Recently the prevalence of both asthma and obesity have increased substantially in many countries. The aim of this study was to evaluate the role of retinol-binding protein (RBP) 4 in childhood asthma and its association with atopy markers, pulmonary function, and bronchial hyperresponsiveness in relation to obesity. We studied 160 children between the ages 6 to 10 yr, including 122 asthmatics and 38 controls. The body mass index, pulmonary function tests, and methacholine challenge tests were measured on the same day. Total eosinophil count, serum total IgE, serum eosinophil cationic protein, and serum RBP4 were measured in all subjects. There was no difference in serum RBP4 levels between the asthmatics and the control group. In all subjects or subgroups, serum RBP4 was not associated with total eosinophil count, serum total IgE, serum eosinophil cationic protein, or PC20. There was no relationship between serum RBP4 and pulmonary function in female asthmatics. Forced expiratory volume in 1 second/forced vital capacity (FVC) and forced expiratory flow between 25% and 75% of FVC contributed to serum RBP4 in male asthmatics. Our findings show an association between RBP4 and pulmonary function in prepubertal male asthmatics. This relationship may indirectly affect the high prevalence of childhood asthma in males.
*Asthma/blood/immunology ; Bronchial Hyperreactivity/blood/immunology ; Bronchial Provocation Tests ; Child ; Female ; Humans ; Male ; Obesity/blood/immunology ; Retinol-Binding Proteins, Plasma/*metabolism

There are increasing evidences that allergic rhinitis (AR) may influence the clinical course of asthma. We conducted methacholine challenge test and nasal eosinophils on nasal smear to patients with allergic rhinitis in order to investigate the mechanism of connecting upper and lower airway inflammation in 35 patients with AR during exacerbation. The methacholine concentration causing a 20% fall in FEV1 (PC20) was used as thresholds of bronchial hyperresponsiveness (BHR). Thresholds of 25 mg/dL or less were assumed to indicate BHR. All patients had normal pulmonary function. Significant differences in BHR were detected in the comparison of patients with cough or postnasal drip and without cough or postnasal drip. There were significant differences of PC20 between patients with cough or postnasal drip and those without cough or postnasal drip (3.41 +/-3.59 mg/mL vs 10.2 +/-1.2 mg/mL, p=0.001). The levels of total IgE were higher in patients with seasonal AR than in patients with perennial AR with exacerbation (472.5 +/-132.5 IU/L vs. 389.0 +/-70.9 IU/L, p<0.05). Nasal eosinophils were closely related to log PC20 (r=-0.65, p<0.01). These findings demonstrated that nasal eosinophilic inflammation might contribute to BHR in patients with AR.
Adult ; Bronchi/*immunology ; Bronchial Hyperreactivity/*immunology ; Eosinophils/*immunology ; Female ; Humans ; Immunoglobulin E/blood ; Inflammation ; Male ; Rhinitis, Allergic, Perennial/*immunology ; Rhinitis, Allergic, Seasonal/*immunology ; Spirometry ; Time Factors

OBJECTIVE This study aimed to determine the relationship between individual allergens with current wheezing and bronchial hyperresponsiveness (BHR) in schoolchildren from three chinese cities: Beijing, Guangzhou and Hong Kong. METHODS Community-based random samples of 10-yr-old schoolchildren from the 3 cities were recruited for study using the International Study of Asthma and Allergies in Childhood (ISAAC) Phase II protocol. The subjects were studied by parental questionnaires (n = 10,902), skin-prick tests (n = 3478), and methacholine challenge tests (n = 608). RESULTS The highest prevalence rates of wheezing in the past 12 months (Beijing, 3.8%; Guangzhou, 3.4%; Hong Kong, 5.8%) and atopy (Beijing, 23.9%; Guangzhou, 30.8%; Hong Kong, 41.2%, defined as having bronchial hyperresponsiveness in Chinese schoolchildren.
Allergens ; classification ; immunology ; Asthma ; etiology ; immunology ; Bronchial Hyperreactivity ; etiology ; immunology ; Child ; China ; Hong Kong ; Humans ; Risk Factors ; Skin Tests ; Surveys and Questionnaires

The nonstinging house ant, Monomorium pharaonis (pharaoh ant), was recently identified as a cause of respiratory allergy. This study was performed to evaluate the extent of sensitization to pharaoh ant, and its clinical significance in asthmatic patients. We carried out skin prick tests in 318 patients with asthma. Specific IgE (sIgE) to pharaoh ant was measured by ELISA, and cross-reactivity was evaluated by ELISA inhibition tests. Bronchial provocation testing was performed using pharaoh ant extracts. Fifty-eight (18.2%) of 318 patients showed positive skin responses to pharaoh ant, and 25 (7.9%) had an isolated response to pharaoh ant. Positive skin responses to pharaoh ant were significantly higher among patients with non-atopic asthma than among those with atopic asthma (26.0% vs. 14.9%, p<0.05). There was significant correlation between sIgE level and skin responses to pharaoh ant (rho=0.552, p<0.001). The ELISA inhibition tests indicated that pharaoh ant allergens had various pattern of cross-reactivity to house dust mites and cockroaches. Bronchial provocation tests to pharaoh ant were conducted for 9 patients, and eight showed typical asthmatic reactions. In conclusion, pharaoh ant is an important source of aeroallergens, and it should be included in the skin test battery for screening the causative allergens in patients with asthma.
Administration, Inhalation ; Adolescent ; Adult ; Allergens/immunology ; Animals ; Ants/*immunology ; Asthma/blood/*immunology ; Bronchial Hyperreactivity/immunology ; Bronchial Provocation Tests ; Female ; Humans ; Immunoglobulin E/blood ; Male ; Middle Aged ; Research Support, Non-U.S. Gov't ; Skin Tests

OBJECTIVETo investigate bronchial responsiveness to acetylcholine in allergic airway inflammation of SD rats.

