Related Experiment Video
Updated: Aug 22, 2026
Monitoring Neutrophil Elastase and Cathepsin G Activity in Human Sputum Samples
Published on: May 21, 2021
Fractional exhaled nitric oxide is a non-invasive disease activity marker of IgG4-related disease
Koki Nakamura1, Masatoshi Kanda1, Yuki Hamakawa1
1Division of Rheumatology and Clinical Immunology, Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.
Insights
Fractional exhaled nitric oxide (FeNO) is elevated in IgG4-related disease (IgG4-RD) patients and correlates with disease activity. This non-invasive marker may also indicate lung involvement in IgG4-RD.
Area of Science:
- Immunology
- Pulmonology
- Rheumatology
Background:
- Immunoglobulin G4-related disease (IgG4-RD) is a fibroinflammatory condition affecting multiple organs.
- Accurate assessment of disease activity and organ involvement is crucial for managing IgG4-RD.
- Non-invasive biomarkers are needed to monitor disease progression and treatment response.
Purpose of the Study:
- To investigate the utility of fractional exhaled nitric oxide (FeNO) as a non-invasive marker for disease activity in IgG4-RD.
- To assess the correlation between FeNO levels and established disease activity indices.
- To determine if FeNO can predict specific organ involvement, particularly in the lungs.
Main Methods:
- Patients meeting the 2019 ACR/EULAR criteria for IgG4-RD were enrolled.
- FeNO measurements and computed tomography scans were performed on treatment-naïve patients.
- Disease activity was assessed using the IgG4-RD responder index (IgG4-RI); statistical analyses included Spearman's rank correlation and ROC analysis.
Main Results:
- A total of 35 patients were included, with a median FeNO of 48.0 ppb, exceeding the 36 ppb cutoff in 65.7%.
- FeNO levels significantly correlated with serum IgG4 levels (r=0.48, p=0.020), number of organ involvements (r=0.47, p=0.020), and IgG4-RI (r=0.47, p=0.020).
- High FeNO levels were associated with a higher frequency of lung involvement (52.2% vs 8.3%, p=0.029), with an optimal cutoff of 55.2 ppb for predicting lung involvement.
Conclusions:
- FeNO is elevated in patients with IgG4-RD and serves as a valuable non-invasive indicator of disease activity.
- FeNO levels are associated with serological markers and the extent of organ involvement.
- FeNO measurement shows potential for identifying lung involvement in IgG4-RD patients.
Objectives:
To evaluate the potential of fractional exhaled nitric oxide (FeNO) value in patients with IgG4-related disease (IgG4-RD) as a non-invasive disease activity marker.
Methods:
Patients fulfilling the 2019 ACR/EULAR classification criteria of IgG4-RD were enrolled. All patients who had never received oral glucocorticoids underwent FeNO measurement and computed tomography. Disease activity was evaluated using the IgG4-RD responder index (IgG4-RI). The cutoff for FeNO was set at 36 parts per billion (ppb), based on a Japanese normal upper limit. Spearman's rank correlation was used to assess the association between FeNO values and clinical parameters. Receiver operating characteristic analysis was used to identify the involvement of specific organs.
Results:
A total of 35 patients (21 males, 72.0 [IQR 64.5, 77.0] years old) were enrolled. The median FeNO value was 48.0 [IQR 33.0, 99.5] ppb, with 23 (65.7%) patients exceeding the cutoff. The FeNO value was correlated with serum IgG4 levels (r = 0.48, P = 0.020), the number of organ involvements (r = 0.47, P = 0.020) and IgG4-RI (r = 0.47, P = 0.020). Dividing into two groups by the FeNO cutoff, lung involvement was more frequent in the high FeNO group (8.3% vs. 52.2%, P = 0.029). Area under the curve for the lung involvement was 0.88, and the optimal cutoff for identifying lung involvement using the Youden index was 55.2 ppb.
Conclusion:
FeNO value was elevated in patients with IgG4-RD and was associated with disease activity. Moreover, it can be associated with lung involvement.
