Characteristics of study subjects
A total of 53 patients in stable phrase of ILDs were enrolled in this study. The majority of the patients were males (62.26%), with the average age of 58.64 ± 13.94 years old, mean %FEV1 of 75.94 ± 18.31%, and mean %FEV1/FVC of 83.04 ± 8.55%. This condition demonstrates a restrictive functional impairment. This group of patients with ILDs had a decreased vital capacity(VC)and TLC of 71.75 ± 17.58% and 75.27 ± 14.07%, respectively. DLCO also declined, with an average level of 38.15 ± 11.10%. The average FeNO value was 20.34 ± 9.97 ppb. The clinical features and PFT data of the study population are shown in Table 1.
Table 1
Clinical features and PFT data of patients with ILD
Parameter | ILD (N = 53) | |
Mean age, years | 58.64 ± 13.94 | |
Sex (M:F),n | 33:20 | |
Height (cm) | 161.51 ± 7.24 | |
Weight (kg) | 61.40 ± 10.78 | |
Body surface area(m2) | 1.64 ± 0.16 | |
BMI in kg/m2 | 23.49 ± 3.67 (range = 14.27–32.05) | |
FVC (% predicted) | 74.08 ± 18.14 | |
FEV1 (% predicted) | 75.94 ± 18.31 | |
FEV1/FVC | 83.04 ± 8.55 | |
PEF (% predicted) | 69.57 ± 20.34 | |
MEF (% predicted) | 79.09 ± 34.34 | |
MEF25 (% predicted) | 56.83 ± 32.48 | |
MEF50 (% predicted) | 77.06 ± 34.12 | |
MEF75 (% predicted) | 63.13 ± 23.00 | |
MVV (% predicted) | 87.23 ± 25.96 | |
VC (% predicted) | 71.75 ± 17.58 | |
TLC (% predicted) | 75.27 ± 14.07 | |
RV(% predicted) | 88.80 ± 19.28 | |
RV/TLC(% predicted) | 44.73 ± 7.20 | |
DLCO (% predicted) | 38.15 ± 11.10 | |
FeNO(ppb) | 20.34 ± 9.97 | |
Notes: Measured pulmonary function values are presented as a predictive percentage. Data are shown as mean ± standard deviation unless indicated otherwise. Abbreviations: M, male; F, female; BMI, body mass index; FEV11, forced expiratory volume in 1 s; FVC, forced vital capacity; PEF, peak expiratory flow; MEF, maximal midexpiratory flow; MEF25, forced expiratory flow after 25% of the FVC; MEF50, forced expiratory flow after 50% of the FVC; MEF75, forced expiratory flow after 75% of the FVC; MVV, maximal voluntary ventilation; VC, vital capacity; RV, residual volume, TLC, total lung capacity, DLCO, diffusion capacity of the lung for carbon monoxide; FeNO, fractional exhaled nitric oxide; ppb, parts per billion; ILD, interstitial lung diseases; PFT, pulmonary function test. |
FeNO And Clinical-radiological Features
According to the characteristics of chest CT, patients were divided into UIP-ILD (n = 24) (with UIP features and predominant fibrosis) and non-UIP-ILD (n = 29). No significant differences were observed with regard to age, gender, height, weight, and body mass index between these two groups. The FeNO value in the UIP-ILD group was 12.58 ± 3.63 ppb. This value was significantly lower than that of the non-UIP-ILD group (26.62 ± 8.61 ppb, P < 0.0001) (Fig. 1). However, no significant differences were observed in the PFT values between these two groups (Table 2). The blood eosinophils and the IgE levels were lower in the UIP-ILD group than those of the non-UIP-ILD group. However, the differences did not reach statistical significance. Concerning the systemic inflammatory markers, such as ESR and CRP, no significant differences were reported between these two groups (Table 2).
