Respiratory syncytial virus infection differentiates airway dysfunction in the central and peripheral airways in OVA-sensitized mice.

Much evidence suggests that respiratory syncytial virus (RSV) infection prolongs airway hyperresponsiveness (AHR) and exacerbates asthma by enhancing airway inflammation. However, the characteristic of airway inflammation and kinetics of airway dysfunction occurred in the central and peripheral airways were not fully delineated. The objective of this study was to investigate the effect of RSV on the allergic airway inflammation in different size airways and to elucidate its possible mechanism. Using a murine model of prior ovalbumin (OVA) sensitization and subsequent RSV challenge, lung resistance (R(L)), and dynamic compliance (Cdyn) was conducted by barometric whole-body plethysmography. Histological examinations were carried out. Differential cells count in bronchoalveolar lavage (BAL) fluid, serum anti-OVA IgE, and IgG1 were measured. Cytokine mRNA expression in lung tissue were determined. RSV triggered a significant increase in R(L) and reduction in Cdyn, as well as greatly prolonged the recovery of Cdyn more than that of R(L) in OVA-sensitized mice. Also, RSV resulted in more severe peripheral airway inflammation which exhibit as globe cell hyperplasia and CD8+ T cell infiltration. Furthermore, the number of lymphocytes, neutrophils and macrophages in BAL fluid, serum anti-OVA IgE and IgG1 were remarkably increased. Additionally, mice increased relative expression of cytokines IL-4, IL-13, and IFN-γ, but not IL-5, IL-17, and IL-17F. These findings demonstrated that RSV could selectively affect pathologic processes that contribute to altered airway function in the central and peripheral airways in OVA-sensitized mice. These processes may be involved in goblet cell hyperplasia and CD8+ T cell infiltration in peripheral airways.

[A survey of knowledge on common cold in outpatient clinics].

OBJECTIVE: To investigate outpatients' cognition towards common cold and their habituated medication so as to provide evidence for future public healthcare education. METHODS: Patients who attended hospital for diagnosis and treatment of common cold at least within past three months were asked to fill a questionnaire independently so as to learn their cognition towards common cold and medication habit. RESULTS: Among the patients underwent survey, 52.21% had incorrect knowledge about common cold; 12.99% didn't know about the hazards of common cold; 34.80% couldn't distinguish common cold from influenza; 30.07% considered common cold couldn't get relief without treatment; 68.24% didn't know about the proper effects of influenza vaccination; 61.14% often took oral medicine even intravenous injection when they caught a common cold; 59.77% often took medication from drugstore without prescription by doctor, and a few asked doctors to prescribe medicine on their request; 19.42% didn't know about the side effects of drug for cold treatment; and 19.72% didn't know about the active ingredients of drug for cold treatment. There were significant differences in the common cold cognition among population of different ages and education background. The older or the higher education status patients had a better cognition (P < 0.01). CONCLUSION: There exist a certain degree of wrong cognition towards common cold among patients of different literacy degree and different age. Public health education on common cold need to be further strengthened.

[A survey of knowledge on common cold and its treatment situation among physicians from various levels of hospitals in mainland China].

OBJECTIVE: To investigate the cognition of the common cold and current situation of the treatment among physicians from various levels of hospitals in Chinese mainland, so as to provide evidence for future continuing medical education and rational medication. METHODS: A questionnaire designed for this survey was used to learn about the general information, cognitive degree of the common cold and prescription habits of physician who prescribed for cold within last three months, from various levels hospitals. RESULTS: A total of 1001 physicians were interviewed. Among them, 749 physicians chose right options that the cold was the common cold and the influenza with 79.84% in resident physicians and 56.76% in chief physicians. A total of 745 physicians chose options that the course of common cold will be lasting 4 to 7 days; 895 physicians chose options that old people are the most susceptible for complication; 669 physicians thought the common cold was the most common infection in winter; 841 physicians used clinical methods to diagnose the common cold; 736 physicians thought although the cold was a kind of self-limited disease and symptomatic treatment could alleviate symptoms and improve life quality, patients should see doctor in time if it turns to severer; and 745 physicians held the opinion that treatment of the common cold should focus on relieving symptoms first. In addition, 61.60% physicians had made prescription based on clinical symptoms; 505 (54.24%) of them thought compound drugs were priority in treating the common cold. However, there were still 43 physicians prescribed antibiotics for common cold. CONCLUSIONS: There is misunderstanding and discrepancy in cognition towards common cold and treatment among physicians from various levels of hospitals in mainland China. Physicians should standardize diagnosis and treatment for the common cold according to the domestic and foreign guidelines.

