Diagnosis of fungal infections a systematic review and meta-analysis supporting American thoracic society practice guideline

Qusay Haydour, Chadi A. Hage, Eva M Carmona Porquera, Oleg Epelbaum, Scott E. Evans, Luke M. Gabe, Kenneth S. Knox, Jay K. Kolls, Nancy L. Wengenack, Larry J. Prokop, Andrew Harold Limper, Mohammad H Murad

Research output: Contribution to journalReview article

1 Citation (Scopus)

Abstract

Rationale: Prompt diagnosis of invasive fungal infections is important because of the associated morbidity and mortality; however, diagnosis is challenging because of the nonspecific symptoms and radiographic findings. Objectives: To conduct a systematic review and meta-analysis of studies that evaluated the diagnostic accuracy of serum and bronchoalveolar lavage (BAL) galactomannan (GM) and serum or BAL polymerase chain reaction (PCR) in patients with suspected invasive aspergillosis (IA), b-D-glucan in critically ill patients at risk for candidiasis or candidemia, and serology testing and antigen detection in patients with endemic mycoses (histoplasmosis, blastomycosis, and coccidioidomycosis). Methods: Studies were selected and appraised by pairs of reviewers. Bivariate random effects meta-analysis was used to generate pooled sensitivity, specificity, and diagnostic likelihood ratios. Results: Serum GM in patients with impaired immunity suspected of having IA had sensitivity of 0.71 (95% confidence interval [CI], 0.64-0.78) and specificity of 0.89 (95% CI, 0.84-0.92). A cutoff of 1 optical density index yielded optimal sensitivity and specificity. BAL GM in patients with impaired immunity suspected of having IA had sensitivity of 0.84 (95% CI, 0.73-0.91) and specificity of 0.88 (95% CI, 0.81-0.91). Serum or whole-blood PCR in immunocompromised patients with suspected IA had sensitivity of 0.81 (95% CI, 0.73-0.86) and specificity of 0.79 (95% CI, 0.68-0.86). BAL PCR in patients at high risk for IA had high sensitivity of 0.90 (95% CI, 0.77-0.96) and specificity of 0.96 (95% CI, 0.93-0.98) for diagnosing IA. b-D-glucan assay in patients in the intensive care unit at risk for invasive candidiasis or candidemia had sensitivity of 0.81 (95% CI, 0.74-0.86) and specificity of 0.60 (95% CI, 0.49-0.71). Data on diagnostic accuracy of antigen detection and serology testing for endemic mycoses were limited and heterogeneous (varied according to test, patient immunity, and suspected endemic disease). Conclusions: The diagnosis of invasive fungal infections remains a challenge. Various serum and BAL markers can aid in diagnosis. This evidence supports the development of clinical practice recommendations by the American Thoracic Society.

Original languageEnglish (US)
Pages (from-to)1179-1188
Number of pages10
JournalAnnals of the American Thoracic Society
Volume16
Issue number9
DOIs
StatePublished - Jan 1 2019

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Mycoses
Practice Guidelines
Meta-Analysis
Thorax
Aspergillosis
Confidence Intervals
Bronchoalveolar Lavage
Candidemia
Immunity
Serum
Serology
Polymerase Chain Reaction
Invasive Candidiasis
Blastomycosis
Coccidioidomycosis
Antigens
Sensitivity and Specificity
Endemic Diseases
Histoplasmosis
Candidiasis

Keywords

  • Diagnostic accuracy
  • Fungal infection
  • Laboratory diagnosis
  • Meta-analysis
  • Systematic review

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Diagnosis of fungal infections a systematic review and meta-analysis supporting American thoracic society practice guideline. / Haydour, Qusay; Hage, Chadi A.; Carmona Porquera, Eva M; Epelbaum, Oleg; Evans, Scott E.; Gabe, Luke M.; Knox, Kenneth S.; Kolls, Jay K.; Wengenack, Nancy L.; Prokop, Larry J.; Limper, Andrew Harold; Murad, Mohammad H.

In: Annals of the American Thoracic Society, Vol. 16, No. 9, 01.01.2019, p. 1179-1188.

