Mini-Symposium: Primary Ciliary Dyskinesia
Management of primary ciliary dyskinesia: the lower airways

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Summary

Primary ciliary dyskinesia (PCD) is a genetic disease associated with defective ciliary structure and function. Chronic oto-sino-pulmonary infection is the most common clinical presentation. Patients should be monitored in centres with expertise in PCD. Regular respiratory monitoring consists of lung function tests, adapted to the patient’s age, and cough swab or sputum cultures. Chest X-rays are insensitive but the use of high-resolution computed tomography should be considered carefully to avoid excessive radiation. Treatment of the chronic suppuration of the lower airways relies on antibiotics to which the isolated bacteria are sensitive, together with respiratory physiotherapy and exercise to clear excessive bronchial secretions. Bronchodilators and anti-inflammatory agents have no proven benefit and should be prescribed, if at all, on an individual basis. Treatment of the lower airways should always be in conjunction with that of the upper airways. Importantly in PCD, respiratory disease may be controlled with the use of early, adequate and aggressive management.

Introduction

Ciliary dysfunction is implicated in a wide spectrum of diseases, including polycystic liver and kidney diseases, diseases of the central nervous system including retinopathy and hydrocephalus, and biliary atresia, but chronic infection of the upper and lower respiratory tract is the most common presentation.

Primary ciliary dyskinesia (PCD) is a genetic disease associated with defective ciliary structure and function and chronic oto-sino-pulmonary infection.1, 2, 3, 4 The triad of mirror image arrangement, bronchiectasis and sinusitis is known as Kartagener syndrome. The estimated prevalence is 1 in 15 000–30 000 live births, although this is likely to be an underestimate as underdiagnosis is common. Indeed, the diagnosis may be difficult because symptoms are not specific and the tests identifying the abnormal ciliary beat pattern, frequency and structure are available only in a few specialized centres.5

The respiratory manifestations of PCD are due to the absence or abnormal beating of the cilia of the epithelial cells, causing impaired mucociliary transport. Airways become infected and inflamed because of the abnormal retention of microorganisms and respiratory irritants. Pulmonary symptoms include excessive phlegm, cough and recurrent infections, which resemble those encountered in other chronic obstructive pulmonary diseases such as cystic fibrosis (CF). However, even though the respiratory management of PCD is often based on that of CF, this is not a safe strategy and differences exist with regard to the pathophysiology, prognosis and response to treatment.4 The genetic and pathophysiological defects in PCD and CF are different. Early and excessive airway inflammation appears to be an inherent part of CF, whereas it seems to be secondary to bacterial and viral infection in PCD. Also, there does not seem to be an inherent abnormal epithelial lining fluid in PCD, as observed in CF. Most importantly, the prognosis of the respiratory disease seems to be much more favourable in PCD with stabilization of the disease with early, adequate and aggressive management.4 Indeed, a longitudinal study in a cohort of patients with PCD indicated that lung function was significantly lower in the patients entering the cohort as adults compared to those entering as children.6 Also, during subsequent surveillance of the adult and paediatric patients for a median of 14 and 7 years, respectively, lung function remained stable in the majority of patients.

Respiratory management of patients with PCD is based on CF clinic practices. Patients should be monitored in (national, tertiary) centres with expertise in PCD. These centres should have a multidisciplinary team, including paediatric and adult respiratory and ENT specialists, physiotherapists, geneticists with expertise in PCD, (coordinating) nurses and psychologists. These reference centres should be able to organize balanced care with regional centres and the district hospital. In PCD, management is not evidence based. Regular respiratory monitoring, together with respiratory physiotherapy and exercise, and antibiotics active against the most commonly isolated bacteria, represent the cornerstones of the respiratory management. The treatment of upper airway disease is an integral part of the respiratory care of patients with PCD. This ENT management is described in detail elsewhere in this mini-symposium. This review is limited to standard care in the respiratory management, with new and emerging therapies described by Amirav and colleagues in this mini-symposium.

Section snippets

Respiratory monitoring

Regular respiratory monitoring is of paramount importance for patients with a chronic suppurative lung disease such as PCD. Lungs are normal and sterile at birth. The airways become infected and inflamed because of excessive secretions which accumulate in the airways due to impaired mucociliary transport. Regular cough swab cultures in young or non-expectorating children, or sputum cultures in productive patients, are recommended. Fibre-optic bronchoscopy may be indicated in non-expectorating

Antibiotics

The common infecting organisms in children are Haemophilus influenzae, Staphyloccocus aureus and Streptococcus pneumoniae.6, 9 Early therapeutic intervention results in better symptom control and slowing of deterioration in lung function. Whenever possible, antibiotics should be chosen on the basis of sputum or cough swab culture and sensitivity. Occasionally, fibre-optic bronchoscopy with bronchoalveolar lavage (BAL) or bronchial washing may be necessary to obtain adequate specimens in

Physiotherapy

Airway clearance by combinations of chest physiotherapy and physical exercise, together with antibiotics, is standard treatment for patients with PCD.16 The optimal moment to initiate physiotherapy, as well as the frequency and duration of the sessions, should be adapted to each patient. At least daily physiotherapy sessions are recommended during respiratory exacerbations and in productive patients, but in other patients the number of sessions per week may be reduced, particularly if the child

Adjunctive measures

Effective treatment of the lower airways is only feasible if it is associated with appropriate treatment of the upper airways, as described by Roger and colleagues in this mini-symposium.

PCD patients should receive all immunizations, including pneumococcal and yearly influenza A. Contact with infected individuals should be avoided. Within the same context, daycare attendance by young infants should be considered carefully on an individual basis. If the diagnosis is made in the first months of

Conclusion

Monitoring and treatment of the lower airways is not evidence based in PCD and derives largely from CF protocols. This aggressive therapeutic attitude has proven to be beneficial in maintaining a relative good and stable lung function in patients, particularly those diagnosed at an early stage of their disease, before the presence of irreversible lung damage. Antibiotics and chest physiotherapy are the cornerstones of the respiratory management, while waiting for new adjunct therapies such as

Practice points

  • Patients with PCD should be managed by a multidisciplinary team in specialized centres with expertise in PCD

  • Respiratory management consists of regular respiratory monitoring, airway clearance by means of chest physiotherapy and exercise, and early and aggressive antibiotic treatment of the upper and lower airways

  • Bronchodilators and anti-inflammatory agents have no proven benefit and may be prescribed on an individual basis

  • Patients should receive all childhood immunizations

Research directions

  • Role of respiratory viruses in symptoms, airway inflammation and lung disease

  • Benefit of anti-inflammatory agents such as azithromycin

  • Benefit of mucoactive agents

References (19)

There are more references available in the full text version of this article.

Cited by (16)

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    It is a rare autosomal recessive disorder presenting a triad of sinusitis, bronchicetasis and situs inversus with or without dextrocardia [2, 3]. Chronic ear, sinusitis and chronic respiratory infections as well as male infertility are the most common, but a congenital heart diseases could also be observed [3–6]. The proper diagnosis and treatment of pulmonary infection can prevent irreversible damage of the lungs [1, 4, 7].

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    However, there is no evidence that regular CT scans affect outcome in PCD5 and the potential lifetime cumulative radiation exposure should be considered.6 7 PCD guidelines suggest that lung function should be evaluated at every visit in cooperative children1 5 8 since it has been shown that the severity of structural abnormalities may correlate with impairment in forced expiratory volume in 1 s (FEV1).3 4 However, a decreased FEV1 is not indicative of the site of airway obstruction9 and, as in cystic fibrosis,10 there are preliminary suggestions that PCD is characterised by marked peripheral airway dysfunction.11

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