Comparison of alpha-1-antitrypsin levels and antineutrophil elastase capacity of blood and lung in a patient with the alpha-1-antitrypsin phenotype null-null before and during alpha-1-antitrypsin augmentation therapy

M. D. Wewers, M. A. Casolaro, Ronald Crystal

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Abstract

The null-null phenotype of α1-antitrypsin (α1AT), a phenotype characterized by no detectable α1AT in serum, presents a rare opportunity to examine the contribution of α1AT to the antineutrophil elastase protection of the lower respiratory tract. The subject, a 35-yr-old lifetime non-smoker with moderate emphysema, has been characterized as having α1AT serum levels of zero resulting from the homozygous inheritance of α1AT genes that do not express detectable α1AT mRNA transcripts. Evaluation of the antineutrophil elastase capacity of the null-null serum showed it was < 5% of normal, whereas that of the epithelial lining fluid (ELF) of the lower respiratory tract was 13% of normal. However, after 60 mg/kg of intravenously administered α1AT augmentation therapy once weekly for 4 wk, the serum α1AT levels peaked at > 300 mg/dl, trough levels just prior to the next infusion were 81 ± 2 mg/dl, and the average serum level integrated for the month of infusions was 138 mg/dl. Consistent with this serum rise in α1AT, the serum antineutrophil elastase capacity increased in parallel (r = 0.98). Importantly, evaluation of the ELF 2 and 6 days after infusion demonstrated increases of α1AT levels (range, 1.4 to 2.1 μM) and antineutrophil elastase capacity (range, 1.6 to 2.5 μM), values within the lower range of normal. Furthermore, the lung ELF α1AT levels rose in direct proportion to the serum α1AT levels, and the ELF antineutrophil elastase capacity rose in direct proportion to the ELF α1AT levels. Taken together, these findings demonstrate that α1AT provides > 85% of the antineutrophil elastase protection for the lower respiratory tract and that this protection can be modulated by the blood levels of α1AT.

Original languageEnglish
Pages (from-to)539-543
Number of pages5
JournalAmerican Review of Respiratory Disease
Volume135
Issue number3
Publication statusPublished - 1 Jan 1987
Externally publishedYes

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Lung Volume Measurements
alpha 1-Antitrypsin
Pancreatic Elastase
Phenotype
Serum
Respiratory System
Therapeutics
Emphysema
Reference Values
Lung
Messenger RNA

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

@article{ced39530cd5c4ac8beb40fe75c7099c8,
title = "Comparison of alpha-1-antitrypsin levels and antineutrophil elastase capacity of blood and lung in a patient with the alpha-1-antitrypsin phenotype null-null before and during alpha-1-antitrypsin augmentation therapy",
abstract = "The null-null phenotype of α1-antitrypsin (α1AT), a phenotype characterized by no detectable α1AT in serum, presents a rare opportunity to examine the contribution of α1AT to the antineutrophil elastase protection of the lower respiratory tract. The subject, a 35-yr-old lifetime non-smoker with moderate emphysema, has been characterized as having α1AT serum levels of zero resulting from the homozygous inheritance of α1AT genes that do not express detectable α1AT mRNA transcripts. Evaluation of the antineutrophil elastase capacity of the null-null serum showed it was < 5{\%} of normal, whereas that of the epithelial lining fluid (ELF) of the lower respiratory tract was 13{\%} of normal. However, after 60 mg/kg of intravenously administered α1AT augmentation therapy once weekly for 4 wk, the serum α1AT levels peaked at > 300 mg/dl, trough levels just prior to the next infusion were 81 ± 2 mg/dl, and the average serum level integrated for the month of infusions was 138 mg/dl. Consistent with this serum rise in α1AT, the serum antineutrophil elastase capacity increased in parallel (r = 0.98). Importantly, evaluation of the ELF 2 and 6 days after infusion demonstrated increases of α1AT levels (range, 1.4 to 2.1 μM) and antineutrophil elastase capacity (range, 1.6 to 2.5 μM), values within the lower range of normal. Furthermore, the lung ELF α1AT levels rose in direct proportion to the serum α1AT levels, and the ELF antineutrophil elastase capacity rose in direct proportion to the ELF α1AT levels. Taken together, these findings demonstrate that α1AT provides > 85{\%} of the antineutrophil elastase protection for the lower respiratory tract and that this protection can be modulated by the blood levels of α1AT.",
author = "Wewers, {M. D.} and Casolaro, {M. A.} and Ronald Crystal",
year = "1987",
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T1 - Comparison of alpha-1-antitrypsin levels and antineutrophil elastase capacity of blood and lung in a patient with the alpha-1-antitrypsin phenotype null-null before and during alpha-1-antitrypsin augmentation therapy

