Prevalence of primary ciliary dyskinesia in consecutive referrals of suspect cases and the transmission electron microscopy detection rate: a systematic review and meta-analysis

Abstract

Diagnostic testing for primary ciliary dyskinesia (PCD) usually includes transmission electron microscopy (TEM), nasal nitric oxide, high-speed video microscopy, and genetics. Diagnostic performance of each test should be assessed toward the development of PCD diagnostic algorithms. We systematically reviewed the literature and quantified PCD prevalence among referrals and TEM detection rate in confirmed PCD patients. Major electronic databases were searched until December 2015 using appropriate terms. Included studies described cohorts of consecutive PCD referrals in which PCD was confirmed by at least TEM and one additional test, in order to compare the index test performance with other test(s). Meta-analyses of pooled PCD prevalence and TEM detection rate across studies were performed. PCD prevalence among referrals was 32% (95% CI: 25-39%, I = 92%). TEM detection rate among PCD patients was 83% (95% CI: 75-90%, I = 90%). Exclusion of studies reporting isolated inner dynein arm defects as PCD, reduced TEM detection rate and explained an important fraction of observed heterogeneity (74%, 95% CI: 66-83%, I = 66%). Approximately, one third of referrals, are diagnosed with PCD. Among PCD patients, a significant percentage, at least as high as 26%, is missed by TEM, a limitation that should be accounted toward the development of an efficacious PCD diagnostic algorithm.

Value of transmission electron microscopy for primary ciliary dyskinesia diagnosis in the era of molecular medicine: Genetic defects with normal and non-diagnostic ciliary ultrastructure

“…Current estimates suggest that approximately 30% of PCD cases have normal or non-diagnostic ciliary ultrastructure, 1,2 and a recent meta-analysis reports at least 26% of PCD, diagnosed through genetics, HSVA, or nasal nitric oxide measurement, lack detectable ultrastructural changes on TEM. 3 Therefore, clinicians cannot conclude that a normal TEM analysis excludes PCD. Respiratory viral infections, environmental pollutants and other airway insults can induce secondary changes in ciliary ultrastructure that may overlap with some of the subtle changes seen in PCD; therefore, care must be taken to avoid misinterpretation of these secondary changes as “consistent with PCD”.…”

Evaluation of the pulmonary radioaerosol mucociliary clearance scan as an adjunctive test for the diagnosis of primary ciliary dyskinesia in children

“…We used a modern reference standard diagnosis for PCD based on widely available clinical tests (cilia TEM, genetics, and nasal nitric oxide) and sensitivity analyses removing the nasal nitric oxide criteria did not change the results. Ciliary ultrastructural analysis by TEM is normal or nondiagnostic in 30% to 50% of patients with PCD and current genetic testing detects only 65% to 70% of PCD cases . Other tests to diagnose PCD, such as functional ciliary beat assessment via high‐speed video microscopy and immunofluorescence testing, also have limitations in feasibility and/or accuracy .…”

European position paper on diagnostic tools in rhinology

“…In cases of suspected PCD in a patient with CRS since birth, a family history of PCD and/or associated features of Kartagener syndrome (situs inversus and infertility), one should consider diagnostic tests of ciliary function by evaluation of CBF, EM evaluation of the dynein arms of the cilia and/or evaluation of the cilia after ciliogenesis in vitro. In a tertiary referral centre, one third of patients referred with suspected PCD are eventually diagnosed with the condition (377) .…”