Comparison of Ambient and Atmospheric Pressure Ion Sources for Cystic Fibrosis Exhaled Breath Condensate Ion Mobility-Mass Spectrometry Metabolomics

Exhaled breath condensate (EBC) analyses promise simple and noninvasive methods to measure airway biomarkers but pose considerable methodological challenges. We utilized mass spectrometry to measure EBC purine biomarkers adenosine and AMP plus urea to control for dilutional variability in two studies: 1) a cross-sectional analysis of 28 healthy, 40 cystic fibrosis (CF), and 11 asthmatic children; and 2) a longitudinal analysis of 26 CF children before and after treatment of a pulmonary exacerbation. EBC adenosine, AMP, and urea were readily detected and quantified by mass spectrometry, and analysis suggested significant dilutional variability. Using biomarker-to-urea ratios to control for dilution, the EBC AMP-to-urea ratio was elevated in CF [median 1.3, interquartile range (IQR) 0.7–2.3] vs. control (median 0.75, IQR 0.3–1.4; P < 0.05), and the adenosine-to-urea ratio was elevated in asthma (median 1.5, IQR 0.9–2.9) vs. control (median 0.4, IQR 0.2–1.6; P < 0.05). Changes in EBC purine-to-urea ratios correlated with changes in percent predicted forced expiratory volume in 1 s (FEV1) ( r = −0.53 AMP/urea, r = −0.55 adenosine/urea; P < 0.01 for both) after CF exacerbation treatment. Similar results were observed using dilution factors calculated from serum-to-EBC urea ratios or EBC electrolytes, and the comparable ratios of EBC electrolytes to urea in CF and control (median 3.2, IQR 1.6–6.0 CF; median 5.5, IQR 1.4–7.7 control) validated use of airway urea as an EBC dilution marker. These results show that mass spectrometric analyses can be applied to measurement of purines in EBC and demonstrate that EBC adenosine-to-urea and AMP-to-urea ratios are potential noninvasive biomarkers of airways disease.

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Exhaled Breath Condensate Detects Baseline Reductions in Chloride and Increases in Response to Albuterol in Cystic Fibrosis Patients

Clinical Medicine Insights Circulatory Respiratory and Pulmonary Medicine ◽

10.4137/ccrpm.s12882 ◽

2013 ◽

Vol 7 ◽

pp. CCRPM.S12882 ◽

Cited By ~ 2

Author(s):

Courtney M. Wheatley ◽

Wayne J. Morgan ◽

Nicholas A. Cassuto ◽

William T. Foxx-Lupo ◽

Cori L. Daines ◽

...

Keyword(s):

Cystic Fibrosis ◽

Exhaled Breath Condensate ◽

Ionic Composition ◽

Membrane Conductance ◽

Pharmacological Therapy ◽

Exhaled Breath ◽

Ion Regulation ◽

Capillary Blood Volume ◽

Pulmonary Capillary Blood ◽

Breath Condensate

Impaired ion regulation and dehydration is the primary pathophysiology in cystic fibrosis (CF) lung disease. A potential application of exhaled breath condensate (EBC) collection is to assess airway surface liquid ionic composition at baseline and in response to pharmacological therapy in CF. Our aims were to determine if EBC could detect differences in ion regulation between CF and healthy and measure the effect of the albuterol on EBC ions in these populations. Baseline EBC Cl−, DLCO and SpO2 were lower in CF (n = 16) compared to healthy participants (n = 16). EBC Cl− increased in CF subjects, while there was no change in DLCO or membrane conductance, but a decrease in pulmonary-capillary blood volume in both groups following albuterol. This resulted in an improvement in diffusion at the alveolar-capillary unit, and removal of the baseline difference in SpO2 by 90-minutes in CF subjects. These results demonstrate that EBC detects differences in ion regulation between healthy and CF individuals, and that albuterol mediates increases in Cl− in CF, suggesting that the benefits of albuterol extend beyond simple bronchodilation.

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Feasibility of Early Detection of Cystic Fibrosis Acute Pulmonary Exacerbations by Exhaled Breath Condensate Metabolomics: A Pilot Study

Journal of Proteome Research ◽

10.1021/acs.jproteome.6b00675 ◽

2016 ◽

Vol 16 (2) ◽

pp. 550-558 ◽

Cited By ~ 19

Author(s):

Xiaoling Zang ◽

María Eugenia Monge ◽

Nael A. McCarty ◽

Arlene A. Stecenko ◽

Facundo M. Fernández

Keyword(s):

Cystic Fibrosis ◽

Pilot Study ◽

Early Detection ◽

Exhaled Breath Condensate ◽

Exhaled Breath ◽

Pulmonary Exacerbations ◽

Breath Condensate

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Sub-nanoliter metabolomics via mass spectrometry to characterize volume-limited samples

Nature Communications ◽

10.1038/s41467-020-19444-y ◽

2020 ◽

Vol 11 (1) ◽

Cited By ~ 2

Author(s):

Yafeng Li ◽

Marcos Bouza ◽

Changsheng Wu ◽

Hengyu Guo ◽

Danning Huang ◽

...

Keyword(s):

Mass Spectrometry ◽

Stromal Cells ◽

Exhaled Breath Condensate ◽

Sample Volume ◽

Triboelectric Nanogenerator ◽

Exhaled Breath ◽

Nanoelectrospray Ionization ◽

External Stimuli ◽

Breath Condensate

Abstract The human metabolome provides a window into the mechanisms and biomarkers of various diseases. However, because of limited availability, many sample types are still difficult to study by metabolomic analyses. Here, we present a mass spectrometry (MS)-based metabolomics strategy that only consumes sub-nanoliter sample volumes. The approach consists of combining a customized metabolomics workflow with a pulsed MS ion generation method, known as triboelectric nanogenerator inductive nanoelectrospray ionization (TENGi nanoESI) MS. Samples tested with this approach include exhaled breath condensate collected from cystic fibrosis patients as well as in vitro-cultured human mesenchymal stromal cells. Both test samples are only available in minimum amounts. Experiments show that picoliter-volume spray pulses suffice to generate high-quality spectral fingerprints, which increase the information density produced per unit sample volume. This TENGi nanoESI strategy has the potential to fill in the gap in metabolomics where liquid chromatography-MS-based analyses cannot be applied. Our method opens up avenues for future investigations into understanding metabolic changes caused by diseases or external stimuli.

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