Research output: Contribution to journalReview article

Haydour, Qusay ; Hage, Chadi A. ; Carmona Porquera, Eva M ; Epelbaum, Oleg ; Evans, Scott E. ; Gabe, Luke M. ; Knox, Kenneth S. ; Kolls, Jay K. ; Wengenack, Nancy L. ; Prokop, Larry J. ; Limper, Andrew Harold ; Murad, Mohammad H. / Diagnosis of fungal infections a systematic review and meta-analysis supporting American thoracic society practice guideline. In: Annals of the American Thoracic Society. 2019 ; Vol. 16, No. 9. pp. 1179-1188.
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abstract = "Rationale: Prompt diagnosis of invasive fungal infections is important because of the associated morbidity and mortality; however, diagnosis is challenging because of the nonspecific symptoms and radiographic findings. Objectives: To conduct a systematic review and meta-analysis of studies that evaluated the diagnostic accuracy of serum and bronchoalveolar lavage (BAL) galactomannan (GM) and serum or BAL polymerase chain reaction (PCR) in patients with suspected invasive aspergillosis (IA), b-D-glucan in critically ill patients at risk for candidiasis or candidemia, and serology testing and antigen detection in patients with endemic mycoses (histoplasmosis, blastomycosis, and coccidioidomycosis). Methods: Studies were selected and appraised by pairs of reviewers. Bivariate random effects meta-analysis was used to generate pooled sensitivity, specificity, and diagnostic likelihood ratios. Results: Serum GM in patients with impaired immunity suspected of having IA had sensitivity of 0.71 (95{\%} confidence interval [CI], 0.64-0.78) and specificity of 0.89 (95{\%} CI, 0.84-0.92). A cutoff of 1 optical density index yielded optimal sensitivity and specificity. BAL GM in patients with impaired immunity suspected of having IA had sensitivity of 0.84 (95{\%} CI, 0.73-0.91) and specificity of 0.88 (95{\%} CI, 0.81-0.91). Serum or whole-blood PCR in immunocompromised patients with suspected IA had sensitivity of 0.81 (95{\%} CI, 0.73-0.86) and specificity of 0.79 (95{\%} CI, 0.68-0.86). BAL PCR in patients at high risk for IA had high sensitivity of 0.90 (95{\%} CI, 0.77-0.96) and specificity of 0.96 (95{\%} CI, 0.93-0.98) for diagnosing IA. b-D-glucan assay in patients in the intensive care unit at risk for invasive candidiasis or candidemia had sensitivity of 0.81 (95{\%} CI, 0.74-0.86) and specificity of 0.60 (95{\%} CI, 0.49-0.71). Data on diagnostic accuracy of antigen detection and serology testing for endemic mycoses were limited and heterogeneous (varied according to test, patient immunity, and suspected endemic disease). Conclusions: The diagnosis of invasive fungal infections remains a challenge. Various serum and BAL markers can aid in diagnosis. This evidence supports the development of clinical practice recommendations by the American Thoracic Society.",
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author = "Qusay Haydour and Hage, {Chadi A.} and {Carmona Porquera}, {Eva M} and Oleg Epelbaum and Evans, {Scott E.} and Gabe, {Luke M.} and Knox, {Kenneth S.} and Kolls, {Jay K.} and Wengenack, {Nancy L.} and Prokop, {Larry J.} and Limper, {Andrew Harold} and Murad, {Mohammad H}",
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TY - JOUR

T1 - Diagnosis of fungal infections a systematic review and meta-analysis supporting American thoracic society practice guideline

AU - Haydour, Qusay

AU - Hage, Chadi A.

AU - Carmona Porquera, Eva M

AU - Epelbaum, Oleg

AU - Evans, Scott E.

AU - Gabe, Luke M.

AU - Knox, Kenneth S.

AU - Kolls, Jay K.

AU - Wengenack, Nancy L.

AU - Prokop, Larry J.

