Lung structural and functional impairments in young children with cystic fibrosis diagnosed following newborn screening - A nationwide observational study.

BACKGROUND: Non-invasive and sensitive clinical endpoints are needed to monitor onset and progression of early lung disease in children with cystic fibrosis (CF). We compared lung clearance index (LCI), FEV1, functional and structural lung magnetic resonance imaging (MRI) outcomes in Swiss children with CF diagnosed following newborn screening. METHODS: Lung function (LCI, FEV1) and unsedated functional and structural lung MRI was performed in 79 clinically stable children with CF (3 - 8 years) and 75 age-matched healthy controls. Clinical information was collected throughout childhood. RESULTS: LCI, ventilation and perfusion defects, and structural MRI scores were significantly higher in children with CF compared with controls, but FEV1 was not different between groups. Lung MRI outcomes correlated significantly with LCI (morphology score (r = 0.56, p < 0.001); ventilation defects (r = 0.43, p = 0.001); perfusion defects (r = 0.64, p < 0.001), but not with FEV1. Lung MRI outcomes were more sensitive to detect impairments in children with CF (abnormal ventilation and perfusion outcomes in 47 %, morphology score in 30 %) compared with lung function (abnormal LCI in 21 % and FEV1 in 4.8 %). Pulmonary exacerbations, respiratory hospitalizations, and increase in patient-reported cough was associated with higher LCI and higher structural and functional MRI outcomes. CONCLUSIONS: The LCI and lung MRI outcomes non-invasively detect even mild early lung disease in young children with CF diagnosed following newborn screening. Pulmonary exacerbations and early respiratory symptoms were risk factors for structural and functional impairment in childhood.

Effects of elexacaftor/tezacaftor/ivacaftor therapy in children with cystic fibrosis - a comprehensive assessment using lung clearance index, spirometry, and functional and structural lung MRI.

BACKGROUND: With improvement in supportive therapies and the introduction of cystic fibrosis transmembrane conductance regulator (CFTR)-modulator treatment in patients with cystic fibrosis (CF), milder disease courses are expected. Therefore, sensitive parameters are needed to monitor disease course and effects of CFTR-modulators. Functional lung MRI using matrix-pencil decomposition (MP-MRI) is a promising tool for assessing ventilation and perfusion quantitatively. This study aimed to assess the treatment effect of elexacaftor/tezacaftor/ivacaftor combination regimen (ELX/TEZ/IVA) on measures of structural and functional lung abnormalities. METHODS: 24 children with CF underwent lung function tests (multiple breath washout, spirometry), functional and structural MRI twice (one year apart) before and once after at least two weeks (mean 4.7 ± 2.6 months) on ELX/TEZ/IVA. Main outcomes were changes (Δ) upon ELX/TEZ/IVA in lung function, defect percentage of ventilation (VDP) and perfusion (QDP), defect distribution index of ventilation and perfusion (DDIV, DDIQ), and Eichinger score. Statistical analyses were performed using paired t-tests and multilevel regression models with bootstrapping. RESULTS: We observed a significant improvement in lung function, structural and functional MRI parameters upon ELX/TEZ/IVA treatment (mean; 95%-CI): ΔLCI2.5 (TO) -0.84 (-1.62 to -0.06); ΔFEV1 (z-score) 1.05 (0.56 to 1.55); ΔVDP (% of impairment) -6.00 (-8.44 to -3.55); ΔQDP (% of impairment) -3.90 (-5.90 to -1.90); ΔDDIV -1.38 (-2.22 to -0.53); ΔDDIQ -0.31 (-0.73 to 0.12); ΔEichinger score -3.89 (-5.05 to -2.72). CONCLUSIONS: Besides lung function tests, functional and structural MRI is a suitable tool to monitor treatment response of ELX/TEZ/IVA therapy, and seems promising as outcome marker in the future.

Adipopenia correlates with higher portal pressure in patients with cirrhosis.

BACKGROUND & AIMS: In cirrhosis, hepatic venous pressure gradient (HVPG) and imaging body composition assessment can influence prognosis. We assessed whether adipose and skeletal muscle tissues reflect the severity of portal hypertension (PH), and whether they improve non-invasive prediction of decompensation and death. METHODS: We included 84 cirrhosis patients with HVPG and computed tomography (CT) within 12 weeks of HVPG at a single centre. L3 vertebra CT images were used for body composition indexes (cm2 /m2 ): total adipose tissue index (TATI), visceral adipose tissue index (VATI), subcutaneous adipose tissue index (SATI), intramuscular adipose tissue index (IMATI), skeletal muscle index (SMI) and psoas muscle index (PMI). Correlations were calculated between indexes, HVPG and standard non-invasive tests for PH. Twelve-month decompensation and death predictors were determined. RESULTS: The following were the characteristics for the patients included in the study: male 61%; BMI 28 ± 5 kg/m2 ; alcoholic liver disease in 51%, non-alcoholic steatohepatitis in 24%; HVPG 14 ± 6 mm Hg; 45% compensated. The median follow-up was 11 (4-17) months. HVPG correlated with SATI (r = -0.282, P = 0.01), TATI (r = -0.220, P = 0.045) and SATI/VATI index (r = -0.240, P = 0.03). In compensated patients, lower VATI (HR 0.94 (0.90-0.99), P = 0.01) was associated with 12-month decompensation. Combining TATI and liver stiffness × spleen size over-platelet count risk score added discriminative capacity for 12-month decompensation (AUROC 0.91 vs 0.87). IMATI was independently associated with mortality in decompensated patients. MELD-Na combined with IMATI discriminated excellently for mortality (AUROC 0.94; P < 0.001). CONCLUSIONS: Hepatic venous pressure gradient inversely correlates with imaging markers of adipose tissue, while markers of sarcopenia were unrelated to PH. In compensated patients, TATI improves non-invasive prediction of decompensation. In decompensated patients, IMATI independently predicted mortality.