introduction and objectives Alpha-1-Antitrypsin Deficiency (A1ATD) is a genetically determined anti-proteinase deficiency which predisposes to emphysema.1 Factors predicting mortality in untreated A1ATD patients include poor FEV1, gas transfer and low lung density.1 Indeed the latter has been shown to be the most sensitive measure of progression and hence has become the primary outcome in recent studies of augmentation therapy.2 We hypothesised that patients with the most rapid decline in lung density would be those most at risk of death and most in need of transplantation as the only viable rescue option.
Methods Augmentation naïve patients with 2 quantitative CT scans were selected from the UK A1ATD registry. The annual decline in lung density was determined using the difference between the 2 scans and patients were divided into those with no decline, a slow decline (0–2 g/l/year) or a rapid decline (> 2). Subsequent death or lung transplant was noted.
A univariate analysis was undertaken dividing the population into 2 groups: Alive without transplant and dead. Median baseline density was significantly higher in the living than the dead group (55.40 g/l and 39.80 g/l respectively; p = 0.002) and thus was included in a multivariate analysis, seeking association with subsequent death in a Cox regression analysis.
Results 77 patients were identified with sufficient data for analysis. 27 had died and 1 was transplanted and excluded from further analysis.
Slow decline in densitometry showed a trend to lower survival compared to no decline (p = 0.065) but rapid decline was significantly associated with death (p = 0.026; Figure).
Conclusions Decline in lung density may be a suitable surrogate measure for survival in AATD, and as augmentation therapy slows the decline in lung density2 could identify a group more likely to benefit from augmentation in the shorter term.
Dawkins P, et al. Mortality in alpha-1-antitrypsin deficiency in the UK. Respir Med. 2009 Oct;103(10):1540–7
Stockley RA, et al. Therapeutic efficacy of alpha-1 antitrypsin augmentation therapy on the loss of lung tissue: an integrated analysis of 2 randomised clinical trials using computed tomography densitometry. Respir Res. 2010;11:136