help button home button
AJRCCM
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by DIRKSEN, A.
Right arrow Articles by STOLK, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by DIRKSEN, A.
Right arrow Articles by STOLK, J.

Am. J. Respir. Crit. Care Med., Volume 160, Number 5, November 1999, 1468-1472

A Randomized Clinical Trial of alpha 1-Antitrypsin Augmentation Therapy

ASGER DIRKSEN, JOOP H. DIJKMAN, FLEMMING MADSEN, BEREND STOEL, DUNCAN C. S. HUTCHISON, CHARLOTTE S. ULRIK, LENE T. SKOVGAARD, AXEL KOK-JENSEN, ARJAN RUDOLPHUS, NIELS SEERSHOLM, HENRI A. VROOMAN, JOHAN H. C. REIBER, NIELS C. HANSEN, THOMAS HECKSCHER, KAJ VISKUM, and JAN STOLK

Department of Respiratory Medicine, The Rigshospital, Copenhagen, Denmark; Departments of Pulmonology and Radiology, Leiden University Medical Center, Leiden, The Netherlands; Department of Respiratory Medicine, King's College Hospital, London, United Kingdom; Department of Biostatistics, The Panum Institute, Copenhagen, Denmark; and Department of Medicine C, Odense University Hospital, Odense, Denmark

We have investigated whether restoration of the balance between neutrophil elastase and its inhibitor, alpha 1-antitrypsin, can prevent the progression of pulmonary emphysema in patients with alpha 1-antitrypsin deficiency. Twenty-six Danish and 30 Dutch ex-smokers with alpha 1-antitrypsin deficiency of PI*ZZ phenotype and moderate emphysema (FEV1 between 30% and 80% of predicted) participated in a double-blind trial of alpha 1-antitrypsin augmentation therapy. The patients were randomized to either alpha 1-antitrypsin (250 mg/kg) or albumin (625 mg/kg) infusions at 4-wk intervals for at least 3 yr. Self-administered spirometry performed every morning and evening at home showed no significant difference in decline of FEV1 between treatment and placebo. Each year, the degree of emphysema was quantified by the 15th percentile point of the lung density histogram derived from computed tomography (CT). The loss of lung tissue measured by CT (mean ± SEM) was 2.6 ± 0.41 g/L/yr for placebo as compared with 1.5 ± 0.41 g/L/yr for alpha 1-antitrypsin infusion (p = 0.07). Power analysis showed that this protective effect would be significant in a similar trial with 130 patients. This is in contrast to calculations based on annual decline of FEV1 showing that 550 patients would be needed to show a 50% reduction of annual decline. We conclude that lung density measurements by CT may facilitate future randomized clinical trials of investigational drugs for a disease in which little progress in therapy has been made in the past 30 yr. Dirksen A, Dijkman JH, Madsen F, Stoel B, Hutchison DCS, Ulrik CS, Skovgaard LT, Kok-Jensen A, Rudolphus A, Seersholm N, Vrooman HA, Reiber JHC, Hansen NC, Heckscher T, Viskum K, Stolk J. A randomized clinical trial of alpha 1-antitrypsin augmentation therapy.




This article has been cited by other articles:


Home page
 ChestHome page
B. R. Celli
Update on the Management of COPD
Chest, June 1, 2008; 133(6): 1451 - 1462.
[Abstract] [Full Text] [PDF]

Home page
 Proc Am Thorac SocHome page
C. P. Hersh, D. L. DeMeo, and E. K. Silverman
National Emphysema Treatment Trial State of the Art: Genetics of Emphysema
Proceedings of the ATS, May 1, 2008; 5(4): 486 - 493.
[Abstract] [Full Text] [PDF]

Home page
 Eur Respir JHome page
M. Cazzola, W. MacNee, F. J. Martinez, K. F. Rabe, L. G. Franciosi, P. J. Barnes, V. Brusasco, P. S. Burge, P. M. A. Calverley, B. R. Celli, et al.
Outcomes for COPD pharmacological trials: from lung function to biomarkers
Eur. Respir. J., February 1, 2008; 31(2): 416 - 469.
[Abstract] [Full Text] [PDF]

Home page
 Therapeutic Advances in Respiratory DiseaseHome page
G. Tirado-Conde, B. Lara, and M. Miravitlles
Augmentation therapy for emphysema due to alpha-1-antitrypsin deficiency
Therapeutic Advances in Respiratory Disease, February 1, 2008; 2(1): 13 - 21.
[Abstract] [PDF]

