Airway disease on CT differs based on primary ciliary dyskinesia defect type
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Key takeaways:
- Mucus plugging was more prevalent in children with inner dynein arm/microtubular disorganization defects.
- Older vs. younger children had greater airway disease.
On chest CTs, children with primary ciliary dyskinesia and inner dynein arm/microtubular disorganization defects had more mucus plugging than other defects, according to results published in Annals of the American Thoracic Society.
“Similar to cystic fibrosis, there are genotype-phenotype relationships in primary ciliary dyskinesia (PCD), and children with PCD and inner dynein arm/microtubular disorganization defects have more severe airway disease compared to children with PCD and other defects,” BreAnna Kinghorn, MD, MS, assistant professor of pediatrics and associate director of the pediatric pulmonary center at Seattle Children’s Hospital, told Healio. “We also found that lower lung function was associated with greater airway disease, and airway disease increased with age. Chest CT is an important clinical tool, particularly in children with PCD for assessing severity of airway.”
In a cross-sectional analysis, Kinghorn and colleagues evaluated 141 children (mean age, 8.5 years; 50.4% boys; 74.5% white; mean FEV1, 82.4) with PCD and chest CT scores from the Genetic Disease Mucociliary Clearance Consortium (GDMCC) study to understand how different ciliary defect genotypes are related to these scores, as well as what clinical characteristics are related to these scores using regression analyses.
Four defect types were studied: outer dynein arm (ODA; n = 57), ODA/inner dynein arm (IDA; n = 20), IDA/microtubular disorganization (MTD; n = 40) and normal/near normal ultrastructure with associated genotypes (n = 24).
To score airway abnormalities — such as atelectasis, bronchiectasis, bronchial wall thickening and mucus plugging/tree-in-bud opacities — that appeared on CT scans, researchers used the Melbourne-Rotterdam Annotated Grid Morphometric Analysis for PCD (MERAGMA-PCD).
For each abnormality, the volume fraction was conveyed as a percentage of total lung volume, and by totaling the percentages of atelectasis, bronchiectasis, airway wall thickening and mucus plugging, researchers calculated the percentage of airway disease.
Of the total study population, mean percentage of airway disease was 4.6% (standard deviation [SD], 3.5), and this was mainly made up by atelectasis (1.6%; SD, 1.8) and bronchiectasis (1.5%; SD, 0.9).
According to researchers, the mean percentage of disease was highest among those with IDA/MTD (5.9%; SD, 4.3) vs. ODA (3.8%; SD, 2.4), ODA/IDA (4.7%; SD, 2.9) and normal/near normal (4.3%; SD, 4.1) defects. Additionally, increased mucus plugging was found in children with IDA/MTD (2.3%; SD, 3.7) compared with ODA (0.5%; SD, 1.1), ODA/IDA (0.9%; SD, 2.1) and normal/near normal (1.1%; SD, 1.6) defects.
This finding was further demonstrated in models adjusted for age and sex, with an elevated mean percentage of disease in IDA/MTD vs. ODA (2.71% higher; 95% CI, 1.37-4.06), as well as more mucus plugging (2.35% higher; 95% CI, 1.43-3.26), which Kinghorn told Healio was a surprising finding.
“This finding could shed light on the underlying mechanism of early airway disease and progression in PCD,” Kinghorn said.
When evaluating what clinical characteristics in children are linked to a greater airway disease, researchers found increasing age (0.23% per year of age; 95% CI, 0.11-0.35), lower BMI (0.03% higher; 95% CI, 0.01-0.04), lower FEV1 percent predicted (0.05% higher; 95% CI, 0.01-0.08) and lower FVC precent predicted (0.07% higher; 95% CI, 0.03-0.1).
“As we gain more understanding of the underlying mechanism of early airway disease in children with PCD, we can utilize this information to guide future interventional trials and clinical endpoints,” Kinghorn told Healio. “Given the progressive structural airway injury in children with PCD, it is essential to increase awareness and diagnosis of PCD, as individuals with specific genotypes will have more severe disease/worse clinical outcomes.”
When asked about future studies, Kinghorn told Healio another analysis is already in the works.
“We are currently completing a longitudinal analysis looking at airway disease progression in children with PCD over a 10-year study period,” Kinghorn told Healio. “We will utilize the MERAGMA-PCD scoring tool to assess [percentage of airway disease] and its sub scores (atelectasis, bronchiectasis, airway wall thickening, mucus plugging/tree-in-bud). We are also utilizing a fully automated artificial intelligence program to measure bronchiectasis (measuring bronchus-arterial diameters), which will be a much more sensitive scoring tool to truly track bronchiectasis progression. By combining multiple CT scoring tools, we hope to gain a better understanding of airway disease progression.”
This study by Kinghorn and colleagues adds to growing literature on understanding PCD genotypes and demonstrates how CT can help identify airway abnormalities that contribute to airway disease, according to an accompanying editorial by Stephanie Adaikalam, MD, and Benjamin Gaston, MD, of the Riley Hospital for Children and the Herman B. Wells Center for Pediatric Research.
In the editorial, Adaikalam and Gaston suggest that Kinghorn and colleagues look at how a study conducted by the Severe Asthma Research Program (SARP), which evaluated CT scans of adults with asthma, addresses uniformity in scanning procedures since they are similar studies.
“Moving forward, however, it may be advisable for the [Genetic Diseases of Mucociliary Clearance Consortium (GDMCC)] to compare notes with the SARP radiology investigators regarding uniformity of scanning procedures,” Adaikalam and Gaston wrote. “The SARP also performed childhood scans, with strict parameters monitored closely by the SARP data safety monitoring board (DSMB). All makes of CT scanners were used in such a way as to generate digitally comparable data, validated on a shared ‘phantom’ dummy with established densities. Inspiratory volumes, cuts and other parameters were strictly uniform across all sites, and extensive details about treatment and laboratory values at the time of each scan were available for analysis. There may be things that the GDMCC can learn from the SARP, and vice versa.”
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For more information:
BreAnna Kinghorn, MD, MS, can be reached at breanna.kinghorn@seattlechildrens.org.