Study | Study design | Results |
---|---|---|
Hubbard et al [32] | Single dose inhalation of different doses of recombinant α1-PI from yeast in 16 α1-PI deficient patients. Pilot study with subcutaneous injection of recombinant α1-PI in 6 α1-PI deficient patients for 6 months. | Strong dose-response relationship between administered α1-PI dose and levels of α1-PI and anti-neutrophil elastase activity in ELF. Levels of α1-PI and anti-neutrophil elastase activity in ELF higher than the normal range 4 h and lower than the normal range 24 h after inhalation. Detection of the inhaled α1-PI in the serum of the patients. No immunisation against administered recombinant α1-PI. Inhalation of α1-PI well tolerated. |
Hubbard et al [12] | Inhalation of α1-PI twice daily for 1 week in 12 α1-PI deficient patients. | Rapid increase of α1-PI concentration and anti-neutrophil elastase activity in ELF. Values of α1-PI concentration and anti-neutrophil elastase activity in ELF at least in the upper normal limit at the end of the study. Detection of inhaled α1-PI in the serum of the patients. Inhalation of α1-PI well tolerated. |
Vogelmeier et al [36] | Inhalation of α1-PI in 29 healthy individuals. | Strong increase of α1-PI concentration and anti-neutrophil (NE) activity in ELF after inhalation with half-life times of 69.2 h and 53.2 h, respectively. No change of the concentration of the α1-PI/NE complex in ELF. No change of the α1-PI uptake by macrophages. Inhalation of α1-PI well tolerated. |
Kropp et al [37] | Inhalation of 125I labelled α1-PI in 18 α1-PI deficient patients grouped according to their individual values of FEV1. | Percentage uptake values and degradation of α1-PI depending on individual values of FEV1 with a greater peripheral deposition and longer half-life times of inhaled α1-PI in patients with mildly impaired lung function compared to patients with severely impaired lung function. |
Brand et al [38] | Inhalation of 99 mTc labelled α1-PI in 6 α1-PI deficient patients by means of different nebulisers. | Significantly higher values of total and peripheral deposition after α1-PI inhalation by means of nebuliser systems based on individualised breathing manoeuvres. Significantly shorter inhalation times required by nebuliser systems based on individualised breathing manoeuvres. |
geraghty et al [39] | Inhalation of α1-PI powder aerosol for 14 days in 11 α1-PI deficient patients, 9 patients with community acquired pneumonia, and 9 healthy controls. | Strong decrease of neutrophil elastase activity which was no more detectable in ELF of α1-PI patients after end of the treatment. No effect on the percentage of neutrophils in BAL fluid of α1-PI patients. Significant decrease of cathepsin B and metalloproteinase-2 (MMP-2) n BAL fluid of α1-PI patients. Significant increase of the lactoferrin level but only minor increase of the secretory leukoprotease inhibitor (SLPI) level in BAL fluid of α1-PI patients. |
Brand et al [40] | Inhalation of 99 mTc labelled α1-PI by means of an individualised breathing technique in 7 α1-PI deficient patients, 7 cystic fibrosis patients, and 6 healthy controls | Homogenous pulmonary deposition of α1-PI in all groups. Higher peripheral (about 42% of the filled activity) than central (about 29% of the filled activity) deposition in all groups. Strong similarity of α1-PI deposition to 81 mKr ventilation scan. No effect of individual FEV1 (%pred) on the deposition. Inhalation of α1-PI well tolerated. |