Asymmetric Dimethylarginine Predicts Long-Term Outcome in Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease

Aug 31, 2017Lung

Asymmetric Dimethylarginine Levels Predict Long-Term Outcome in Patients with Sudden Worsening of Chronic Lung Disease

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Abstract

Six-year all-cause mortality was 54% in patients with acute exacerbation of COPD.

Non-survivors had higher median admission levels of ADMA (0.60 vs. 0.46, p = 0.004) and SDMA (1.05 vs. 0.85, p = 0.012) compared to survivors.
Higher levels of ADMA were associated with long-term mortality, yielding an age- and comorbidity-adjusted hazard ratio of 4.55 (95% confidence interval 1.02-20.43, p = 0.048).
SDMA showed an association with mortality only in univariate models.
No association between L-arginine levels and outcomes was observed.

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INTRODUCTION: In chronic obstructive pulmonary disease (COPD), there is an activation of the L-arginine nitric oxide pathway. Pulmonary obstruction causes to elevated nitric oxide (NO) levels, which lead to higher production of the NO-inhibiting metabolites asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA).

METHODS: We investigated the association of L-arginine, ADMA, and SDMA with clinical outcomes in a well-defined observational cohort of 150 patients with acute exacerbation of COPD. We measured L-arginine, ADMA, and SDMA by mass spectrometry in patients with pneumonic or non-pneumonic exacerbation of COPD included in a Swiss multicenter trial. We used Cox regression models to investigate the associations between blood marker levels and disease severity as well as all-cause mortality over a follow-up of 6.1 years.

RESULTS: Six-year all-cause mortality was 54%. Admission levels of ADMA and SDMA (μmol L) were increased in 6-year non-survivors compared to survivors' median (0.60 vs. 0.46, p = 0.004; and 1.05 vs. 0.85, p = 0.012). In a multivariate Cox regression analysis, ADMA was associated with long-term mortality resulting in an age- and comorbidity-adjusted hazard ratio (HR) of 4.55 (95% confidence interval 1.02-20.43, p = 0.048). SDMA was only associated in univariate models and no association of L-arginine with outcome was found. -1

CONCLUSION: ADMA was found to be an independent risk factor for long-term all-cause mortality in patients with acute exacerbation of COPD. Whether therapeutic modification of the L-arginine-nitric oxide pathway has the potential to improve outcome should be evaluated in future interventional trials.

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Asymmetric Dimethylarginine Predicts Long-Term Outcome in Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease

Abstract

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