Table 2
Clinical features in patients with ILDs with UIP pattern and non-UIP pattern
Parameter | UIP pattern (N = 24) | Non-UIP pattern (N = 29) | P value |
Mean age, years | 57.54 ±15.45 | 59.55 ± 12.77 | 0.606 |
Sex (M:F),n | 13:11 | 20:9 | |
Height (cm) | 160.83 ± 8.16 | 162.07 ± 6.47 | 0.542 |
Weight (kg) | 60.58 ± 11.80 | 62.07 ± 10.02 | 0.622 |
Body surface area (m2) | 1.63 ± 0.18 | 1.65 ± 0.14 | 0.528 |
BMI in kg/m2 | 23.35 ±4.02 | 23.62 ± 3.42 | 0.794 |
FVC (% predicted) | 75.96 ± 17.13 | 72.52 ± 19.09 | 0.497 |
FEV1 (% predicted) | 77.75 ± 19.92 | 74.45 ± 17.07 | 0.519 |
FEV1/FVC | 82.79 ±10.72 | 83.24 ± 6.42 | 0.851 |
PEF (% predicted) | 67.83 ± 17.94 | 71.00 ± 22.34 | 0.578 |
MEF (% predicted) | 82.96 ±43.37 | 75.90± 24.94 | 0.462 |
MEF25 (% predicted) | 63.88 ± 41.17 | 51.00 ± 22.11 | 0.153 |
MEF50 (% predicted) | 78.42 ± 40.29 | 75.93 ± 28.73 | 0.795 |
MEF75 (% predicted) | 61.88 ± 20.76 | 64.17 ± 25.02 | 0.721 |
MVV (% predicted) | 86.04 ±28.48 | 88.21 ± 24.14 | 0.766 |
VC (% predicted) | 74.08 ± 16.76 | 69.83 ± 18.29 | 0.385 |
TLC (% predicted) | 76.14 ± 11.76 | 74.62 ± 15.77 | 0.707 |
RV(% predicted) | 90.50 ±19.16 | 87.52 ± 19.60 | 0.589 |
RV/TLC(% predicted) | 44.86 ± 7.03 | 44.62 ± 7.44 | 0.906 |
DLCO (% predicted) | 45.38 ±17.25 | 50.00 ± 18.27 | 0.450 |
Total serum IgE (IU/ml) | 140.04 ± 139.16 | 202.36 ± 177.83 | 0.290 |
Blood eosinophils absolute (cells/µl) | 164.57 ± 159.88 | 240.74 ± 198.09 | 0.126 |
Blood eosinophil percentage | 2.05 ± 2.04 | 3.07 ± 2.08 | 0.083 |
CRP (mg/L) | 20.60 ± 15.53 | 18.47 ± 17.34 | 0.873 |
ESR (mm/h) | 48.56 ± 36.23 | 39.92 ± 28.37 | 0.386 |
FeNO (ppb) | 12.58 ± 3.63 | 26.62 ± 8.61 | < 0.0001 |
Notes: Measured pulmonary function values are presented as a predictive percentage. Data are shown as mean ± standard deviation unless indicated otherwise. Abbreviations: M, male; F, female; BMI, body mass index; FEV11, forced expiratory volume in 1 s; FVC, forced vital capacity; PEF, peak expiratory flow; MEF, maximal midexpiratory flow; MEF25, forced expiratory flow after 25% of the FVC; MEF50, forced expiratory flow after 50% of the FVC; MEF75, forced expiratory flow after 75% of the FVC; MVV, maximal voluntary ventilation; VC, vital capacity; RV, residual volume, TLC, total lung capacity; DLCO, diffusion capacity of the lung for carbon monoxide; CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; FeNO, fractional exhaled nitric oxide; ppb, parts per billion; UIP, usual interstitial pneumonia; PFT, pulmonary function test. |
FeNO And CTD-ILD
According to the etiology, all patients with ILDs were divided into CTD-ILD (n = 30) and non-CTD-ILD (n = 23). There were more female patients in CTD-ILD group compared to non-CTD ILD group (50.00% vs 21.74%). Patients in CTD-ILD group were younger than non-CTD ILD group (P = 0.022). No significant differences were observed with regard to height, weight, and body mass index between these two groups. Regarding the FeNO value and PFT values, no significant differences were observed between groups. No significant differences were reported in systemic inflammatory markers, such as ESR and CRP, between groups (Table 3).
