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Different Doses Of Seretide Treatment Of Stable COPD And Cytokine Related To Research

Posted on:2012-11-04Degree:MasterType:Thesis
Country:ChinaCandidate:R H ZhangFull Text:PDF
GTID:2214330368478840Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
Background: Chronic obstructive pulmonary disease (COPD) is character- ized as a non-fully reversible airflow limitation .It not only involves the lungs, but also can cause significant systemic effects, which has become an important problem of public health.COPD becomes one of the major cause of morbidity and mortality.According to the WHO statistics, it is forecasted that the prevalence of COPD was 6.3% in the twelve Asia-Pacific countries and regions. the mortality of COPD is ranked the fourth in the world. Thus reducing the acute exacerbation of COPD seizure frequency and severity is an important goal of COPD treatment. AT the most of the time, the COPD patients are in a stable state in the development of the disease process, so how to treat the patients in a stable state is very important to reduce exacerbations of COPD. The Global Initiative for Chronic Obstructive Lung Disease in 2006 and the COPD treatment guidelines of our country in 2007 sugested that: For the COPD patients who's FEV1 <50% (Ⅲperiod,Ⅳperiod) and the patients with recurrent acute attacks (such as episodes of the past three years, three times), the inhaled corticosteroids is need to add on the basis of bronchodilator .It can reduce the number of acute episodes and improve health condition.COPD has complex and diverse pathological manifestations. Patients with different clinical symptoms, disease severity and rate of progress have significant heterogeneity. In Current, the disease markers is limited to assess patients with COPD and compared the efficacy.The forced expiratory volume in 1s (FEV1)is still widely used in the Clinic as a COPD diagnosis, classification and prognosis of the gold standard measure.Many extrapulmonary manifesta -tions have not been very good interpretation. Blood test is becoming a hotspot,since it's a small Invasion, high repeatability and it has a reliable, standardized testing methods.CRP is the most representative marker in the plasma.At least two large epidemiological studies were confirmed that about 60% of the COPD patients with stable state have high CRP levels compared to normal levels (<3mg / L) . 11% of them is for the 3 ~ 5mg / L, 48% of patients exceed this level, and this increase is not contained with ischemic heart disease or smoke cause. This phenomenon prompted that COPD is not only lung inflammation, but also is a continuous and low intensity of systemic inflam -matory response.At present, many studies have shown that there is a certain degree of increase of IL-8 in the bronchoalveolar lavage fluid(BALF), sputum, plasma and lung tissue of the patients with COPD. They presume that IL-8 is involved in the neutrophil recruitment and involved in the inflammatory process of COPD,and it may correlate with the classification of COPD severity. However, it is not clear yet what mediate its specific regulatory mechanisms between the T cells, CXC chemokines (eg IL-8, LTB4, IL-6, MIP-2, etc.) and neutrophil activation. Recent studies have shown that IL-17 may play in mediating between the three roles, and participate in its control mechanism.Seretide is an inhaled mixture of long-actingβ2 agonists-salmeterol and corticosteroids-fluticasone.Fluticasone propionate has the characteristics which inhaled corticosteroids has, such as fat-soluble, easy to penetrate the cell membrane, a high degree of affinity with the glucocorticoid receptor;high concentrations in lung tissue, a long residence time; strong activity of local anti-inflammatory, a higher proportion of pulmonary and systemic distribution, light systemic effects and so on. Salmeterol is a selectiveβ2-adrenergic receptor agonist, it can produce effects at least 12 hours one time. A number of major studies have confirmed that ICS jointed with LABA may reduce the frequency of COPD worsening, slow decline in the quality of life, and give help with controlling the symptoms. Currently Seretide 50/250 (salmeterol 50μg / flutica -sone 500μg) and Seretide 50/500 (salmeterol 50μg / fluticasone 250μg) has been widely used in the treatment of the COPD patients with stable states. It's mostly reported as a single-species formulations of Seretide efficacy study, and there is no comparision between Seretide 50/250 and Seretide 50/500 for the efficacy of treating the COPD patients with stable states.Objective: Compare the efficacy of Seretide 50/250 and Seretide 50/500 in treating COPD patients(stageⅢ) with stable states through determining pulmonary function ,C-reactive protein and plasma IL-8, IL-17 changes before and after treatment . Methods: 108 cases of eligible patients with COPD