TABLE 5.

Utility of BAL fluid viral load determination for diagnosis of CMV pneumonia in HCT recipients^m

Author (reference)	Yr	Transplant type(s)	Study design/population	Total no. of patients	No. of CMV pneumonia cases	Median BAL VL		% of CMV pneumonia cases with positive blood PCR result (no. of positive cases/total no. of cases)	Findings	Conclusion(s)
						CMV pneumonia cases	Non-CMV pneumonia cases
Boeckh et al. (66)	2017	HCT	Case-control study; CMV pneumonia patients vs controls (asymptomatic, IPS, or non-CMV pneumonia)	271	132a	3.9 log10 IU/ml	1.63 log10 IU/mlb ; 0 log10 IU/mlc	86 (18/21), plasma	84.1% sensitivity and 76.2% sensitivity at a VL cutoff of 203 IU/mld ; 90.2% sensitivity and 80.5% specificity at a VL cutoff of 99.7 IU/mle	CMV BAL PCR threshold of 500 IU/ml is suggested to differentiate between CMV pneumonia and pulmonary shedding
Lee et al. (67)	2017	Hematological malignancy, BMT	Retrospective case-control study; CMV pneumonia vs non-CMV pneumonia	94; 59 BMT	24,f 16g	187,224 copies/ml	3,055 copies/ml	NR	For HCT patients, CMV BAL fluid PCR had an 81.3% sensitivity and an 81.4% specificity at a VL cutoff of 18,900 copies/ml; for all patients, CMV BAL fluid PCR had a 75% sensitivity and an 88.6% specificity at a VL cutoff of 28,774 copies/ml	BAL fluid PCR can aid in the diagnosis of CMV pneumonia; the VL threshold for pneumonia diagnosis in BMT patients was suggested to be 18,900 copies/ml
Iglesias et al. (68)	2017	HCT	Retrospective cohort study; positive CMV PCR on BAL fluid	56	6h	53,250 copies/ml	<150 copies/mli	83 (5/6), plasma	All CMV pneumonia patients’ plasma PCR values were lower than those from BAL fluid PCR; 75% of patients with a VL of >50,000 copies/ml died of refractory pneumonia	Any value for CMV VL in BAL fluid, especially if it is higher than that in plasma and clinically correlated, should be considered suggestive of CMV pneumonia
Pinana et al. (69)	2019	HCT	Retrospective cohort study; patients with BAL fluid data	123	2,i 4j	7,225 IU/ml	1,210 IU/ml	NR	Increased mortality had a sensitivity of 84.2% and a specificity of 53.1% at a VL cutoff of 500 IU/ml	500 IU/ml is unlikely to be discriminative between CMV pneumonia and viral shedding in this setting
Beam et al. (64)	2018	Lung, OLT, KT, HCT, nontransplant	Retrospective case-control study; CMV pneumonia vs non-CMV pneumonia	38, 4g	17, 3k	34,800 IU/ml	7,500 IU/ml	100 (3/3), plasma	For all transplant patients, CMV BAL fluid PCR for pneumoniae had 91.7% sensitivity and 100% specificity at a VL cutoff of 34,800 IU/mll	CMV BAL fluid PCR may improve the clinician’s ability to diagnose CMV pneumonia without the need for and associated risks of lung biopsy; of note, none of the HCT patients underwent biopsy and histopathology to confirm CMV pneumonia

^aPneumonia defined as symptoms or signs of pneumonia with positive results by shell vial or conventional culture or by direct fluorescent-antibody (DFA) testing.

^bAsymptomatic CMV shedder.

^cNon-CMV pneumonia and idiopathic pneumonia syndrome (IPS) groups.

^dCompared to asymptomatic controls.

^eCMV pneumonia patients compared to IPS or non-CMV pneumonia patients.

^fPossible, probable, proven, or indeterminate by IHC of bronchial wash and TBB specimens.

^gHCT patients.

^hProbable CMV pneumonia.

ⁱProven pneumonia.

^jFor possible-probable CMV pneumonia, with 4 events (1 recurrence from proven), CMV PCR values for BAL fluid ranged from 1,382 to 40,048 IU/ml, and plasma PCR values ranged from 3,510 to 54,540 IU/ml, with 1 negative cytospin result.

^kPossible pneumonia, only HCT.

^lPossible, probable, and proven pneumonia (n = 12).

^mNR, not reported; VL, viral load; BMT, bone marrow transplant.