title: Detection of Airway Colonization by Aspergillus fumigatus by Use of Electronic Nose Technology in Patients with Cystic Fibrosis.
abstract: Currently, there is no noninvasive test that can reliably diagnose early invasive pulmonary aspergillosis (IA). An electronic nose (eNose) can discriminate various lung diseases through an analysis of exhaled volatile organic compounds. We recently published a proof-of-principle study showing that patients with prolonged chemotherapy-induced neutropenia and IA have a distinct exhaled breath profile (or breathprint) that can be discriminated with an eNose. An eNose is cheap and noninvasive, and it yields results within minutes. We determined whether Aspergillus fumigatus colonization may also be detected with an eNose in cystic fibrosis (CF) patients. Exhaled breath samples of 27 CF patients were analyzed with a Cyranose 320. Culture of sputum samples defined the A. fumigatus colonization status. eNose data were classified using canonical discriminant analysis after principal component reduction. Our primary outcome was cross-validated accuracy, defined as the percentage of correctly classified subjects using the leave-one-out method. The P value was calculated by the generation of 100,000 random alternative classifications. Nine of the 27 subjects were colonized by A. fumigatus. In total, 3 subjects were misclassified, resulting in a cross-validated accuracy of the Cyranose detecting IA of 89% (P = 0.004; sensitivity, 78%; specificity, 94%). Receiver operating characteristic (ROC) curve analysis showed an area under the curve (AUC) of 0.89. The results indicate that A. fumigatus colonization leads to a distinctive breathprint in CF patients. The present proof-of-concept data merit external validation and monitoring studies.
authors.affiliation: Department of Hematology, Academic Medical Center, Amsterdam, the Netherlands koen@de-heer.eu.
authors.forename: K
authors.initials: K
authors.lastname: de Heer
authors.affiliation: Department of Hematology, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: M G M
authors.initials: MG
authors.lastname: Kok
authors.affiliation: Department of Respiratory Medicine, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: N
authors.initials: N
authors.lastname: Fens
authors.affiliation: Department of Respiratory Medicine, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: E J M
authors.initials: EJ
authors.lastname: Weersink
authors.affiliation: Department of Clinical Epidemiology, Biostatistics, and Bioinformatics, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: A H
authors.initials: AH
authors.lastname: Zwinderman
authors.affiliation: Department of Respiratory Medicine, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: M P C
authors.initials: MP
authors.lastname: van der Schee
authors.affiliation: Department of Medical Microbiology, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: C E
authors.initials: CE
authors.lastname: Visser
authors.affiliation: Department of Hematology, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: M H J
authors.initials: MH
authors.lastname: van Oers
authors.affiliation: Department of Respiratory Medicine, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: P J
authors.initials: PJ
authors.lastname: Sterk
mesh_terms: D000293:Adolescent; D000328:Adult; D001232:Aspergillus fumigatus / Q000302:isolation & purification*; D001944:Breath Tests / Q000379:methods*; D003550:Cystic Fibrosis / Q000150:complications*; D042241:Early Diagnosis; D062609:Electronic Nose; D005260:Female; D006801:Humans; D055744:Invasive Pulmonary Aspergillosis / Q000175:diagnosis* / Q000382:microbiology; D008297:Male; D008875:Middle Aged; D012372:ROC Curve; D012680:Sensitivity and Specificity; D055815:Young Adult