Meta-analysis On The Efficacy And Side-effect Of Inhaled Corticosteroids For Asthma

Asthma is one of the common respiratory diseases. It is a chronic inflammatory disorder defined by variable and reversible airway obstruction, inflammation and hyperresponsiveness. The typical symptoms are wheeze, cough, chest tightness, and shortness of breath. It often attacks or intensifies at night or in the early morning, and most of the patients can be relieved by themselves or after treatment.The main changes for the patients with asthma are the examinations of respiratory function on diagnosis and assessment of therapeutic efficacy. It presents obstructive ventilatory disturbance and a significant drop in expiratory flow rate. The indexes,such as forced expiratory volume in one second (FEV1),FEV1 percent predicted, maximal mid-expiratory flow(MMEF) and peak expiratory flow (PEF),also decrease. It shows the decrease of forced vital capacity, the increase of residual volume,total lung capacity and the percentage of residual volume to total lung capacity,in the indexes of lung capacity. The above-mentioned indexes can gradually restored to normal levels during remission in asthma symptoms.Peak expiratory flow can respond the change of ventilation function of airways,and it decreases when asthmatic attack. In addition,for the character of rhythm change of ventilation, asthma often intensifies at night or in the early morning, and ventilation decreases.If the variation rate of PEF between day and night is not less than 20%,which consists with the character of reversible airway obstruction, it helps to diagnose and evaluate therapeutic efficacy. Now asthma can not be cured, and the purpose of treatment is to control symptoms and prevent the illness from worsening as far as possible, maintain a normal lung function and normal activities,avoid the side effects of treatment,prevent irreversible airflow obstruction and avoid death. In addition to the current drug relieving asthma, the drug controlling asthma,which mainly treats airway inflammation, is also known as anti-inflammatory drugs including glucocorticoids, leukotriene modifier, sodium cromoglicate,ketotifen,a new generation of histamine H1 receptor antagonist, and other categories.With the research progress of pathogenesis of asthma,inhaled corticosteroids has become a preferred drug for long-term treatment of choice asthma.The way of inhalation is better in local anti-inflammatory.Administrating though inspiratory process,the drug can act on respiratory directly, and small dose is required.Most of the drug,entering blood through the digestive tract and respiratory,is inactivated by liver, thus systemic adverse effects is less.More and more results of studies show that ICS has better clinical efficacy and smaller side effects,but there has been less evidence of evidence-based medicine. The alleged evidence-based medicine is the clinical medicine following evidence that utilizes the best evidence at present to constitute the scheme about diagnosis and treatment on the individual patient consciously,definitely and prudently. The study taking effective document retrieval methods,adopting appropriate literatures and then appraising them,selects meta-analysis method , the core research approach of evidence-based medicine,to analysis clinical efficacy and side effects of the ICS qualitatively and quantitatively and to provide evidence-based medical evidence for asthma treatment with ICS in clinical application.Using "Meta-analysis", "asthma", "Inhaled Corticosteroids", "efficacy", "side effects" as keywords, through the computer, manual retrieval, as well as linking with authors,407 relevant literatures,published in MEDLINE,PubMed,Cochrane Controlled Trials Register,China National Knowledge Infrastructure,and so on,till 2007 for Chinese papers and from 2002 to 2007 for foreign,have been obtained.Then according to including and excluding standards,there are 13 papers,about randomized controlled trail on asthma treatment with ICS,involved in this study. On the basis of Jadad scale,8 of the 13 papers are studies of high-quality and 5 are low-quality. Meta-analysis method,the core research method of evidence-based medicine, is used to analysis test results quantitatively.WMD or SMD is selected to describe the research indicators which are continuous variables,while RR,OR or RD is for those belonging to two classification of variables.The test for heterogeneity of 14 targets have been carried on by Peto method and inverted variance.Fixed effect model is used for the targets with homogeneity to combine statistics,while random effects model is for the targets with heterogeneity.Forest plots generated by software have been adopted to test combining variables;the sensitiveness analysis have been finished by changing effect variances(WMD and SMD or OR and RR),random effects model and fixed effects model;through estimating funnel plots,the publication biases analysis have been described. The results show that:In addition to some papers about the impact of Beclometasone on FEV1,the impact of all of ICS drugs on FEV1,the impact of Budesonide on FEV1,the impact of all of ICS drugs on FEV1%,the occurrence of adverse events in the studies and ineffective treatment for asthma displaying heterogeneity,the other targets all display homogeneity, which indicates literatures with small differences.Only the results on 95% CI of the effect variances about the impact of Budesonide on FEV1 and the impact of Budesonide on FEV1%,obtained by changing random effects model and fixed effects model and the effect variances(WMD and SMD),show some differences,while other results all have small differences,which proves the analysis results are relatively steady , and the conclusion is reliable basically.The funnel plots of most literatures display asymmetric in various degrees,which explains that there are still certain publication biases. When literatures have heterogeneity and the results of sensitivity analysis present unstable , definite conclusions cannot be obtained ; whereas definite conclusions can be gotten.The results of meta-analysis:That treatment of mild to moderate asthma with ICS in adults and adolescents can improve FEV1 and FEV1% of asthma patients, significantly improve the morning PEF of patients with asthma;The remission rate of asthma symptoms of treatment with ICS group is higher than that of control group;in the course of treatment,the incidences of invalid treatment,asthma symptoms aggravation and even withdrawing from the trial, are less in treatment with ICS group than those in the control group,and occurrence adverse events are less in treatment with ICS group than that in the control group significantly.As for side effects of throat discomfort, pharyngitis, hoarseness and oral candidiasis , the incidence of throat discomfort is not different between short-term (12 weeks) inhaled corticosteroid therapy in patients with asthma and control group.Therefore,compared with fundamental treatment of asthma,ICS has better clinical effects and smaller side effects.That the potential publication bias and low quality of trails reduces the authenticity and reliability of the datas in the meta-analysis in various degrees,which makes the existing evidence unable to fully substantiate that the ICS is better than other drugs in asthma treatment. Currently, there is no precise evidence of clinical application, so it is necessary to carry out a series of large-scale,multi-center, prospective, randomized, double-blind,controlled clinical trials designed well, to provide evidence-based medical evidence for asthma treatment with ICS in clinical application as soon as possible.