Introduction: Smoking accelerates lung function decline, especially in those with alpha-1 antitrypsin (a1-AT) deficiency. Smoking cessation is a primary therapeutic intervention for all, but less is known about its impact in heterozygote a1-AT patients.

Aims and Objectives: We assessed how smoking cessation impacted lung function decline in heterozygote a1-AT patients.

Methods: Among heterozygote a1-AT patients (blood a1-AT ?0.5 g/L) attending COPD clinics at the Royal Brompton Hospital, we retrospectively investigated how lung function decline (spirometry, body plethysmography, diffusion capacity) differed in those who quit versus to ongoing smokers. The most recent lung function tests were analyzed and smoking history was retrieved by the medical file. Analysis was performed with Student?s t-test or ANOVA and LSD post hoc test. Data presented as mean±SD.

Results: 79 patients (21 PiMS, 34 PiMZ, 24 PiSZ) were included. Ex-smokers with ?10 yr since quitting (n=21) reported comparable cumulative smoking exposure to current/ex-smokers with <10 yr since quitting (n=43) (pack-years, 34.1±23.5 vs 37.1±15.9, p=0.58 respectively) and exhibited greater gas diffusion (TLco% 54.9±26.4 vs 41.3±18.4, p=0.02) but no significant difference in FEV1%pred (54.0±26.7 vs 45.4±24.2, p=0.2) or hyperinflation (RV/TLC% 127.0±30.9 vs 140.1±33.2, p=0.15). FEV1 decline among ex-smokers appeared substantially lower compared to current (ml/y 19.9±89.7 vs 132.8±168.2, p=0.006] and not different to never smokers (ml/y -22.28±80.14, p=0.96).

Conclusion: Smoking cessation should be vigorously encouraged among heterozygote a1-AT patients who continue to smoke as it may significantly improve their lung function trajectory.