Morphological changes during CLAD development after lung transplantation

Abstract

<b>Background:</b> Chronic lung allograft dysfunction (CLAD) is a major complication after lung transplantation, with 2 main phenotypes: bronchiolitis obliterans syndrome (BOS) and restrictive lung allograft syndrome (RAS). Our aim was to study morphological changes over time of lung (volume and density) and airways (number, length, diameter) using serial <i>in-</i> and <i>ex vivo</i> High Resolution (HR)CT. <b>Methods:</b> A total of 3 consecutive <i>in vivo</i> HRCTs were assessed (pre-CLAD at best FEV1, middle of FEV1 decline, severe CLAD) in 4 individual CLAD patients (2 BOS, 2 RAS). Following explantation, <i>ex vivo</i> HRCT of 1 explant lung (2 BOS, 2 RAS) was analysed, with 2 unused donor lungs serving as controls. Using Mimics Innovation Suite 24, airways were segmented and lung volume/densities of all <i>in vivo</i> and <i>ex vivo</i> scans were analysed (18 scans). Airway number, length and diameter per generation on <i>ex vivo</i> HRCT were assessed (6 scans) with NeuronStudio. <b>Results:</b><i>In vivo</i> BOS lung volumes increased (+115 mL), density decreased slightly (-42 HU) during follow-up, due to air trapping and hyperinflation. <i>Ex vivo</i> airways demonstrated increased airway diameter at generations 9-12 (2027 µm, vs 1383 µm in control), due to distal obliteration. <i>In vivo</i> RAS lung volumes decreased (-845 mL), density increased over time (+212 HU), due to parenchymal/interstitial fibrosis. Airways <i>ex vivo</i> shortened (length generation 9-12 6975 µm, vs. 14830 µm in controls), and became more visible: visibility increased up to the 26th generation (alveolar ducts), attributable to increased airway diameter and wall thickness. <b>Conclusion:</b> Post-transplant morphological changes over time may help better understand the underlying pathophysiology in different CLAD phenotypes.