. 2017 May 4;38(2):317–331. doi: 10.1016/j.ccm.2016.12.008

Table 3.

Diagnostic evaluation of bronchoscopic specimens for specific infectious pulmonary complications of hematologic malignancies and HCT

Infectious Etiology	Microbiology (BAL, PSB, TBLB)	Pathology (BAL, EBB, TBLB)	Additional Studies (BAL, Other)	Comments
Bacteria • Common pathogens • Mycobacteria • Nocardia	• Stain (Gram, acid-fast) and culture^a • PCR^b	• Cytology (BAL)^c	• Legionella DFA (BAL) • Urine antigens, serology^d	• Nosocomial and community-acquired Gram-positive and Gram-negative bacteria • 10⁵ CFU (BAL) and 10³ CFU (PSB) suggests pneumonia • Patterns of antimicrobial resistance for example, MRSA, VRE, ESBL
Fungi • Candida spp. • Pneumocystis • Aspergillus • Atypical molds • Endemic fungi	Stain (KOH, Giemsa, Silver, Calcofluor white) and culture^a PCR^b	Cytology (BAL)^c Tissue invasion (TBLB) Airway infection (EBB) II	Pneumocystis IFA/DFA/PCR (BAL) A Galactomannan (BAL, serum) Urine and serum antigens, serology^d	• Atypical molds: Mucorales, Fusarium, Scedosporium species • Endemic fungi: C neoformans, H capsulatum, C immitis, B dermatitidis
Viruses Herpesviruses, respiratory viruses	Stain (Papanicolaou) and culture^a PCR^b	Cytology (BAL)^c Tissue invasion (TBLB)^e	CMV DFA (BAL) Serum antigen and viral load^d Nasal swab PCR^b	• Herpesviruses: CMV, EBV, HSV, VZV, HHV-6, • CARVs: adenovirus, coronaviruses, enterovirus, human metapneumovirus, influenza, parainfluenza, respiratory syncytial virus, rhinovirus
Parasites Toxoplasma, Strongyloides	PCR	Immunostain (BAL) Larvae (BAL)	Serology, peripheral cell count, stool studies^d	• BAL microscopy and serology for evaluation of protozoal lung diseases, such as pulmonary malaria or leishmaniasis, and other parasitic processes may be considered in the context of specific travel exposures.

Abbreviations: BAL, bronchoalveolar lavage; CARV, community-acquired respiratory virus; CFU, colony forming unit; CMV, cytomegalovirus; DFA, direct fluorescent antibody; EBB, endobronchial biopsy; EBV, Epstein–Barr virus; ESBL, extended spectrum beta lactam; HCT, hematopoietic cell transplantation; HHV-6, human herpes virus-6; HSV, herpes simplex virus; IFA, indirect fluorescent antibody; KOH, potassium hydroxide stain; MRSA, methicillin-resistant S aureus; PCR, polymerase chain reaction; PSB, protected specimen brushing; spp, species; TBLB, transbronchial lung biopsy; VRE, vancomycin-resistant Enterococcus; VZV, varicella zoster virus.

Direct stains are lacking for atypical organisms such as M pneumoniae and C pneumonia, and special media is required for culture of L pneumophila. Culture is unavailable for P jirovecii, and most fungi are difficult to cultivate in the clinical laboratory. Viral staining and culture is predominantly done for CMV. Culture is uncommonly performed for the identification of T gondii or S stercoralis.

Multiplex PCR is available for a comprehensive panel of respiratory viruses and atypical bacteria, including L pneumoniae, C pneumoniae, M pneumoniae, and B pertussis. PCR for M tuberculosis is routinely performed on samples with a positive acid-fast stain or in smear-negative specimens from a high-risk patient.

Cytology with special stains is generally performed for the identification of organisms that are difficult to cultivate in the laboratory, including acid-fast bacteria, fungi (including Pneumocystis) and CMV.

Other tests that may assist in microbiologic diagnosis include complement fixation and cold agglutinins for Mycoplasma in serum and urine antigen testing for S pneumonia and L pneumophilia serotype 1. Non-BAL antigen testing may also be done for C neoformans (serum), H capsulatum (serum, urine), and B dermatitidis (serum, urine), as well as HSV, RSV, influenza A and B, and adenovirus 40/41 (all serum). Viral load provides information pertaining to CMV activity. Nasopharyngeal swab for PCR of CARV may be useful before bronchoscopy. Serology, peripheral cell count (eg, eosinophilia) and stool studies may be useful adjunctive tests for parasitic causes of infection, notably Strongyloides.

Tissue invasion is commonly caused by fungi (Aspergillus and atypical molds) and CMV. EBB may be useful to establish airway infection caused by Aspergillus.

Reprinted from Harris B, Lowy FD, Stover DE, et al. Diagnostic bronchoscopy in solid-organ and hematopoietic stem cell transplantation. Ann Am Thorac Soc 2013;10(1):45; with permission.