Home page
 ChestHome page
R. Yuan, J. R. Mayo, J. C. Hogg, P. D. Pare, A. M. McWilliams, S. Lam, and H. O. Coxson
The Effects of Radiation Dose and CT Manufacturer on Measurements of Lung Densitometry
Chest, August 1, 2007; 132(2): 617 - 623.
[Abstract] [Full Text] [PDF]

Home page
 Eur Respir JHome page
H. O. Coxson
Computed tomography and monitoring of emphysema
Eur. Respir. J., June 1, 2007; 29(6): 1075 - 1077.
[Full Text] [PDF]

Home page
 Eur Respir JHome page
J. Stolk, M. I. M. Versteegh, L. J. Montenij, M. E. Bakker, E. Grebski, M. Tutic, S. Wildermuth, W. Weder, M. el Bardiji, J. H. C. Reiber, et al.
Densitometry for assessment of effect of lung volume reduction surgery for emphysema
Eur. Respir. J., June 1, 2007; 29(6): 1138 - 1143.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Roentgenol.Home page
B. M. Trotta, A. V. Stolin, M. B. Williams, S. B. Gay, A. S. Brody, and T. A. Altes
Characterization of the Relation Between CT Technical Parameters and Accuracy of Quantification of Lung Attenuation on Quantitative Chest CT
Am. J. Roentgenol., June 1, 2007; 188(6): 1683 - 1690.
[Abstract] [Full Text] [PDF]

Home page
 RadiologyHome page
A. Madani, V. De Maertelaer, J. Zanen, and P. A. Gevenois
Pulmonary Emphysema: Radiation Dose and Section Thickness at Multidetector CT Quantification--Comparison with Macroscopic and Microscopic Morphometry
Radiology, April 1, 2007; 243(1): 250 - 257.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Roentgenol.Home page
D. S. Gierada, T. K. Pilgram, B. R. Whiting, C. Hong, A. J. Bierhals, J. H. Kim, and K. T. Bae
Comparison of Standard- and Low-Radiation-Dose CT for Quantification of Emphysema
Am. J. Roentgenol., January 1, 2007; 188(1): 42 - 47.
[Abstract] [Full Text] [PDF]

Home page
 ThoraxHome page
D Soy, C de la Roza, B Lara, C Esquinas, A Torres, and M Miravitlles
Alpha-1-antitrypsin deficiency: optimal therapeutic regimen based on population pharmacokinetics
Thorax, December 1, 2006; 61(12): 1059 - 1064.
[Abstract] [Full Text] [PDF]

Home page
 Proc Am Thorac SocHome page
E. A. Hoffman, B. A. Simon, and G. McLennan
State of the Art. A Structural and Functional Assessment of the Lung via Multidetector-Row Computed Tomography: Phenotyping Chronic Obstructive Pulmonary Disease
Proceedings of the ATS, August 1, 2006; 3(6): 519 - 532.
[Abstract] [Full Text] [PDF]

Home page
 ThoraxHome page
D G Parr, B C Stoel, J Stolk, and R A Stockley
Validation of computed tomographic lung densitometry for monitoring emphysema in {alpha}1-antitrypsin deficiency
Thorax, June 1, 2006; 61(6): 485 - 490.
[Abstract] [Full Text] [PDF]

Home page
 RadiologyHome page
A. Madani, J. Zanen, V. de Maertelaer, and P. A. Gevenois
Pulmonary Emphysema: Objective Quantification at Multi-Detector Row CT--Comparison with Macroscopic and Microscopic Morphometry
Radiology, March 1, 2006; 238(3): 1036 - 1043.
[Abstract] [Full Text] [PDF]

Home page
 Proc Am Thorac SocHome page
B. R. Celli
Chronic Obstructive Pulmonary Disease: From Unjustified Nihilism to Evidence-based Optimism.
Proceedings of the ATS, January 1, 2006; 3(1): 58 - 65.
[Abstract] [Full Text] [PDF]

Home page
 Eur Respir JHome page
P. J. Barnes and R. A. Stockley
COPD: current therapeutic interventions and future approaches
Eur. Respir. J., June 1, 2005; 25(6): 1084 - 1106.
[Abstract] [Full Text] [PDF]

Home page
 ChestHome page
J. K. Stoller, J. Tomashefski Jr, R. G. Crystal, A. Arroliga, C. Strange, D. N. Killian, M. D. Schluchter, H. P. Wiedemann, and for the {alpha}1-Antitrypsin Deficiency Registry S
Mortality in Individuals With Severe Deficiency of {alpha}1-Antitrypsin: Findings From the National Heart, Lung, and Blood Institute Registry
Chest, April 1, 2005; 127(4): 1196 - 1204.
[Abstract] [Full Text] [PDF]

