Limits...
Combining standard clinical methods with PCR showed improved diagnosis of invasive pulmonary aspergillosis in patients with hematological malignancies and prolonged neutropenia.

Paholcsek M, Fidler G, Konya J, Rejto L, Mehes G, Bukta E, Loeffler J, Biro S - BMC Infect. Dis. (2015)

Bottom Line: Sera were successively screened for galactomannan antigen and for Aspergillus fumigatus specific nucleic acid targets.Although bronchoalveolar lavage proved negative in 93 % of controls it did not detect IPA in 86 % of the cases.The data from this pilot-study demonstrate that the consideration of standard clinical methods combined with biomarker testing improves the capacity to make early and more accurate diagnostic decisions.

View Article: PubMed Central - PubMed

Affiliation: Faculty of Medicine, Department of Human Genetics, University of Debrecen, Nagyerdei krt. 98, H-4032, Debrecen, Hungary. paholcsek.melinda@med.unideb.hu.

ABSTRACT

Background: We assessed the diagnostic value of standard clinical methods and combined biomarker testing (galactomannan assay and polymerase chain reaction screening) in a prospective case-control study to detect invasive pulmonary aspergillosis in patients with hematological malignancies and prolonged neutropenia.

Methods: In this observational study 162 biomarker analyses were performed on samples from 27 febrile neutropenic episodes. Sera were successively screened for galactomannan antigen and for Aspergillus fumigatus specific nucleic acid targets. Furthermore thoracic computed tomography scanning was performed along with bronchoscopy with lavage when clinically indicated. Patients were retrospectively stratified to define a case-group with "proven" or "probable" invasive pulmonary aspergillosis (25.93 %) and a control-group of patients with no evidence for of invasive pulmonary aspergillosis (74.07 %). In 44.44 % of episodes fever ceased in response to antibiotic treatment (group II). Empirical antifungal therapy was administered for episodes with persistent or relapsing fever (group I). 48.15 % of patients died during the study period. Postmortem histology was pursued in 53.85 % of fatalities.

Results: Concordant negative galactomannan and computed tomography supported by a polymerase chain reaction assay were shown to have the highest discriminatory power to exclude invasive pulmonary aspergillosis. Bronchoalveolar lavage was performed in 6 cases of invasive pulmonary aspergillosis and in 15 controls. Although bronchoalveolar lavage proved negative in 93 % of controls it did not detect IPA in 86 % of the cases. Remarkably post mortem histology convincingly supported the presence of Aspergillus hyphae in lung tissue from a single case which had consecutive positive polymerase chain reaction assay results but was misdiagnosed by both computed tomography and consistently negative galactomannan assay results. For the galactomannan enzyme-immunoassay the diagnostic odds ratio was 15.33 and for the polymerase chain reaction assay it was 28.67. According to Cohen's kappa our in-house polymerase chain reaction method showed a fair agreement with the galactomannan immunoassay. Combined analysis of the results from the Aspergillus galactomannan enzyme immunoassay together with those generated by our polymerase chain reaction assay led to no misdiagnoses in the control group.

Conclusion: The data from this pilot-study demonstrate that the consideration of standard clinical methods combined with biomarker testing improves the capacity to make early and more accurate diagnostic decisions.

Show MeSH

Related in: MedlinePlus

Data on CBT in fevered neutropenia episodes at the University Hospitals of Debrecen. (✤) Neutrophil count less than 500/mm3. (✔) persistent fever for more than 96 h, refractory to antibiotic treatment, (group I patients); (✘) lack of persistent fever more than 96 h, (group II patients); (‡) according to European Organization for Research and Treatment of Cancer criteria. (FNE); febrile neutropenia episode. There were in total 162 tests (mean; 2.93 ± 2.14/FNE) performed. 77 serum specimens (mean; 2.79 ± 1.89/FNE) were screened for the presence of GM antigen and 85 PCRs (mean; 3,07 ± 2.39/FNE) were performed supported by 249 runs (mean; 9 ± 7.02/FNE) and targeting special fungal nucleic acid marker genes (facC-PCR) of prokaryotic origin. Reporting of descriptivce statistics with mean values and standard error (±SE) are shown
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC4487853&req=5

Fig2: Data on CBT in fevered neutropenia episodes at the University Hospitals of Debrecen. (✤) Neutrophil count less than 500/mm3. (✔) persistent fever for more than 96 h, refractory to antibiotic treatment, (group I patients); (✘) lack of persistent fever more than 96 h, (group II patients); (‡) according to European Organization for Research and Treatment of Cancer criteria. (FNE); febrile neutropenia episode. There were in total 162 tests (mean; 2.93 ± 2.14/FNE) performed. 77 serum specimens (mean; 2.79 ± 1.89/FNE) were screened for the presence of GM antigen and 85 PCRs (mean; 3,07 ± 2.39/FNE) were performed supported by 249 runs (mean; 9 ± 7.02/FNE) and targeting special fungal nucleic acid marker genes (facC-PCR) of prokaryotic origin. Reporting of descriptivce statistics with mean values and standard error (±SE) are shown

Mentions: On completion of combined biomarker testing categorical data; median, mean, standard deviations (±SD) were calculated for GM screening (GM-EIA) and for the nucleic acid based diagnostic method (facC-PCR). Data are shown in Fig. 2.Fig. 2


Combining standard clinical methods with PCR showed improved diagnosis of invasive pulmonary aspergillosis in patients with hematological malignancies and prolonged neutropenia.

