Skip to main content

Main menu

  • Home
  • Current issue
  • ERJ Early View
  • Past issues
  • Authors/reviewers
    • Instructions for authors
    • Submit a manuscript
    • Open access
    • COVID-19 submission information
    • Peer reviewer login
  • Alerts
  • Podcasts
  • Subscriptions
  • ERS Publications
    • European Respiratory Journal
    • ERJ Open Research
    • European Respiratory Review
    • Breathe
    • ERS Books
    • ERS publications home

User menu

  • Log in
  • Subscribe
  • Contact Us
  • My Cart

Search

  • Advanced search
  • ERS Publications
    • European Respiratory Journal
    • ERJ Open Research
    • European Respiratory Review
    • Breathe
    • ERS Books
    • ERS publications home

Login

European Respiratory Society

Advanced Search

  • Home
  • Current issue
  • ERJ Early View
  • Past issues
  • Authors/reviewers
    • Instructions for authors
    • Submit a manuscript
    • Open access
    • COVID-19 submission information
    • Peer reviewer login
  • Alerts
  • Podcasts
  • Subscriptions

Pulmonary arterial hypertension in systemic sclerosis: a distinctive endotheliopathy?

S. E. Orfanos, D. Langleben
European Respiratory Journal 2010 35: 223-224; DOI: 10.1183/09031936.00130409
S. E. Orfanos
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
D. Langleben
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Info & Metrics
  • PDF
Loading

To the Editors:

We read with great interest the recent article by Overbeek et al. 1 on the histological differences in pulmonary vessels from patients with pulmonary arterial hypertension (PAH) related to systemic sclerosis (SSc) versus idiopathic PAH (IPAH). The study demonstrates that pulmonary pathological features in patients suffering from limited cutaneous SSc (lcSSc) differ from the ones seen in IPAH, in relation to the occurrence of small vessel intimal fibrosis, the presence of pulmonary veno-occlusive disease-like lesions, and the absence of plexiform lesions in the former group. Overbeek et al. 1 correctly suggest that their findings point to the presence of a distinct vasculopathy in the SSc cohort that may contribute to the lower transfer factor of the lung for carbon monoxide (TL,CO) and, more importantly, to the worse prognosis in PAH-SSc versus IPAH. The authors further propose that different pathogenetic mechanisms should underlie PAH development in the two groups, and that pulmonary endothelial function should be a determinant of such dissimilar mechanisms 1.

In support of the this hypothesis, we have recently provided evidence that different degrees of pulmonary endothelial dysfunction may be present in patients suffering from IPAH and PAH related to connective tissue disease (PAH-CTD) 2. Using first-pass lung metabolic studies at the bedside, by means of indicator dilution-type techniques, we have been studying human pulmonary endothelial function by estimating pulmonary capillary endothelium-bound enzymatic activity in vivo 3. This technique allows direct and quantifiable measurements of pulmonary endothelial metabolic function, and may distinguish between functional alterations at the capillary endothelial cell level and loss of functional capillary surface area (i.e. perfused and metabolically active lung microvascular bed) 3.

By applying such techniques we have, in the past, provided in vivo evidence that pulmonary endothelial dysfunction is a feature of early systemic sclerosis, being already present prior to the development of PAH and overt interstitial lung disease 4. Patients suffering from both lcSSc and diffused cutaneous SSc (dcSSc) demonstrated functional alterations at the capillary endothelial cell level, whereas the functional capillary surface area was reduced only in dcSSc 4. More recently, we have extended these studies to investigate pulmonary endothelial metabolic functional patterns in subjects with IPAH and PAH-CTD, prior to receiving PAH-related treatments 2. Approximately two-thirds of the PAH-CTD patients suffered from SSc. Indices reflecting “true” pulmonary endothelial dysfunction (i.e. functional alteration at the capillary endothelial cell level) were only present in the CTD group, supporting the intriguing hypothesis that PAH-CTD and IPAH posses different pulmonary endothelial phenotypes, and thus different metabolic functions as implied by Overbeek et al. 1. In contrast, both groups exhibited similar functional capillary surface area reductions, mainly reflecting the PAH-related small vessel loss and remodelling. Furthermore, our study provided the first functional evidence that the reduced TL,CO values in PAH-CTD are related in a linear fashion to the degree of functional capillary surface area loss 2. It should be noted that similar studies performed in patients suffering from chronic thromboembolic pulmonary hypertension revealed a different pattern, in that pulmonary endothelial metabolism was maintained, although functional capillary surface area loss was present 5.

Based on the evidence above, we feel that the study by Overbeek et al. 1 may provide a partial explanation for our findings, and the endothelial dysfunction we described may contribute to the diverse histological abnormalities that Overbeek et al. 1 have presented. Techniques that allow direct quantification of pulmonary endothelial function at the bedside might, in the future, identify varied pulmonary endothelial phenotypes in PAH patients, and assist the clinician in choosing the right treatment and monitoring its effects.

