Allergen injection therapy may improve nonallergic bronchial hyperresponsiveness, but results at the moment are less than convincing. The present study was conducted to evaluate the effect of immunotherapy on the degree of nonspecific bronchial hyperresponsiveness in patients with allergic bronchial asthma (BA) and/or allergic rhinitis (AR). Methacholine challenge bronchial provocation test, allergic skin test, serum IgE and peripheral blood eosinophil counts were performed before and after 12 months or more of immunotherapy. The improved group, as determined by a shift of at least two doubling concentrations of methacholine, was 75% of AR (n=16), 41.7% of BA (n=24) and 53.8% of BA+ AR (n=13). The geometric mean of the methacholine provocational concentration (PC20) changed from 3.40 to 14.36 mg/ml (P <0.05) in AR, from 0.73 to 1.04 mg/ml in BA (not significant), and from 1.43 to 5.07 mg/ml (P <0.05) in BA+ AR. In conclusion, nonspecific bronchial hyperresponsiveness was improved by immunotherapy in three quarters of the allergic rhinitis cases and in about a half of the allergic bronchial asthma patients, which suggests that immunotherapy might be helpful at preventing the development of bronchial hyperresponsiveness in allergic rhinitis patients, and that it does not improve bronchial hyperresponsiveness in about a half of allergic bronchial asthma patients.
Adult ; Asthma/therapy* ; Bronchial Hyperreactivity/therapy* ; Hay Fever/therapy* ; Human ; IgE/blood ; Immunotherapy* ; Methacholine Chloride/pharmacology ; Middle Age ; Rhinitis, Allergic, Perennial/therapy*

BACKGROUNDAirway hyperresponsiveness (AHR) is one of the most important characteristics of asthma. This study investigated the parameters, by which assess the airway responsiveness under tidal ventilation.

METHODSFemale BALB/c mice were sensitized and challenged with ovalbumin (OVA) (group A), and part of them were treated with budesonide aerosol (group B). All the mice were anaesthetized and mechanically ventilated. The values of tidal volume (Vt), airway pressure (PA), airway flow (F), expiratory lung resistance (RL) and dynamic compliance of the thorax and lung (CT-L) were recorded by the AniRes2003 animal lung function system. In addition, the expiratory volume in the first 0.1 second after the start of expiration (EV0.1) was obtained according to the flow-volume (F-V) curve. The maximal or minimal values of EV0.1, RL and CT-L were documented after each dose of methacholine (MCH) and compared with values from negative control group (group C).

RESULTS(1) When the dose of MCH reached 100 ng/g or 200 ng/g, the decrease of Vt in group A was much more significant than group C (P = 0.001, < 0.001 respectively), but not so between groups B and group C (P = 0.974, 0.362 respectively). (2) With the dose of 25, 50, 100 or 200 ng/g MCH, the decrease in percentage of EV0.1 in group A was much higher than group C (P = 0.012, 0.025, 0.001, 0.003 respectively), while that in group B showed no significant difference as compared with group C (P = 0.507, 0.896, 0.972, 0.785). (3) RL and CT-L: with the dose of 200 ng/g MCH, there was a statistically significant increase of RL in group A compared to group B or group C (P < 0.001, < 0.001 respectively), but no significant difference between groups B and C (P = 0.266). With doses of 100 ng/g and 200 ng/g MCH, there was a statistically significant decrease of CT-L in group A compared to group B (P = 0.001, = 0.001) and group C (P < 0.001, < 0.001 respectively), but no significant difference between groups B and C (P = 0.775, 0.310). (4) Histopathology: there were eosinophilic predominant peribronchial and perivascular inflammatory influx in murine lungs after OVA sensitizing and challenging, which could be counteracted by inhalation of budesonide in group B.

CONCLUSIONSThe decline in EV0.1 in response to MCH challenge correlated with simultaneous changes in Vt, RL and CT-L, but more sensitively than all the other parameters. The decline in EV0.1 and inflammation in murine lung could be significantly alleviated by inhalation of nebulized budesonide solution, which indicated that EV0.1 to MCH is a valid measure of AHR in mice.

