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.
ObjectiveTo explore the application of pulmonary ventilation and perfusion imaging (V/P SPECT/CT) in quantitative evaluation of ventilation and perfusion function and its potential value in guiding local treatment of lung in patients with asthma.MethodsA total of 20 patients with asthma were included in this study. All patients underwent V/P SPECT/CT and pulmonary function test, and symptoms were assessed by the ACT questionnaire. Patients were graded for degree of airway obstruction according to V/ P SPECT/CT image visual scoring criteria. The comprehensive lung function (%) of the patients was quantitatively evaluated by combining the ventilation and perfusion defect of each lung segment in V/P imaging. The correlation between the degree of airway obstruction, comprehensive lung function, pulmonary function test and ACT score was analyzed.ResultsV/P SPECT/CT imaging can be used to grade the degree of airway obstruction in asthma patients (0-3 grade). Airway obstruction grading by V/P SPECT/CT visual score was associated with predictive forced expiratory volume in one second (FEV1%pred) of patients (r=–0.74, P<0.001). V/P SPECT/CT can also comprehensively evaluate ventilation and perfusion function in patients with asthma, and comprehensive lung function measured by this method was also correlated with FEV1%pred (r=0.629, P=0.003). V/P SPECT/CT can be used to quantitatively analyze the percentage of ventilation and perfusion function in each lung lobe. Compared with V/P SPECT/CT results, the CT volume overestimates the contribution in the upper lobes, and underestimates the lower lobes contribution to overall function.ConclusionsV/P SPECT/CT can be used as a new method to directly reflect the degree of airway obstruction in patients with asthma. Moreover, it can comprehensively and quantitatively evaluate the ventilation and perfusion function of asthma patients. V/P SPECT/CT can also be used to evaluate lobe function in patients with asthma, helping to identify the heterogeneity of changes in pulmonary function in patients with asthma, and has potential value for future treatment targeting specific areas of the lung.
Objective To investigate the effects of dust mite allergen Derp1 on the expressions of IL-6 and IL-8 in primary rat bronchial epithelial cells. Methods The primary rat bronchial epithelial cells were divided into a control group and three experimental groups. In the experimental groups, the cells were cultured with 3 different concentrations of Derp1 ( 1, 5, 10 μg/mL) for 3 different time ( 4, 8, 24 h) .Inverted microscope was employed to observe the morphological changes of bronchial epithelial cells and intercellular space, and supernatants were assayed for IL-6 and IL-8 with ELISA. Results Complete flattening of single cells layer was observed in the control group. In the experimental groups, the cells treated with Derp1 allergen showed no obvious changes in the cell morphology and intercellular space. However,There was a significant change in the level of cytokines production compared with the control group. The levels of IL-6 and IL-8 began to rise at 4 h, and reach to high level at 8 h, especially in the 5 and 10 μg/mL groups ( P lt;0. 01) . In the 24h group, the concentrations further increased but not reach statistical difference compared with 8h group ( P gt; 0. 05) . Conclusions The Derp1 allergen can stimulate the release of inflammatory cytokines such as IL-6 and IL-8 fromthe rat trachea- bronchia epithelial cells. It is suggested that dust mite allergen -induced cytokines may play important roles in the pathogenesis of allergic asthma.