AU - Limper, Andrew Harold

AU - Murad, Mohammad H

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Rationale: Prompt diagnosis of invasive fungal infections is important because of the associated morbidity and mortality; however, diagnosis is challenging because of the nonspecific symptoms and radiographic findings. Objectives: To conduct a systematic review and meta-analysis of studies that evaluated the diagnostic accuracy of serum and bronchoalveolar lavage (BAL) galactomannan (GM) and serum or BAL polymerase chain reaction (PCR) in patients with suspected invasive aspergillosis (IA), b-D-glucan in critically ill patients at risk for candidiasis or candidemia, and serology testing and antigen detection in patients with endemic mycoses (histoplasmosis, blastomycosis, and coccidioidomycosis). Methods: Studies were selected and appraised by pairs of reviewers. Bivariate random effects meta-analysis was used to generate pooled sensitivity, specificity, and diagnostic likelihood ratios. Results: Serum GM in patients with impaired immunity suspected of having IA had sensitivity of 0.71 (95% confidence interval [CI], 0.64-0.78) and specificity of 0.89 (95% CI, 0.84-0.92). A cutoff of 1 optical density index yielded optimal sensitivity and specificity. BAL GM in patients with impaired immunity suspected of having IA had sensitivity of 0.84 (95% CI, 0.73-0.91) and specificity of 0.88 (95% CI, 0.81-0.91). Serum or whole-blood PCR in immunocompromised patients with suspected IA had sensitivity of 0.81 (95% CI, 0.73-0.86) and specificity of 0.79 (95% CI, 0.68-0.86). BAL PCR in patients at high risk for IA had high sensitivity of 0.90 (95% CI, 0.77-0.96) and specificity of 0.96 (95% CI, 0.93-0.98) for diagnosing IA. b-D-glucan assay in patients in the intensive care unit at risk for invasive candidiasis or candidemia had sensitivity of 0.81 (95% CI, 0.74-0.86) and specificity of 0.60 (95% CI, 0.49-0.71). Data on diagnostic accuracy of antigen detection and serology testing for endemic mycoses were limited and heterogeneous (varied according to test, patient immunity, and suspected endemic disease). Conclusions: The diagnosis of invasive fungal infections remains a challenge. Various serum and BAL markers can aid in diagnosis. This evidence supports the development of clinical practice recommendations by the American Thoracic Society.

AB - Rationale: Prompt diagnosis of invasive fungal infections is important because of the associated morbidity and mortality; however, diagnosis is challenging because of the nonspecific symptoms and radiographic findings. Objectives: To conduct a systematic review and meta-analysis of studies that evaluated the diagnostic accuracy of serum and bronchoalveolar lavage (BAL) galactomannan (GM) and serum or BAL polymerase chain reaction (PCR) in patients with suspected invasive aspergillosis (IA), b-D-glucan in critically ill patients at risk for candidiasis or candidemia, and serology testing and antigen detection in patients with endemic mycoses (histoplasmosis, blastomycosis, and coccidioidomycosis). Methods: Studies were selected and appraised by pairs of reviewers. Bivariate random effects meta-analysis was used to generate pooled sensitivity, specificity, and diagnostic likelihood ratios. Results: Serum GM in patients with impaired immunity suspected of having IA had sensitivity of 0.71 (95% confidence interval [CI], 0.64-0.78) and specificity of 0.89 (95% CI, 0.84-0.92). A cutoff of 1 optical density index yielded optimal sensitivity and specificity. BAL GM in patients with impaired immunity suspected of having IA had sensitivity of 0.84 (95% CI, 0.73-0.91) and specificity of 0.88 (95% CI, 0.81-0.91). Serum or whole-blood PCR in immunocompromised patients with suspected IA had sensitivity of 0.81 (95% CI, 0.73-0.86) and specificity of 0.79 (95% CI, 0.68-0.86). BAL PCR in patients at high risk for IA had high sensitivity of 0.90 (95% CI, 0.77-0.96) and specificity of 0.96 (95% CI, 0.93-0.98) for diagnosing IA. b-D-glucan assay in patients in the intensive care unit at risk for invasive candidiasis or candidemia had sensitivity of 0.81 (95% CI, 0.74-0.86) and specificity of 0.60 (95% CI, 0.49-0.71). Data on diagnostic accuracy of antigen detection and serology testing for endemic mycoses were limited and heterogeneous (varied according to test, patient immunity, and suspected endemic disease). Conclusions: The diagnosis of invasive fungal infections remains a challenge. Various serum and BAL markers can aid in diagnosis. This evidence supports the development of clinical practice recommendations by the American Thoracic Society.

KW - Diagnostic accuracy

KW - Fungal infection

KW - Laboratory diagnosis

KW - Meta-analysis

KW - Systematic review

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