PULMONARY DEPOSITION AND DISAPPEARANCE OF AEROSOLIZED SECRETORY LEUKOCYTE PROTEASE INHIBITOR

Background - The neutrophil elastase inhibitor, secretory leucocyte pr otease inhibitor (SLPI), is a potential therapeutic tool in inflammato ry lung diseases such as cystic fibrosis and pulmonary emphysema. The distribution and disappearance in the lung of aerosolised recombinant SLPI (rSLPI) was investigated in healthy humans and in patients with c ystic fibrosis or alpha(1)-antitrypsin-associated emphysema. Methods - To distinguish aerosalised rSLPI from endogenous SLPI the recombinant inhibitor was radiolabelled with 99m-technetium (Tc-99m) pertechnetat e. Distribution and disappearance of aerosolised Tc-99m-rSLPI in the l ungs were studied by gamma radiation imaging. Results - The deposition of Tc-99m-rSLPI in normal volunteers was homogeneous in all lung lobe s, while in patients with cystic fibrosis or emphysema only well venti lated areas showed deposition of the aerosol. The disappearance rate o f Tc-99m-rSLPI was biexponential. The half life of the rapid phase was 0.2-2.8 hours, while that of the slow phase was more than 24 hours. C onclusions - Future aerosol therapy with rSLPI will be most beneficial for well ventilated lung tissue that needs protection against neutrop hil derived elastase. It may be more difficult to neutralise the burde n of elastase in poorly ventilated, highly inflamed areas as are seen in cystic fibrosis.