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Primary Ciliary Dyskinesia and Cystic FibrosisPrimary Ciliary Dyskinesia and Cystic Fibrosis: Different Diseases Require Different Treatment FREE TO VIEW

Jane S. Lucas, BM, PhD; Mary Carroll, MD
Author and Funding Information

From the Southampton Primary Ciliary Dyskinesia and Cystic Fibrosis Centers, National Institute for Health Research Southampton Respiratory Biomedical Research Unit, University of Southampton and University Hospital Southampton, National Health Service Foundation Trust.

Correspondence to: Jane S. Lucas, BM, PhD, University Hospital Southampton Foundation Trust, Tremona Rd, Mailpoint 803, Southampton, SO16 6YD, England; e-mail: jlucas1@soton.ac.uk


Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2014;145(4):674-676. doi:10.1378/chest.13-2590
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Orphan diseases are often managed according to evidence from similar, more common conditions. This should be avoided, since differences in pathophysiology, morbidity, and prognosis will likely lead to problems of treatment failure and lack of adherence. The prevalence of primary ciliary dyskinesia (PCD)1 is approximately one-fourth that of cystic fibrosis (CF) (one in 10,000 and one in 2,500, respectively), and it is, therefore, not particularly rare. Despite recent advances in PCD research and clinical infrastructure,2 there have been no randomized controlled trials, and current management guidelines are mostly limited to expert consensus extrapolated from evidence from CF.3

The article by Cohen-Cymberknoh et al4 in this issue of CHEST (see page 738) highlights that PCD is clinically distinct not only from CF with pancreatic insufficiency (CF-PI) but also from CF with pancreatic sufficiency (CF-PS). This observational study of the three patient groups attending a single specialist center additionally dispels any myths that PCD is a mild disease.

Similarly to CF-PS, diagnosis of PCD is often delayed, with consequent impact on onset of treatment.4,5 The assumption that CF-PS and PCD are milder diseases than CF-PI has falsely reassured us that these patient groups will do reasonably well despite delay in starting appropriate treatment. The findings of Cohen-Cymberknoh et al4 add to the evidence that some patients with PCD have significant morbidity.6,7 The authors unexpectedly found that patients with PCD had substantially lower BMIs than patients with CF-PS or CF-PI (BMI percentiles: PCD, 21; CF-PI, 42; CF-PS, 49). Contrary to patients with CF, their patients with PCD did not receive dietetic input, but care was otherwise similar. From this observational study it is unclear whether the discrepancy in BMI really demonstrates worse nutritional status in patients with PCD than CF, but at face value the data appear clinically relevant and raise an issue that requires further evaluation. Similarly, the data relating to lung function in PCD and CF-PS raises concern for lung disease in these patient groups. Although the cross-sectional data suggest that lung function (FEV1) declines with age most rapidly in patients with CF-PI,4 a significant proportion of teenagers and young adults with PCD and CF-PS had clinically relevant low FEV1. It is worth noting that this study provides further support, that FEV1 correlates well with high-resolution CT imaging evidence of disease severity in CF, but not in PCD, bringing into question the options for regular monitoring of disease progression in this patient group.

The radiologic distribution of lung disease in patients with PCD (predominantly middle and lower lobes) and CF (upper lobes)4,8 highlights differences in underlying cause of lung damage and, therefore, the need to consider different treatment options in the two diseases. Differences in lower airway pathogens and chronic colonization between PCD and CF are likely to reflect impaired mucociliary clearance, a primary defect in PCD and a secondary defect in CF, together with differences between altered mucus properties, inflammatory status, and innate immune responses. As previously described in CF, Cohen-Cymberknoh et al4 found chronic infection with Pseudomonas aeruginosa correlates with declining FEV1 in CF. However, they found no correlation with PCD lung disease. This is in contrast to a recent study using molecular techniques to characterize the microbiome of the airways in PCD.9 Using 16S rRNA quantitative polymerase chain reaction and pyrosequencing to determine bacterial load and composition, P aeruginosa was found to correlate positively with patient age and negatively with FEV1 percent predicted.9

In addition to comparisons of pulmonary disease and nutrition between PCD, CF-PS, and CF-PI highlighted by Cohen-Cymberknoh et al,4 other characteristics require consideration.1 Sinus disease is common in both CF and PCD, but nasal polyps are a feature of CF. Unremitting rhinitis from birth is suggestive of PCD, as is persistent or recurrent serous otitis media (glue ear).1 The underlying causes of ear, nose, and throat disease in CF and PCD differ and require management by specialists with experience of the idiosyncrasies of each disease. Although male patients with CF and PCD are usually infertile, the underlying cause and the treatment options are different. Men with CF have congenital absence of the vas deferens, whereas male infertility in PCD is generally caused by immotile sperm due to the homologous ultrastructure of sperm flagella and respiratory cilia. Assisted fertility, therefore, requires different approaches. In CF, sperm needs to be aspirated from the epididymis. Intracytoplasmic sperm injection is then often used because the sperm retrieval procedure does not achieve sufficient sperm for conventional insemination. In PCD, immotile sperm from the ejaculate are injected directly into ova by intracytoplasmic sperm injection to overcome motility issues.

