Validity of Asthma Control Test in Chinese patients

Background So far, in China, there has been no effective or easy procedure to define the control of asthma. This study assesses the validity of Asthma Control Test in Chinese patients. Methods Three questionnaires （Asthma Control Test, Asthma Control Questionnaire and the 30 second asthma test） were administered to 305 asthma patients from 10 teaching hospitals across China. Spirometry was also used. Asthma specialists rated the control of asthma according to patients＇ symptoms, medications and forced expiratory volume in first second. The patients were divided into noncontrolled group and controlled group according to the specialists＇ rating. Reliability, empirical validity and screening accuracy were conducted for Asthma Control Test scores. Screening accuracy was compared among 3 questionnaires. The patients＇ self rating and the specialists＇ rating were also compared. Results The internal consistency reliability of the 5-item Asthma Control Test was 0.854. The correlation coefficient between Asthma Control Test and the specialists＇ rating was 0.729, which was higher than other instruments. Asthma Control Test scores discriminated between groups of patients differing in the percent predicted forced expiratory volume in first second （F=-26.06, P〈0.0001）, the specialists＇ rating of asthma control （F=-88.24, P〈0.0001） and the Asthma Control Questionnaire scores （F=-250.57, P〈0.0001）. Asthma Control Test showed no significant difference with Asthma Control Questionnaire in the percent correctly classified, while the percent correctly classified by Asthma Control Test was much higher than 30 second asthma test. The patients＇ self rating was the same as assessment of the specialists （t=0.65, P=-0.516）. Conclusion The Asthma Control Test is an effective and practicable method for assessing asthma control in China.

Association among plasma interleukin-18 levels, carotid intimamedia 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 bv 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, miniSaO2, and reducing plasma IL-18 levels, CPAP treatment may slow down or prevent the development of AS in OSAHS patients.

Adenovirus-mediated overexpression of novel mutated IκBα inhibits nuclear factor κB activation in endothelial cells

Nuclear factor κB （NF-κB） overactivation, requiring phosphorylation and degradation of its inhibitor IκBα, is the basis for chronicity of airway inflammation in asthma. Based on our previous plasmid pShuttle-IκBα, carrying an IκBα gene from human placenta, we optimized a novel IκBα mutant （IκBα） gene, constructed and characterized its replication-deficient recombinant adenovirus （AdIκBαM）, and tested whether AdIκBαM-mediated overexpression of IκBαM could inhibit the NF-κB activation in endothelial cells.

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.

Correlation among obstructive sleep apnea syndrome,coronary atherosclerosis and coronary heart disease

Epidemiologic investigations have shown that the morbidity of obstructive sleep apnea syndrome （OSAS） among adults is 2%-4%, among the population aged 30 years and over is 4.63%, and among patients with hypertension or coronary atherosclerostic disease （CAD） is as high as 30%-50%.1 Many studies have indicated that OSAS may be closely associated with the development of CAD since increased incidence and mortality of CAD were found in OSAS patients. However, although it has been confirmed that OSAS is an independent risk factor for hypertension, its exact correlation with CAD has not been entirely elucidated. The aim of the present study was to explore the correlation between the degrees of OSAS and CAD with the application of coronary artery angiography （CAA）, Gensini scoring evaluation system, and other risk factors which may contribute to CAD.

Efficacy of adaptive servoventilation in patients with congestive heart failure and Cheyne-Stokes respiration

