ADOPTING ORPHAN DISEASES RARE INTERSTITIAL LUNG DISEASES

adoptingorphandiseaseskapak

LUNG TRANSPLANTATION INRARE INTERSTITIAL LUNG DISEASES

Ayşe Nigar İzgi1 Sevinç Çıtak2

1Kartal Koşuyolu High Specialization Training and Research Hospital, Department of Pulmonology and Lung Transplantation, İstanbul, Türkiye
2Kartal Koşuyolu High Specialization Education and Research Hospital, Department of Thoracic Surgery and Lung Transplantation, İstanbul, Türkiye

İzgi AN, Citak S. Lung Transplantation in Rare Interstitial Lung Diseases. In: Altinisik G, McCormack FX, editors. Adopting Orphan Diseases: Rare Interstitial Lung Diseases. 1st ed. Ankara: Türkiye Klinikleri; 2025. p.245-256.

ABSTRACT

In rare interstitial lung diseases (ILDs), diagnostic uncertainty, limited access to effective pharmacologic therapies, and difficulties in reaching experienced centers complicate patient management. These challenges often persist in the lung transplantation process when the disease progresses to end-stage respiratory failure. Lung transplantation can significantly improve both survival and quality of life in selected subtypes of rare ILDs. However, standardized, disease-specific criteria for referral to transplant centers and listing remain undefined.

Given the heterogeneous clinical course of these diseases, the success of transplantation largely depends on appropriate patient selection. All available medical treatment options should be exhausted prior to listing, and surgical feasibility must be carefully assessed. Certain ILD subtypes present with technical challenges during surgery, for example, recurrent pneumothorax and pleural adhesions in cystic ILDs, extensive mediastinal calcifications in silicosis, or pleural thickening and chest wall rigidity in pleuroparenchymal fibroelastosis.

In diseases associated with a risk of extrapulmonary involvement, such as Langerhans cell histiocytosis and lymphangioleiomyomatosis (LAM), early referral to a transplant center is critical for excluding systemic spread, thoroughly evaluating comorbidities, and treating any existing infections. Early referral also allows sufficient time to address potentially preventable or correctable contraindications. Otherwise, patients presenting in a severely debilitated state may be unsuitable for rehabilitation or may not have adequate time on the waiting list to receive a suitable donor.

The choice between single and double lung transplantation is determined by factors including the underlying disease, patient age, comorbidities, and the presence of pulmonary hypertension. While double lung transplantation provides a greater volume of healthy parenchyma and may offer long-term functional benefits, it is associated with longer operative times and an increased risk of perioperative complications. Consequently, single lung transplantation is generally preferred in patients with idiopathic pulmonary fibrosis and elderly individuals with ILD, whereas double lung transplantation is recommended for patients with cystic fibrosis, bronchiectasis, LAM, and severe pulmonary hypertension.

For patients with rare ILDs who experience progressive disease despite medical therapy or who lack effective treatment options and develop end-stage lung failure, lung transplantation remains the only curative option that can prolong survival and improve quality of life. There is a continued need to develop standardized, disease-specific clinical criteria to guide transplant decision-making in this population.

Keywords: Rare interstitial lung diseases; Lung transplantation; Curative treatment; Patient selection; Waiting list

