Williams-Campbell Syndrome

Williams-Campbell syndrome is a rare congenital deficiency of bronchial cartilage in the fourth to sixth generation bronchi, leading to cystic bronchiectasis of the segmental and subsegmental airways. The trachea and main bronchi are normal.

It presents in infancy or childhood with recurrent chest infection and wheeze, and some are diagnosed in adulthood. The cause is unknown, and familial cases suggest a genetic basis.

Pathophysiology. Absent or defective cartilage plates in the affected bronchi mean the airways balloon on inspiration and collapse on expiration. Secretions are retained, and chronic infection leads to cystic bronchiectasis, usually with air trapping.

Recurrent pneumonia, chronic productive cough, wheeze, exertional dyspnoea, hyperinflated chest, coarse crackles and clubbing, with growth failure in children. Haemoptysis and pneumothorax occur.

Respiratory failure, severe pneumonia or massive haemoptysis need urgent care.

• High resolution CT with inspiratory and expiratory slices: ballooning of fourth to sixth order bronchi on inspiration with collapse on expiration, bronchiectasis in those generations with normal proximal airways, and air trapping. The central location and the normal trachea and main bronchi separate it from Mounier-Kuhn syndrome.
• Bronchoscopy: collapse of the segmental bronchi on expiration, with normal cartilage rings in larger airways.
• Spirometry: obstruction with air trapping and poor reversibility.
• Exclude cystic fibrosis (sweat chloride), primary ciliary dyskinesia (nasal nitric oxide), immunodeficiency (immunoglobulins) and a retained foreign body or post-infective damage, since all are more common.
• Sputum cultures for Pseudomonas, Staphylococcus, Haemophilus, mycobacteria and fungi.

• Airway clearance twice daily (chest physiotherapy, positive expiratory pressure), and hypertonic saline 3 to 7% nebulised after salbutamol where tolerated.
• Exacerbation: antibiotics directed by culture for 14 days, empirically amoxicillin-clavulanate 625 mg three times daily or doxycycline 200 mg on day 1 then 100 mg daily in adults, and weight based doses in children. Intravenous therapy for severe infection or Pseudomonas, for example ceftazidime 2 g every 8 hours.
• Prophylaxis in frequent exacerbations: azithromycin 500 mg three times weekly in adults (250 mg daily under 50 kg), and 10 mg/kg three times weekly in children, after excluding nontuberculous mycobacteria and checking QTc.
• Bronchodilators when there is reversibility, continuous positive airway pressure to stent collapsing airways in some, and supplemental oxygen for hypoxaemia.
• Vaccination against influenza, pneumococcus and COVID-19. Nutritional support in children.
• Lobectomy for localised, severe disease, and lung transplantation for end stage disease.

Complications and prognosis. Chronic infection, haemoptysis, respiratory failure. The course is variable, and many patients have a stable course with good care.

Monitoring. Review every 3 to 6 months with spirometry, oximetry and sputum culture, and CT only when clinically needed.

Referral and escalation. Refer to a paediatric or adult respiratory specialist, and to the transplant team for progressive disease.