rush or ultra-rush immunotherapy. In conclusion, ASAI was safe and well tolerated in patients with AD. ASAI can be a useful therapeutic option for AD.
Adolescent ; Adult ; Allergens/*therapeutic use ; Aluminum Hydroxide/chemistry ; Animals ; Asthma/therapy ; Dermatitis, Atopic/immunology/*therapy ; Desensitization, Immunologic/*methods ; Drug Administration Schedule ; Female ; Humans ; Infusions, Subcutaneous ; Male ; Pyroglyphidae/*immunology/metabolism