Overview
Definition:
Primary Ciliary Dyskinesia (PCD) is a rare, inherited autosomal recessive disorder characterized by defective ciliary function, leading to impaired mucociliary clearance in the respiratory tract, middle ear, and reproductive organs
Nasal nitric oxide (nNO) measurement is a crucial diagnostic tool.
Epidemiology:
The prevalence of PCD is estimated to be between 1 in 10,000 to 30,000 live births
It is a significant cause of chronic respiratory disease in children, often presenting with symptoms mimicking cystic fibrosis
Genetic mutations in over 40 different genes have been identified, highlighting its genetic heterogeneity.
Clinical Significance:
Accurate and timely diagnosis of PCD is critical for initiating appropriate management to prevent irreversible lung damage, reduce morbidity, and improve the quality of life
Impaired mucociliary clearance leads to recurrent sinopulmonary infections, otitis media, male infertility, and situs inversus
Nasal NO measurement provides a non-invasive, sensitive, and specific biomarker for ciliary dysfunction.
Clinical Presentation
Symptoms:
Neonatal respiratory distress
Persistent neonatal tachypnea
Chronic wet cough
Recurrent otitis media, often with effusion
Chronic rhinosinusitis
Frontal headache
Palpable nasal polyps
Recurrent pneumonia
Bronchiectasis
Situs inversus or heterotaxy in approximately 50% of cases (Kartagener's syndrome)
Male infertility.
Signs:
Rhinorrhea
Nasal congestion
Postnasal drip
Ear discharge
Tympanic membrane abnormalities
Crackles or wheezes on lung auscultation
Clubbing in severe, long-standing cases
Signs of bronchiectasis on imaging.
Diagnostic Criteria:
No single definitive diagnostic criterion exists for PCD
Diagnosis relies on a combination of clinical suspicion, characteristic symptoms, family history, and specific diagnostic tests including high-resolution transmission electron microscopy (HR-TEM) of respiratory cilia, genetic testing, and nasal nitric oxide (nNO) measurement
A reduced nNO level (typically < 77 nL/min in children and < 80 nL/min in adults) is highly suggestive of PCD
Confirmation often requires a combination of abnormal ciliary ultrastructure and/or genetic mutations.
Diagnostic Approach
History Taking:
Detailed history of recurrent sinopulmonary infections from infancy
History of otitis media, hearing loss, or speech delay
Presence of neonatal symptoms like persistent cough or tachypnea
Family history of similar symptoms or known PCD
Infertility in adult males
Ask about a personal or family history of situs inversus.
Physical Examination:
Thorough examination of the ears, nose, and throat
Auscultation of the lungs for signs of infection or chronic airway disease
Assess for clubbing
Assess for general signs of chronic illness
Screen for situs inversus using palpation or auscultation (e.g., heart sounds).
Investigations:
Nasal Nitric Oxide (nNO) Measurement: This is a key investigation
A low fractional exhaled nitric oxide (FeNO) in exhaled breath, specifically measured from the nasal airways, strongly suggests PCD
Values below 77 nL/min in children are highly suspicious
However, nNO can be affected by factors like nasal obstruction, infection, and age
High-Resolution Transmission Electron Microscopy (HR-TEM): Examination of respiratory cilia (obtained via nasal brushing) for characteristic ultrastructural defects (e.g., absence of dynein arms, radial spoke defects)
Genetic Testing: Detects mutations in genes known to cause PCD
Used to confirm diagnosis, especially when other tests are equivocal
Lung Function Tests (Spirometry): To assess the degree of airway obstruction and disease severity, typically in older children and adults
Chest Imaging (X-ray, CT Scan): To identify bronchiectasis, mucus plugging, and sinus disease
Sputum Microbiology: To identify causative pathogens and guide antibiotic therapy
Sweat Chloride Test: To rule out cystic fibrosis (important differential diagnosis).
Differential Diagnosis:
Cystic Fibrosis (CF): Distinguishing PCD from CF is crucial, as management differs
CF typically presents with pancreatic insufficiency and elevated sweat chloride
Asthma: Chronic cough and wheezing can mimic PCD, but asthmatic airways have increased FeNO, not reduced nasal NO
Recurrent Bronchopulmonary Infections of other etiologies: Including immunodeficiencies, aspiration syndromes, or congenital airway anomalies
Chronic Rhinosinusitis: Can be a symptom of PCD but also a primary condition.
Nasal Nitric Oxide Testing
Principle:
Nasal nitric oxide (nNO) is produced by the paranasal sinuses and transported into the nasal cavity
In PCD, impaired ciliary function leads to reduced clearance of mucus and inflammatory mediators from the paranasal sinuses, affecting nNO production and/or transport, resulting in lower measured levels in the nasal airway.
