Objective To observe the eotaxin expression of rat airway smooth muscle cells ( ASMCs) induced by serum from asthmatic rats, and explore the possible mechanism. Methods ASMCs isolated fromrat tracheas were cultured in vivo. Then they were treated with serum from asthmatic rats, or treated with serum and dexamethasone simultaneously. The level of eotaxin protein in supernatant and eotaxin mRNA in ASMCs were measured by ELISA and reverse transcription-polymerase chain reaction. The expression of cAMP in ASMCs was examined by radioimmunoassay. Results After the treatment with sensitized serum, the eotaxin level in supernatant and mRNA expression in ASMCs were significantly higher [ ( 107. 09 ±7. 12) ng/L vs. ( 0. 63 ±0. 56) ng/L, P lt; 0. 05; 1. 39 ±0. 04 vs. 0. 05 ±0. 01, P lt;0. 05] , and the level of cAMP in ASMCs was significantly lower compared with the control group [ ( 17. 58 ±3. 62) ng/L vs. ( 32. 39 ±3. 36) ng/L, P lt; 0. 05] . After intervened by the sensitized serum and dexamethasone simultaneously, the protein and mRNA expressions of eotaxin were lower compared with those intervened by sensitized serumalone [ ( 64. 18 ±4. 04) ng/L and 0. 77 ±0. 19] . The level of eotaxin in supernatant was negatively correlated with cAMP level in ASMCs ( r = - 0. 788, P lt; 0. 01) . Conclusions There is anautocrine function in ASMCs as inflammatory cells after stimulation with sensitized serum. Eotaxin may play an important roll in the pathogenesis of asthma via a cAMP-dependent pathway.
Objective To investigate the expression of RNP（alpha defensins） in guinea pigs with bronchial asthma and the influences of P2Y2 receptors on the expression. Methods Seventy-two adult male guinea pigs were randomly divided into a control group （group A） and an asthma group （group B）. The asthma model was established by sensitizing with ovalbumin injection intraperitoneally and challenging with ovalbumin inhalation. Then the A and B groups were divided into following subgroups,ie,the saline groups （A1/B1），ATP groups （A2/B2），and Suramin groups （A3/B3），in which the animals were intervented with saline，ATP，and suramin respectively. Total pulmonary resistance （RL） was measured.Total and differential cell counts in bronchoalveolar lavage fluid （BALF） were measured. Pathological changes of lung were observed under light microscope using HE staining. The plasma levels of RNP and IL-8 were measured by ELISA. The protein and mRNA expressions of RNP and P2Y2 were detected by immunohistochemistry and RT-PCR. Results The RL increased significantly as much as 10% in group B compared with group A. Pathological study revealed that luminal narrowing of bronchus and inflammatory cells infiltration in the asthma group. The total cell and polymorphonuclear neutrophil （PMN） counts in BALF in group B1 were significantly higher than group A1 and B3，but lower than group B2 （Plt;0.05）,but no significant difference among group A1，A2，or A3 was found. The RNP expression in plasma and lung tissue in group B1 was higher than group A1 and B3，but lower than group B2 （Plt;0.05）. The RNP expression in plasma and lung tissue was lower in group A1 than group A2，but higher than group A3（Plt;0.05）. The IL-8 expression in plasma in group B1 was significantly higher than group A and B3，but lower than group B2 （Plt;0.05） but no significant difference among group A1，A2，or A3 was found（Pgt;0.05）. RNP protein expressed predominantly in lung tissues，especially where the PMN infiltrated. The expression of RNP mRNA were consistent with the RNP protein expression in all groups. P2Y2 mRNA expression in group A1 was lower than group A2，and higher than group A3 （Plt;0.05）.P2Y2 mRNA expression in group B1 was lower than group B2 but higher than group B3 （Plt;0.05）. The linear correlation analysis showed that RNP had no significant correlation with PMN and IL-8 in group A，and was positively correlated with P2Y2 mRNA （Plt;0.05） while RNP was positively correlated with PMN，IL-8，and P2Y2 mRNA in group B. Conclusion RNP expression increases in bronchial asthma guinea pigs and may be related to P2Y2 receptors.
