Serum YKL-40 as predictor of outcome in hypersensitivity pneumonitis

Abstract

YKL-40, a chitinase-like protein mainly secreted by macrophages, neutrophils and epithelial cells, is increased in patients with idiopathic interstitial pneumonia and sarcoidosis. We aimed to investigate the role of YKL-40 as a biomarker in hypersensitivity pneumonitis (HP).72 HP patients, 100 interstitial lung disease (ILD) controls and 60 healthy controls were studied. YKL-40 was measured by ELISA in serum and bronchoalveolar lavage fluid (BALF) at baseline and follow-up. The relationship between YKL-40 levels, clinical variables and disease outcome was evaluated.Baseline serum YKL-40 levels were significantly higher in HP patients than in healthy controls (p<0.001), but lower than in patients with other ILDs. Baseline BALF YKL-40 levels in HP patients were the highest among ILD patients. In HP patients, serum YKL-40 correlated with the diffusing capacity of the lung for carbon monoxide at baseline (p<0.01) and over time (p<0.001). HP patients whose disease progressed or who died had higher baseline YKL-40 levels than those who remained stable and survived (p<0.001). At a cut-off of 119 ng·mL, the baseline serum YKL-40 level predicted disease progression (hazard ratio 6.567; p<0.001), and at a cut-off of 150 ng·mL was associated with mortality (hazard ratio 9.989; p<0.001).Serum YKL-40 may be a useful prognostic biomarker in HP patients.

Serum YKL‐40 in workers at an indium‐tin oxide production facility – Reply

“…In addition, we observed the correlation of serum lactate dehydrogenase (LDH) with YKL-40 only in PAP and HP patients 2 but not in healthy controls, subjects who had normal LDH serum values similar to the ITOexposed workers.…”

“…[1][2][3][4] An important aspect is that these ITOexposed workers did not suffer from PAP. In our PAP cohort, the mean YKL-40 serum level was sevenfold higher than in our healthy cohort.…”

“…In a multicentre analysis of 7325 measurements in 1058 subjects from the general population with normal spirometry (78%) or slight abnormalities (22%), Guerra et al found that serum YKL-40 levels were linked to lung function deficit (both forced expiratory volume in 1 s (FEV 1 ) and forced vital capacity (FVC)) and decline over time, particularly in smokers. 3 In addition, an inverse correlation with diffusing capacity of the lung for carbon monoxide (DL CO ) has been reported for sarcoidosis, 4 idiopathic pulmonary fibrosis (IPF) 5 and hypersensitivity pneumonitis (HP) 2 patients. Similar to Harvey et al, we also found a weak correlation (r = 0.264, P < 0.05) of serum YKL-40 with age in patients affected by HP, 2 and Kruit et al found that this correlation could explain 5% of the variation of this biomarker in serum.…”

“…3 In addition, an inverse correlation with diffusing capacity of the lung for carbon monoxide (DL CO ) has been reported for sarcoidosis, 4 idiopathic pulmonary fibrosis (IPF) 5 and hypersensitivity pneumonitis (HP) 2 patients. Similar to Harvey et al, we also found a weak correlation (r = 0.264, P < 0.05) of serum YKL-40 with age in patients affected by HP, 2 and Kruit et al found that this correlation could explain 5% of the variation of this biomarker in serum. 4 That we did not find such a correlation in our patients with autoimmune PAP can be explained by the fact that they are relatively homogeneous in age (40-50 years old), similar to our healthy controls.…”

Personalised medicine in interstitial lung diseases

“…Increased YKL-40 levels were found in patients with a variety of ILDs compared with healthy controls, with highest levels in those with more severe fibrosis and worse prognosis [42]. Increased levels have also been observed in patients with sarcoidosis [43], PAP [44] and hypersensitivity pneumonitis [45]. In hypersensitivity pneumonitis, higher baseline YKL-40 levels were associated with worse survival [45].…”