Abstract Introduction Alpha-1 antitrypsin deficiency (AATD), particularly the severe ZZ phenotype, is associated with obstructive lung disease and an increased risk for pulmonary exacerbations. Exacerbations may be classified based on patient reported changes in symptoms or by an acute event requiring treatment. Exacerbations in AATD are implicated in disease progression, yet many events are underrecognized. We have explored the characteristics of frequent exacerbators in our ZZ AATD cohort consisting of those with and without COPD. We analyzed the characteristics of both groups focusing on frequency, severity, and impact of exacerbations. Methods This is a prospective Irish National AATD registry study of ZZ individuals. We compare severely deficient ZZ patients with an FEV1/FVC ratio 0.7 (Group 1) with those with an FEV1/FVC ratio 0.7(Group 2). A baseline telephone survey was completed by the clinical team to establish clinical information including baseline respiratory symptoms. This was followed by a monthly call to establish the presence of increased symptoms suggestive of exacerbation or any event requiring treatment with antibiotics or steroids. Results 150 ZZ participants were enrolled consisting of 90 with an FEV1/FVC ratio 0.7 and to date 60 with an FEV1/FVC ratio 0.7. 11% were on IV augmentation therapy. We observed a high symptom burden with daily dyspnea reported in 73% of group 1, in contrast to 42% of group 2 who describe never experiencing dyspnea. 67% of those in group 1 report an exacerbation requiring antibiotics +/- steroids in the prior 12 months with 36% reporting 3 exacerbations. This is significantly higher than the exacerbation rate reported in routine COPD. In contrast, 57% of group 2 reported no exacerbations in the previous 12 months. Monthly follow up highlighted a high rate of exacerbations in group 1 in addition to frequently increased symptoms which may represent under reported exacerbations. This is in contrast to group 2 where in the absence of COPD, symptoms and exacerbations are significantly reduced. Conclusions Exacerbations in ZZ AATD are more frequent in those with airflow obstruction who also have a large symptom burden at baseline and increased frequency of symptoms suggestive of exacerbations which were often under reported. We advocate for a combined symptom and event-based approach when evaluating exacerbations. There remains no single, standardized and validated method for quantifying exacerbations in AATD. We also identify pulmonary function, exercise tolerance, age, and frailty to be important prognostic factors in severe AATD. This abstract is funded by: none
Carroll et al. (Fri,) studied this question.