Elevated Airway Purines in COPD

Abstract

Purinergic signaling pathways regulate airways defense mechanisms, including mucociliary clearance and infl ammatory responses. These pathways are activated by extracellular purines, which include adenosine triphosphate (ATP) and its metabolites adenosine diphosphate, adenosine monophosphate (AMP), and adenosine. Adenosine, in particular, has been linked to infl ammatory airways diseases, 1 including twofold to fourfold elevations in blood 2,3 and BAL fl uid 4 of subjects with asthma. Similarly, adenosine concentrations in exhaled breath condensate (EBC) are elevated in subjects with stable asthma, 5,6 increased with asthma exacerbations, 7 and decreased with successful treatment. Findings from animal models, particularly the adenosine deaminase knockout mouse, 8,9 further support a link between airway infl ammation and lung adenosine.These data suggest that purinergic signaling pathways may be active in infl ammatory lung diseases such as COPD and may be targets for therapeutic intervention. 10 Indeed, elevated airway adenosine concentrations in COPD have been inferred from studies of human airway adenosine receptors, 11 and several reviews have touted potential benefi ts of pharmacologic blockade of adenosine receptors. 10,12 Although these benefi ts are a reasonable extrapolation from the animal 8,13 and human studies, 4,5 a recent investigation suggested that airway adenosine concentrations (as measured in sputum) may actually be lower in COPD. 14 However, adenosine concentrations in respiratory samples such as sputum or BAL can be altered unpredictably by extracellular metabolism during processing or by mechanical and osmotic forces that trigger purine release during collection.

Metabolomic Evaluation of Neutrophilic Airway Inflammation in Cystic Fibrosis

“…MS methods similar to those used in this study have been used to assess EBC as a noninvasive airway sample. 14,20,38 However, although biomarkers such as AMP function similarly in BALF and EBC, 4,38 the relationships between infl ammation and adenosine and phenylalanine in the current study diff er from previous observations in EBC. 14,20,38 Th us, EBC and BALF may diff er in the metabolites that function optimally as biomarkers, perhaps refl ecting diff erent sites of origin of the airway secretions, 39,40 and further study will be needed to identify the most eff ective metabolomic biomarkers for noninvasive detection.…”

“…Chromatographic conditions similar to those of the metabolomics (UPLC BEH C18 column, acetonitrile/formic acid gradients) and previous work (UPLC T3 HSS C18 column, methanol/formic acid gradients 13 ) were explored, with the T3 column judged superior and used for validation. Validation BALF samples were spiked with isotopically labeled internal standard 14 and were fi ltered through a 10-kDa-size selection fi lter (EMD Millipore). Biomarker signals were defi ned as ratios to the internal standard with the closest column run time.…”

The Relationship of Mucus Concentration (Hydration) to Mucus Osmotic Pressure and Transport in Chronic Bronchitis

“…However, these results differed from our exhaled breath condensate (EBC) data from subjects with COPD that showed raised ADO levels (49). Induced sputum is believed to originate from large airways, whereas EBC is thought to originate from the small airways of the peripheral lung (25,50,51).…”

Aberrant Circulating Levels of Purinergic Signaling Markers Are Associated With Several Key Aspects of Peripheral Atherosclerosis and Thrombosis

“…24,25 It is also well-documented from lung tissue and bronchial fluid samples that purinergic markers, especially CD73, are elevated in the presence of COPD and hypoxia, 26,27 and in in vivo animal studies demonstrating the effects of CD73 in hypoxia transduction. 17 In the present study, the same effects were observed in blood samples from patients with PAD.…”