Home page
 ThoraxHome page
M Decramer, R Gosselink, M Rutten-Van Molken, J Buffels, O Van Schayck, P-A Gevenois, R Pellegrino, E Derom, and W De Backer
Assessment of progression of COPD: report of a workshop held in Leuven, 11-12 March 2004
Thorax, April 1, 2005; 60(4): 335 - 342.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
D. G. Parr, B. C. Stoel, J. Stolk, and R. A. Stockley
Pattern of Emphysema Distribution in {alpha}1-Antitrypsin Deficiency Influences Lung Function Impairment
Am. J. Respir. Crit. Care Med., December 1, 2004; 170(11): 1172 - 1178.
[Abstract] [Full Text] [PDF]

Home page
 ThoraxHome page
S B Shaker, T Stavngaard, J Stolk, B Stoel, and A Dirksen
{alpha}1-Antitrypsin deficiency {middle dot} 7: Computed tomographic imaging in {alpha}1-antitrypsin deficiency
Thorax, November 1, 2004; 59(11): 986 - 991.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
D. G. Parr, B. C. Stoel, J. Stolk, P. G. Nightingale, and R. A. Stockley
Influence of Calibration on Densitometric Studies of Emphysema Progression Using Computed Tomography
Am. J. Respir. Crit. Care Med., October 15, 2004; 170(8): 883 - 890.
[Abstract] [Full Text] [PDF]

Home page
 ThoraxHome page
R A Sandhaus
{alpha}1-Antitrypsin deficiency {middle dot} 6: New and emerging treatments for {alpha}1-antitrypsin deficiency
Thorax, October 1, 2004; 59(10): 904 - 909.
[Abstract] [Full Text] [PDF]

Home page
 ThoraxHome page
J K Stoller and L S Aboussouan
{alpha}1-Antitrypsin deficiency {middle dot} 5: Intravenous augmentation therapy: current understanding
Thorax, August 1, 2004; 59(8): 708 - 712.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
G. L. Snider
Only Cell and Molecular Biology Can Lead to an Understanding of Pathogenesis of Lung Disease
Am. J. Respir. Crit. Care Med., July 1, 2004; 170(1): i - ii.
[Full Text]

Home page
 Eur Respir JHome page
J.D. Newell Jr, J.C. Hogg, and G.L. Snider
Report of a workshop: quantitative computed tomography scanning in longitudinal studies of emphysema
Eur. Respir. J., May 1, 2004; 23(5): 769 - 775.
[Abstract] [Full Text] [PDF]

Home page
 ThoraxHome page
J K Stoller
{alpha}1-Antitrypsin deficiency
Thorax, February 1, 2004; 59(2): 92 - 93.
[Full Text] [PDF]

Home page
 ThoraxHome page
A Dirksen
Outcome measures in chronic obstructive pulmonary disease (COPD)
Thorax, December 1, 2003; 58(12): 1007 - 1008.
[Full Text] [PDF]

Home page
 ThoraxHome page
P A Dawkins, L J Dowson, P J Guest, and R A Stockley
Predictors of mortality in {alpha}1-antitrypsin deficiency
Thorax, December 1, 2003; 58(12): 1020 - 1026.
[Abstract] [Full Text] [PDF]

Home page
 ThoraxHome page
J Stolk, W H Ng, M E Bakker, J H C Reiber, K F Rabe, H Putter, and B C Stoel
Correlation between annual change in health status and computer tomography derived lung density in subjects with {alpha}1-antitrypsin deficiency
Thorax, December 1, 2003; 58(12): 1027 - 1030.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
American Thoracic Society/European Respiratory Society Statement: Standards for the Diagnosis and Management of Individuals with Alpha-1 Antitrypsin Deficiency
Am. J. Respir. Crit. Care Med., October 1, 2003; 168(7): 818 - 900.
[Full Text] [PDF]

