Lower leptin/adiponectin ratio and risk of rapid lung function decline in chronic obstructive pulmonary disease.
BACKGROUND
The rate of annual change in FEV1 is highly variable among patients with chronic obstructive pulmonary disease (COPD). Reliable blood biomarkers are needed to predict prognosis.


OBJECTIVE
To explore plasma biomarkers associated with an annual change in FEV1 in patients with COPD.


METHODS
Plasma samples of 261 subjects, all Japanese, with COPD from the 5-year Hokkaido COPD cohort study were analyzed as a hypothesis-generating cohort, and the results were validated using data of 226 subjects with and 268 subjects without airflow limitation, mainly white, from the 4-year COPD Quantification by Computed Tomography, Biomarkers, and Quality of Life (CBQ) study conducted in Denmark. The plasma samples were measured using Human CardiovascularMAP (Myriad RBM, Austin, TX), which could analyze 50 biomarkers potentially linked with inflammatory, metabolic, and tissue remodeling pathways, and single ELISAs were used to confirm the results.


RESULTS
Higher plasma adiponectin levels and a lower leptin/adiponectin ratio at enrollment were significantly associated with an annual decline in FEV1 even after controlling for age, sex, height, and body mass index in the Hokkaido COPD cohort study (P = 0.003, P = 0.004, respectively). A lower plasma leptin/adiponectin ratio was also significantly associated with an annual decline in FEV1 in subjects with airflow limitation in the CBQ study (P = 0.014), the patients of which had largely different clinical characteristics compared with the Hokkaido COPD cohort study. There were no significant associations between lung function decline and adipokine levels in subjects without airflow limitation.


CONCLUSIONS
A lower leptin/adiponectin ratio was associated with lung function decline in patients with COPD in two independent Japanese and Western cohort studies of populations of different ethnicity. Measure of systemic adipokines may provide utility in predicting patients with COPD at higher risk of lung function decline.
1 First Department of Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
Masaru
M
Suzuki
Hironi
H
Makita
Jörgen
J
Östling
Laura H
LH
Thomsen
Satoshi
S
Konno
Katsura
K
Nagai
Kaoruko
K
Shimizu
Jesper H
JH
Pedersen
Haseem
H
Ashraf
Piet L B
PL
Bruijnzeel
Rose A
RA
Maciewicz
Masaharu
M
Nishimura
D052242:Adiponectin / Q000097:blood*; D000368:Aged; D015415:Biomarkers / Q000097:blood; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D005541:Forced Expiratory Volume; D006801:Humans; D020738:Leptin / Q000097:blood*; D008297:Male; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood / Q000175:diagnosis / Q000503:physiopathology*; D012307:Risk Factors; D012720:Severity of Illness Index; D014057:Tomography, X-Ray Computed
D052242:Adiponectin; D015415:Biomarkers; D020738:Leptin
adipokines; biological markers; cohort studies