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 crossvalidated 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.T he diagnosis of invasive pulmonary aspergillosis (IA) in patients with prolonged chemotherapy-induced neutropenia (PCIN) remains a frequently occurring and difficult challenge (1-3). The signs and symptoms are nonspecific (4, 5). Mortality is high, especially in case of a diagnostic delay (3, 6, 7). The Platelia galactomannan assay (Bio-Rad) performed on bronchoalveolar lavage fluid samples is the only test with sufficient sensitivity and specificity to demonstrate or rule out IA (8). Its major drawback is the invasive and highly uncomfortable nature of bronchoalveolar lavage (9-13).The Platelia galactomannan assay was originally developed to be used on serum. Although diagnostic accuracy is significantly lower in this setting, it creates the opportunity to serially monitor patients who are at high risk, such as acute myeloid leukemia (AML) patients treated with intensive induction chemotherapy (14). This might enable earlier diagnosis and thus a better prognosis. This is the topic of a number of ongoing studies. Unfortunately, two already-published studies did not show that serial monitoring of galactomannan leads to an earlier diagnosis (15, 16). Previously, we showed that patients with PCIN and IA have a distinct exhaled breath profile that can be discriminated by an electronic nose (eNose) (17). Very recently, this was confirmed by using gas chromatography-mass spectrometry (GC-MS), dem...