Toward an Earlier Diagnosis of Primary Ciliary Dyskinesia. Which Patients Should Undergo Detailed Diagnostic Testing?

Abstract

Primary ciliary dyskinesia (PCD) is a rare, heterogeneous, recessive, genetic disorder of motile cilia, leading to chronic upper and lower respiratory symptoms. Prevalence is estimated at around 1:10,000, but many patients remain undiagnosed, whereas others receive the label incorrectly. Proper diagnosis is complicated by the fact that the key symptoms, such as wet cough, chronic rhinitis, and recurrent upper and lower respiratory infection, are common and nonspecific. There is no single gold standard test to diagnose PCD. Currently, the diagnosis is made in patients with a compatible medical history after a demanding combination of tests including nasal nitric oxide, high-speed video microscopy, and transmission electron microscopy and genetic and ciliary culture testing. These tests are costly and need sophisticated equipment and experienced staff, restricting use to highly specialized centers. Therefore, it would be desirable to have a screening test for identifying those patients who should undergo detailed diagnostic testing. Three recent studies focused on potential screening tools: one study assessed the validity of nasal nitric oxide for screening, and two studies developed new symptom-based screening tools. These simple tools are welcome, and it is hoped that they will assist physicians in determining whom to refer for definitive testing. However, they have been developed in tertiary care settings, where 10 to 50% of tested patients have PCD. The sensitivity and specificity of the tools are reasonable, but positive and negative predictive values may be poor in primary or secondary care settings. Although these studies are an important step toward an earlier diagnosis of PCD, more remains to be done before we have tools tailored to different health care settings.