Bronchiectasis Occurs Independently of Chronic Obstructive Pulmonary Disease in Alpha-1 Antitrypsin Deficiency.

Abstract

Introduction: Bronchiectasis occurs in patients with alpha-1 antitrypsin deficiency (AATD), but it is unknown whether an association exists independently of chronic obstructive pulmonary disease (COPD). We assessed whether bronchiectasis was associated with COPD in our cohort, and whether it has clinical significance for lung function decline, exacerbation rate, or symptoms.

Study design and methods: PiZZ, PiSZ and PiMZ patients from the Birmingham AATD Research Database were studied. Demographics were recorded, along with the outcomes of symptoms, FEV1, TLCO, KCO, and annualised exacerbation rate. Lung function decline was calculated for those with ≥3 measurements. Multivariate regression analyses were conducted to assess for associations of bronchiectasis with each outcome. A further binomial logistic regression model assessed for predictors of bronchiectasis diagnosis, including COPD. Those with alternative bronchiectasis causes were excluded from statistical models.

Results: 1290 patients were eligible. PiZZ patients with bronchiectasis were older at presentation (54 vs 49 years, p<0.001), less likely to have smoked (65 vs 76.1%, p = 0.001), and had higher mMRC scores (mMRC 2 vs 0 OR 1.97, 95% CI 1.20 - 3.25, p = 0.008; mMRC 3 vs 0 OR 2.58 95% CI 1.59 - 4.19, p<0.001; mMRC 4 vs 0 OR 2.2 95% CI 1.23 - 3.92; p=0.008) than those without. The odds ratio of bronchiectasis diagnosis was not associated with COPD diagnosis in any phenotype. Bronchiectasis was associated with lower serum alpha-1 antitrypsin levels in PiZZ patients (p = 0.012). Bronchiectasis was not associated with a difference in FEV1 pp/year decline, KCO pp/year, TLCO pp/year decline, or exacerbation rate in multivariate analysis.

Conclusion: Bronchiectasis exists in a significant minority of AATD patients independently of COPD, and is associated with more severe shortness of breath. Appropriate treatment of bronchiectasis in AATD is essential.

Keywords: COPD; alpha-1 antitrypsin deficiency; bronchiectasis.