Long-term pulmonary outcome of children with congenital diaphragmatic hernia: functional lung MRI using matrix-pencil decomposition enables side-specific assessment of lung function.

OBJECTIVES: In patients with congenital diaphragmatic hernia (CDH) the exact functional outcome of the affected lung side is still unknown, mainly due to the lack of spatially resolved diagnostic tools. Functional matrix-pencil decomposition (MP-) lung MRI fills this gap as it measures side-specific ventilation and perfusion. We aimed to assess the overall and side-specific pulmonary long-term outcomes of patients with CDH using lung function tests and MP-MRI. METHODS: Thirteen school-aged children with CDH (seven with small and six with large defect-sized CDH, defined as > 50% of the chest wall circumference being devoid of diaphragm tissue) and thirteen healthy matched controls underwent spirometry, multiple-breath washout, and MP-MRI. The main outcomes were forced expiratory volume in 1 second (FEV1), lung clearance index (LCI2.5), ventilation defect percentage (VDP), and perfusion defect percentage (QDP). RESULTS: Patients with a large CDH showed significantly reduced overall lung function compared to healthy controls (mean difference [95%-CIadjusted]: FEV1 (z-score) -4.26 [-5.61, -2.92], FVC (z-score) -3.97 [-5.68, -2.26], LCI2.5 (TO) 1.12 [0.47, 1.76], VDP (%) 8.59 [3.58, 13.60], QDP (%) 17.22 [13.16, 21.27]) and to patients with a small CDH. Side-specific examination by MP-MRI revealed particularly reduced ipsilateral ventilation and perfusion in patients with a large CDH (mean difference to contralateral side [95%-CIadjusted]: VDP (%) 14.80 [10.50, 19.00], QDP (%) 23.50 [1.75, 45.20]). CONCLUSIONS: Data indicate impaired overall lung function with particular limitation of the ipsilateral side in patients with a large CDH. MP-MRI is a promising tool to provide valuable side-specific functional information in the follow-up of patients with CDH. CLINICAL RELEVANCE STATEMENT: In patients with congenital diaphragmatic hernia, easily applicable MP-MRI allows specific examination of the lung side affected by the hernia and provides valuable information on ventilation and perfusion with implications for clinical practice, making it a promising tool for routine follow-up. KEY POINTS: • Functional matrix pencil decomposition (MP) MRI data from a small sample indicate reduced ipsilateral pulmonary ventilation and perfusion in children with large congenital diaphragmatic hernia (CDH). • Easily applicable pencil decomposition MRI provides valuable side-specific diagnostic information on lung ventilation and perfusion. This is a clear advantage over conventional lung function tests, helping to comprehensively follow up patients with congenital diaphragmatic hernia and monitor therapy effects.

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.

Effect of Salbutamol on Lung Ventilation in Children with Cystic Fibrosis: Comprehensive Assessment Using Spirometry, Multiple-Breath Washout, and Functional Lung Magnetic Resonance Imaging.

BACKGROUND: Inhalation therapy is one of the cornerstones of the daily treatment regimen in patients with cystic fibrosis (CF). Recommendations regarding the addition of bronchodilators, especially salbutamol are conflicting due to the lack of evidence. New diagnostic measures such as multiple-breath washout (MBW) and functional magnetic resonance imaging (MRI) have the potential to reveal new insights into bronchodilator effects in patients with CF. OBJECTIVE: The objective of the study was to comprehensively assess the functional response to nebulized inhalation with salbutamol in children with CF. METHODS: Thirty children aged 6-18 years with stable CF performed pulmonary function tests, MBW, and matrix pencil-MRI before and after standardized nebulized inhalation of salbutamol. RESULTS: Lung clearance index decreased (improved) by -0.24 turnover (95% confidence interval [CI]: -0.53 to 0.06; p = 0.111). Percentage of the lung volume with impaired fractional ventilation and relative perfusion decreased (improved) by -0.79% (CI: -1.99 to 0.42; p = 0.194) and -1.31% (CI: -2.28 to -0.35; p = 0.009), respectively. Forced expiratory volume (FEV1) increased (improved) by 0.41 z-score (CI: 0.24-0.58; p < 0.0001). We could not identify specific clinical factors associated with a more pronounced effect of salbutamol. CONCLUSIONS: There is a positive short-term effect of bronchodilator inhalation on FEV1 in patients with CF, which is independent of ventilation inhomogeneity. Heterogeneous response between patients suggests that for prediction of a therapeutic effect this should be tested by spirometry in every patient individually.

Alternate gas washout indices: Assessment of ventilation inhomogeneity in mild to moderate pediatric cystic fibrosis lung disease.

INTRODUCTION: Normalized phase III slope (SnIII ) indices from multiple breath washout (MBW) estimate ventilation inhomogeneity. Alternate (*) protocols for SnIII indices exist, however the utility of these outcomes in children with mild-to-moderate cystic fibrosis (CF) is unknown. METHODS: We measured nitrogen MBW and spirometry in 135 children (43 controls) aged 4-18 years. We assessed validity, practicability, and reliability of SnIII protocols. Outcomes included the ability to detect abnormal lung function, test agreement, measurement duration, intra-test repeatability, and quality. RESULTS: Lung clearance index (LCI) was abnormal in 80 (87%), Scond in 55 (60%), Scond* in 17 (19%), Sacin in 10 (11%), Sacin* in 11 (12%), and FEV1 in 28 (30%). Alternate protocols reduced measurement duration. Agreement of indices to detect abnormal lung function was poor. The quality of analysis and repeatability deteriorated with the alternate technique compared to standard. CONCLUSION: In children with mild-to-moderate CF lung disease, alternate protocols seem practical but clinimetric properties of standard SnIII protocols are preferable.