Ligustrazine corrects Th1/Th2 and Treg/Th17 imbalance in a mouse asthma model.

Asthma is an inflammatory disease closely associated with activated T cells in the lung. Imbalances in Th1/Th2 and Treg/Th17 have been found in asthmatic patients. Ligustrazine from the Chinese herb chuanxiong has been used in China in combination with glucocorticoids to treat asthma. Previous studies have proved that ligustrazine can modulate the expression of transcription factors for Th1 (T-bet) and Th2 (Gata-3) in asthma. In the present study, ligustrazine alleviated allergic airway inflammation in a mouse asthmatic model by reducing the influx of eosinophils and neutrophils, which was mediated, at least in part, by the regulation of Th1/Th2 and Treg/Th17 via the re-balance of cytokine profiles and of ratios of transcription factors, T-bet/Gata-3 and Foxp3/RORγt, thus providing new insights into the mechanisms of action for asthma treatment with ligustrazine.

Effect of ß2 -adrenergic receptor gene Arg16Gly polymorphisms on response to long-acting ß2-agonist in Chinese Han asthmatic patients.

BACKGROUND: To evaluate the effect of variation of the Arg16Gly polymorphism of the ß2-adrenergic receptor gene on clinical response to salmeterol administered with fluticasone propionate in Chinese Han asthmatic patients. METHODS: Moderate persistent asthmatic patients (n = 62) currently receiving short-acting ß2-agonists were administered twice-daily therapy with salmeterol/fluticasone propionate 50/250 µg in a single inhaler for 12 weeks, followed by a 2-to-4-day run-out period. Using direct DNA sequencing, five single nucleotide polymorphisms (SNPs) in the promoter and coding block regions of ß2-adrenergic receptor gene were determined in 62 subjects and haplotypes were combined. RESULTS: There was sustained and significant improvement (p < 0.001) over baseline in all measures of asthma control in subjects receiving salmeterol and fluticasone, regardless of Arg16Gly genotype. However, there was no significant difference in the improvement among three genotypes (p > 0.05). Responses to salmeterol did not appear to be modified by haplotype pairs (p > 0.05). During the run-out period, all subjects had similar decreases in measures of asthma control, with no differences between genotypes (p > 0.05). CONCLUSIONS: Response to salmeterol does not vary with Arg16Gly polymorphisms after chronic dosing with inhaled corticosteroids in Chinese Han asthmatic patients.

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.

Budesonide/formoterol maintenance and reliever therapy in Chinese patients with asthma.

BACKGROUND: Many studies have shown the superior efficacy of budesonide (BUD)/formoterol (FORM) maintenance and reliever therapy, but still lack evidence of its efficacy in Chinese asthma patients in a relative large patient-group. We finished this research to compare BUD/FORM maintenance and reliever therapy and high-dose salmeterol (SALM)/fluticasone (FP) maintenance plus an as-needed short-acting ß(2)-agonist in Chinese patients with persistent uncontrolled asthma. This was a post hoc analysis based on a 6-month, multicenter, randomized, double-blind study (NCT00242775). METHODS: A total of 222 eligible asthma patients from nine centers in China were randomized to either BUD/FORM+as-needed BUD/FORM (160/4.5 µg/inhalation) (640/18 µg/d; n = 111), or SALM/FP+as-needed terbutaline (0.4 mg/inhalation) (100/1000 µg/d; n = 111). The primary endpoint was time to first severe exacerbation while secondary endpoints included various measures of pulmonary function, symptom control and quality-of-life. RESULTS: Time to first severe exacerbation over six months was lower with the BUD/FORM than with the SALM/FP treatment (risk ratio = 0.52, 95%CI 0.22 - 1.22), but the difference did not achieve statistical significance (P = 0.13). The cumulative number of severe exacerbations in the BUD/FORM group was lower than in the SALM/FP group (7.2% vs. 13.5%; risk ratio = 0.45, P = 0.028). BUD/FORM produced significantly better improvements in reliever use, cumulative mild exacerbations, symptom-free days (%), and morning/evening peak expiratory flow (PEF) than SALM/FP (P < 0.05 in all cases). The two groups achieved similar improvements in their time to first mild exacerbation, forced expiratory volume in one second (FEV(1)), asthma control questionnaire and asthma symptom scores, and percentage of nights with awakening(s). Both treatments were well tolerated. CONCLUSIONS: In Chinese patients with persistent asthma, BUD/FORM decreased severe and mild exacerbations, decreased reliever use, increased symptom-free days, and improved morning/evening PEF compared with SALM/FP. There were no significant differences in time to first severe exacerbation or other assessments regarding daily asthma control between BUD/FORM and SALM/FP. BUD/FORM was more effective in this Chinese sub-group than in the total cohort involved in the original study.

[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.

[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.

[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.

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.

[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.

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.

GATA3 siRNA inhibits the binding of NFAT1 to interleukin-13 promoter in human T cells.

BACKGROUND: Interleukin-13 (IL-13) is recognized to be a key modulator in the pathogenesis of Th2-induced allergic inflammation. Transcription factors GATA3 and NFAT1 have been both implicated in the regulation of Th2 cytokines. We previously demonstrated the GATA3-NFAT1 association during human T cell activation. However, the function of the GATA3-NFAT1 complex in Th2 cytokines regulation is still unknown. Small interference RNA (siRNA) was constructed to knock down GATA3 expression in Hut-78 cells to investigate the possible role of GATA3-NFAT1 complex in IL-13 transcription. METHODS: Cells were stimulated with anti-CD3 plus anti-CD28 antibodies to mimic in vivo antigen-mediated co-stimulation; the expression of IL-13 mRNA was determined by real-time PCR; chromation immunoprecipitation (CHIP) assay was employed to investigate the NFAT1 binding to IL-13 promoter. RESULTS: GATA3 siRNA suppressed the expression of GATA3 both in mRNA and protein levels in Hut-78 cells. The binding of NFAT1 to IL-13 promoter was inhibited by GATA3 siRNA in activated T cells, which was followed by the reduction of IL-13 transcription. CONCLUSION: GATA3-NFAT1 complex may play an important role in the regulation of IL-13 transcription in human T cells.