Airway Resistance ; drug effects ; Animals ; Bronchial Hyperreactivity ; drug therapy ; Budesonide ; therapeutic use ; Female ; Lung Compliance ; drug effects ; Methacholine Chloride ; pharmacology ; Mice ; Mice, Inbred BALB C ; Ovalbumin ; immunology

OBJECTIVETo evaluate the effect of traditional Chinese medicine preparations on bronchial hyperesponsiness (BHR)-induced cough.

METHODSixty patients with cough due to BHR (shown by positive bronchial provocation test) were randomly divided into Chinese medicine group (n = 30) and control group (n = 30) to receive Bufeishenqingre decoction twice a day and 100 mg theophylline sustained-release capsules twice a day for one month, respectively. The changes of the clinical symptoms were observed during the treatment and bronchial infrared imaging was performed before and after the treatment.

RESULTSThe symptoms of patients in the Chinese medicine group were more effectively alleviated than those of the control group (P < 0.05). The difference in the temperature between the bronchial lesions and the surrounding normal mucosa changed more obviously in the Chinese medicine group (P < 0.01).

CONCLUSIONBufeishenqingre decoction can relieve the symptoms and improve the abnormalities in infrared imaging of patients with BHR-induced cough.

Adult ; Bronchial Hyperreactivity ; complications ; drug therapy ; Bronchial Provocation Tests ; Bronchodilator Agents ; administration & dosage ; Cough ; drug therapy ; etiology ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Male ; Middle Aged ; Phytotherapy ; Theophylline ; administration & dosage ; Young Adult

Antibodies, Anti-Idiotypic ; therapeutic use ; Asthma ; etiology ; immunology ; physiopathology ; therapy ; Bronchial Hyperreactivity ; physiopathology ; Desensitization, Immunologic ; Humans ; Reflex ; Rhinitis, Allergic, Perennial ; etiology ; immunology ; physiopathology ; therapy ; Rhinitis, Allergic, Seasonal ; etiology ; immunology ; physiopathology ; therapy

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

BACKGROUNDEosinophils are highly related to allergic asthma inflammation. Interleukin (IL)-5 is the major chemokine of eosinophils, inhibition of the activity of IL-5 thus seems to be a potential approach to asthma therapy. The current study was performed to determine whether a recombinant human IL-5 protein as a xenogeneic vaccine has the capability of inducing anti-asthma activities.

METHODSRecombinant human IL-5 was used as a protein vaccine. Mouse asthma model was established to observe the anti-asthma activities. Lung histology was observed; eosinophils in blood and bronchoalveolar lavage were stained and counted. Airway hyperresponsiveness was determined by whole body plethysmograph. Antibody characters and cytokines were detected with enzyme linked immunosorbent assay (ELISA) and Western blot assay.

RESULTSVaccination with recombinant human IL-5 protein as vaccine significantly reduced airway inflammation and airway hyperresponsiveness, and shifted the cytokine production from Th2 (IL-4) to Th1 (INF-gamma) in mice allergic-asthma model. Immunization with recombinant human IL-5 protein vaccine bypassed the immunological tolerance and induced production of polyclonal antibodies that were cross-reactive with murine IL-5.

CONCLUSIONSActive immunization with xenogeneic homologous IL-5 may be a possible therapeutic approach to the treatment of asthma and potentially of other eosinophilic disorders.

Animals ; Asthma ; therapy ; B-Lymphocytes ; immunology ; Bronchial Hyperreactivity ; prevention & control ; Cytokines ; biosynthesis ; Disease Models, Animal ; Interleukin-5 ; immunology ; Male ; Mice ; Mice, Inbred BALB C ; Recombinant Proteins ; immunology ; Th2 Cells ; immunology ; Vaccination

OBJECTIVETo study the effects of polysaccharides of cultured Cryptoporus volvatus(CVPS) on airway hyperresponsiveness of ovalbumin-sensitized rats and to evaluate their mechanisms.