目前哮喘的治疗已经取得了显著的进步, 大多数哮喘按全球哮喘防治创议( GINA) 推荐的治疗方案进行规范治疗都可以获得良好的临床控制, 但仍有部分中重度患者难以获得良好的临床控制, 所以仍有必要探索针对这一部分哮喘人群的更好的干预措施。
ObjectiveTo survey the current asthma impact on quality of life and related factors in China. MethodsTwo thousand and thirty-four asthmatic patients, from bronchial asthma prevalence epidemiology survey in the population over 14 years old in 8 areas of China from 2009 to 2013, were enrolled. The data about medical resource use, control status and quality of life were collected by detailed questionnaire and analysed using the Epidata database and SAS 9.2 software. ResultsOut of the 2034 asthma patients, 1213 patients (59.6%) reported that their activities including entertainment, learning, fertility and employment were limited due to asthma. In the four aspects of entertainment, education, family and employment, 688 patients (33.8%) had one limited activity in one aspect, 165 patients (8.19%) had most of activities limited in one aspect, 246 patients (12.1%) had limited activities in two or three aspects, 114 patients (5.6%) had limited activities in all aspects. One hundred and eighty-one patients (8.9%) needed help in daily life, such as cooking, shopping, doing housework. Seventy-one patients (3.5%) even needed help in eating, personal hygiene, toilet, and their daily activities were remarkably restricted. Eighty-one patients (4.0%) had motive of suicide. Aging, comorbidity, and medication use were the most important factors. ConclusionAsthma has a significant negative effects on the life and emotion of patients, and proper control of comorbidity and regular treatment of asthma are effective ways to improve the life and emotional state of patients with asthma.
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.
ObjectiveTo determine whether there is an imbalance of KLF2/RelA in peripheral blood neutrophils in patients with bronchial asthma, and explore the relationship between KLF2/RelA imbalance and neutrophil apoptosis.MethodsFrom April 2011 to April 2012, a total of 39 patients with acute attack of asthma in Hunan People's Hospital and Third People's Hospital of Changsha were enrolled, with 13 cases in mild asthma group, 17 cases in moderate asthma group, and 9 cases in severe asthma group. Fifteen healthy subjects were recruited as control group. Peripheral blood were collected from all subjects followed by separation of neutrophils. The apoptosis of neutrophils were measured by flow cytometry. The expression of KLF2 and RelA were detected by Western blot. The relationship between the ratio of KLF2/RelA and neutrophil apoptosis rate was analyzed by Pearson correlation test.ResultsNeutrophil apoptosis rates in the mild, moderate and severe asthma groups [(4.45±0.76)%, (2.10±0.25)%, (1.81±0.67)%, repectively] were lower than that in the healthy control group [(5.36±0.57)%, all P<0.01]. The apoptosis rates of neutrophils in the moderate and severe asthma groups were lower than that in the mild asthma group (bothP<0.01), but there was no significant difference between the moderate asthma group and the severe asthma group (P>0.05). The ratios of neutrophil KLF2/RelA in the mild, moderate and severe asthma groups were lower than that in the normal control group (0.667±0.351, 0.384±0.203, 0.536±0.293vs. 4.038±2.011, all P<0.01). There was no significant difference between the groups of mild, moderate and severe asthma (P>0.05). The neutrophil apoptosis rate was positively correlated with the percentage of neutrophil KLF2/RelA (r=0.592 0, P<0.000 1).ConclusionThere is an imbalance of KLF2/RelA in peripheral blood neutrophils in patients with bronchial asthma, and the imbalance of KLF2/RelA may be the mechanism of apoptosis of peripheral blood neutrophils.
Objective To investigate the percentage of CD4 + CD25 + Treg cells and expression of Foxp3 mRNA in asthmatic patients and the impacts of inhaled steroids.Methods The percentages of CD4 +CD25 + Treg cells was assayed by flow cytometry and the expression of Foxp3 mRNA was detected by RT-PCR in peripheral blood mononuclear cells from the patients with chronic persistent asthma before and after steroids inhalation in comparison with healthy control. The forced expired volumin one second/predicted value( FEV1% pred) and peak expired flow( PEF) were measured by spirometry. Results The level of CD4 + CD25 + Treg cells and the expression of Foxp3 mRNA were lower in asthmatics before steroids treatment than those in control ( P lt; 0. 05) which were increased significantly after steroids treatment ( P lt; 0. 05) .FEV1% pred and PEF were declined significantly than those in control but improved markedly after treatment ( P lt; 0. 05) . Conclusions The insufficiency of amount and function of immue-suppressive CD4 + CD25 +Treg cells may play a role in the pathogenesis of asthma. Inhaled steroids can improve the lung function of asthmatics by upregulating the level of CD4 + CD25 + Treg and Foxp3.
