Clinical Evaluation Of Minghuang Decoction On CVA Patients And Assessment Of Antitussive, Anti-inflammatory And Immunomodulation Effects In Experimental Animal Model

Objective: The aim of this study is to evaluate the therapeutic effects of Minghuang decoction, a traditional Chinese medicine prescription developed in our hospital by senior traditional Chinese medicine physicians on cough variant asthma(CVA)patients selected according to the cough treatment guideline(2009) by Chinese Medical Association. Additional objectives include investigation of the antitussive, anti-inflammatory and immunomodulation effects of Minghuang decoction in mouse and guinea pig model. Methods: For the clinical evaluation, 82 outpatients who met the diagnosis criteria were randomly assigned into two groups. Classical treatment group(40 patients) received Salmeterol Xinafoate and Fluticasone Propionate powder(one dose, b.i.d.). Minghuang decoction group(42 patients) received Minghuang decoction(200 m L, qd). The treatment lasted for six weeks. Both group received compound Salbutamol Sulfate aerosol(one press, t.i.d.) until remission.General clinical score was evaluated daily during treatment according to the symptom, and the time point when the score significantly decreased was recorded as cough remission time. Time course changes of the general clinical score at 1, 4 and 6week treatment were evaluated. The clinical total effective rate after six week treatment was calculated(Sum of the number of clinical controlled, clinical markedly effective and clinical effective patients divided by the total number of treated patients).Spirometer was used to assess lung function before and after treatments. Electronic automatic blood cell counter was used to count the amount of eosinophil(EOS) in peripheral blood. Serum levels of Ig E, interleukin 13(IL-13) and interleukin 8(IL-8)were measured with enzyme-linked immunosorbent assay(ELISA). Hepatic and renal functions were assessed with enzymatic assays. Six months after the treatment, follow ups surveyed patients about cough remission time, recurrence rate and common cold incidences. For the animal study, cyclophosphamide(CTX) was used to reproduce immunodeficiency model in mouse; 17.5% citric acid solution was used to induce cough model in guinea pig, mouse right auricle inflammation model was reproduced by applying xylene solution. Experimental design: control group, model group(CTX, citric acid or xylene), Minghuang decoction high or low dose groups(24 or 12 g/kg, equavilent to 12 or 6 times of clinical dose,respectively), positive control group(Pidotimod 0.04 g/kg, codeine 0.03 g/kg, or dexamethasone 0.45 mg/kg). Treatments were administered via gavage for seven days(immunodeficiency or inflammatory mouse) or three days(cough guinea pig),respectively. For immunodeficiency mouse, phagocytic rate and index for chicken erythrocyte was calculated and serum hemolysin levels were assessed; for cough guniea pig, cough incubation period and cough time in five minutes were recorded;for auricle inflammation mouse, the auricle swollen degree and inhibition rate were calculated. Statistics were performed with SPSS 13.0. Results: The cough remission time of Minghuang decoction was approximately four day. The clinical general score improvement was time-dependent. The clinical total effective rate was 88.1%. Regarding to lung function, the ratio of forced expiratory volume in one second to forced vital capacity(FEV1%) and peak expiratory flow(PEF) significantly improved, while the counting of EOS, serum levels of Ig E, IL-13 and IL-8 remarkably decreased(P<0.05). No hepatic or renal toxicity were observed during treatment(P>0.05). Follow up after six months revealed that the average cough remission time was about 60 days, recurrence rate and common cold incidences significantly decreased in Minghuang decoction treated patients(P<0.05). Animal studies with Minghuang decoction revealed increased phagocytic rate, index and serum hemolysin level in immunodeficency mouse as well as decreased auricle swollen degree and increased swollen inhibition rate in auricle inflammation mouse(P<0.05). In cough guinea pigs, Minghunag decoction significantly prolonged cough incubation period and decreased cough number(P<0.01). Conclusions: Minghuang decoction is a reasonable prescription which could significantly improve the clinical symptom and lung function of CVA patients. The mechanism is associated with antitussive,anti-inflammatory(decrease the level of inflammatory factors) and immunopotentiation effects.