Serum α-Klotho level, lung function, airflow obstruction and inflammatory markers in US adults

BACKGROUND: α-Klotho is a pleiotropic protein that may have anti-oxidative and anti-inflammatory properties in the lung, but its role in airflow obstruction or lung function is largely unknown. METHODS: This was a cross-sectional study of 6046 adults aged 40–79 years in the US National Health and Nutrition Examination Survey (NHANES) 2007–2012. We used multivariable logistic or linear regression to examine the relation between serum α-Klotho level and airflow obstruction, defined as forced expiratory volume in 1 s (FEV(1)) <80% of predicted and FEV(1)/forced vital capacity (FVC) ratio <0.70; FEV(1), FVC and FEV(1)/FVC as percentage of predicted; and inflammatory markers in blood (white blood cell count, eosinophils, neutrophils and C-reactive protein (CRP)). RESULTS: α-Klotho levels in the second to fourth quartiles (Q2–Q4) were associated with significantly decreased odds of airflow obstruction (adjusted OR for Q2–Q4 versus lowest quartile (Q1) 0.54 (95% CI 0.35–0.81)) in never-smokers and ex-smokers with <10 pack-years of smoking, but not in current smokers or ex-smokers with ≥10 pack-years of smoking. In all participants, each unit increment in log(10)-transformed α-Klotho level was significantly associated with 5.0% higher FEV(1) % pred and 3.7% higher FVC % pred. Higher α-Klotho was also associated with lower eosinophils, neutrophils and CRP in participants both with and without airflow obstruction. CONCLUSIONS: Higher serum α-Klotho is associated with lower inflammatory markers and higher lung function in adults with and without airflow obstruction, and with decreased odds of airflow obstruction in never-smokers and ex-smokers with <10 pack-years of smoking. Further studies are warranted to replicate our findings and evaluate underlying mechanisms.