Endogenous Adenosine 5'-Monophosphate, But Not Acetylcholine or Histamine, is Associated with Asthma Control, Quality of Life, and Exacerbations.

Abstract

Endogenous adenosine 5'-monophosphate (AMP), acetylcholine (ACh), and histamine (HA) are known to be important in bronchial contraction, but their clinical relevance to asthma is poorly understood. We aimed to quantify endogenous AMP, ACh, and HA in induced sputum samples and explore their relationships with asthma control and exacerbations. 20 healthy subjects and 112 asthmatics underwent clinical assessment, sputum induction, and blood sampling. The level of asthma control was determined by the asthma control test (ACT) questionnaire. Asthma exacerbation was evaluated according to the criteria of the American Thoracic Society/European Respiratory Society. Levels of AMP, ACh, and HA in sputum were measured by liquid chromatography coupled to tandem mass spectrometry. IL-β, IL-4, IL-5, IL-6, IL-8, IL-13, IL-17A, TNF-α, IFN-γ, and macrophage-derived chemokine (MDC) were also measured. Compared to healthy controls, asthmatics had higher levels of HA, lower levels of ACh, and similar levels of AMP in induced sputum samples. Compared to controlled asthma (n=54), uncontrolled asthma (n=58) showed higher AMP levels (P=0.002), but similar HA and ACh levels. AMP was negatively correlated with ACT scores (r=-0.348) and asthma quality of life questionnaire scores (r=-0.188) and positively correlated with blood monocytes percentage (r=0.195), sputum MDC (r=0.214), and IL-6 levels (r=0.196). Furthermore, AMP was associated with an increased risk of exacerbations in the preceding year. Endogenous AMP, but not ACh or HA, was associated with asthma control, quality of life, and exacerbations in the previous year, which indicates that AMP could be a clinically useful biomarker of asthma.