Saksirisampant et al., 2022. [12] | - -
Overall, 45 BALs and the plasma from 45 IMS adult patients with clinical and radiological findings compatible with pneumonia were tested by HCMV qPCR.
| - -
Eleven (24%) patients developed HCMV pneumonitis. All of these patients had detectable plasma HCMV VL (median VL 41,939 UI/mL) and detectable BAL HCMV VL (median VL 379,652 IU/mL) - -
Thirty-four (76%) patients without HCMV pneumonitis, with median plasma and BAL HCMV VL of 0 IU/mL. - -
A significant positive correlation was observed between plasma and BAL HCMV VL (R2 = 0.887, p < 0.001). - -
A HCMV VL in BAL was established as an optimal cut-off value to distinguish between HCMV pneumonitis and non-pneumonitis: 831 IU/mL in the plasma and 24,565 IU/mL in BAL. - -
Undetectable plasma HCMV excluded HCMV pneumonitis.
| - -
BAL and plasma samples were collected in parallel, which were prospectively qPCR on fresh samples. - -
A fully automated and highly sensitive qPCR assay was used.
| - -
Small number of patients with HCMV pneumonitis (n = 11). - -
Viral culture was not used to establish virus replication. - -
Potential bias in selecting patients for bronchoscopy. - -
Heterogeneous group of immunocompromised patients included. - -
Not all patients could be studied by histopathology or cytology.
|
Leuzinger et al., 2020. [9] | - -
In 1109 BALs from 799 IMS patients (median age: 61 years), the presence of HCMV was tested by viral culture, specific immunofluorescence, and qPCR. - -
Overall, 76 patients with a HCMV-positive load in BAL were also tested by HCMV qPCR in the plasma.
| - -
Median HCMV VL was significantly higher in culture-positive than in culture-negative BAL. - -
The likelihood for HCMV detection by culture in BAL increased with higher VL (85% for VL >10,000 copies/mL). - -
BAL HCMV VL of 10,000 copies/mL was indicative of relevant replication. - -
HCMV VL cut-off is likely to vary depending on BAL procedure and processing or the assay used for qPCR. - -
One-third of patients with HCMV-positive BAL had undetectable plasma loads, indicating local HCMV replication in the lung.
| - -
High number of patients and samples studied. - -
Viral culture performed on all BAL as a significantly relevant indicator of replication. - -
In a group of patients (112), BALs were prospectively analyzed (in parallel culture and qPCR of fresh samples) to assess the effect of sample freezing on virus DNA degradation.
| - -
Most BALs (997) were tested by qPCR retrospectively from frozen samples. - -
Heterogeneous group of immunocompromised patients included. - -
qPCR assay not fully automated (requires prior DNA extraction). - -
Non-availability of lung biopsy to be able to define more accurately the cases of HCMV pneumonia.
|
Piñana et al., 2019. [11] | - -
Overall, 144 BALs and the plasma from 123 allogenic hematopoietic stem cell transplant recipients (allo-HSCT) with signs and/or symptoms of pneumonia were tested by HCMV qPCR in 2 different hospitals
| - -
The detection of HCMV DNA in BAL is a very common finding in allo-HSCT, since HCMV DNA was detected in 56 (38.9%) of BALs. - -
Overall, 60% of the patients had non-proven HCMV pneumonia, having VL >500 IU/mL. - -
Furthermore, 500 IU/mL is unlikely to be discriminative between pneumonia and pulmonary DNA HCMV shedding. - -
HCMV VL cut-off is likely to vary depending on patients’ characteristics, BAL procedure and processing or the assay used for qPCR. - -
Differences in HCMV VL in BAL provided by qPCR assays used in each centre.
| - -
BALs were included consecutively, and fresh samples were tested (prospective). - -
A highly sensitive real-time qPCR assay was used.
| - -
Reference techniques, such as viral culture, were not used to establish virus replication. - -
Two hospitals with different qPCR assays are included. - -
Retrospective data analysis. - -
qPCR assay not fully automated (requires prior DNA extraction).
|
Beam et al., 2018. [13] | - -
Thirty-eight BALs and the plasma from 38 IMS patients (the majority were transplant recipients, median age: 55.9 years) were tested by HCMV qPCR. In BAL, VL results were adjusted for the number of cells in each BAL (normalized VL)
| - -
There were 17 (44.7%) patients with HCMV pneumonia (6 proven) and 21 (55.3%) without HCMV pneumonia. - -
Higher HCMV median VL in BAL was observed in patients with proven pneumonitis (>18,200,000 IU/mL), followed by probable cases (1,305,000 IU/mL) and lower VL in possible cases (32,400 IU/mL). - -
HCMV VL threshold in BAL of 34,800 IU/mL would identify patients with pneumonitis.
