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Evidence for excessive bronchial inflammation during an acute exacerbation of chronic obstructive pulmonary disease in patients with alpha(1)-antitrypsin deficiency (PiZ).
- Source :
-
American journal of respiratory and critical care medicine [Am J Respir Crit Care Med] 1999 Dec; Vol. 160 (6), pp. 1968-75. - Publication Year :
- 1999
-
Abstract
- Patients with homozygous (PiZ) alpha(1)-antitrypsin (AAT) deficiency have not only low baseline serum AAT levels (approximately 10 to 15% normal) but also an attenuated acute phase response. They are susceptible to the development of premature emphysema but may also be particularly susceptible to lung damage during bacterial exacerbations when there will be a significant neutrophil influx. The purposes of the present study were to assess the inflammatory nature of acute bacterial exacerbations of chronic obstructive pulmonary disease (COPD) in subjects with AAT deficiency, to compare this with COPD patients without deficiency, and to monitor the inflammatory process and its resolution following appropriate antibacterial therapy. At the start of the exacerbation, patients with AAT deficiency had lower sputum AAT (p < 0.001) and secretory leukoprotease inhibitor (SLPI; p = 0.02) with higher elastase activity (p = 0.02) compared with COPD patients without deficiency. Both groups had a comparable acute phase response as assessed by C-reactive protein (CRP) but the AAT-deficient patients had a minimal rise in serum AAT (to < 6 microM). After treatment with antibiotics, in patients with AAT deficiency, there were significant changes in many sputum proteins including a rise in SLPI levels, and a reduction in myeloperoxidase (MPO) and elastase activity (p < 0. 005 for all measures); the sputum chemoattractants interleukin-8 (IL-8) and leukotriene B(4) (LTB(4)) fell (p < 0.01), and protein leak (sputum/serum albumin ratio) became lower (p < 0.01). The changes were rapid and within 3 d of the commencement of antibiotic therapy the biochemical markers had decreased significantly, but took a variable time thereafter to return to baseline values. In conclusion, patients with AAT deficiency had evidence of increased elastase activity at the start of the exacerbation when compared with nondeficient COPD patients which probably reflects a deficient antiproteinase screen (lower sputum AAT and SLPI). The increased bronchial inflammation at presentation resolved rapidly with 14 d of antibiotic therapy.
- Subjects :
- Acute Disease
Acute-Phase Reaction etiology
Aged
Bacterial Infections complications
Bacterial Infections drug therapy
C-Reactive Protein analysis
Female
Humans
Interleukin-8 analysis
Leukotriene B4 analysis
Lung Diseases, Obstructive complications
Lung Diseases, Obstructive drug therapy
Lung Diseases, Obstructive pathology
Male
Middle Aged
Pancreatic Elastase analysis
Peroxidase analysis
Phenotype
Proteinase Inhibitory Proteins, Secretory
Proteins analysis
Respiratory Tract Infections complications
Respiratory Tract Infections drug therapy
Secretory Leukocyte Peptidase Inhibitor
Serine Proteinase Inhibitors analysis
Serum Albumin analysis
Sputum chemistry
alpha 1-Antitrypsin analysis
alpha 1-Antitrypsin Deficiency genetics
alpha 1-Antitrypsin Deficiency metabolism
Bronchi pathology
Inflammation Mediators analysis
Lung Diseases, Obstructive metabolism
alpha 1-Antitrypsin Deficiency complications
Subjects
Details
- Language :
- English
- ISSN :
- 1073-449X
- Volume :
- 160
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- American journal of respiratory and critical care medicine
- Publication Type :
- Academic Journal
- Accession number :
- 10588615
- Full Text :
- https://doi.org/10.1164/ajrccm.160.6.9904097