Referanslar

  1. Chambers DC, Cherikh WS, Harhay MO, et al. The International Thoracic Organ Transplant Registry of the International Society for Heart and Lung Transplantation: thirty-sixth adult lung and heart-lung transplantation report-2019; focus theme: donor and recipient size match. J Heart Lung Transplant 2019;38:1042-55. [Crossref]  [PubMed]  [PMC]
  2. Singh TP, Hsich E, Cherikh WS, et al. The International Thoracic Organ Transplant Registry of the International Society for Heart and Lung Transplantation: 2025 Annual Report of Heart and Lung Transplantation. The Journal of Heart and Lung Transplantation. (article in press) [Crossref]  [PubMed]
  3. Leard LE, Holm AM, Valapour M, et al. Consensus document for the selection of lung transplant candidates: An update from the International Society for Heart and Lung Transplantation. J Heart Lung Transplant. 2021;40(11):1349-79. [Crossref]  [PubMed]  [PMC]
  4. Yusen RD, Edwards LB, Dipchand AI, et al. International Society for Heart and Lung Transplantation. The Registry of the International Society for Heart and Lung Transplantation: thirty-third adult lung and heart-lung transplant report-2016; focus theme: primary diagnostic indications for transplant. J. Heart Lung Transplant. 2016; 35:1170-84. [Crossref]  [PubMed]
  5. Wajda N, Zhu Z, Jandarov R, Dilling DF, Gupta N. Clinical outcomes and survival following lung transplantation in patients with pulmonary Langerhans cell histiocytosis. Respirology. 2020;25(6):644-50. [Crossref]  [PubMed]  [PMC]
  6. Dauriat G, Mal H, Thabut G, et al. Lung transplantation for pulmonary langerhans cell histiocytosis: a multicenter analysis. Transplantation. 2006;81(5):746-50. [Crossref]  [PubMed]
  7. Goyal G, Abeykoon JP, Hu M, et al. Single-agent cladribine as an effective front-line therapy for adults with Langerhans cell histiocytosis. Am J Hematol. 2021;96(5):E146-E150. [Crossref]  [PubMed]
  8. Warrior K, Dilling DF. Lung transplantation for lymphangioleiomyomatosis. J Heart Lung Transplant. 2023;42(1):40- [Crossref]  [PubMed]
  9. King-Biggs MB, Dunitz JM, Park SJ, Kay Savik S, Hertz MI. Airway anastomotic dehiscence associated with use of sirolimus immediately after lung transplantation. Transplantation. 2003;75(9):1437-43. [Crossref]  [PubMed]
  10. Khawar MU, Yazdani D, Zhu Z, et al. Clinical outcomes and survival following lung transplantation in patients with lymphangioleiomyomatosis. J Heart Lung Transplant 2019;38:949-55. [Crossref]
  11. McCarthy C, Bonella F, O’Callaghan M, et al. European Respiratory Society guidelines for the diagnosis and management of pulmonary alveolar proteinosis. Eur Respir J. 2024;64(5):2400725. [Crossref]  [PubMed]
  12. Schwarz S, Prosch H, Yekeler E , et al. Lung Transplantation for Pulmonary Alveolar Proteinosis A Retrospective International Multicenter Analysis. The Journal of Heart and Lung Transplantation. 2025;44(4):S126. [Crossref]  [PubMed]
  13. Kosciuk P, Meyer C, Wikenheiser-Brokamp KA, McCormack FX. Pulmonary alveolar microlithiasis. Eur Respir Rev. 2020;29(158):200024. [Crossref]  [PubMed]  [PMC]
  14. Klikovits T, Slama A, Hoetzenecker K, et al. A rare indication for lung transplantation pulmonary alveolar microlithiasis: institutional experience of five consecutive cases. Clin Transplant. 2016;30(4):429-34. [Crossref]  [PubMed]
  15. Hashim MY, Yousef YR, Alkattan KY, et al. Lung Transplantation Outcomes of Patients with Pulmonary Alveolar Microlithiasis the Largest Series from a Single Centre Experience. The Journal of Heart and Lung Transplantation, 2024;43(4):S443-S444. [Crossref]  [PubMed]
  16. Dotan M, Rosengarten D, Azem K. Survival Analysis and Surgical Considerations in Lung Transplantation for Silicosis: Single vs. Double Lung Transplants. The Journal of Heart and Lung Transplantation, Volume 43, Issue 4, S654 S655. [Crossref]  [PubMed]
  17. Hayes D Jr, Hayes KT, Hayes HC, Tobias JD. Long-Term Survival After Lung Transplantation in Patients with Silicosis and Other Occupational Lung Disease. Lung. 2015;193(6):927-31. [Crossref]  [PubMed]
  18. Perin FA, Altmayer S, Nascimento DZ, et al. Long-term survival following unilateral lung transplantation for end-stage silicosis relative to idiopathic pulmonary fibrosis. J Bras Pneumol. 2022;48(2):e20210513. [Crossref]  [PubMed]  [PMC]
  19. Clermidy H, Mercier O, Brioude G, et al. Outcomes of lung transplantation for pleuroparenchymal fibroelastosis: A French multicentric retrospective study. J Heart Lung Transplant. 2024;43(10):1727-1736. [Crossref]  [PubMed]
  20. Shiiya H, Nakajima J, Date H, et al. Outcomes of lung transplantation for idiopathic pleuroparenchymal fibroelastosis. Surg Today. 2021;51(8):1276-1284. [Crossref]  [PubMed]
  21. Ikegami N, Nakajima N, Yoshizawa A, et al. Clinical, radiological and pathological features of idiopathic and secondary interstitial pneumonia with pleuroparenchymal fibroelastosis in patients undergoing lung transplantation. Histopathology. 2022;80(4):665-676. [Crossref]  [PubMed]
  22. Faccioli E, Verzeletti V, Giraudo C, et al. Lung Transplantation for Pleuroparenchymal Fibroelastosis: A Single-Center Experience with Revision of Literature. Biomedicines. 2023;11(6):1505. [Crossref]  [PubMed]  [PMC]
  23. Chambers DC, Cherikh WS, Harhay MO, et al. The International Thoracic Organ Transplant Registry of the International Society for Heart and Lung Transplantation: thirty-sixth adult lung and heart-lung transplantation report-2019; focus theme: donor and recipient size match. J Heart Lung Transplant 2019;38:1042-1055. [Crossref]  [PubMed]  [PMC]
  24. Ronan NJ, Helly F, Murray MA. Lung transplantation for interstitial lung disease. Breathe (Sheff). 2025;21(2):240169. [Crossref]  [PubMed]  [PMC]
  25. Watanabe T, Hirama T, Onodera K, Notsuda H, Oishi H, Niikawa H, Imaizumi K, Okada Y. Native-lung complications following single-lung transplantation for interstitial lung disease: an in-depth analysis. BMC Pulm Med. 2024;24(1):202. [Crossref]  [PubMed]  [PMC]
  26. Goyal G, Abeykoon JP, Hu M, et al. Single-agent cladribine as an effective front-line therapy for adults with Langerhans cell histiocytosis. Am J Hematol. 2021;96(5):E146– E150. [Crossref]  [PubMed]
  27. Citak S, Saribas E, Halis AN, Alkilic FF, Cardak ME, Vayvada M, Tasci AE. Expanding horizons: lung transplantation for non-IPF interstitial lung diseases. BMC Pulm Med. 2024;24(1):482. [Crossref]  [PubMed]  [PMC]