The spectrum of ciliary disease has widened from a primary upper and lower respiratory tract problem with the appreciation of the key role of sensory cilia. Five disease causing mutations have been discovered, but given the complexity of cilia, many more are likely to be found in the future. Primary ciliary dyskinesia may present with upper or lower airway disease, or be diagnosed after the discovery of associated conditions such as heterotaxy, complex congenital heart disease, and severe esophageal disease. Screening tests include nasal nitric oxide and in vivo measurements of mucociliary transport. Definitive diagnosis is by ciliary biopsy with measurement of ciliary beat frequency and pattern, followed by electron microscopy. Ciliary culture may help distinguish primary ciliary dyskinesia from ciliary abnormalities secondary to infection. Increasingly, genetic testing is becoming available. Once diagnosed, the severity is assessed, and follow-up should be in clinics with expertise in all areas of the condition. The evidence base for current treatment is weak, with no randomized controlled trials; all therapies are directed at complications, not the underlying abnormality. Lower airway disease is treated with airway clearance, antibiotics, and encouragement of exercise. A conservative approach to chronic secretory otitis media is advised. Although in many cases the patient is stabilized by medical therapy, some will go on to lung transplantation. In the future, specific therapies to reverse the ciliary dysfunction may become available. (Clin Pulm Med 2009;16: 219 -225) T raditionally, cilia have been thought of as part of the initial stage of the mucociliary escalator, an essential airway defense mechanism. Dysfunction in this system underlies primary ciliary dyskinesia (PCD). It is now clear that cilia have wide importance during embryogenesis and in multiple organs. Defective ciliary function is implicated in polycystic hepatic and renal disease, hydrocephalus, biliary atresia, retinal degeneration, and rare syndromes such as Bardet-Biedl, Alstrom and Meckel-Gruber, and oro-facial-digital syndromes in addition to nephronophthisis. 1,2 Jeune asphyxiating thoracic dystrophy now appears to be a ciliopathy. 3 As well as the motile cilia responsible for airway defenses, sensory cilia are important in many aspects of embryonic development. Motile nodal cilia have long been known to be responsible for normal right-left orientation, but there are likely to be important roles for cilia also in the development of the kidney, neural tube, the cochlear apparatus, the central nervous system, and the limb bud. 1,2 Although this review focuses on motile cilia and PCD, ciliopathies are a truly multisystem issue.
GENETICSPCD is an autosomal recessive inherited disorder, with an estimated incidence of 1:15-30,000, 4 although the requirement for specialized diagnostics and variability of disease symptoms means that this is likely to be an underestimate. PCD has a much higher incidence in certain consanguineous and isolated p...
