Hepatopulmonary syndrome is a frequent cause of dyspnea in the short telomere disorders

Amany I. Gorgy, Naudia L. Jonassaint, Susan E. Stanley, Ayman Koteish, Amy Dezern, Jolan E. Walter, Sabrina C. Sopha, James Hamilton, Julie E Hoover Fong, Allen R Chen, Robert A Anders, Ihab R Kamel, Mary Armanios

Research output: Contribution to journalArticle

Abstract

Background: Telomere syndromes have their most common manifestation in idiopathic pulmonary fibrosis and emphysema. The short telomere defect in these patients may manifest systemically as bone marrow failure and liver disease. We sought to understand the causes of dyspnea in telomerase and telomere gene mutation carriers who have no parenchymal lung disease. Methods: Clinical and pathologic data were reviewed as part of a Johns Hopkins -based natural history study of short telomere syndromes including dyskeratosis congenita. Results: Hepatopulmonary syndrome (HPS) was diagnosed in nine of 42 cases (21 %). Their age at presentation was significantly younger than that of cases initially presenting with pulmonary fibrosis and emphysema (median, 25 years vs 55 years; P <.001). Cases had evidence of intra- and extrapulmonary arteriovascular malformations that caused shunt physiology. Nodular regenerative hyperplasia was the most frequent histopathologic abnormality, and it was seen in the absence of cirrhosis. Dyspnea and portal hypertension were progressive, and the median time to death or liver transplantation was 6 years (range, 4-10 years; n = 6). In cases that underwent liver transplantation, dyspnea and hypoxia improved, but pulmonary fibrosis subsequently developed. Conclusions: This report identifies HPS as a frequent cause of dyspnea in telomerase and telomere gene mutation carriers. While it usually precedes the development of parenchymal lung disease, HPS may also co-occur with pulmonary fibrosis and emphysema. Recognizing this genetic diagnosis is critical for management, especially in the lung and liver transplantation setting.

Original languageEnglish (US)
Pages (from-to)1019-1026
Number of pages8
JournalChest
Volume148
Issue number4
DOIs
StatePublished - Oct 1 2015

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Hepatopulmonary Syndrome
Telomere
Dyspnea
Pulmonary Emphysema
Pulmonary Fibrosis
Liver Transplantation
Telomerase
Lung Diseases
Dyskeratosis Congenita
Bone Marrow Diseases
Idiopathic Pulmonary Fibrosis
Mutation
Lung Transplantation
Portal Hypertension
Natural History
Genes
Hyperplasia
Liver Diseases
Fibrosis

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine
  • Cardiology and Cardiovascular Medicine

Cite this

Gorgy, A. I., Jonassaint, N. L., Stanley, S. E., Koteish, A., Dezern, A., Walter, J. E., ... Armanios, M. (2015). Hepatopulmonary syndrome is a frequent cause of dyspnea in the short telomere disorders. Chest, 148(4), 1019-1026. https://doi.org/10.1378/chest.15-0825

Hepatopulmonary syndrome is a frequent cause of dyspnea in the short telomere disorders. / Gorgy, Amany I.; Jonassaint, Naudia L.; Stanley, Susan E.; Koteish, Ayman; Dezern, Amy; Walter, Jolan E.; Sopha, Sabrina C.; Hamilton, James; Hoover Fong, Julie E; Chen, Allen R; Anders, Robert A; Kamel, Ihab R; Armanios, Mary.

In: Chest, Vol. 148, No. 4, 01.10.2015, p. 1019-1026.

