Serum Methylarginines and Spirometry-Measured Lung Function in Older Adults

Mark A Mcevoy,Wayne T Smith,John R Attia,Roy L Soiza,Arduino A Mangoni,Angelo Zinellu,Peter W Schofield,Roseanne Peel,Ciriaco Carru,Stephen J Hancock,Kingsley Agho,Manlio Vinciguerra

doi:10.1371/journal.pone.0058390

Abstract

RationaleMethylarginines are endogenous nitric oxide synthase inhibitors that have been implicated in animal models of lung disease but have not previously been examined for their association with spirometric measures of lung function in humans.ObjectivesThis study measured serum concentrations of asymmetric and symmetric dimethylarginine in a representative sample of older community-dwelling adults and determined their association with spirometric lung function measures.MethodsData on clinical, lifestyle, and demographic characteristics, methylated arginines, and L-arginine (measured using LC-MS/MS) were collected from a population-based sample of older Australian adults from the Hunter Community Study. The five key lung function measures included as outcomes were Forced Expiratory Volume in 1 second, Forced Vital Capacity, Forced Expiratory Volume in 1 second to Forced Vital Capacity ratio, Percent Predicted Forced Expiratory Volume in 1 second, and Percent Predicted Forced Vital Capacity.Measurements and Main ResultsIn adjusted analyses there were statistically significant independent associations between a) higher asymmetric dimethylarginine, lower Forced Expiratory Volume in 1 second and lower Forced Vital Capacity; and b) lower L-arginine/asymmetric dimethylarginine ratio, lower Forced Expiratory Volume in 1 second, lower Percent Predicted Forced Expiratory Volume in 1 second and lower Percent Predicted Forced Vital Capacity. By contrast, no significant associations were observed between symmetric dimethylarginine and lung function.ConclusionsAfter adjusting for clinical, demographic, biochemical, and pharmacological confounders, higher serum asymmetric dimethylarginine was independently associated with a reduction in key measures of lung function. Further research is needed to determine if methylarginines predict the decline in lung function.

Highlights

Lung health and obstructive lung disease (OLD) are considered health priorities in Australia and worldwide due to the significant burden of disease associated with a decline in lung function
After adjusting for clinical, demographic, biochemical, and pharmacological confounders, higher serum asymmetric dimethylarginine was independently associated with a reduction in key measures of lung function
Further research is needed to determine if methylarginines predict the decline in lung function

Summary

Introduction

Lung health and obstructive lung disease (OLD) are considered health priorities in Australia and worldwide due to the significant burden of disease associated with a decline in lung function. Agerelated decline in lung function is associated with increased risk of OLD [1] as well as cardiovascular [2] and all-cause mortality [3]. NO plays a major role in airway and vascular smooth muscle relaxation, ventilation perfusion matching, neurotransmission, mucociliary clearance, airway mucus secretion, and host defence [6]. It is involved in the pathophysiology of lung diseases including pulmonary hypertension, airway hyper-responsiveness (AHR), asthma, chronic obstructive pulmonary disease (COPD), and Cystic Fibrosis (CF) [6,7]

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