The Relationship Between Blood Eosinophils and Outcomes in Alpha-1 Antitrypsin Deficiency

Abstract

Background: Alpha-1 antitrypsin deficiency (AATD) is an inherited cause of early emphysema and chronic lung disease. Whether blood eosinophil counts predict outcomes in AATD remains uncertain. Methods: I conducted a retrospective cohort study using the UK AATD Registry, including 401 adults with chronic lung disease and baseline eosinophil counts. Outcomes were annual exacerbation frequency and all-cause mortality, analysed with regression models adjusted for demographic factors, AATD phenotype, smoking, and major respiratory comorbidities. Eosinophil thresholds were evaluated at ≥0.2×10⁹/L (primary), ≥0.3×10⁹/L, and <0.1×10⁹/L as a secondary analysis. Sensitivity analyses incorporated multiple imputation (N=482) and models including FEV₁ decline. Results: At thresholds of ≥0.2×10⁹/L and ≥0.3×10⁹/L, eosinophils showed no significant association with exacerbation frequency or mortality. However, very low counts (<0.1×10⁹/L) were associated with higher mortality risk. Prognostic factors independent of eosinophils included older age (fewer exacerbations but greater mortality risk), bronchiectasis (increased exacerbations), cumulative smoking exposure (higher mortality), and accelerated FEV₁ decline (mortality only). Findings were unchanged after imputation. Conclusions: In AATD, baseline blood eosinophil levels (≥0.2×10⁹/L and ≥0.3×10⁹/L) do not predict exacerbation burden or survival. Very low eosinophils (<0.1×10⁹/L) may indicate higher mortality risk. Prognosis is more related to age, smoking exposure, bronchiectasis, and FEV₁ decline than eosinophil levels, suggesting that COPD eosinophil thresholds are not applicable for risk stratification or treatment in AATD.