Serum Alpha-1 Antitrypsin Levels and the Clinical Course of Chronic Obstructive Pulmonary Disease

Abstract

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 (<116 mg/dL, n = 66); middle group (116 to ≤141 mg/dL, n = 145); and higher 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

Acknowledgments

The authors would like to thank all of the Hokkaido COPD cohort study investigators (listed below) for patient recruitment and follow-up, as well as Hideka Ashikaga, Ayako Kondo, and Yuko Takagi of the Central Office of the Hokkaido COPD cohort study (Sapporo, Japan) and the staff of Exam Co., Ltd. (Sapporo, Japan) for data management. This study was supported by a scientific research grant from the Ministry of Education, Science, Culture and Sports of Japan; a grant to the Respiratory Failure Research Group from the Ministry of Health, Labor and Welfare, Japan; and from Boehringer Ingelheim, Pfizer, and AstraZeneca.

Abbreviations

COPD, chronic obstructive pulmonary disease; CRP, C-reactive protein; QOL, quality of life; GOLD, Global Initiative for Chronic Obstructive Lung Disease; CT, computed tomography; SGRQ, St. George’s Respiratory Questionnaire; FEV₁, forced expiratory volume in 1 s; FVC, forced vital capacity; ANOVA, one-way analysis of variance; BMI, body mass index; mMRC, modified Medical Research Council.

Author Contributions

NT and MS equally contributed to the acquisition and interpretation of data, statistical analysis, and drafting of the manuscript. SK, KS, Hiroki Kimura, and Hirokazu Kimura acquired and interpreted the data. HM and MN conceived of and designed the study, acquired and interpreted data, and finalized the manuscript. All authors made substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data; took part in drafting the article or revising it critically for important intellectual content; gave final approval of the version to be published; and agree to be accountable for all aspects of the work.

Disclosure

Masaru Suzuki has received research funding from GlaxoSmithKline, AstraZeneca, and Novartis. Masaharu Nishimura has received research funding from Boehringer Ingelheim, Pfizer, AstraZeneca, and Novartis. Nozomu Takei reports grants from Boehringer Ingelheim, grants from Pfizer, grants from AstraZeneca, grants from the Ministry of Education, Science, Culture and Sports of Japan, grants from the Respiratory Failure Research Group from the Ministry of Health, Labor and Welfare, Japan, during the conduct of the study. Satoshi Konno reports grants from Astra Zeneca, KYORIN Pharmaceutical Co. Ltd, Novartis, Japan Allergy Foundation, and the Ministry of Education, Culture, Sports, Science and Technology of Japan, during the conduct of the study. Hiroki Kimura report grants from MSD Life Science Foundation, Public Interest Incorporated Foundation, outside the submitted work. The authors report no other conflicts of interest in this work.