Effect of fluticasone on the elastase:antielastase profile of the normal lung.
BACKGROUND
Excessive elastolytic activity contributes to the pathogenesis of several inflammatory respiratory diseases. The effect of glucocorticoids, which are potent anti-inflammatory agents, on the elastase:antielastase balance of the human respiratory tract is unclear, as studies on patients and in vitro have yielded inconsistent results.


METHODS
To clarify this, bronchoalveolar lavage and lavage fluids from the upper and central airways were collected from 10 healthy, nonsmoking volunteers before and after a 2-week course of inhaled fluticasone propionate (2 x 500 micrograms day-1). Concentrations of two neutrophil elastase inhibitors, alpha-1-proteinase inhibitor (PI) and secretory leukoproteinase inhibitor (SLPI), as well as neutrophil elastase (NE) activity and NE inhibitory capacity (NEIC) were quantified in all lavage fluids.


RESULTS
Concentrations of SLPI were highest in the proximal airways and decreased distally. Neutrophil elastase inhibitory capacity activity followed the same gradient and correlated positively and consistently with SLPI, suggesting that this inhibitor makes an important contribution to the regulation of elastolytic activity in the healthy human respiratory tract. Inhaled fluticasone propionate had no effect on any component of the elastase:antielastase balance at any level of the respiratory tract, even though circulating cortisol levels were reduced in all subjects, confirming subject compliance and adequate pulmonary delivery of the drug.


CONCLUSIONS
This lack of action in the respiratory tract may contribute to the ineffectiveness of inhaled glucocorticoids in respiratory conditions characterised by excessive elastolytic activity.
Kamal
A M
AM
Department of Respiratory Medicine, National Heart and Lung Institute, Faculty of Medicine, Imperial College, UK.
Corrigan
C J
CJ
Tetley
T D
TD
Alaghband-Zadeh
J
J
Smith
S F
SF
D000287:Administration, Topical; D000328:Adult; D000730:Androstadienes / Q000494:pharmacology*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D005260:Female; D000068298:Fluticasone; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D019272:Leukocyte Elastase / Q000032:analysis / Q000037:antagonists & inhibitors / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins / Q000032:analysis / Q000378:metabolism; D053481:Secretory Leukocyte Peptidase Inhibitor; D015842:Serine Proteinase Inhibitors / Q000032:analysis / Q000378:metabolism; D018709:Statistics, Nonparametric; D000515:alpha 1-Antitrypsin / Q000032:analysis
D000730:Androstadienes; D000893:Anti-Inflammatory Agents; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins; C506814:SLPI protein, human; D053481:Secretory Leukocyte Peptidase Inhibitor; D015842:Serine Proteinase Inhibitors; D000515:alpha 1-Antitrypsin; D000068298:Fluticasone; D019272:Leukocyte Elastase; D006854:Hydrocortisone