Increased lymphatic vessel length is associated with the fibroblast reticulum and disease severity in usual interstitial pneumonia and nonspecific interstitial pneumonia

Abigail R. Lara, Gregory P. Cosgrove, William J. Janssen, Tristan J. Huie, Ellen L. Burnham, David E. Heinz, Douglas Curran-Everett, Hakan Sahin, Marvin I. Schwarz, Carlyne D. Cool, Steve D. Groshong, Mark W. Geraci, Rubin M. Tuder, Dallas M. Hyde, Peter M. Henson

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Background: Lymphangiogenesis responds to tissue injury as a key component of normal wound healing. The development of fibrosis in the idiopathic interstitial pneumonias may result from abnormal wound healing in response to injury. We hypothesize that increased lymphatic vessel (LV) length, a marker of lymphangiogenesis, is associated with parenchymal components of the fibroblast reticulum (organizing collagen, fibrotic collagen, and fibroblast foci), and its extent correlates with disease severity. Methods: We assessed stereologically the parenchymal structure of fibrotic lungs and its associated lymphatic network, which was highlighted immunohistochemically in age-matched samples of usual interstitial pneumonia (UIP), nonspecific interstitial pneumonia (NSIP) with FVC <80%, COPD with a Global Initiative for Obstructive Lung Disease stage 0, and normal control lungs. Results: LV length density, as opposed to vessel volume density, was found to be associated with organizing and fibrotic collagen density(P <.0001). Length density of LVs and the volume density of organizing and fibrotic collagen were significantly associated with severity of both % FVC(P <.001) and diffusing capacity of the lung for carbon monoxide(P <.001). Conclusions: Severity of disease in UIP and NSIP is associated with increased LV length and is strongly associated with components of the fibroblast reticulum, namely organizing and fibrotic collagen, which supports a pathogenic role of LVs in these two diseases. Furthermore, the absence of definable differences between UIP and NSIP suggests that LVs are a unifying mechanism for the development of fibrosis in these fibrotic lung diseases.

Original languageEnglish (US)
Pages (from-to)1569-1576
Number of pages8
JournalChest
Volume142
Issue number6
DOIs
StatePublished - Dec 2012
Externally publishedYes

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Reticulum
Idiopathic Pulmonary Fibrosis
Lymphatic Vessels
Interstitial Lung Diseases
Collagen
Fibroblasts
Lymphangiogenesis
Wound Healing
Fibrosis
Idiopathic Interstitial Pneumonias
Lung Volume Measurements
Obstructive Lung Diseases
Lung
Wounds and Injuries
Carbon Monoxide
Chronic Obstructive Pulmonary Disease
Lung Diseases

ASJC Scopus subject areas

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

Cite this

Increased lymphatic vessel length is associated with the fibroblast reticulum and disease severity in usual interstitial pneumonia and nonspecific interstitial pneumonia. / Lara, Abigail R.; Cosgrove, Gregory P.; Janssen, William J.; Huie, Tristan J.; Burnham, Ellen L.; Heinz, David E.; Curran-Everett, Douglas; Sahin, Hakan; Schwarz, Marvin I.; Cool, Carlyne D.; Groshong, Steve D.; Geraci, Mark W.; Tuder, Rubin M.; Hyde, Dallas M.; Henson, Peter M.

In: Chest, Vol. 142, No. 6, 12.2012, p. 1569-1576.

Research output: Contribution to journalArticle

Lara, AR, Cosgrove, GP, Janssen, WJ, Huie, TJ, Burnham, EL, Heinz, DE, Curran-Everett, D, Sahin, H, Schwarz, MI, Cool, CD, Groshong, SD, Geraci, MW, Tuder, RM, Hyde, DM & Henson, PM 2012, 'Increased lymphatic vessel length is associated with the fibroblast reticulum and disease severity in usual interstitial pneumonia and nonspecific interstitial pneumonia', Chest, vol. 142, no. 6, pp. 1569-1576. https://doi.org/10.1378/chest.12-0029
Lara, Abigail R. ; Cosgrove, Gregory P. ; Janssen, William J. ; Huie, Tristan J. ; Burnham, Ellen L. ; Heinz, David E. ; Curran-Everett, Douglas ; Sahin, Hakan ; Schwarz, Marvin I. ; Cool, Carlyne D. ; Groshong, Steve D. ; Geraci, Mark W. ; Tuder, Rubin M. ; Hyde, Dallas M. ; Henson, Peter M. / Increased lymphatic vessel length is associated with the fibroblast reticulum and disease severity in usual interstitial pneumonia and nonspecific interstitial pneumonia. In: Chest. 2012 ; Vol. 142, No. 6. pp. 1569-1576.
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abstract = "Background: Lymphangiogenesis responds to tissue injury as a key component of normal wound healing. The development of fibrosis in the idiopathic interstitial pneumonias may result from abnormal wound healing in response to injury. We hypothesize that increased lymphatic vessel (LV) length, a marker of lymphangiogenesis, is associated with parenchymal components of the fibroblast reticulum (organizing collagen, fibrotic collagen, and fibroblast foci), and its extent correlates with disease severity. Methods: We assessed stereologically the parenchymal structure of fibrotic lungs and its associated lymphatic network, which was highlighted immunohistochemically in age-matched samples of usual interstitial pneumonia (UIP), nonspecific interstitial pneumonia (NSIP) with FVC <80{\%}, COPD with a Global Initiative for Obstructive Lung Disease stage 0, and normal control lungs. Results: LV length density, as opposed to vessel volume density, was found to be associated with organizing and fibrotic collagen density(P <.0001). Length density of LVs and the volume density of organizing and fibrotic collagen were significantly associated with severity of both {\%} FVC(P <.001) and diffusing capacity of the lung for carbon monoxide(P <.001). Conclusions: Severity of disease in UIP and NSIP is associated with increased LV length and is strongly associated with components of the fibroblast reticulum, namely organizing and fibrotic collagen, which supports a pathogenic role of LVs in these two diseases. Furthermore, the absence of definable differences between UIP and NSIP suggests that LVs are a unifying mechanism for the development of fibrosis in these fibrotic lung diseases.",
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T1 - Increased lymphatic vessel length is associated with the fibroblast reticulum and disease severity in usual interstitial pneumonia and nonspecific interstitial pneumonia

