Feasibility of Early Detection of Cystic Fibrosis Acute Pulmonary Exacerbations by Exhaled Breath Condensate Metabolomics: A Pilot Study.
Progressive lung function decline and, ultimately, respiratory failure are the most common cause of death in patients with cystic fibrosis (CF). This decline is punctuated by acute pulmonary exacerbations (APEs), and in many cases, there is a failure to return to baseline lung function. Ultraperformance liquid chromatography quadrupole-time-of-flight mass spectrometry was used to profile metabolites in exhaled breath condensate (EBC) samples from 17 clinically stable CF patients, 9 CF patients with an APE severe enough to require hospitalization (termed APE), 5 CF patients during recovery from a severe APE (termed post-APE), and 4 CF patients who were clinically stable at the time of collection but in the subsequent 1-3 months developed a severe APE (termed pre-APE). A panel containing two metabolic discriminant features, 4-hydroxycyclohexylcarboxylic acid and pyroglutamic acid, differentiated the APE samples from the stable CF samples with 84.6% accuracy. Pre-APE samples were distinguished from stable CF samples by lactic acid and pyroglutamic acid with 90.5% accuracy and in general matched the APE signature when projected onto the APE vs stable CF model. Post-APE samples were on average more similar to stable CF samples in terms of their metabolomic signature. These results show the feasibility of detecting and predicting an oncoming APE or monitoring APE treatment using EBC metabolites.
School of Chemistry and Biochemistry, Georgia Institute of Technology , Atlanta, Georgia 30332, United States.
Xiaoling
X
Zang
School of Chemistry and Biochemistry, Georgia Institute of Technology , Atlanta, Georgia 30332, United States.|Centro de Investigaciones en Bionanociencias (CIBION), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) , Godoy Cruz 2390, C1425FQD, Ciudad de Buenos Aires, Argentina.
María Eugenia
ME
Monge
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, Georgia 30322, United States.
Nael A
NA
McCarty
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, Georgia 30322, United States.
Arlene A
AA
Stecenko
School of Chemistry and Biochemistry, Georgia Institute of Technology , Atlanta, Georgia 30332, United States.
Facundo M
0000-0002-0302-2534
FM
Fernández
D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D001944:Breath Tests; D002853:Chromatography, Liquid; D003510:Cyclohexanes / Q000378:metabolism*; D003550:Cystic Fibrosis / Q000175:diagnosis* / Q000378:metabolism* / Q000503:physiopathology; D042241:Early Diagnosis; D045853:Exhalation; D005260:Female; D006801:Humans; D019344:Lactic Acid / Q000378:metabolism*; D008297:Male; D013058:Mass Spectrometry; D055432:Metabolomics / Q000379:methods*; D010865:Pilot Projects; D011761:Pyrrolidonecarboxylic Acid / Q000378:metabolism*; D012720:Severity of Illness Index
D015415:Biomarkers; D003510:Cyclohexanes; D019344:Lactic Acid; D011761:Pyrrolidonecarboxylic Acid
acute pulmonary exacerbations; cystic fibrosis; metabolomics; ultraperformance liquid chromatography mass spectrometry