Novel tests for diagnosis of invasive aspergillosis in patients with underlying respiratory diseases

Am J Respir Crit Care Med. 2014 Oct 15;190(8):922-9. doi: 10.1164/rccm.201407-1275OC.

Abstract

Rationale: Invasive pulmonary aspergillosis has been increasingly reported in nonneutropenic patients, including those with underlying respiratory diseases.

Objectives: 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.

Measurements and main 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).

Trial registration: ClinicalTrials.gov NCT02058316.

Keywords: 1,3-β-D-glucan; Aspergillus lateral-flow device test; bronchoalveolar lavage; galactomannan; mycological culture.

Publication types

  • Clinical Trial
  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal*
  • Antigens, Fungal / analysis
  • Aspergillus / immunology
  • Aspergillus / isolation & purification*
  • Bronchoalveolar Lavage Fluid / microbiology*
  • Cell Culture Techniques
  • Female
  • Humans
  • Invasive Pulmonary Aspergillosis / complications
  • Invasive Pulmonary Aspergillosis / diagnosis*
  • Invasive Pulmonary Aspergillosis / microbiology
  • Male
  • Mannans*
  • Middle Aged
  • Point-of-Care Systems*
  • Prospective Studies
  • Respiratory Tract Diseases / complications
  • Retrospective Studies
  • Sensitivity and Specificity
  • Young Adult
  • beta-Glucans*

Substances

  • Antibodies, Monoclonal
  • Antigens, Fungal
  • Mannans
  • beta-1,3-D-glucan
  • beta-Glucans
  • galactomannan

Associated data

  • ClinicalTrials.gov/NCT02058316