Deficient alpha-1-antitrypsin phenotypes and persistent airflow limitation in severe asthma

Respir Med. 2006 Sep;100(9):1534-9. doi: 10.1016/j.rmed.2006.01.009. Epub 2006 Feb 14.


Background: Persistent airflow limitation is common among patients with severe asthma, but its pathogenesis has not been fully clarified. Severe alpha-1-antitrypsin (AAT) deficiency is a risk factor of chronic airflow limitation and emphysema, and partially deficient phenotypes have been associated with an accelerated decline in lung function. We hypothesized that partial deficiency of AAT (non-PiM AAT phenotype) is a risk factor of persistent airflow limitation in asthma.

Methods: In 122 patients with severe asthma (86 females; age (median (range)): 44.0 yr (18-75)) postbronchodilator FEV1 and FEV1/VC were measured and the AAT phenotype was determined. Persistent airflow limitation was defined as postbronchodilator FEV1 or FEV1/VC < 75% pred. with TLC > 75% pred.

Results: Six patients (4.9%) had a non-PiM phenotype (1 MF, 3 MS, 1 MZ and 1 SZ). Of the 58 patients with persistent airflow limitation only 1 patient (1.7%) had a non-PiM phenotype vs. 7.8% among the patients without persistent airflow limitation (P = 0.21). Postbronchodilator FEV1/VC (% pred.) was higher in the non-PiM patients than in the PiM patients (P = 0.02), the other lung function parameters were not different. Linear regression analysis showed no association between AAT phenotype and FEV1% predicted (P = 0.26).

Conclusions: AAT heterozygoty does not seem to be an important risk factor of persistent airflow limitation in patients with asthma. Although confirmation by longitudinal follow-up studies with larger sample sizes is needed, these results suggest that routine assessment of the AAT phenotype is not indicated in asthmatic patients even if they exhibit fixed airflow limitation.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Asthma / blood*
  • Asthma / genetics
  • Female
  • Forced Expiratory Volume
  • Humans
  • Male
  • Middle Aged
  • Netherlands
  • Phenotype
  • Risk Factors
  • Vital Capacity
  • alpha 1-Antitrypsin / analysis*
  • alpha 1-Antitrypsin / genetics
  • alpha 1-Antitrypsin Deficiency / blood*
  • alpha 1-Antitrypsin Deficiency / genetics


  • alpha 1-Antitrypsin