Prognosticating outcomes in interstitial lung disease by mediastinal lymph node assessment

Ayodeji Adegunsoye, Justin Oldham, Catherine Bonham, Cara Hrusch, Paul Nolan, Wesley Klejch, Shashi Bellam, Uday Mehta, Kiran Thakrar, Janelle Vu Pugashetti, Aliya N. Husain, Steven M. Montner, Christopher M. Straus, Rekha Vij, Anne I. Sperling, Imre Noth, Mary E. Strek, Jonathan H. Chung

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Rationale: Mediastinal lymph node (MLN) enlargement on chest computed tomography (CT) is prevalent in patients with interstitial lung disease (ILD) and may reflect immunologic activation and subsequent cytokine-mediated immune cell trafficking. Objectives: We aimed to determine whether MLN enlargement on chest CT predicts clinical outcomes and circulating cytokine levels in ILD. Methods: MLN measurements were obtained from chest CT scans of patients with ILD at baseline evaluation over a 10-year period. Patients with sarcoidosis and drug toxicity–related ILD were excluded. MLN diameter and location were assessed. Plasma cytokine levels were analyzed in a subset of patients. The primary outcome was transplant-free survival (TFS). Secondary outcomes included all-cause and respiratory hospitalizations, lung function, and plasma cytokine concentrations. Cox regression was used to assess mortality risk. Outcomes were assessed in three independent ILD cohorts. Measurements and Main Results: Chest CT scans were assessed in 1,094 patients (mean age, 64 yr; 52% male). MLN enlargement (>10 mm) was present in 66% (n = 726) and strongly predicted TFS (hazard ratio [HR], 1.53; 95% confidence interval [CI], 1.12–2.10; P = 0.008) and risk of all-cause and respiratory hospitalizations (internal rate of return [IRR], 1.52; 95% CI, 1.17–1.98; P = 0.002; and IRR, 1.71; 95% CI, 1.15–2.53; P = 0.008, respectively) when compared with subjects with MLN,10 mm. Patients with MLN enlargement had lower lung function and decreased plasma concentrations of soluble CD40L (376 pg/ml vs. 505 pg/ml, P = 0.001) compared with those without MLN enlargement. Plasma IL-10 concentration .45 pg/ml predicted mortality (HR, 4.21; 95% CI, 1.21–14.68; P = 0.024). Independent analysis of external datasets confirmed these findings. Conclusions: MLN enlargement predicts TFS and hospitalization risk in ILD and is associated with decreased levels of a key circulating cytokine, soluble CD40L. Incorporating MLN and cytokine findings into current prediction models might improve ILD prognostication.

Original languageEnglish (US)
Pages (from-to)747-759
Number of pages13
JournalAmerican journal of respiratory and critical care medicine
Volume199
Issue number6
DOIs
StatePublished - Mar 15 2019

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Interstitial Lung Diseases
Lymph Nodes
Cytokines
Thorax
Tomography
Confidence Intervals
CD40 Ligand
Hospitalization
Transplants
Survival
Lung
Mortality
Sarcoidosis
Interleukin-10

Keywords

  • Interstitial lung disease
  • Mediastinal lymph nodes
  • Mortality
  • Pulmonary fibrosis

ASJC Scopus subject areas

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

Cite this

Prognosticating outcomes in interstitial lung disease by mediastinal lymph node assessment. / Adegunsoye, Ayodeji; Oldham, Justin; Bonham, Catherine; Hrusch, Cara; Nolan, Paul; Klejch, Wesley; Bellam, Shashi; Mehta, Uday; Thakrar, Kiran; Pugashetti, Janelle Vu; Husain, Aliya N.; Montner, Steven M.; Straus, Christopher M.; Vij, Rekha; Sperling, Anne I.; Noth, Imre; Strek, Mary E.; Chung, Jonathan H.

In: American journal of respiratory and critical care medicine, Vol. 199, No. 6, 15.03.2019, p. 747-759.

