Primary ciliary dyskinesia

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

Motile cilia clear mucus from the respiratory tract and help establish embryonic left-right orientation. Pathogenic variants in many different genes can disrupt ciliary assembly, beat pattern or regulatory function. The resulting phenotype ranges from classic neonatal disease with situs inversus to later recognition in an adult labelled as having idiopathic bronchiectasis, chronic sinusitis or recurrent childhood chest infections. The older term Kartagener syndrome describes the triad of situs inversus, chronic sinus disease and bronchiectasis but captures only a subset of PCD.

Diagnosis should be centralised because sampling technique and interpretation are specialised. Nasal nitric oxide is usually low in cooperative older patients, but low values also occur with viral infection, cystic fibrosis and technical error. High-speed video microscopy evaluates ciliary beat, transmission electron microscopy examines ultrastructure, and immunofluorescence or genomic testing can identify defects missed by microscopy. Tests may need repeating after an infection because secondary ciliary dyskinesia can produce misleading abnormalities.

After diagnosis, care resembles a cause-specific bronchiectasis programme with additional nasal, ear, cardiac, fertility and genetic dimensions. NHS England commissions a specialist adult PCD management service; local teams should share plans with that service. Evidence for many treatments is extrapolated, making documented individual trials and multidisciplinary review important, especially when inhaled agents, long-term antibiotics or surgery are considered.

Key points

PCD is a genetically heterogeneous disorder of motile cilia causing impaired mucociliary clearance, chronic upper and lower airway infection, and sometimes abnormal left-right organ arrangement.
A daily wet cough from early infancy, persistent rhinitis, recurrent otitis media and unexplained neonatal respiratory distress in a term baby form a high-value diagnostic pattern.
Situs inversus or heterotaxy is a clue rather than a requirement; many affected people have ordinary situs, and heterotaxy can include clinically important congenital heart disease.
There is no single universal gold-standard test: diagnosis integrates nasal nitric oxide, ciliary functional and ultrastructural studies, immunofluorescence and genetics in an accredited specialist pathway.
Normal transmission electron microscopy does not exclude PCD because several genetic subtypes have apparently normal ultrastructure; genotype and function may resolve these cases.
Management centres on regular airway clearance, exercise, surveillance cultures, prompt tailored treatment of exacerbations, vaccination and specialist bronchiectasis care rather than a curative respiratory medicine.
Chronic hearing difficulty can affect language, education and work; audiology and ENT input should account for the possibility that ventilation tubes may produce prolonged discharge.
Subfertility affects people of any sex through impaired sperm motility or fallopian-tube ciliary function, so reproductive goals and ectopic-pregnancy risk deserve timely, sensitive discussion.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Inherited ciliary variants

Biallelic variants in numerous motile-cilia genes commonly cause disease, while some forms follow other inheritance patterns and many genes remain under study.

Ultrastructural or functional defects

Abnormal dynein arms, radial spokes, central apparatus or regulatory proteins impair coordinated ciliary beating even when ultrastructure appears normal.

Family predisposition

Consanguinity, affected siblings and unexplained neonatal or laterality disease increase suspicion, but absence of family history does not exclude a recessive disorder.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Defective mucociliary transport
Airway cilia fail to move mucus and inhaled organisms effectively from nose, sinuses, middle ear and bronchi.
2
Persistent infection and inflammation
Retained secretions support bacterial infection and neutrophilic injury from early life, with effects that increase as the pathological process progresses.
3
Progressive bronchiectasis
Repeated airway-wall damage produces irreversible bronchial dilatation, airflow obstruction and declining gas exchange, with effects that increase as the pathological process progresses.
4
Embryonic laterality disturbance
Dysfunctional nodal cilia randomise left-right organ positioning, causing situs inversus or heterotaxy in a subset, thereby altering ventilation, gas transfer or respiratory mechanics.
5
Reproductive tract dysfunction
Impaired sperm flagella and fallopian-tube cilia reduce fertility or increase ectopic pregnancy risk, with effects that increase as the pathological process progresses.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Neonatal origin

Unexplained respiratory distress requiring oxygen for more than 24 hours in a term neonate, especially with lobar collapse or situs abnormality, is a strong historical clue even when adult symptoms later seem modest.

Year-round wet cough

A productive or wet-sounding cough beginning in infancy and never fully disappearing distinguishes impaired clearance from isolated episodic viral wheeze. Adults may regard daily sputum as normal and need direct questioning.

