Rationale: It is not known how the 2011 Global Initiative for Chronic Obstructive Lung Disease (GOLD) strategy predicts clinical course of α1-antitrypsin deficiency (AATD).
Objectives: To determine how the new strategy relates to outcomes (i.e., mortality, lung function decline, and exacerbations) in patients with AATD.
Methods: All PiZZ patients (patients with ZZ genotype causing severe AATD) on the AATD registry with a physiological diagnosis of chronic obstructive pulmonary disease were grouped into four GOLD categories (A, B, C, and D) on the basis of their combined risk. We then compared mortality and lung function decline in these categories and also assessed the predictive ability of exacerbation history in the patients.
Measurements and main results: Mortality (GOLD categories A: 6 [5.8%]; B: 7 [5.93%]; C: 11 [9.32%]; D: 94 [79.66%]) was greatest in high-symptom, high-risk category D (P = 0.0001), which also showed a faster decline in Kco (mmol/min/kPa/L/yr, mean [SD], A: -0.021 [0.03]; B: -0.022 [0.03]; C: -0.032 [0.03]; D: -0.031 [0.03]) (P = 0.012). The fastest mean decline in FEV1 (ml/yr, mean [SD], A: -66.59 [61.39]; B: -53.00 [47.09]; C: -56.96 [48.87]; D: -41.25 [62.09]) was observed in category A and least in category D (P = 0.002). Multivariate analysis showed that GOLD category was significant for all outcomes (P < 0.05).
Conclusions: The new strategy performs well in identifying patients with increased risk of poorer outcomes in AATD. This has therapeutic implications enabling more aggressive therapy to be directed to those in the highest-risk group. Further studies to identify subgroups of patients most likely to benefit from augmentation therapy are indicated.
Keywords: exacerbations; lung function decline; mortality.