Prognosticating Outcomes in Interstitial Lung Disease by Mediastinal Lymph Node Assessment. An Observational Cohort
Ayodeji Adegunsoye1, Justin M Oldham2, Catherine Bonham1
11 Section of Pulmonary and Critical Care, Department of Medicine.
Insights
Mediastinal lymph node enlargement on CT scans predicts worse transplant-free survival and higher hospitalization risk in interstitial lung disease (ILD). This finding, linked to lower soluble CD40L levels, may improve ILD prognostication.
Area of Science:
- Pulmonology
- Radiology
- Immunology
Background:
- Mediastinal lymph node (MLN) enlargement is common in interstitial lung disease (ILD) and may indicate immune system activity.
- This enlargement could be linked to cytokine-mediated immune cell movement.
Purpose of the Study:
- To investigate if MLN enlargement on chest CT scans predicts clinical outcomes in ILD patients.
- To determine the association between MLN enlargement and circulating cytokine levels.
Main Methods:
- Chest CT scans from 1,094 ILD patients (excluding sarcoidosis and drug toxicity) were analyzed over 10 years.
- MLN size and location were measured; plasma cytokine levels were assessed in a subset.
- Transplant-free survival (TFS), hospitalizations, lung function, and cytokine levels were primary and secondary outcomes.
Main Results:
- MLN enlargement (≥10 mm) was found in 66% of patients and predicted significantly lower TFS and higher hospitalization risk.
- Patients with MLN enlargement showed reduced lung function and lower plasma soluble CD40L levels.
- Elevated plasma IL-10 (>45 pg/ml) was also associated with increased mortality risk.
Conclusions:
- MLN enlargement on chest CT is a significant predictor of poor transplant-free survival and increased hospitalization risk in ILD.
- The association with decreased soluble CD40L suggests an underlying immunologic link.
- Integrating MLN and cytokine data into prognostication models could enhance ILD outcome prediction.
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.
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