Table 3
Clinical characteristics in CTD-ILD and non-CTD patients with ILD
Parameter | CTD-ILD (N = 30) | non-CTD-ILD (N = 23) | P value |
Mean age, years | 54.83 ± 14.17 | 63.61 ± 12.22 | 0.022 |
Sex (M/F), n | 15:15 | 18:5 | |
Height (cm) | 161.87 ± 7.09 | 161.04 ± 7.56 | 0.686 |
Weight (kg) | 58.80 ± 11.85 | 64.78 ± 10.27 | 0.054 |
Body surface area (m2) | 1.62 ± 0.18 | 1.68 ± 0.12 | 0.142 |
BMI in kg/m2 | 23.30 ± 3.56 | 24.06 ± 3.25 | 0.235 |
FVC (% predicted) | 75.40 ± 18.80 | 72.35 ± 17.50 | 0.549 |
FEV1 (% predicted) | 77.10 ± 20.08 | 74.43 ±16.02 | 0.604 |
FEV1/FVC | 83.67± 9.17 | 82.22 ± 7.79 | 0.546 |
PEF (% predicted) | 69.03 ± 22.84 | 70.26 ± 17.00 | 0.830 |
MEF (% predicted) | 82.43 ± 35.42 | 74.74 ± 33.15 | 0.424 |
MEF25 (% predicted) | 63.20 ± 35.48 | 48.52 ± 26.58 | 0.103 |
MEF50 (% predicted) | 79.17 ± 35.47 | 74.30 ± 32.85 | 0.612 |
MEF75 (% predicted) | 65.77 ± 24.65 | 59.70 ± 20.67 | 0.346 |
MVV (% predicted) | 82.33 ± 23.49 | 93.61 ± 28.11 | 0.118 |
VC (% predicted) | 72.27 ± 18.06 | 71.09 ± 17.30 | 0.811 |
TLC (% predicted) | 76.43 ± 14.74 | 73.87 ±13.39 | 0.523 |
RV (% predicted) | 91.54 ± 21.26 | 85.48 ± 16.39 | 0.268 |
RV/TLC (% predicted) | 43.61 ± 7.43 | 46.09 ± 6.81 | 0.224 |
DLCO (% predicted) | 48.05± 18.34 | 47.64 ± 17.37 | 0.948 |
Total serum IgE (IU/ml) | 213.80 ± 184.28 | 131.23 ± 126.00 | 0.155 |
Blood eosinophils absolute (cells/µl) | 168.29 ± 164.82 | 253.18 ± 199.20 | 0.094 |
Blood eosinophil percentage | 2.04 ± 1.85 | 3.07 ± 2.24 | 0.073 |
CRP (mg/L) | 20.33 ± 18.70 | 17.42 ± 15.25 | 0.737 |
ESR (mm/h) | 47.34 ± 36.19 | 38.20 ± 23.86 | 0.374 |
FeNO (ppb) | 18.33 ± 8.35 | 22.78 ± 11.05 | 0.101 |
Notes: Measured pulmonary function values are presented as a percentage of predictive. Data are shown as mean ± standard deviation unless indicated otherwise. Abbreviations: M, male; F, female; BMI, body mass index; FEV1, forced expiratory volume in 1 s; FVC, forced vital capacity; PEF, peak expiratory flow; MEF, maximal midexpiratory flow; MEF25, forced expiratory flow after 25% of the FVC; MEF50, forced expiratory flow after 50% of the FVC; MEF75, forced expiratory flow after 75% of the FVC; MVV, maximal voluntary ventilation; VC, vital capacity; RV, residual volume, TLC, total lung capacity, DLCO, diffusion capacity of the lung for carbon monoxide; CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; FeNO, fractional exhaled nitric oxide; ppb, parts per billion; CTD-ILD, connective tissue diseases associated with interstitial lung disease.
Correlation of FeNO and blood eosinophil, IgE, and systemic inflammatory markers
In the overall ILD population, the FeNO level correlated with blood eosinophil (r = 0.3066, P = 0.0333). No statistically significant correlations were observed between the FeNO and blood eosinophil percentage, IgE or systemic inflammatory markers. (Fig. 2).
Notes The correlations between FeNO values and blood eosinophil, IgE or systemic inflammatory markers were determined by calculating Spearman’s rank correlation coefficients. Abbreviations: CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; FeNO, fractional exhaled nitric oxide.
Discriminating UIP-ILDs and UIP-ILDs
Receiver operating characteristic (ROC) curve was performed to find the optimal cut-off value of FeNO to identify non-UIP-ILDs. The area under the ROC curve was 0.933 with a cut-off value of 18.5 ppb, showing a sensibility of 83.3% and a specificity of 95.8% in discriminating non-UIP-ILDs from UIP ILDs (Fig. 3). Table 4 shows the sensitivity and specificity values for different criteria tested.
Table 4
Sensitivity and specificity of different cut-points used to identify non-UIP-ILDs
Parameter | Threshold | Sensitivity (%) | Specificity (%) |
FeNO level | > 12.5 ppb | 93.1 | 50.0 |
FeNO level | > 13.5 ppb | 93.1 | 58.3 |
FeNO level | > 14.5 ppb | 93.1 | 66.7 |
FeNO level | > 15.5 ppb | 93.1 | 75.0 |
FeNO level | > 16.5 ppb | 83.3 | 83.3 |
FeNO level | > 17.5 ppb | 83.3 | 91.7 |
FeNO level | > 18.5 ppb | 83.3 | 95.8 |
FeNO level | > 20.0 ppb | 66.7 | 100 |
Abbreviations: FeNO, fractional exhaled nitric oxide; ppb, part per billion. |