TY - JOUR
T1 - Airway Disease in Children with Primary Ciliary Dyskinesia
T2 - Impact of Ciliary Ultrastructure Defect and Genotype
AU - Kinghorn, Bre Anna
AU - Rosenfeld, Margaret
AU - Sullivan, Erin
AU - Onchiri, Frankline
AU - Ferkol, Thomas W.
AU - Sagel, Scott D.
AU - Dell, Sharon D.
AU - Milla, Carlos
AU - Shapiro, Adam J.
AU - Sullivan, Kelli M.
AU - Zariwala, Maimoona A.
AU - Pittman, Jessica E.
AU - Mollica, Federico
AU - Tiddens, Harm A.W.M.
AU - Kemner-van de Corput, Mariette
AU - Knowles, Michael R.
AU - Davis, Stephanie D.
AU - Leigh, Margaret W.
PY - 2023/4/1
Y1 - 2023/4/1
N2 - Rationale: Primary ciliary dyskinesia (PCD) is characterized by impaired mucociliary clearance, recurrent respiratory infections, progressive airway damage, and obstructive lung disease. Although the association of ciliary ultrastructure defect/genotype with the severity of airflow obstruction has been well characterized, their association with airway abnormalities on chest computed tomography (CT) has been minimally evaluated. Objectives: We sought to delineate the association of ciliary defect class/genotype with chest CT scores in children with PCD. Methods: Cross-sectional analysis of children with PCD (N = 146) enrolled in a prospective multicenter observational study, stratified by defect type: outer dynein arm (ODA), ODA/inner dynein arm (IDA), IDA/microtubular disorganization (MTD), and normal/near normal ultrastructure with associated genotypes. CTs were scored using the MERAGMA-PCD (Melbourne-Rotterdam Annotated Grid Morphometric Analysis for PCD), evaluating airway abnormalities in a hierarchical order: atelectasis, bronchiectasis, bronchial wall thickening, and mucus plugging/tree-in-bud opacities. The volume fraction of each component was expressed as the percentage of total lung volume. The percentage of disease was computed as the sum of all components. Regression analyses were used to describe the association between clinical predictors and CT scores. Results: Acceptable chest CTs were obtained in 141 children (71 male): 57 ODA, 20 ODA/IDA, 40 IDA/MTD, and 24 normal/near normal. The mean (standard deviation) age was 8.5 (4.6) years, forced expiratory volume in 1 second (FEV1) percent predicted was 82.4 (19.5), and %Disease was 4.6 (3.5). Children with IDA/MTD defects had a higher %Disease compared with children with ODA defects (2.71% higher [95% confidence interval (CI), 1.37-4.06; P < 0.001]), driven by higher %Mucus plugging (2.35% higher [1.43-3.26; P < 0.001]). Increasing age, lower body mass index, and lower FEV1 were associated with a higher %Disease (0.23%; 95% CI, 0.11-0.35; P < 0.001 and 0.03%; 95% CI, 0.01-0.04; P = 0.008 and 0.05%; 95% CI, 0.01-0.08; P = 0.011, respectively). Conclusions: Children with IDA/MTD defects had significantly greater airway disease on CT, primarily mucus plugging, compared with children with ODA defects.
AB - Rationale: Primary ciliary dyskinesia (PCD) is characterized by impaired mucociliary clearance, recurrent respiratory infections, progressive airway damage, and obstructive lung disease. Although the association of ciliary ultrastructure defect/genotype with the severity of airflow obstruction has been well characterized, their association with airway abnormalities on chest computed tomography (CT) has been minimally evaluated. Objectives: We sought to delineate the association of ciliary defect class/genotype with chest CT scores in children with PCD. Methods: Cross-sectional analysis of children with PCD (N = 146) enrolled in a prospective multicenter observational study, stratified by defect type: outer dynein arm (ODA), ODA/inner dynein arm (IDA), IDA/microtubular disorganization (MTD), and normal/near normal ultrastructure with associated genotypes. CTs were scored using the MERAGMA-PCD (Melbourne-Rotterdam Annotated Grid Morphometric Analysis for PCD), evaluating airway abnormalities in a hierarchical order: atelectasis, bronchiectasis, bronchial wall thickening, and mucus plugging/tree-in-bud opacities. The volume fraction of each component was expressed as the percentage of total lung volume. The percentage of disease was computed as the sum of all components. Regression analyses were used to describe the association between clinical predictors and CT scores. Results: Acceptable chest CTs were obtained in 141 children (71 male): 57 ODA, 20 ODA/IDA, 40 IDA/MTD, and 24 normal/near normal. The mean (standard deviation) age was 8.5 (4.6) years, forced expiratory volume in 1 second (FEV1) percent predicted was 82.4 (19.5), and %Disease was 4.6 (3.5). Children with IDA/MTD defects had a higher %Disease compared with children with ODA defects (2.71% higher [95% confidence interval (CI), 1.37-4.06; P < 0.001]), driven by higher %Mucus plugging (2.35% higher [1.43-3.26; P < 0.001]). Increasing age, lower body mass index, and lower FEV1 were associated with a higher %Disease (0.23%; 95% CI, 0.11-0.35; P < 0.001 and 0.03%; 95% CI, 0.01-0.04; P = 0.008 and 0.05%; 95% CI, 0.01-0.08; P = 0.011, respectively). Conclusions: Children with IDA/MTD defects had significantly greater airway disease on CT, primarily mucus plugging, compared with children with ODA defects.
KW - PCD
KW - bronchiectasis
KW - computed tomography
KW - lung function
KW - pediatric lung disease
UR - http://www.scopus.com/inward/record.url?scp=85151574606&partnerID=8YFLogxK
U2 - 10.1513/AnnalsATS.202206-524OC
DO - 10.1513/AnnalsATS.202206-524OC
M3 - Article
C2 - 36442147
AN - SCOPUS:85151574606
SN - 2325-6621
VL - 20
SP - 539
EP - 547
JO - Annals of the American Thoracic Society
JF - Annals of the American Thoracic Society
IS - 4
ER -