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Am J Respir Crit Care Med. 2014 Feb 15;189(4):419-27. doi: 10.1164/rccm.201311-1984OC.

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

Author information

  • 11 Respiratory Research Division, Department of Medicine, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital, Dublin, Ireland; and.

Abstract

RATIONALE:

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.

OBJECTIVES:

This was a family-based study to determine the risk of COPD in PiMZ individuals.

METHODS:

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.

MEASUREMENTS AND MAIN RESULTS:

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.

CONCLUSIONS:

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.

PMID:
24428606
[PubMed - indexed for MEDLINE]
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