Kartagener Syndrome (Primary Ciliary Dyskinesia)

Definition

Primary ciliary dyskinesia (PCD) is an inherited condition in which the motile cilia — the hair-like structures that line the airways, the sinuses, the middle ear and the reproductive tract — are built incorrectly and therefore beat weakly, in the wrong pattern, or not at all.^1,3

Kartagener syndrome is the historical name for the combination of three findings: situs inversus (the internal organs arranged as a mirror image of normal), chronic sinusitis, and bronchiectasis.⁴ It is not a separate disease. It is PCD in the roughly half of people who also have mirror-reversed organs, and the underlying ciliary defect is identical.^3,9

The link between the two was explained in 1976, when the cilia of affected patients were shown to be immotile under the microscope.⁵ That single observation accounts for both halves of the syndrome, and it is worth understanding, because it explains why the organs end up reversed at all.

Pathophysiology

Why the cilia fail

A normal cilium contains an internal scaffold of microtubules and a set of molecular motors — the dynein arms — that make it bend. Most people with PCD carry variants in one of more than fifty genes that build these components. The commonest affect the outer dynein arms, and the cilia are then either still or beating in a stiff, ineffective way.³ Because the fault is in the structure itself, it is present from birth and does not fluctuate.

Why the organs can end up reversed

Very early in development, a patch of cilia at the embryonic node beats in a rotating pattern that generates a leftward flow of fluid. That flow is the signal that tells the body which side is which. If those cilia do not beat, the signal is absent and left–right orientation is decided at random — so about half of people with PCD have normal anatomy and about half have situs inversus.^3,9 The reversal itself causes no harm; it is a marker of the ciliary defect, not a cause of illness.

The infection cycle in the lungs

Mucus that is not moved becomes a place where bacteria settle. Persistent bacteria provoke inflammation, inflammation damages and widens the airway wall, and a widened, scarred airway clears even less well than before. This self-sustaining loop produces bronchiectasis, usually in the lower lobes and the middle lobe.^9,10 It is the same cycle seen in other causes of bronchiectasis, with one crucial difference: in PCD the mucociliary escalator was never working, so the only clearance mechanism available is airflow and cough.

Symptoms

PCD is present from birth, and the pattern over a lifetime is more useful for recognising it than any single symptom:

• A wet cough, every day, since infancy. This is the single most characteristic feature. A daily productive cough in a child is not normal and should not be attributed to recurrent viral illness indefinitely.⁹
• Unexplained breathing difficulty as a newborn. Most babies with PCD have respiratory distress at or near term, often needing oxygen for several days — an unusual pattern in a baby born at full term.^2,9
• A constantly blocked or running nose from early life, with chronic sinus disease later.
• Repeated middle-ear infections and glue ear, frequently with hearing loss during childhood.⁹
• Recurrent chest infections, and in time the persistent sputum production and breathlessness of established bronchiectasis.

Adults are still being diagnosed in their thirties, forties and later, often after years of being told they have difficult asthma or unexplained bronchiectasis.^1,9

Diagnosis

There is no single test that settles it, and that is the main reason diagnosis is so often delayed. European and American guidelines both recommend combining a suggestive clinical history with more than one investigation.^1,2

• Nasal nitric oxide — strikingly low in PCD. It is quick and non-invasive, and it is the recommended first-line screening test in cooperative patients over about five years of age, but it is a screen and not a diagnosis.^1,2
• High-speed video microscopy of a nasal or bronchial brushing, to look directly at how the cilia beat.¹
• Transmission electron microscopy, which shows the missing dynein arms — definitive when abnormal, but normal in a substantial minority of genetically confirmed cases.^1,3
• Genetic testing, which now identifies a causative variant in the majority of patients and is increasingly used alongside the other tests rather than after them.^2,3

Testing is done in specialist centres, and results can be affected by recent infection, so tests are sometimes repeated when the clinical suspicion is high.¹

Management

There is no treatment that repairs the cilia. Care is therefore built around removing mucus, treating infection early, and monitoring for decline — an approach adapted from bronchiectasis care and delivered by a specialist team.^6,10

• Daily airway clearance, for life, whether or not the person feels unwell. This is the foundation of treatment and is discussed below.⁶
• Regular exercise, which increases airflow and assists clearance as well as maintaining fitness.^6,10
• Prompt, adequate antibiotic treatment of exacerbations, guided by regular sputum cultures.⁶
• Surveillance — lung function, sputum microbiology, and imaging when indicated. Lung function in PCD varies widely between individuals, so the trend for one person matters more than the comparison with anyone else.^6,12
• Long-term antibiotics in selected people. Azithromycin taken three times a week halved the rate of chest exacerbations in the only large trial conducted in PCD, and is used where flare-ups are frequent.⁷
• Nebulised treatments are not routine here. Inhaled hypertonic saline was tested specifically in PCD and did not improve quality of life or lung function, and the mucus-thinning drug used in cystic fibrosis has no evidence base in this condition — so a treatment that helps a friend with CF may not be appropriate.^6,8
• ENT and audiology review, because the ears and sinuses are affected by the same defect.^6,9
• Vaccination against influenza, COVID-19 and pneumococcus, and avoidance of tobacco smoke.⁶

Ears, sinuses and hearing

Cilia line the middle ear and the sinuses too. Children with PCD commonly have persistent glue ear and fluctuating hearing loss during the years when speech and schooling develop, and chronic sinus disease is near-universal in adults.⁹ Grommets are used cautiously in PCD because they can be followed by prolonged discharge, and decisions are usually made by an ENT surgeon familiar with the condition.⁶ Hearing should be checked rather than assumed — a child who seems inattentive may simply not be hearing well.

