Background and aim: The value of the forced expiratory volume in one second (FEV 1 ) is useful in the diagnosis and prognosis of chronic obstructive pulmonary disease (COPD). Previous studies on lung function in individuals with severe alpha-1 antitrypsin deficiency (AATD) have shown a variable annual decline in FEV 1 (∆FEV 1 ). The aim of this study was to analyze ∆FEV 1 and to identify risk factors for ∆FEV 1 in individuals with severe AATD. Material and methods: Data on smoking habits, symptoms, results of lung function tests and exacerbations were obtained from the Swedish AATD Register and the Swedish National Patient Register (SNPR). The ∆FEV 1 was analyzed by random-effects modeling and adjusted for age and FEV 1 at baseline. Results: One hundred and four (9%) current smokers, 539 (48%) ex-smokers and 489 (43%) never-smokers were included in the study and followed-up from 1991 to 2016. A total of 584 (52%) individuals with severe AATD had COPD at inclusion. The median (IQR) annual severe exacerbation rate was 0.66 (1.4). The adjusted mean ∆FEV 1 was significantly higher in the current smokers compared with the ex-smokers and never-smokers (70 [95% CI 56–83] vs 42 [95% CI 36–48] and 32 [95% CI 25–38) mL·yr −1 ], in the middle–aged individuals compared with the young individuals (48 [95% CI 41–55] vs 32 [95% CI 18–45] mL·yr −1 ), in the individuals with respiratory symptoms at inclusion compared with the asymptomatic individuals (46 [95% CI 40–52] vs 30 [95% CI 22–38]mL·yr −1 ), and in the individuals with frequent exacerbations compared with those with infrequent exacerbations (57 [95% CI 47–68] vs 27 [95% CI 17–37] mL·yr −1 ). Conclusion: Active smoking, age, respiratory symptoms at baseline and repeated severe exacerbations of COPD are factors associated with an accelerated decline of lung function in individuals with severe AATD.

BackgroundSevere alpha-1-antitrypsin deficiency (AATD), phenotype PiZZ, is a risk factor for pulmonary emphysema and liver disease, but its effect on cancer risk is unknown. Our aim was to evaluate the risk and the risk factors for incident cancer in PiZZ individuals compared with the general population with known smoking habits.MethodsA longitudinal study of PiZZ individuals (n=1595) from the Swedish National AATD Register, and controls (n=5999) from Swedish population-based cohorts. Data on cancer and mortality were obtained by cross-linkage with national registers. Individuals who had undergone lung transplantation (n=10) and those with a cancer diagnosis within 5 years prior to inclusion (n=63) were excluded. The risk factors for developing cancer were analyzed using proportional hazards and Fine-Gray regression models, adjusting for age, sex, smoking habits and the presence of liver disease.ResultsThe median follow-up time was 17 years (IQR 11) for the whole study population. The incidence rate of hepatic and non-hepatic cancer per 1000 person-years was 1.6 (95% CI 1.1–2.3) and 8.5 (95% CI 7.2–10.0) for the PiZZ individuals, and 0.1 (95% CI 0.04–0.2) and 6.6 (95% CI 6.0–7.1) for the controls, respectively. The adjusted hazard ratios (HR) for hepatic and for non-hepatic cancer were 23.4 (95% CI 9.9–55.4) and 1.3 (95% CI 1.1–1.5) respectively, in the PiZZ individuals compared with the controls.ConclusionThese results suggest that individuals with severe alpha-1-antitrypsin deficiency may have an increased risk of developing both hepatic and non-hepatic cancer, compared with the general population.

No abstract