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Table 2 Clinical trials of α1-PI inhalation in patients with cystic fibrosis and healthy individuals.

From: Lung deposition of inhaled Alpha-1-proteinase inhibitor (Alpha1-PI) - problems and experience of Alpha1-PI inhalation therapy in patients with hereditary Alpha1-PI deficiency and cystic fibrosis

Study

Study design

Results

McElvaney et al [41]

Inhalation of α1-PI twice daily for 1 week in 12 cystic fibrosis patients. i.v. administration of α1-PI once weekly for 4 weeks in 5 cystic fibrosis patients and 12 healthy controls.

No difference of α1-PI concentration in ELF of cystic fibrosis patients and controls prior to treatment.

Large amounts of neutrophil elastase in ELF of cystic fibrosis patients, but not in controls prior to treatment.

Inhalation followed by a strong increase of α1-PI concentration in ELF.

Inhalation of α1-PI followed by suppression of neutrophil elastase in ELF up to a restoration of the anti-neutrophil elastase activity.

Inhalation of α1-PI improved the killing of P. aeruginosa by neutrophils.

No effect of intravenous administration of α1-PI on the respiratory neutrophil elastase burden.

Inhalation of α1-PI well tolerated.

Griese et al [42, 43]

Inhalation of α1-PI in 8 cystic fibrosis patients twice daily for 8 weeks.

Reduction of free elastase in BAL, however a surplus of elastase activity remained.

Correlation between α1-PI concentration and neutrophils in BAL before, but not after inhalation.

Reduction of total protein, number and amount of proteins with a molecular mass < 20 kDa, total phospholipid content and phospholipids in small and large surfactant aggregates (SA/LA).

No effect on minimal surface tension and the conversion of LA to SA.

Cantin et al [44]

Saline inhalation twice daily (phase 1), α1-PI inhalation twice daily (phase 2), and wash out (phase 3) in 17 cystic fibrosis patients.

Increase of α1-PI in sputum at end of phase 2 compared to phases 1 and 3.

No changes of elastase and IL-8 in sputum.

Slight decrease of taurine in sputum in phases 2 and 3.

No effect of α1-PI inhalation on FEV1.

Martin et al [45]

Double-blinded, randomised, placebo-controlled parallel-group trial with 4 groups and inhalation of 3 different doses of recombinant α1-PI once daily in 39 cystic fibrosis patients for 16 weeks.

Decrease of free neutrophil elastase (NE) concentration in sputum in one group.

Decrease of the concentrations of α1-PI/NE complexes in sputum in two groups

Decrease of the activity of myeloperoxidase (MPO) in sputum in two groups. Trend towards lower sputum concentration of interleukin-8 (IL-8) in one group.

No effect on the concentration of tumour necrosis factor (TNF) p55 receptors in sputum.

No changes in bacterial ecology and colony counts in sputum.

No effect of α1-PI inhalation on pulmonary function tests.

Inhalation of α1-PI well tolerated.

Griese et al [46]

Prospective, randomised study with inhalation of α1-PI for bronchial and peripheral deposition in 52 cystic fibrosis patients for 4 weeks.

No differences between peripheral and bronchial deposition of inhaled α1-PI.

Increase of α1-PI level and 54kDa IgG fragments in induced sputum. Decrease of neutrophils, IL-8, IL-1β, TNF-α and LTB4 levels in induced sputum.

Reduction of P. aeruginosa load in induced sputum. Effects more pronounced after 4 than after 2 weeks of treatment. No effect of α1-PI inhalation on FEV1.

Brand et al [40]

Inhalation of 99 m Tc labelled α1-PI by means of an individualised breathing technique in 7 α1-PI 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.

  1. Data of studies investigating patients with α1-PI are also compiled in Table 1.
  2. Abbreviations: BAL - Bronchoalveolar lavage fluid, ELF - Epithelial lining fluid.