Bronchiectasis but not emphysema is more prevalent in non-PiZ alpha-1 antitrypsin deficiency (AATD) COPD than in usual COPD

Abstract

Bronchiectasis (BE) is associated with PiZ phenotypes of AATD. An association with non-PiZ phenotypes (SS, MS, MZ) is less certain. We wished to conduct a case-control study of BE prevalence among SS, MS and MZ genotypes vs. usual COPD. 16 subjects with non-PiZ phenotypes (NZ) (3 SS, 8 MS, 5 MZ) from community COPD screening for AATD had undergone chest CT scans. They were compared with 16 age, sex and FEV₁ matched COPD patients with AAT levels<1.15g/L but MM genotype (MM) and 16 similarly matched COPD patients with serum AAT levels≥1.15g/L and not genotyped (NG). Spirometry, lung volumes and diffusing capacity (D_Lco) were measured within 5.9±5.2SD months of imaging. CT scans were read for BE using a visual grading system. Lung emphysema on CT scan was determined using Airway Inspector (www.airwayinspector.org) to measure lung %area<-950HU (LAA%). Group differences between continuous variables were determined with ANOVA and proportions with z-statistic. Gender was M30:F18, age 70±18 years (mean±SD), smoking history 47±26 pack-years, FEV₁ 68±23 %predicted and FEV₁/FVC 55±13 % in the 48 subjects. Serum AAT levels were NZ 0.89±0.01SE g/L, MM 0.90±0.05 and NG 1.59±0.07. BE on CT scan occurred in 13/16 NZ (3/3 SS, 6/8 MS, 4/5 MZ), 4/16 MM (p=0.00071) and 5/16 NG (p=0.00219). Groups were similar for spirometry, lung volumes and D_Lco. LAA% did not differ between groups (NZ 12.3±3.7SE, MM 12.0±2.7, NG 11.0±3.2, p=0.97). In this small group of COPD patients, BE was present more often in non-PiZ phenotype AATD subjects than MM genotype subjects, or COPD subjects with normal serum AAT levels. This may be a novel observation requiring confirmation in larger populations.