The trend and the disease prediction of vascular endothelial growth factor and placenta growth factor in nontuberculous mycobacterial lung disease

Abstract

Nontuberculous mycobacteria (NTM)-lung disease (LD) is an increasing health problem worldwide. The diagnosis of this disease remains difficult, however the application of placenta growth factor (PlGF) and vascular endothelial growth factor (VEGF) has not yet been studied. We screened patients with Mycobacterium avium complex or M. abscessus isolated from sputum, and enrolled 32 patients with NTM-LD and 93 with NTM pulmonary colonization. The NTM-LD group had a lower body mass index, higher proportion of bronchiectasis, more respiratory symptoms and pulmonary lesions, and higher titers of sputum acid-fast stain than the NTM pulmonary colonization group. The plasma level of PlGF was lower in the NTM-LD group than in the NTM colonization group, whereas the level of VEGF was higher in the NTM-LD group. In multivariable logistic regression analysis excluding NTM cultures, the predictive model for NTM-LD included sputum AFS titer, a nodular-bronchiectasis radiographic pattern, plasma VEGF/PlGF ratio, and chest radiographic score (VEGF/P1GF ratio became not significant as a factor in multivariable generalized linear model). The four-factor predictive index had good positive likelihood ratio and negative likelihood ratio for predicting NTM-LD in the patients with NTM in their sputum.

Figure 1. Flow chart of screening and enrolling participants with sputum positive for nontuberculous mycobacteria (NTM).

Because enrolling period and parent population of the control group are not the same as participants with NTM in sputum. We did not describe the control group in the flow chart. LD, lung disease.

Figure 2

Plasma levels of (A) placenta growth factor (PlGF), (B) vascular endothelial growth factor (VEGF), and (C) their ratio according to nontuberculous mycobacteria (NTM)-lung disease (LD), pulmonary colonization (col), and control group. The cross lines are mean value and error bars are standard error of the mean. ns, not statistically significant.

Figure 3

Receiver operating characteristic (ROC) curves for predicting nontuberculous mycobacteria (NTM)-lung disease in patients with sputum positive for NTM by (A) the four significant factors in the multivariable regression and by (B) the numbers of sputum culture positive for NTM, the probability (ǂ) from the multivariable logistc regression analysis, and the predictive index score (*) by the four factors. The four factors using for the predictive index score were ratio of plasma vascular endothelial growth factor (VEGF)/placenta growth factor (PlGF) >1.8, positive sputum acid fast smear (AFS), radiographic pattern of nodular-bronchiectasis (NB) pattern, and radiographic (chest X film, CXR) score >2. One point was given for each factor and the sum was the predictive index score.