Primary ciliary dyskinesia
Primary ciliary dyskinesia (PCD) is a rare disease that affects tiny hair-like structures on the walls of airways, ears and sinuses called cilia. Cilia move in a sweeping motion to remove mucus and bacteria to help prevent infections.
In people with PCD, the cilia do not move normally which leads to frequent chest, ear and sinus infections from birth and if diagnosed late, can develop into permanent lung damage and hearing loss.
We’re a multidisciplinary group of over 20 clinicians and researchers investigating how lung disease progresses in children and adults, and seeking ways to improve diagnosis and treatment of PCD. Our team includes doctors, nurses, physiotherapists, diagnostic scientists, imaging experts, epidemiologists, geneticists, microbiologists and physiologists.
Key investigator: Professor Jane Lucas
Southampton is a national centre for PCD, and we are using this key role to underpin long-term studies of children and adults with PCD to enable better understanding of disease progression, and investigating ways to improve health. Our research includes basic science, translational studies, clinical trials, epidemiology and qualitative methods.
- Chronic lung infection and persistence of bacterial biofilms are the main factors associated with deteriorating lung function in patients with PCD. We’re tackling this by researching approaches to prevent infection and disintegrate bacterial biofilms. For example we have shown that drugs that release nitrogen oxide (NO) improve antibiotic treatment of bacterial infections in PCD patients. We were the first group to describe the airway microbiome, identifying the bacteria typically found in the lungs of people with PCD.
- There were no good outcome measures to assess disease progression in clinical practice or clinical care. We developed and validated instruments to monitor children and adults with PCD, by assessing their symptoms and quality of life (QOL-PCD). We are leading an international study to investigate the normal fluctuations in lung function over time and to better understand deterioration in lung function (PROVALF-PCD).
- Because PCD is rare, international collaboration is essential to ensure sufficient patients for research. Southampton leads an international network of over 250 PCD researchers and clinicians, all seeking to improve the diagnosis and treatment of PCD (BEAT-PCD). We are investigating the long term course of PCD, including predictors of good clinical outcomes, contributing to international collaborations such as the iPCD cohort and European PCD Registry.
- PCD is difficult to diagnose and there is no ‘gold-standard’ test. Our group led the European Respiratory Society Task Force to develop evidence based guidelines for diagnosis in 2016. We have led a number of studies to improve the diagnosis of PCD. For example we led a multicentre validation of high-speed video analysis to diagnose PCD; we have demonstrated the potential of radioaerosol mucociliary clearance to diagnose ‘difficult cases’; we have demonstrated that reanalysing cilia having cultured them in an incubator helps differentiate PCD from other causes of ciliary abnormalities.
- Under-diagnosis of PCD is a major problem. We have demonstrated that late or missed diagnoses often occur because general physicians fail to recognise the symptoms of this rare disease. We have developed and validated a short questionnaire which can be used by physicians to know who to refer for testing (PICADAR). We have led a number of studies demonstrating the role of nasal nitric oxide analysers to identify patients who might have PCD.
- We have demonstrated that poor nutrition is associated with worse lung function in patients with PCD. We are now considering ways to improve nutrition, and improve clinical outcomes.
- In collaboration with other PCD groups we have identified the genes that cause PCD. We are now inviting patients to participate in the 100,000 Genome project, to identify new genes which may improve diagnosis and help develop new treatments. We are investigating the effect of genotype on patient outcomes.
- We have developed a number of models of the PCD airway which we are using to investigate the effects of drug treatments, environmental pollutants, or bacterial and viral infections.
- We are participating the first multicentre clinical trial for PCD, aiming to prevent respiratory exacerbations caused by infections (BESTCILIA). We are also participating in the first commercial study to investigate a treatment that might help patients with PCD (CLEAN-PCD).
- UHS is one of 4 nationally commissioned PCD centres in England and we collaborate closely with our partner centres. We are collating clinical and management data on all children with PCD in England in order establish the present management of our cohort. We then plan to collect longitudinal data across the English PCD cohort in order to better understand factors that influence important clinical outcome measures such as lung function and frequency of respiratory exacerbations.