Evidence for excessive bronchial inflammation during an acute exacerbationof chronic obstructive pulmonary disease in patients with alpha(1)-antitrypsin deficiency (PiZ)

Patients with homozygous (PiZ) alpha-antitrypsin (AAT) deficiency have not only low baseline serum AAT levels (approximately 10 to 15% normal) but als o an attenuated acute phase response. They are susceptible to the developme nt of premature emphysema but may also be particularly susceptible to lung damage during bacterial exacerbations when there will be a significant neut rophil influx. The purposes of the present study were to assess the inflamm atory nature of acute bacterial exacerbations of chronic obstructive pulmon ary disease (COPD) in subjects with AAT deficiency, to compare this with CO PD patients without deficiency, and to monitor the inflammatory process and its resolution following appropriate antibacterial therapy. At the start o f the exacerbation, patients with AAT deficiency had lower sputum AAT (p < 0.001) and secretory leukoprotease inhibitor (SLPI; p = 0.02) with higher e lastase activity (p = 0.02) compared with COPD patients without deficiency. Both groups had a comparable acute phase response as assessed by C-reactiv e protein (CRP) but the AAT-deficient patients had a minimal rise in serum AAT (to < 6 mu M) After treatment with antibiotics, in patients with AAT de ficiency, there were significant changes in many sputum proteins including a rise in SLPI levels, and a reduction in myeloperoxidase (MPO) and elastas e activity (p < 0.005 for all measures); the sputum chemoattractants interl eukin-8 (IL-8) and leukotriene B-4 (LTB4) fell (p < 0.01), and protein leak (sputum/serum albumin ratio) became lower (p < 0.01). The changes were rap id and within 3 d of the commencement of antibiotic therapy the biochemical markers had decreased significantly, but took a variable time thereafter t o return to baseline values. In conclusion, patients with AAT deficiency ha d evidence of increased elastase activity at the start of the exacerbation when compared with nondeficient COPD patients which probably reflects a def icient antiproteinase screen (lower sputum AAT and SLPI). The increased bro nchial inflammation at presentation resolved rapidly with 14 d of antibioti c therapy.