Research output: Contribution to journalArticle

Gorgy AI, Jonassaint NL, Stanley SE, Koteish A, Dezern A, Walter JE et al. Hepatopulmonary syndrome is a frequent cause of dyspnea in the short telomere disorders. Chest. 2015 Oct 1;148(4):1019-1026. https://doi.org/10.1378/chest.15-0825
Gorgy, Amany I. ; Jonassaint, Naudia L. ; Stanley, Susan E. ; Koteish, Ayman ; Dezern, Amy ; Walter, Jolan E. ; Sopha, Sabrina C. ; Hamilton, James ; Hoover Fong, Julie E ; Chen, Allen R ; Anders, Robert A ; Kamel, Ihab R ; Armanios, Mary. / Hepatopulmonary syndrome is a frequent cause of dyspnea in the short telomere disorders. In: Chest. 2015 ; Vol. 148, No. 4. pp. 1019-1026.
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abstract = "Background: Telomere syndromes have their most common manifestation in idiopathic pulmonary fibrosis and emphysema. The short telomere defect in these patients may manifest systemically as bone marrow failure and liver disease. We sought to understand the causes of dyspnea in telomerase and telomere gene mutation carriers who have no parenchymal lung disease. Methods: Clinical and pathologic data were reviewed as part of a Johns Hopkins -based natural history study of short telomere syndromes including dyskeratosis congenita. Results: Hepatopulmonary syndrome (HPS) was diagnosed in nine of 42 cases (21 {\%}). Their age at presentation was significantly younger than that of cases initially presenting with pulmonary fibrosis and emphysema (median, 25 years vs 55 years; P <.001). Cases had evidence of intra- and extrapulmonary arteriovascular malformations that caused shunt physiology. Nodular regenerative hyperplasia was the most frequent histopathologic abnormality, and it was seen in the absence of cirrhosis. Dyspnea and portal hypertension were progressive, and the median time to death or liver transplantation was 6 years (range, 4-10 years; n = 6). In cases that underwent liver transplantation, dyspnea and hypoxia improved, but pulmonary fibrosis subsequently developed. Conclusions: This report identifies HPS as a frequent cause of dyspnea in telomerase and telomere gene mutation carriers. While it usually precedes the development of parenchymal lung disease, HPS may also co-occur with pulmonary fibrosis and emphysema. Recognizing this genetic diagnosis is critical for management, especially in the lung and liver transplantation setting.",
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AU - Jonassaint, Naudia L.

AU - Stanley, Susan E.

AU - Koteish, Ayman

AU - Dezern, Amy

AU - Walter, Jolan E.

AU - Sopha, Sabrina C.

AU - Hamilton, James

AU - Hoover Fong, Julie E

AU - Chen, Allen R

AU - Anders, Robert A

AU - Kamel, Ihab R

AU - Armanios, Mary

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N2 - Background: Telomere syndromes have their most common manifestation in idiopathic pulmonary fibrosis and emphysema. The short telomere defect in these patients may manifest systemically as bone marrow failure and liver disease. We sought to understand the causes of dyspnea in telomerase and telomere gene mutation carriers who have no parenchymal lung disease. Methods: Clinical and pathologic data were reviewed as part of a Johns Hopkins -based natural history study of short telomere syndromes including dyskeratosis congenita. Results: Hepatopulmonary syndrome (HPS) was diagnosed in nine of 42 cases (21 %). Their age at presentation was significantly younger than that of cases initially presenting with pulmonary fibrosis and emphysema (median, 25 years vs 55 years; P <.001). Cases had evidence of intra- and extrapulmonary arteriovascular malformations that caused shunt physiology. Nodular regenerative hyperplasia was the most frequent histopathologic abnormality, and it was seen in the absence of cirrhosis. Dyspnea and portal hypertension were progressive, and the median time to death or liver transplantation was 6 years (range, 4-10 years; n = 6). In cases that underwent liver transplantation, dyspnea and hypoxia improved, but pulmonary fibrosis subsequently developed. Conclusions: This report identifies HPS as a frequent cause of dyspnea in telomerase and telomere gene mutation carriers. While it usually precedes the development of parenchymal lung disease, HPS may also co-occur with pulmonary fibrosis and emphysema. Recognizing this genetic diagnosis is critical for management, especially in the lung and liver transplantation setting.

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