Objective To analyze the risk factors of hospitalized children with acute asthma exacerbation in Chongqing region. Methods A total of 193 cases were randomly selected from the hospitalized children with acute asthma exacerbation in Chongqing Children’s hospital and Jiangjin District People’s Hospital from January 2009 to December 2009. A self-designed questionnaire was used to collect data. A control group of children were randomly selected from the out-patients who received regular maintain therapy without asthma attacks for more than 3 months. Results The first independent risk factor of asthma hospitalization was respiratory infection ( 85. 5%, 165 /193) . Irregular use of control medications was the second important factor for the acute exacerbation. There were 75% ( 138 /193) patients didn’t take controlmedications regularly, includes 102 undiagnosed and 36 pre-diagnosed cases which was more common than that in regular maintain therapy group ( 21/110, 19. 1% ) . A variety of allergen-induced acute exacerbation of asthma was also common, which accountted for 9. 3 % ( 18/193) . There were more boys than girls ( M/F:124 /69) and no significant difference in the family history of allergic diseases ( P gt; 0. 05) . Conclusion Respiratory infection, under-diagnosis of asthma, and irregular use of the control medications are risk factors of acute exacerbation in children with asthma in Chongqing region. Meanwhile allergen exposure warrantsmore attention.
ObjectiveIn order to improve the prevention and treatment of bronchial asthma, the prevalence and risk factors of asthma in Chengdu among residents over 14 years old were investigated.MethodsA cross-sectional survey was conducted in Chengdu. The inhabitants (age > 14 years) recruited in this household questionnaire survey were through multi-stage cluster random sampling. Univariate and multivariate logistic regression were used to analyze the risk factors of asthma.ResultsA total of 3 477 subjects were finally recruited in this study. Of them, 131 were asthmatic patients; and the prevalence rate was 3.8%. There were significant differences observed in the prevalence of asthma among people of different ages, residences, occupations and educational levels (χ2=191.084, P<0.05; χ2=9.114, P<0.05; χ2=114.268, P<0.05; χ2=62.123, P<0.05). Univariate regression analysis showed that the risk factors of asthma included five factors (measles, chickenpox, pneumonia, tracheobronchitis and intestinal parasitic diseases) related to childhood illness, and two factors (asthma and chronic bronchitis) related to the first-degree relatives (P<0.05). In addition, active smoking history was a risk factor for asthma in men (P<0.05). Multivariate logistic regression indicated that measles, pneumonia, tracheobronchitis, intestinal parasitic diseases in childhood and first-degree relatives suffering from asthma were independent risk factors for asthma.ConclusionsThis study describes the epidemiological characteristics of asthma in Chengdu among adolescents (age>14 years) and adults. The history of measles, pneumonia, tracheobronchitis, and intestinal parasitic diseases in childhood, and first-degree relatives suffering from asthma are the independent risk factors for asthma. In addition, active smoking history is a risk factor for asthma in men.
ObjectiveTo explore the predictive value of fractional exhaled nitric oxide (FeNO) in the treatment response of adult asthmatic patients. Methods64 adult outpatients with asthma from Peking Union Hospital between March and September 2013 were recruited in the study. All patients completed asthma control test (ACT) together with exhaled nitric oxide (FeNO) and pulmonary function test. Then the patients were classified into a higher FeNO group (n=33) and a normal FeNO group (n=31) according to FeNO level. All patients accepted regular inhaled ICS/LABA treatment (salmeterol and fluticasone 50/250). Three months later all patients reaccepted ACT,FeNO and pulmonary function test. ResultsThe ACT score increased in all patients,and was significantly higher in the higher FeNO group than that in the normal FeNO group[22.07±5.49 vs. 19.23±5.48,t=2.893,P<0.05]. The complete control rate of the higher FeNO group was higher than that in the normal FeNO group (42.42% vs. 19.35%,χ2=3.960,P<0.05). The FEV1 and FEV1%pred of two groups both increased significantly (P<0.05),but there was no significant difference between two groups (P>0.05). Correlation analysis showed that FeNO and the declined rate of FeNO was negatively correlated with the ACT score(r=-0.302,P<0.05;r=0.674,P<0.01) and positively correlated with the improvement of ACT score (r=0.514,P<0.01;r=0.674,P<0.01). No significant correlation was found between FeNO and FEV1 or FEV1%pred. ConclusionThe effect of ICS/LABA therapy is better for asthma patients with higher FeNO. FeNO can be used for predicting the response to ICS/LABA therapy in patients with asthma and guiding the treatment.