Paholcsek M, Fidler G, Konya J, Rejto L, Mehes G, Bukta E, Loeffler J, Biro S - BMC Infect. Dis. (2015)

Data on CBT in fevered neutropenia episodes at the University Hospitals of Debrecen. (✤) Neutrophil count less than 500/mm3. (✔) persistent fever for more than 96 h, refractory to antibiotic treatment, (group I patients); (✘) lack of persistent fever more than 96 h, (group II patients); (‡) according to European Organization for Research and Treatment of Cancer criteria. (FNE); febrile neutropenia episode. There were in total 162 tests (mean; 2.93 ± 2.14/FNE) performed. 77 serum specimens (mean; 2.79 ± 1.89/FNE) were screened for the presence of GM antigen and 85 PCRs (mean; 3,07 ± 2.39/FNE) were performed supported by 249 runs (mean; 9 ± 7.02/FNE) and targeting special fungal nucleic acid marker genes (facC-PCR) of prokaryotic origin. Reporting of descriptivce statistics with mean values and standard error (±SE) are shown
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4487853&req=5

Fig2: Data on CBT in fevered neutropenia episodes at the University Hospitals of Debrecen. (✤) Neutrophil count less than 500/mm3. (✔) persistent fever for more than 96 h, refractory to antibiotic treatment, (group I patients); (✘) lack of persistent fever more than 96 h, (group II patients); (‡) according to European Organization for Research and Treatment of Cancer criteria. (FNE); febrile neutropenia episode. There were in total 162 tests (mean; 2.93 ± 2.14/FNE) performed. 77 serum specimens (mean; 2.79 ± 1.89/FNE) were screened for the presence of GM antigen and 85 PCRs (mean; 3,07 ± 2.39/FNE) were performed supported by 249 runs (mean; 9 ± 7.02/FNE) and targeting special fungal nucleic acid marker genes (facC-PCR) of prokaryotic origin. Reporting of descriptivce statistics with mean values and standard error (±SE) are shown
Mentions: On completion of combined biomarker testing categorical data; median, mean, standard deviations (±SD) were calculated for GM screening (GM-EIA) and for the nucleic acid based diagnostic method (facC-PCR). Data are shown in Fig. 2.Fig. 2

Bottom Line: Sera were successively screened for galactomannan antigen and for Aspergillus fumigatus specific nucleic acid targets.Although bronchoalveolar lavage proved negative in 93 % of controls it did not detect IPA in 86 % of the cases.The data from this pilot-study demonstrate that the consideration of standard clinical methods combined with biomarker testing improves the capacity to make early and more accurate diagnostic decisions.

View Article: PubMed Central - PubMed

Affiliation: Faculty of Medicine, Department of Human Genetics, University of Debrecen, Nagyerdei krt. 98, H-4032, Debrecen, Hungary. paholcsek.melinda@med.unideb.hu.

ABSTRACT

Background: We assessed the diagnostic value of standard clinical methods and combined biomarker testing (galactomannan assay and polymerase chain reaction screening) in a prospective case-control study to detect invasive pulmonary aspergillosis in patients with hematological malignancies and prolonged neutropenia.

Methods: In this observational study 162 biomarker analyses were performed on samples from 27 febrile neutropenic episodes. Sera were successively screened for galactomannan antigen and for Aspergillus fumigatus specific nucleic acid targets. Furthermore thoracic computed tomography scanning was performed along with bronchoscopy with lavage when clinically indicated. Patients were retrospectively stratified to define a case-group with "proven" or "probable" invasive pulmonary aspergillosis (25.93 %) and a control-group of patients with no evidence for of invasive pulmonary aspergillosis (74.07 %). In 44.44 % of episodes fever ceased in response to antibiotic treatment (group II). Empirical antifungal therapy was administered for episodes with persistent or relapsing fever (group I). 48.15 % of patients died during the study period. Postmortem histology was pursued in 53.85 % of fatalities.

Results: Concordant negative galactomannan and computed tomography supported by a polymerase chain reaction assay were shown to have the highest discriminatory power to exclude invasive pulmonary aspergillosis. Bronchoalveolar lavage was performed in 6 cases of invasive pulmonary aspergillosis and in 15 controls. Although bronchoalveolar lavage proved negative in 93 % of controls it did not detect IPA in 86 % of the cases. Remarkably post mortem histology convincingly supported the presence of Aspergillus hyphae in lung tissue from a single case which had consecutive positive polymerase chain reaction assay results but was misdiagnosed by both computed tomography and consistently negative galactomannan assay results. For the galactomannan enzyme-immunoassay the diagnostic odds ratio was 15.33 and for the polymerase chain reaction assay it was 28.67. According to Cohen's kappa our in-house polymerase chain reaction method showed a fair agreement with the galactomannan immunoassay. Combined analysis of the results from the Aspergillus galactomannan enzyme immunoassay together with those generated by our polymerase chain reaction assay led to no misdiagnoses in the control group.

Conclusion: The data from this pilot-study demonstrate that the consideration of standard clinical methods combined with biomarker testing improves the capacity to make early and more accurate diagnostic decisions.

Show MeSH
Related in: MedlinePlus