Diagnostic Criteria for Chronic GVHD in the Lung
Lung chronic GVHD manifests as bronchiolitis obliterans syndrome (BOS) and requires either pathologic confirmation via lung biopsy OR clinical characteristics on pulmonary function tests PLUS distinctive features of chronic GVHD in another organ. 1
Diagnostic Pathways
Pathologic Diagnosis
- Lung biopsy showing bronchiolitis obliterans is sufficient alone to diagnose pulmonary chronic GVHD without requiring evidence of GVHD in other organs. 2, 3
- Biopsy is not always feasible and is not mandatory if clinical criteria are met. 1
Clinical Diagnosis (Without Biopsy)
Clinical characteristics of BOS assessed by pulmonary function tests are ONLY diagnostic of lung chronic GVHD if distinctive features of chronic GVHD are present in another organ. 1, 2, 3
This means you must identify chronic GVHD manifestations in at least one other organ system, which can include: 2, 4
- Skin and appendages: Poikiloderma, lichen planus-like features, sclerotic features, lichen sclerosus-like features
- Mouth: Lichen-type features, xerostomia, mucoceles
- Eyes: New onset dry, gritty, or painful eyes
- Female genitalia: Lichen planus-like features, vaginal scarring or stenosis
- Esophagus: Esophageal web, strictures, or stenosis in the upper to mid-third of esophagus
- Connective tissues: Fasciitis, joint stiffness, contractures
Pulmonary Function Test Criteria
The NIH Consensus Development Project defines BOS based on: 1
- FEV1 < 75% of predicted value (or decline of ≥10% from baseline)
- FEV1/FVC ratio < 0.7 or ≥25% decline in FEF25-75
- Evidence of air trapping on expiratory CT or residual volume > 120% of predicted on pulmonary function tests
- Absence of infection in the respiratory tract
Severity Grading
Once diagnosed, lung chronic GVHD is graded according to NIH Consensus Development Project criteria: 1
- Score 1: FEV1 60-79% predicted
- Score 2: FEV1 40-59% predicted
- Score 3: FEV1 < 40% predicted
Critical Diagnostic Considerations
Rule Out Alternative Diagnoses
Before confirming pulmonary chronic GVHD, you must exclude: 2
- Infection (bacterial, viral, fungal)
- Drug-induced lung injury or toxicity
- Malignancy recurrence
- Other causes of obstructive or restrictive lung disease
Emerging Phenotypes
Recent research suggests the traditional NIH criteria may miss high-risk patients with restrictive or mixed obstructive/restrictive patterns. 5 A 2022 study adapted the ISHLT chronic lung allograft dysfunction criteria and identified that patients with FEV1 < 80% predicted with restrictive, mixed, or undefined patterns had similar mortality risk to those meeting traditional BOS criteria. 5 However, current NCCN guidelines still rely on the NIH Consensus criteria focusing on obstructive patterns. 1
Restrictive Disease from Chest Wall Sclerosis
Be aware that advanced sclerotic skin changes of the chest wall from chronic GVHD can cause restrictive lung defects that may overshadow or coexist with the obstructive pattern of BOS. 6 This represents a distinct mechanism of pulmonary impairment in chronic GVHD patients.
Common Pitfalls
- Do not diagnose lung chronic GVHD based on pulmonary function tests alone without either lung biopsy confirmation or documented chronic GVHD in another organ. 1, 2, 3
- Do not delay treatment while awaiting biopsy if the patient has typical clinical features and chronic GVHD in other organs. 2, 3
- Do not overlook infectious causes, particularly in immunosuppressed post-transplant patients—always perform appropriate microbiologic testing. 2