Change Of Inspiratory Capacity In Stable COPD Patients After Inhaling Bronchodilator: A Meta-Analysis

BACKGROUNDAirflow limitation in expiration and lung hyperinflation induced by the increased residual capacity are the major features of Chronic Obstructive Pulmonary Disease (COPD) in pathophysiology, which is the main cause of exertional dyspnea and decreased exercise tolerance in COPD patients.Stop smoking is the most effective intervention to disturb the development of COPD, which is different from cardiovascular and cerebrovascular diseases and AIDS. Except that, there is still no effective medication to prolong the lifetime of COPD patients. Now most of the drugs to cure COPD are from those treating asthma, and just has limit effects to alleviate the symptoms. There are two reasons for this situation:first, the molecular mechanism of COPD is still unknown; second, the biomarkers to assess the drug in the stageⅡorⅢof clinical trials are still in lack.Forced expiratory volume in 1 second (FEV1) is widely used in the clinical work as a biomarker reflecting the degree of airflow limitation. For FEV1 can be obtained and repeated easily, it is the most commonly used biomarker to assess the clinical trials. But FEV1 still has some limitations. On one hand, FEV1 has weak associations with the long-term clinic outcome such as quality of life, frequency of exacerbation, hospitalization rates and mortality in COPD patients. On the other hand, the phenomenon that the FEV1 changed little while dyspnea and exercise tolerance improved in the stable COPD patients after inhaling the bronchodilator exists.Inspiratory capacity (IC) can reflect the dynamic hyperinflation (DH) indirectly. DH has better correlation with the degree of dyspnea and exercise tolerance of COPD patients. Previous studies reported that the increased IC has significant correlation with the improvement of dyspnea and exercise tolerance after inhaling bronchodilator in COPD patients. So IC can act as a biomarker to reflect the improvement of functional ventilation. At present, there have been considerable studies on the IC in COPD patients after inhaling bronchodilator but the number of cases included are few and little research has been done on the comparison between FEV1 and IC in stable COPD patients after inhaling bronchodilator.OBJECTIVES1. To compare the change of IC and FEV1 in static condition of stable COPD patients after inhaling bronchodilators.2. To detect the change of Borg scale of the stable COPD patients who receive the treatment of inhaling bronchodilators after the exercise tests.3. To detect IC and the extent of change of IC of stable COPD patients who receive the treatment of inhaling bronchodilators after the exercise tests.4. To compare IC and FEV1 acting as therapeutic biomarkers in stable COPD patients after inhaling bronchodilators.METHODSReview the clinic studies published in biologic and medical journals at home and abroad from 1993 to 2009, which is on the change of IC in the stable patients after inhaling the bronchodilator. Choose "randomized controlled trial, COPD, inspiratory capacity" as the index terms to search for the literatures in the Cochrane Library and MEDLINE and searched the conference paper manually. The time range was between the built-up time of the database and November 30th 2009.Two independent reviewers evaluated the titles, abstracts, and methods sections of all identified reports of clinical trials. The studies that seemed to fulfill the inclusion criteria were selected and crosschecked. They would discuss to solve the divergence of views.Jadad scale, the common method for quality assessment in Cochrane systematic reviews, was used to estimate the quality of the included essays. The evaluation items included:①generation of random sequence;②randomized concealment;③blinding method;④leaving and loss to follow-up. The quality of included researches was divided into two groups according to the final score of the Jadad scale. Low-quality researches got 1 to 3 points while high-quality ones got 4 to 7 points. Two reviewers did this assessment independently.Meta-analysis was done on the change of IC and FEV1 of stable COPD patients before and after inhaling bronchodilators, Borg scale and IC after exercise tests, the change of IC before and after exercise tests with the RevMan 4.2 statistical software. Sensitivity analysis included①excluding unpublished articles;②excluding low-quality researches;③excluding the particular long course of treatment or studies with large sample to valuate their impacts to the results. RevMan 4.2 statistical software used random effect model and fixed random model to analyze the data. And the results was expressed with WMD and SMD. Compare these results respectively to evaluate the sensitivity of the Meta-analysis. Funnel plots were used to estimate the possible publication bias.RESULTS74 articles were found with the search strategy mentioned above.7 articles were included after screening one by one according to the inclusion and exclusion criteria. Among the 4 included articles, all of them described the change of IC and FEV1 before and after inhaling bronchodilators.2 articles conducted symptom-limited constant-load exercise tests on the COPD patients after the treatment of inhaling bronchodilators and reported the Borg scale and IC.The results of Meta analysis are below:1. Meta-analysis of the change of IC and FEV1 after inhaling bronchodilators at rest The change of IC (χ2=2.42, P=0.49,I2=0%) and FEV1 (χ2=1.60, P=0.66, I2=0%) after inhaling bronchodilators at rest had homogeneity. Change of IC in WMD (fixed effect model) is -0.22; 95%CI is (-0.28 to -0.15); Test for overall effect is Z=6.27, P<0.00001. Change of FEV1 in WMD (fixed effect model) is -0.21; 95%CI is (-0.26 to -0.15); Test for overall effect is Z=7.60, P<0.00001. The rise of IC and FEV1 after inhaling bronchodilators at rest is of statistical meaning. Maximum of the rise of IC is 0.28L while minimum 0.15L. And the maximum of the rise of FEV1 is 0.25L, while minimum 0.18L. The rise of both IC and FEV1 are similar.2. Meta-analysis of change of Borg scale after exercise tests in the stable COPD patients after inhaling bronchodilators.The test of heterogeneity isχ2=2.82, P=0.09,I2=64.5% and the articles are of homogeneity. WMD (fixed effect model) is -0.63% CI is (-0.92 to -0.34); the test for overall effect is Z=4.28, P<0.00001. The Borg scale of treatment group is significantly lower than that of control group.3. Meta-analysis of IC after exercise tests and the change of IC before and after exercise tests in the stable COPD patients inhaling bronchodilators.IC:The test of heterogeneity isχ2=24.71, P<0.01,I2=96% and the articles are of heterogeneity. WMD (random effect model) is 0.22; 95% CI is (0.06 to 0.39); the test for overall effect is Z=2.61, P=0.009. The IC of treatment group is significantly higher than that of control group. Change of IC before and after exercise tests:The test of heterogeneity isχ2= 14.42, P< 0.01,I2=93.1% and the articles are of heterogeneity. WMD (random effect model) is 0.01; 95% CI is (-0.15 to 0.16); the test for overall effect is Z=0.07, P=0.95. The difference between treatment group and control group in the change of IC before and after exercise tests is not statistically significant.CONCLUSIONSIC and FEV1 both increased significantly and the extents are close in static condition of stable COPD patients after inhaling bronchodilators. After the exercise test, IC of treatment group increased significantly compared with that of control group. The Borg scale decreased. However, the change of IC during the exercise test was not of significant difference. The measurement of IC is simple and well repeatable. At rest, both IC and FEV1 can reflect the improvement of pulmonary function of COPD patients after inhaling bronchodilators. During exercise, IC is of good sensitivity to check the change of airflow obstruction and agrees on dypnea of the patients. So IC can make up the limitation of FEV1 and plays an important role in the pulmonary function test.