Background Congestive heart failure （CHF） is associated with Cheyne-Stokes respiration （CSR）, which may hasten CHF. Adaptive servoventilation （ASV） is a novel method of ventilatory support designed for removal of CSF in CHF patients. This study compares the efficacy of ASV in patients with CHF and CSR with the efficacy of oxygen therapy. Methods Fourteen patients with CHF and CSR were recruited. During sleep, nasal oxygen therapy and ASV treatment were each performed for two weeks. Comparison before and after each treatment was made for the following items： a） parameters of sleep respiration, sleep structure and quality; b） left ventricle ejection fraction （LVEF） and 6-minute walk distance. Results Compared with the baseline levels of apnoea hypopnoea index of 34.5±6.1 before treatment, the apnoea hypopnoea index significantly decreased following oxygen therapy to 27.8±8.2, P〈0.05 and further reduced following ASV treatment to 6.5 ±0.8, P〈0.01. The minimal pulse oxygen saturation markedly increased following oxygen therapy from a baseline of （84.3±2.6）% to （88.6±3.7）%, P〈0.05 and further increased following ASV treatment （92.1 ±4.9）%, P〈0.01. Stages Ⅰ ＋Ⅱ sleep as percentage of total sleep time decreased from （81.9±7.1）% to （78.4±6.7）% following oxygen therapy and further to （72.4±5.0）% following ASV treatment. Stages Ⅲ＋Ⅳ sleep as percentage of total sleep time decreased from （8.4±5.5）% to （6.0±3.0）% following oxygen therapy and but increased to （11.9 ± 5.4）% following ASV treatment. The arousal index of 30.4 ±8.1 before treatment significantly decreased following oxygen therapy to 25.6±5.7, P〈0.05 and further declined following ASV treatment to 18.2±6.1, P〈0.01. No significant difference was shown in above percentages between day 14 of oxygen therapy and before treatment （P 〉 0.05）. LVEF was significantly higher on day 14 of ASV treatment （37.2 ±4.1）% than on day 14 of oxygen therapy （33.2 ± 5.1）% and before treatment （30.2±4.6）% （all P〈0.05）. Six-minute walk distance was the shortest before treatment （226±28） m, longer on day 14 of oxygen therapy （289±26） m, and the longest on day 14 of ASV treatment （341 ±27） m （all P 〈 0.01）. Conclusion ASV treatment is of better efficacy and greater clinical significance in improvement of CHF by eliminating CSR than oxygen therapy.

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 IB2-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 pg/inhalation） （640/18 pg/d; n=111 ）, or SALM/FP＋as-needed terbutaline （0.4 mg/inhalation） （100/1000 pg/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 （FEV1）, 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 oriclinal study. （Clinical Trial Registry Number： NCT00242775）

Effect of valsartan on the expression of angiotensin II receptors in the lung of chronic antigen exposure rats

Background Many studies have suggested that angiotensin Ⅱ （Ang Ⅱ） and its receptors may be involved in the development of asthma. However, the expression of angiotensin Ⅱ receptors （AGTR） is not clear in the lung tissue of chronic asthmatics. This study was designed to determine the relationship between airway remodeling, dysfunction and the expression of AGTRs in a rat model of asthma. Methods Rats were sensitized with ovalbumin （OVA） for 2 weeks. Sixty minutes before an inhalation challenge, the rats were pretreated either with valsartan （15, 30, 50 mg.kg-1.d-1） or saline intragastrically. Then the rats received an OVA challenge for 30 alternative days. Acetylcholine （Ach）-induced bronchoconstriction was measured after the final antigen challenge. White cell counts in bronchoalveolar lavage fluid （BALF） and morphological changes in the airways were then assessed. The levels of transforming growth factor-beta 1 （TGF-β1） and platelet-derived growth factor （PDGF） in BALF were detected by ELISA. The levels of AGTR1 and AGTR2 mRNA and protein in lung tissues were measured by RT-PCR and Western blotting. Results AGTR1 mRNA and protein levels in repeatedly OVA-challenged rats were significantly increased as compared with negative controls. The AGTR1 mRNA expression versus white cell counts of BALF and airway wall thickness （mainly in small airways） in lungs of chronic antigen-exposed rats were positively correlated. Valsartan decreased the level of AGTR1 in repeatedly OVA-challenged rats. However, AGTR2 mRNA and protein levels in the OVA-challenged rats and high-dose valsartan-treated rats （50 mg.kg-1.d-1） were also increased. Valsartan significantly decreased inflammatory cell accumulation and attenuated Ach-evoked bronchoconstriction in repeatedly antigen-challenged rats. Valsartan also decreased allergen-induced structural changes in rat airway （including total airway wall thickness and smooth muscle area） and the levels of TGF-β1 and PDGF in BALE Conclusions AGTR1 expression is potentially associated with airway remodeling and dysfunction in asthma. Ang Ⅱ and AGTR1 may participate in airway inflammation and airway remodeling of chronic antigen-exposed rats. Valsartan, a AGTR1 antagonist, could inhibit AGTR1 expression and partially inhibits structural airway changes as well as airway inflammation in chronic OVA-exposed rats.

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.