Research output: Contribution to journalArticle

Adegunsoye, A, Oldham, J, Bonham, C, Hrusch, C, Nolan, P, Klejch, W, Bellam, S, Mehta, U, Thakrar, K, Pugashetti, JV, Husain, AN, Montner, SM, Straus, CM, Vij, R, Sperling, AI, Noth, I, Strek, ME & Chung, JH 2019, 'Prognosticating outcomes in interstitial lung disease by mediastinal lymph node assessment', American journal of respiratory and critical care medicine, vol. 199, no. 6, pp. 747-759. https://doi.org/10.1164/rccm.201804-0761OC
Adegunsoye, Ayodeji ; Oldham, Justin ; Bonham, Catherine ; Hrusch, Cara ; Nolan, Paul ; Klejch, Wesley ; Bellam, Shashi ; Mehta, Uday ; Thakrar, Kiran ; Pugashetti, Janelle Vu ; Husain, Aliya N. ; Montner, Steven M. ; Straus, Christopher M. ; Vij, Rekha ; Sperling, Anne I. ; Noth, Imre ; Strek, Mary E. ; Chung, Jonathan H. / Prognosticating outcomes in interstitial lung disease by mediastinal lymph node assessment. In: American journal of respiratory and critical care medicine. 2019 ; Vol. 199, No. 6. pp. 747-759.
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title = "Prognosticating outcomes in interstitial lung disease by mediastinal lymph node assessment",
abstract = "Rationale: Mediastinal lymph node (MLN) enlargement on chest computed tomography (CT) is prevalent in patients with interstitial lung disease (ILD) and may reflect immunologic activation and subsequent cytokine-mediated immune cell trafficking. Objectives: We aimed to determine whether MLN enlargement on chest CT predicts clinical outcomes and circulating cytokine levels in ILD. Methods: MLN measurements were obtained from chest CT scans of patients with ILD at baseline evaluation over a 10-year period. Patients with sarcoidosis and drug toxicity–related ILD were excluded. MLN diameter and location were assessed. Plasma cytokine levels were analyzed in a subset of patients. The primary outcome was transplant-free survival (TFS). Secondary outcomes included all-cause and respiratory hospitalizations, lung function, and plasma cytokine concentrations. Cox regression was used to assess mortality risk. Outcomes were assessed in three independent ILD cohorts. Measurements and Main Results: Chest CT scans were assessed in 1,094 patients (mean age, 64 yr; 52{\%} male). MLN enlargement (>10 mm) was present in 66{\%} (n = 726) and strongly predicted TFS (hazard ratio [HR], 1.53; 95{\%} confidence interval [CI], 1.12–2.10; P = 0.008) and risk of all-cause and respiratory hospitalizations (internal rate of return [IRR], 1.52; 95{\%} CI, 1.17–1.98; P = 0.002; and IRR, 1.71; 95{\%} CI, 1.15–2.53; P = 0.008, respectively) when compared with subjects with MLN,10 mm. Patients with MLN enlargement had lower lung function and decreased plasma concentrations of soluble CD40L (376 pg/ml vs. 505 pg/ml, P = 0.001) compared with those without MLN enlargement. Plasma IL-10 concentration .45 pg/ml predicted mortality (HR, 4.21; 95{\%} CI, 1.21–14.68; P = 0.024). Independent analysis of external datasets confirmed these findings. Conclusions: MLN enlargement predicts TFS and hospitalization risk in ILD and is associated with decreased levels of a key circulating cytokine, soluble CD40L. Incorporating MLN and cytokine findings into current prediction models might improve ILD prognostication.",
keywords = "Interstitial lung disease, Mediastinal lymph nodes, Mortality, Pulmonary fibrosis",
author = "Ayodeji Adegunsoye and Justin Oldham and Catherine Bonham and Cara Hrusch and Paul Nolan and Wesley Klejch and Shashi Bellam and Uday Mehta and Kiran Thakrar and Pugashetti, {Janelle Vu} and Husain, {Aliya N.} and Montner, {Steven M.} and Straus, {Christopher M.} and Rekha Vij and Sperling, {Anne I.} and Imre Noth and Strek, {Mary E.} and Chung, {Jonathan H.}",
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doi = "10.1164/rccm.201804-0761OC",
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volume = "199",
pages = "747--759",
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T1 - Prognosticating outcomes in interstitial lung disease by mediastinal lymph node assessment

AU - Adegunsoye, Ayodeji

AU - Oldham, Justin

AU - Bonham, Catherine

AU - Hrusch, Cara

AU - Nolan, Paul

AU - Klejch, Wesley

AU - Bellam, Shashi

AU - Mehta, Uday

AU - Thakrar, Kiran

AU - Pugashetti, Janelle Vu

AU - Husain, Aliya N.

AU - Montner, Steven M.

AU - Straus, Christopher M.

AU - Vij, Rekha

AU - Sperling, Anne I.

AU - Noth, Imre

AU - Strek, Mary E.

