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

Alpha-1-proteinase inhibitor (α(1)-PI) is the most relevant protease inhibitor in the lung. Patients with hereditary deficiency of α(1)-PI suffer from an impaired hepatic synthesis of α(1)-PI in the liver and in consequence an insufficient concentration of the protease inhibitor in the lung followed by development of lung emphysema due to an impaired protease antiprotease balance and a local relative excess of neutrophil elastase (NE). In contrast, patients with cystic fibrosis (CF) are characterised by a normal synthesis of α(1)-PI and a severe pulmonary inflammation with a strong excess of NE in the lung followed by progressive loss of lung function. In principle, both patient groups may benefit from an augmentation of α(1)-PI. Intravenous augmentation, which is established in patients with α(1)-PI deficiency only, is very expensive, subject to controversial discussions and only about 2% of the administered protein reaches lung interstitium. Inhalation of α(1)-PI may serve as an alternative to administer high α(1)-PI doses into the lungs of both patient groups to restore the impaired protease antiprotease balance and to diminish the detrimental effects of NE. However, prerequisites of this therapy are the reproducible administration of sufficient doses of active α(1)-PI into the lung without adverse effects. In our review we describe the results of studies investigating the inhalation of α(1)-PI in patients with α(1)-PI deficiency and CF. The data demonstrate the feasibility of α(1)-PI inhalation for restoration of the impaired protease antiprotease balance, attenuation of the inflammation and neutralisation of the excess activity of NE. Likely, inhalation of α(1)-PI serves as cheaper and more convenient therapy than intravenous augmentation. However, inhalation will be further optimised by use of novel nebulisers and optimised breathing techniques.