Serum Alpha-1 Antitrypsin Levels and the Clinical Course of Chronic Obstructive Pulmonary Disease
Received 1 August 2019
Accepted for publication 2 December 2019
Published 10 December 2019 Volume 2019:14 Pages 2885—2893
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 3
Editor who approved publication: Dr Richard Russell
Nozomu Takei,1,* Masaru Suzuki,1,* Hironi Makita,2 Satoshi Konno,1 Kaoruko Shimizu,1 Hiroki Kimura,1 Hirokazu Kimura,1 Masaharu Nishimura1,2
1Department of Respiratory Medicine, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan; 2Hokkaido Medical Research Institute for Respiratory Diseases, Sapporo, Japan
*These authors contributed equally to this work
Correspondence: Masaharu Nishimura
Department of Respiratory Medicine, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, North 15 West 7, Kita-ku, Sapporo 060-8638, Japan
Tel +81 11 706 5911
Fax +81 11 706 7899
Purpose: Alpha-1 antitrypsin deficiency is associated with the development of chronic obstructive pulmonary disease (COPD), whereas increased levels of serum alpha-1antitrypsin occur in response to inflammation. The effects of alpha-1 antitrypsin levels on the clinical course of COPD had been unclear. We investigated the association of serum alpha-1 antitrypsin levels with the clinical course of COPD patients based on data from a 10-year prospective cohort study.
Patients and methods: We analyzed 278 COPD patients who participated in the Hokkaido COPD cohort study and who did not meet the criteria for alpha-1 antitrypsin deficiency. We divided the subjects into 3 groups according to quartiles of serum alpha-1 antitrypsin levels at baseline: lower group (141 mg/dL, n = 67). The annual change in forced expiratory volume in 1 s (FEV1) and events of COPD exacerbation were monitored during the first 5 years, and mortality was followed-up during the entire 10 years.
Results: At baseline, the higher group showed lower body mass index; higher computed tomography emphysema score; lower diffusing capacity; higher levels of acute-phase proteins; and higher blood neutrophil counts. Longitudinal analyses revealed that in the higher group, the annual decline in FEV1 was rapid and the 10-year mortality was higher, but there was no association between serum alpha-1 antitrypsin levels and time to first exacerbation.
Conclusion: COPD subjects with higher serum alpha-1 antitrypsin levels were associated with a worse systemic inflammation status and higher 10-year mortality.
Keywords: chronic obstructive pulmonary disease, alpha-1 antitrypsin, inflammation, lung function decline, mortality