Objectives To investigate the frequency of LTC4S A-444C polymorphism in Chinese Han population in Beijing and to evaluate its association with susceptibility to asthma，asthma severity and clinical response to leukotriene receptor antagonist.Methods The LTC4S A-444C polymorphism was analyzed in 101 patients with asthma and 105 healthy controls.Then 18 asthmatics were recruited，and a 2-week prospective，open trial of montelukast was performed in addition to the previous medications.Results In the asthma group，the frequencies of A and C allele at -444 locus of LTC4S gene were 81.0% and 19.0%，respectively，and genotype frequencies of AA，AC and CC were 65.4%，30.5% and 3.8%，respectively.There was no significant difference in LTC4S A-444C polymorphism between the asthmatics and healthy controls（Pgt;0.05）.The asthmatics with the C-444 allele had significantly lower forced expiratory volume in one second（FEV1） than wild-type A homozygotes [（58.6±21.6）% predicted vs （70.3±22.4）% predicted，Plt;0.05）].A correlation was observed between the variant C-444 allele and asthma severity（Plt;0.05）.After administered montelukast 1 week，the A-444 allele homozygotes（n=9） responded better than the C（-444） allele carriers（n=7）[（10.8±10.2）% vs （–9.8±16.2）% improvement of FEV1，Plt;0.05].After 2 weeks，the A-444 allele hemozygotes also responded better，although there was no statistical difference（Pgt;0.05）.Conclusion In Chinese Han population LTC4S A-444C polymorphism is associated with asthma severity and probably contributes to the clinical response to leukotriene receptor antagonists.
Objective To investigate the changes of 8-isoprostane ( 8-isoPG) , leukotriene B4 ( LTB4 ) , TNF-α, IL-10 and hypersensitive C-reactive protein( Hs-CRP) in serum of patients with obstructive sleep apnea hypopnea syndrome ( OSAHS) . Methods Forty OSAHS patients ( 20 cases underwent therapeutic Auto-CPAP or UPPP treatment for over three months) and 30 normal controls were included in the study. Serum 8-isoPG, LTB4, TNF-α and IL-10 were measured by ELISA. Hs-CRP was detected by automatic biochemistry analyzer. Results ①The serum levels of 8-isoPG, LTB4, TNF-α, Hs-CRP were significantly higher and IL-10 was considerably lower after sleep in 40 OSAHS patients [ ( 36. 59 ±14. 89) ng/L, ( 14. 75 ±6. 25) μg/L, ( 1022. 13 ±97. 57 ) ng/L, ( 2. 46 ±1. 58 ) mg/L, ( 4. 68 ±3. 42) ng/L, respectively ] than those in the normal controls [ ( 19. 91 ±7. 76 ) ng/L, ( 1. 43 ±0. 72) μg/L, ( 540. 00 ±78. 70) ng/L, ( 0. 30 ±0. 16) mg/L, ( 7. 41 ±4. 49) ng/L, respectively] ( P lt;0. 01) . ② Serum 8-isoPG, LTB4, TNF-α, and Hs-CRP levels elevated gradually following the severity of OSAHS while serum IL-10 level was decreased( P lt; 0. 05) . ③Serum 8-isoPG, LTB4, TNF-α, and Hs-CRP levels in OSAHS patients after sleep were correlated positively with AHI ( r =0. 863, 0. 746, 0. 868, 0. 842,all P lt; 0. 01) and negatively with LSpO2 ( r = - 0. 623, - 0. 524, - 0. 618, - 0. 562, all P lt; 0. 01) and MSpO2 ( r = - 0. 654, - 0. 573, - 0. 537, - 0. 589, all P lt;0. 01) . SerumIL-10 level in OSAHS patients was correlated negatively with AHI ( r = - 0. 722, P lt; 0. 01) and positively with LSpO2 ( r = 0. 564, P lt; 0. 01) and MSpO2 ( r = 0. 505, P lt; 0.01) . ④ After three months of auto continuous positive air pressure( Auto-CPAP) or uvulopalatopharyngoplasty( UPPP) treatment, serum 8-isoPG, LTB4, TNF-α, and Hs-CRP levels of the OSAHS patients after sleep were obviously decreased [ ( 23. 10 ±9. 54) ng/L, ( 4. 02 ±2. 15) μg/L, ( 810. 25 ±135. 85) ng/L, ( 0. 79 ±0. 60) mg/L, respectively] , and serum IL-10 level was obviously increased[ ( 6. 93 ±3. 91) ng/L] ( P lt; 0. 01) . ⑤ serum 8-isoPG and IL-10 had no statistics difference and serum LTB4, TNF-α, Hs-CRP levels were higher in OSAHS underwent therapy compared with the normal controls. Conclusions The results suggest that inflammation and oxidative stress are activated and antiflammatory cytokines are decreased in the OSAHS patients. The serum levels of 8-isoPG, LTB4 , TNF-α, Hs-CRP and IL-10 may prove to be useful in severity monitoring and intervention efficacy judgement in OSAHS patients.
Objective To investigate the effects of TiotropiumBromide on airway inflammation in a rat model of chronic obstructive pulmonary disease( COPD) . Methods Thirty Wistar rats were randomly divided into three groups. Group A received normal breeding as normal control. Group B and group C received LPS( 200 μg, intratracheally injected at the 1st and the 14th day) and tobacco exposure( from the 2nd day to the 30th day except the 14th day) to establish COPD model. And group C received a nebulized dose of Tiotropium Bromide( 0. 12 mmol / L, 10 minutes) 30 minutes before the tobacco exposure each time. Airway resistance and compliance were measured before sacrificed. Histological examination was performed with Hematoxylin-Eosin staining. The concentrations of IL-8 and LTB4 , total and differential cells counts in bronchoalveolar lavage fluid( BALF) were examined, and the concentrations of IL-8 and LTB4 in blood serum were also examined by ELISA. Results Severe lung inflammation and decreased lung function were demonstrated in the rats in the group B compared with those in the group A. The inflammatory cell counts in BALF, and the levels of IL-8 and LTB4 in BALF and serum were significantly increased in the group B compared with those in the group A. Tiotropium Bromide administration improved the parameters above. Conclusions The results suggest that Tiotropium Bromide can alleviate the lung inflammation and improve the lung function in a rat COPD model. These effects may be exerted through reducing the mediators of inflammation.
