Primary Ciliary Dyskinesia

Primary ciliary dyskinesia is an inherited disorder of ciliary structure and function that impairs mucociliary clearance. It leads to chronic wet cough, sinusitis, otitis media and bronchiectasis from early childhood. The estimated prevalence is about 1 in 10 000 to 1 in 20 000, and it is underdiagnosed.

Inheritance is autosomal recessive in most cases (over 50 genes, including DNAH5 and DNAI1 and CCDC39), with a few X-linked. About half of patients have situs inversus, and the combination of sinusitis, bronchiectasis and situs inversus is called Kartagener syndrome.

Pathophysiology. Defects of the dynein arms, radial spokes or central apparatus cause immotile or dyskinetic cilia in the airway, middle ear, sinus, ependyma, oviduct and sperm flagella. Retained secretions lead to recurrent infection, inflammation and progressive bronchiectasis, with middle lobe and lingula usually first.

Neonatal respiratory distress at term (in about 80%) with lobar collapse, and persistent wet cough and nasal congestion from the first weeks of life that do not improve. Later, recurrent otitis media with effusion and hearing loss, chronic rhinosinusitis, bronchiectasis and, in adults, a chronic productive cough and exertional dyspnoea.

Situs inversus or heterotaxy (with congenital heart disease) occurs in some. Male infertility from immotile sperm is typical, and women have reduced fertility and ectopic pregnancy risk. Hydrocephalus is rare.

Fever with worsening dyspnoea or haemoptysis needs prompt assessment, as does respiratory failure from advanced bronchiectasis.

• Suspect in any child with daily wet cough since infancy, neonatal respiratory distress, and ear and nose disease, and in adults with unexplained bronchiectasis, particularly with sinus and ear disease or situs inversus.
• Nasal nitric oxide measured during breath hold or velum closure (from age 5 to 6 years): very low values (under 77 nL/min) strongly suggest the diagnosis. Measure at least 2 weeks after any respiratory infection.
• High speed video microscopy of nasal brushings for ciliary beat pattern and frequency, repeated after culture of cells when infection confounds the result.
• Transmission electron microscopy of cilia (normal in up to 30% of cases) and genetic testing with a multigene panel, which is now often the confirmatory step.
• Chest CT for bronchiectasis and imaging of situs. Sputum culture, spirometry and audiometry.
• Immunoglobulin levels and a sweat chloride test to exclude other causes of bronchiectasis.

Differential diagnosis.

• Cystic fibrosis
• Primary antibody deficiency
• Recurrent aspiration or an inhaled foreign body
• Post-infectious bronchiectasis
• Asthma with rhinosinusitis
• Chronic suppurative lung disease from tuberculosis

• Airway clearance twice daily from diagnosis (chest physiotherapy, positive expiratory pressure device, active cycle of breathing, exercise), with hypertonic saline 7% nebulised 4 mL twice daily after salbutamol, first tested for tolerance (bronchospasm). Avoid cough suppressants.
• Long term azithromycin for those with 3 or more exacerbations in a year or progressive lung disease: 500 mg three times weekly in adults (250 mg daily in those under 50 kg), and 10 mg/kg three times weekly in children (maximum 500 mg), after excluding nontuberculous mycobacteria, with QTc and hearing checks.
• Exacerbation: culture directed antibiotics for 14 days, usually amoxicillin-clavulanate 625 mg three times daily or doxycycline 100 mg twice daily (200 mg on day 1) for adults, and weight based doses in children, increasing to 2 to 3 weeks with severe disease. Use an intravenous route for severe exacerbation or Pseudomonas, for example ceftazidime 2 g every 8 hours.
• Pseudomonas aeruginosa eradication after first growth: ciprofloxacin 500 to 750 mg twice daily for 2 to 3 weeks (children 15 to 20 mg/kg twice daily), with nebulised tobramycin 300 mg twice daily for 28 days (or colistimethate 1 to 2 million units twice daily), and long term inhaled antibiotic for chronic infection.
• Vaccination against influenza, pneumococcus, and COVID-19, and exercise and weight control.
• ENT care: hearing assessment with a hearing aid for persistent effusion, since grommets are used cautiously by specialists. Nasal saline and corticosteroid spray, and sinus surgery only for clear indication.
• Fertility: referral for assisted reproduction (intracytoplasmic sperm injection in men). Genetic counselling for families.
• Lobectomy for localised severe disease, and lung transplantation for end stage disease.

Complications and prognosis. Progressive bronchiectasis, chronic Pseudomonas infection and, in a minority, respiratory failure. Lung function decline is slower with early diagnosis and regular care.

Monitoring. Specialist review every 3 months with spirometry, sputum culture and oxygen saturation, yearly CT only when clinically needed, audiology yearly, and growth in children.

Referral and escalation. Refer to a national or regional primary ciliary dyskinesia service for diagnosis and shared care, and refer urgently for severe exacerbation, haemoptysis or respiratory failure.