Airway disease in alpha-1 antitrypsin deficiency

Although less well appreciated than pulmonary emphysema, inflammation of the airways is an early and important finding in alpha-1 antitrypsin deficiency (AATD). The spectrum of clinical presentations of airways disease includes cough and wheezing that is frequently diagnosed as asthma. Study of the airways inflammation in sputum or the proximal airways usually reveals neutrophilic inflammation. Although there is significant phenotypic variation, tubular airways dilation consistent with bronchiectasis is a common finding in areas of panlobular emphysema in severely deficient AATD. Other phenotypes of varicose and saccular bronchiectasis have been described. Since AAT may impact the course of bacterial, mycobacterial and viral clearance, future studies of the airway microbiota will inform whether airway pathogens are responsible for some pulmonary AATD phenotypes. Whether airways disease improves with AAT augmentation therapy remains unknown.