Yearly MRI offers chronic rhinosinusitis monitoring in pediatric cystic fibrosis
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Key takeaways:
- From infancy to preschool age, average chronic rhinosinusitis MRI score went up, signaling more severe sinus abnormalities.
- This score went down by 0.5 following initiation of lumacaftor/ivacaftor therapy.
Yearly paranasal sinus MRI imaging allowed physicians to track chronic rhinosinusitis development in children with cystic fibrosis, according to results published in Annals of the American Thoracic Society.
“Our study demonstrates an early onset of [chronic rhinosinusitis] in children with cystic fibrosis (CF) and a marked progression of [chronic rhinosinusitis]-related abnormalities of the paranasal sinuses until preschool age,” Lena Wucherpfennig, MD, of the department of diagnostic and interventional radiology at University Hospital Heidelberg, and colleagues wrote. “Taken together, these results suggest that noninvasive monitoring of [chronic rhinosinusitis] should be considered from birth.”
In a longitudinal study, Wucherpfennig and colleagues assessed 64 children (mean age at baseline, 1.1 year) with CF and annual paranasal sinus MRIs (435 total) to track chronic rhinosinusitis from infancy to preschool age (1 to 5 years) and school age (6 years and older) using this noninvasive form of monitoring.
Within this cohort, researchers also compared MRIs taken prior to and after lumacaftor/ivacaftor (Orkambi, Vertex Pharmaceuticals) therapy in 24 children (mean age, 9.2 years) homozygous for the F508del mutation.
Researchers used the chronic rhinosinusitis MRI score in this analysis, which focuses on four sinuses — maxillary, frontal, sphenoid and ethmoid — and rates opacity, mucosal swelling, mucopyoceles, polyps and effusion on scales ranging from 0 to 2-3, with a maximum score of68. Deformation semilunar hiatus was only evaluated in maxillary sinus.
Overall, as the children in this study grew older, researchers found that a greater percentage of paranasal sinuses (maxillary, sphenoid and ethmoid) were opacified. This occurrence started between 65% to 87% at infancy and increased to 91% to 94% (P < .05) at preschool age and to 96% to 99% (P < .001 vs. infancy) at school age. An additional finding at school age was that 71% of frontal sinuses were opacified.
The most frequent abnormality was mucosal swelling in infancy (58% to 97%) and at preschool age (79% to 94%; P < .05 vs. infancy); however, this shifted to mucopyoceles in maxillary and frontal sinuses (53% to 56%) at school age despite mucosal swelling appearing in every opacified sinus at this age.
During the evaluation of chronic rhinosinusitis MRI sum scores at each age level, researchers observed a significant increase as the children grew older (infancy, 22.4 ± 9.6 vs. preschool age, 34.2 ± 9.6; P < .001). The score at school age was comparable to the score found during preschool age (34 ± 5.7).
When divided into those homozygous for the F508del mutation (n = 34), those heterozygous for the F508del mutation (n = 21) and those without this genotype (n = 9), researchers found greater chronic rhinosinusitis MRI sum scores at all age levels among those homozygous for the mutation.
Additionally, those with pancreatic insufficiency (n = 57) had significantly higher scores at the preschool age level than those with pancreatic sufficiency (P < .001).
Notably, the chronic rhinosinusitis MRI sum score among those who received lumacaftor/ivacaftor improved by 0.5 (± 3.3; P < .05) at least 2 months after treatment initiation. Researchers observed a similar improvement in the maxillary sinus subscore (–0.5; ± 1.2; P < .05).
“These results emphasize the potential of comprehensive paranasal sinus as a supplement to lung MRI as a sensitive, noninvasive and radiation-free diagnostic tool for the detection and monitoring of CF-related abnormalities of the upper and lower airway tract and as a potential endpoint in clinical trials,” Wucherpfennig and colleagues wrote.
Perspective
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The important findings from this study were earlier development of sinuses in the group than was previously known. In the youngest group, abnormal findings were found in a majority of the children. They determined a more accurate picture of the pace of developing sinuses through early childhood. With sequential MRI in the cohort, they noted progression of sinus involvement over the ages between infancy and early adolescence. The youngest group, aged 1 to 5 years, regularly needed sedation with chloral hydrate to allow imaging.
In addition, among a separate cohort, 24 children aged 3 to 17 years of all F508 homozygotes were studied prior to and at least 2 months after introduction of ivacaftor/lumacaftor per clinical eligibility. In these paired studies they noted some improvement in sinus scores by 2 or more months after beginning modulator therapy.
There are several points to consider from this study. One, this is the first study of longitudinal development of paranasal sinuses in children starting in infancy using annual MRI assessment. Two, MRI offers imaging which is more sensitive and does not involve radiation exposure as the authors point out. Three, chronic rhinosinusitis is widely considered to be part of the process of colonization and infection of the lower respiratory tract. The authors speculate that early sinus MRI to determine infection/inflammation of the upper respiratory tract (throat and sinuses) could avert the need for chest imaging. I am not sure that is entirely clear, although cleaning up the sinuses might delay or lessen lower respiratory tract involvement. Sinus CT in preschool children also requires sedation, and radiation exposure in early life can lead to risks in later life, including cataracts and cancer.
Additionally, the small changes in sinus findings in CFTR pre- and post-modulator treatment (with lumacaftor/ivacaftor) reflect the lack of highly effective modulator therapy (HEMT) availability at the time of the study, whereas older individuals placed on HEMT have shown widespread, long-lasting sinus improvements (on CT) with HEMT. With the advent of HEMT being approved in the U.S. for use among those aged as young as 2 years, the care of people with CF is rapidly evolving in the eligible population.
Noteworthy is the finding for 5-year increments in median expected survival increasing from 44 years in 2017 to 56 years in 2022, per the United States CF Patient Data Registry, and the wonderful truth that we have to alter practices (such as radiation exposure) as we plan for more normal longevity among people with CF.
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