ObjectiveTo study and compare the effects of inhaled preparations with open airway and conventional inhaled preparation on asthma patients.MethodsThe patients diagnosed with asthma and treated with the same inhaled preparation only who visited the outpatient department of West China Hospital of Sichuan University, were selected as the study subjects from April to September, 2019. The subjects were divided into the test group and the control group according to random ratio 1∶1. The conventional inhaled preparations were used in the control group. The inhaled preparations with open airway were used in the test group. Asthma control, life quality and treatment satisfaction rate were compared between the two groups after 3 months.ResultsA total of 150 subjects were included and one case dropped-off, then 149 effective subjects were obtained in which 75 cases in the test group and 74 cases in the control group. After 3 months’ treatment of inhaled preparations, the proportion of effective asthma control patients in the test group was higher than that in the control group, and the number of patients satisfied with the treatment of inhaled preparations was higher than that in the control group, with statistically significant differences (all P<0.05). The life quality of patients in both groups was improved compared with baseline, and the difference was statistically significant (P<0.05). However, the increase of scores in the test group was more than that in the control group, and the difference was also statistically significant (P<0.05). ConclusionInhaed preparations with open airway is superior to conventional inhaled preparation on asthma patients in asthma control, life quality and treatment satisfaction rate.
Objective To explore the effects of prolonged inhalation of Aspergillus fumigatus ( Af)spores on epithelial cell injury and expression of epidermal growth factor receptor( EGFR) in airways of asthmatic rats. Methods 64 male Wistar rats were randomly divided into 8 groups, ie. chronic asthma group ( group A) , chronic asthma plus Af spores inhalation for 1 week ( group B) , 3 weeks ( group C) and 5 weeks ( group D) , chronic asthma plus saline inhalation for 5 weeks ( group E) , OVA-sensitized and salinechallenged group ( group F) , and OVA-sensitized and saline-challenged plus Af spores inhalation for 5 weeks ( group G) ( each n =8) . The airway resistance ( Raw) and change of Raw after acetylcholine provocation were detected using a computerized system. The concentrations of epidermal growth factor ( EGF) andtransforming growth factor alpha( TGF-α) in BALF were measured by ELISA. The extents of epithelial cell injury and goblet cell hyperplasia were evaluated on hematoxylin and eosin-stained( HE) and periodic acidschiff ( PAS) stained lung sections. The expression of EGFR in airway epithelia was demonstrated byimmunohistochemistry, and the level of EGFR protein in the rat lung tissues was measured by western blot.Results The concentration of EGF( pg/mL) ( 51. 72 ±8. 54, 68. 12 ±7. 85, 86. 24 ±9. 12, respectively)and TGF-α( pg/mL) ( 55. 26 ±9. 30, 75. 58 ±11. 56, 96. 75 ±14. 66, respectively) , detached/ inner perimeter of epithelium( % ) ( 11. 25 ±3. 12, 26. 45 ±5. 56, 28. 50 ±7. 50, respectively) , the ratio of goblet cell area to epithelial cell area ( % ) ( 16. 42 ±5. 24, 22. 64 ±6. 82, 36. 38 ±9. 21, respectively) , the integrated optical density ( IOD) of EGFR positive stain in airway epithelial cells ( 82 ±15,120 ±19, 165 ±21, respectively) , and the EGFR protein levels in lung tissues ( 0. 91 ±0. 26, 1. 61 ±0. 52, 2. 52 ±0. 78,respectively) in group B, C, and D were higher than those in group A, E, F and G( P lt; 0. 05 or P lt;0. 01) .The change rates of Raw( % ) ( 61. 91 ±5. 26, 84. 69 ±6. 38) in group C and D were higher than those in group A, E, F and G ( P lt; 0. 05 or P lt;0. 01) . The IOD of EGFR was positively correlated with detached/inner perimeter of epithelium( % ) and the ratio of goblet cell area to epithelial cell area( % ) ( r = 0. 692,P lt;0. 01; r = 0. 657, P lt; 0. 01, respectively) . Conclusion Prolonged inhalation of Aspergillus fumigatus spores can aggravate airway epithelial cell injury, up-regulate the expression of EGFR in airway epithelial cell and induce goblet cell hyperplasia, thus increase the airway responsiveness in rats with chronic asthma.
