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Several reports indicated an association among inherited A1ATD, pulmonary infections and bronchiectasis. Most reported A1ATD cases with bronchiectasis are elderly homozygous PiZZ (Glu342Lys) smokers with emphysema. Whether there is an increased risk for bronchiectasis in heterozygous PiMZ A1ATD carriers is not clear. We describe a non-smoking 18 years old male with bronchiectasis. Pulmonary function testing showed a moderate airflow obstruction and hyperinflation. Capillary blood gas analysis showed moderate respiratory failure and hyperventilation. A high-resolution CT scan of the chest revealed bronchiectasis in both lower lobes with thickening of bronchial walls and additional tree-in-bud sign, indicating bronchiolitis and mucus plugging, but no emphysema. Analysis of the serum A1AT and phenotyping revealed that this patient had reduced A1AT levels of 0.78 g/L (normal is 0.9-2.0g/L) associated with an intermediate PiMZ A1ATD. Although microscopic examination of Giemsa-stained cytospins revealed normal appearance of PiMZ neutrophils, they had significantly lower A1AT (SERPINA1) but higher elastase (ELANE) expression when compared to PiMM neutrophils. Affinity purified MZ A1AT protein contained a mixture of polymeric forms and lower ability to inhibit endotoxin-induced TNFα and IL-1β expression than MM A1AT. Our findings highlight the quantitative and qualitative deficiency of MZ A1AT and increased expression of neutrophil elastase, which may explain the early-age onset of bronchiectasis. Our data suggest that patients with bronchiectasis, even in the absence of emphysema, need to be tested for A1ATD.

Recurrent infections of the upper airways in early life may be a warning sign of inherited α 1 -antitrypsin deficiency http://ow.ly/iJsF300kbyV