Primary Ciliary Dyskinesia (PCD)

Autosomal Recessive Disease

INTRODUCTION

FUNCTION OF THE CILIA


The cilia are hair-like structures that line the upper and lower respiratory airways (mucous membranes of the lungs, nose, and sinuses) as well as the ventricular system of the brain and spinal cord.Normal cilia move in a wave-like motion.

In fact biologically, Motile Cilia are also found in the female fallopian tubes and are components of the male sperm flagellum which required for sperm motility.

They transport mucus up and out of the airways through the nose and mouth. This action, called motility, clears the sinuses and lungs of germs that can cause infection.

Pathophysiology

PCD is a rare inherited lung disease. It causes the airways to become blocked with mucus resulting in impaired mucociliary clearance. The defects in the ciliary are due to an abnormal ciliary movement, which is manifest as recurrent and persistent or chronic sinopulmonary infections, among other problems as well as respiratory failure. Some individuals with primary ciliary dyskinesia have abnormally placed organs within their chest and abdomen.(Situs Inversus Totalis).

It is a Classic triad of Situs Inversus, Bronchiectasis, and Sinusitis.

PCD is estimated to occur in 1 about every 15,000 to 20,000 individuals worldwide.

Also, infants with PCD have difficulty breathing and may initially require supplemental oxygen or even breathing support. At some point, their breathing improves, but other symptoms may increase with age such as persistent ear infections, runny nose, and a daily wet cough.

The build-up of mucus can result in bronchiectasis, which causes bronchial tubes to weaken and stretch out, and often leads to pneumonia

Etiology

PCD is a genetically heterogeneous disorder affecting motile cilia which are made up of approximately 250 proteins. Around 90% of individuals with PCD have ultrastructural defects affecting proteins in the outer and inner dynein arms which give cilia their motility, with roughly 38%of these defects caused by mutations in two genes, DNAI1 and DNAH5 (code for proteins found in the ciliary outer dynein arm.)

Risk factors

Genes:

The genetic status of a patient biological parents ( PCD carrier) determines whether he/she is at risk for PCD. Usually, carriers don't have any symptoms of PCD, but they can pass faulty PCD genes on to their children.

Early diagnosis:

Early diagnosis of PCD is critical because early treatment is considered essential to help slow the progression of PCD lung disease.

Environment and Lifestyle:

Just like any other disease, other factors are involved and may influence the progress of the disease, especially environmental influences.

Not smoking

Avoiding direct contact with people who have a cold or chest infection

Receiving appropriate vaccines like the flu shot

Eating well and staying active

Practicing good "airway clearance."

Age:

PCD over time is unpredictable. Some patients do very well for a full lifetime while others have severe lung disease by the time they are young adults.

Prevention

According to Clinical Research in University Southampton, patients with PCD should regularly be seen by a pulmonologist. He/she can recommend some preventive and therapeutic treatment to alleviate the symptoms by following the progression of the disease. Also, regularly check ears, nose, and throat are essential for sinus problems and/or ear infections. The most definitively hearing should frequently be checked, especially in patients susceptible to many ear infections. Since PCD causes men infertility, the idea is to consult an infertility specialist to discuss their options for having children, if desired.


PREVENTION

Immunized against common infections

Haemophilus influenza type b (Hib)

Pneumococcus

Seasonal flu

Pertussis (a whooping cough)


PCD SHOULD AVOID

Using cough suppressants, because a productive cough is the body's best way to remove mucus from the airways

Smoking

Environment: air pollution or chemicals that irritate the lungs

Therapeutic interventions

PHARMACOLOGICAL TREATMENT

Typical therapy involved prompt treatment of recurrences, antibiotics to suppress infection.

A prescription of a bronchodilator is needed to decrease resistance in the respiratory airway and increasing airflow to the lungs (LABA, SABA). Also, a corticosteroid medicine to reduce and prevent inflammation in the respiratory airway is vital.

Secretion clearance interventions are the key option to avoid infection cause by PCD because patients are unable to remove pulmonary secretions naturally. They rely on daily airway clearance therapy.

THERAPEUTIC INTERVENTION
Many physicians prescribe airway clearance therapy at the time of diagnosis consist of chest percussion and postural drainage, oscillatory vest, and breathing exercises to facilitate clearance of distal airways

Therapeutic intervention lessening exposure to excess, bacteria-laden mucus, respiratory health is sustained, and disease progression is moderated.

In a severe case of PCD lung transplantation can be performed in the end-stage lung of the disease

New research

According to Royal Brompton and Harefield journal for the National Health Service in the United Kingdom, Dr. Amelia Shoemark, a senior clinical scientist in Primary Ciliary Dyskinesia is conduction and investigating new diagnostic tools for Primary Ciliary Dyskinesia. The study will test new more powerful microscopy methods, electron tomography, and immunofluorescence techniques, to analyze the aspect of the cilia and help to diagnose better the disease in the future. If successful the project will lead to the blend of the proficiency into the diagnostic service for PCD by improving the diagnosis pathway for these patients