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

SummaryBackgroundFour 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.MethodsCause 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.ResultsThere 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.ConclusionMortality 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.