Introduction

Primary ciliary dyskinesia (PCD) is a rare genetic disease that has been estimated to affect 1 in 7500 people globally.¹ In Europe, the disease affects between 1 in 10,000 and 1 in 20,000 individuals. The prevalence is noticeably higher in the Asian community of Britain.² PCD is an autosomal recessive genetic condition. This basically means that it is primarily inherited by individuals if both parents are genetic carriers of the disease. These genetic carriers are typically unaffected by the actual disease for which they are genetic carriers. 

PCD is a disease that is marked by dysfunctional cilia (singular: cilium). This has some serious health implications for the people involved. Cilia are microscopic appendages that are found on almost all human cells. They cover various surfaces inside and outside the body. Cilia serve various functions that are essential for the physiology of the human body. A good example of cilia is found in the lungs. Cilia in the airways play a role in the removal of pathogens, and other impurities that are trapped in the mucus.

This article will take you through the various functions of cilia in your body. It will also give you an account of the pathophysiology of PCD and how the disease is diagnosed and treated.

Biological roles of cilia and why defects may result in sickness

Overview of cilia

Cilia are microscopic features that comprise an arrangement of tiny protein structures referred to as microtubules. They can be found in most eukaryotic organisms, but not in prokaryotes. There are two main types of cilia, the primary cilia and the secondary cilia. Primary cilia do not move (are non-motile), thereby serving a sensory role. Conversely, secondary cilia can actually move by beating around.

In humans, primary cilia are found on almost all the cells, each cell having a single cilium sticking out from its surface. Secondary cilia, on the other hand, are only found in specific organs of the human body. Unlike primary cilia, multiple secondary cilia cover the surface of each cell. Apart from the respiratory organs, secondary cilia are also found in the fallopian tubes and the brain. The tails of sperm cells are also secondary cilia.

Pathophysiology and symptoms of PCD

PCD is a condition that is caused by defective secondary cilia. The symptoms of the disease manifest from infancy and are lifelong. The clinical manifestations of the disease are mainly respiratory. However, there are symptoms of PCD that do not involve the lungs. This is because cilia are also found in other parts of the body other than the lungs. In the lungs, the secondary cilia sweep mucus-containing impurities up the respiratory tract. The cilia do so by beating upwards so that the mucus may ultimately be ejected through the nose or the mouth. The respiratory symptoms of PCD include:³

• Chronic sinusitis starts from infancy and occurs all year round. In some patients, nasal polyps may also appear
• Chronic cough usually begins in infancy, with sufferers presenting with a wet cough all year round
• Susceptibility to infections of the respiratory tract is elevated in sufferers of PCD
• Obstructive lung disease is a common occurrence in patients of PCD whereby breathing gets more difficult with age
• Bronchiectasis also occurs in the vast majority of adult sufferers of PCD whereby the airways widen, resulting in an accumulation of mucus within the lungs
• Chronic otitis media damages the middle ear and is characterised by recurrent infections 

Complications of PCD

Since secondary cilia are also present in non-respiratory organs, PCD may also affect these ciliated organs. Described here are some of the other conditions that may arise in patients of PCD.⁴

1. Ectopic pregnancy: Since cilia are also present in the fallopian tubes, it may be more difficult for PCD sufferers to fall pregnant. They are at an increased risk of experiencing ectopic pregnancies. This is because the cilia in the fallopian tubes are responsible for moving ova (egg cells) from the ovaries into the uterus
2. Fertility issues: For people assigned male at birth (AMAB) with PCD, it may be difficult to naturally impregnate a woman. This is because PCD also affects the sperm cells. The cilia tail of the sperm is defective. Therefore, the sperm may find it difficult to move up a woman’s reproductive tract to reach an ovum (egg cell) to fertilise
3. Situs inversus: The vital organs of PCD patients may be flipped whereby they are on the opposite side of where they are supposed to be. This condition is referred to as situs inversus. It is caused by dysfunctional cilia in certain embryonic cells. The cilia in these cells are crucial for the correct positioning of organs during foetal growth inside the womb
4. Kartagener’s syndrome: Patients of PCD presenting with sinusitis, bronchiectasis and situs inversus are said to have Kartagener’s syndrome. This is the case for at least half of the people suffering from PCD

How is primary ciliary dyskinesia diagnosed and treated?

Diagnostic procedures for PCD

There are numerous approaches that are employed for the accurate diagnosis of PCD. These range from the observation of symptoms to the analysis of the structure of the cilia in patients. Described here are some of the approaches that are employed in the diagnosis of PCD.³

• The patients are observed for symptoms, taking into account their medical history. Patients presenting with the 3 symptoms of Kartagener’s syndrome most likely suffer from PCD
• The anatomy of the cilia is analysed for any anomalies using techniques such as electron microscopy. Sometimes electron microscopy is unable to pick up ciliary defects. In those cases,  diagnostic methods such as immunofluorescence may be used as well
• PCD may also be diagnosed by measuring the levels of nitric oxide in the sinuses. This is because sufferers of PCSD have strongly reduced nitric oxide levels compared to people who do not have the disease
• The saccharin test may also be performed in the diagnosis of PCD. In this test, a small grain of saccharin is placed on the floor of the nasal cavity. The time it takes for the patient to taste saccharin is recorded. It takes PCD sufferers longer to taste the saccharin in this test⁵

Diagnostic criteria of PCD

Children presenting with a chronic wet cough, situs inversus and/or bronchiectasis should be referred to diagnostic testing for PCD. Neonatal respiratory illnesses of unknown cause also point to PCD in infants. In individuals with AMAB, PCD could be indicated by immotile sperm. People assigned female at birth could be suffering from PCD if they keep on having ectopic pregnancies.⁵ Additionally, patients presenting with at least 3 of the following symptoms are likely to be having PCD:

• Neonatal respiratory illness
• Situs inversus
• Chronic year-round nasal congestion
• Chronic year-round wet cough
• Respiratory infections
• Bronchiectasis
• Chronic otitis media
• Male infertility
• Chronic sinusitis

Treatment for PCD

There are no therapeutics that have been developed to specifically treat PCD. However, there are numerous interventions that could be used to treat PCD patients.⁶

1. An inhaled medicine called N-acetylcysteine is used to reduce the thickness of mucus. This makes it easier to remove the mucus from the airways
2. Nebulising patients with hyperosmolar agents increases coughing so that the airways may be cleared of mucus
3. Inhaled dornase alfa is used to lessen the thickness of mucus in the airways to promote lung clearance
4. Antibiotics may also be given to patients in order to treat bacterial infections
5. In PCD patients with chronic wheezing, asthma medications may also be used

Summary

PCD is a rare and inherited disease that mainly affects the lungs. In this disease, the cilia that are supposed to help sweep mucus and sputum up the airways are defective. This causes a variety of respiratory symptoms such as a chronic cough and chronic sinusitis. There are no diagnostic tests available for the direct diagnosis of PCD. However, there are procedures and criteria that may ensure an accurate diagnosis. Diagnostic methods include measuring the amounts of nitric oxide exhaled by patients. Assessing the cilia to determine if they are structurally sound or are beating in the correct patterns is another diagnostic method for PCD. To treat PCD, drugs such as N-acetylcysteine and dornase alfa can be administered to loosen up the mucus. This allows it to be cleared from the airways. Asthma medications are also considered for patients who also present with wheezing. Since genetics have a role to play in PCD, people who may be carriers of the disease may have to seek genetic counselling with their partners. Doing so will allow them to be made aware of the risks of passing the disease on to their children.