Lung Transplantation: CT Assessment of Chronic Lung Allograft Dysfunction (CLAD)

Abstract

Chronic lung allograft rejection remains one of the major causes of morbi-mortality after lung transplantation. The term Chronic Lung Allograft Dysfunction (CLAD) has been proposed to describe the different processes that lead to a significant and persistent deterioration in lung function without identifiable causes. The two main phenotypes of CLAD are Bronchiolitis Obliterans Syndrome (BOS) and Restrictive Allograft Syndrome (RAS), each of them characterized by particular functional and imaging features. These entities can be associated (mixed phenotype) or switched from one to the other. If CLAD remains a clinical diagnosis based on spirometry, computed tomography (CT) scan plays an important role in the diagnosis and follow-up of CLAD patients, to exclude identifiable causes of functional decline when CLAD is first suspected, to detect early abnormalities that can precede the diagnosis of CLAD (particularly RAS), to differentiate between the obstructive and restrictive phenotypes, and to detect exacerbations and evolution from one phenotype to the other. Recognition of early signs of rejection is crucial for better understanding of physiopathologic pathways and optimal management of patients.

Keywords: chronic lung allograft dysfunction; computed tomography (CT) scan; lung transplantation.

Figure 1

Examples of non-CLAD conditions (red arrow). (A) Right lower lobe bronchial stenosis responsible for obstructive changes on PFT; (B) post-surgical right phrenic nerve damage responsible for restrictive changes; (C) development of Kaposi’s sarcoma on the lung graft responsible for mixed obstructive and restrictive changes.

Figure 2

A 32-year-old man, bilateral LT in 2009 for cystic fibrosis. Diagnosis of BOS in 2011. (A) CT scan in January 2012 (FEV1 48%) shows no evidence of small or large airway disease; (B) CT scan in December 2017 (FEV1 18%, CLAD 4). Severe and diffuse bronchial wall thickening (red arrows), associated with mild bronchiectatic changes. Note the paucity of vascular markings in 2017 (yellow circles) compared to 2012 and subsequent hypoattenuation of lung parenchyma, related to small airway hypoventilation and fibrosis.

Figure 3

BOS in a 42-year-old patient. CT scans at CLAD diagnosis (A) and 2 years later (B–D); (A) August 2018: CLAD is diagnosed on spirometry with an obstructive profile. The CT scan does not show significant abnormality, confirming the BOS phenotype; (B) June 2020: inspiratory CT scan. Although the density of the lung parenchyma looks rather homogeneous, global hypoperfusion is obvious when comparing this CT to the baseline scan. The vessels are smaller and the overall density of the lung parenchyma is lower. There is no significant bronchial wall thickening nor large airway abnormality; (C) June 2020: expiratory scan unveils mosaicism and heterogeneous air trapping related to BOS; (D) June 2020: minimum intensity projection (mIP) technique applied on the inspiratory images (soft tissue kernel, parenchymal windowing) improves detection of mosaic perfusion with good correlation with expiratory images. This technique can be helpful in the absence of expiratory images or if the expiration has not been optimal.

Figure 4

Diffuse opacities associated with RAS in a 38-year-old woman showing slowly progressive clinical symptoms and functional decline. (A) CT scan at CLAD onset, showing subtle reticular changes in the right upper lobe; (B) 2 years later, the patient has developed upper and subpleural predominant consolidation and reticulations, associated with paraseptal emphysema. Note the diffuse ground glass opacities consistent with inflammation and a possible NSIP pattern (C).

Figure 5

Early detection and evolution of RAS in a 24-year-old man, who underwent bilateral LT in 2007 for cystic fibrosis. Axial and coronal images of CT scans at optimal spirometry (A) 4 months before the diagnosis of CLAD (B), 8 (C) and 22 months (D) after the diagnosis of CLAD. (A) May 2008: normal CT scan; (B) August 2008: first visualization of subtle subpleural ground glass areas and consolidation (red arrows), considered nonspecific and treated with antibiotics. The diagnosis of CLAD was confirmed in December 2008 with a RAS profile; (C) August 2009: rapid evolution towards destructive, upper predominant cystic lesions, and interstitial fibrosis; (D) October 2010: late RAS. CT changes suggestive of pleuroparenchymal fibroelastosis with dense subpleural fibrosis and pleural thickening; dramatic loss of volume of the upper lobes.

Figure 6

Unilateral RAS in a 61-year-old woman, who underwent right LT for α1-antitrypsin deficiency. (A): Baseline CT scan. Note the diffuse hypo attenuation and hypoperfusion of the left native lung, compared to the right allograft. An adapted normal FEV1 must be defined in this patient, taking into account the severe obstruction from the left lung; (B) Diagnosis of CLAD, with concomitant apparition of subpleural interstitial opacities in the right lung; (C) 3 years later, the allograft has been replaced by dense fibrosis and is totally collapsed. There is marked-over expansion of the left lung.

Figure 7

Acute exacerbation of RAS in a 67-year-old woman; (A) baseline CT scan. Stable obstructive pattern on PFT related to right main bronchus stenosis, treated by endo-bronchial stenting (yellow circle); (B) diagnosis of CLAD with restrictive profile. CT shows persistent subpleural opacities (ground glass mostly), consistent with RAS; (C) 1 month later, the patient presented with acute clinical and functional deterioration. CT shows extensive and rapidly progressive ground glass opacities, suggesting diffuse alveolar damage and/or AFOP. The patient died a few days later.

Figure 8

Mixed CLAD in a 30-year-old patient. (A) Diagnosis of CLAD in 2007 with initial obstructive phenotype. CT shows mild bronchial wall thickening; (B) progressive decline in TLC, suggesting an evolution towards a mixed CLAD (oct 2009). Note the apparition of subpleural opacities in the upper lobes (red arrows) and mild and diffuse ground glass opacities; (C) rapid functional and radiological deterioration, with upper predominant fibrosis and subpleural consolidation suggesting PPFE, mild cylindrical bronchiectasis in the lung bases (yellow circles).