Restrictive Allograft Syndrome (RAS) as a Form of Restrictive Chronic Lung Allograft Dysfunction (rCLAD) with a Pleuroparenchymal Fibroelastosis (PPFE) CT Pattern: A Case-Based Review

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Restrictive Allograft Syndrome (RAS) as a Form of Restrictive Chronic Lung Allograft Dysfunction (rCLAD) with a Pleuroparenchymal Fibroelastosis (PPFE) CT Pattern: A Case-Based Review

Case Presentation

A 46-year-old woman with a prior history of lung cancer and right upper lobectomy presented with progressive abdominal distension, bilateral lower extremity edema, and exertional dyspnea over several months.

Initial Chest CT Findings with IV Contrast:

[Figure 1] Axial C+ – Demonstrates a markedly enlarged right atrium bulging into the left atrium, consistent with an atrial septal aneurysm.

[Figure 2] Axial C+ – Flattening of the interventricular septum with an increased right ventricle to left ventricle ratio, indicating elevated RV pressure.

[Figure 3] Axial C+ – Contrast reflux deep into the hepatic veins. The main pulmonary artery is dilated to approximately 3.5 cm, a common finding in pulmonary hypertension.

Quiz 1

Q1. Which diagnosis is most consistent with these findings?
(1) Left heart failure
(2) Hepatic cirrhosis
(3) Right heart failure
(4) Unremarkable CT chest

Q2. Which is the least likely cause of the chest CT findings?
(1) Idiopathic pulmonary hypertension
(2) Chronic thromboembolism
(3) Systemic hypertension
(4) Chronic lung disease

Q3. Lung transplantation is a good option for idiopathic pulmonary hypertension.
(1) True
(2) False

Answer & Explanation

1. Answer: (3) Right heart failure. Explanation: The combination of right atrial enlargement, interventricular septal flattening, and main pulmonary artery dilatation suggests right heart failure secondary to severe pulmonary hypertension.

2. Answer: (3) Systemic hypertension. Explanation: Systemic hypertension typically causes left ventricular hypertrophy and left heart failure, not isolated right heart strain.

3. Answer: (1) True. Explanation: Especially for those unresponsive to medical therapy, lung transplantation significantly improves survival and quality of life.

Post-Transplant Course

The patient underwent bilateral lung transplantation for refractory idiopathic pulmonary hypertension.
Five years later, she presented with worsening exertional dyspnea and fatigue.

Chest Radiography and CT:

[Figure 4] Chest P-A – Shows diffuse, upper lobe–predominant reticulation and volume loss.

[Figure 5] Axial lung window – Coarse reticulation with architectural distortion.

[Figure 6] Coronal lung window – Upper lobe volume loss with traction bronchiectasis.

[Figure 7] Sagittal lung window – Pleural thickening and subpleural fibrosis consistent with PPFE.

Quiz 2

Q1. Best next step in management?
(1) Initiate antibiotics
(2) Chest CT scan 
(3) Optimize immunosuppression
(4) Diuretics

Q2. Which pattern best describes the disease?
(1) Upper-lobe predominant ground-glass opacity and micronodules
(2) Upper-lobe predominant coarse reticulation, traction bronchiectasis, thick confluent scars
(3) Lower-lobe predominant ground-glass opacity and micronodules
(4) Lower-lobe predominant coarse reticulation and scarring

Q3. Most likely diagnosis?
(1) Bronchiolitis obliterans syndrome
(2) Restrictive chronic lung allograft dysfunction
(3) Idiopathic pulmonary fibrosis
(4) Fibrotic hypersensitivity pneumonitis

Q4. The FEV1/FVC ratio is usually decreased in rCLAD patients.
(1) True
(2) False 

Answer & Explanation

1. Answer: (2) Chest CT scan. Explanation: Chest X-ray findings warrant further characterization with high-resolution CT to evaluate fibrotic changes.

2. Answer: (2) Upper-lobe predominant coarse reticulation, traction bronchiectasis, thick confluent scars.

3. Answer: (2) Restrictive chronic lung allograft dysfunction. Explanation: The combination of progressive dyspnea, upper-lobe fibrosis, and a history of lung transplantation strongly supports RAS, a restrictive phenotype of CLAD. Histology typically reveals PPFE.