AU - Chung, Jonathan H.

PY - 2019/3/15

Y1 - 2019/3/15

N2 - Rationale: Mediastinal lymph node (MLN) enlargement on chest computed tomography (CT) is prevalent in patients with interstitial lung disease (ILD) and may reflect immunologic activation and subsequent cytokine-mediated immune cell trafficking. Objectives: We aimed to determine whether MLN enlargement on chest CT predicts clinical outcomes and circulating cytokine levels in ILD. Methods: MLN measurements were obtained from chest CT scans of patients with ILD at baseline evaluation over a 10-year period. Patients with sarcoidosis and drug toxicity–related ILD were excluded. MLN diameter and location were assessed. Plasma cytokine levels were analyzed in a subset of patients. The primary outcome was transplant-free survival (TFS). Secondary outcomes included all-cause and respiratory hospitalizations, lung function, and plasma cytokine concentrations. Cox regression was used to assess mortality risk. Outcomes were assessed in three independent ILD cohorts. Measurements and Main Results: Chest CT scans were assessed in 1,094 patients (mean age, 64 yr; 52% male). MLN enlargement (>10 mm) was present in 66% (n = 726) and strongly predicted TFS (hazard ratio [HR], 1.53; 95% confidence interval [CI], 1.12–2.10; P = 0.008) and risk of all-cause and respiratory hospitalizations (internal rate of return [IRR], 1.52; 95% CI, 1.17–1.98; P = 0.002; and IRR, 1.71; 95% CI, 1.15–2.53; P = 0.008, respectively) when compared with subjects with MLN,10 mm. Patients with MLN enlargement had lower lung function and decreased plasma concentrations of soluble CD40L (376 pg/ml vs. 505 pg/ml, P = 0.001) compared with those without MLN enlargement. Plasma IL-10 concentration .45 pg/ml predicted mortality (HR, 4.21; 95% CI, 1.21–14.68; P = 0.024). Independent analysis of external datasets confirmed these findings. Conclusions: MLN enlargement predicts TFS and hospitalization risk in ILD and is associated with decreased levels of a key circulating cytokine, soluble CD40L. Incorporating MLN and cytokine findings into current prediction models might improve ILD prognostication.

AB - Rationale: Mediastinal lymph node (MLN) enlargement on chest computed tomography (CT) is prevalent in patients with interstitial lung disease (ILD) and may reflect immunologic activation and subsequent cytokine-mediated immune cell trafficking. Objectives: We aimed to determine whether MLN enlargement on chest CT predicts clinical outcomes and circulating cytokine levels in ILD. Methods: MLN measurements were obtained from chest CT scans of patients with ILD at baseline evaluation over a 10-year period. Patients with sarcoidosis and drug toxicity–related ILD were excluded. MLN diameter and location were assessed. Plasma cytokine levels were analyzed in a subset of patients. The primary outcome was transplant-free survival (TFS). Secondary outcomes included all-cause and respiratory hospitalizations, lung function, and plasma cytokine concentrations. Cox regression was used to assess mortality risk. Outcomes were assessed in three independent ILD cohorts. Measurements and Main Results: Chest CT scans were assessed in 1,094 patients (mean age, 64 yr; 52% male). MLN enlargement (>10 mm) was present in 66% (n = 726) and strongly predicted TFS (hazard ratio [HR], 1.53; 95% confidence interval [CI], 1.12–2.10; P = 0.008) and risk of all-cause and respiratory hospitalizations (internal rate of return [IRR], 1.52; 95% CI, 1.17–1.98; P = 0.002; and IRR, 1.71; 95% CI, 1.15–2.53; P = 0.008, respectively) when compared with subjects with MLN,10 mm. Patients with MLN enlargement had lower lung function and decreased plasma concentrations of soluble CD40L (376 pg/ml vs. 505 pg/ml, P = 0.001) compared with those without MLN enlargement. Plasma IL-10 concentration .45 pg/ml predicted mortality (HR, 4.21; 95% CI, 1.21–14.68; P = 0.024). Independent analysis of external datasets confirmed these findings. Conclusions: MLN enlargement predicts TFS and hospitalization risk in ILD and is associated with decreased levels of a key circulating cytokine, soluble CD40L. Incorporating MLN and cytokine findings into current prediction models might improve ILD prognostication.

KW - Interstitial lung disease

KW - Mediastinal lymph nodes

KW - Mortality

KW - Pulmonary fibrosis

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