Indirect evaluation of lung condition by means of LF-NMR following chest physiotherapy or ETI administration in cystic-fibrosis patients

Background: As most cystic fibrosis (CF) patients progress to respiratory failure, lung functionality assessment is pivotal. We previously developed a test that monitors airways measuring the spin-spin relaxation time (T2m) of water hydrogens present in sputum using Low Field-Nuclear Magnetic resonance (LF-NMR). Objectives: To investigate further the significance of T2m exploring: 1) T2m correlation with the effects of chest physiotherapy (CP); 2) the influence of sputum contamination by saliva on T2m; 3) T2m relation with sputum mesh size; 4) T2m correlation with the effects of the CFTR-modulator Elexa-caftor/Tezacaftor/Ivacaftor (ETI). Methods: T2m was measured in the sputum of 16 CF-patients before/after CP and in 9/16 patients before/after ETI administration. FEV1/C reactive protein (CRP)/erythrocyte-sedimentation rate (ESR) and sweat chloride concentration were measured using standard techniques. Sputum contamination by saliva/sputum mesh size were determined mathematically. Results: We prove that T2m can be used to detect the lack of significant effects on lung function by CP (confirmed by FEV1). Moreover, we developed of a mathematical approach to correct T2m value in sputum samples contaminated by saliva and to determine the relationship between T2m and sputum mesh size. Finally, we show that T2m can effectively detect the positive effects of ETI on lung function (evaluated by FEV1) and that T2m inversely correlates with the CRP/ESR/chloride sweat concentration. Conclusion: This data strengthens the rationale for T2m employment in CF lung disease monitoring and show that T2m can be profitably used to complement the FEV1 test.