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Abstract
Rationale: Early onset and progression of lung disease in children with cystic fibrosis (CF) indicates that sensitive noninvasive outcome measures are needed for diagnostic monitoring and early intervention clinical trials. The lung clearance index (LCI) and chest magnetic resonance imaging (MRI) were shown to detect early lung disease in CF; however, the relationship between the two measures remains unknown.
Objectives: To correlate the LCI with abnormalities detected by MRI and compare the sensitivity of the two techniques to detect responses to therapy for pulmonary exacerbations in children with CF.
Methods: LCI determined by age-adapted multiple breath washout techniques and MRI studies were performed in 97 clinically stable children with CF across the pediatric age range (0.2-21.1 yr). Furthermore, LCI (n = 26) or MRI (n = 10) were performed at the time of pulmonary exacerbation and after antibiotic therapy. MRI was evaluated using a dedicated morphofunctional score.
Measurements and Main Results: The LCI correlated with the global MRI score as well as MRI-defined airway wall abnormalities, mucus plugging, and abnormal lung perfusion in infants and toddlers (P < 0.05 to P < 0.001) and in older children (P < 0.001) with CF. LCI and MRI were sensitive to detect response to antibiotic therapy for pulmonary exacerbations.
Conclusions: Our results indicate that LCI and MRI may be useful complementary tools for noninvasive monitoring and as quantitative endpoints in early intervention trials in children with CF. In this context, MRI enables detection of disease heterogeneity, including regional mucus plugging associated with abnormal lung perfusion in early CF lung disease.
Clinical trial registered with www.clinicaltrials.gov (NCT 02270476).
Keywords: lung clearance index; magnetic resonance imaging; noninvasive monitoring; cystic fibrosis; lung disease
Chronic progressive lung disease remains the primary cause of morbidity and mortality in patients with cystic fibrosis (CF) (1-3). Recent studies demonstrating early onset and progression of lung disease in children with CF suggest that sensitive noninvasive outcome measures of abnormal lung structure and function will be instrumental for further improvement of clinical management and the development of novel treatment strategies that may delay or even prevent irreversible lung damage and improve the long-term prognosis of patients with CF (4-7).
Traditionally, FEV1 has been used for noninvasive monitoring and as a clinical trial endpoint of lung...