Version May 2024
| Disease process | Risk factors | Associated manifestations | Radiographic findings | Useful diagnostic tests | Lung biopsy needed |
| Bacterial pneumonia | Focal or patchy consolidation, may be peribronchial Occasionally mass-like "round-pneumonia" | Blood cultures, Legionella and pneumococcal urinary antigens, BAL for Gram stain and aerobic and anaerobic cultures, Legionella culture, Mycoplasma PCR, and modified AFB stain and culture for Nocardia | Rarely | ||
| Mycobacterial pneumonia | Total body irradiation, chronic GVHD | M. haemophilum is associated with skin nodules and/or joint inflammation | Miliary pattern | TST after HCT not helpful; AFB staining and cultures of induced sputum and BAL are helpful | Rarely |
| CMV pneumonitis | Seropositive recipient with seronegative donor; delayed reconstitution, prior treatment for CMV | CT: patchy or diffuse ground-glass opacities, patchy consolidation, small nodular opacities; rarely tree-in-bud pattern | Serology, blood test for pp65 antigen or CMV PCR, BAL and endobronchial brush for cytologic examination for inclusion bodies and BAL shell vial cultures for CMV | Rarely | |
| Respiratory viruses | Exposure to someone with active viral infection | URI symptoms prior to onset of lower respiratory tract symptoms | Diffuse ground glass opacities are the most common | PCR, culture, or rapid immunofluorescence of nasopharyngeal lavage or swab and BAL fluid | Sometimes to completely exclude other possibilities |
| Fungal infection (eg, invasive aspergillosis, Fusarium, agents of mucormycosis, Candida, Scedosporium, Pneumocystis) | Presence and severity GVHD, older patient age, cytopenia, CMV infection | Focal nodular and consolidative opacities, "halo sign," "reverse halo sign," sometimes subpleural wedge-shaped densities | Broad microbiologic testing of blood and BAL; blood tests for β-D-glucan and Aspergillus galactomannan EIA; BAL for Aspergillus galactomannan EIA; and induced sputum and BAL for Pneumocystis staining | Sometimes when cultures are negative and no response to initial therapy | |
| Idiopathic pneumonia syndrome | Busulfan, high dose cyclophosphamide, radiation, nonmyeloablative conditioning regimen | Extensive opacities | Negative stains, cultures, antigen testing, and PCR of blood, sputum, urine, and BAL | Yes, either transbronchial or surgical | |
| Heart failure | Anthracycline treatment; coronary artery disease | Bibasilar crackles, peripheral edema | CT: patchy or diffuse ground-glass opacities, pleural effusion | BNP, echocardiogram | No |
| Diffuse alveolar hemorrhage | Underlying mucopolysaccharidosis | CT: patchy or diffuse opacities, may have air bronchograms | BAL showing increasingly bloody return in sequential lavages and >20 percent hemosiderin-laden macrophages | Not usually | |
| Connective tissue disease | Myeloablative conditioning regimen | Extrapulmonary manifestations such as dry mouth/dry eyes, joint pain/swelling, muscle weakness | CT: subpleural, ground-glass opacities; septal thickening | Autoantibody tests positive | Often to identify specific type of interstitial pneumonitis |
| Cryptogenic organizing pneumonia/organizing pneumonia (formerly known as bronchiolitis obliterans organizing pneumonia) | Irradiation, CMV infection, HCT associated connective tissue disease, chronic GVHD | CT: patchy air-space consolidation, ground-glass opacities, small nodular opacities, "reverse halo sign" | Lung biopsy | Yes | |
| Bronchiolitis obliterans | Chronic GVHD, postviral | CT initially clear; as progresses, CT may show mosaic ground glass opacities and bronchiectasis | Spirometry showing airflow limitation Skin biopsy for GVHD | Sometimes, if diagnosis uncertain | |
| Malignancy | Underlying lymphoma, EBV infection in posttransplant lymphoproliferative disorder | Nodular opacities, lymphangitic pattern | BAL cytology and flow cytometry, biopsy | Biopsy usually needed | |
| Pulmonary alveolar proteinosis | HCT for myeloid disorder | Perihilar opacities in a "bat-wing" distribution often with air bronchograms | Bronchoalveolar lavage showing characteristic milky appearance and positive stain for lipoproteins | Not usually | |
| Pulmonary cytolytic thrombi | Chronic GVHD is a risk factor | Low grade fever, cough | CT: peripheral nodules | BAL to rule out infection; lung biopsy | Yes, findings are basophilic cytolytic thrombi in the small to medium distal pulmonary vessels with entrapped monocytes |
| Pulmonary veno-occlusive disease | Onset after first 100 days, chronic GVHD | Reduced DLCO | CXR: pleural effusion and Kerley B lines; CT chest: centrilobular ground glass opacities; no emboli on CTPA | Right heart catheterization; BAL showing occult hemorrhage | For definitive diagnosis |
| Drug toxicity | History of pneumotoxic drug use (eg, busulfan, cyclophosphamide) | May be associated with rash, peripheral eosinophilia | Varied | Increased BAL eosinophils may be seen; other processes excluded by negative blood and BAL stains and cultures, negative fungal studies | Sometimes to completely exclude other possibilities |
| Radiation pneumonitis | History of radiation therapy involving lungs | Acute: onset usually 4 to 12 weeks following irradiation Late: onset after 6 to 12 months | Acute CT: ground-glass attenuation within the area of irradiated lung Late CT: linear opacities (scarring) or an area of dense consolidation and volume loss | Other processes excluded by negative blood and BAL stains and cultures, negative fungal studies | Sometimes to completely exclude other possibilities |
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