Procedure:
The patient breathes through a mouthpiece with a nasal occluder or clips to isolate nasal exhalation
They are instructed to perform a specific breathing maneuver (e.g., exhalation against resistance or a controlled slow exhalation) to measure the nasal NO concentration
Standardized protocols are essential for accurate and reproducible results.
Interpretation:
Low nasal NO levels (< 77 nL/min in children, < 80 nL/min in adults) are highly suggestive of PCD
However, this value should be interpreted in conjunction with other clinical and laboratory findings
A normal nNO level does not entirely exclude PCD, especially in milder cases or if the nasal passages are severely obstructed
Serial measurements may be useful
Other factors influencing nNO include recent upper respiratory tract infection, atopic status, and inhaled corticosteroids.
Advantages:
Non-invasive
Relatively easy to perform
Provides a quantitative biomarker
Good negative predictive value (a normal result makes PCD less likely)
Can be used for screening and diagnostic workup.
Limitations:
Interference from nasal obstruction, inflammation, or infection
Age-dependent reference ranges
Requires specialized equipment and trained personnel
Not definitive on its own
requires confirmation with other tests.
Management
Initial Management:
Early diagnosis and referral to a PCD center of expertise are paramount
Management focuses on optimizing airway clearance and treating infections to prevent progressive lung damage.
Medical Management:
Antibiotic therapy: For acute exacerbations and sometimes prophylactic use to suppress chronic bacterial colonization
Airway clearance techniques (ACTs): Including chest physiotherapy, positive expiratory pressure (PEP) devices, and oscillating PEP devices
Mucolytics: May be considered in some cases
Bronchodilators: For symptomatic relief if bronchospasm is present
Nasal saline irrigation and topical corticosteroids: For sinonasal symptoms.
Surgical Management:
Generally reserved for complications such as chronic otitis media requiring tympanostomy tubes or severe bronchiectasis that fails to respond to medical management, though surgical intervention for bronchiectasis is rare and controversial
Sinus surgery may be considered for severe, refractory chronic rhinosinusitis.
Supportive Care:
Nutritional support: To maintain healthy growth and weight
Pulmonary rehabilitation
Audiology and speech therapy: For recurrent ear infections and related issues
Genetic counseling
Vaccination: Against influenza and pneumococcal disease.
Complications
Early Complications:
Persistent neonatal respiratory distress
Neonatal pneumonia
Progressive bronchiectasis leading to impaired gas exchange
Recurrent otitis media with hearing loss and speech delay.
Late Complications:
Severe lung disease requiring lung transplantation
Infertility (especially in males due to immotile sperm)
Nasal polyposis
Pleural effusion
Pneumothorax.
Prevention Strategies:
Prompt diagnosis and initiation of airway clearance strategies
Aggressive treatment of respiratory infections
Regular follow-up with a PCD specialist
Avoiding environmental irritants like smoke
Annual influenza vaccination.
Prognosis
Factors Affecting Prognosis:
Age at diagnosis
Severity of lung disease at diagnosis
Presence and type of genetic mutations
Adherence to treatment and airway clearance
Development of bacterial resistance
Presence of situs inversus (generally has a better prognosis).
Outcomes:
With early diagnosis and consistent management, many individuals with PCD can lead relatively healthy lives, though chronic respiratory issues persist
Lung function declines over time in most patients, but the rate of decline can be significantly influenced by management
Survival into adulthood is common.
Follow Up:
Lifelong follow-up with a multidisciplinary PCD care team is essential
This includes regular pulmonary function testing, chest imaging as indicated, sinonasal assessments, audiology, and management of associated conditions.
Key Points
Exam Focus:
Nasal nitric oxide is a critical screening tool for PCD, with low levels (<77 nL/min in children) being highly suggestive
Remember that other conditions can affect nNO
HR-TEM and genetic testing are confirmatory
Kartagener's syndrome (PCD, situs inversus, bronchiectasis) is a classic triad.
Clinical Pearls:
Always consider PCD in neonates with persistent respiratory symptoms, and in children with recurrent unexplained sinopulmonary infections and otitis media
Differentiate from Cystic Fibrosis by sweat chloride test and clinical presentation
Emphasize aggressive airway clearance and early antibiotic use.
Common Mistakes:
Attributing recurrent respiratory infections solely to common viral illnesses without considering underlying chronic conditions
Delaying diagnostic workup for PCD due to low suspicion or lack of access to specialized testing
Misinterpreting nNO levels without considering other factors like concurrent infection or nasal obstruction.