Therapeutic effects of BCG vaccination in adult asthmatic patients: a randomized, controlled trial.

BACKGROUND: Bacille Calmette-Guérin (BCG) vaccination in humans induces Th1 immune responses. Th1 and Th2 cells are reciprocally regulated. Objective: To examine whether BCG vaccination of adult patients with asthma, a Th2-associated allergic disease, is clinically effective. METHODS: Forty-three moderate-to-severe asthma patients were randomly assigned into groups that received percutaneous injection of 58.2 x 10(7) CFUs BCG (n = 22) or placebo (n = 21) in a double-blinded fashion, on the first day of a 12-week treatment period. Medications were adjusted every 4 weeks to maintain optimal asthma control. Spirometric measurements were performed before treatment and at weeks 4, 8, and 12 after vaccination. The daily peak expiratory flow rate values, asthma symptoms, and medications were also recorded. Tuberculin skin tests, and sputum inflammatory cell and cytokine analyses were carried out before treatment and 12 weeks after vaccination. RESULTS: BCG vaccination significantly increased forced expiratory volume in 1 second and forced expiratory flow rate 25% to 75% at weeks 4, 8, and 12. Morning peak expiratory flow rate was significantly increased only during the first 4 weeks. Although the asthma symptom scores were not significantly changed, the weekly medication scores were significantly decreased. Tuberculin skin reactivities were significantly increased without significant alterations in induced sputum profiles. In contrast, medication scores and sputum eosinophils were significantly increased, and the interferon-gamma:interleukin-4 ratio in sputum was significantly decreased in the placebo group. CONCLUSIONS: BCG vaccination improved lung function and reduced medication use in adults with moderate-to-severe asthma. This amelioration was accompanied by a suppressed Th2-type immune response, suggesting that BCG vaccination might be an effective therapeutic modality against asthma.