Hyaluronic acid : perspectives in lung diseases

Hyaluronic acid (HA) is a non-sulphated glycosaminoglycan. It is a natural polymer characterised by a coiled linear chain in particularly well-hydrated configuration composed of repeating disaccaride units. In mammals, its molecular weight can be extremely wide, ranging from 20 to 4,000 kDa. High molecular mass forms are provided with anti-inflammatory properties. A unique characteristic of HA is hydration (up to 6,000 molecules water/molecule of HA) with a major role in the regulation of fluid balance in the interstitium, a fundamental activity on the amorphous colloidal matrix gluing connective cell and fibers, and many other biological functions including lubrication, solute transport and microcirculatory exchange. HA has been widely used in the treatment of eye, ear, joint and skin disorders; in the last 15 years HA has been also proposed successfully in the treatment of a number of lung diseases in vitro, experimental animals and humans. In particular, inhaled HA at relatively high molecular weight has been proven to prevent bronchoconstiction induced in asthmatics by direct and indirect challenges such as inhalation of methacholine, inhalation of ultrasonically nebulised distilled water, muscular exercise. More recently, in patients affected by chronic obstructive pulmonary diseases, we have demonstrated that repeated administrations of inhaled HA (daily, for 8 weeks) induce significant increase in bronchial patency as well as progressive lung deflation with decrease of residual volume. In conclusion there are elements that can let us state that is perhaps time to change the focus to connective tissue and extracellular matrix substances such as HA, in order to prevent and treat chronic lung diseases.