[Effects of astragaloside IV on the expressions of transforming growth factor-ß1 and thymic stromal lymphopoietin in a murine model of asthma].

OBJECTIVE: To observe the effects of astragaloside IV on the airway remodeling and the expressions of transforming growth factor (TGF)-ß1 and thymic stromal lymphopoietin (TSLP) in a murine model of asthma. METHODS: Forty-eight BALB/c mice were randomly divided into 4 groups, i.e. control group, asthma group, astragaloside IV group and budesonide group (n = 12 each). The BALB/c mice sensitized to ovalbumin (OVA) were chronically challenged with aerosolized OVA for 8 weeks while the mice in the astragaloside IV group were intragastrically administered with astragaloside IV (50 mg/kg) daily for 8 consecutive weeks. Pulmonary functions were measured to evaluate the resistance of expiration. And pulmonary histopathological analysis was performed to observe the infiltration of inflammatory cells, the hyperplasia of airway global cells and the deposition of collagen. The levels of interleukin (IL)-4 and IL-13 in bronchoalveolar lavage fluid (BALF) were measured by ELISA (enzyme linked immunosorbent assay). The pulmonary expression of α-SMA (alpha-smooth muscle actin) was evaluated by immunohistochemistry. The mRNA and protein expressions of TGF-ß1 and TSLP were measured by real-time PCR (polymerase chain reaction) and Western blot respectively. RESULTS: The treatment of astragaloside IV or budesonide led to a sharp decrease in airway resistance compared with the asthma group at a concentration of acetylcholine in 30 µg/kg (P < 0.05). The PAS(+) epithelial/bronchial epithelial cells, the area of collagen staining and α-SMA staining area were significantly elevated in the asthma group compared with the control group (all P < 0.01) while those in the astragaloside and budesonide groups were obviously inhibited compared with the asthma group (all P < 0.05). The BALF levels of IL-4 and IL-13 were markedly elevated in the asthma group versus the control group (P < 0.01) while those markedly decreased in the astragaloside and budesonide groups versus the asthma group (all P < 0.05). The relative expressions of TGF-ß1 and TSLP mRNA (5.23 ± 1.44, 5.70 ± 1.65) were significantly up-regulated in the asthma group versus the control group (1.02 ± 0.21, 1.02 ± 0.25) (P < 0.01) while those in the astragaloside (2.27 ± 0.65, 2.97 ± 1.03) and budesonide groups (2.10 ± 0.57, 3.32 ± 1.11) were obviously down-regulated versus the asthma group (all P < 0.05). The protein levels of TGF-ß1 and TSLP in the asthma group (0.89 ± 0.11, 0.74 ± 0.10) were markedly elevated versus the control (0.39 ± 0.04, 0.44 ± 0.05), the astragaloside (0.51 ± 0.08, 0.59 ± 0.12) and the budesonide groups (0.55 ± 0.08, 0.60 ± 0.08) (all P < 0.05). CONCLUSION: Astragaloside IV can suppress the progression of airway inflammation, airway hyperresponsiveness and remodeling in a murine model of asthma. The above effects may be partially due to the inhibited expressions of TGF-ß1 and TSLP.

[Induction of monocyte-derived dendritic cell differentiation by asthmatic serum in a transendothelial trafficking model].

