Abstract

BACKGROUND Alpha-1 antitrypsin (α₁-AT) is the most abundant proteinase inhibitor within the lung. We have recently reported the surprising observation that cystic fibrosis patients with mild to moderate deficiency of α₁-antitrypsin have significantly better pulmonary function than non-deficient patients. This study may have been biased as it did not include the most severely affected patients who have died in childhood or those who have undergone orthotopic lung transplantation. The prevalence of α₁-antitrypsin deficiency alleles in this most severely affected group of patients with cystic fibrosis was therefore assessed.

METHODS DNA was obtained from neonatal blood spots from children with cystic fibrosis who had died from pulmonary disease and from formalin fixed lung tissue from transplanted cystic fibrosis patients. The common S and Z deficiency alleles of α₁-AT were sought by amplification mutagenesis of the appropriate region of the α₁-AT gene followed by restriction enzyme digestion with Xmn I and Taq I, respectively.

RESULTS Seventy nine patients were identified (seven dead, 72 transplanted). Two patients (2.5%) were heterozygous for the Z allele of α₁-AT and four (5.1%) were heterozygous for the S allele. This is not significantly different from the incidence in the normal population of 4% and 8% for the S and Z alleles, respectively.

CONCLUSIONS These data support previous findings that deficiency of α₁-AT is not associated with more severe pulmonary disease in cystic fibrosis and may be associated with milder lung disease. Further work is needed to clarify the mechanisms underlying the progressive lung damage in cystic fibrosis.