Relationship between urinary tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and lung function: Evidence from NHANES 2007-2012.

INTRODUCTION: 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), a metabolite of tobacco-specific nitrosamine (TSNA) 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), is a tobacco-specific carcinogen. Spirometry values (FEV1%, PEF%, etc.) are commonly used as clinical indicators to assess the condition of lung function and the results can be used to diagnose respiratory diseases. However, the relationship between urinary NNAL levels and lung function is unclear. METHODS: We performed a secondary dataset analysis of the three cycles of the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2012. The association of urinary NNAL with spirometry values was assessed using weighted linear models. In addition, subgroup analyses by gender were also tested. RESULTS: One unit increased in urinary NNAL could result in a 28% decrease of FEV1/FVC% (mean difference, MD= -0.28; 95% CI: -0.39 - -0.17), 44% decrease of FEV1% (MD= -0.44; 95% CI: -0.69 - -0.18), and FEV1/FEV6% and FEV3/FEV6% decreased by 20% and 8%, respectively. Increased urinary NNAL was associated with lower PEF% (MD= -0.85; 95% CI: -1.19 - -0.51), FEF25-75% (MD= -1.40; 95% CI: -1.94 - -0.87), and FENO (MD= -0.67; 95% CI: -0.92 - -0.42). But forced expiratory time (FET) showed an increment (MD=0.10; 95% CI: 0.03-0.16). The FEV1/FEV6% and FEV3/FEV6% showed decreasing trend from the lowest urinary NNAL quartiles to the highest urinary NNAL quartiles, while FET showed an increased trend. PEF%, FEF 25-75%, and FENO showed the same decreasing trend (all p<0.05). In addition, urinary NNAL seemed to affect spirometry values more in males. CONCLUSIONS: Urinary NNAL was negatively correlated with FEV1/FVC%, FEV1%, FEV1/FEV6%, FEV3/FEV6%, PEF%, FEF25-75%, and FENO, which was closely related to lung function.