Secretory leukocyte proteinase inhibitor, alpha-1-antitrypsin deficiency and emphysema: Preliminary study, speculation and an hypothesis

Objectives: This study investigated (i) whether adequate concentrations of secretory leukocyte proteinase inhibitor (SLPI) in the lungs of alpha-1-antitrypsin (AlAT) deficient patients can explain the variability in the development of emphysema in these individuals, and (ii) whether cigarette smoking jeopardises the protective screen provided by functional SLPI. Methodology: Four subjects [two normal proteinase inhibitor M (PiM), two abnormal PiZ] were selected from patients presenting for diagnostic bronchoscopy and lung function testing (spirometry, DLCO). Each subject underwent BAL and had blood taken for MAT and SLPI estimation. Results: As expected serum and BAL MAT concentrations were within the normal range in the normal PiM subjects. In normal subjects, SLPI concentrations in serum and BAL were within the normal range. AlAT-deficient subjects had reduced serum and BAL levels of AlAT reflecting their genetic disorder but showed increased concentrations of SLPI in BAL and serum. Percentage neutrophil elastase (NE) inhibitory capacity of BAL fluid was low in both AlAT-deficient subjects and a cigarette-smoking normal subject. In contrast, the NE inhibitory capacity for the normal subject who had never smoked was normal. Conclusions: These findings suggest that in AlAT deficiency there may be a compensatory increase in SLPI. This may protect the lung against the development of emphysema in AlAT-deficient individuals. Cigarette smokers may have a lower SLPI concentration than non-smokers. This provides an explanation for at least some of the observed variation in the development of emphysema in AlAT deficient subjects.