Mortality in alpha-1-antitrypsin deficiency in the United Kingdom.

BACKGROUND: Four hundred and eighty-eight PiZ alpha-1-antitrypsin deficient patients, who had joined the UK registry over a 9-year period, were followed in an observational study to determine mortality. None had received A1AT augmentation therapy.
METHODS: Cause of death was confirmed from death certification and medical records. Patients were censored according to length of time on the program or until they withdrew from the program.
RESULTS: There were 56 deaths of which 30 were attributed to respiratory causes. Of the remaining 26 deaths, 4 were due to complications from lung transplant, 6 due to liver disease (including 2 post-liver transplant) and the other 16 due to a variety of causes. Kaplan-Meier plots indicated a cumulative hazard for mortality of 18.1% in 9 years, correcting for time of follow up. When categorised for FEV1 percent-predicted, the group with severe impairment had increased mortality (p = <0.001) compared with the mild group and there was a direct relationship between severity and mortality. The severe group had increased mortality compared with the mild group when categorised for KCO percent-predicted (p<0.001), RV/TLC ratio (p<0.001) or emphysema score on CT scan (p<0.001 upper zone). Cox regression analyses indicated that these relationships remained when corrected for age. There were no differences in mortality after categorisation for educational level or occupational group.
CONCLUSION: Mortality in a cohort of A1AT deficient patients (PiZ phenotype) in the UK was 2% per year and was associated with lung function impairment and emphysema severity on CT scan, but not social status.