| - -
Normalization results in VL by cells in BAL.
| - -
Small number of proven pneumonitis (6). - -
Heterogeneous group of immunocompromised patients included. - -
Viral culture was not used to establish virus replication. - -
qPCR performed on BAL samples stored at −80 °C (not fresh). - -
qPCR assay not fully automated (requires prior DNA extraction).
|
Lodding et al., 2017. [14] | - -
Overall, 972 BALs and the plasma from 141 lung transplant recipients were tested by HCMV qPCR. - -
In 859 lung biopsies, HCMV was studied by IHC.
| - -
In 145 (15%) BALs, HCMV was detected by qPCR, of which 34 had pneumonia criteria and 111 without. - -
BAL HCMV VL was consistently higher in episodes with HCMV pneumonia in lung transplant recipients. Median VL in BAL was 32,940 IU/mL in HCMV pneumonia and 1260 IU/mL without pneumonia (p < 0.001). - -
Optimal cut-off HCMV VL in BAL for diagnosing HMCV pneumonia is 4545 IU/mL (91% sensitivity and 77% specificity). - -
qPCR in BAL had high diagnostic accuracy for diagnosing HCMV pneumonia and was better than qPCR in plasma. BAL HCMV VL was log10 1.4-fold higher than the corresponding positive HCMV VL in plasma. - -
Episodes of HCMV pneumonia were more likely to be HCMV-positive in the plasma (63%) compared with those without pneumonia (24%) (p < 0.001). - -
Overall, 37% of the HCMV pneumonia episodes had a negative PCR in the plasma; thus plasma HCMV PCR had limited sensitivity for the diagnosis of pneumonia.
| - -
High number of patients and samples studied. - -
BAL and plasma samples collected consecutively and in parallel, which were prospectively qPCR on fresh samples. - -
Lung biopsies were included for histological study.
| - -
Viral culture was not used to establish virus replication. - -
qPCR assay not fully automated (requires prior DNA extraction).
|
Iglesias et al., 2017. [15] | - -
Fifty-six recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT, median age: 51 years, range 17–68) were studied. 16 (28.6%) of these patients presented symptoms of lung disease, and a BAL and plasma sample was collected. BAL was tested by HCMV culture and qPCR, and plasma by qPCR.
| - -
VL of CMV in BAL was positive in 10 (62.5%) patients (in 7 VL >150 copies/mL and in 3 VL <150 copies/mL). - -
Of the 7 patients with BAL VL >150 copies/mL, 6 (85.7%) were diagnosed with probable HCMV pneumonia, and in 1 (14.3%) case, HCMV disease was discounted. - -
In 6 patients with HCMV pneumonia (10.7% of all patients), the median BAL VL was 53,250 copies/mL. In 5 cases, the plasma VL was positive, with a median of 538 copies/mL. - -
Only one BAL sample was positive for CMV by virological culture, with a VL >10,000,000 copies/mL. - -
All patients’ plasma VL was lower than in BAL. - -
Any value of CMV VL in BAL, with compatible signs or symptoms, should be considered suggestive of CMV pneumonia in allo-HSCT.
| - -
Fresh BAL samples were used and tested by viral culture. - -
BAL and plasma samples were collected in parallel, which were prospectively qPCR on fresh samples. - -
A fully automated and highly sensitive qPCR assay was used.
| - -
Small number of patients with HCMV pneumonitis (6). - -
Not all patients underwent BAL (only 16).
|
Young Lee et al., 2017. [16] | - -
In 565 BALs from 565 adult patients (median age: 48 years) with hematologic malignancies and signs and/or symptoms of pneumonia who underwent bronchoscopy, HCMV was tested by qPCR, Shell-vial culture and IHC. - -
Additional assays such as blood HCMV qPCR and lung biopsies were also reviewed.
| - -
There were 464 (82.1%) patients negative for HCMV or <380 copies/mL in BAL. - -
There were 101 (17.9%) patients with HCVM qPCR >380 copies/mL in BAL. 24 (23.8%) of them were diagnosed with HCMV pneumonia. - -
Patients with HCMV pneumonia had significantly higher VL in BAL than patients without (7,378,508 vs. 10,899 copies/mL). - -
Patients with HCMV pneumonia had significantly higher VL in plasma than patients without (683,659 vs. 20,915 copies/mL). - -
Cut-off value of 28,774 copies/mL HCMV in BAL was correlated with HCMV pneumonia.
| - -
High number of patients and samples studied. - -
Fresh BAL samples were used, which were tested by reference techniques such as shell vial culture and immunohistochemical (IHQ). - -
Lung biopsies were included for histological study.
| - -
Retrospective data analysis. - -
qPCR assay not fully automated (requires prior DNA extraction).
