Exacerbations and duration of smoking abstinence are associated with the annual loss of FEV(1) in individuals with PiZZ alpha-1-antitrypsin deficiency.

Alpha-1-antitrypsin deficiency (AATD) is a genetic disorder that is associated with a higher risk of chronic obstructive pulmonary disease (COPD) and emphysema. The annual declines in lung function (FEV1) and transfer factor of the lung for carbon monoxide (TLCO) predict all-cause mortality. We investigated the longitudinal follow-up data over 11 years (mean follow-up period of 4.89 years) from the German AATD registry and analyzed the relationship between annual loss of FEV1 and TLCO and sex, age, body mass index (BMI), nicotine consumption, occupational dust exposure, St. George's Respiratory Questionnaire (SGRQ) score, baseline FEV1 or TLCO, alpha-1-antitrypsin (AAT) serum level, exacerbation frequency and the duration of smoking abstinence by multiple linear generalized estimating equations models (GEE-models). We evaluated the data of 100 individuals with post-bronchodilator FEV1 measurements and from 116 individuals with TLCO measurements. The mean overall decline was -54.06 ± 164.62 ml/year in FEV1 and -0.17 ± 0.70 mmol/min/kPa/year in TLCO. Accelerated deterioration of FEV1 was associated with occupational dust exposure (p = 0.026), shorter duration of smoking abstinence (p = 0.008), higher baseline FEV1 (p = 0.003), higher annual exacerbation frequency (p = 0.003) and higher frequency of glucocorticoids intake (p = 0.004). Furthermore, patients with an elevated decline in TLCO showed significant impaired health-related quality of life at baseline (p = 0.039) and lower AAT serum levels (p < 0.001) in multivariate analysis. Annual decline in FEV1 is related to the exacerbation rate, occupational dust exposure and the duration of smoking abstinence.

Fähndrich S ，Bernhard N ，Lepper PM ，Vogelmeier C ，Seibert M ，Wagenpfeil S ，Bals R ... -  《-》

Intensive smoking diminishes the differences in quality of life and exacerbation frequency between the alpha-1-antitrypsin deficiency genotypes PiZZ and PiSZ.

Alpha-1-antitrypsin deficiency (AATD) is a rare genetic disorder that is associated with low levels of circulating alpha-1-antitrypsin in serum. In comparison to the genotype PiZZ, PiSZ usually leads to lower risk of emphysema, better lung function and better survival. The aim of this study was to analyze the relationship between cigarette smoking (packyears) and the AATD genotypes (PiZZ and PiSZ) concerning quality of life (SGRQ), transfer factor of the lung for carbon monoxide (TLCO), forced expiratory volume in one second (FEV1) and exacerbation rate. We compared PiZZ and PiSZ individuals from the German registry for individuals with AATD (AATDR) in univariate analysis and multivariate linear regression models. All subjects were stratified into three groups according to their cumulative nicotine consumption (0 py; 0 < py < 30; ?30 py). 868 PiZZ individuals (mean age 52.6 ± 12.8 years (43.5% female)) and 114 PiSZ individuals (mean age 50.3 ± 17.4 years (46.5% female)) were compared. In contrast to never- and intensive (ex-) smokers, moderate (ex-) smoking PiSZ individuals had a significantly better SGRQ total score (B = ?8.148; p = 0.020) and less exacerbations (B = ?0.354; p = 0.037) than individuals with PiZZ in multivariate analysis. The differences in quality of life and exacerbation frequency between PiZZ and PiSZ individuals diminish by intensive (ex-) smoking.

Bernhard N ，Lepper PM ，Vogelmeier C ，Seibert M ，Wagenpfeil S ，Bals R ，Fähndrich S ... -  《-》

Deterioration of quality of life is associated with the exacerbation frequency in individuals with alpha-1-antitrypsin deficiency - analysis from the German Registry.

Bernhard N ，Lepper PM ，Vogelmeier C ，Seibert M ，Wagenpfeil S ，Bals R ，Fähndrich S ... -  《International Journal of Chronic Obstructive Pulmonary Disease》

Decline in FEV(1) and hospitalized exacerbations in individuals with severe alpha-1 antitrypsin deficiency.

Hiller AM ，Piitulainen E ，Jehpsson L ，Tanash H ... -  《International Journal of Chronic Obstructive Pulmonary Disease》

Long-term evolution of lung function in individuals with alpha-1 antitrypsin deficiency from the Spanish registry (REDAAT).

Esquinas C ，Serreri S ，Barrecheguren M ，Rodriguez E ，Nuñez A ，Casas-Maldonado F ，Blanco I ，Pirina P ，Lara B ，Miravitlles M ... -  《International Journal of Chronic Obstructive Pulmonary Disease》