【Abstract】 Objective To investigate the effect of allogeneic bone marrow-derived mesenchymal stem cells ( BMSCs) transplantation on the airway inflammation and airway remodeling in chronic asthmatic mice. Methods Forty female BALB/c mice were equally randomized into four groups, ie. a normal control group, a BMSCs control group, an asthma model group, and a BMSCs transplantation group. BMSCs were generated from male donor mice, then the mice in the asthma model group and the BMSCs transplantation group were sensitized and challenged with OVA to establish chronic asthmatic mice model. Hematoxylin and eosin staining and Alcian blue-periodic acid-Schiff staining were used to analyze the effects on airway inflammation and airway remodeling after BMSC engraftment. The number of CD4 + CD25 + regulatory T cells in spleen was detected by flow cytometry. Results In lungs of the asthmamodel group, there were intensive inflammatory cells infiltration around airway and blood vessels, goblet cell proliferation, epithelial desquamation, patchy airway occlusion by hyperviscous mucus, and hypertrophy of airway smooth muscle.Airway inflammation and airway remodeling were significantly relieved in the BMSCs transplantation group.There was no obvious inflammatory cells infiltration in the airway and airway remodeling both in the normal control group and the BMSCs control group. The number of CD4 + CD25 + regulatory T cells in spleensignificantly decreased in the asthma model group compared with the two control groups ( P lt; 0. 05) , and significantly increased in the BMSCs transplantation group compared with the asthma model group ( P lt;0. 05) . There was no significant difference in the number of CD4 + CD25 + regulatory T cells in spleen betweenthe control groups and the BMSCs transplantation group. Conclusion BMSCs engraftment can up-regulate CD4 + CD25 + regulatory T cells and relieve airway inflammation and airway remodeling in asthmatic mice.
Objective To invesitgate the relationship between 8-isoprostane ( 8-iso-PG) level in exhaled breath condensates ( EBCs) and severity of asthma and explore the role of 8-iso-PG in asthma evaluation and monitoring. Methods Fifty-nine patients with asthma were enrolled. In which 15 cases were acute exacerbation, 13 cases were mild intermittent, 15 cases were mild persistent, and 16 cases were moderate-to-severe persistent. Thirteen healthy volunteers were recruited as control. EBCs were collected using EcoScreen system. The 8-iso-PG levels in EBCs were measured by a specific enzyme immunoassay.The patients with mild intermittent asthma were treated with inhaled corticosteroid ( ICS) for one month and their EBCs were recollected for 8-iso-PG measurement. Results Exhaled 8-iso-PG levels were obviously increased in the patients with acute asthma compared with those chronic asthmatics [ ( 47. 2 ±6. 8) pg/mL vs ( 24. 5 ±12. 0) pg/mL, P lt; 0. 01] . In the chronic persistent asthma, the levels were significantly higher in patients with mild persistent and moderate-to-severe asthma [ ( 17. 9 ±1. 2) pg/mL and ( 39. 7 ±4. 0) pg/mL,P lt; 0. 01] . While 8-iso-PG level did not differ significantly in intermittent asthma [ ( 13. 5 ±1. 1) pg/mL]compared with the control subjects ( P gt; 0. 05 ) . After one-month ICS treatment the 8-iso-PG level in the patients with mild intermittent asthma did not change significantly although the ACT score improved. Conclusions 8-iso-PG levels in EBC are associated with the severity of asthma, implicating 8-iso-PG may be useful in monitoring airway oxidative stress in asthma. ICS treatment is incapable of decreasing the 8-iso-PG, suggesting the ICS has minor impact on oxidative stress.
The number of clinical guidelines developed and published in different countries is increasing worldwide. Too many guidelines do not remain in regular use, even though the aim is to implement them in clinical practice. The scientific validity and reliability of the guidelines need to be reviewed. Here is a case presented to show how to optimally use the evidence-based guideline to improve clinical decision making.