Inhalations of ultra-low doses of alkylating drugs in the treatment of asthma

Abstract

The treatment of severe steroid-dependent asthma is a very serious problem. Our aim was to work out a new method of asthma treatment with inhalations of ultra-low (non-cytotoxic) doses of an alkylating drug (Melphalan) and to investigate its efficacy and tolerability.
Forty-two patients with moderate and severe asthma, enrolled into a randomized, double-blind, placebo-controlled trial, were divided into two groups: 21 patients from the Melphalan-treated group (MTG) were treated with the standard therapy plus 5 daily inhalations of 0.1 mg of Melphalan, while the control group (CG) patients (21 persons) were treated with the standard therapy plus placebo inhalations. Spirometric, biochemical, hematological and immunological data were obtained before and 10 days after the treatment. Fiberoptic bronchoscopy with further investigation of bronchial mucosa biopsies was performed in 33 of 42 patients. There were no adverse events during the study. No patient dropped out of this study. An exertion tolerance increased and exacerbation severity and frequency of p2-agonist inhalations markedly reduced in MTG. A positive dynamics of lung ventilation parameters (p<0.05) and of the exertion tolerance was revealed in MTG, while changes in the CG were unreliable. In 60% of MTG patients histo-ultrastructural signs of bronchial epithelium regeneration were revealed.
In conclusion, our data suggest that combined therapy with inhalation of ultra-low doses of Melphalan is a safe and effective method of asthma treatment and needs further investigations.