Objective To compare the value of fractional exhaled nitric oxide ( FENO) measurement and leukotriene D4 bronchial provocation test ( LTD4-BPT) in diagnosis and evaluation of asthma. Methods 20 uncontrolled,22 partially controlled, 20 controlled asthmatics, and 21 normal subjects were enrolled in the study. Measurement of FENO was performed followed by LTD4-BPT. The distribution characteristics and relationship of both results were analyzed, and the diagnostic value was compared using receiver operation characteristic ( ROC) curve.Results FENO was above 25. 0ppb in 80. 7% of the asthmatics. The proportion of asthmatics with FENO between 26.0ppb and 49.0ppb was larger in the uncontrolled and partially controlled subjects than that in the controlled subjects. Both the median and interquartile range of cumulative dosage ( PD20FEV1-LTD4) were much higher in the controlled asthmatics as compared with the uncontrolled and partially controlled asthmatics. The area under the ROC curve ( AUC) for PD20FEV1-LTD4 [ AUC: 0.914, 95% CI: ( 0.855, 0.974) ] was larger than that of FENO [ AUC: 0.820, 95% CI: ( 0.718, 0.921) ] . Higher sensitivity ( 0.8570 vs. 0.8065) and specificity ( 0.9048 vs. 0.7619) were in favor of PD20 FEV1 -LTD4 ≤ 4.800 nmol as compared with FENO ≥ 26.0ppb being the positive threshold. Conclusion Compared with FENO measurement, LTD4-BPT has higher sensitivity and specificity and is of higher diagnostic value for asthma.
Objective To investigate the effects of montelukast ( MK) on the airway inflammation and the risk of the recurrence of wheezing in the treatment of infants with RSV bronchiolitis.Methods 60 infants ( aged 6-24 months) with RSV bronchiolitis admitted between December 2010 and December 2011 were recruited in the study. They were randomly assigned into a conventional group and a MK group ( n =30 in each group) . All patients received conventional treatments including inhalation of budsonide and so on.The subjects in the MK group received oral montelukast ( 4 mg qn for 12 weeks) additionally. The levels of serum cysteinyl leukotrienes ( CysLTs ) , total immunoglobuline E ( T-IgE) , eosinophil cationic protein ( ECP) and fractional exhaled nitric oxide ( FeNO) were assayed before and after the treatments. Thenumber of recurrence of wheezing was recorded through outpatient and telephone follow-up for 12 months. 30 healthy infants participating the health examination in outpatient were selected as control, and those who got atopic disease or respiratory tract infections recently were excluded. Results The levels of CysLTs, ECP and FeNO of the patients with RSV bronchiolitis before treatment were significantly higher than those in the normal control group, and the levels of CysLTs and FeNO were significantly decreased after treatment ( P lt;0. 05) . The levels of CysLTs and FeNO after treatment in the MK group was significantly lower than those in the conventional group. The level of ECP was significantly decreased after treatment in the MK group ( P lt;0. 05) ,·186· Chin J Respir Crit Care Med, March 2013 , Vol. 12 , No. 2 http: / /www. cjrccm. com which was not significantly changed in the conventional group( P gt; 0. 05) . The number of recurrence of wheezing in the MK group was more less that that in the conventional group ( P lt; 0. 05) . Conclusion Maintenance treatment with montelukast after the treatment of the acute phase of bronchiolitis can prevent recurrence of wheezing by suppressing airway inflammation in infants with RSV bronchiolitis.
Objective To explore the effect of leukotriene receptor antagonist montelukast on physicochemical property of sputum and airway mucus hypersecretion in patients with acute exacerbation of bronchiectasis. Methods Eighty-four inpatients with acute exacerbation of bronchiectasis were randomly divided into a control group and an experiment group, with 42 cases in each group. The control group received conventional therapy and the experiment group took orally montelukast 10 mg before sleep every day based on conventional therapy for two weeks. At admission and 15 days after admission, the amount in 24 hours, dry/wet weight ratio and viscosity of sputum were observed while the levels of neutrophil elastase (NE) and mucin MUC5ac in sputum were determined by ELISA. The pulmonary ventilation function, airway resistance and blood gas analysis were also measured. Results The sputum amount in 24 hours, dry/wet weight ratio and viscosity of sputum, NE and MUC5ac of sputum, pulmonary ventilation function, blood gas analysis and airway resistance were declined or improved remarkably after treatment compared with before treatment in two groups (P<0.05). Meanwhile, the sputum amount in 24 hours [(5.62±1.83) g vs. (7.53±2.32) g], NE [(3.85±0.97) μg/ml vs. (4.54±1.03) μg/ml], MUC5ac [(0.65±0.21) μg/ml vs. (0.82± 0.29) μg/ml] and the airway resistance [(119.16±11.76)% vs. (128.37±12.08)%] were declined remarkably in the experiment group compare with the control group after treatment (all P<0.05). The viscosity of sputum between the two groups after treatment showed no significant difference. Conclusion In patients with acute exacerbation of bronchiectasis, montelukast can reduce amount of sputum and airway resistance, reduce expression of mucin MUC5ac through down-regulation of NE, thus inhibit airway mucus hypersecretion.