OBJECTIVE: To explore the effect of asthmatic and healthy serum on differentiation and function of monocyte-derived dendritic cells (MDDC) in a transendothelial trafficking model. METHODS: The sera and peripheral blood mononuclear cells (PBMC) were separated from 12 asthmatic patients and 12 healthy volunteers, and monocytes were selected from PBMC using magnetic beads. The trypsin-digested human umbilical vein endothelial cells (HUVEC) at passage 2 from 5 healthy lying-in women were used to construct the transendothelial trafficking model under asthmatic or healthy serum, wherein MDDC were identified by silver nitrate staining and scanning electron microscopy. Nuclear factor κB (NF-κB) activity was determined by electrophoretic mobility shift assay. Flow cytometry, ELISA and mixed leukocyte reaction were relevantly utilized to detect the phenotype, cytokine and T cell proliferation. RESULTS: (1) Monocytes traversed through HUVEC monolayer after 2 h, and reverse-transmigrated to develop into DC 48 h later. (2) The healthy serum stimulated monocytes into immature MDDC with lower CD(14) [(20 ± 5)%] (F = 49.01, P < 0.05), and higher HLA-DR, CD(80), CD(86) and CD(83) [(43 ± 4)%, (17.9 ± 3.5)%, (43 ± 11)% and (6.7 ± 1.8)%, respectively] (F = 10.35 - 40.17, all P < 0.05) than monocytes did before transmigration at 0 h [CD(14) (81 ± 6)%, HLA-DR (24 ± 5)%, CD(80) (2.8 ± 2.0)%, CD(86) (14 ± 4)% and CD(83) (0.9 ± 0.8)%, respectively]. (3) The asthmatic serum stimulated monocytes into mature MDDC, characteristic of dendrites, with similar HLA-DR and CD(86) [(55 ± 6)% and (59 ± 12)%] (F = 15.29 and 35.97, all P > 0.05), higher CD(80) and CD(83) [(49.7 ± 10.2)% and (30.2 ± 6.8)%] (F = 4.01 and 20.68, all P < 0.05), accompanied by increased levels of NF-κB activity, IL-12 p70 and T cell proliferation [(100 ± 11)%, (568 ± 43) ng/L and (2033 ± 198) cpm, respectively] (F = 49.23 - 350.84, all P < 0.05) relative to the healthy serum-stimulated immature MDDC [(12 ± 3)%, (220 ± 35) ng/L and (952 ± 64) cpm, respectively]. CONCLUSION: The asthmatic serum induces mature MDDC in association with NF-κB overactivation in the transendothelial trafficking model, which provides a promising experimental platform for both investigation of immunological mechanisms in asthma and screening of novel anti-asthma drugs in vitro.

Unusual life-threatening Rosai-Dorfman disease of the trachea: role of NF-κB.

Rosai-Dorfman disease (RDD) is a rare non-neoplastic histioproliferative disorder characterised by painless lymphadenopathy, low fever, high erythrocyte sedimentation rate, leucocytosis and hypergammaglobulinaemia. Overactivity of nuclear factor κB (NF-κB) is linked with inflammatory, cancerous and autoimmune diseases. The first case is described of an unusual life-threatening RDD of the trachea with no lymphadenopathy at risk of suffocation in a 39-year-old Chinese woman. A diagnosis of RDD was made following CT scans, thoracotomy and histological examination. Gel shift assay revealed an essential role for NF-κB overactivity in RDD. The patient remains well with no evidence of progression without treatment. Histological confirmation should be sought in all cases as the clinical manifestation of RDD is similar to asthma or lung carcinoma.

Beta(2)-adrenergic receptor haplotype/polymorphisms and asthma susceptibility and clinical phenotype in a Chinese Han population.

