title: Alpha-1 antitrypsin augmentation therapy and biomarkers of elastin degradation.
abstract: BACKGROUND
  Intravenous alpha-1 antitrypsin protein (AAT) augmentation is a prescribed therapy for severe, genetically determined, alpha-1 antitrypsin deficiency (AATD), a genetic basis for pulmonary emphysema. AAT, a predominant systemic inhibitor of neutrophil elastase thus far has not been shown to decrease elastin degradation in a significant number of patients on this therapy. The objective of this study was to compare levels of biomarkers of elastin degradation in plasma, bronchoalveolar lavage (BALF) fluid and urine before and after beginning AAT augmentation therapy in patients with AATD.
  
  
  METHODS
  Desmosine and isodesmosine (DI), which occur only in elastin, are amino acid cross-links in mature elastin. Levels of DI in body fluids measure degradation of elastin and can be measured more specifically by mass spectrometry. This method was used to measure DI levels in plasma, bronchoalveolar lavage fluid and urine in cohorts of severe AATD patients on augmentation, not on augmentation and before and after the initiation of augmentation therapy.
  
  
  RESULTS
  Statistically significant reductions in plasma DI and in BALF DI were demonstrated in AATD patients receiving intravenous (IV) augmentation therapy as compared with those not receiving it. Administration by aerosol also produced statistically significant reductions in levels of DI in BALF.
  
  
  CONCLUSIONS
  Results indicate that the currently prescribed doses of AAT augmentation inhibit neutrophil elastase adequately to reduce elastin degradation, both systemically and in the lung per se. The currently prescribed doses did not reduce elastin degradation to control levels, which may be possible with higher doses.
authors.affiliation: James P. Mara Center for Lung Disease, New York, NY, USA.
authors.forename: Shuren
authors.initials: S
authors.lastname: Ma
authors.forename: Yong Y
authors.initials: YY
authors.lastname: Lin
authors.forename: Jiangtao
authors.initials: J
authors.lastname: He
authors.forename: Farshid N
authors.initials: FN
authors.lastname: Rouhani
authors.forename: Mark
authors.initials: M
authors.lastname: Brantly
authors.forename: Gerard M
authors.initials: GM
authors.lastname: Turino
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid; D004549:Elastin / Q000378:metabolism*; D005260:Female; D006720:Homozygote; D006801:Humans; D007524:Isodesmosine / Q000097:blood / Q000378:metabolism* / Q000652:urine; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D014361:Trypsin Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D000515:alpha 1-Antitrypsin / Q000008:administration & dosage / Q000627:therapeutic use*; D019896:alpha 1-Antitrypsin Deficiency / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D014361:Trypsin Inhibitors; D000515:alpha 1-Antitrypsin; D004549:Elastin; D007524:Isodesmosine; D019272:Leukocyte Elastase