Alpha 1 antitrypsin and cystic fibrosis

Alpha-1-antitrypsin and secretory leukoprotease inhibitor (SLPI)

Jan, 2001. Alpha-1-antitrypsin and secretory leukoprotease inhibitor (SLPI) [online]. Seacroft and St James's University Hospitals, UK. Available from http://www.cysticfibrosismedicine.com

Two natural defences which protect the lung against the destructive impact of the enzyme elastase, released by the neutrophil dominated inflammatory infiltrate in the lung tissue, are alpha-1-antitrypsin (a -1AT) (PPL Therapeutics Ltd, Scotland, UK) and secretory leukoprotease inhibitor (SLPI). These anti-proteases can be administered by aerosol to supplement the inadequate amount of anti-proteases present in the cystic fibrosis airway (Vogelmeier et al, 1996; McElvaney et al, 1991; Allen, 1996). A phase II trial to assess the clinical efficacy of transgenic alpha-1-antitrypsin as an effective treatment of cystic fibrosis showed a trend towards improvement in terms of time to first pulmonary exacerbation and total number of exacerbations when treatment groups were compared to placebo. There were no differences in the reported adverse events in the different treatment groups and placebo and the product were well tolerated. In this small study of nebulised transgenic alpha-1-antitrypsin in CF there were indications of clinical benefit warranting further investigation (Bilton et al, 1999). The reports from longer-term trials are awaited. Although anti-proteases remain therapeutically promising much research needs to be completed in this area and their efficacy and safety needs to be fully established before they will become available in routine clinical use.

References

Allen ED. Opportunities for the use of aerosolised a 1 anti-trypsin for the treatment of cystic fibrosis. Chest 1996; 110: 256S-260S

Bilton D, Ellborn S, Conway S, Edgar J, Redmond A. Phase II trial to assess the clinical efficacy of transgenic alpha-1-antitrypsin as an effective treatment of cystic fibrosis. Pediatr Pulmonol 1999; Suppl 19: 246

McElvaney NG, Hubbard RC, Birrer P et al. Aerosol a 1 anti-trypsin for cystic fibrosis. Lancet 1991; 337: 392-394

Vogelmeier C, Gillisen A, Buhl R. Use of secretory leukoprotease inhibitor to augment lung anti-neutrophil elastase activity. Chest 1996; 110: 261S-266S