title: Comparison of Ambient and Atmospheric Pressure Ion Sources for Cystic Fibrosis Exhaled Breath Condensate Ion Mobility-Mass Spectrometry Metabolomics.
abstract: Cystic fibrosis (CF) is an autosomal recessive disorder caused by mutations in the gene that encodes the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The vast majority of the mortality is due to progressive lung disease. Targeted and untargeted CF breath metabolomics investigations via exhaled breath condensate (EBC) analyses have the potential to expose metabolic alterations associated with CF pathology and aid in assessing the effectiveness of CF therapies. Here, transmission-mode direct analysis in real time traveling wave ion mobility spectrometry time-of-flight mass spectrometry (TM-DART-TWIMS-TOF MS) was tested as a high-throughput alternative to conventional direct infusion (DI) electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI) methods, and a critical comparison of the three ionization methods was conducted. EBC was chosen as the noninvasive surrogate for airway sampling over expectorated sputum as EBC can be collected in all CF subjects regardless of age and lung disease severity. When using pooled EBC collected from a healthy control, ESI detected the most metabolites, APCI a log order less, and TM-DART the least. TM-DART-TWIMS-TOF MS was used to profile metabolites in EBC samples from five healthy controls and four CF patients, finding that a panel of three discriminant EBC metabolites, some of which had been previously detected by other methods, differentiated these two classes with excellent cross-validated accuracy. Graphical Abstract ᅟ.
authors.affiliation: School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA, 30332, USA.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Zang
authors.affiliation: School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA, 30332, USA.
authors.forename: José J
authors.initials: JJ
authors.lastname: Pérez
authors.affiliation: School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA, 30332, USA.|National Institute of Standards and Technology, Chemical Science Division, Hollings Marine Laboratory, 331 Fort Johnson Road, Charleston, SC, 29412, USA.
authors.forename: Christina M
authors.initials: CM
authors.lastname: Jones
authors.affiliation: School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA, 30332, USA.|Centro de Investigaciones en Bionanociencias (CIBION), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Godoy Cruz 2390, C1425FQD, Ciudad de Buenos Aires, Argentina.
authors.forename: María Eugenia
authors.initials: ME
authors.lastname: Monge
authors.affiliation: Emory+Children's Center for Cystic Fibrosis and Airways Disease Research and Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA, 30322, USA.|Institute of Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, GA, 30332, USA.
authors.forename: Nael A
authors.initials: NA
authors.lastname: McCarty
authors.affiliation: Emory+Children's Center for Cystic Fibrosis and Airways Disease Research and Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA, 30322, USA.
authors.forename: Arlene A
authors.initials: AA
authors.lastname: Stecenko
authors.affiliation: School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA, 30332, USA. facundo.fernandez@chemistry.gatech.edu.|Institute of Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, GA, 30332, USA. facundo.fernandez@chemistry.gatech.edu.
authors.forename: Facundo M
authors.initials: FM
authors.lastname: Fernández
mesh_terms: D001274:Atmospheric Pressure; D001944:Breath Tests / Q000379:methods*; D003550:Cystic Fibrosis / Q000175:diagnosis* / Q000378:metabolism; D045853:Exhalation; D006801:Humans; D000075663:Ion Mobility Spectrometry / Q000379:methods; D013058:Mass Spectrometry / Q000379:methods; D055432:Metabolomics / Q000379:methods*; D015999:Multivariate Analysis
keywords: Breath metabolomics; Cystic fibrosis; Exhaled breath condensate; Transmission mode direct analysis in real time; Traveling wave ion mobility spectrometry-mass spectrometry