Optimizing the diagnostic approach for Primary Ciliary Dyskinesia with normal ultrastructure

Abstract

<b>Introduction:</b> Primary ciliary dyskinesia (PCD) is a heterogeneous, multisystem disorder characterized by dysfunctional motile cilia. Diagnostic approaches of the American Thoracic (ATS) and European Respiratory Society (ERS) include nasal nitric oxide (nNO) measurement, transmission electron microscopy, evaluation of ciliary beating and genetic analyses for PCD diagnosis. <b>Methods:</b> All included subjects were evaluated according to ERS diagnostic guidelines. PCD individuals were categorized in subgroups with normal and abnormal ciliary ultrastructure. Diagnostic cutoffs for nNO-production rates as well as ciliary beat frequencies (CBFs) and laterality status were determined. <b>Results:</b> The study cohort comprised 180 PCD individuals (160 with genetic diagnosis) and 105 disease controls. The optimal diagnostic cutoff for the nNO-production rate for the whole PCD cohort was 69.8 nl/min (sensitivity 0.92, specificity 0.89), while it was 107.8 nl/min (sensitivity 0.89, specificity 0.78) for the subgroup of PCD with normal ultrastructure. This subgroup also showed higher ciliary motility and less laterality defects. <b>Conclusions:</b> Higher nNO-production rates, higher residual ciliary motility and lower prevalence of laterality defects make diagnosis of PCD with normal ultrastructure difficult. In distinct cases, only genetic analyses lead to PCD diagnosis. A frequent use of genetic testing and adjusting the cutoff for the nNO-production rate to 107.8 nl/min will promote diagnosing PCD with normal ultrastructure. We thank the PCD-affected families and the German support group. This work was supported by grants from the “Deutsche Forschungsgemeinschaft” (DFG) (e.g. CRU326 (RA3522/1-1; OM6/11) and "IZKF" Münster.