title: Secretory leukocyte proteinase inhibitor, alpha-1-antitrypsin deficiency and emphysema: Preliminary study, speculation and an hypothesis.
abstract: OBJECTIVE
  This study investigated (i) whether adequate concentrations of secretory leukocyte proteinase inhibitor (SLPI) in the lungs of alpha-1-antitrypsin (A1AT) 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.
  
  
  METHODS
  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 A1AT and SLPI estimation.
  
  
  RESULTS
  As expected serum and BAL A1AT 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. A1AT-deficient subjects had reduced serum and BAL levels of A1AT 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 A1AT-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 A1AT deficiency there may be a compensatory increase in SLPI. This may protect the lung against the development of emphysema in A1AT-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 A1AT deficient subjects.
authors.affiliation: Department of Respiratory Medicine, St. Vincent's Hospital, Fitzroy, Victoria, Australia.
authors.forename: Monna S
authors.initials: MS
authors.lastname: Ayad
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Knight
authors.forename: Jonathan G W
authors.initials: JG
authors.lastname: Burdon
authors.forename: Sue
authors.initials: S
authors.lastname: Brenton
mesh_terms: D000368:Aged; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D004646:Emphysema / Q000097:blood* / Q000209:etiology / Q000473:pathology; D005260:Female; D006801:Humans; D019272:Leukocyte Elastase; D008297:Male; D008565:Membrane Proteins / Q000032:analysis; D008875:Middle Aged; D010641:Phenotype; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins / Q000032:analysis*; D012016:Reference Values; D012129:Respiratory Function Tests; D053481:Secretory Leukocyte Peptidase Inhibitor; D012907:Smoking / Q000009:adverse effects / Q000097:blood*; D000515:alpha 1-Antitrypsin / Q000032:analysis; D019896:alpha 1-Antitrypsin Deficiency / Q000097:blood* / Q000150:complications / Q000235:genetics
chemical_list: D008565:Membrane Proteins; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins; C506814:SLPI protein, human; D053481:Secretory Leukocyte Peptidase Inhibitor; D000515:alpha 1-Antitrypsin; D019272:Leukocyte Elastase