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.

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.

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.

Inhibitory effects of sunitinib on ovalbumin-induced chronic experimental asthma in mice.

BACKGROUND: Tyrosine kinase signaling cascades play a critical role in the pathogenesis of allergic airway inflammation. Sunitinib, a multitargeted receptor tyrosine kinase inhibitor, has been reported to exert potent immunoregulatory, anti-inflammatory and anti-fibrosis effects. We investigated whether sunitinib could suppress the progression of airway inflammation, airway hyperresponsiveness (AHR), and airway remodeling in a murine model of chronic asthma. METHODS: Ovalbumin (OVA)-sensitized mice were chronically challenged with aerosolized OVA for 8 weeks. Some mice were intragastrically administered with sunitinib (40 mg/kg) daily during the period of OVA challenge. Twelve hours after the last OVA challenge, mice were evaluated for the development of airway inflammation, AHR and airway remodeling. The levels of total serum immunoglobulin E (IgE) and Th2 cytokines (interleukin (IL)-4 and IL-13) in bronchoalveolar lavage fluid (BALF) were measured by ELISA. The expression of phosphorylated c-kit protein in the lungs was detected by immunoprecipitation/Western blotting (IP/WB) analysis. RESULTS: Sunitinib significantly inhibited eosinophilic airway inflammation, persistent AHR and airway remodeling in chronic experimental asthma. It reduced levels of total serum IgE and BALF Th2 cytokines and also lowered the expression of phosphorylated c-kit protein in remodelled airways. CONCLUSIONS: Sunitinib may inhibit the development of airway inflammation, AHR and airway remodeling. It is potentially beneficial to the prevention or treatment of asthma.

Association among plasma interleukin-18 levels, carotid intima- media thickness and severity of obstructive sleep apnea.

BACKGROUND: Epidermic studies have suggested a pathophysiological link between obstructive sleep apnea hypopnea syndrome (OSAHS) and atherosclerosis (AS); for which carotid intima-media thickness (IMT) has been considered as an early marker. The pathogenesis by which OSAHS can induce AS has not been elucidated. This study was conducted to investigate the association among plasma interleukin-18 (IL-18) levels, carotid IMT and the severity of OSAHS. METHODS: Based on the apnea hypopnea index (AHI) during sleep monitored by polysomnography, 52 male patients with OSAHS were recruited as the OSAHS group which was further divided into mild OSAHS (n = 16), moderate OSAHS (n = 18), and severe OSAHS (n = 18) subgroups. Eighteen healthy subjects were selected as the control group. Of all OSAHS patients, 20 with moderate-to-severe OSAHS underwent continuous positive airway pressure (CPAP) treatment for 90 days. HDL5000 color Doppler ultrasonography was used to measure carotid IMT. Plasma IL-18 levels were measured by ELISA. RESULTS: Compared with the plasma IL-18 levels in the control group ((250.27 +/- 76.48) pg/ml), there was a significant increase in the mild OSAHS subgroup ((352.08 +/- 76.32) pg/ml), the moderate subgroup ((600.17 +/- 83.91) pg/ml), and the severe OSAHS subgroup ((9797.64 +/- 109.83) pg/ml) (all P < 0.01). Moreover, there was a significant difference in plasma IL-18 levels among the three OSAHS subgroups (P < 0.01). Carotid IMT was significantly greater in the severe OSAHS subgroup than in the mild OSAHS subgroup (P < 0.01). Before CPAP treatment, plasma IL-18 levels were positively correlated with carotid IMT (r = 0.486, P < 0.001) and with AHI (r = 0.865, P < 0.001). On day 90 of CPAP treatment, plasma IL-18 levels were significantly declined but carotid IMT was not changed significantly. CONCLUSIONS: In untreated OSAHS patients carotid IMT and plasma IL-18 were positively correlated and were significantly higher than in normal controls; the elevation of plasma IL-18 levels was correlated with the severity of OSAHS. Inflammatory response associated with OSAHS may be related to the development of AS. By improving AHI, miniSaO(2), and reducing plasma IL-18 levels, CPAP treatment may slow down or prevent the development of AS in OSAHS patients.

Validity of asthma control test for asthma control assessment in Chinese primary care settings.

OBJECTIVE: To evaluate the validity of the Asthma Control Test (ACT) for assessing clinical asthma control in Chinese patients in primary care settings. METHODS: This multicenter study involved 403 asthma patients from 15 primary care settings in China, who had completed the ACT, Asthma Control Questionnaire (ACQ), and spirometry testing. According to the rating of asthma control by asthma specialists in line with the Global Initiative for Asthma 2006 guidelines, patients were divided into uncontrolled, partly controlled, and controlled groups to evaluate the reliability, empirical validity, and screening accuracy of the ACT. The screening accuracy of the ACT and ACQ was analyzed comparatively, and the asthma control levels rated by the patients and the specialists were also compared. RESULTS: The five-item ACT had an internal consistency reliability of 0.861 and a correlation coefficient with the specialists' rating of 0.697. The ACT scores showed significant differences between different levels of FEV(1) percent predicted (F = 37.59; p < 0.0001) and specialists' ratings of asthma control (F = 169.53; p < 0.0001), and also between patients requiring different treatment adjustments (F = 111.33; p < 0.0001). The asthma was controlled for an ACT score of >/= 20, partly controlled for scores of 19 and 18, and uncontrolled for a score of