Association and linkage studies of beta2-adrenergic receptor (beta2AR) polymorphisms in relation to the expression of asthmatic phenotypes and immune regulatory mechanisms have shown inconsistent results. This study was designed to analyze the relationship of particular combinations of single nucleotide polymorphisms (SNPs) or haplotypes of the beta2AR gene with bronchial asthma, bronchodilator response, and total IgE. By direct DNA sequencing, five SNPs (in positions -47, -20, 46, 79, and 252) of beta2AR gene were determined and combined with haplotypes in 201 asthmatic patients and 276 normal controls recruited from the Chinese Han population. Significantly higher bronchodilator response was observed in patients with homozygotic genotype 46A/A (13.40 ± 3.48%), compared with those with homo-46G/G (7.25 ± 3.11%) and heterozygotes 46A/G (7.39 ± 3.14%), respectively (p < 0.0001). There was also a significant difference in bronchodilator response when beta2AR haplotypes were analyzed (p = 0.003). From two common SNPs at positions 46A/G and 79C/G, we had determined three haplotypes that constructed six haplotype pairs. Comparison of the mean delta forced expiratory volume in 1 second (FEV1) values for the six haplotype pairs showed significant difference. Subjects homozygous for 46A/79C (Arg16/Gln27) had the highest deltaFEV1 (13.40 ± 3.48%) and those with 46G/79C (Gly16/Gln27) homozygote had the lowest (6.43 ± 0.55%). The two SNP haplotype pairs were significantly associated with delta FEV1 (p < 0.0001). Significantly higher total IgE levels were found in patients with homozygotic carriers of 79C genotypes (p = 0.022) and homozygotic haplotype -47 T/-20 T/46 A/79 C/252 G (p < 0.0001). These results indicate that the manifestation of asthma might be affected by either an individual beta2AR SNPs or beta2AR haplotype.

Apigenin inhibits allergen-induced airway inflammation and switches immune response in a murine model of asthma.

Many flavonoids were demonstrated to possess the antiallergic effect. Here we detected whether apigenin, a flavonoid, can attenuate allergen-induced airway inflammation and what is the possible mechanism in a murine model of asthma. Apigenin decreased the degree of the inflammatory cell infiltration, airway hyperresponsiveness, and total immunoglobulin E levels compared with the ovalbumin group. In addition, apigenin triggered the switching of the immune response to allergens toward a T-helper type 1 (Th1) profile. Our data clearly demonstrated that apigenin exhibits an anti-inflammatory activity in a murine asthma model, and can switch the immune response to allergens toward the Th1 profile.

[A randomized, double-blind, placebo-control study of once-daily inhaled tiotropium in chronic obstructive pulmonary disease].

OBJECTIVE: To compare the efficacy and safety between tiotropium capsule and placebo in a 12-week treatment in patients with chronic obstructive pulmonary disease (COPD). METHODS: A multi-center, randomized, double-blind, and placebo-control clinical trial was conducted in 205 patients with stable COPD. They were randomized into inhaled tiotropium 18 µg once daily or placebo, lasting for 12 weeks. The spirometry was conducted at baseline, 6 and 12 weeks after treatment. RESULTS: A total of 205 patients with stable stage I or II COPD were randomized to tiotropium and placebo groups. The improvement rate of clinical symptom in the tiotropium group was 25.2% (26/103) after a 12 week treatment, but that of the control group was 4.9% (5/102). The forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) in the tiotropium group increased (0.2 ± 0.3) L and (19.2 ± 29.1)% after the 12 week therapy, but only (0.0 ± 0.2) L and (0.8 ± 18.2)% in the placebo group. The rate of adverse reaction in the tiotropium group was 7.8% (8/103), but in the placebo group was 12.8% (13/102). The difference between the 2 groups was not significant. All adverse reactions were mild, including dry mouth and sore throat. CONCLUSIONS: This trial confirmed that tiotropium powder 18 µg once daily relieved dyspnea, prevented aggravation and improved pulmonary function, clinical symptoms and life quality. Tiotropium was a safe and effective once-daily anticholinergic bronchodilator as first-line maintenance therapy in COPD.

Targeted NF-kappaB inhibition of asthmatic serum-mediated human monocyte-derived dendritic cell differentiation in a transendothelial trafficking model.

Transendothelial trafficking model mimics in vivo differentiation of monocytes into dendritic cells (DC). The serum from patients with systemic lupus erythematosus promotes the differentiation of monocytes into mature DC. We have shown that selective inhibition of NF-kappaB by adenoviral gene transfer of a novel mutated IkappaBalpha (AdIkappaBalphaM) in DC contributes to T cell tolerance. Here we demonstrated for the first time that asthmatic serum facilitated human monocyte-derived DC (MDDC) maturation associated with increased NF-kappaB activation in this model. Furthermore, selective blockade of NF-kappaB by AdIkappaBalphaM in MDDC led to increased apoptosis, and decreased levels of CD80, CD83, CD86, and IL-12 p70 but not IL-10 in asthmatic serum-stimulated MDDC, accompanied by reduced proliferation of T cells. These results suggest that AdIkappaBalphaM-transferred MDDC are at a more immature stage which is beneficial to augment the immune tolerance in asthma.

