Pulmonary deposition and disappearance of aerosolised secretory leucocyte protease inhibitor.
BACKGROUND
The neutrophil elastase inhibitor, secretory leucocyte protease inhibitor (SLPI), is a potential therapeutic tool in inflammatory 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 cystic fibrosis or alpha 1-antitrypsin-associated emphysema.


METHODS
To distinguish aerosolised rSLPI from endogenous SLPI the recombinant inhibitor was radiolabelled with 99m-technetium (99mTc) pertechnetate. Distribution and disappearance of aerosolised 99mTc-rSLPI in the lungs were studied by gamma radiation imaging.


RESULTS
The deposition of 99mTc-rSLPI in normal volunteers was homogeneous in all lung lobes, while in patients with cystic fibrosis or emphysema only well ventilated areas showed deposition of the aerosol. The disappearance rate of 99mTc-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.


CONCLUSIONS
Future aerosol therapy with rSLPI will be most beneficial for well ventilated lung tissue that needs protection against neutrophil derived elastase. It may be more difficult to neutralise the burden of elastase in poorly ventilated, highly inflamed areas as are seen in cystic fibrosis.
Stolk
J
J
Department of Pulmonology, University Hospital, Leiden, The Netherlands.
Camps
J
J
Feitsma
H I
HI
Hermans
J
J
Dijkman
J H
JH
Pauwels
E K
EK
D000328:Adult; D000336:Aerosols; D000818:Animals; D006224:Cricetinae; D003550:Cystic Fibrosis / Q000000981:diagnostic imaging / Q000378:metabolism*; D006207:Half-Life; D006801:Humans; D008168:Lung / Q000000981:diagnostic imaging / Q000378:metabolism*; D008297:Male; D008647:Mesocricetus; D010641:Phenotype; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins; D011656:Pulmonary Emphysema / Q000000981:diagnostic imaging / Q000378:metabolism*; D011877:Radionuclide Imaging; D011994:Recombinant Proteins / Q000493:pharmacokinetics; D053481:Secretory Leukocyte Peptidase Inhibitor; D015842:Serine Proteinase Inhibitors / Q000493:pharmacokinetics*; D013670:Sodium Pertechnetate Tc 99m; D019896:alpha 1-Antitrypsin Deficiency
D000336:Aerosols; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins; D011994:Recombinant Proteins; C506814:SLPI protein, human; D053481:Secretory Leukocyte Peptidase Inhibitor; D015842:Serine Proteinase Inhibitors; D013670:Sodium Pertechnetate Tc 99m