4. Answer: (2) False. Explanation: rCLAD shows a restrictive pattern with a normal or elevated FEV1/FVC ratio, unlike BOS, which demonstrates an obstructive pattern. 

Discussion

Chronic Lung Allograft Dysfunction (CLAD) refers to a significant, often progressive, decline in lung function following lung transplantation.
CLAD subtypes are classified based on PFTs and imaging findings:

  • Obstructive phenotype: Bronchiolitis obliterans syndrome (BOS)

  • Restrictive phenotype: Restrictive allograft syndrome (RAS)

  • Mixed phenotype

  • Unclassified CLAD

Pathogenesis & Histology:
RAS is characterized by parenchymal fibrosis, most often pleuroparenchymal fibroelastosis (PPFE). Unlike BOS, which primarily affects small airways with obliterative bronchiolitis, RAS involves subpleural and upper-lobe fibrosis.

Epidemiology:

  • CLAD affects up to 40–50% of recipients within 5 years post-transplant.

  • RAS accounts for ~30% of CLAD cases, and BOS for the remainder.

Clinical Presentation:

  • Some are asymptomatic, detected by PFT decline.

  • Others present with progressive exertional dyspnea and dry cough.

Imaging:

  • RAS: Upper-lobe predominant fibrosis, pleural thickening, PPFE pattern.

  • BOS: Air trapping and mosaic attenuation on expiratory CT.

Treatment & Prognosis:

  • Management includes optimizing immunosuppression and treating concurrent infections.

  • Azithromycin has been shown to delay CLAD onset.

  • Nintedanib and Pirfenidone are under investigation for antifibrotic benefit.

  • Prognosis is generally worse for RAS compared to BOS, with lower post-retransplant survival.

References

[1] W. S. Aronow, “Hypertension and left ventricular hypertrophy,” Ann Transl Med, vol. 5, no. 15, p. 310, 2017.
[2] M. Cristeto Porras et al., “Early onset of azithromycin to prevent CLAD in lung transplantation: Promising results of a retrospective single centre experience,” Clin Transplant, vol. 37, no. 1, e14832, 2023.
[3] J. M. Gauthier, R. R. Hachem, and D. Kreisel, “Update on chronic lung allograft dysfunction,” Curr Transplant Rep, vol. 3, no. 3, pp. 185–191, 2016.
[4] M. P. George, H. C. Champion, and J. M. Pilewski, “Lung transplantation for pulmonary hypertension,” Pulm Circ, vol. 1, no. 2, pp. 182–191, 2011.
[5] M. L. Gunn et al., “High-resolution CT findings of bronchiolitis obliterans syndrome after hematopoietic stem cell transplantation,” J Thorac Imaging, vol. 23, no. 4, pp. 244–250, 2008.
[6] P. Hota et al., “High-resolution CT findings of obstructive and restrictive phenotypes of chronic lung allograft dysfunction: More than just bronchiolitis obliterans syndrome,” AJR Am J Roentgenol, vol. 211, no. 1, W13–W21, 2018.
[7] A. L. Magee et al., “Imaging of hypersensitivity pneumonitis,” Radiol Clin North Am, vol. 54, no. 6, pp. 1033–1046, 2016.
[8] A. Nykänen et al., “Incidence and impact of chronic lung allograft dysfunction after lung transplantation — single-center 14-year experience,” Scand Cardiovasc J, vol. 54, no. 3, pp. 192–199, 2020.
[9] E. Ofek et al., “Restrictive allograft syndrome post lung transplantation is characterized by pleuroparenchymal fibroelastosis,” Mod Pathol, vol. 26, no. 3, pp. 350–356, 2013.
[10] S. E. Verleden et al., “Chronic lung allograft dysfunction phenotypes and treatment,” J Thorac Dis, vol. 9, no. 8, pp. 2650–2659, 2017.
[11] R. Vos et al., “Pirfenidone: A potential new therapy for restrictive allograft syndrome?,” Am J Transplant, vol. 13, no. 11, pp. 3035–3040, 2013.
[12] N. Yoshiyasu and M. Sato, “Chronic lung allograft dysfunction post-lung transplantation: The era of bronchiolitis obliterans syndrome and restrictive allograft syndrome,” World J Transplant, vol. 10, no. 5, pp. 104–116, 2020.

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