AU - Lara, Abigail R.

AU - Cosgrove, Gregory P.

AU - Janssen, William J.

AU - Huie, Tristan J.

AU - Burnham, Ellen L.

AU - Heinz, David E.

AU - Curran-Everett, Douglas

AU - Sahin, Hakan

AU - Schwarz, Marvin I.

AU - Cool, Carlyne D.

AU - Groshong, Steve D.

AU - Geraci, Mark W.

AU - Tuder, Rubin M.

AU - Hyde, Dallas M.

AU - Henson, Peter M.

PY - 2012/12

Y1 - 2012/12

N2 - Background: Lymphangiogenesis responds to tissue injury as a key component of normal wound healing. The development of fibrosis in the idiopathic interstitial pneumonias may result from abnormal wound healing in response to injury. We hypothesize that increased lymphatic vessel (LV) length, a marker of lymphangiogenesis, is associated with parenchymal components of the fibroblast reticulum (organizing collagen, fibrotic collagen, and fibroblast foci), and its extent correlates with disease severity. Methods: We assessed stereologically the parenchymal structure of fibrotic lungs and its associated lymphatic network, which was highlighted immunohistochemically in age-matched samples of usual interstitial pneumonia (UIP), nonspecific interstitial pneumonia (NSIP) with FVC <80%, COPD with a Global Initiative for Obstructive Lung Disease stage 0, and normal control lungs. Results: LV length density, as opposed to vessel volume density, was found to be associated with organizing and fibrotic collagen density(P <.0001). Length density of LVs and the volume density of organizing and fibrotic collagen were significantly associated with severity of both % FVC(P <.001) and diffusing capacity of the lung for carbon monoxide(P <.001). Conclusions: Severity of disease in UIP and NSIP is associated with increased LV length and is strongly associated with components of the fibroblast reticulum, namely organizing and fibrotic collagen, which supports a pathogenic role of LVs in these two diseases. Furthermore, the absence of definable differences between UIP and NSIP suggests that LVs are a unifying mechanism for the development of fibrosis in these fibrotic lung diseases.

AB - Background: Lymphangiogenesis responds to tissue injury as a key component of normal wound healing. The development of fibrosis in the idiopathic interstitial pneumonias may result from abnormal wound healing in response to injury. We hypothesize that increased lymphatic vessel (LV) length, a marker of lymphangiogenesis, is associated with parenchymal components of the fibroblast reticulum (organizing collagen, fibrotic collagen, and fibroblast foci), and its extent correlates with disease severity. Methods: We assessed stereologically the parenchymal structure of fibrotic lungs and its associated lymphatic network, which was highlighted immunohistochemically in age-matched samples of usual interstitial pneumonia (UIP), nonspecific interstitial pneumonia (NSIP) with FVC <80%, COPD with a Global Initiative for Obstructive Lung Disease stage 0, and normal control lungs. Results: LV length density, as opposed to vessel volume density, was found to be associated with organizing and fibrotic collagen density(P <.0001). Length density of LVs and the volume density of organizing and fibrotic collagen were significantly associated with severity of both % FVC(P <.001) and diffusing capacity of the lung for carbon monoxide(P <.001). Conclusions: Severity of disease in UIP and NSIP is associated with increased LV length and is strongly associated with components of the fibroblast reticulum, namely organizing and fibrotic collagen, which supports a pathogenic role of LVs in these two diseases. Furthermore, the absence of definable differences between UIP and NSIP suggests that LVs are a unifying mechanism for the development of fibrosis in these fibrotic lung diseases.

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DO - 10.1378/chest.12-0029

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SN - 0012-3692

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