Home page
 ChestHome page
J. K. Stoller, R. Fallat, M. D. Schluchter, R. G. O'Brien, J. T. Connor, N. Gross, K. O'Neil, R. Sandhaus, and R. G. Crystal
Augmentation Therapy With {alpha}1-Antitrypsin: Patterns of Use and Adverse Events
Chest, May 1, 2003; 123(5): 1425 - 1434.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
G. L. Snider
Understanding Inflammation in Chronic Obstructive Pulmonary Disease: The Process Begins
Am. J. Respir. Crit. Care Med., April 15, 2003; 167(8): 1045 - 1046.
[Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
T. L. Croxton, G. G. Weinmann, R. M. Senior, R. A. Wise, J. D. Crapo, and A. S. Buist
Clinical Research in Chronic Obstructive Pulmonary Disease: Needs and Opportunities
Am. J. Respir. Crit. Care Med., April 15, 2003; 167(8): 1142 - 1149.
[Abstract] [Full Text] [PDF]

Home page
 Eur Respir JHome page
M. Luisetti, M. Miravitlles, and R.A. Stockley
{alpha}1-antitrypsin deficiency: a report from the 2nd meeting of the Alpha One International Registry, Rapallo (Genoa, Italy), 2001
Eur. Respir. J., October 1, 2002; 20(4): 1050 - 1056.
[Abstract] [Full Text] [PDF]

Home page
 ChestHome page
J. K. Stoller, F. Rouhani, M. Brantly, S. Shahin, R. A. Dweik, J. M. Stocks, J. Clausen, E. Campbell, and F. Norton
Biochemical Efficacy and Safety of a New Pooled Human Plasma {alpha}1-Antitrypsin, Respitin*
Chest, July 1, 2002; 122(1): 66 - 74.
[Abstract] [Full Text] [PDF]

Home page
 NEJMHome page
R. W. Carrell and D. A. Lomas
Alpha1-Antitrypsin Deficiency -- A Model for Conformational Diseases
N. Engl. J. Med., January 3, 2002; 346(1): 45 - 53.
[Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
L. J. DOWSON, P. J. GUEST, and R. A. STOCKLEY
Longitudinal Changes in Physiological, Radiological, and Health Status Measurements in alpha 1-Antitrypsin Deficiency and Factors Associated with Decline
Am. J. Respir. Crit. Care Med., November 15, 2001; 164(10): 1805 - 1809.
[Abstract] [Full Text] [PDF]

Home page
 Eur Respir JHome page
A. Madani, C. Keyzer, and P.A. Gevenois
Quantitative computed tomography assessment of lung structure and function in pulmonary emphysema
Eur. Respir. J., October 1, 2001; 18(4): 720 - 730.
[Abstract] [Full Text] [PDF]

Home page
 ChestHome page
J. G. W. Burdon, S. Brenton, M. Ayad, K. Knight, and J. Lieberman
Augmentation Therapy in {alpha}1-Antitrypsin Deficiency
Chest, August 1, 2001; 120(2): 687 - 687.
[Full Text] [PDF]

Home page
 Arch. Dis. Child.Home page
R A PRIMHAK and M S TANNER
Alpha-1 antitrypsin deficiency
Arch. Dis. Child., July 1, 2001; 85(1): 2 - 5.
[Full Text] [PDF]

Home page
 Eur Respir JHome page
M.G. Cosio and G.L. Snider
Chest computed tomography: is it ready for major studies of chronic obstructive pulmonary disease?
Eur. Respir. J., June 1, 2001; 17(6): 1062 - 1064.
[Full Text] [PDF]

Home page
 Eur Respir JHome page
L.J. Dowson, P.J. Guest, S.L. Hill, R.L. Holder, and R.A. Stockley
High-resolution computed tomography scanning in {alpha}1-antitrypsin deficiency: relationship to lung function and health status
Eur. Respir. J., June 1, 2001; 17(6): 1097 - 1104.
[Abstract] [Full Text] [PDF]

Home page
 ChestHome page
M. Wencker, B. Fuhrmann, N. Banik, and N. Konietzko
Longitudinal Follow-up of Patients With {{alpha}}1-Protease Inhibitor Deficiency Before and During Therapy With IV {{alpha}}1-Protease Inhibitor
Chest, March 1, 2001; 119(3): 737 - 744.
[Abstract] [Full Text] [PDF]

Home page
 ChestHome page
J. Lieberman
Augmentation Therapy Reduces Frequency of Lung Infections in Antitrypsin Deficiency : A New Hypothesis With Supporting Data
Chest, November 1, 2000; 118(5): 1480 - 1485.
[Abstract] [Full Text] [PDF]

Home page
 ThoraxHome page
R A Stockley
Alpha-1-antitrypsin deficiency: what next?
Thorax, July 1, 2000; 55(7): 614 - 618.
[Full Text]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Proc. Am. Thorac. Soc. Am. J. Respir. Cell Mol. Biol.
Copyright © 1999 American Thoracic Society