Use of low field nuclear magnetic resonance to monitor lung inflammation and the amount of pathological components in the sputum of cystic fibrosis patients

Abstract

Purpose To develop a novel approach to monitor lung ventilation/inflammation in cystic fibrosis (CF) patients. Lung assessment in CF patients is relevant given that most patients succumb to respiratory failure. Respiratory functional tests (forced expiratory volume in the first second; FEV1) and inflammatory markers are used to test pulmonary ventilation/inflammation, respectively. However, FEV1 is effort dependent and might be uncomfortable for CF patients. Furthermore, inflammatory marker detection is costly and not rapid. To overcome these limitations, we propose the measurement, by means of low field nuclear magnetic resonance, of the spin‐spin relaxation time (T2m) of water hydrogens present in CF patient sputum. In CF sputum, different biological components are pathologically increased and inversely related to lung functionality. Moreover, we showed that these components alter in a dose‐dependent manner the T2m in synthetic CF sputum. Methods Sputum samples were obtained from 42 CF subjects by voluntary expectoration; FEV1, C‐reactive protein (CRP), blood neutrophil counts together with cytokine (tumor necrosis factor alpha [TNFα], interleukin [IL]‐1β, IL‐4, and vascular endothelial growth factor) quantifications were then evaluated. Results In sputum samples, we observe that T2m directly correlates (rFEV1 = 0.44; P < 10−4; 169 samples) with FEV1. Moreover, T2m inversely correlates with the circulating inflammation markers CRP/neutrophil number (rCRP = −0.44, P < 10−4; rNC = −0.37, P < 2 * 10−4; 103 and 86 samples, respectively) and with the sputum inflammatory cytokines TNFα/IL‐β1 (rTNFα = −0.72, P < 10−4; rIL‐1β = −0.685, P < 10−4; 27 samples). T2m variations also correspond to FEV1 values over time in defined patients. Conclusion These findings, together with the fast, reliable, and simple determination of T2m, make our approach a novel tool potentially usable in the real world of CF patients.

Combined use of rheology and portable low-field NMR in cystic fibrosis patients

“…Moreover, the data extrapolated from Fig. 4A and B confirm our previous findings [8,9], i.e. there is a significant correlation (r sp = 0.55, p = 4*10 − 3 ) between T 2m and FEV 1 (correlation line: FEV 1 = (1.7 ± 0.5)*10 − 2 *T 2m + (40 ± 6)).…”

“…There are evident differences in the decay curves, which depend on the increased concentration and spatial organization of the solids within the sputum. This, in turn, determines a higher sputum dehydration [8,9] and viscosity.…”

“…Recently [8,9], we studied the characteristics of CF sputum using low field nuclear magnetic resonance (LF-NMR). Expectorated sputum is easily obtained from patients and its properties mirror those of mucus [5,10].…”

“…The LF-NMR technique we used allows for the measurement of the spin-spin relaxation time (T 2m ) of the water hydrogens present in the CF sputum. Our previous data showed [8,9] that the T 2m measured in CF sputum has an indirect correlation with circulating/local inflammation markers and a direct correlation with FEV 1 (forced expiratory volume in the first second, i.e. the amount that is exhaled in the first second purposefully trying to breath out as much air as possible), the most commonly used test in clinical practice for the evaluation of lung function [11].…”

Effect of chest physiotherapy on cystic fibrosis sputum nanostructure: an experimental and theoretical approach

“…Figure 2 remarkably shows that there is a statistically significant correlation between T 2m measured in CF sputum and FEV 1 before (dark circles; r sp = 0.69, p = 0.006) and after (white circles; r sp = 0.44, p = 0.044) chest physiotherapy. As lung functionality increases with FEV 1 [53], Fig. 2 indicates that T 2m increase is connected with improved patient clinical conditions.…”