Plasma Vascular Endothelial Growth Factor Concentration and Alveolar Nitric Oxide as Potential Predictors of Disease Progression and Mortality in Idiopathic Pulmonary Fibrosis

Abstract

Background: Declining lung function signifies disease progression in idiopathic pulmonary fibrosis (IPF). Vascular endothelial growth factor (VEGF) concentration is associated with declining lung function in 6 and 12-month studies. Alveolar nitric oxide concentration (CANO) is increased in patients with IPF, however its significance is unclear. This study investigated whether baseline plasma VEGF concentration and CANO are associated with disease progression or mortality in IPF. Methods: 27 IPF patients were studied (maximum follow-up 65 months). Baseline plasma VEGF concentration, CANO and pulmonary function tests (PFTs) were measured. PFTs were performed the preceding year and subsequent PFTs and data regarding mortality were collected. Disease progression was defined as one of: death, relative decrease of ≥10% in baseline forced vital capacity (FVC) % predicted, or relative decrease of ≥15% in baseline single breath diffusion capacity of carbon monoxide (TLCO-SB) % predicted. Results: Plasma VEGF concentration was not associated with progression-free survival or mortality. There was a trend towards shorter time to disease progression and death with higher CANO. CANO was significantly higher in patients with previous declining versus stable lung function. Conclusion: The role of VEGF in IPF remains uncertain. It may be of value to further investigate CANO in IPF.

Breath Biomarkers in Idiopathic Pulmonary Fibrosis: A Systematic Review

“…An alternative role for C alv NO may be in disease monitoring. Kotecha et al [68] suggested that C alv NO levels were reflective of deteriorating lung function. This is consistent with other studies suggesting that C alv NO levels are inversely related to lung function parameters in fibrotic ILD, a phenomenon not seen with FeNO [73,81,83].…”

“…Two studies compared breath biomarkers in IPF patients receiving treatment. Kotecha et al [68], found no difference in C alv NO levels in IPF patients receiving treatment with immunosuppression (either corticosteroids alone or in combination with azathioprine) and untreated patients. Corradi et al [59] found that there was no treatment effect on the presence of…”

“…Six studies assessed correlation between breath biomarkers and lung function in IPF patients [58,59,63,[66][67][68]. Kotecha et al [68] compared C alv NO levels in 27 IPF patients whose lung function had been declining in the previous 6-12 months to those with stable lung function. C alv NO levels were noted to be significantly higher in the 16 patients with declining lung function.…”

Extended Exhaled Nitric Oxide Analysis in Interstitial Lung Diseases: A Systematic Review

“…Concerning the association with pulmonary functional parameters, an inverse correlation between CaNO values and FVC and DLCO has been repeatedly observed, suggesting a potential value of this biomarker in the monitoring of disease progression [ 8 , 40 , 42 , 44 , 45 ]. One study also reported a significant correlation of CaNO with Composite Physiological Index (CPI), further supporting its potential as a severity biomarker in this setting [ 46 ].…”

“…One study also reported a significant correlation of CaNO with Composite Physiological Index (CPI), further supporting its potential as a severity biomarker in this setting [ 46 ]. Only two studies have specifically investigated the prognostic value of extended FeNO analysis in IPF, reporting a significantly worse survival and functional disease progression in patients with more elevated CaNO values [ 44 , 45 ]. No data are currently available regarding the dynamics of eNO parameters through the follow-up of IPF patients.…”