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American Journal of Respiratory and Critical Care Medicine Vol 165. pp. 1494-1498, (2002)
© 2002 American Thoracic Society

Original Article

The Effect of Augmentation Therapy on Bronchial Inflammation in {alpha}1-Antitrypsin Deficiency

Robert A. Stockley, Darren L. Bayley, Ipek Unsal and Lee J. Dowson

Department of Medicine, Queen Elizabeth Hospital, Edgbaston, Birmingham, United Kingdom

Correspondence and requests for reprints should be addressed to Professor Robert A. Stockley, Department of Medicine, Queen Elizabeth Hospital, Edgbaston, Birmingham B15 2TH, UK. E-mail: r.a.stockley{at}bham.ac.uk

{alpha}1-Antitrypsin (AAT) deficiency predisposes to bronchitis and emphysema associated with neutrophilic airway inflammation. The efficacy of augmentation therapy has not been proven clinically or by demonstrating an effect on airway inflammation. We treated 12 patients with four infusions of Prolastin (60 mg/kg) at weekly intervals and monitored both the serum and secretion concentrations of AAT as well as markers of neutrophilic inflammation, including myeloperoxidase, elastase, and the neutrophil chemoattractants interleukin-8 and leukotriene B4. Serum AAT rose and was maintained above the protective threshold. In addition, AAT concentrations in the sputum rose from a mean of 0.17 µM (SEM ± 0.04) before therapy to concentrations similar to nondeficient subjects (0.43 ± 0.12) 1 week after the first infusion (p < 0.01). This was associated with a reduction in elastase activity (p < 0.002) and the chemoattractant leukotriene B4 (p < 0.02), which fell from a median baseline value of 13.46 nM (range, 4.17–55.00) to 8.62 nM (4.23–21.59) the day following the last infusion. Although median values for myeloperoxidase and interleukin-8 also fell, the changes failed to achieve statistical significance. In summary, short-term therapy with AAT increased lung secretion concentrations and was associated with a fall in leukotriene B4, which is thought to be central to the airway inflammation of AAT deficiency.

Key Words: {alpha}1-antitrypsin • sputum • inflammation • leukotriene B4




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