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

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.

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 (FEV₁) <80% of predicted and FEV₁/forced vital capacity (FVC) ratio <0.70; FEV₁, FVC and FEV₁/FVC as percentage of predicted; and inflammatory markers in blood (white blood cell count, eosinophils, neutrophils and C-reactive protein (CRP)).

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 log₁₀-transformed α-Klotho level was significantly associated with 5.0% higher FEV₁ % 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.

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.