Naringenin inhibits allergen-induced airway inflammation and airway responsiveness and inhibits NF-kappaB activity in a murine model of asthma.

Naringenin, a flavonoid, has antiinflammatory and immunomodulatory properties. We investigated whether naringenin could attenuate allergen-induced airway inflammation and its possible mechanism in a murine model of asthma. Mice were sensitized and challenged with ovalbumin. Some mice were administered with naringenin before ovalbumin challenge. We evaluated the development of airway inflammation and airway reactivity. Interleukin (IL)4, IL13, chemokine (C-C motif) ligand (CCL)5, and CCL11 in bronchoalveolar lavage fluid and serum total IgE were detected by ELISA. IkappaBalpha degradation and inducible nitric oxide synthase (iNOS) in lungs were measured by Western blot. We also tested NF-kappaB binding activity by electrophoretic mobility shift assay. The mRNA levels of iNOS, CCL5, and CCL11 were detected by real-time PCR. Naringenin attenuated ovalbumin-induced airway inflammation and airway reactivity in experimental mice. The naringenin-treated mice had lower levels of IL4 and IL13 in the bronchoalveolar lavage fluid and lower serum total IgE. Furthermore, naringenin inhibited pulmonary IkappaBalpha degradation and NF-kappaB DNA-binding activity. The levels of CCL5, CCL11, and iNOS were also significantly reduced. The results indicated that naringenin may play protective roles in the asthma process. The inhibition of NF-kappaB and the decreased expression of its target genes may account for this phenomenon.

Imiquimod, a toll-like receptor 7 ligand, inhibits airway remodelling in a murine model of chronic asthma.

1. Imiquimod, a synthetic Toll-like receptor (TLR) 7 ligand, has been shown to attenuate airway inflammation and airway hyperresponsiveness (AHR) in acute murine models of allergic asthma. In the present study, we investigated the effect of imiquimod on allergen-induced airway remodelling in chronic experimental asthma. 2. Ovalbumin (OVA)-sensitized mice were chronically challenged with aerosolized OVA for 8 weeks. Some mice were exposed to an aerosol of 0.15% imiquimod daily during the period of OVA challenge. Twenty-four hours after the last OVA challenge, mice were evaluated for the development of airway inflammation, AHR and airway remodelling. The levels of total serum IgE and Th2 cytokines (interleukin (IL)-4, IL-5 and IL-13) in bronchoalveolar lavage fluid (BALF) and the expression of transforming growth factor (TGF)-beta1 protein in lungs were measured by ELISA and immunohistochemistry, respectively. 3. The results demonstrated that imiquimod significantly inhibited chronic inflammation, persistent AHR and airway remodelling in chronic experimental asthma. In addition, imiquimod reduced levels of total serum IgE and BALF Th2 cytokines and diminished expression of TGF-beta1 in remodelled airways. 4. In summary, the results of the present study indicate that imiquimod may attenuate the progression of airway inflammation and remodelling, providing potential in the treatment of asthma.

Inhibition of CD8+ T lymphocytes attenuates respiratory syncytial virus-enhanced allergic inflammation.

