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.

Highlights

  • Combining these factors with biomarkers may be more useful

  • The plasma level of vascular endothelial growth factor (VEGF) was higher in the patients with nontuberculous mycobacteria (NTM)-lung disease (LD) than in those with NTM pulmonary colonization, while the plasma Placenta growth factor (PlGF) level had an opposite trend

  • A radiographic nodular-bronchiectasis pattern, sputum Acid fast smears (AFS) titer, radiographic score, and VEGF/PlGF ratio were correlated with NTM-LD status when blinded to data from a second set or later of sputum microbiology for NTM

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Summary

Introduction

Combining these factors with biomarkers may be more useful. systemic inflammatory molecules in the blood such as interferon-gamma and C-reactive protein have been reported to be poorly associated with making a diagnosis, indicating that host cellular immunity may not be adequately responding to a NTM infection[14]. Local pulmonary biomarkers may be better predictors Of these markers, vascular endothelial growth factor (VEGF) is responsible for angiogenesis in granulomatous inflammation and is produced by macrophages to induce an immune recruitment response when mycobacteria enter the airway[15,16]. Placenta growth factor (PlGF) is produced from bronchial epithelial cells and is a biomarker that shares significant sequence homology with VEGF at an amino acid level. It can inhibit proliferation, promote cell death, and it has been reported to potentially represent local inflammation[20,21,22]. The aim of this prospective study, was to investigate dynamic changes in PlGF and VEGF between NTM-LD and pulmonary colonization, and analyze the potential diagnostic value of these biomarkers

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