Figures
- FIGURE 1
Autotaxin (ATX) levels in patients with fibrosing interstitial lung disease (ILD) and healthy controls (HC). Fibrosing ILD patients showed significantly increased ATX levels in a) male patients (0.743±0.160 mg ·L−1 versus 0.626±0.092 mg ·L−1; p=0.008) and b) female patients (0.975±0.236 mg· L−1 versus 0.786±0.133 mg· L−1; p=0.001).
- FIGURE 2
Survival curve of fibrosing interstitial lung disease (ILD) patients according to serum autotaxin (ATX) levels. a) Male patients with high ATX levels (>0.721 mg· L−1) showed significantly better outcome than patients with low ATX levels (log rank p=0.003). b) No such difference outcome was observed between high (>0.946 mg ·L−1) and low ATX levels in female patients (log rank p=0.478).
- FIGURE 3
Autotaxin (ATX) levels in male patients with chronic idiopathic pulmonary fibrosis (IPF) and acute exacerbation of IPF (AE-IPF). ATX levels were significantly decreased after the onset of AE-IPF compared with stable IPF (0.746±0.163 mg· L−1 versus 0.564±0.199 mg· L−1; p=0.006).
Tables
- TABLE 1
Baseline characteristics of patients with stable fibrosing interstitial lung disease (ILD)
Patients Healthy controls Subjects, n 119 38 Age years 70±9 52±11 Sex (male), n (%) 69 (58) 16 (42) Smoking history (yes), n (%) 73 (61) 11 (29) Diagnosis of fibrosing ILD, n IPF 78 NSIP 11 Unclassifiable ILD 10 PPFE 8 CTD-ILD 12 Treatment at the time of analysis, n Corticosteroids 25 Pirfenidone 19 Nintedanib 15 Laboratory data LDH U· L−1 252±54 KL-6 U m·L−1 1029±680 SP-D ng· mL−1 215±148 Pulmonary function FVC mL 2133±743 %FVC 75.9±20.4 DLCO % 59.8±20.9 Data are presented as mean±sd, unless otherwise stated. IPF: idiopathic pulmonary fibrosis; NSIP: nonspecific interstitial pneumonia; CTD-ILD: connective tissue disease-associated ILD; PPFE: pleuroparenchymal fibroelastosis; LDH: lactate dehydrogenase; SP-D: surfactant protein-D; KL-6: Krebs von den Lungen-6; FVC: forced vital capacity; DLCO: diffusing capacity of the lung for carbon monoxide.
- TABLE 2
Autotaxin (ATX) activity by sex in fibrosing interstitial lung disease (ILD) patients without corticosteroid therapy at the time of blood sampling
Diagnosis of ILD IPF NSIP Unclassifiable ILD PPFE CTD-ILD Male Subjects, n 53 3 1 4 0 ATX activity mg· L−1 0.746±0.163 0.793±0.221 0.661 0.683±0.988 Female Subjects, n 16 4 3 4 6 ATX activity mg· L−1 1.003±0.258 0.933±0.105 1.217±0.376 0.869±0.195 0.876±0.101 Data are presented as mean±sd, unless otherwise stated. IPF: idiopathic pulmonary fibrosis; NSIP: nonspecific interstitial pneumonia; PPFE: pleuroparenchymal fibroelastosis; CTD-ILD: connective tissue disease-associated ILD.
- TABLE 3
Correlation between autotaxin levels and clinical parameters
r p-value Male (n=61) KL-6 −0.117 0.370 SP-D 0.040 0.757 %FVC −0.093 0.481 DLCO % −0.191 0.146 Δ1 year %FVC (n=28) 0.142 0.472 Female (n=33) KL-6 −0.009 0.957 SP-D 0.218 0.223 %FVC 0.051 0.784 DLCO % −0.135 0.471 Δ1 year %FVC (n=13) −0.676 0.014 KL-6: Krebs von den Lungen-6; SP-D: surfactant protein-D; FVC: forced vital capacity; DLCO : diffusing capacity of the lung for carbon monoxide.
- TABLE 4
Receiver operating characteristic (ROC) curve analysis to determine the optimal cut-off value of autotaxin for predicting the worse outcome of fibrosing interstitial lung disease
Cut-off value mg ·dL−1 AUC Sensitivity % Specificity % Male (n=61) 0.721 0.766 92.9 61.7 Female (n=33) 0.946 0.608 62.5 64.0 AUC: area under curve.
- TABLE 5
Multivariate analysis using Cox proportional hazards model for predicting independent predictors of worse outcome in male patients with fibrosing interstitial lung disease (n=61)
Hazard ratio 95% CI p-value Age years 1.005 0.943–1.072 0.868 Smoking history (yes) 1.257 0.156–10.100 0.830 KL-6 0.999 0.998–1.001 0.228 %FVC 0.964 0.930–0.999 0.043 ATX >0.721 mg ·L−1 8.295 1.049–65.558 0.045 KL-6: Krebs von den Lungen-6; FVC: forced vital capacity; ATX: autotaxin.
- TABLE 6
Baseline characteristics of male patients with acute exacerbation of idiopathic pulmonary fibrosis (n=6)
Age years 71±6 PaO2/FIO2 315±52 LDH U·L−1 332±43 KL-6 U·mL−1 1808±990 SP-D ng·mL−1 318±137 CRP mg ·dL−1 9.3±10.9 Data are presented as mean±sd. PaO2: arterial oxygen tension; FIO2: inspiratory oxygen fraction; LDH: lactate dehydrogenase; KL-6: Krebs von den Lungen-6; SP-D: surfactant protein-D; CRP: C-reactive protein.
Supplementary Material
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Supplementary material 00683-2021.SUPPLEMENT