BACKGROUND: CD8+ T cells have an important role in the pathogenesis of respiratory virus-induced asthma exacerbations. However, the cellular mechanism of CD8+ T cells, linking viral respiratory infections to the development of airway inflammation, is not well defined. OBJECTIVES: To clarify the role of CD8+ T cells in the development of respiratory virus-induced asthma exacerbations. METHODS: Using a murine model of prior ovalbumin exposure and subsequent respiratory syncytial virus infection, the airway responsiveness was assessed by barometric whole-body plethysmography. Airway eosinophils, lymphocytes, neutrophils as well as IFN-gamma, IL-4, IL-5 and IL-13 in bronchoalveolar lavage fluid were measured by Diff-Quick staining and ELISA. The frequency of cytokine-producing CD8+ T lymphocytes in peribronchial lymph nodes was detected using 2-color immunofluorescence analysis. Histological examinations were carried out using hematoxylin and eosin and immunohistochemistry. RESULTS: Anti-CD8 monoclonal antibody (1 mg/kg) clearly inhibited increases in airway responsiveness to acetylcholine and markedly reduced the number of eosinophils, neutrophils, lymphocytes as well as IL-4, IL-5 and IL-13 levels in bronchoalveolar lavage fluid. Furthermore, the antibody also attenuated airway inflammation and CD8+ T lymphocyte infiltration in lung tissue. CONCLUSIONS: These findings suggest that CD8+ T lymphocytes play a critical role for the development of respiratory syncytial virus-induced airway inflammation and airway hyperresponsiveness.

High-sensitivity C-reactive protein: a predicative marker in severe asthma.

BACKGROUND AND OBJECTIVE: Serum levels of high-sensitivity CRP (hs-CRP) are associated with asthma but the relationship between higher levels of hs-CRP and the degree of asthma severity remains unclear. This study investigated whether hs-CRP is associated with asthma severity as well as with other clinical indices of asthma activity (pulmonary function, total serum IgE, and peripheral blood eosinophil counts). METHODS: Levels of hs-CRP and clinical indices of asthma were determined among 177 control subjects and 281 asthmatic patients (84 intermittent, 30 mild, 63 moderate and 104 severe). RESULTS: The level of hs-CRP was examined as both a continuous variable and by quartiles (<0.23, 0.23-0.51, 0.51-1.42 and >or=1.42 mg/L) in the five groups. Compared with the first quartile of hs-CRP, patients with higher levels were at increased risk of severe asthma independently of other clinical indices (adjusted OR 3.49, 95% CI: 1.51-8.12 for the third quartile; adjusted OR 6.46, 95% CI: 2.85-16.62 for fourth quartile, respectively). CONCLUSIONS: These findings suggest that hs-CRP might be a sensitive marker for severe asthma.

Expression of surface markers on peripheral CD4+CD25high T cells in patients with atopic asthma: role of inhaled corticosteroid.

BACKGROUND: CD4(+)CD25(+) regulatory T cells (Tregs) mediate immune suppression through cell-cell contact with surface molecules, particularly cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), glucocorticoid-induced tumor necrosis factor receptor family-related protein (GITR), and transforming growth factor beta (TGF-beta), but little is known about the exact role of Tregs in the pathogenesis of asthma. This study sought to characterize the expression of surface markers on peripheral blood mononuclear cells-derived Tregs in patients with atopic asthma and healthy subjects, and to investigate the effect of inhaled corticosteroid on them. METHODS: The expression of surface molecules on CD4(+)CD25(high) Tregs was detected by flow cytometry. The effect of inhaled corticosteroid on expression of the surface molecules on Tregs was determined in vivo and in vitro. Total serum immunoglobulin E (IgE) and high-sensitivity C-reactive protein were measured by enzyme linked immunosorbent assay and latex enhanced immunoturbidimetric assay, respectively. RESULTS: Equivalent numbers of peripheral Tregs were found in patients with atopic asthma (stable and acute) and healthy subjects. Tregs preferentially expressed CTLA-4, GITR, toll-like receptor 4 (TLR4), latency-associated peptide (LAP/TGF-beta1), and forkhead box P3 (FOXP3). Patients with acute asthma had decreased numbers of CD4(+)CD25(high)LAP(+) T cells compared to healthy subjects and stable asthmatics. Inhaled corticosteroid enhanced the percentage of Tregs expressing LAP in vivo and in vitro dose-dependently. Furthermore, the percentages of Tregs expressing LAP were negatively correlated with total serum IgE levels and severity of asthma, but positively correlated with forced expiratory volume in one second percentage of the predicted value in patients with asthma. CONCLUSIONS: The results suggest that membrane-bound TGF-beta1 is a potential candidate for predicting the severity of asthma, and may contribute to the sustained remission of asthma. Strategies targeting Tregs on their surface markers, especially TGF-beta1, are promising for future therapy of asthma.

