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The association of neonatal respiratory distress with ciliary ultrastructure and genotype in primary ciliary dyskinesia
  • +14
  • Andrew T. Barber,
  • Stephanie Davis,
  • Thomas Ferkol,
  • Adam Shapiro,
  • Jeff Atkinson,
  • Scott Sagel,
  • Sharon Dell,
  • Ken Olivier,
  • Carlos Milla,
  • Margaret Rosenfeld,
  • Lang Li,
  • Feng-Chang Lin,
  • Kelli Sullivan,
  • Nicole A. Capps,
  • Maimoona zariwala,
  • Michael Knowles,
  • Margaret Leigh
Andrew T. Barber
Virginia Commonwealth University Department of Pediatrics

Corresponding Author:[email protected]

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Stephanie Davis
The University of North Carolina at Chapel Hill School of Medicine
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Thomas Ferkol
The University of North Carolina at Chapel Hill School of Medicine
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Adam Shapiro
Montreal Children's Hospital
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Jeff Atkinson
Washington University in St Louis School of Medicine
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Scott Sagel
University of Colorado Anschutz Medical Campus Department of Pediatrics
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Sharon Dell
BC Children's Hospital Department of General Pediatrics
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Ken Olivier
The University of North Carolina at Chapel Hill School of Medicine
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Carlos Milla
Stanford University Department of Pediatrics
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Margaret Rosenfeld
University of Washington Department of Pediatrics
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Lang Li
The University of North Carolina at Chapel Hill
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Feng-Chang Lin
The University of North Carolina at Chapel Hill
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Kelli Sullivan
The University of North Carolina at Chapel Hill
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Nicole A. Capps
The University of North Carolina at Chapel Hill
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Maimoona zariwala
The University of North Carolina at Chapel Hill
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Michael Knowles
The University of North Carolina at Chapel Hill
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Margaret Leigh
The University of North Carolina at Chapel Hill
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Abstract

Objective: To evaluate the relationship between ciliary ultrastructure/genotype and prevalence of neonatal respiratory distress in primary ciliary dyskinesia (PCD). Study Design: This was a retrospective analysis from a multicenter, prospective study of children and adults with PCD. Participants were classified by ultrastructural defect associated with their diagnostic genetic variants: 1) outer dynein arm defect alone (ODA), 2) outer plus inner dynein arm defect (ODA/IDA), 3) inner dynein arm defect with microtubular disorganization (IDA/MTD), 4) DNAH11 (encodes ODA protein but has normal ultrastructure), and 5) normal/near normal/other. The likelihood of neonatal respiratory distress between ultrastructure groups or genotypes was evaluated by multivariate analysis using logistic regression, controlled for age, gender, race, and variant type. Similar analysis was performed within individual genotypes to assess association of neonatal respiratory distress with the presence of 2 loss-of-function variants. Results: Of the 455 participants analyzed, 305 (67.0%) reported neonatal respiratory distress. The odds ratio for neonatal respiratory distress in the DNAH11 group was significantly lower (OR 0.35, 95% CI 0.16-0.76) compared to neonatal respiratory distress in the ODA group. Within the DNAH5 group, those with 2 loss-of-function variants were more likely to have neonatal respiratory distress compared to those with possible residual function variants (OR 3.06, 95% CI 1.33-7). Conclusion: Neonatal respiratory distress is less common in those with DNAH11 variants, thus a high index of suspicion should remain for PCD in the absence of neonatal respiratory distress.
22 Sep 2024Submitted to Pediatric Pulmonology
30 Sep 2024Submission Checks Completed
30 Sep 2024Assigned to Editor
30 Sep 2024Review(s) Completed, Editorial Evaluation Pending
07 Oct 2024Reviewer(s) Assigned
22 Nov 2024Editorial Decision: Revise Major