PMID- 28558837
OWN - NLM
STAT- MEDLINE
DCOM- 20180614
LR  - 20181113
IS  - 1465-993X (Electronic)
IS  - 1465-9921 (Print)
IS  - 1465-9921 (Linking)
VI  - 18
IP  - 1
DP  - 2017 May 30
TI  - Long-term clinical outcomes following treatment with alpha 1-proteinase inhibitor 
      for COPD associated with alpha-1 antitrypsin deficiency: a look at the evidence.
PG  - 105
LID - 10.1186/s12931-017-0574-1 [doi]
LID - 105
AB  - Alpha-1 antitrypsin deficiency (AATD) is a common hereditary disorder caused by 
      mutations in the SERPINA1 gene, which encodes alpha-1 antitrypsin (AAT; also 
      known as alpha 1-proteinase inhibitor, A(1)-PI). An important function of A(1)-PI 
      in the lung is to inhibit neutrophil elastase, one of various proteolytic enzymes 
      released by activated neutrophils during inflammation. Absence or deficiency of 
      A(1)-PI leads to an imbalance between elastase and anti-elastase activity, which 
      results in progressive, irreversible destruction of lung tissue, and ultimately 
      the development of chronic obstructive pulmonary disease with early-onset 
      emphysema. AATD is under-diagnosed, patients can experience long delays before 
      obtaining an accurate diagnosis, and the consequences of delayed diagnosis or 
      misdiagnosis can be severe. Currently, A(1)-PI therapy is the only available 
      treatment that addresses disease etiology in patients with AATD; however, 
      demonstrating clinical efficacy of A(1)-PI therapy is challenging. In order to 
      show therapeutic efficacy with traditional endpoints such as forced expiratory 
      volume in one second and mortality, large sample sizes and longer duration trials 
      are required. However, AATD is a rare, slow progressive disease, which can take 
      decades to manifest clinically and recruiting sufficient numbers of patients into 
      prolonged placebo-controlled trials remains a significant obstacle. Despite this, 
      the Randomized, placebo-controlled trial of augmentation therapy in Alpha 
      1-Proteinase Inhibitor Deficiency (RAPID) and RAPID Extension trial, the largest 
      clinical program completed to date, utilized quantitative chest computed 
      tomography as a sensitive and specific measure of the extent of emphysema. 
      Findings from the RAPID/RAPID Extension program definitively confirmed the 
      benefits of A(1)-PI therapy in slowing disease progression and provided evidence 
      of a disease-modifying effect of A(1)-PI therapy in patients with AATD. These 
      findings suggest that the early introduction of treatment in patients with severe 
      emphysema-related AATD may delay the time to death, lung transplantation or 
      crippling respiratory complaints. In addition, there is now limited evidence that 
      A(1)-PI therapy provides a gain of more than five life-years, supporting previous 
      observations based on registry data. With the clinical efficacy of A(1)-PI 
      therapy now demonstrated, further studies are required to assess long-term 
      outcomes.
FAU - Rahaghi, Franck F
AU  - Rahaghi FF
AD  - Pulmonary and Critical Care Division, Cleveland Clinic Florida, 2950 Cleveland 
      Clinic Blvd, Weston, FL, 33331, USA. rahaghf@ccf.org.
FAU - Miravitlles, Marc
AU  - Miravitlles M
AD  - Pneumology Department, Hospital Universitari Vall d'Hebron, Ciber de Enfermedades 
      Respiratorias (CIBERES), Passeig de la Vall d'Hebron, 119-129, 08035, Barcelona, 
      Spain.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20170530
PL  - England
TA  - Respir Res
JT  - Respiratory research
JID - 101090633
RN  - 0 (SERPINA1 protein, human)
RN  - 0 (alpha 1-Antitrypsin)
SB  - IM
MH  - Disease Progression
MH  - *Enzyme Replacement Therapy
MH  - Female
MH  - Genetic Predisposition to Disease
MH  - Humans
MH  - Lung/*drug effects/enzymology/physiopathology
MH  - Male
MH  - Middle Aged
MH  - Mutation
MH  - Phenotype
MH  - Pulmonary Disease, Chronic Obstructive/*drug 
      therapy/enzymology/mortality/physiopathology
MH  - Time Factors
MH  - Treatment Outcome
MH  - alpha 1-Antitrypsin/genetics/*therapeutic use
MH  - alpha 1-Antitrypsin Deficiency/*drug therapy/enzymology/genetics/mortality
PMC - PMC5450185
OTO - NOTNLM
OT  - Alpha-1 antitrypsin
OT  - Alpha-1 antitrypsin deficiency
OT  - Chronic obstructive pulmonary disease
OT  - Emphysema
OT  - Mortality
OT  - Outcome
OT  - Treatment
EDAT- 2017/06/01 06:00
MHDA- 2018/06/15 06:00
PMCR- 2017/05/30
CRDT- 2017/06/01 06:00
PHST- 2017/01/31 00:00 [received]
PHST- 2017/05/05 00:00 [accepted]
PHST- 2017/06/01 06:00 [entrez]
PHST- 2017/06/01 06:00 [pubmed]
PHST- 2018/06/15 06:00 [medline]
PHST- 2017/05/30 00:00 [pmc-release]
AID - 10.1186/s12931-017-0574-1 [pii]
AID - 574 [pii]
AID - 10.1186/s12931-017-0574-1 [doi]
PST - epublish
SO  - Respir Res. 2017 May 30;18(1):105. doi: 10.1186/s12931-017-0574-1.