Unified upper-airway disease

Persistent nasal congestion, chronic rhinosinusitis, recurrent otitis media, glue ear and hearing impairment alongside bronchiectasis should be treated as one mucociliary phenotype rather than unrelated diagnoses.

Laterality and cardiac cluesRed flag

Dextrocardia, complete situs inversus or heterotaxy strengthens suspicion. Heterotaxy can accompany complex cardiac or splenic abnormalities, so anatomy and previous surgical history must be defined accurately.

Adult reproductive presentation

Male-factor infertility with immotile sperm, recurrent ectopic pregnancy or otherwise unexplained subfertility may uncover PCD when combined with lifelong sinonasal and chest symptoms.

Escalating suppurative diseaseRed flag

Increasing sputum, breathlessness, haemoptysis, fever or falling oxygen saturation may represent an exacerbation or complication and should be managed promptly using previous airway microbiology.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
Nasal nitric oxideFirst stepFirst line
Why
Provide a sensitive first-line physiological test in an appropriate specialist setting.
Interpretation and limitations
PCD typically produces persistently very low values, but one low measurement is not diagnostic. Repeat when free of acute viral illness and interpret using age-appropriate equipment, technique and centre reference standards.
02
High-speed video microscopy analysis
Why
Assess ciliary beat pattern and frequency from a nasal epithelial sample.
Interpretation and limitations
A reproducible disease-associated beat abnormality supports PCD. Acute infection and poor sampling can cause secondary dyskinesia, so culture of epithelial cells or a repeat specimen may be required before classification.
03
Transmission electron microscopy
Why
Look for characteristic defects in axonemal ultrastructure.
Interpretation and limitations
Outer or combined dynein-arm defects and certain microtubular disorganisation patterns can be diagnostic in the right context. Normal ultrastructure is compatible with several confirmed genetic forms and cannot exclude PCD.
04
Immunofluorescence and genomic testing
Why
Demonstrate missing ciliary proteins or identify causative gene variants.
Interpretation and limitations
A validated biallelic pathogenic genotype can secure diagnosis for most recessive forms, while other inheritance patterns exist. A variant of uncertain significance should not be promoted to a diagnosis without phenotype and functional correlation.
05
Chest imaging and lung function
Why
Stage structural disease and establish a respiratory baseline.
Interpretation and limitations
High-resolution CT commonly shows middle- and lower-lobe bronchiectasis, mucus plugging, atelectasis and tree-in-bud change. Spirometry may underestimate early regional injury, so trend results alongside symptoms, cultures and imaging.
06
Airway microbiology
Why
Guide acute and preventive antimicrobial decisions in chronically impaired clearance.
Interpretation and limitations
Obtain stable and exacerbation sputum for routine culture, with mycobacterial sampling when indicated. Track Pseudomonas aeruginosa, resistance and new organisms rather than treating every positive culture identically.
07
Audiology, ENT and fertility assessment
Why
Measure important extra-pulmonary consequences that patients may under-report.
Interpretation and limitations
Formal hearing tests guide educational and occupational support. ENT examination characterises middle-ear and sinus disease; fertility referral should match the individual's goals and include ectopic-pregnancy counselling where relevant.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Cystic fibrosis

Bronchiectasis, sinus disease and infertility overlap, but CFTR testing and sweat chloride distinguish epithelial ion-channel dysfunction.

Immunodeficiency

Abnormal immunoglobulins or vaccine responses explain recurrent infection without primary ciliary dysfunction, though both can coexist.

Post-infective bronchiectasis

Disease beginning after a discrete severe infection without neonatal symptoms, chronic ear disease or laterality clues favours acquired damage.

Young-child normality or protracted bacterial bronchitis

Frequent viral infections or wet cough may be common in children, but persistent year-round symptoms from infancy and neonatal distress are discriminating.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01ReferBuild the diagnostic phenotypeFirst stepA lifelong wet cough, neonatal respiratory history, laterality anomaly or combined ear, sinus and bronchiectatic disease suggests PCD.

1Construct a timeline from birth, including neonatal oxygen, year-round rhinitis and cough, ear disease, situs, congenital heart disease, fertility history and affected relatives.
2Exclude common mimics with immune testing, cystic fibrosis assessment and aspiration review as indicated, but send a convincing phenotype to the national diagnostic pathway rather than awaiting every local result.
3Let the specialist centre sequence nasal nitric oxide, functional microscopy, ultrastructure, immunofluorescence and genetics, repeating infection-affected samples before declaring the evaluation negative.

