Hyaluronidase: A Potential New Treatment for Acute Respiratory Distress Syndrome

Abstract

Acute respiratory distress syndrome, also known as diffuse alveolar damage, is an acute injury to the lungs. Patients experience severe shortness of breath and require mechanical ventilation. It is not a specific disease, but an acute lung dysfunction associated with a variety of disorders: pneumonia, shock, sepsis, and trauma. A similar lesion occurs in newborn infants, called hyaline disease of the newborn. It occurs in premature babies and has the same pathophysiological mechanism as acute respiratory distress syndrome. Hyaline membranes are a pathologic feature of acute respiratory distress syndrome, consisting of basophilic structures that coat alveolar surfaces. They prevent oxygen exchange and are the basis of the lethality of this disorder. The syndrome is associated with very high levels of hyaluronan in broncho-alveolar lavage specimens. We postulate that the hyaline membranes of acute respiratory distress syndrome are hyaluronan-rich structures associated with serum hyaluronan-binding proteins such as fibrinogen and fibrin. Potent infectious influenza viruses are recurrent pandemics and potential terrorist threats. Lethality of influenza infection correlates with the presence of hyaline membranes. Installation of hyaluronidase as an aerosol would provide a new treatment for acute respiratory respiratory distress syndrome, for which there has been no new treatment in 45 years. The pig is the only species other than humans that develop hyaline membranes. Employing this treatment in the porcine model would provide a direct test of the hypothesis.