METHODSPolysaccharides A, B (5mg/kg, 20mg/kg) and ketotifen(5mg/kg) or vehicle(same volume of saline) were administrated orally for 10 days in ovalbumin -sensitized rats, methacholine bronchial provocation tests were performed to determine airway hyperresponsiveness. Bronchoalveolar lavage fluid (BALF) and peritoneal lavage fluid were prepared after the animals were challenged by nebulized antigen. The differential white cell count in BALF,and the degranulated mast cell count as well as differential white cell count in peritoneal lavage fluid were performed.

RESULTPolysaccharides markedly inhibited the increased lung resistance and the decreased lung compliance induced by antigen challenge,significantly reduced total cell counts and absolute eosinophil counts in BALF(P<0.05); polysaccharides B was more effective than polysaccharides A. They also inhibited recruitment of inflammatory cells in peritoneal lavage fluid and inhibited the allergen-induced mast cell degranulation.

CONCLUSIONPolysaccharides of CVPS inhibit airway hyperresponsiveness by stabilizing mast cell membranes and reducing infiltration and chemotaxis of eosinophils and may be developed as a potential anti-asthmatic drug.

Animals ; Anti-Asthmatic Agents ; pharmacology ; Bronchial Hyperreactivity ; drug therapy ; Bronchoalveolar Lavage Fluid ; cytology ; Cell Degranulation ; drug effects ; Male ; Mast Cells ; drug effects ; physiology ; Ovalbumin ; immunology ; Polyporaceae ; chemistry ; Polysaccharides ; pharmacology ; Rats ; Rats, Sprague-Dawley

Interleukin-5 (IL-5) accompanies the development of airway inflammation and hyperresponsiveness through the activation of eosinophils. Therefore, interference of IL-5 expression in lung tissue seems to be an accepted approach in asthma therapy. In this study, we designed a small interfering RNA (siRNA) to inhibit the expression of IL-5. The siRNAs against IL-5 were constructed in a lentivirus expressing system, and 1.5x10(6) IFU (inclusion-forming unit) lentiviruses were administered intratracheally to ovalbumin (OVA)-sensitized murine asthmatic models. Our results show that lentivirus-delivered siRNA against IL-5 efficiently inhibited the IL-5 messenger ribonucleic acid (mRNA) expression and significantly attenuated the inflammation in lung tissue. Significant decrease of eosinophils and inflammatory cells were found in peripheral blood, bronchoalveolar lavage fluid (BALF), and lung tissue. In addition, significant inhibition of airway hyperresponsiveness (AHR) was found in the mice treated with siRNA against IL-5. These observations demonstrate that siRNA delivered by means of the lentivirus system is possibly an efficacious therapeutic approach for asthma.
Animals ; Asthma ; immunology ; prevention & control ; Bronchial Hyperreactivity ; immunology ; prevention & control ; Disease Models, Animal ; Genetic Therapy ; methods ; Humans ; Interleukin-5 ; genetics ; immunology ; Male ; Mice ; Mice, Inbred BALB C ; Pneumonia ; immunology ; prevention & control ; RNA ; therapeutic use ; Treatment Outcome