|
Govender et al., 2017. [17] | - -
Eighty-seven infants (median age: 3.7 months) with suspected HCMV infection and severe pneumonia requiring ventilation, included in the intensive care unit, were tested for HCMV by qPCR on BAL and plasma samples.
| - -
Twenty-nine patients (33.3%) were HCMV-infected and diagnosed with HCMV pneumonitis. - -
Twenty-five patients (28.7%) were HCMV-infected without HCMV pneumonitis. - -
Thirty-three patients (37.9%) were HCMV-uninfected. - -
There was a significant difference in mean HCMV VL in BAL between patients HCMV-infected without pneumonitis (3.78 log10 IU/mL) and those with HMCV pneumonitis (5 log10 IU/mL). - -
There was a significant difference in mean HCMV VL in plasma between patients HCMV-infected without pneumonitis (3.5 log10 IU/mL) and those with HMCV pneumonitis (4.17 log10 IU/mL). - -
The threshold of 4.03 log10 IU/mL in BAL was chosen for predicting HCMV pneumonitis. - -
qPCR in BAL is more predictive of HCMV pneumonitis than in plasma.
| - -
BAL and plasma samples were collected in parallel, and fresh samples were used for qPCR.
| - -
Viral culture was not used to establish virus replication. - -
qPCR assay not fully automated (requires prior DNA extraction) and less sensitive than current qPCR.
|
Boeckh et al., 2017. [18] | - -
Overall, 271 BALs and plasma samples from 271 hematopoietic stem cell transplant recipients (132 patients with HCMV pneumonitis and 139 controls) were tested by HCMV qPCR. - -
All BAL were also tested for the presence of B-globin DNA by PCR.
| - -
Median HCMV VL in BAL of patients with HCMV pneumonitis (2.9 log10 IU/mL) was significantly higher than in the 3 control groups (0 log10 IU/mL in patients with non-CMV pneumonia and idiopathic pneumonia syndrome, and 1.63 log10 IU/mL in asymptomatic patients). - -
HCMV VL in BAL > 500 IU/mL reliably differentiates HCMV disease, good PPV and excellent NPV. - -
BAL storage time did not appear to affect VL. - -
Pulmonary haemorrhage, co-pathogens and radiographic presentation do not seem to affect BAL VL.
| - -
High number of cases o HCMV pneumonitis (132). - -
Fresh BAL samples were used and tested by viral culture. - -
Analysis of the effect of pulmonary haemorrhage, co-pathogens, and radiological presentation on HCMV VL in BAL. - -
Analysis of BAL cellularity and quality of DNA extraction by BAL B-globin amplification.
| - -
qPCR performed on BAL samples stored at −80 °C (not fresh). - -
qPCR assay not fully automated (requires prior DNA extraction). - -
Plasma samples separated up to 7 days from the performance of the bronchoscopy are included.
|
K. Tan et al., 2015. [10] | - -
Retrospective analysis of 1074 BALs from 699 IMS patients (range 18–92.6 years old), testing HCMV by qPCR and culture (conventional and shell vial). - -
In 20 cases with positive BAL for HCMV, a lung biopsy was performed for histopathological study.
| - -
Ninety (12.9%) patients were HCMV-positive (PCR and/or culture) in BAL, and 609 (87.1%) were HCMV-negative. - -
Sensitivity of qPCR (91.3%) was significantly higher than both SV-culture (54.4%) and conventional-culture (28.3%). - -
Specificity of qPCR (94.6%) was significantly lower than both SV-culture (97.4%) and conventional-culture (96.5%). - -
NPV of qPCR (99.6%) was significantly higher than both SV-culture (97.9%) and conventional-culture (96.9%). - -
VL HCMV in BAL not statistically different between patients with or without pneumonitis.
| - -
Fresh BAL samples were used and tested by traditional culture and shell-vial. - -
High number of cases of HCMV pneumonitis were included.
| - -
Retrospective data analysis. - -
Heterogeneous group of immunocompromised patients included. - -
qPCR assay not fully automated (requires prior DNA extraction) and less sensitive than current qPCR. - -
Not all patients underwent HCMV analysis in blood by qPCR. - -
Not all patients could be studied by histopathology or cytology.
|
Westall et al., 2004. [19] | - -
Overall, 182 paired samples (BAL and plasma) from 41 lung transplant recipients (range 18–64 years old) were tested by HCMV qPCR. - -
In the BAL samples, qPCR was undertaken using the supernatant and the cell pellet. - -
Fourty-two patients also underwent a transbronchial biopsy for a histological study of HCMV.
