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

Michela Abrami; Massimo Maschio; Massimo Conese; Marco Confalonieri; Sante Di Gioia; Fabio Gerin; Barbara Dapas; Federica Tonon; Rossella Farra; Erminio Murano; Giada Zanella; Francesco Salton; Lucio Torelli; Gabriele Grassi; Mario Grassi

doi:10.1002/mrm.28115

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

Magn Reson Med. 2020 Jul;84(1):427-436. doi: 10.1002/mrm.28115. Epub 2019 Dec 1.

Authors

Affiliations

¹ Department of Engineering and Architecture, University of Trieste, Trieste, Italy.
² Institute for Maternal and Child Health, IRCCS Burlo Garofolo, Trieste, Italy.
³ Department of Medical and Surgical Sciences, Foggia University, Ospedali Riuniti, Foggia, Italy.
⁴ Pulmonology Department, Cattinara University Hospital, Pulmonology Department, Trieste, Italy.
⁵ Department of Life Sciences, Cattinara University Hospital, Trieste University, Trieste, Italy.
⁶ Nealys S.R.L., Trieste, Italy.
⁷ Cattinara University Hospital, Department of Clinical, Surgery and Health Sciences, Trieste, Italy.

PMID: 31788856
DOI: 10.1002/mrm.28115

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 (T_2m ) 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 T_2m 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 T_2m directly correlates (r_FEV1 = 0.44; P < 10^-4 ; 169 samples) with FEV₁ . Moreover, T_2m inversely correlates with the circulating inflammation markers CRP/neutrophil number (r_CRP = -0.44, P < 10^-4 ; r_NC = -0.37, P < 2 * 10^-4 ; 103 and 86 samples, respectively) and with the sputum inflammatory cytokines TNFα/IL-β1 (r_TNFα = -0.72, P < 10^-4 ; r_IL-1β = -0.685, P < 10^-4 ; 27 samples). T_2m variations also correspond to FEV₁ values over time in defined patients.

Conclusion: These findings, together with the fast, reliable, and simple determination of T_2m , make our approach a novel tool potentially usable in the real world of CF patients.

Keywords: FEV1; cystic fibrosis; inflammation; low field NMR; monitoring; sputum.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Biomarkers
C-Reactive Protein
Cystic Fibrosis* / diagnostic imaging
Cytokines
Humans
Inflammation
Magnetic Resonance Spectroscopy
Pneumonia*
Sputum
Vascular Endothelial Growth Factor A

Substances

Biomarkers
Cytokines
Vascular Endothelial Growth Factor A
C-Reactive Protein