No abstract

We have investigated whether restoration of the balance between neutrophil elastase and its inhibitor, alpha(1)-antitrypsin, can prevent the progression of pulmonary emphysema in patients with alpha(1)-antitrypsin deficiency. Twenty-six Danish and 30 Dutch ex-smokers with alpha(1)-antitrypsin deficiency of PI*ZZ phenotype and moderate emphysema (FEV(1) between 30% and 80% of predicted) participated in a double-blind trial of alpha(1)-antitrypsin augmentation therapy. The patients were randomized to either alpha(1)-antitrypsin (250 mg/kg) or albumin (625 mg/kg) infusions at 4-wk intervals for at least 3 yr. Self-administered spirometry performed every morning and evening at home showed no significant difference in decline of FEV(1) between treatment and placebo. Each year, the degree of emphysema was quantified by the 15th percentile point of the lung density histogram derived from computed tomography (CT). The loss of lung tissue measured by CT (mean +/- SEM) was 2.6 +/- 0.41 g/L/yr for placebo as compared with 1.5 +/- 0.41 g/L/yr for alpha(1)-antitrypsin infusion (p = 0.07). Power analysis showed that this protective effect would be significant in a similar trial with 130 patients. This is in contrast to calculations based on annual decline of FEV(1) showing that 550 patients would be needed to show a 50% reduction of annual decline. We conclude that lung density measurements by CT may facilitate future randomized clinical trials of investigational drugs for a disease in which little progress in therapy has been made in the past 30 yr.

From 1978 to 1985 96 patients with their first spontaneous pneumothorax were randomised into three groups, receiving either treatment with simple drainage (34 patients), drainage with tetracycline pleurodesis (33 patients), or drainage with talc pleurodesis (29 patients). There were 58 men and 38 women, aged 18-88 years. There was no significant difference between the three groups in the mean time in hospital or the period for which the drains were retained. The incidence of infection, persistent pneumothorax, and relapse while in hospital was also similar for the three groups. At follow up in 1987 89 patients could be accounted for, with an average follow up period of 4 6 years. The incidence of recurrence was 36% in the simple drainage group, 13% in the tetracycline pleurodesis group, and 8% in the talc pleurodesis group. The difference between the talc and simple drainage groups was significant. None of the methods caused severe short or long term side effects or changes in the follow up chest radiograph. Thoracoscopy, performed on admission in 85 patients, showed normal appearances in 73 patients and small cysts in 12. The thoracoscopic findings were of no value in predicting recurrence. Talc pleurodesis resulted in a significantly lower recurrence rate than simple drainage, tetracycline pleurodesis having intermediate efficacy.

for the "Wissenschaftliche Arbeitsgemeinschaft zur Therapie von Lungenerkrankungen (WATL) α 1 -AT study group" Does α 1 -antitrypsin augmentation therapy slow the annual decline in FEV1 in patients with severe hereditary α 1 -antitrypsin deficiency? N. Seersholm, M. Wencker, N. Banik, K. Viskum, A. Dirksen, A. Kok-Jensen, N. Konietzko The ∆FEV1 in the treated group was significantly lower than in the untreated group, with annual declines of 53 mL·yr -1 (95% confidence interval (95% CI) 48-58 mL·yr -1 ) and 75 mL·yr -1 (95% CI 63-87 mL·yr -1 ), respectively (p=0.02). The two groups differed with respect to gender and initial FEV1% predicted. Gender did not have any influence on the ∆FEV1. Stratification by initial FEV1% pred showed a significant effect of the treatment only in the group of patients with an initial FEV1% pred of 31-65%, and ∆FEV1 was reduced by 21 mL·yr -1 .This nonrandomized study suggests that weekly infusion of human α 1 -antitrypsin in patients with moderately reduced lung function may slow the annual decline in forced expiratory volume in one second.

This study does not support the theory of an association between sarcoidosis and malignancy, and the main reason other studies have shown such an association is most likely to have been due to selection bias and misclassification.