Approximately one-half of patients with PCD have situs inversus due to immotile cilia on the embryonic node leading to random laterality of organs. A smaller proportion of patients with PCD (6%) have complex laterality defects, including complex congenital heart disease, polysplenia, and saddle liver.10

In summary, most doctors have little experience of rarer causes of bronchiectasis such as PCD, and management is based on evidence from CF. Indeed, the evidence base for managing PCD is poor, with no clinical trials in PCD. This is clearly inappropriate, as demonstrated by the data presented by Cohen-Cymberknoh et al4; PCD is clinically distinct from CF-PI and CF-PS and is likely to benefit from different treatment strategies. Substantial advances have been made in CF management in recent decades, resulting in improved morbidity and mortality. These advances have been beneficial to the care of patients with PCD, but we now require clinical standards and evidence-based guidelines individualized for PCD.

References

Lucas JS, Walker WT, Kuehni CE, et al;. Primary ciliary dyskinesia.. In:Courdier J-F., ed. Orphan Lung Diseases. European Respiratory Monograph. Sheffield, England; European Respiratory Society; 2011:201-217.
 
Lucas JS, Chetcuti P, Copeland F, et al. Overcoming challenges in the management of primary ciliary dyskinesia: the UK model [published online ahead of print June 11, 2013]. Paediatr Respir Rev. doi:10.1016/j.prrv.2013.04.007.
 
Barbato A, Frischer T, Kuehni CE, et al. Primary ciliary dyskinesia: a consensus statement on diagnostic and treatment approaches in children. Eur Respir J. 2009;34(6):1264-1276. [CrossRef]
 
Cohen-Cymberknoh M, Simanovsky N, Hiller N, Gileles Hillel A, Shoseyov D, Kerem E. Differences in disease expression between primary ciliary dyskinesia and cystic fibrosis with and without pancreatic insufficiency. Chest. 2014;145(4):738-744.
 
Kuehni CE, Frischer T, Strippoli MP, et al; ERS Task Force on Primary Ciliary Dyskinesia in Children. Factors influencing age at diagnosis of primary ciliary dyskinesia in European children. Eur Respir J. 2010;36(6):1248-1258. [CrossRef]
 
Marthin JK, Petersen N, Skovgaard LT, Nielsen KG. Lung function in patients with primary ciliary dyskinesia: a cross-sectional and 3-decade longitudinal study. Am J Respir Crit Care Med. 2010;181(11):1262-1268. [CrossRef]
 
Noone PG, Leigh MW, Sannuti A, et al. Primary ciliary dyskinesia: diagnostic and phenotypic features. Am J Respir Crit Care Med. 2004;169(4):459-467. [CrossRef]
 
Jain K, Padley SP, Goldstraw EJ, 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;62(10):986-993. [CrossRef]
 
Rogers GB, Carroll MP, Zain NM, et al. Complexity, temporal stability, and clinical correlates of airway bacterial community composition in primary ciliary dyskinesia. J Clin Microbiol. 2013;51(12):4029-4035. [CrossRef]
 
Kennedy MP, Omran H, Leigh MW, et al. Congenital heart disease and other heterotaxic defects in a large cohort of patients with primary ciliary dyskinesia. Circulation. 2007;115(22):2814-2821. [CrossRef]
 

Figures

Tables

References

Lucas JS, Walker WT, Kuehni CE, et al;. Primary ciliary dyskinesia.. In:Courdier J-F., ed. Orphan Lung Diseases. European Respiratory Monograph. Sheffield, England; European Respiratory Society; 2011:201-217.
 
Lucas JS, Chetcuti P, Copeland F, et al. Overcoming challenges in the management of primary ciliary dyskinesia: the UK model [published online ahead of print June 11, 2013]. Paediatr Respir Rev. doi:10.1016/j.prrv.2013.04.007.
 
Barbato A, Frischer T, Kuehni CE, et al. Primary ciliary dyskinesia: a consensus statement on diagnostic and treatment approaches in children. Eur Respir J. 2009;34(6):1264-1276. [CrossRef]
 
Cohen-Cymberknoh M, Simanovsky N, Hiller N, Gileles Hillel A, Shoseyov D, Kerem E. Differences in disease expression between primary ciliary dyskinesia and cystic fibrosis with and without pancreatic insufficiency. Chest. 2014;145(4):738-744.
 
Kuehni CE, Frischer T, Strippoli MP, et al; ERS Task Force on Primary Ciliary Dyskinesia in Children. Factors influencing age at diagnosis of primary ciliary dyskinesia in European children. Eur Respir J. 2010;36(6):1248-1258. [CrossRef]
 
Marthin JK, Petersen N, Skovgaard LT, Nielsen KG. Lung function in patients with primary ciliary dyskinesia: a cross-sectional and 3-decade longitudinal study. Am J Respir Crit Care Med. 2010;181(11):1262-1268. [CrossRef]
 
Noone PG, Leigh MW, Sannuti A, et al. Primary ciliary dyskinesia: diagnostic and phenotypic features. Am J Respir Crit Care Med. 2004;169(4):459-467. [CrossRef]
 
Jain K, Padley SP, Goldstraw EJ, 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;62(10):986-993. [CrossRef]
 
Rogers GB, Carroll MP, Zain NM, et al. Complexity, temporal stability, and clinical correlates of airway bacterial community composition in primary ciliary dyskinesia. J Clin Microbiol. 2013;51(12):4029-4035. [CrossRef]
 
Kennedy MP, Omran H, Leigh MW, et al. Congenital heart disease and other heterotaxic defects in a large cohort of patients with primary ciliary dyskinesia. Circulation. 2007;115(22):2814-2821. [CrossRef]
 
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