| BackgroundPost infectious cough has high incidence, and it is the common cause of sub-acute cough. Frequent medical visits and treatments have serious impact on quality of life and also increase the economic burden of patients. For some patients cough is not relieved and they could even develop chronic bronchitis or bronchial asthma. Western treatments for this disease, which mainly limit to symptomatic treatment, are not proved effective for all cases. Also, these treatments are often accompanied by side effects and relapses after patients stop taking medication. The frequently used TCM syndrome differentiation treatment for post infectious cough is to relieve superficies for dispelling exogenous pathogen or strengthen healthy qi to eliminate pathogens. This TCM treatment has been reported to have good clinical effictiveness, low recurrence rate and few side effects. But in existing research, the diagnosis of post infectious cough is not clearly defined, the evaluation criteria of curative effect is too simple, and the quality of research needs to be improved.ObjectivesTo evaluate the the efficacy and safety of TCM treatment for post infectious cough including wind-cold persist lung and wind-heat stagnate lung, then to form effective, safe and reliable TCM treatment regime of post infectious cough.MethodsStudy Design:A multicenter, randomized, double-blind, placebo controlled clinical trial was designed for the patients who met the inclusion criteria for post infectious cough. The sample size has been decided in this superiority trail by using cough score as main index effectiveness. (268 patients in both groups with the ratio of 1:1). The syndrome (wind-cold persist lung and wind-heat stagnate lung 2:1) and center (5) were defined as the central randomization stratification factors.Interventions:The trial group (wind-cold persist lung and wind-heat stagnate lung) received oral granules of differentiation Chinese medicine formula. The control group received corresponding placebo treatment. The medication was given by one dose twice a day (morning and evening) after meal. The course of treatment was continued for 10 days with one week post-treament follow-up.Observations:Baseline data (sex, age, disease duration, body temperature, respiratory rate, allergies history, medical history, medication for this cough, etc.); daily cough score (day, night and total) and numeric rating scale before and during treatment, and follow-up; syndrome score before, in the middle of and after treatment, and after follow-up; cough relief time; cough relapse frequency; the safety index (blood routine, urine routine, stool routine and occult blood, liver function, kidney function, EKG) before and after treatment, adverse events, drug records and their relationship; drop off and compliance (drug count). Patients of the two centers, Guangdong Provincial Hospital of TCM and Guangzhou Institute of Respiratory Diseases, were performed capsaicin cough sensitivity test.Efficacy, safety and compliance assessment:?ough score (day, night and total), numeric rating scale, syndrome score after treatment and follow-up, cough relief and time of remission beginning, cough recurrence and relapse frequency, cough sensitivity, comprehensive theraputic effect;?the occurrence of adverse events;?drop off rate and the medication situation.Statistical analysis:Data were analyzed with SPSS 17.0, including the ITT analysis, PP analysis. Baseline, efficacy, safety and compliance were analyzed, and syndrome stratified analysis was employed. Significance level was a=0.05, two-sided test.ResultsThis study included 280 patients of post infectious cough, among them, 185 was wind-cold persist lung and 95 wind-heat stagnate lung. The trial group had 143 patients, in which 15 cases dropped off but no case was excluded; the control group had 137 patients in which 3 cases was excluded,8 cases dropped off. The gender, age, disease duration, body temperature, respiratory rate, allergies, medical history, medication for this cough, cough score (day, night and total), numeric rating scale, syndrome score before treatment between two groups showed no statistical significance (P>0.05).1. The overall analysis:?Both the trial group and the control group indicate decline trend in cough score (day, nitht and total) and numeric rating scale. Total and day cough score after treatment and follow-up, night cough score and numeric rating scale after follow-up of the trial group were lower than that of the control group(P <0.05).?The trial group showed a downward trend in syndrome score, and the syndrome score after treatment and follow-up in the trial group were lower than the control group (P<0.01).?The cough remission rate of the trial group was higher than that of the control group (92.2%vs 75.4%, P<0.01). It took shorter period for coughing started to relieve than that of the control group (7.2 days vs 8.4 days, P <0.05); the recurrence rate (15.3% vs 22.1%) and recurrence times (1.4 vs 1.2) of the trial group were also lower than that of the control group, but not statistically significant (P>0.05).?Comprehensive theraputic effect of the trial group was better than that of the control group (cure rate 41.4% vs 29.4%, total effective rate 92.2% vs 75.4%, P<0.05).?The data of two centers of Guangzhou showed that differences of cough sensitivity lgC5 before and after treatment between the two groups were not statistically significant (P>0.05). After treatment, the cough sensitivity of two groups decreased compared to that of before treatment.?There were mild adverse events occurred to both groups of patients, the incidence difference was not statistically significant(13.4% vs 15.4%, P> 0.05), and the medication causality is questionable and impossible. Drop off rate difference was not statistically significant (10.5% vs 6.0%).?ITT and PP analysis showed the elementarily same results.2. Stratification (syndrome) analysis?Wind-cold persist lung:Total cough score and syndrome score after treatment and follow-up, day and night cough score and numeric rating scale after follow-up of the trial group were lower than that of the control group (P <0.05). The cough remission rate of the trial group was higher than that of the control group (92.9% vs 73.8%, P<0.01). It took shorter period for coughing started to relieve than that of the control group (7.4 days vs 8.3 days), but the recurrence rate (11.4% vs 22.6%) and recurrence times(1.7 vs 1.3) had no significant difference (P>0.05). Comprehensive theraputic effect of the trial group was better than that of the control group (cure rate 44.7% vs 28.6%, total effective rate 92.9% vs 73.8%, P<0.05).?ind-heat persist lung:Cough score (day, night and total), numeric rating scale, syndrome score in each time point were lower than that of the control group (P<0.05). The cough remission rate of the trial group was higher than that of the control group (90.7% vs 78.6%). It took shorter period for coughing started to relieve than that of the control group (6.9 days vs 8.5 days), but the recurrence rate(23.1% vs 21.2%) and recurrence times(1.2 vs 1.0) were slightly higherthan that of the control group. Comprehensive theraputic effect was better than that of the control group (cure rate 34.9% vs 31.0%, total effective rate 90.7% vs 78.6%), but not statistically significant (P>0.05).Conclusion1. The TCM syndrome differentiation treatment "expelling wind to eliminate pathogens and facilitating lung to stop coughing" of post infectious cough has good effect. It can alleviate the cough, throat itching and other symptoms in patients, shorten cough relief time. It is safe, has low recurrent rate, and is easy to be accepted.2. The cold-wind formula can relieve cough, throat itching and other symptoms in patients with post infectious cough of wind-cold persist lung, reduce cough severity, and has higher remission rate. It has positive trend of lowering recurrence and shortening cough relief time.3. This study can't prove advantages of wind-heat formula on relieving cough, throat itching and other symptoms, and lowering recurrence in patients with post infectious cough of wind-heat persist lung. But compared with placebo, a certain tendency to be confirmed by further studies.4.This study doesn't show the impact that the TCM syndrome differentiation treatment has on patients of post infectious cough, due to lack of sufficient sample size. The impact needs to be overserved and studyed through larger sample size collected from more than two centers in Guangzhou.5.Though there exists a self-healing tendency in post infectious cough patients, the TCM syndrom differentiation treatment is highly recommended for its obvious advantadges in alleviating coughing and shortening the duration of disease. Otherwise, the delayed duration could affect patients life adversely. |
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