Journal
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
Volume 165, Issue 11, Pages 1494-1498Publisher
AMER THORACIC SOC
DOI: 10.1164/rccm.2109013
Keywords
alpha 1-antitrypsin; sputum; inflammation; leukotriene B-4
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alpha1-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 B-4. Serum AAT rose and was maintained above the protective threshold, In addition, AAT concentrations in the sputum rose from a mean of 0.17 muM (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 B-4 (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 B-4 which is thought to be central to the airway inflammation of AAT deficiency.
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