期刊
ANNALS OF THE AMERICAN THORACIC SOCIETY
卷 13, 期 8, 页码 1305-1313出版社
AMER THORACIC SOC
DOI: 10.1513/AnnalsATS.201511-748OC
关键词
primary ciliary dyskinesia; clinical features; laterality defects; neonatal respiratory distress
资金
- National Institutes of Health (NIH) - Office of Rare Diseases Research (ORDR) of the National Center for Advancing Translational Sciences (NCATS) [5 U54 HL09640958-11, 5R01 HL071798]
- National Heart, Lung, and Blood Institute (NHLBI)
- Clinical and Translational Science Awards (CTSA) NIH/NCATS UNC [ULTR000083]
- CTSA NIH/NCATS Colorado [UL1TR000154]
- NHLBI, NIH
- Genetic Disorders of Mucociliary Clearance Consortium is a part of the NIH Rare Disease Clinical Research Network (RDCRN) [5 U54HL096458]
Rationale: Primary ciliary dyskinesia (PCD), a genetically heterogeneous, recessive disorder of motile cilia, is associated with distinct clinical features. Diagnostic tests, including ultrastructural analysis of cilia, nasal nitric oxide measurements, and molecular testing for mutations in PCD genes, have inherent limitations. Objectives: To define a statistically valid combination of systematically defined clinical features that strongly associates with PCD in children and adolescents. Methods: Investigators at seven North American sites in the Genetic Disorders of Mucociliary Clearance Consortium prospectively and systematically assessed individuals (aged 0-18 yr) referred due to high suspicion for PCD. The investigators defined specific clinical questions for the clinical report form based on expert opinion. Diagnostic testing was performed using standardized protocols and included nasal nitric oxide measurement, ciliary biopsy for ultrastructural analysis of cilia, and molecular genetic testing for PCD-associated genes. Final diagnoses were assigned as definite PCD (hallmark ultrastructural defects and/or two mutations in a PCD-associated gene), probable/possible PCD (no ultrastructural defect or genetic diagnosis, but compatible clinical features and nasal nitric oxide level in PCD range), and other diagnosis or undefined. Criteria were developed to define early childhood clinical features on the basis of responses to multiple specific queries. Each defined feature was tested by logistic regression. Sensitivity and specificity analyses were conducted to define the most robust set of clinical features associated with PCD. Measurements and Main Results: From 534 participants 18 years of age and younger, 205 were identified as having definite PCD (including 164 with two mutations in a PCD-associated gene), 187 were categorized as other diagnosis or undefined, and 142 were defined as having probable/possible PCD. Participants with definite PCD were compared with the other diagnosis or undefined group. Four criteria-defined clinical features were statistically predictive of PCD: laterality defect; unexplained neonatal respiratory distress; early-onset, year-round nasal congestion; and early-onset, year-round wet cough (adjusted odds ratios of 7.7, 6.6, 3.4, and 3.1, respectively). The sensitivity and specificity based on the number of criteria-defined clinical features were four features, 0.21 and 0.99, respectively; three features, 0.50 and 0.96, respectively; and two features, 0.80 and 0.72, respectively. Conclusions: Systematically defined early clinical features could help identify children, including infants, likely to have PCD.
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