02MaintainPreserve airway healthPCD is confirmed or strongly suspected and chronic secretion retention requires an ongoing plan.

1Teach an individualised daily airway-clearance technique through a respiratory physiotherapist and combine it with regular physical activity, adapting treatment during exacerbations, pregnancy or postoperative periods.
2Collect scheduled sputum cultures, maintain influenza, COVID-19 and pneumococcal vaccination according to national eligibility, avoid tobacco exposure and treat coexisting asthma only when objectively supported.
3Coordinate the national PCD service, local bronchiectasis team, ENT, audiology, primary care and reproductive services through a written shared-care plan with transition and emergency details.

03ExacerbateRespond to clinical deteriorationSputum volume or purulence, cough, breathlessness, fatigue, haemoptysis or systemic features worsen beyond daily variation.

1Assess severity and complications, send sputum where feasible and retrieve earlier cultures, drug reactions and Pseudomonas history before selecting a locally approved antibiotic.
2Increase airway-clearance support and hydration, arrange hospital treatment when oral therapy or home physiology is inadequate, and seek urgent help for hypoxaemia, major bleeding or sepsis.
3After recovery, document duration and organism, restore the stable regimen and investigate frequent events for adherence barriers, NTM, ABPA, reflux, sinus burden or preventive-treatment eligibility.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Bronchiectasis and respiratory failure

Cumulative infection and inflammation cause structural destruction, chronic hypoxaemia and occasionally advanced respiratory failure, particularly when baseline cardiopulmonary reserve is limited.

Chronic ear and hearing disease

Poor middle-ear clearance produces recurrent otitis, effusions and conductive hearing loss affecting speech and education, creating an additional need for recognition and targeted treatment.

Chronic rhinosinusitis

Persistent sinonasal mucus and infection cause obstruction, facial symptoms, anosmia and repeated treatment burden, and potentially prolonging treatment and functional recovery.

Infertility and ectopic pregnancy

Dysfunctional reproductive cilia reduce sperm motility and ovum transport, affecting conception and pregnancy safety, adding morbidity beyond the initial pulmonary disorder.

Complex congenital heart disease

Heterotaxy can accompany serious cardiac and vascular malformations requiring lifelong specialist care, and increasing the burden of otherwise local respiratory disease.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

Review respiratory symptoms, sputum volume, haemoptysis, exacerbation frequency, weight, oxygenation and exercise tolerance at intervals agreed with the specialist service.
Perform spirometry serially using the same technique and compare with the person's trajectory; a meaningful decline warrants cultures, adherence review and complication assessment.
Send routine airway cultures while stable and whenever treatment failure or a new exacerbation occurs, adding mycobacterial testing before relevant long-term antimicrobial strategies.
Reassess airway-clearance technique with physiotherapy rather than assuming a device remains effective as disease, lifestyle or pregnancy changes.
Maintain scheduled hearing and ENT review, particularly through education, employment transitions and periods of recurrent middle-ear discharge.
Address fertility intentions proactively and keep genetic counselling available for patients and relatives without presuming that everyone wants testing or assisted conception.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

Ordinary situs is common

Absence of dextrocardia should never close the diagnostic pathway; laterality is effectively randomised only in subtypes that disturb embryonic nodal cilia.

Microscopy can look normal

Some molecular defects alter regulation rather than visible ultrastructure, which is why a normal electron micrograph cannot outweigh a strong phenotype and complementary testing.

Repeat after infection

Damaged epithelium during a viral or bacterial illness may beat abnormally for secondary reasons; repeat or cultured-cell testing prevents a false-positive functional interpretation.

Ears affect adulthood too

Hearing loss may persist beyond childhood and influence consultations, safety and work, so clinicians should face the patient, check communication needs and arrange objective assessment.

Anatomy changes procedures

In situs inversus, ECG placement, radiograph labelling, central access and abdominal or thoracic interventions require deliberate confirmation of mirrored anatomy.

11Common pitfallsFrequent interpretation and management errors.

01
Using the absence of situs inversus to rule out primary ciliary dyskinesia.
02
Treating a single low nasal nitric oxide value during a cold as a definitive diagnosis.
03
Reassuring a strongly affected patient solely because transmission electron microscopy is normal.
04
Labelling abnormal ciliary motion during infection as inherited disease without repeat specialist sampling.
05
Focusing on the lungs while missing hearing impairment, congenital cardiac anatomy, fertility goals or ectopic-pregnancy risk.
06
Applying generic bronchiectasis treatment without maintaining contact with the commissioned adult PCD service.