Alpha1-antitrypsin phenotypes in patients with cryptogenic fibrosing alveolitis: a case-control study

Abstract

Cryptogenic fibrosing alveolitis (CFA) is an interstitial lung disease, which by definition is of unknown aetiology. Recent evidence has suggested that smoking and occupational exposure to dusts may be environmental risk factors for the disease, but there has been little research into potential host risk factors. One previous study has suggested that the prevalence of abnormal alpha1-antitrypsin phenotypes may be increased in patients with CFA. Since alpha1-antitrypsin is important in regulating inflammation within the lung in response to environmental exposures, such abnormalities may be of aetiological importance in this disease. We have compared the alpha1-antitrypsin phenotypes of 189 patients with CFA with 189 age-, sex-, and community-matched controls. This sample size was sufficient to provide more than 95% power to detect an odds ratio (OR) of 2.5. Alpha1-antitrypsin phenotype was established by isoelectric focusing, and the prevalence of abnormal phenotypes in cases and controls was compared by conditional logistic regression. Personal smoking histories were obtained by postal questionnaire. The prevalence of abnormal alpha1-antitrypsin phenotypes was similar in cases and controls (12.7 versus 15.3%; OR 0.88; 95% confidence interval 0.49-1.57; p=0.66). No interaction was found between the presence of abnormal alpha1-antitrypsin phenotypes and a history of smoking. We conclude that cryptogenic fibrosing alveolitis is not associated with abnormal alpha1-antitrypsin phenotypes.

Recent advances in the aetiology of cryptogenic fibrosing alveolitis

“…78 One study carried out to investigate the aetiology of rheumatoid arthritis found an unexpected association between the presence of abnormal alpha-1-antitrypsin phenotypes and CFA, 79 but this finding was not confirmed in a subsequent larger study. 80 More recently we have reported evidence of an association between CFA and proinflammatory gene polymorphisms relating to the interleukin-1 receptor antagonist and the tumour necrosis factor promoter. 81…”

An Official ATS/ERS/JRS/ALAT Statement: Idiopathic Pulmonary Fibrosis: Evidence-based Guidelines for Diagnosis and Management

“…Polymorphisms of genes encoding for cytokines (interleukin [IL]-1 a, tumor necrosis factor-a, lymphotoxin a, IL-4, IL-6, IL-8, IL-10, and IL-12 [79][80][81][82][83][84][85][86][87][88]), enzymes (a 1 -antitrypsin [89,90] and angiotensinconverting enzyme [91]), profibrotic molecules (transforming growth factor-b1 [92]), coagulation pathway genes (plasminogen activator inhibitors-1 and -2), genes for surfactant protein-A and -B (70), immunomodulatory genes (complement receptor 1, NOD2/CARD15 [93]), and matrix metalloproteinase (MMP)-1 (94) have been reported to have increased frequencies in patients with sporadic IPF. Many of these have also been related to disease progression.…”

Alpha-1 antitrypsin deficiency alleles and severe cystic fibrosis lung disease

“…The common S ( 264 Glu→Val) and Z ( 342 Glu→Lys) deficiency alleles are found in approximately 12% of the UK population3 and result in plasma α 1 -AT concentrations in the homozygote of 60% and 10%, respectively, compared with the normal M homozygote. Deficiency of α 1 -AT is associated with early onset panlobar emphysema,4 bronchiectasis,5asthma,6 and cryptogenic fibrosing alveolitis,7 although this last association was not confirmed in a subsequent study 8. Current thinking would predict that α 1 -AT deficiency in patients with cystic fibrosis would lead to a greater excess of elastase and hence more severe pulmonary disease.…”