In 2005, a 30-year-old, never-smoker, Caucasian woman with normal body mass index (BMI: 20 kg  m-2) was diagnosed with Hodgkin's lymphoma. She received chemotherapy and autologous HSCT and, one year later, allogeneic HSCT preceded by a myeloablative treatment including cyclophosphamide, cyclosporine A, methotrexate and 12 Gy total body irradiation (TBI). PFTs were all within their respective normality range before allogenic HSCT (Fig. 1), but at 3-month follow-up they revealed a moderate decrement of TLC (3.70 L; 72% of predicted; z-score: -2.47), forced vital capacity (FVC) (2.63 L; 66% of predicted; z-score: -2.80), forced expiratory volume in 1 s (FEV1) (2.21 L; 67% of predicted; z-score: -2.72) and DLCO (15.6 mL min-1  mmHg-1; 67% of predicted; z-score: -2.70) whereas residual volume (RV) was within the normal range but increased from pre-HSCT value, thus resulting in an RV % of predicted to TLC % of predicted ratio (RV/TLC) of 140%. This pattern and computed tomography (CT) scan findings were considered consistent with IPS and eventually treated with oral corticosteroids in addition to maintenance cyclosporine A. Over the following months, the patient experienced progressive exertional dyspnea with dry cough. At 18-months follow-up, PFTs showed the new onset of a severe (FEV1: 1.80 L; 48% of predicted; z-score: -4.01) obstructive abnormality with borderline decrement of FEV1/FVC ratio (0.72; z-score: -1.73) and TLC (4.03 L; 78% of predicted; z-score: -1.91) but RV still within the normal range. Thereafter, TLC returned above the lower limit of normal but FEV1/FVC further decreased, without significant bronchodilator response to 400 mug inhaled salbutamol, while RV/TLC remained >120%. These findings, in the absence of respiratory infections, supported a diagnosis of BOS. A course of inhaled fluticasone/formoterol, oral azithromycin, montelukast, and corticosteroids led to symptom relief. At 7-year follow-up, chest auscultation revealed short wheezes preceded by crackles from mid-to-end inspiration over the lower lung zones bilaterally and full-expiration CT showed bilateral mosaic hypo-attenuation areas suggestive of air trapping. Subsequently, over the next five years TLC and DLCO decreased progressively, while severe obstruction persisted and RV tended to decrease. At 12-year follow-up, TLC and DLCO were severely decreased while RV/TLC was 149% and FEV1/FVC marginally reduced. CT scans showed "wedge-shaped" pleural thickening of upper and middle lung zones bilaterally, with reticular fibrotic pattern involving 16% of lung volume, without inspiratory low-attenuation areas suggestive of emphysema (Fig. 2A and B). Three months later, the patient had a right pneumothorax requiring apical resection by video-assisted thoracoscopy. Histology showed fibro-elastosis of sub-pleural lung parenchyma and visceral pleura, with no inflammation, or granulomas, or emphysematous areas (Fig. 2C and D). Eventually, her condition improved and she was discharged from the hospital.
B) Automatic quantitative 3D analysis of the entire lungs. It is noteworthy, the significant extent of high attenuation areas (HAA-200 to -700 HU) consistent with fibrosis (16% of CT volume) and the lack of low attenuation areas (LAA<-950 HU) consistent with emphysema.