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Reinwald, Mark; Spiess, Birgit; Heinz, Werner J.; Vehreschild, Jörg J.; Lass‐Flörl, Cornelia; Kiehl, Michael; Schultheis, Beate; Krause, Stefan W.; Wolf, Hans‐Heinrich; Bertz, Hartmut; Maschmeyer, Georg; Hofmann, Wolf‐Karsten; Buchheidt, Dieter

Diagnosing pulmonary aspergillosis in patients with hematological malignancies: a multicenter prospective evaluation of an Aspergillus PCR assay and a galactomannan ELISA in bronchoalveolar lavage samples

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  • Media type: E-Article
  • Title: Diagnosing pulmonary aspergillosis in patients with hematological malignancies: a multicenter prospective evaluation of an Aspergillus PCR assay and a galactomannan ELISA in bronchoalveolar lavage samples
  • Contributor: Reinwald, Mark; Spiess, Birgit; Heinz, Werner J.; Vehreschild, Jörg J.; Lass‐Flörl, Cornelia; Kiehl, Michael; Schultheis, Beate; Krause, Stefan W.; Wolf, Hans‐Heinrich; Bertz, Hartmut; Maschmeyer, Georg; Hofmann, Wolf‐Karsten; Buchheidt, Dieter
  • imprint: Wiley, 2012
  • Published in: European Journal of Haematology
  • Language: English
  • DOI: 10.1111/j.1600-0609.2012.01806.x
  • ISSN: 0902-4441; 1600-0609
  • Keywords: Hematology ; General Medicine
  • Origination:
  • Footnote:
  • Description: <jats:title>Abstract</jats:title><jats:sec><jats:title>Objectives</jats:title><jats:p>Diagnosing invasive pulmonary aspergillosis (<jats:styled-content style="fixed-case">IPA</jats:styled-content>) remains a challenge in patients with hematological malignancies. The clinical significance of testing bronchoalveolar lavage (<jats:styled-content style="fixed-case">BAL</jats:styled-content>) samples both with polymerase chain reaction (<jats:styled-content style="fixed-case">PCR</jats:styled-content>) and <jats:italic><jats:styled-content style="fixed-case">A</jats:styled-content>spergillus</jats:italic> galactomannan <jats:styled-content style="fixed-case">ELISA</jats:styled-content> (<jats:styled-content style="fixed-case">GM</jats:styled-content>) is unclear, and the <jats:styled-content style="fixed-case">BAL</jats:styled-content> cutoff for <jats:styled-content style="fixed-case">GM</jats:styled-content> has not been clearly evaluated yet.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Using a validated nested <jats:styled-content style="fixed-case">PCR</jats:styled-content> assay and a <jats:styled-content style="fixed-case">GM ELISA</jats:styled-content>, we prospectively examined <jats:styled-content style="fixed-case">BAL</jats:styled-content> samples from 87 hematological patients at high risk of <jats:styled-content style="fixed-case">IPA</jats:styled-content>. Of 76 (87%) evaluable patients, 29 patients had proven or probable disease.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>The receiver operating characteristic (<jats:styled-content style="fixed-case">ROC</jats:styled-content>) analysis of <jats:styled-content style="fixed-case">GM</jats:styled-content> optical density (<jats:styled-content style="fixed-case">OD</jats:styled-content>) cutoff levels yielded a <jats:styled-content style="fixed-case">BAL OD</jats:styled-content> of 0.5 to be optimal. We identified 29 probable or proven cases based on this <jats:styled-content style="fixed-case">OD</jats:styled-content>. Sensitivity and specificity for <jats:styled-content style="fixed-case">BAL GM</jats:styled-content> were 0.79 (95% <jats:styled-content style="fixed-case">CI</jats:styled-content>, 0.62–0.9) and 0.96 (95% <jats:styled-content style="fixed-case">CI</jats:styled-content>, 0.86–0.99), respectively. For <jats:styled-content style="fixed-case">BAL PCR</jats:styled-content>, sensitivity and specificity were 0.59 (95% <jats:styled-content style="fixed-case">CI</jats:styled-content>, 0.41–0.75) and 0.87 (95% <jats:styled-content style="fixed-case">CI</jats:styled-content>, 0.75–0.94), respectively. Combining <jats:styled-content style="fixed-case">BAL GM</jats:styled-content> and <jats:styled-content style="fixed-case">PCR</jats:styled-content> for diagnosis showed a sensitivity and specificity rate of 0.55 (95% <jats:styled-content style="fixed-case">CI</jats:styled-content>, 0.38–0.72) and 1.0 (95% <jats:styled-content style="fixed-case">CI</jats:styled-content>, 0.93–1.0), respectively, if positivity was defined by positive results for both tests. If either positive <jats:styled-content style="fixed-case">BAL GM</jats:styled-content> or positive <jats:styled-content style="fixed-case">BAL PCR</jats:styled-content> results defined test positivity, the sensitivity was 0.83 (95% <jats:styled-content style="fixed-case">CI</jats:styled-content>, 0.65–0.92), and the specificity was 0.83 (95% <jats:styled-content style="fixed-case">CI</jats:styled-content>, 0.70–0.91)</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>In terms of optimal sensitivity and specificity, a <jats:styled-content style="fixed-case">GM OD</jats:styled-content> cutoff of 0.5 was determined for <jats:styled-content style="fixed-case">BAL</jats:styled-content> samples. Positivity for both <jats:styled-content style="fixed-case">GM</jats:styled-content> and <jats:italic><jats:styled-content style="fixed-case">A</jats:styled-content>spergillus </jats:italic><jats:styled-content style="fixed-case">PCR</jats:styled-content> in <jats:styled-content style="fixed-case">BAL</jats:styled-content> makes a pulmonary aspergillosis highly likely.</jats:p></jats:sec>