Importance: Despite receiving Global Initiative for Asthma (GINA) guideline-directed care of asthma,there are partly asthmatic exacerbated.Early studies suggested that two anti-asthma herbal formulae(A and B) could prevent asthmatic exacerbation by improving the depression symptoms and normalizing the HPA axis disturbances of asthmatics,it also has anti-inflammatory and immunomodulatory effects but it does require further validation through testing large sample,multicenter,randomized double-blind evidence-based clinical studies.Objective: To investigate the efficacy and mechanisms of the two anti-asthma formulae for prevention of exacerbations in mild-to-moderate asthmatic patients.Design,Setting,and Patients: This was a 12-month,randomized double-blind placebo-controlled parallel-group multi-centre study.328 eligible patients enrolled from five trial sites cities in mainland China were randomly sent to formula A(109),formula B(112) and placebo(107) group.Interventions: Formula A,formula B and placebo group were received as add-on therapy to their current maintenance treatment from baseline to month 6 and followed up 6 additional months without add-on therapy.Main Outcome and Measure: Time to next exacerbation,Hamilton Rating Scale for Depression (HAM-D) score,Asthma Control Test (ACT) score,HPA axis function,inflammatory cytokines and the safety of the drugs were measured before and after treatment.Results:Time to next exacerbation (the rate of exacerbation) was not significantly reduced from baseline after 6 months treatment,however,the conditions of the subgroup patients with HAM-D score>5 were improved in formula B (P=0.0265).HPA axis function was also significantly improved in formula both A and B group as shown by increased basal CRH (P <0.05) and CORT (P<0.05),in addition,ACTH was increased in formula A group (P <0.05) too.Th2 cytokines IL-4,5,13 were reduced in both formula A (P<0.05) and formula B (P<0.05) group,Th1 cytokine,IL-2,was increased in the formula B group (P<0.05) and IFN-γ levels was increased in both two formulae while both of two cytokines (IL-2 and IFN-γ) reduced in placebo group (P =0.06).TNF-α were suppressed in both two treatment group (P<0.05).The incidences of adverse events were similar among groups,no serious adverse events occurred.