Increased RhoGDI2 and peroxiredoxin 5 levels in asthmatic murine model of beta2-adrenoceptor desensitization: a proteomics approach.

BACKGROUND: Beta(2)-adrenoceptor (beta(2)AR) desensitization is a common problem in clinical practice. beta(2)AR desensitization proceeds by at least such three mechanisms as heterologous desensitization, homologous desensitization and a kind of agonist-induced rapid phosphorylation by a variety of serine/threonine kinases. It is not clear whether there are other mechanisms. This study aimed to investigate potential mechanisms of beta(2)AR desensitization. METHODS: Twenty-four BALB/c (6-8 weeks old) mice were divided into three groups, which is, group A, phosphate buffered saline (PBS)-treated; group B, ovalbumin (OVA)-induced; and group C, salbutamol-treated. Inflammatory cell counts, cytokine concentrations of bronchoalveolar lavage fluid (BALF), pathological sections, total serum IgE, airway responsiveness, membrane receptor numbers and total amount of beta(2)AR were observed. Asthmatic mouse model and beta(2)AR desensitization asthmatic mouse model were established. Groups B and C were selected for two-dimensional gel electrophoresis (2DE) analysis so as to find key protein spots related to beta(2)AR desensitization. RESULTS: Asthmatic mouse model and beta(2)AR desensitization asthmatic mouse model were verified by inflammatory cell count, cytokine concentration of BALF, serum IgE level, airway hyperreactivity measurement, radioligand receptor binding assay, Western blot analysis, and pathologic examination. Then the two groups (groups B and C) were subjected to 2DE. Two key protein spots associated with beta(2)AR desensitization, Rho GDP-dissociation inhibitor 2 (RhoGDI(2)) and peroxiredoxin 5, were found by comparative proteomics (2DE and mass spectrum analysis). CONCLUSION: Oxidative stress and small G protein regulators may play an important role in the process of beta(2)AR desensitization.

[Association between beta2-adrenergic receptor haplotype/polymorphisms and asthma phenotype].

OBJECTIVE: To analyze the association of single nucleotide polymorphisms (SNP)/ haplotypes of beta2-adrenergic receptor (beta2-AR) gene with bronchodilator response and total serum immunoglobulin E (IgE). METHODS: Five SNP (in positions: -47, -20, 46, 79, 252) genotypes of beta2-AR gene in 201 asthmatic patients and 276 controls were determined by direct DNA sequencing, and the haplotypes were combined from 2006 February to 2007 February. Statistical analyses were performed with SPSS 11.5 software. The genotype frequencies for each polymorphism were tested for deviation from the Hardy-Weinberg equilibrium by chi2 goodness-of-fit analysis. The frequencies of the five polymorphic genotypes were compared with chi2 test, and the degree of linkage disequilibrium occurring between these polymorphic loci were analyzed by fisher' s exact. For the comparison of quantitative traits among different genotypes/haplotypes, ANOVA was used. Least significant difference (LSD) was used if there was statistical significant. RESULTS: The bronchodilator response in patients with Argl6Argl6 was (13 +/- 4)L, significantly higher than those with Arg16Gly16 [(7 +/- 3) L and Gly16Gly16 (7 +/- 3)L, F = 81.55, P < 0.01]. When beta2-AR haplotypes were analyzed, bronchodilator response was highest in patients with haplotype Arg16Gln27/Arg16Gln27 [(13.4 +/- 3.5) L], compared to that with Gly16Gln27/Gly16Gln27 [(6.4 +/- 0.6) L], Gly16Glu27/Gly16Glu27 [(7.6 +/- 3.1)L], Gly16Gln27/Gly16Glu27 [(6.9 +/- 3.5)L], Gly16Gln27/Arg16Gln27 [(7.2 +/- 3.3) L, and Gly16Glu27/Arg16Gln27 (7.9 +/- 2.7) L, F = 32.55, P < 0.01]. The total IgE level was (2.51 +/- 0.33) IU/L in patients with genotype Gln27Gln27, significantly higher than that with Gln27Glu27 [(2.30 +/- 0.82) IU/L, F = 3.89, P < 0.05]. The total IgE level was significantly lowest in patients with haplotype Gly16Gln27/Arg16Gln27 (2.13 +/- 0.15) IU/L, compared to that with Arg16Gln27/Arg16Gln27 (2.56 +/- 0.14) IU/L, Gly16Glu27/Gly16Glu27 (2.40 +/- 0.16) IU/L, Gly16Gln27/Gly16Glu27 (2.54 +/- 1.26) IU/L, Gly16Gln27/Arg16Gln27 [(2.48 +/- 0.48) IU/L, F = 3.56, P < 0.01]. CONCLUSIONS: These results indicate that depending on phenotypes studied, either an individual beta2-AR SNP or haplotype might affect disease manifestations.