Fertility

The same motors that drive cilia also drive the tail of a sperm, and cilia line the fallopian tubes. Many men with PCD are infertile or have reduced fertility, and women have a higher rate of reduced fertility and of ectopic pregnancy.^3,9 This is not universal and it is not a reason to avoid contraception. It is a subject worth raising early rather than discovering later.

Living with it

The practical burden of PCD is that treatment is daily, indefinite, and required most on the days it is least appealing. Two things make it sustainable in practice: a routine short enough to survive a bad week, and a technique the person can actually do without supervision. A twenty-minute session that happens every day is worth considerably more than a forty-minute session that happens twice.

Because the condition is rare, many people with PCD find they are explaining it to health professionals who have not met it before. A brief written summary of the diagnosis, the usual organisms in their sputum and their normal treatment is useful to carry.

Role of the physiotherapist

In most lung conditions airway clearance is one intervention among several. In PCD it occupies a different position, and the reason is mechanical rather than a matter of emphasis: the mucociliary escalator has never worked, so the clearance the rest of us get without thinking has to be produced deliberately, every day, by breathing technique and cough.^6,11

What that involves in practice:

• Choosing a technique against the imaging. Where the bronchiectasis actually sits determines which technique and which positions are worth using. This should be read off a recent CT report, not assumed.^10,11
• Teaching it to the point of independence — the active cycle of breathing techniques, autogenic drainage, or an oscillating positive expiratory pressure device, chosen to suit the person rather than the clinic's habit.¹¹
• Reviewing it. Technique drifts. A routine that has stopped working is more often a drifted technique than a progressing disease, and this is the commonest thing we correct.
• Adapting during exacerbations, when sputum volume rises and the usual routine is no longer enough.
• Exercise prescription, both for its clearance effect and for the fitness and quality-of-life benefits shown in bronchiectasis populations.¹⁰

We work alongside the respiratory physician and the ENT team rather than instead of them. Bring a recent CT report and recent sputum results to a first appointment — they change what we recommend.

Part 1 · References

1. Lucas JS, Barbato A, Collins SA, et al. European Respiratory Society guidelines for the diagnosis of primary ciliary dyskinesia. Eur Respir J 2017;49(1):1601090.
2. Shapiro AJ, Davis SD, Polineni D, et al. Diagnosis of primary ciliary dyskinesia: an official American Thoracic Society clinical practice guideline. Am J Respir Crit Care Med 2018;197(12):e24–e39.
3. Knowles MR, Daniels LA, Davis SD, Zariwala MA, Leigh MW. Primary ciliary dyskinesia: recent advances in diagnostics, genetics, and characterization of clinical disease. Am J Respir Crit Care Med 2013;188(8):913–922.
4. Kartagener M. Zur Pathogenese der Bronchiektasien: Bronchiektasien bei Situs viscerum inversus. Beitr Klin Tuberk 1933;83:489–501.
5. Afzelius BA. A human syndrome caused by immotile cilia. Science 1976;193(4250):317–319.
6. Shapiro AJ, Zariwala MA, Ferkol T, et al. Diagnosis, monitoring, and treatment of primary ciliary dyskinesia: PCD Foundation consensus recommendations based on state of the art review. Pediatr Pulmonol 2016;51(2):115–132.
7. Kobbernagel HE, Buchvald FF, Haarman EG, et al. Efficacy and safety of azithromycin maintenance therapy in primary ciliary dyskinesia (BESTCILIA): a multicentre, double-blind, randomised, placebo-controlled phase 3 trial. Lancet Respir Med 2020;8(5):493–505.
8. Paff T, Daniels JM, Weersink EJ, et al. A randomised controlled trial on the effect of inhaled hypertonic saline on quality of life in primary ciliary dyskinesia. Eur Respir J 2017;49(2):1601770.
9. Goutaki M, Meier AB, Halbeisen FS, et al. Clinical manifestations in primary ciliary dyskinesia: systematic review and meta-analysis. Eur Respir J 2016;48(4):1081–1095.
10. Hill AT, Sullivan AL, Chalmers JD, et al. British Thoracic Society guideline for bronchiectasis in adults. Thorax 2019;74(Suppl 1):1–69.
11. Lee AL, Burge AT, Holland AE. Airway clearance techniques for bronchiectasis. Cochrane Database Syst Rev 2015;11:CD008351.
12. Halbeisen FS, Goutaki M, Spycher BD, et al. Lung function in patients with primary ciliary dyskinesia: an iPCD Cohort study. Eur Respir J 2018;52(2):1801040.