Objective To evaluate the applicability of the cut-off points of different versions of the Asthma Control Questionnaire (ACQ) in the Chinese population and their consistency with the symptom control criteria of the Global Initiative for Asthma (GINA), so as to provide strategies for cut-off point selection in clinical practice. Methods Based on baseline data from a multicenter prospective cohort study, asthma patients who completed pulmonary function tests, GINA symptom control assessments, and the ACQ-7 questionnaire were included. Taking the GINA symptom control level as the gold standard, the Receiver Operating Characteristic Curve (ROC) was used to determine the optimal cut-off points of the ACQ for discriminating the GINA symptom control levels, and the consistency was analyzed by kappa statistics. Results Among 399 patients (58.9% female; mean age 44.5 ± 12.8 years), asthma symptom control, partial control, and uncontrolled rates were 61.7%, 27.6%, and 10.8%, respectively. ROC analysis revealed the following optimal cutoffs for identifying symptom control: ACQ-5 (0.5), ACQ-6Res (0.42), ACQ-6PFT (0.92), and ACQ-7 (0.93); for identifying uncontrolled symptoms: ACQ-5 (0.9), ACQ-6Res (1.08), ACQ-6PFT (1.42), and ACQ-7 (1.36). All corresponding areas under the ROC curve (AUC) exceeded 0.9. Consistency between ACQ and GINA symptom control levels was moderate (Fleiss’ κ = 0.453–0.531). Performance characteristics varied between traditional (0.75/1.5) and optimized cutoffs. After optimization, ACQ-5 emerged as the only version achieving balanced sensitivity-specificity (Youden index = 0.75) in dual tasks: ACQ-5 ≤ 0.5 demonstrated sensitivity (91%) and specificity (84%) for symptom control, while ACQ-5 ≥ 0.9 showed sensitivity (95%) and specificity (80%) for uncontrolled status. Conclusions Region-specific calibration of ACQ cutoffs enhances clinical utility in the Chinese population. A stratified application strategy is recommended: high-sensitivity cutoffs for initial screening to reduce underdiagnosis, high-specificity cutoffs for resource-constrained settings to minimize overtreatment, and optimized ACQ-5 cutoffs (≤0.5/≥0.9) for comprehensive management to balance sensitivity and specificity. Flexible combination of cutoff protocols tailored to screening objectives may optimize hierarchical asthma management.
Objective To evaluate the effects of different inspiratory flow waveforms on the respiratory function of patients with severe exacerbation of asthma during mechanical ventilation. Methods Twenty-one patients with severe exacerbation of asthma were ventilated with square waveform and decelerating waveform respectively for 30 minutes when the tidal volume was set at 6 mL/ kg, 8 mL/ kg and 10 mL/ kg in ICUof Zhejiang Hospital of Integrated Traditional Chinese and Western Medicine fromJanuary 2006 to December 2007. Meanwhile shunt fraction ( Q·S /Q·T ) , dead space value ( VD/VT ) , airway peak pressure ( Ppeak ) , plateau pressure ( Pplat) ,intrinsic positive end-expiratory pressure( PEEPi) and arterial blood gas analysis were measured. Results The Q ·S /Q·T in the decelerating waveformgroup was less than that of the square waveform group( P lt;0. 05) when tidal volume was set at 6 mL/ kg. When tidal volume was set at 10 mL/ kg, PEEPi and VD /VT in the decelerating waveform group were higher than those of the square waveform group. On the contrary, the Ppeak was lower than that of square waveform group( P lt; 0. 05) . Conclusion For patients with severe exacerbation of asthma treated with mechanical ventilation, decelerating waveform is preferable at low tidal volume( 6 mL/ kg) , and square waveform is preferable at high tidal volume( 10 mL/kg) .