Statement of interest

None declared.

    • © ERS Journals Ltd

    References

    1. ↵
      Overbeek MJ, Vonk MC, Boonstra A, et al. Pulmonary arterial hypertension in limited cutaneous systemic sclerosis: a distinctive vasculopathy. Eur Respir J 2009;34:371–379.
      OpenUrlAbstract/FREE Full Text
    2. ↵
      Langleben D, Orfanos SE, Giovinazzo M, et al. Pulmonary capillary endothelial metabolic dysfunction: severity in pulmonary arterial hypertension related to connective tissue disease versus idiopathic pulmonary arterial hypertension. Arthritis Rheum 2008;58:1156–1164.
      OpenUrlCrossRefPubMedWeb of Science
    3. ↵
      Orfanos SE, Langleben D, Khoury J, et al. Pulmonary capillary endothelium-bound angiotensin-converting enzyme activity in humans. Circulation 1999;99:1593–1599.
      OpenUrlAbstract/FREE Full Text
    4. ↵
      Orfanos SE, Psevdi E, Stratigis N, et al. Pulmonary capillary endothelial dysfunction in early systemic sclerosis. Arthritis Rheum 2001;44:902–911.
      OpenUrlCrossRefPubMedWeb of Science
    5. ↵
      Orfanos SE, Hirsch AM, Giovinazzo M, et al. Pulmonary capillary endothelial metabolic function in chronic thromboembolic pulmonary hypertension. J Thromb Haemost 2008;6:1275–1280.
      OpenUrlCrossRefPubMedWeb of Science
    PreviousNext
    Back to top
    View this article with LENS
    Vol 35 Issue 1 Table of Contents
    European Respiratory Journal: 35 (1)
    • Table of Contents
    • Index by author
    Email

    Thank you for your interest in spreading the word on European Respiratory Society .

    NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

    Enter multiple addresses on separate lines or separate them with commas.
    Pulmonary arterial hypertension in systemic sclerosis: a distinctive endotheliopathy?
    (Your Name) has sent you a message from European Respiratory Society
    (Your Name) thought you would like to see the European Respiratory Society web site.
    CAPTCHA
    This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
    Print
    Citation Tools
    Pulmonary arterial hypertension in systemic sclerosis: a distinctive endotheliopathy?
    S. E. Orfanos, D. Langleben
    European Respiratory Journal Jan 2010, 35 (1) 223-224; DOI: 10.1183/09031936.00130409

    Citation Manager Formats

    • BibTeX
    • Bookends
    • EasyBib
    • EndNote (tagged)
    • EndNote 8 (xml)
    • Medlars
    • Mendeley
    • Papers
    • RefWorks Tagged
    • Ref Manager
    • RIS
    • Zotero

    Share
    Pulmonary arterial hypertension in systemic sclerosis: a distinctive endotheliopathy?
    S. E. Orfanos, D. Langleben
    European Respiratory Journal Jan 2010, 35 (1) 223-224; DOI: 10.1183/09031936.00130409
    del.icio.us logo Digg logo Reddit logo Technorati logo Twitter logo CiteULike logo Connotea logo Facebook logo Google logo Mendeley logo
    Full Text (PDF)

    Jump To

    • Article
      • Statement of interest
      • References
    • Info & Metrics
    • PDF
    • Tweet Widget
    • Facebook Like
    • Google Plus One

    More in this TOC Section

    • Clinical outcomes of bronchiectasis in India
    • Reply: Clinical outcomes of bronchiectasis in India
    • Risk factors for disease progression in fibrotic hypersensitivity pneumonitis
    Show more Correspondence

    Related Articles

    Navigate

    • Home
    • Current issue
    • Archive

    About the ERJ

    • Journal information
    • Editorial board
    • Reviewers
    • Press
    • Permissions and reprints
    • Advertising

    The European Respiratory Society

    • Society home
    • myERS
    • Privacy policy
    • Accessibility

    ERS publications

    • European Respiratory Journal
    • ERJ Open Research
    • European Respiratory Review
    • Breathe
    • ERS books online
    • ERS Bookshop

    Help

    • Feedback

    For authors

    • Instructions for authors
    • Publication ethics and malpractice
    • Submit a manuscript

    For readers

    • Alerts
    • Subjects
    • Podcasts
    • RSS

    Subscriptions

    • Accessing the ERS publications

    Contact us

    European Respiratory Society
    442 Glossop Road
    Sheffield S10 2PX
    United Kingdom
    Tel: +44 114 2672860
    Email: journals@ersnet.org

    ISSN

    Print ISSN:  0903-1936
    Online ISSN: 1399-3003

    Copyright © 2023 by the European Respiratory Society