Clarification of the Risk of COPD in Alpha-1 antitrypsin (MZ) Individuals

June 25, 2014 Alpha1 Admin Comments Off

Monday, 24 November 2008 12:20

Funding Body: Alpha-1 Foundation (USA)

Project Description: This clinical research study, to clarify the risk of COPD in MZ individuals, commenced in July 2007 and is supervised by Professor Gerry McElvaney, Department of Medicine RCSI, Smurfit Building, Beaumont Hospital, Dublin 9, Ireland.

The purpose of this study is to obtain information about individuals (and their family members) that are carriers of alpha-1 antitrypsin (AAT) deficiency. Acquisition of an abnormal alpha-1 gene from each parent leads to severe deficiency in alpha-1 protein levels which may result in serious lung disease in adults and/or liver disease in infants, children and adults. If an individual inherits an abnormal alpha-1 gene from only one parent, they are a carrier and may be predisposed to developing lung disease. The main objective of this study is to determine whether carriers of alpha-1 antitrypsin deficiency are at an increased risk of developing lung disease. We aim to identify subtle changes in lung function especially in close family members that may allow earlier intervention and treatment. We also aim to investigate whether there are any environmental factors that interact with the abnormal alpha-1 gene that predisposes some but not others to serious lung disease. If identified correctly, such environmental factors may then be avoided thus preventing the development of serious lung disease in carriers of alpha-1 antitrypsin deficiency. Our aim is to enroll 400 parents and siblings of 100 alpha-1 antitrypsin carriers (PiMZ) with diagnosed GOLD Stage 3 or 4 COPD into this study. The inclusion criteria for PiMZ carriers are as follows:

  • Age >30
  • GOLD Stage 3 or 4 COPD (post-bronchodilator FEV1 <50% predicted; FEV1/FVC ratio 0.7)
  • Confirmed PiMZ genotype
  • No other lung diseases that would affect pulmonary function testing (PFT)

The exclusion criteria for relatives of the above PiMZ carriers are as follows:

  • Any interstitial lung diseases
  • Genotypes other than PiMM or PiMZ
  • Non-biological siblings of the PiMZ COPD proband 

Each individual will perform a lung function test (using a portable spirometer), complete a detailed questionnaire (respiratory and liver questions, family history, smoking history etc) and provide blood samples to confirm their carrier status and allow DNA extraction. In the last year, we have recruited 125 individuals into the study from 25 families. Our preliminary results have shown approximately equal numbers of MZ carriers and MM individuals within each family. Our goal is to include as many siblings and parents from each family as possible to participate in this ground-breaking clinical research study. We will determine whether the PiMZ carrier status is associated with an increased risk of COPD and whether cigarette smoking confers an increased risk of COPD in carriers of alpha-1 antitrypsin deficiency. 

If you are an MZ carrier, fulfill the above criteria and are interested in partaking in this clinical research study, please contact:

Dr. Valerie Morris
Respiratory Research Laboratory, Smurfit Building, Beaumont Hospital, Dublin 9.
Tel: +353-1-8093861 or 085-7255506