PMID- 27172295
OWN - NLM
STAT- MEDLINE
DCOM- 20171201
LR  - 20180914
IS  - 1541-2563 (Electronic)
IS  - 1541-2563 (Linking)
VI  - 13
IP  - 6
DP  - 2016 Dec
TI  - Disease Modification in Emphysema Related to Alpha-1 Antitrypsin Deficiency.
PG  - 807-815
AB  - Alpha-1 antitrypsin deficiency (AATD) is associated with premature onset of 
      emphysema resulting from low serum A(1)-PI levels. The only available 
      pharmacological treatment affecting the underlying cause of AATD is A(1)-PI 
      therapy. AATD-related emphysema is considered a good model to study 
      disease-modifying effects of treatment as the causative process has been 
      identified. Disease modification is a sustained improvement in disease state 
      following therapeutic intervention that persists when therapy is discontinued. 
      Appropriate trial design and the use of valid study endpoints are key to 
      illustrating disease modification, particularly in clinical trials of rare 
      diseases where it can be difficult to recruit sufficient numbers of patients. 
      Delayed-start trials are advantageous ethically as all patients ultimately 
      receive active treatment and imaging techniques have proven promising as valid 
      study endpoints. Specifically, computed tomography (CT) measured lung density has 
      been used to monitor emphysema and is considered a more sensitive outcome than 
      pulmonary function tests to monitor disease progression. This review will discuss 
      the importance of clinical endpoints and trial design to determine disease 
      modification and will review the evidence for disease modification in 
      AATD-related emphysema. Until recently, clinical studies have not shown a 
      significant effect of A(1)-PI therapy, possibly due to insufficient numbers of 
      patients, short duration of clinical trials and lack of appropriate trial design. 
      A recently completed randomised trial and open-label extension study followed a 
      larger study population for a longer duration and incorporated a delayed-start 
      design. The results demonstrated clinical efficacy of A(1)-PI therapy and 
      indicate that treatment is disease-modifying.
FAU - Chorostowska-Wynimko, Joanna
AU  - Chorostowska-Wynimko J
AD  - a Department of Genetics and Clinical Immunology , National Institute of 
      Tuberculosis and Lung Diseases , Warsaw , Poland.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20160512
PL  - England
TA  - COPD
JT  - COPD
JID - 101211769
SB  - IM
MH  - Endpoint Determination
MH  - Humans
MH  - Pulmonary Emphysema/diagnostic imaging/*drug therapy/*etiology
MH  - Randomized Controlled Trials as Topic
MH  - Research Design
MH  - Tomography, X-Ray
MH  - Treatment Outcome
MH  - alpha 1-Antitrypsin Deficiency/*complications
OTO - NOTNLM
OT  - A1-PI therapy
OT  - Disease modification
OT  - alpha-1 antitrypsin deficiency
OT  - computed tomography
OT  - emphysema
EDAT- 2016/05/14 06:00
MHDA- 2017/12/02 06:00
CRDT- 2016/05/13 06:00
PHST- 2016/05/14 06:00 [pubmed]
PHST- 2017/12/02 06:00 [medline]
PHST- 2016/05/13 06:00 [entrez]
AID - 10.1080/15412555.2016.1178224 [doi]
PST - ppublish
SO  - COPD. 2016 Dec;13(6):807-815. doi: 10.1080/15412555.2016.1178224. Epub 2016 May 
      12.