Type

Journal Article

Authors

Noel G McElvaney
Edwin K Silverman
Shane J O'Neill
Catherine M Greene
Jessica A Lasky-Su
Catherine A O'Connor
Tomás P Carroll
Valerie B Morris
Craig P Hersh
Kevin Molloy

Subjects

Medicine & Nursing

Topics
questionnaires odds ratio serpina1 protein human smoking etiology physiopathology adult humans heterozygote gene environment interaction forced expiratory volume female vital capacity genetics diagnosis genetic markers spirometry male phenotype alpha 1 antitrypsin aged middle aged adverse effects risk factors alpha 1 antitrypsin deficiency pulmonary disease chronic obstructive complications

Clarification of the risk of chronic obstructive pulmonary disease in α1-antitrypsin deficiency PiMZ heterozygotes. (2014)

Abstract Severe α1-antitrypsin deficiency (typically PiZZ homozygosity) is associated with a significantly increased risk of airflow obstruction and emphysema but the risk of chronic obstructive pulmonary disease (COPD) in PiMZ heterozygotes remains uncertain. This was a family-based study to determine the risk of COPD in PiMZ individuals. We compared 99 PiMM and 89 PiMZ nonindex subjects recruited from 51 index probands who were confirmed PiMZ heterozygotes and also had a diagnosis of COPD Global Initiative for Chronic Obstructive Lung Disease stage II-IV. The primary outcome measures of interest were quantitative variables of pre- and post-bronchodilator FEV1/FVC ratio, FEV1 (liters), FEV1 (% predicted), forced expiratory flow midexpiratory phase (FEF25-75; liters per second), FEF25-75 (% predicted), and a categorical outcome of COPD. PiMZ heterozygotes compared with PiMM individuals had a reduced median (interquartile range) post-bronchodilator FEV1 (% predicted) (92.0 [75.6-105.4] vs. 98.6 [85.5-109.7]; P = 0.04), FEV1/FVC ratio (0.75 [0.66-0.79] vs. 0.78 [0.73-0.83]; P = 0.004), and FEF25-75 (% predicted) (63.84 [38.45-84.35] vs. 72.8 [55.5-97.7]; P = 0.0013) compared with PiMM individuals. This effect was abrogated in never-smoking and accentuated in ever-smoking PiMZ individuals. PiMZ heterozygosity was associated with an adjusted odds ratio for COPD of 5.18 (95% confidence interval, 1.27-21.15; P = 0.02) and this was higher (odds ratio, 10.65; 95% confidence interval, 2.17-52.29; P = 0.004) in ever-smoking individuals. These results indicate that PiMZ heterozygotes have significantly more airflow obstruction and COPD than PiMM individuals and cigarette smoke exposure exerts a significant modifier effect.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed

Full list of authors on original publication

Noel G McElvaney, Edwin K Silverman, Shane J O'Neill, Catherine M Greene, Jessica A Lasky-Su, Catherine A O'Connor, Tomás P Carroll, Valerie B Morris, Craig P Hersh, Kevin Molloy

Experts in our system

1
Noel G McElvaney
Royal College of Surgeons in Ireland
Total Publications: 194
 
2
Shane J O'Neill
Royal College of Surgeons in Ireland
Total Publications: 84
 
3
Catherine M Greene
Royal College of Surgeons in Ireland
Total Publications: 150
 
4
Tomás P Carroll
Royal College of Surgeons in Ireland
Total Publications: 26
 
5
Kevin Molloy
Royal College of Surgeons in Ireland
Total Publications: 19