Situs Ambiguus Is Associated With Adverse Clinical Outcomes in Children With Primary Ciliary Dyskinesia.

Autor:	Kaspy KR; McGill University Health Centre Research Institute, Montreal Children's Hospital, Montreal, QC., Dell SD; BC Children's Hospital, University of British Columbia, Vancouver, BC., Davis SD; Department of Pediatrics, Marsico Lung Institute, University of North Carolina School of Medicine, Chapel Hill, NC., Ferkol TW; Department of Pediatrics, Marsico Lung Institute, University of North Carolina School of Medicine, Chapel Hill, NC., Rosenfeld M; Department of Pediatrics, Seattle Children's Research Institute, University of Washington School of Medicine, Seattle, WA., Sagel SD; Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO., Milla C; Department of Pediatrics, Stanford University, Palo Alto, CA., Olivier KN; Department of Medicine, Marsico Lung Institute, University of North Carolina School of Medicine, Chapel Hill, NC., Barber AT; Department of Pediatrics, Virginia Commonwealth University, Richmond, VA., Wee W; Hospital for Sick Children, University of Toronto, Toronto, ON, Canada., Lin FC; Department of Biostatistics, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC., Li L; Department of Biostatistics, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC., Rampakakis E; McGill University Health Centre Research Institute, Montreal Children's Hospital, Montreal, QC., Zariwala MA; Department of Pathology/Lab Medicine, Marsico Lung Institute, University of North Carolina School of Medicine, Chapel Hill, NC., Knowles MR; Department of Medicine, Marsico Lung Institute, University of North Carolina School of Medicine, Chapel Hill, NC., Leigh MW; Department of Pediatrics, Marsico Lung Institute, University of North Carolina School of Medicine, Chapel Hill, NC., Shapiro AJ; McGill University Health Centre Research Institute, Montreal Children's Hospital, Montreal, QC. Electronic address: adam.shapiro@muhc.mcgill.ca.
Jazyk:	angličtina
Zdroj:	Chest [Chest] 2024 May; Vol. 165 (5), pp. 1070-1081. Date of Electronic Publication: 2023 Dec 09.
DOI:	10.1016/j.chest.2023.12.005
Abstrakt:	Background: Primary ciliary dyskinesia (PCD) is a rare disorder of motile cilia associated with situs abnormalities. At least 12% of patients with PCD have situs ambiguus (SA), including organ laterality defects falling outside normal arrangement (situs solitus [SS]) or mirror image inversion (situs inversus totalis [SIT]). Research Question: Do patients with PCD and SA achieve worse clinical outcomes compared with those with SS or SIT? Study Design and Methods: This cross-sectional, multicenter study evaluated participants aged 21 years or younger with PCD. Participants were classified as having SA, including heterotaxy, or not having SA (SS or SIT). Markers of disease severity were compared between situs groups, adjusting for age at enrollment and severe CCDC39 or CCDC40 genotype, using generalized linear models and logistic and Poisson regression. Results: In 397 participants with PCD (mean age, 8.4 years; range, 0.1-21), 42 patients were classified as having SA, including 16 patients (38%) with complex cardiovascular malformations or atrial isomerism, 13 patients (31%) with simple CVM, and 13 patients (31%) without cardiovascular malformations. Of these, 15 patients (36%) underwent cardiac surgery, 24 patients (57%) showed an anatomic spleen abnormality, and seven patients (17%) showed both. The remaining 355 participants did not have SA, including 152 with SIT and 203 with SS. Overall, 70 participants (17%) harbored the severe CCDC39 or CCDC40 genotype. Compared with participants without SA, those with SA showed lower median BMI z scores (P = .03), lower FVC z scores (P = .01), and more hospitalizations and IV antibiotic courses for acute respiratory infections during the 5 years before enrollment (P < .01). Participants with cardiovascular malformations requiring surgery or with anatomic spleen abnormalities showed lower median BMI z scores and more hospitalizations and IV therapies for respiratory illnesses compared with participants without SA. Interpretation: Children with PCD and SA achieve worse nutritional and pulmonary outcomes with more hospitalizations for acute respiratory illnesses than those with SS or SIT combined. Poor nutrition and increased hospitalizations for respiratory infections in participants with SA and PCD are associated with cardiovascular malformations requiring cardiac surgery, splenic anomalies, or both. Trial Registry: ClinicalTrials.gov; Nos.: NCT02389049 and NCT00323167; URL: www. Clinicaltrials: gov. Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: S. D. Dell, S. D. Davis, T. W. F., M. R., S. D. S., C. M., K. N. O., M. A. Z., M. R. K., M. W. L., A. J. S. report financial support was provided by National Institutes of Health. S. D. Davis, T. W. F., M. W. L., A. J. S. report a relationship with The PCD Foundation that includes: board membership. A. J. S. reports a relationship with The PCD Foundation that includes: employment. S. D. Davis receives grant support from ReCode Therapeutics. A. J. S. receives grant support from The Chest Foundation. T. W. F. served as a consultant for Translate Bio and Arrowhead Pharmaceuticals. T. W. F. and A. J. S. are advisory board members for Parion Sciences and ReCode Therapeutics. None declared (K. R. K., A. T. B., W. W., F.-C. L., L. L., E. R.). (Copyright © 2023 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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