Pilot application of lipoxin A4 analog and lipoxin A4 receptor agonist in asthmatic children with acute episodes.

Abstract

Previous studies have demonstrated that lipoxin A4 (LXA4) analogs blocked both airway hyper-responsiveness and pulmonary inflammation in a murine model of asthma. The present pilot study investigated the initial efficacy and safety of inhaled 5(S),6(R)-LXA4 methyl ester and BML-111, a LXA4 agonist, in the treatment of asthmatic children with acute episodes. A total of 50 asthmatic children diagnosed with acute moderate asthma were randomly assigned into groups and subjected to an inhalation challenge with pulmicort (n=10), ventolin (n=10), 5(S),6(R)-LXA4 methyl ester (n=10), BML-111 (n=10) or normal saline as a placebo (n=10). Pulmonary function was assessed prior to and following the challenge. Acute toxicity and safety of the inhaled 5(S),6(R)-LXA4 methyl ester and BML-111 in normal BALB/c mice were investigated prior to the current pilot study conducted in patients. Following the inhalation challenge, pulmonary function parameters in all groups with the exception of the normal saline-treated group indicated an improvement. The efficacies of 5(S),6(R)-LXA4 methyl ester and BML-111 were superior to the efficacy of pulmicort but reduced when compared to the efficacy of ventolin with regard to the improvement of pulmonary function following the inhalation challenge. No clinical adverse events were observed in the enrolled patients. All safety parameters in the full blood counts, routine urine and feces examination, electrocardiogram and liver and kidney function tests at baseline and the end of the current study were within normal limits for all patients. No significant differences in kidney or liver function tests were observed in mice treated with 5(S),6(R)-LXA4 methyl ester and BML-111. Light and electron microscopy demonstrated no airway epithelium or alveolar epithelial cell damage in the treated mice. The present preliminary study of a small sample demonstrates the initial efficacy and safety of inhaled 5(S),6(R)-LXA4 methyl ester and BML-111 in the treatment of asthmatic children with acute moderate episodes, and suggests that an inhaled LXA4 analog and LXA4 receptor agonist may exhibit potential as a novel therapeutic strategy for asthma.

• Authors: Xia Kong, Sheng-Hua Wu, Li Zhang, Xiao-Qing Chen
• Journal: Experimental and therapeutic medicine (Exp Ther Med) Vol. 14 Issue 3 Pg. 2284-2290 (Sep 2017) ISSN: 1792-0981 [Print] Greece
• PMID: 28962156 (Publication Type: Journal Article)