Bacterial colonisation doubles the risk of exacerbation in alpha-1 antitrypsin deficiency.

Abstract

Pulmonary exacerbations in alpha-1 antitrypsin deficiency (AATD) are associated with worse disease outcomes, including accelerated lung function decline. As with non-deficient COPD, subjects with AATD are predisposed to bacterial colonisation of the lower respiratory tract, a known risk factor for exacerbations. Despite this, the extent to which colonising bacteria contribute to exacerbations remains relatively unexplored. Sputum samples were collected longitudinally from AATD subjects, when clinically stable and during exacerbations, and were processed for quantitative culture to identify bacterial pathogens. Using contemporaneous clinical data, a post-hoc analysis was performed to calculate the odds of an exacerbation in the presence of recognised, potentially pathogenic bacteria (PPB) of the lower respiratory tract. 324 sputum samples were collected from 29 patients with AATD plus radiological evidence of bronchiectasis and 671 samples from 62 patients without bronchiectasis (AATD alone). Both groups contained patients with AATD-associated lung disease (emphysema and chronic bronchitis). At least half of the samples (55.5%) from AATD alone were positive for a PPB and almost three quarters (72.8%) of those with bronchiectasis. Presence of a Pseudomonas species, Staphylococcus aureus or Moraxella catarrhalis during stable state disease were all significantly associated with increased likelihood of a subsequent exacerbation (OR: 1.89, p=0.0013; 1.98, 0.0022; 1.98, 0.0047; 2.19, 0.0047, respectively), independent of age, sex, disease severity (FEV1 impairment), smoking status and presence or absence of bronchiectasis. Disease progression in AATD is variable and identification of traits which may contribute may prove influential. Here, we report that bacterial colonisation is an important predictor of exacerbation in AATD, likely attributed to the associated levels of increased inflammation. Thereby, this may represent a sub cohort of patients that could benefit from additional, targeted therapy.