IN-PCD
Research type
Research Study
Full title
The Effects of Inhaled Corticosteroids on Inflammation and Infection in Primary Ciliary Dyskinesia
IRAS ID
256504
Contact name
Jane Davies
Contact email
Sponsor organisation
Imperial College London
Duration of Study in the UK
2 years, 1 months, 6 days
Research summary
Primary Ciliary Dyskinesia (PCD) is a rare multisystem condition, with lung and ear/nose/throat being the most significant. Patients experience frequent chest infections because the lungs do not clear mucus effectively. This leads to inflammation and lung scarring. PCD treatment guidelines are largely derived from more common lung diseases. However, building a PCD-specific evidence base is important to provide the best care for these patients.
Inhaled corticosteroids (ICS) are commonly prescribed to PCD patients but there are no studies to suggest that they are beneficial (or perhaps harmful). ICS are effective in treating asthma but in diseases similar to PCD, ICS can lead to increased infection risk.
Current guidelines suggest that ICS should be reserved for PCD patients who also have asthma. However, a study looking at markers of asthma in PCD patients found that there is no rational pattern to ICS prescription. As a result, the clinical team at the Royal Brompton are stopping ICS in some patients. In order to determine if this is helpful, we would like to compare PCD patients who are prescribed ICS with those who are not. We would also like to study the group of patients who are having their ICS stopped by their regular clinicians.
We aim to recruit all patients at the Royal Brompton Hospital aged from 6 years to adult patients who have transitioned to adult services within the last 12 months. We will look in-depth at their specific characteristics and examine markers of inflammation and infection in samples from the airway (e.g. phlegm, nose swabs and washings) and blood to determine the effects of ICS.
We will also look at how samples from the nose, compare with samples from the lungs (e.g. phlegm) in PCD, to help design future studies.
The funding for this study is from the senior investigator's research funds.Lay Summary of Results
The purpose of this study was to understand more about infection and inflammation in the nose and chest of patients with primary ciliary dyskinesia. During this study, participants kindly filled out questionnaires about their symptoms, gave various samples (including nose swabs and rinses, sputum and blood) and undertook different lung function tests. Consenting participants undertook this during their usual routine clinical visits.
In terms of infection, we found that when there was evidence of bacterial infection in the nose, there was a relatively low likelihood of finding the same bacterial infection in the chest (this is called a low positive predictive value in research terms). However, we found there was a higher likelihood of finding no evidence of infection in the chest when there was no infection detected in the nose (known as a high negative predictive value). This is relevant to our largely paediatric population because nose samples are relatively easy to obtain when compared to asking a child to cough up sputum from their chest. So, if we were able to predict chest infections from the nose samples alone, then that would help guide treatments like antibiotic choice in young children who aren’t able to cough up sputum yet. However, the results suggest that the nose samples do not reliably predict chest infections in children with primary ciliary dyskinesia.
We tested the nose, sputum and blood samples for 11 inflammatory markers in the research laboratory. We are currently completing complex analyses to compare these to the infection results as part of a doctorate thesis and we aim to present this at the British Thoracic Society Winter Meeting 2024. In the meantime, we are submitting a related work which reviews all the published studies looking at inflammation in primary ciliary dyskinesia to the Worldwide Bronchiectasis Conference in Summer 2024.
Unfortunately, whilst we had hoped to learn more about the impact of using inhaled steroids (steroid inhalers which are most commonly used to manage asthma) in primary ciliary dyskinesia - we found that because of changes in how patients attended clinic throughout the COVID-19 pandemic that the numbers were too limited to draw conclusions. This is due to our patient group being in the shielded population throughout the pandemic and largely switching to a remote clinic template (video conferencing rather than attendance at clinic).
Has the registry been updated to include summary results?: No
If yes - please enter the URL to summary results:
If no – why not?: N/A This observational study was not on a registry.
Did you follow your dissemination plan submitted in the IRAS application form (Q A51)?: Pending
If yes, describe or provide URLs to disseminated materials:
If pending, date when dissemination is expected: 27/11/2024
If no, explain why you didn't follow it:
Have participants been informed of the results of the study?: Yes
If yes, describe and/or provide URLs to materials shared and how they were shared: Participants were updated with a lay summary via email to update them about results and upcoming plans to dIsseminate results at conference. Additionally, I have also had the opportunity to meet with many participants at their subsequent routine clinical reviews and to discuss the project and results. Our patient group has a genuine enthusiasm for research and it has been a pleasure getting to know many of the families better throughout the study visits.Correspondance to participants:
"Hello from the INPCD study team,
We wanted to get in touch with a brief update for all those who kindly gave their time to contribute to the INPCD research study at the Royal Brompton which was open between 2019-2022.
The purpose of this study was to understand more about infection and inflammation in the nose and chest. During this study, participants kindly filled out questionnaires about their symptoms, gave various samples (you may recall the nose sponges!) and undertook different lung function tests during their usual clinical visits.
In terms of infection, we found that when there was evidence of bacterial infection in the nose, there was a relatively low likelihood of finding the same bacterial infection in the chest (this is called a low positive predictive value in research terms). However, we found there was a higher likelihood of finding no evidence of infection in the chest when there was no infection detected in the nose.
We tested the nose, sputum and blood samples for 11 inflammatory markers in the research laboratory. We are currently completing complex analyses to compare these to the infection results and we aim to present this at the British Thoracic Society Winter Meeting. In the meantime, we are submitting a related work which reviews all of the published studies looking at inflammation in primary ciliary dyskinesia to the Worldwide Bronchiectasis Conference in Summer.
Unfortunately, whilst we had hoped to learn more about the impact of using inhaled steroids - we found that because of changes in how patients attended clinic throughout the COVID-19 pandemic that the numbers were too limited to draw conclusions.
Thank you so much for your time and contributions. We plan to update you with any further publications or presentations that stem from this work in the future."
Our results will form the basis of an MD(res) thesis due in February 2025 with Imperial College and we aim to submit for peer reviewed publication prior to submission for presentation at the British Thoracic Society Winter meeting 2024.
If pending, date when feedback is expected:
If no, explain why they haven't:
Have you enabled sharing of study data with others?: Yes
If yes, describe or provide URLs to how it has been shared: I have presented and discussed results at various clinical and research meetings including the Royal Brompton research team, the cystic fibrosis and chronic lung infection team and the primary ciliary dyskinesia research team meetings.
If no, explain why sharing hasn't been enabled:
Have you enabled sharing of tissue samples and associated data with others?: No
If yes, describe or provide a URL:
If no, explain why: We were able to complete the planned testing within our own team laboratories - within our Imperial College campus and Royal Brompton Hospital Laboratories. Therefore, no additional sharing of tissues was required.REC name
London - Stanmore Research Ethics Committee
REC reference
19/LO/1444
Date of REC Opinion
24 Sep 2019
REC opinion
Favourable Opinion