Ciliary Function

A cylindrical pseudostratified mucosa covers the respiratory epithelium, which ensures mucociliary transport. This structure is one of the most important first-line defenses of the airway, for both the lower tract and upper tract, including the paranasal sinus and middle ear. Thus, the entrance of particles and infection agents is avoided, protecting the person. This function is the so-called mucociliary clearance . Impairment of this system may cause infections in the respiratory tract.

The movement of the microtubule doublets determines the ciliary beat. The external arm of dynein controls ciliary frequency, and the internal arm of the dynein directs the shape of the wave. Radial spokes, which are related to the central pair of microtubules, are in charge of activating the dynein arms. The central pair/radial spoke complex is the regulating key for the activation of the dynein arms.

Cilia have a rhythmic beat. Each cycle has two active components: one movement during which the cilium is completely extended perpendicularly relative to the cellular surface, and a recovery movement in which the inclined cilium moves parallel to the cellular surface, toward its original position. The duration of this phase depends on the frequency of the ciliary beating.

Cilia in adjacent cells are coordinated to beat simultaneously and at the same time. In this way, an effective cilia motility is caused, which expels the mucus. The frequency of the ciliary beat oscillates between 13 and 27 Hz in the respiratory mucosa. It is known that multiple factors affect ciliary motility, such as neural control, external factors (temperature, humidity), and pharmacological effects.

To have an efficient motility and effective mucociliary clearance, it is crucial to conserve the ciliary structure intact, besides keeping an adequate amount and quality of secretions that allow good movement, as well as a good synchronization in the ciliary motility with a correct frequency of ciliary beat.

Age has no impact on the frequency of ciliary beat, which is similar for patients between 3 months old and 74 years old.

Ciliary function can be affected by external factors, such as bacterial toxins and inflammation mediators, which cause ultrastructural cilium alterations and ciliary dysfunction.

Alterations in Ciliary Structure

The ciliary structure may sustain different types of morphological alterations, such as the absence of internal and external dynein arms, alteration of the radial spokes, and cilium fusion.

Anomalies of the cilium ultrastructure may be divided into primary defects, which are those observed in PCD, and secondary defects, which are caused by infections, cigarette smoke, or pollutants. These secondary alterations are different from those found in PCD, and they consist mainly of defects in the microtubules and composed cilia, affecting up to 10% of cilia in normal patients, and when challenged by severe respiratory infections, up to 17% of the cilia may be affected.

In one phenotype of PCD, the ultrastructure is normal, but the cilia are not normally oriented in relation to other cilia. This orientation disorder may be primary, but it may as well occur secondary to an infection.

Analysis using a scanning electron microscope shows the number of studied cilia that present a specific anomaly. In this way, the percentage and type of alterations present can be classified. Most authors consider 20% or more of absent dynein internal and/or external arms as significant to classify the case as a PCD. Some examples can be seen in Figs. 43.3 and 43.4.

The most frequent ultrastructural findings, as published in several studies, are the absence of both dynein arms (range, 24–57%), absence of only the external dynein arm (range, 2.9–43%), absence of only the internal dynein arm (range, 29–37%), and anomalies of the central microtubules (4%).

Ultrastructural diagnosis requires trained and experienced specialists, as well as the strict application of morphological and diagnostic criteria. Diagnosis is more reliable when samples have been optimally obtained and processed. Up to 40% of the samples can be labeled as useless, as they do not contain ciliary cells in adequate numbers and lack preservation quality.

Clinical Condition

Clinical characteristics in PCD depend on the age of the patient.

The clinical manifestations most commonly published in the different series are recurrent sinusitis (77%), persistent rhinitis (76%), neonatal respiratory distress syndrome or tachypnea (20–67%), recurrent otitis media (57%), recurrent pneumonia (46–56%), difficult-to-control asthma (26%), bronchiectasis (8.6–24%), and situs inversus (18–69%). The average age at diagnosis is 4 years, but with a high clinical suspicion it can be diagnosed earlier, even within the first month of life.

Diagnosis

The diagnosis of PCD is based on a combination of clinical evaluation and analysis of the ciliary ultrastructure and function, and it can be difficult to determine this diagnosis in some patients. The clinical phenotype is wide and overlaps with other chronic diseases of the airway.

The patient must be thoroughly studied to rule out other pathologies (allergies and immunological studies, X-rays, gastroesophageal reflux, sweat test, etc.) that may be responsible for the clinical condition.

The screening and diagnosis methods for ciliary dyskinesia are detailed next.