|Title||Primary Ciliary Dyskinesia: Longitudinal Study of Lung Disease by Ultrastructure Defect and Genotype.|
|Publication Type||Journal Article|
|Year of Publication||2019|
|Authors||Davis, SD, Rosenfeld, M, Lee, H-S, Ferkol, TW, Sagel, SD, Dell, SD, Milla, C, Pittman, JE, Shapiro, AJ, Sullivan, KM, Nykamp, KR, Krischer, JP, Zariwala, MA, Knowles, MR, Leigh, MW|
|Journal||Am J Respir Crit Care Med|
|Date Published||2019 01 15|
|Keywords||Child, Cilia, Cohort Studies, Female, Genotype, Humans, Kartagener Syndrome, Longitudinal Studies, Lung, Male, Mutation, Phenotype, Prospective Studies, Respiratory Function Tests|
RATIONALE: In primary ciliary dyskinesia, factors leading to disease heterogeneity are poorly understood.
OBJECTIVES: To describe early lung disease progression in primary ciliary dyskinesia and identify associations between ultrastructural defects and genotypes with clinical phenotype.
METHODS: This was a prospective, longitudinal (5 yr), multicenter, observational study. Inclusion criteria were less than 19 years at enrollment and greater than or equal to two annual study visits. Linear mixed effects models including random slope and random intercept were used to evaluate longitudinal associations between the ciliary defect group (or genotype group) and clinical features (percent predicted FEV and weight and height z-scores).
MEASUREMENTS AND MAIN RESULTS: A total of 137 participants completed 732 visits. The group with absent inner dynein arm, central apparatus defects, and microtubular disorganization (IDA/CA/MTD) (n = 41) were significantly younger at diagnosis and in mixed effects models had significantly lower percent predicted FEV and weight and height z-scores than the isolated outer dynein arm defect (n = 55) group. Participants with CCDC39 or CCDC40 mutations (n = 34) had lower percent predicted FEV and weight and height z-scores than those with DNAH5 mutations (n = 36). For the entire cohort, percent predicted FEV decline was heterogeneous with a mean (SE) decline of 0.57 (0.25) percent predicted/yr. Rate of decline was different from zero only in the IDA/MTD/CA group (mean [SE], -1.11 [0.48] percent predicted/yr; P = 0.02).
CONCLUSIONS: Participants with IDA/MTD/CA defects, which included individuals with CCDC39 or CCDC40 mutations, had worse lung function and growth indices compared with those with outer dynein arm defects and DNAH5 mutations, respectively. The only group with a significant lung function decline over time were participants with IDA/MTD/CA defects.
|Alternate Journal||Am. J. Respir. Crit. Care Med.|
|PubMed Central ID||PMC6353004|
|Grant List||R01 HL071798 / HL / NHLBI NIH HHS / United States |
UM1 HG006504 / HG / NHGRI NIH HHS / United States
U54 HG006493 / HG / NHGRI NIH HHS / United States
S10 OD018521 / OD / NIH HHS / United States
U54 HL096458 / HL / NHLBI NIH HHS / United States
UL1 TR001082 / TR / NCATS NIH HHS / United States
UC2 HL102926 / HL / NHLBI NIH HHS / United States
RC2 HL102926 / HL / NHLBI NIH HHS / United States