BACKGROUND: Asthma is a common cause of breathing difficulty in children and adults, and is characterized by chronic airway inflammation that is poorly controlled by available treatments. This results in severe disability and applies a huge burden to the public health system. Methane has been demonstrated to function as a therapeutic agent in many diseases. The aim of the present study was to explore the effect of methane-rich saline (MRS) on the pathophysiology of a mouse model of asthma and its underlying mechanism. METHODS: A murine model of ovalbumin (OVA)-induced allergic asthma was applied in this study. Mice were divided into three groups: a control group, an OVA group, and OVA-induced asthmatic mice treated with MRS as the third group. Lung resistance index (RI) and dynamic compliance (Cdyn) were measured to determine airway hyper-responsiveness (AHR). Haematoxylin and eosin (H&E) staining was performed and scored to show histopathological changes. Cell counts of bronchoalveolar lavage fluid (BALF) were recorded. Cytokines interleukin (IL)-4, IL-5, IL-13, tumor necrosis factor α (TNF-α), and C-X-C motif chemokine ligand 15 (CXCL15) from BALF and serum were measured by enzyme-linked immunosorbent assay (ELISA). The oxidative stress indexes, including malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), myeloperoxidase (MPO), and 8-hydroxydeoxyguanosine (8-OHdG), were determined using commercial kits. Apoptosis was evaluated by western blot, quantitative real-time polymerase chain reaction (qRT-PCR), and biochemical examination. RESULTS: MRS administration reversed the OVA-induced AHR, attenuated the pathological inflammatory infiltration, and decreased the cytokines IL-4, IL-5, IL-13, TNF-α, and CXCL15 in serum and BALF. Moreover, following MRS administration, the oxidative stress was alleviated as indicated by decreased MDA, MPO, and 8-OHdG, and elevated SOD and GSH. In addition, MRS exhibited an anti-apoptotic effect in this model, protecting epithelial cells from damage. CONCLUSIONS Methane improves pulmonary function and decreases infiltrative inflammatory cells in the allergic asthmatic mouse model. This may be associated with its anti-inflammatory, antioxidative, and anti-apoptotic properties.
Animals ; Apoptosis/drug effects* ; Asthma/metabolism* ; Bronchial Hyperreactivity/drug therapy* ; Cytokines/analysis* ; Female ; Inflammation/prevention & control* ; Methane/pharmacology* ; Mice ; Mice, Inbred BALB C ; Oxidative Stress/drug effects* ; Saline Solution

Reactive oxygen species (ROS) performs a pivotal function as a signaling mediator in receptor-mediated signaling. However, the sources of ROS in this signaling have yet to be determined, but may include lipoxygenases (LOXs) and NADPH oxidase. The stimulation of lymphoid cells with TNF-alpha, IL-1beta, and LPS resulted in significant ROS production and NF-kappaB activation. Intriguingly, these responses were markedly abolished via treatment with the LOXs inhibitor nordihydroguaiaretic acid (NDGA). We further examined in vivo anti-inflammatory effects of NDGA in allergic airway inflammation. Both intraperitoneal and intravenous NDGA administration attenuated ovalbumin (OVA)-induced influx into the lungs of total leukocytes, as well as IL-4, IL-5, IL-13, and TNF-alpha levels. NDGA also significantly reduced serum levels of OVA-specific IgE and suppressed OVA-induced airway hyperresponsiveness to inhaled methacholine. The results of our histological studies and flow cytometric analyses showed that NDGA inhibits OVA-induced lung inflammation and the infiltration of CD11b+ macrophages into the lung. Collectively, our findings indicate that LOXs performs an essential function in pro-inflammatory signaling via the regulation of ROS regulation, and also that the inhibition of LOXs activity may have therapeutic potential with regard to the treatment of allergic airway inflammation.
Animals ; Antioxidants/metabolism ; Asthma/complications/metabolism/pathology/physiopathology ; Bronchial Hyperreactivity/drug therapy/pathology ; Bronchial Provocation Tests ; Bronchoalveolar Lavage Fluid/cytology ; Cells, Cultured ; Drug Evaluation, Preclinical ; Humans ; Inflammation/*etiology/metabolism ; Jurkat Cells ; Lipoxygenase/*physiology ; Lipoxygenase Inhibitors/pharmacology/therapeutic use ; Lymphocytes/drug effects/metabolism ; Male ; Mice ; Mice, Inbred BALB C ; Nordihydroguaiaretic Acid/pharmacology/therapeutic use ; Reactive Oxygen Species/*adverse effects/*metabolism