Aerosolized hyaluronic acid prevents exercise-induced bronchoconstriction, suggesting novel hypotheses on the correction of matrix defects in asthma

Hyaluronic acid (HA), a biopolymer, member of the family of the glycosaminoglicanes (GAGs) is one of the major natural components of the connective amorphous matrix. The lungs, together with skin and intestine, contain >50% of HA of the body: it provides to several biologic functions and presents the unique capacity to link and retain a particularly relevant number of water molecules. Since other GAGs have been proven to be provided with anti-asthmatic properties and HA has been employed with positive results by intra-tracheal instillation in experimental models of lung emphysema and COPD, we have explored the efficacy of the pre-administered aerosol of HA (compared to placebo) in preventing in asthmatic patients the bronchoconstriction induced by a challenge test such as that obtained with muscular exercise. In a randomised, cross-over, single-blind study design, saline as placebo (P) or HA have been administered by aerosol, in two non-consecutive days, 30 min prior to the beginning of the challenge (10 min free running), to 14 patients (13-36 years old; 7 teenagers, 7 young adults; 11 males, 3 females; 12 allergic, 2 non-allergic), all suffering from mild bronchial asthma. The bronchoconstrictive effect induced by the muscular exercise has been relevant and statistically significant. With the P pre-treatment, the average FEV1 measured 5 min after the end of exercise was reduced by 36.14% from the baseline FEV1. Pre-treatment with HA determined a partial but clear-cut protection of the FEV1 impairment due to the challenge: the average post-challenge FEV1 resulted to be 12.43% less than the pre-challenge baseline value. No significant difference was observed in the level of HA protection in the subgroup of teenagers when compared to that of young adults. The protection induced by HA, when compared with P, resulted particularly significant by the statistical point of view (p<0.0001). We conclude that aerosol HA administration significantly reduces the bronchial hyper-reactivity to muscular exercise in asthmatics. Such effect could be attributed to the correction of the pathological remodelling, one of the main features of asthma: a correction which could be attributed to the unique physicochemical properties of this major component of the loose connective amorphous matrix of the airways, which is undoubtedly involved in the remodelling process.