Olfactory Dysfunction in Primary Ciliary Dyskinesia: A Systematic Review and Meta-analysis
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Objective
Primary ciliary dyskinesia (PCD) is a rare congenital motile ciliopathy associated with significant sinopulmonary disease, alongside marked genetic and phenotypic variability. Olfactory dysfunction in PCD remains poorly characterised. This systematic review aimed to synthesise the available evidence on the prevalence, assessment methods, and clinical correlates of olfactory dysfunction in individuals with PCD.
Methods
A PRISMA-compliant systematic review was conducted. Medline, Embase, Scopus, Web of Science, and the Cochrane Library were searched up to 28/02/26. Observational studies and clinical trials reporting on olfactory function in confirmed PCD were included. Data were extracted, and study quality was assessed using the Newcastle-Ottawa Scale (NOS). A random-effects meta-analysis using the Freeman-Tukey double arcsine transformation was performed to calculate the pooled prevalence, 95% confidence interval (CI), and 95% prediction interval (PI). The review protocol was registered with PROSPERO (CRID: 1006332).
Results
Of 159 records screened, 12 studies (n=865) met the inclusion criteria. The prevalence of olfactory dysfunction varied widely, from 1.5% to 100%. The overall pooled prevalence was 43.4% (95% CI 25.2%–62.5%), but with a very wide 95% prediction interval of 0.1%–99.0%, reflecting significant heterogeneity (I²=96.2%). Objective psychophysical tests (n=6 studies) identified a pooled prevalence of 66.1% (95% CI 55.5%–76.0%; 95% PI 38.4%–88.9%), which was significantly higher than that from patient-reported outcome measures (30.5%; 95% CI 11.4%–54.0%; 95% PI 11.4%–97.1%) and clinical history (5.6%; 95% CI 0.2%–24.8%). Older age, specific ciliary ultrastructural defects, and greater sinonasal disease burden on imaging were associated with worse olfactory function.
Conclusion
Olfactory dysfunction is a highly prevalent yet profoundly under-recognised comorbidity in Primary Ciliary Dyskinesia, with over two-thirds of patients affected when assessed objectively. The pathophysiology extends beyond simple conductive obstruction to likely include a primary neurosensory deficit linked to the underlying genetic defect. These findings carry a clear mandate for clinicians to integrate objective olfactory testing into routine PCD care to improve patient safety and quality of life.
