Table 3.
Pulmonary Syndromes After Allogeneic HCT
| Entity | Established in definition of lung GVHD | PFT pattern | High Resolution Chest CT Findings | Lung Histology | Comment |
|---|---|---|---|---|---|
| Bronchiolitis obliterans syndrome | Yes | Fixed obstructive pattern: FEV1 decline >10%, FEV1/FVC < LLN. Elevated residual volume or residual volume/Total Lung Capacity. FEV1/FVC > LLN with preserved TLC may be seen. DLCO may be normal or reduced. | Signs of air trapping (mosaic attenuation on expiratory phase) or bronchiolitis (centrilobular micronodules, bronchial wall thickening) or late sequalae (bronchiectasis) | Obliterative bronchiolitis: partial or complete fibroproliferative occlusion of terminal small bronchioles, lymphocytic bronchiolitis may also be seen | Subtypes of BOS have been defined based on timing of onset after HCT, initial tempo of onset, FEV1 decline, histology, response to therapy, and prognosis. |
| Restrictive impairment caused by ILD entities* | |||||
| Organizing pneumonia [267] | No, but evidence supports association with acute and chronic GVHD. | Restrictive impairment with reduced TLC with FEV1/FVC > LLN most common. Obstructive or mixed pattern may be seen. Reduced DLCO. | Patchy and peribronchial infiltrates or consolidation, and reticular ground glass opacities, often predominant in upper lobes and periphery [268] | Bronchiolar and alveolar granulation tissue | Bronchoscopy should be performed to rule out infection. Clinical diagnosis often made without lung histology and is empirically based on steroid-responsiveness |
| Nonspecific interstitial pneumonia [266] | No | Reduced TLC and DLCO | Confluent bilateral lower lobe ground glass opacities, bronchiectasis and lower lobe volumes loss, classically sparing the subpleural area | Diffuse alveolar wall thickening by uniform fibrosis; interstitial inflammation | Bronchoscopy should be performed to rule out infection |
| Pleuroparenchymal pulmonary fibroelastosis [266,269] | No | Reduced TLC and DLCO, occasionally obstructive and restrictive pattern. Progressive and severe impairment over time | Upper lobe fibrosis with subpleural and pleural thickening, loss of lung volume, and lower lobe traction bronchiectasis | Subpleural and pleural fibroelastic proliferation with minimal inflammation | Diagnosis is usually made by typical chest CT findings |
| Restrictive impairment not attributed to ILD† | |||||
| Truncal sclerosis | No. Sclerosis due to chronic GVHD is an indirect cause of ventilatory impairment | Reduced TLC; RV/TLC may be elevated but usually does not necessarily indicate small airways disease | No parenchymal infiltrates. Parametric response mapping shows low inspiratory volumes. | N/A. | |
| Respiratory muscle weakness | No. Weakness may result from chronic GVHD-related myositis or prolonged steroid use to treat chronic GVHD. | Concomitant reduction in FVC and FEV1, reduced TLC with relative sparing of RV. Reduced supine FVC. Maximal inspiratory and expiratory pressures may be reduced. | Low lung volumes, normal parenchyma. If diaphragmatic weakness or paralysis is suspected, a fluorographic sniff test may show reduced diaphragmatic excursion | N/A. Evidence of myositis in a peripheral muscle. | Diagnosis of exclusion |
RAS has been defined for lung transplantation [89] as a manifestation of chronic allograft dysfunction. BOS is the obstructive form of chronic lung allograft destruction after lung transplantation. RAS after lung transplantation is defined by restrictive physiology and persistent pulmonary infiltrates that represent heterogeneous histology. A similar syndrome of restrictive impairment as a manifestation of alloimmunity in the context of chronic GVHD may also exist; however, the epidemiologic associations and definitions remain to be determined. It is possible that ILD entities that occur in the context of chronic GVHD could be considered as an “RAS-like” condition, or “restrictive alloimmune syndrome” after HCT.
ILD indicates interstitial lung disease; RAS, restrictive allograft syndrome.
Multiple entities, as per the ATS/ERS classification of ILD may occur after HCT, beyond what is listed here [85,266]. If restrictive impairment is seen on PFT (i.e., reduced FVC with preserved FEV1/FVC and reduced TLC), high resolution chest CT should be performed to evaluate for ILD and other entities.
These entities are secondary to extrathoracic consequences of chronic GVHD.