title: Novel tests for diagnosis of invasive aspergillosis in patients with underlying respiratory diseases.
abstract: BACKGROUND
  Invasive pulmonary aspergillosis has been increasingly reported in nonneutropenic patients, including those with underlying respiratory diseases.
  
  
  OBJECTIVE
  We compared the diagnostic performances of galactomannan, 1,3-β-D-glucan, and Aspergillus-specific lateral-flow device tests with that of conventional culture by using bronchoalveolar lavage fluid samples from patients with underlying respiratory diseases.
  
  
  METHODS
  We analyzed 268 bronchoalveolar lavage samples from 221 patients with underlying respiratory diseases (and without hematologic malignancy or previous solid organ transplantation) that were collected for routine microbiological workup between February 2012 and May 2014 at the University Hospital of Graz, Austria. Invasive pulmonary aspergillosis was defined according to European Organization of Research and Treatment of Cancer/Mycoses Study Group criteria modified for patients with respiratory diseases.
  
  
  RESULTS
  Thirty-one patients (14%) had probable or proven, 25 possible, and the remaining 165 patients no invasive pulmonary aspergillosis. Probable/proven aspergillosis was associated with a significantly higher (P = 0.034) 30-day mortality rate of 32%. Sensitivities, specificities, and diagnostic odd ratios differed markedly between galactomannan (cut-off 0.5: optical density index, 0.97, 0.81, 124.4; cut-off 1.0: 0.97, 0.93, 422.1; cut-off 3.0: 0.61, 0.99, 109.8), β-D-glucan (cut-off 80 pg/ml: 0.90, 0.42, 6.57; cut-off 200 pg/ml: 0.70, 0.61, 3.7), lateral-flow device tests (0.77, 0.92, 41.8), and mycological culture (0.29, 0.97, 14).
  
  
  CONCLUSIONS
  Probable or proven invasive pulmonary aspergillosis was diagnosed in 14% of our study population and associated with significantly higher 30-day mortality rates. Although the performance of β-D-glucan was limited by low specificity and that of mycological culture by low sensitivity, the Aspergillus lateral-flow device seems to be a promising alternative to galactomannan testing, which remains the diagnostic gold standard for aspergillosis. Clinical trial registered with www.clinicaltrials.gov (NCT 02058316).
authors.affiliation: 1 Section of Infectious Diseases and Tropical Medicine and.
authors.forename: Juergen
authors.initials: J
authors.lastname: Prattes
authors.forename: Holger
authors.initials: H
authors.lastname: Flick
authors.forename: Florian
authors.initials: F
authors.lastname: Prüller
authors.forename: Christoph
authors.initials: C
authors.lastname: Koidl
authors.forename: Reinhard B
authors.initials: RB
authors.lastname: Raggam
authors.forename: Michael
authors.initials: M
authors.lastname: Palfner
authors.forename: Susanne
authors.initials: S
authors.lastname: Eigl
authors.forename: Walter
authors.initials: W
authors.lastname: Buzina
authors.forename: Ines
authors.initials: I
authors.lastname: Zollner-Schwetz
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Thornton
authors.forename: Robert
authors.initials: R
authors.lastname: Krause
authors.forename: Martin
authors.initials: M
authors.lastname: Hoenigl
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal; D000946:Antigens, Fungal / Q000032:analysis; D001230:Aspergillus / Q000276:immunology / Q000302:isolation & purification*; D001992:Bronchoalveolar Lavage Fluid / Q000382:microbiology*; D018929:Cell Culture Techniques; D005260:Female; D005690:Galactose / Q000031:analogs & derivatives; D006801:Humans; D055744:Invasive Pulmonary Aspergillosis / Q000150:complications / Q000175:diagnosis* / Q000382:microbiology; D008297:Male; D008351:Mannans; D008875:Middle Aged; D019095:Point-of-Care Systems; D011446:Prospective Studies; D011509:Proteoglycans; D012140:Respiratory Tract Diseases / Q000150:complications; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D055815:Young Adult; D047071:beta-Glucans
chemical_list: D000911:Antibodies, Monoclonal; D000946:Antigens, Fungal; D008351:Mannans; D011509:Proteoglycans; D047071:beta-Glucans; C012990:galactomannan; C010770:polysaccharide-K; D005690:Galactose
keywords: 1,3-β-D-glucan; Aspergillus lateral-flow device test; bronchoalveolar lavage; galactomannan; mycological culture