Intravenous stem cell dose and changes in quantitative lung fibrosis and DLCO in the AETHER trial: A pilot study

J. E. Fishman, G. H.J. Kim, N. Y. Kyeong, J. G. Goldin, M. K. Glassberg

Research output: Contribution to journalArticle

Abstract

OBJECTIVE: Our purpose was to compare quantitative CT-derived changes in lung fibrosis with pulmonary function, including DLCO, in human subjects with idiopathic pulmonary fibrosis who received an injection of one of two different intravenous doses of human bone-marrow-derived mesenchymal stem cells. PATIENTS AND METHODS: Two three-subject cohorts from the AETHER trial (Allogeneic Human Cells in subjects with Idiopathic Pulmonary Fibrosis via Intravenous Delivery) underwent high-resolution CT and clinical testing at baseline, 24 weeks, and 48 weeks after injection. Cohort 1 received 2x107 stem cells, and cohort 2 received 1x108 stem cells. CT scans were quantitatively analyzed for lung fibrosis using 510K cleared validated software. The percent predicted DLCO and other pulmonary function studies were obtained. RESULTS: The cohorts were well matched in lung fibrosis at baseline as assessed by CT scan and lung function. The mean QLF in cohort 1 increased from 13.1% at baseline to 17.1% at 48 weeks, while mean QLF in cohort 2 increased from 15.4% at baseline to 16.5% at 48 weeks. The subjects in cohort 2 progressed more slowly in whole lung fibrosis by a mean of 2.87% compared with cohort 1 (p=0.001 with adjustment of baseline covariates) during the baseline to the 48-week interval. The baseline DLCO was lower in cohort 2 than in cohort 1 (p<0.0001). Over 48 weeks of the study, cohort 2 subjects demonstrated a mean DLCO decline of only 2% compared with a decline of 17% in cohort 1 subjects (p=0.02). CONCLUSIONS: In this pilot study, the subjects receiving 1x108 stem cells demonstrated slower progression in quantitative lung fibrosis and a smaller decrease in DLCO than subjects receiving 2x107 stem cells.

Original languageEnglish (US)
Pages (from-to)7568-7572
Number of pages5
JournalEuropean review for medical and pharmacological sciences
Volume23
Issue number17
DOIs
StatePublished - Jan 1 2019

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Fibrosis
Stem Cells
Lung
Idiopathic Pulmonary Fibrosis
Injections
Pulmonary Fibrosis
Mesenchymal Stromal Cells
Cohort Studies
Software
Bone Marrow

Keywords

  • Idiopathic pulmonary fibrosis
  • Mesenchymal stem cells
  • Pulmonary fibrosis
  • Pulmonary function tests
  • Tomography
  • X-ray computed

ASJC Scopus subject areas

  • Pharmacology (medical)

Cite this

Intravenous stem cell dose and changes in quantitative lung fibrosis and DLCO in the AETHER trial : A pilot study. / Fishman, J. E.; Kim, G. H.J.; Kyeong, N. Y.; Goldin, J. G.; Glassberg, M. K.

In: European review for medical and pharmacological sciences, Vol. 23, No. 17, 01.01.2019, p. 7568-7572.

Research output: Contribution to journalArticle

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abstract = "OBJECTIVE: Our purpose was to compare quantitative CT-derived changes in lung fibrosis with pulmonary function, including DLCO, in human subjects with idiopathic pulmonary fibrosis who received an injection of one of two different intravenous doses of human bone-marrow-derived mesenchymal stem cells. PATIENTS AND METHODS: Two three-subject cohorts from the AETHER trial (Allogeneic Human Cells in subjects with Idiopathic Pulmonary Fibrosis via Intravenous Delivery) underwent high-resolution CT and clinical testing at baseline, 24 weeks, and 48 weeks after injection. Cohort 1 received 2x107 stem cells, and cohort 2 received 1x108 stem cells. CT scans were quantitatively analyzed for lung fibrosis using 510K cleared validated software. The percent predicted DLCO and other pulmonary function studies were obtained. RESULTS: The cohorts were well matched in lung fibrosis at baseline as assessed by CT scan and lung function. The mean QLF in cohort 1 increased from 13.1{\%} at baseline to 17.1{\%} at 48 weeks, while mean QLF in cohort 2 increased from 15.4{\%} at baseline to 16.5{\%} at 48 weeks. The subjects in cohort 2 progressed more slowly in whole lung fibrosis by a mean of 2.87{\%} compared with cohort 1 (p=0.001 with adjustment of baseline covariates) during the baseline to the 48-week interval. The baseline DLCO was lower in cohort 2 than in cohort 1 (p<0.0001). Over 48 weeks of the study, cohort 2 subjects demonstrated a mean DLCO decline of only 2{\%} compared with a decline of 17{\%} in cohort 1 subjects (p=0.02). CONCLUSIONS: In this pilot study, the subjects receiving 1x108 stem cells demonstrated slower progression in quantitative lung fibrosis and a smaller decrease in DLCO than subjects receiving 2x107 stem cells.",
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AU - Fishman, J. E.

AU - Kim, G. H.J.

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AU - Goldin, J. G.

AU - Glassberg, M. K.

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