patients(stageⅢ) in the stationary phases in our horspital from the September 2010 to the August 2011 are randomly divided into three groups, Seretide 50/250 treatment group, Seretide 50/500 treatment group and conventional treatment group,each group has 36 patients.The healthy control group has 20samples. The conventional treatment groups uses conventional therapy contain: (1) For smoking patients, persuade them to quit smoking. (2) rehabilitation of patients such as reduced lip movement, abdominal breathing exercises and nutritional support. (3) advise patients with home oxygen therapy which daily oxygen time is 10-12 hour/day and 1-2L/min. The two seretide treatment groups use conventional therapy and they also use Seretide 50/250 or Seretide 50/500 with continuous application for three months.The healthy control group has no history of COPD, no smoking, no history of chronic cough, sputum and wheezing history, pulmonary function tests of airway obstruction is normal, and they are free volunteers. We measured the results of C-reactive protein, pulmonary function and inflammatory media -tors (IL-8, IL-17) levels before treatment and after 3 months of treatment in the three groups of patients and analyzed statistically. We also measured the results of media -tors (IL-8, IL-17) levels for the healthy control group.Results: (1) The FEV1/FVC %andFEV1% are significantly increased (P <0.05) after Seretide treatment. Conventional therapy showes no statistically significant (P> 0.05). The efficacy of Seretide 50/500 is better than Seretide 50/250. (2)Before treatment, the IL-8 levels in blood are higher in the COPD patients(stageⅢ) in the stationary phases than the healthy control group, it has significant difference (P <0.05). Before treatment, the IL-8 levels in blood are not significantly different (P> 0.05) between the seretide treatment groups and the conventional therapy group. The IL-8 levels in blood are not significantly different (P> 0.05) before and after treatment in the Conventional treatment group. The IL-8 levels in blood are significantly different (P < 0.05) in the seretide treatment groups before and after treatment. The IL-8 levels in blood are significantly different (P < 0.05) in the two seretide treatment groups . the efficacy of Seretide 50/500 is better than Seretide 50/250 at the aspect of declin -ing the IL-8 levels in blood.it has significantly different (P < 0.05).(3) Before treatment, the IL-17 levels in blood are higher in the COPD patients(stageⅢ) in the stationary phases than the healthy control group, it has significant difference (P <0.05). Before treatment, the IL-17 levels in blood are not significantly different (P> 0.05) between the seretide treatment groups and the conventional therapy group. The IL-17 levels in blood are not significantly different (P> 0.05) before and after treatment in the Conventional treatment group. The IL-17 levels in blood are significantly different (P < 0.05) in the seretide treatment groups before and after treatment. The IL-17 levels in blood are not significantly different (P>0.05) in the two seretide treatment groups after treatment.(4)Before treatment, the CRP levels in blood are not significantly different (P> 0.05) between the seretide treatment groups and the conventional therapy group. The CRP levels in blood are not significantly different (P> 0.05) before and after treatment in the Conventional treatment group. The CRP levels in blood are significantly different (P < 0.05) in the seretide treatment groups before and after treatment. The CRP levels in blood are not significantly different (P > 0.05) in the two seretide treatment groups after treatment. (5) The most common adverse reactions of long-term use of inhaled corticosteroids are dysphonia, hoarseness and oropharyngeal candidiasis. In this study, the seretide 50/250 treatment group has one case of hoarseness and one case of oropharyn -geal candidiasis , and the seretide 50/500 treatment group has one case of hoarseness and three cases of oropharyngeal candidiasis.Conclusions: (1)Seretide can improve lung function especially at the aspect of increasing of the FEV1% and FEV1/ FVC% and it can relieve airflow limitation. The increase of the inhaled corticosteroid dose can improve lung function more significantly. (2) The IL-8 and IL-17 levels in blood are higher in the COPD patients(stageⅢ) in the stationary phases than the healthy control group.(3)It is convinced that using Seretide can decrease the IL-8, IL-17and CRP levels in blood in the COPD patients(stageⅢ) in the stationary phases , and increasing the dose of inhaled corticosteroid the level of IL-8 can decrease more obviously, but the levels of IL-17and CRP have no difference.
Keywords/Search Tags:Chronic obstructive pulmonary disease (COPD), Seretide (salmeterol / fluticasone), IL-8, IL-17, CRP, lung function
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