Mini-Symposium: Primary Ciliary DyskinesiaManagement of primary ciliary dyskinesia: the lower airways
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)
- et al.
Primary ciliary dyskinesia in the paediatric population: range and severity of radiological findings in a cohort of patients receiving tertiary care
Clin Radiol
(2007) - et al.
Long-term use of nebulized human recombinant DNase1 in two siblings with primary ciliary dyskinesia
Respir Med
(2007) - et al.
Primary ciliary dyskinesia: diagnosis and standards of care
Eur Respir J
(1998) - et al.
Primary ciliary dyskinesia (PCD)
Pediatr Pulmonol
(2000) - et al.
Primary ciliary dyskinesia: current state of the art
Arch Dis Child
(2007) Primary ciliary dyskinesia
Semin Respir Crit Care Med
(2003)- et al.
Diagnosing primary ciliary dyskinesia
Thorax
(2007) - et al.
Longitudinal study of lung function in a cohort of primary ciliary dyskinesia
Eur Respir J
(1997) - et al.
High-resolution CT of patients with primary ciliary dyskinesia
AJR Am J Roentgenol
(2007)
Cited by (16)
Cyanotic Episodes in an Infant With Known Situs Inversus: Indications for an Apparent Life-Threatening Event Evaluation
2012, Journal of Pediatric Health CareCitation Excerpt :Situs inversus also can be associated with other defects of laterality. When bronchiectasis, situs abnormalities, and sinusitis occur together, it is commonly referred to as Kartagener syndrome (Fauroux, Tamalet, & Clement, 2009). New research in cilia function and laterality defects has demonstrated strong associations with congenital heart defects, hydrocephalus, retinitis pigmentosa, and kidney abnormalities.
Kartagener's syndrome - Anaesthetic considerations for ENT surgery
2012, Otolaryngologia PolskaCitation Excerpt :Patients with combined bronchospastic and coronary artery diseases might benefit from the administration of alpha-2 adrenergic agonists [14]. Because the lack of effective pain relief as well as drowsiness and respiratory depression associated with the use of long-acting systemic opioids may result in diminished chest expansion and ineffective cough, leading to basal atelectasis, hypoxaemia and nosocomial infection, use of short-acting opioid during general anesthesia and adequate postoperative pain management is very important [1, 5, 7]. When we have dextrocardia with situs inversus the heart is mostly normal.
Primary ciliary dyskinesia revisited: Based on three clinical reports
2010, Revista Portuguesa de PneumologiaEvaluation of pulmonary disease using static lung volumes in primary ciliary dyskinesia
2012, ThoraxCitation Excerpt :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