Primary Ciliary Dyskinesia

Mucociliary clearance of the respiratory tract is an important defence mechanism against inhaled pathogens. Cilia, which line both the upper and lower airways, are covered by a thin layer of mucus, and beat rapidly in a co-ordinated fashion propelling particles trapped in the mucus layer to the pharynx. Defective mucociliary clearance predisposes the respiratory tract to recurrent infection, manifested by bronchiectasis and chronic sinusitis. Cilial defects may be either congenital (primary) or acquired secondary to infection, toxins or drugs.

Video of ciliated epithelial cells

Primary ciliary dyskinesia (PCD) is a recessively inherited group of disorders with abnormal ciliary activity, absent mucociliary transport and often abnormal ciliary ultrastructure. An ultrastructural abnormality of cilia was recognised in patients with Kartagener's syndrome who have the classic triad of sinusitis, bronchiectasis and situs inversus. In this condition, the heart is transposed to the right side of the chest, and the internal abdominal organs may also be transposed. Patients with similar clinical and cilial abnormalities, but without situs inversus, were later recognised and together with patients with Kartagener's syndrome they were classified as having immotile cilia syndrome. Immotile cilia syndrome was renamed PCD when functional studies of cilia from these patients showed them to have abnormal motility rather than being completely immotile.

The lungs, nose, middle ear and sinuses are primarily affected as they rely on the co-ordinated, effective beating of cilia to remove secretions. Clinical manifestations of PCD include recurrent lower respiratory tract infections, chronic rhinitis, sinusitis and otitis media. Bronchiectasis may follow repeated pulmonary infections; in a recent series of children investigated with proven bronchiectasis 17% were found to have PCD. Infertility occurs in virtually all males. The diagnosis of PCD is complicated by the fact that ciliary defects can be caused by infections (secondary dyskinesias) and so abnormal ciliary motility must be demonstrated from at least two sites in the respiratory tract and confirmed on more than one occasion. Ultrastructural defects, such as a deficiency in the number of dynein arms supports the diagnosis, however normal cilial ultrastructure does not exclude it.

Management

Management of patients with PCD involves daily chest physiotherapy including postural drainage and coughing. These techniques compensate for deficient mucociliary clearance. We recommend the prompt use of oral antibiotics for even trivial respiratory symptoms and intravenous antibiotics for pulmonary exacerbations. Regular review by a physiotherapist, a paediatrician with a respiratory interest, and a specialist in Ear, Nose and Throat diseases is important. Middle ear disease is often difficult to treat and insertion of grommets is generally fruitless. Hearing aids are used for significant conductive hearing loss. Polypectomy and partial turbinectomy has been beneficial in a number of patients for relief of sinusitis.

The object of infertility needs to be discussed as male patients approach adulthood with counseling and semen analysis offered to these patients.

Prognosis

PCD has a relatively good prognosis with the rate of decline of lung function being much slower than that with cystic fibrosis. The life expectancy with adequate treatment is normal, however, it may be reduced if chronic suppurative lung disease is allowed to progress.

Secondary Ciliary Dysfunction

Secondary ciliary dyskinesia may be of considerable clinical importance, especially in young infants with relatively small airways, and in neonatal patients whose ability to clear mucus by coughing is poor. Secondary dyskinesia may be induced by drugs, toxins and environmental factors such as halothane and cocaine, sulphur dioxide and breathing dry air. Dyskinesia may also be secondary to the damaging effect of either pathogens or host factos, including bacteria and viruses and leukocyte elastase. These secondary dyskinesias may be associated with microtubular abnormalities but are usually present in a much lesser proportion of the cilia than in PCD. It is, however, for this reason that repeated examination of cilia is required before a confident ultrastructural diagnosis of PCD can be made. Secondary cilial defects return to normal with time and appropriate treatment.

Brain Ependymal Cilia

Densely ciliated ependymal cells line the walls of the ventricles and aqueducts in the brain and the central canal of the spinal cord forming a barrier between cerebrospinal fluid and neuronal tissue. Their precise function is unclear. Approximately forty cilia, which are 10 micron long hair-like structures, project from each ependymal cell anbd beat, continuously, at 30-40 beats per second (20 Hz).

Although their precise function is unknown their importance may lie in the continual, directinal movement of cerebrospinal fluid. This action will help to maintain a diffusioin gradient, between the CSF and brain tissue, facilitating the movement of toxins and metabolites to the CSF for clearance. As with respiratory cilia they may have a host defence role, keeping the surface of the brain clear of debris and preventing margination of bacteria during meningitis.

Defective brain ciliary movement has been linked to the development of hydrocephalus.

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