Sub-lingual administration of a polyvalent mechanical bacterial lysate (PMBL) in patients with moderate, severe, or very severe chronic obstructive pulmonary disease (COPD) according to the GOLD spirometric classification: A multicentre, double-blind, randomised, controlled, phase IV study (AIACE study: Advanced Immunological Approach in COPD Exacerbation).

Polyvalent mechanical bacterial lysates (PMBLs) have been shown to reduce the number of infectious episodes in patients with recurrent infections of the respiratory tract. Some previous investigations have also shown the effectiveness of PMBLs in reducing exacerbations of chronic obstructive pulmonary disease (COPD). The AIACE study, which was developed according to criteria of evidence-based medicine, evaluated whether the administration of PMBLs to COPD patients, in addition to the recommended treatment, was able to reduce the number of exacerbations by 25%. Two hundred eighty-eight patients with moderate to very severe COPD were recruited and randomly assigned to either placebo or PMBLs. The placebo or PMBLs were administered according to the standard scheme. The primary outcome of the study was not achieved. However, the number of days with fever (21 days per year versus 40.15; p < 0.001), the days of hospitalisation (65 days vs 162 days; p < 0.001), the interval between the first and second exacerbations (123.89 days vs 70.36; p = 0.03) and the number of days in poor health (109 days/year vs 171 days/year; p < 0.001) were significantly better in the PMBL group than in the placebo group. In conclusion, the results of this trials showed that Ismigen, in addition to guideline-suggested treatment, could not significantly reduce the number of exacerbations in the considered population; nevertheless, the secondary outcome results demonstrated potential benefits of this compound for relevant clinical outcomes.