Protease inhibitor phenotypes and serum alpha-1-antitrypsin levels in patients with COPD: A study from Hong Kong

Objective: Many studies have suggested that an imbalance of protease activation and inhibition might result in COPD with emphysema. Levels of alpha-1-antitrypsin (alpha(1)-AT), the key protease inhibitor, are genetically determined by alleles that present in many phenotypes/subtypes, some of which are associated with deficiency of the protein. We prospectively evaluated the prevalence of the protease inhibitor (Pi) alleles and phenotypes together with the serum alpha(1)-AT levels in Chinese patients with COPD. Methodology: The study population comprised 356 patients with COPD. The male-to-female ratio was 4: 1 with a mean age of 72.4 years (range 44-93 years). Isoelectric focusing was used for Pi phenotyping/subtyping. The frequencies of Pi alleles and phenotypes were compared with the frequencies in 1085 healthy unrelated Chinese control subjects. The serum alpha(1)-AT levels were measured by the Cobas Fara assay. Results: PiZ was not detected. No significant difference in distribution of PiM phenotypes/subtypes between patients with COPD and healthy controls was observed, except for M1M3 and M2M3. There was also a significant difference in the proportion of variant S and F alleles between the disease group and the control population. Conclusion: The low prevalence of deficiency Pi phenotypes/subtypes suggests a lack of contribution of alpha(1)-AT deficiency to the pathogenesis of COPD in Chinese patients. The strategy of launching an alpha(1)-AT deficiency detection program among COPD patients, based on the recommendation of the World Health Organization, may not be readily applicable in our local setting.