Increased Exacerbations of Chronic Obstructive Pulmonary Disease in Alpha-1 Antitrypsin Carriers

Abstract

Rationale: There is an increased incidence of alpha-1 antitrypsin deficiency carrier state in patients with chronic obstructive pulmonary disease, but the clinical relevance of a single pathogenic SERPINA1 allele needs investigation, with a limited understanding of clinical course in these patients.

Methods: A single-center cohort of 309 consecutive patients with chronic obstructive pulmonary disease and SERPINA1 genotype was assembled between 2011 and 2018. Frequent exacerbators were defined as patients with 2 or more exacerbations per year.

Results: 277 patients with the normal MM genotype were compared to 32 patients with an abnormal SERPINA1 genotype (20 MS and 12 MZ patients). There was no difference with regard to severity of chronic obstructive pulmonary disease determined by pulmonary function testing and Global Initiative for Chronic Obstructive Lung Disease stage between the groups. However, 35 of 277 MM patients (12.6%) were frequent exacerbators, compared to 8 of 20 patients with MS (40%) and 6 of 12 patients with MZ (50%), p<0.001. MM patients had 0.79±1.33 exacerbations per year compared to 1.37±1.13 in MS and 2.31±3.30 in MZ patients (p< 0.001).

Conclusions: MS and MZ patients are phenotypically different than patients with MM with more frequent exacerbations of chronic obstructive pulmonary disease despite similar disease stage and degree of obstruction based on spirometry. These results emphasize the importance of genetic testing in patients with chronic obstructive pulmonary disease as a method to determine disease phenotype as well as the potential for abnormal SERPINA1 alleles to independently cause manifestations of disease progression.