Early detection and sensitive monitoring of CF lung disease: Prospects of improved and safer imaging

Abstract

Summary. Recent imaging studies using chest computed tomography (CT) in presymptomatic infants and young children with cystic fibrosis (CF) diagnosed by newborn screening presented compelling evidence of early onset and progression of structural lung damage in CF. These data argue persuasively that non-invasive outcome measures for early detection and sensitive monitoring of lung disease applicable in the clinical setting will be instrumental for further improvement of clinical care and the development of early intervention therapies that have the potential to prevent irreversible lung damage. In this context, the use of CT imaging for early detection and long-term monitoring has the disadvantage of the risk to induce malignancies due to cumulating ionizing radiation exposure. More recently, magnetic resonance imaging (MRI) has emerged as an alternative radiation-free imaging technique for quantitative assessment of CF lung disease. In addition to structural lung damage, chest MRI enables non-invasive assessment of abnormalities in lung perfusion and ventilation characteristically associated with mucus plugging in CF lung disease. Here, we review recent developments and the prospects of MRI for improved and safer imaging with a focus on recent studies that support its utility as a sensitive non-invasive outcome measure of early lung disease in young children with CF. Pediatr Pulmonol. 2016;51:S49-S60.

Nebulized gentamicin in combination with systemic antibiotics for eradicating early Pseudomonas aeruginosa infection in children with cystic fibrosis

“…A likely reason for older children being at greater risk could be undetected previous or early Pa infections, where infrequent or sub‐optimal sampling led to false negative results. A second reason for increased risk of failing Pa eradication treatment could be that older children are likely to have more advanced airway disease; which may not have been detected using FEV1, which is relatively insensitive at detecting differences in mild disease …”

Three-center feasibility of lung clearance index in infants and preschool children with cystic fibrosis and other lung diseases

“…In contrast to other organs such as the pancreas, the lungs are structurally normal at birth in children with CF and early diagnosis by newborn screening has created a unique opportunity for early therapeutic intervention that may delay or ultimately prevent the onset of irreversible lung damage [8,31,32]. Therefore, clinical trials testing this early intervention paradigm and outcome measures that are feasible and sensitive to detect early lung disease in infants and preschool children with CF in a multicenter setting are urgently needed.…”

“…Therefore, quantitative non-invasive endpoints sensitive to detect early lung abnormalities and disease progression in multicenter studies are warranted for clinical testing of preventive therapies in infants and preschool children with CF [3]. In addition to work focusing on infant pulmonary function tests (PFT) and imaging by chest CT and MRI as outcome measures in this age group [4][5][6][7][8], emerging evidence suggests that lung clearance index (LCI) derived from multiple-breath washout (MBW) may be a suitable outcome measure for this purpose. First, a series of single center studies demonstrated that LCI detects ventilation inhomogeneity and response to therapeutic interventions such as inhaled hypertonic saline and Dornase alpha in school age children with normal spirometry, as well as preschool children and infants with CF [5,[9][10][11][12][13][14][15].…”

Differing Pulmonary Structural Abnormalities Detected on Pulmonary MR Imaging in Cystic Fibrosis Patients with Varying Pancreatic Function

“…Collectively these findings, especially the milder appearance of pulmonary structural changes in CF-PS patients, suggest that pancreatic function should be considered when determining disease severity and estimating course of progression. The combination of CF newborn screening and early imaging of clinically pre-symptomatic patients is an opportunity to delay and possibly prevent irreversible pulmonary changes and disease progression by early patient-based individualized therapeutic interventions [30].…”