Editorials

Primary Ciliary Dyskinesia and Cystic Fibrosis: Different Diseases Require Different Treatment

Cystic fibrosis (CF) and Primary ciliary dyskinesia (PCD) are both rare chronic diseases, inherited disorders associated with multiple complications, namely respiratory complications, due to impaired mucociliary clearance that affect severely patients’ lives. Although both are classified as rare diseases, PCD has a much lower prevalence than CF, particularly among Caucasians. As a result, CF is well studied, better recognized by clinicians, and with some therapeutic approaches already available. Whereas PCD is still largely unknown, and thus the approach is based on consensus guidelines, expert opinion, and extrapolation from the larger evidence base available for patients with CF. Both diseases have some clinical similarities but are very different, necessitating different treatment by specialists who are familiar with the complexities of each disease.This review aims to provide an overview of the knowledge about the two diseases with a focus on the similarities and differences between both in terms of disease mechanisms, common clinical manifestations, genetics and the most relevant therapeutic options. We hoped to raise clinical awareness about PCD, what it is, how it differs from CF, and how much information is still lacking. Furthermore, this review emphasises the fact that both diseases require ongoing research to find better treatments and, in particular for PCD, to fill the medical and scientific gaps.

Primary ciliary dyskinesia is a genetically and clinically heterogeneous syndrome. Impaired function of motile cilia causes failure of mucociliary clearance. Patients typically present with neonatal respiratory distress of unknown cause and then continue to have a daily wet cough, recurrent chest infections, perennial rhinosinusitis, otitis media with effusion, and bronchiectasis. Approximately 50% of patients have situs inversus, and infertility is common. While understanding of the underlying genetics and disease mechanisms have substantially advanced in recent years, there remains a paucity of evidence for treatment. Next-generation sequencing has increased gene discovery, and mutations in more than 40 genes have been reported to cause primary ciliary dyskinesia, with many other genes likely to be discovered. Increased knowledge of cilia genes is challenging perceptions of the clinical phenotype, as some genes reported in the last 5 years are associated with mild respiratory disease. Developments in genomics and molecular medicine are rapidly improving diagnosis, and a genetic cause can be identified in approximately 70% of patients known to have primary ciliary dyskinesia. Groups are now investigating novel and personalised treatments, although gene therapies are unlikely to be available in the near future.

Primary ciliary dyskinesia (PCD), also known as immotile-cilia syndrome, is a rare genetic disease that is inherited in an autosomal recessive manner. Several studies have explored certain aspects of PCD in the Arab world, yet much is still lacking in terms of identifying the different characteristics of this disease. In this paper, we aim to briefly cover those studies published about PCD in Arab countries, as well as to provide recommendations and guidelines for future studies.

Peak oxygen uptake (VO_2peak) is associated with morbidity and mortality in health and disease, and provides important information of global physical health not achieved from standard pulmonary function tests. Primary ciliary dyskinesia (PCD) and cystic fibrosis (CF) are genetically determined diseases involving different basic defects, but both showing impaired mucociliary clearance leading to chronic infections and pulmonary destruction early in life. PCD is generally considered a milder disease than CF and it is hypothesized that children with CF would have consistently lower VO_2peak and pulmonary function than children with PCD.

We performed a prospective, observational single-center, clinical cohort study of VO_2peak and pulmonary function in age and gender matched schoolchildren, at two occasions 12 months apart.

VO_2peak was persistently (at baseline and after 12 months) and significantly reduced in the 22 patients with PCD (z-score = −0.89 and −1.0) and 24 with CF (z-score = −0.94 and −1.1), included in the study. Abnormal VO_2peak was detected in a larger proportion of children with PCD (≈30%) than CF (≈13%). Moreover, children with PCD exhibited persistently lower FEV₁ (p < 0.0001 at first visit and p = 0.001 at second visit) while FEF_25–75 and FVC differed only at baseline. Indeed, a retrospective analysis comparing lung function over the last year in our entire PCD and CF populations between 6 and 18 years of age, revealed lower values in patients with PCD (FEV₁ z-score, p = 0.0004, FVC z-score p < 0.0001, FEF_25–75 z-score p = 0.008).

This is the first report indicating that cardiopulmonary fitness is equally and consistently reduced in both children with PCD and CF along with a consistent lower pulmonary function in PCD compared with CF. A certain reservation for possible selection bias and the small number of patients is necessary. However, increased focus on early diagnosis, evidence-based treatment regimens and close clinical monitoring in PCD are warranted.

Primary Ciliary Dyskinesia (PCD) is a rare inherited disease with impaired mucociliary clearance. Airway clearance techniques (ACTs) are commonly recommended for patients with PCD to facilitate mucus clearance, despite a lack of evidence in this group. Current physiotherapy practice in PCD is based on evidence extrapolated from the field of Cystic Fibrosis (CF). This paper focuses on the available evidence and outlines challenges in extrapolating evidence between the conditions for best clinical practice.

Primary ciliary dyskinesia is an autosomal recessive genetic disorder leading to structural and/or functional abnormalities of motor cilia. Impaired mucociliary clearance is responsible for the development of a multi-organ disease, which particularly affects the upper and lower airways.

In adults, primary ciliary dyskinesia is mainly characterized by bronchiectasis and chronic ear and sinus disorders. Situs inversus is found in half of patients and fertility disorders are commonly associated. Diagnosis is based on specialized tests: reduced level of nasal nitric oxide concentrations is suggestive of primary ciliary dyskinesia, but only a nasal or bronchial biopsy/brushing with analysis of beat pattern by videomicroscopy and/or analysis of cilia morphology by electronic microscopy can confirm the diagnosis. However, the diagnosis is difficult to achieve due to the limited access to these specialized tests and to difficulties in interpreting them. Genetic tests are under development and may provide new diagnostic tools. Treatment is symptomatic, based on airway clearance techniques (e.g., physiotherapy) and systemic and/or inhaled antibiotics. Prognosis is related to the severity of the respiratory impairment, which can be moderate or severe.

Diagnosis and management of primary ciliary dyskinesia remain poorly defined and should be supported by specialized centers to standardize the diagnosis, improve the treatment and promote research.

La dyskinésie ciliaire primitive est une maladie génétique autosomique récessive, à l’origine d’anomalies structurales et fonctionnelles des cils moteurs. Les altérations de la clairance mucociliaire sont responsables d’une atteinte multi-organes prédominant sur les voies aériennes supérieures et inférieures.

L’atteinte clinique est marquée chez l’adulte par des dilatations des bronches et une atteinte oto-sinusienne chronique. Un situs inversus est présent dans la moitié des cas et les troubles de la fertilité sont fréquents. Le diagnostic repose sur des tests spécialisés : un effondrement du monoxyde d’azote nasal est évocateur mais seuls un prélèvement de l’épithélium nasal ou bronchique pour une étude du battement ciliaire et une analyse en microscopie électronique permettent un diagnostic de certitude. Des tests génétiques sont en développement et pourraient favoriser le diagnostic dans les prochaines années. Le traitement est symptomatique, fondé sur la kinésithérapie respiratoire et l’antibiothérapie par voie systémique et/ou inhalée. Le pronostic est lié à l’atteinte respiratoire qui peut être modérée ou sévère.

La prise en charge de la dyskinésie ciliaire primitive reste mal codifiée et doit s’appuyer sur des centres spécialisés afin d’améliorer le diagnostic et les traitements, et de promouvoir la recherche.