[Impulse oscillometry for estimation of airway obstruction].

OBJECTIVE: To explore the application of impulse oscillometry (IOS) in the estimation of airway obstruction and to evaluate the correlation between spirometry indices and IOS parameters. METHODS: From Nov.2007 to May 2008, spirometry and IOS measurements were performed in 100 participants (male 72, female 28). FEV(1), FVC, FEV(1)/FVC, airway resistance at 5 Hz (R(5)), airway resistance at 20 Hz (R(20)), central resistance (Rc) and peripheral resistance (Rp) of structural parameters interpretation graph, FEV(1)% pred, R(5)% pred, R(20)% pred, and FEV(1)/FVC were analyzed. Correlations between spirometry and IOS parameters were studied. RESULTS: All participants had satisfactory impulse oscillometry results. R(5) and Rp were significantly increased in FEV(1)/FVC < 70% group [(5.3 +/- 2.1) and (6.2 +/- 2.9) cm H(2)OxL(-1)xs(-1) (1 cm H2O = 0.098 kPa)], respectively. There was significant negative correlation between FEV(1) and R(5) and Rp (correlation coefficient was -0.38 and -0.47 respectively, all P < 0.01). There was also negative correlation between FVC and R(5) and Rp (correlation coefficient was -0.28 and -0.37, respectively, all P < 0.01). A significant negative correlation between FEV(1)% pred, FVC% pred, FEV(1)/FVC% pred and R(5)% pred was also observed (correlation coefficient -0.49, -0.39 and -0.43, respectively). CONCLUSIONS: IOS parameters can be used to evaluate airway obstruction. Among IOS parameters, R(5) was the most sensitive, which was also significantly correlated with spirometric parameters.

Effect of continuous positive airway pressure treatment on serum adiponectin level and mean arterial pressure in male patients with obstructive sleep apnea syndrome.

BACKGROUND: Recent research suggested that obstructive sleep apnea syndrome (OSAS) might be independently associated with hypoadiponectinemia, which was linked to some complications of OSAS, such as hypertension, diabetes, etc. This study was conducted to investigate the effect of continuous positive airway pressure (CPAP) treatment on changes of both serum adiponectin levels and mean arterial pressure and their possible links in male OSAS patients. METHODS: Twenty-three adult male patients with moderate-to-severe OSAS but without obesity, coronary heart disease and diabetes were recruited. Their blood samples were collected and morning mean arterial pressure (MAP) was measured before CPAP treatment and on day 3, 7, 14 of CPAP treatment respectively. The serum adiponectin concentration was tested with radioimmunoassay. RESULTS: Compared with the serum adiponectin level before CPAP treatment, no significant change was found in OSAS patients on day 3 and day 7 of CPAP treatment (P > 0.05). It was not until day 14 of CPAP treatment did a significant elevation in serum adiponectin level occur (P < 0.01). Meanwhile, the MAP showed no statistically significant difference among its levels before CPAP, on day 3 and day 7 of CPAP treatment (P > 0.05). However, on day 14 of CPAP treatment, a significantly lower MAP than that obtained before treatment was observed (P < 0.05). CONCLUSIONS: CPAP treatment can gradually reverse hypoadiponectinemia and reduce MAP in OSAS patients. Hypoadiponectinemia might be involved in the pathogenesis of OSAS-mediated hypertension.