METHODSSD rats were immunized and challenged by chicken ovalbumin (OVA). Airway responsiveness, acetylcholine (Ach) provocation concentration needed to increase baseline airway resistance by 200% (PC(200)) were measured.

RESULTSThe value of baseline airway resistance in asthma group was significantly higher than that in control group (2.282 +/- 0.128 vs 3.193 +/- 0.239; P < 0.01). After multiple ovalbumin exposures, airway responsiveness to intravenous injection of acetylcholine decreased significantly (-LogPC(200): 4.006 +/- 0.554 vs 2.059 +/- 0.262; P < 0.01). Bronchial alveolar lavage fluid (BALF) and lung tissue specimen analysis indicated that airway allergic inflammation was present.

CONCLUSIONSThe study demonstrates a dissociation between the bronchoconstrictor response and bronchial hyper-responsiveness and indicates that multiple ovalbumin exposures induces persistent bronchoconstriction with airway hypo-responsiveness despite airway allergic inflammation.

Acetylcholine ; pharmacology ; Airway Resistance ; Allergens ; immunology ; Animals ; Bronchi ; drug effects ; physiology ; Bronchial Hyperreactivity ; etiology ; Bronchoconstriction ; Lung ; pathology ; Male ; Ovalbumin ; immunology ; Rats ; Rats, Sprague-Dawley

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

AIMTo study the relation between Respiratory Syncytial Virus infection and asthma development by measuring airway responsiveness (AR) and M2R function.

METHODSGuinea pigs (n = 34) were randomly divided into 4 groups: Hep-2/NS group (group A, n = 9), RSV/NS group (group B, n =9), Hep-2/OVA group (group C, n = 8) and RSV/OVA group(group D, n = 8). On day 21 after infection we tested AR and M2R. Then counted eosinophils in BALF and observed pathological change.

RESULTSIntraairway pressure(IP mmH20) of group B had no significant difference with group A(P > 0.01), and the extent of IP decrease also had no difference between groups A and B (P > 0. 05), but IP of C group were much higher than group A (P<0.05), with extent of IP decrease lower than group A (P < 0.05). And IP of group D were higher than group C (P < 0.01), with the extent of IP decrease much lower than group C (P < 0.05).

CONCLUSIONRSV infection could enhance OVA-induced M2R dysfunction, then develop AHR.

Animals ; Asthma ; immunology ; physiopathology ; virology ; Bronchial Hyperreactivity ; immunology ; physiopathology ; virology ; Female ; Guinea Pigs ; Male ; Ovalbumin ; immunology ; Random Allocation ; Receptor, Muscarinic M2 ; physiology ; Respiratory Syncytial Virus Infections ; immunology ; Respiratory Syncytial Viruses ; immunology

PURPOSE: Japanese hop (Humulus spp.) and mugwort (Artemisia spp.) are notable causes of autumn pollinosis in East Asia. However, Japanese hop and mugwort pollen extracts, which are widely used for the diagnosis, have not been standardized. This study was performed to standardize Japanese hop and mugwort pollen extracts. MATERIALS AND METHODS: Allergen extracts were prepared in a standardized way using locally collected Humulus japonicus and purchased Artemisia vulgaris pollens. The immunoglobulin E (IgE) reactivities of prepared extracts were compared with commercial extracts via IgE immunoblotting and inhibition analyses. Intradermal skin tests were performed to determine the bioequivalent allergy unit (BAU). RESULTS: The IgE reactive components of the extracts via IgE immunoblotting were similar to those of commercial extracts. A 11-kDa allergen showed the strongest IgE reactivity in Japanese hop, as did a 28-kDa allergen in mugwort pollen extracts. Allergenic potencies of the investigatory Japanese hop and mugwort extracts were essentially indistinguishable from the commercial ones. Sums of erythema of 50 mm by the intradermal skin test (SigmaED50) were calculated to be 14.4th and 13.6th three-fold dilutions for Japanese hop and mugwort extracts, respectively. Therefore, the allergenic activity of the prepared extracts was 90827.4 BAU/mg for Japanese hop and 34412 BAU/mg for mugwort. CONCLUSION: We produced Japanese hop and mugwort pollen extracts using a standardized method. Standardized Japanese hop and mugwort pollen extracts will facilitate the production of improved diagnostic and immunotherapeutic reagents.
Allergens/*analysis/*immunology ; Antibody Specificity ; *Artemisia ; Bronchial Hyperreactivity/blood/immunology ; Cross Reactions ; Enzyme-Linked Immunosorbent Assay ; Humans ; Immunoblotting ; Immunoglobulin E/blood/*immunology ; Pollen/*chemistry/*immunology ; Reference Standards ; Republic of Korea ; Rhinitis, Allergic, Seasonal

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

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