[Clinical trial endpoints in alpha-1-antitrypsin deficiency: interdisciplinary aspects].

TY - JOUR

T1 - [Clinical trial endpoints in alpha-1-antitrypsin deficiency: interdisciplinary aspects].

AU - Steinkamp, G

AU - Köhnlein, T

AU - Ley-Zaporozhan, J

AU - Wegscheider, Karl

AU - Buhl, R

PY - 2011

Y1 - 2011

N2 - Patients with alpha-1-antitrypsin deficiency (AAD) represent a small subgroup of subjects with chronic obstructive pulmonary disease (COPD). Only about 800 patients are registered in the German AAD registry, so that about 90 % of the estimated 8000 afflicted individuals have not yet been diagnosed. Clinical trials to demonstrate the efficacy of alpha-1-antitrypsin augmentation therapy are difficult not only due to the small number of potential participants. As in recent COPD trials, FEV (1) and other standard respiratory function parameters have failed to demonstrate statistically significant differences between treatment groups. The present article reviews and discusses both established and potentially new study endpoints. Novel parameters emerge within the field of diagnostic imaging. IT-supported analysis of lung density allows to quantify the extent of emphysema. The EXACTLE trial has shown that CT densitometry is able to document the progression of emphysema over 2 to 3 years. Magnetic resonance imaging (MRI) can serve as an adjunct to assess lung perfusion, ventilation, and breathing dynamics. In the future, prospective multi-centre studies will rather use imaging endpoints than classical respiratory function measurements such as FEV (1). In addition, diffusion capacity and combined endpoints such as the BODE index, which correlates with mortality in COPD, should be considered.

AB - Patients with alpha-1-antitrypsin deficiency (AAD) represent a small subgroup of subjects with chronic obstructive pulmonary disease (COPD). Only about 800 patients are registered in the German AAD registry, so that about 90 % of the estimated 8000 afflicted individuals have not yet been diagnosed. Clinical trials to demonstrate the efficacy of alpha-1-antitrypsin augmentation therapy are difficult not only due to the small number of potential participants. As in recent COPD trials, FEV (1) and other standard respiratory function parameters have failed to demonstrate statistically significant differences between treatment groups. The present article reviews and discusses both established and potentially new study endpoints. Novel parameters emerge within the field of diagnostic imaging. IT-supported analysis of lung density allows to quantify the extent of emphysema. The EXACTLE trial has shown that CT densitometry is able to document the progression of emphysema over 2 to 3 years. Magnetic resonance imaging (MRI) can serve as an adjunct to assess lung perfusion, ventilation, and breathing dynamics. In the future, prospective multi-centre studies will rather use imaging endpoints than classical respiratory function measurements such as FEV (1). In addition, diffusion capacity and combined endpoints such as the BODE index, which correlates with mortality in COPD, should be considered.

KW - Comorbidity

KW - Humans

KW - Risk Factors

KW - Sensitivity and Specificity

KW - Prevalence

KW - Outcome Assessment (Health Care)/methods

KW - Risk Assessment/methods

KW - Endpoint Determination/methods

KW - Pulmonary Disease, Chronic Obstructive/diagnosis/epidemiology

KW - alpha 1-Antitrypsin Deficiency/diagnosis/epidemiology

KW - Comorbidity

KW - Humans

KW - Risk Factors

KW - Sensitivity and Specificity

KW - Prevalence

KW - Outcome Assessment (Health Care)/methods

KW - Risk Assessment/methods

KW - Endpoint Determination/methods

KW - Pulmonary Disease, Chronic Obstructive/diagnosis/epidemiology

KW - alpha 1-Antitrypsin Deficiency/diagnosis/epidemiology

M3 - SCORING: Zeitschriftenaufsatz

VL - 65

SP - 229

EP - 235

JO - PNEUMOLOGIE

JF - PNEUMOLOGIE

SN - 0934-8387

IS - 4

M1 - 4

ER -