CT lung densitometry in young adults with alpha-1-antitrypsin deficiency.

BACKGROUND: Severe (PiZZ) and moderate (PiSZ) alpha-1-antitrypsin (AAT) deficiency predispose to lung emphysema, especially in smokers. We hypothesized that multi-slice computed tomography (CT) might be superior to pulmonary function tests (PFT) to detect lung emphysema in AAT-deficient individuals at the age of 32 years. METHODS: A subgroup of PiZZ and PiSZ individuals identified during the Swedish newborn screening programme in 1972-74 underwent multi-slice CT and PFT at the age of 32 years. From the CT scans the percentile density at 15% (PD(15)) and the relative area below -910 Hounsfield Units (RA(-910) HU) were calculated. The results of PFT and CT were compared between the AAT-deficient individuals and an age-matched control group. RESULTS: Twenty-five PiZZ, 11 PiSZ and 17 PiMM individuals participated in the study. All Pi subgroups had normal lung function. The mean PD(15) was 81 (SD 22) g/L in the PiZZ individuals, 96 (SD 35) g/L in the PiSZ individuals and 79 (SD 17) g/L in the PiMM individuals (ns), and the RA-910 were 30 (SD 18)%, 24 (SD 20)%, and 32 (SD 18)%, respectively (ns). For the never-smoker subgroups, in the PiZZ (n = 23), PiSZ (n = 8) and PiMM (n = 12), the mean PD(15) were 95 (SD 35) g/L, 81 (SD 22) g/L, and 75 (SD 12) g/L, respectively (ns). PD(15) was significantly correlated to CT derived lung size (r = -0.72; p < 0.001). CONCLUSIONS: CT densitometry revealed no signs of emphysema and no differences between the AAT-deficient individuals identified by neonatal screening and age-matched control subjects.

Lung function in 30-year-old alpha-1-antitrypsin-deficient individuals.

BACKGROUND: Alpha-1-antitrypsin (AAT) deficiency increases the risk of emphysema, especially in smokers. In 1972-1974, all 200,000 Swedish new-born infants were screened for AAT deficiency and individuals with severe (PiZZ) and moderate (PiSZ) deficiency have been followed-up regularly. The aim of the present study was to examine their lung function at the age of 30 years, comparing them to a group of age-matched control subjects (PiMM) recruited from the general population, and to compare current smokers with never-smokers. METHOD: Static and dynamic spirometry, including TLC, FRC, RV, VC, FEV(1,)K(CO) and D(L,CO), was performed for all participants. All values were expressed as percentages of the expected values. FEV(1)/VC was expressed both as percentage of the expected value and in absolute numbers. RESULTS: Four of 60 PiZZ, none of 19 PiSZ and 9 of 33 PiMM participating individuals were current smokers. All Pi groups had a normal mean FEV(1). The mean (SD) FEV(1)/VC ratio was 75% (7.4) in the PiZZ smokers and 84% (5.5) in the PiZZ never-smokers (p<0.01). The mean (SD) K(CO) was 81 (13) in the PiZZ smokers and 99 (14) in the PiZZ never-smokers (p<0.05). CONCLUSION: AAT-deficient individuals identified by neonatal screening have normal lung function at the age of 30. The PiZZ smokers had changes in lung function that may be signs of early emphysema.

Respiratory symptoms and lung function in 30-year-old individuals with alpha-1-antitrypsin deficiency.

INTRODUCTION: Individuals with severe alpha-1-antitrypsin (AAT) deficiency have a well-known risk of developing emphysema but it is not known at which age the first symptoms occur and lung function declines. The aim of this study was to examine the prevalence of smoking, respiratory symptoms and lung function at the age of 30 in AAT-deficient individuals (PiZ and PiSZ) identified by neonatal screening. MATERIAL AND METHODS: One hundred and seven PiZ, 45 PiSZ and 197 control subjects (PiMM) filled in a questionnaire regarding smoking habits and symptoms. Ninety PiZ, 40 PiSZ and 84 control subjects underwent spirometry including FEV(1) and FVC. RESULTS: Twenty-one percent of PiZ, 23% of PiSZ and 34% of PiMM subjects had smoked at some time (p<0.05). Sixty-five percent of PiZ, 55% of PiSZ and 35% of PiMM ever-smokers reported shortness of breath on exertion (p<0.05 PiZ vs PiMM). The mean FEV(1) was 101% predicted (95% CI 98-104) in PiZ, 101% predicted (95% CI 97-106) in PiSZ, and 96% predicted (95% 93-98) in PiMM individuals (p<0.05). There was no difference in mean FEV(1) when comparing ever- and neversmokers in the different Pi groups separately. CONCLUSION: At the age of 30, the AAT-deficient individuals in this cohort report more symptoms than the control subjects. Smoking is less common in the cohort compared to controls. Their lung function is normal.

Tailored pharmacokinetic dosing allows self-administration and reduces the cost of IV augmentation therapy with human alpha(1)-antitrypsin.

OBJECTIVE: Severe alpha(1)-Antitrypsin (AAT) deficiency (PiZZ) predisposes to the development of emphysema. Intravenous augmentation therapy with purified human AAT has been available since 1988. The dosage has varied from 60 mg/kg body weight once weekly to 250 mg/kg once monthly. We have found the dosage of 120 mg/kg every 2 weeks to be the most convenient for the patients. The treatment is very expensive. The objective of this investigation was to study whether tailored pharmacokinetic dosing of human AAT allows self-administration and reduces the total annual dose and cost of intravenous augmentation therapy. METHODS: Five PiZZ individuals receiving purified human AAT at a dose of 120 mg/kg every 2 weeks were included in the study. Three patients had a percutaneous and one patient had a subcutaneous intravenous injection port system. After a 4-week interruption of the treatment an ordinary dose of 120 mg/kg human AAT was infused. Plasma AAT levels were determined preinfusion, postinfusion, and once daily for 10-14 days. The pharmacokinetic parameters of exogenous AAT were calculated for each patient. Based on these, individual dosage schemes were designed by computer simulation. The patients were treated with the new dose twice weekly for 4 weeks, and plasma AAT was determined immediately before the last two infusions. RESULTS: At a dose of 1 or 2 g twice weekly the median annual consumption of human AAT was reduced from 286 to 156 g/patient. The trough plasma AAT level was maintained above 0.70 g/l, which is considered as protective. The three patients who had an implanted percutaneous venous port system learned to administer the treatment by themselves at home. The other two patients were treated at home by the district nurse. CONCLUSIONS: The results of our study indicate that tailored pharmacokinetic dosing of human AAT reduces the total annual dose and cost of IV augmentation therapy. In addition, this dosing facilitates self-administration of AAT and allows treatment at home.