A 45-year-old man undergoes allogeneic hematopoietic stem cell transplantation (HSCT) for acute myeloid leukemia. At 8 months post-transplant, he presents with progressive dyspnea and dry cough. Spirometry shows FEV1/FVC ratio of 0.68, FEV1 decline of 14% from baseline, and minimal response to bronchodilators (3% improvement). High-resolution expiratory CT demonstrates mosaic attenuation and air trapping. Respiratory cultures and bronchoscopy are negative for infection. The pattern marked **A** in the diagram represents the pulmonary physiology findings consistent with this clinical presentation. Which of the following best describes the underlying pathophysiological mechanism of this condition?
A. Acute inflammatory response with eosinophilic infiltration of airways and reversible smooth muscle constriction responsive to bronchodilators
B. Reduced alveolar surface area due to parenchymal fibrosis with preserved airway patency and normal spirometric ratios
C. Donor T-cell-mediated alloimmune injury to small-airway epithelium leading to lymphocytic bronchiolitis, concentric fibrosis, and constrictive obliteration of bronchioles <2 mm in diameter
D. Diffuse interstitial pneumonitis with reduced DLCO and restrictive physiology due to cytotoxic T-cell infiltration of lung parenchyma
Explanation
Why option 1 is correct
Bronchiolitis obliterans syndrome (BOS) is the most common noninfectious pulmonary complication of allogeneic HSCT and represents pulmonary chronic graft-versus-host disease (cGVHD). The pathophysiology is characterized by donor T-cell-mediated alloimmune injury to small-airway epithelium and submucosa, which triggers lymphocytic bronchiolitis that evolves into concentric fibrosis and obliteration of bronchioles <2 mm in diameter (constrictive bronchiolitis). This produces irreversible airflow obstruction with the fixed obstructive pattern shown in structure A: FEV1/FVC <0.7, FEV1 decline ≥10% over <2 years post-HCT, minimal bronchodilator reversibility (<12%), and air trapping on expiratory CT (NIH cGVHD Consensus Criteria 2014).
Why each distractor is wrong
Option 2: This describes reversible obstruction with eosinophilic airway disease (pattern B in the diagram), which shows >12% FEV1 improvement to bronchodilators and eosinophilic sputum. BOS is characterized by fixed obstruction with blunted bronchodilator response, not reversible airway obstruction.
Option 3: This describes isolated diffusing capacity reduction (pattern D) or early restrictive disease, which would show reduced TLC and reduced DLCO with preserved or normal spirometric ratios. BOS presents with fixed obstructive physiology (FEV1/FVC <0.7), not a restrictive pattern.
Option 4: While cGVHD can affect the lung parenchyma, this describes restrictive interstitial pneumonitis (pattern C), which presents with reduced TLC, reduced DLCO, and restrictive spirometry. BOS is an obstructive disease of small airways, not a parenchymal restrictive disease.
High-YieldNEET PG
BOS = constrictive bronchiolitis from donor T-cell alloimmunity → fixed airflow obstruction with FEV1/FVC <0.7, FEV1 decline ≥10% in <2 years, minimal bronchodilator response, and air trapping on expiratory CT.
NIH Consensus Criteria for cGVHD 2014; Williams KM et al., Blood 2016
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