| - -
Fourteen samples (8.1%) had HCMV DNA detected in both BAL and plasma. - -
Overall, in 123 (71.5%) samples, HCMV DNA was not detected in either BAL or plasma. - -
In 35 samples (20.3%), HCMV DNA was detected in BAL but not in the plasma. - -
Qualitative HCMV PCR in BAL low specificity (76%). - -
Mean VL HCMV in BAL with proven HCMV pneumonitis was significantly higher than those without pneumonitis (19,460 ± 4917 vs. 5873 ± 1543 copies/mL). - -
Mean VL HCMV in plasma with proven HCMV pneumonitis was significantly higher than those without pneumonitis (6791 ± 2942 vs. 561 ± 445 copies/mL). - -
All episodes of histologically proven HCMV infection were associated with VL in BAL > 46,000 copies/mL. - -
The detection of HCMV DNA in BAL, compared with detection in plasma, was better correlated with HCMV pneumonitis.
| - -
Patients were enrolled consecutively and prospectively. - -
BAL and plasma samples were collected in parallel, and fresh samples were used for qPCR. - -
Lung biopsies were included for histological study.
| - -
Small number of histologically proven HCMV disease (8). - -
Viral culture was not used to establish virus replication. - -
qPCR assay not fully automated (requires prior DNA extraction).
|
Chemaly et al., 2004. [20] | - -
Overall, 43 BALs from 27 lung transplant recipients (range 21–65 years old) were tested by shell vial culture and quantitative hybrid capture assay (Q-HCA). - -
In patients with positive BAL for HCMV, IHC of the transbronchial biopsy was performed. - -
HCMV was also studied in 18 blood samples using Q-HCA
| - -
15 (27%) patients had both positive BAL culture and Q-HCA. - -
5 (33%) of these 15 were diagnosed as HCMV pneumonitis (positive lung biopsy), all with VL > 500,000 copies/mL in BAL (mean of 1,638,457 copies/mL). - -
The remaining 10 (66%) without HCMV pneumonitis, all with VL < 500,000 copies/mL in BAL (mean of 81,820 copies/mL). - -
Significantly higher VL in BAL in patients with HCMV pneumonitis compared to those without HCMV pneumonitis (0.002). - -
Patients with HCMV pneumonitis (5) had a mean VL in the blood of 347,515 copies/mL, while those without pneumonitis (5) had a mean VL in the blood of 3151 copies/mL (p < 0.02). - -
HCMV VL in BAL was more predictive of pneumonitis than the blood VL.
| - -
Patients were enrolled consecutively and prospectively. - -
Fresh BAL samples were used and tested by traditional culture and shell vial. - -
All patients underwent lung biopsy for cytological and histological study.
| - -
Small number of patients with HCMV pneumonitis (5). - -
The quantitative hybrid capture assay (Q-HCA) was used, a less sensitive and automated technique than qPCR. - -
Not all patients underwent HCMV analysis in blood by qPCR.
|
Chemaly et al., 2003. [21] | - -
Overall, 42 BALs from 27 lung transplant recipients were tested by HCMV quantitative hybrid capture assay (Q-HCA). - -
In addition, the presence of HCMV in 39 lung biopsies was studied by histology and IHC. - -
HCMV was also studied in 32 blood samples using Q-HCA.
| - -
HCMV was detected in lung biopsy samples by H&E in 3 (8%) and by IHC in 13 (33%). - -
VL in BAL was significantly higher than in blood. - -
HCMV VL in both BAL and blood in patients with histological evidence of HCMV disease was significantly higher than in those without evidence. - -
Median HCMV VL in BAL was 0 copies/mL in patients with IHQ-negative biopsy, 47,678 copies/mL in biopsy positive-atypical straining and 1,548,827 copies/mL biopsy positive-typical straining (p < 0.001).
| - -
Patients were enrolled consecutively and prospectively. - -
Fresh BAL samples were used. - -
All patients underwent lung biopsy for cytological and histological study.
| - -
Small number of patients with HCMV pneumonitis. - -
Viral culture was not used to establish virus replication. - -
The quantitative hybrid capture assay (Q-HCA) was used, a less sensitive and automated technique than qPCR. - -
Not all patients underwent HCMV analysis in blood by qPCR.
|
Riise et al., 2000. [22] | - -
Overall, 340 BALs from 35 consecutive lung transplant recipients (adults and infants) were tested by HCMV qPCR and culture
| - -
Seventeen (49%) of the patients developed HCMV pneumonitis. - -
Patients that developed HCMV disease had a significantly higher mean VL in BAL (1120 ± 4.379 copies/mL) compared with those without (180 ± 1177 copies/mL). - -
qPCR HCMV in BAL is not useful as a diagnostic tool for HCMV disease.
| - -
Patients were enrolled consecutively and prospectively. - -
Fresh BAL samples were used and tested by viral culture.
| - -
Small number of patients with HCMV pneumonitis (17). - -
qPCR assay not fully automated (requires prior DNA extraction).
|