AU - Wewers, M. D.

AU - Casolaro, M. A.

AU - Crystal, Ronald

PY - 1987/1/1

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N2 - The null-null phenotype of α1-antitrypsin (α1AT), a phenotype characterized by no detectable α1AT in serum, presents a rare opportunity to examine the contribution of α1AT to the antineutrophil elastase protection of the lower respiratory tract. The subject, a 35-yr-old lifetime non-smoker with moderate emphysema, has been characterized as having α1AT serum levels of zero resulting from the homozygous inheritance of α1AT genes that do not express detectable α1AT mRNA transcripts. Evaluation of the antineutrophil elastase capacity of the null-null serum showed it was < 5% of normal, whereas that of the epithelial lining fluid (ELF) of the lower respiratory tract was 13% of normal. However, after 60 mg/kg of intravenously administered α1AT augmentation therapy once weekly for 4 wk, the serum α1AT levels peaked at > 300 mg/dl, trough levels just prior to the next infusion were 81 ± 2 mg/dl, and the average serum level integrated for the month of infusions was 138 mg/dl. Consistent with this serum rise in α1AT, the serum antineutrophil elastase capacity increased in parallel (r = 0.98). Importantly, evaluation of the ELF 2 and 6 days after infusion demonstrated increases of α1AT levels (range, 1.4 to 2.1 μM) and antineutrophil elastase capacity (range, 1.6 to 2.5 μM), values within the lower range of normal. Furthermore, the lung ELF α1AT levels rose in direct proportion to the serum α1AT levels, and the ELF antineutrophil elastase capacity rose in direct proportion to the ELF α1AT levels. Taken together, these findings demonstrate that α1AT provides > 85% of the antineutrophil elastase protection for the lower respiratory tract and that this protection can be modulated by the blood levels of α1AT.

AB - The null-null phenotype of α1-antitrypsin (α1AT), a phenotype characterized by no detectable α1AT in serum, presents a rare opportunity to examine the contribution of α1AT to the antineutrophil elastase protection of the lower respiratory tract. The subject, a 35-yr-old lifetime non-smoker with moderate emphysema, has been characterized as having α1AT serum levels of zero resulting from the homozygous inheritance of α1AT genes that do not express detectable α1AT mRNA transcripts. Evaluation of the antineutrophil elastase capacity of the null-null serum showed it was < 5% of normal, whereas that of the epithelial lining fluid (ELF) of the lower respiratory tract was 13% of normal. However, after 60 mg/kg of intravenously administered α1AT augmentation therapy once weekly for 4 wk, the serum α1AT levels peaked at > 300 mg/dl, trough levels just prior to the next infusion were 81 ± 2 mg/dl, and the average serum level integrated for the month of infusions was 138 mg/dl. Consistent with this serum rise in α1AT, the serum antineutrophil elastase capacity increased in parallel (r = 0.98). Importantly, evaluation of the ELF 2 and 6 days after infusion demonstrated increases of α1AT levels (range, 1.4 to 2.1 μM) and antineutrophil elastase capacity (range, 1.6 to 2.5 μM), values within the lower range of normal. Furthermore, the lung ELF α1AT levels rose in direct proportion to the serum α1AT levels, and the ELF antineutrophil elastase capacity rose in direct proportion to the ELF α1AT levels. Taken together, these findings demonstrate that α1AT provides > 85% of the antineutrophil elastase protection for the lower respiratory tract and that this protection can be modulated by the blood levels of α1AT.

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