Nebulised HS in children with NMD and CP

• Research type

  Research Study

• Full title

  A Chart Review assessing the effects of Nebulised Hypertonic Saline on Respiratory-related complication in children with Neuromuscular disease and Cerebral Palsy

• IRAS ID

  243535

• Contact name

  Hui-Leng Tan

• Contact email

  h.tan@rbht.nhs.uk

• Sponsor organisation

  Imperial College London

• Duration of Study in the UK

  0 years, 6 months, 0 days

• Research summary

  Chart review of children with Neuromuscular disease or Cerebral Palsy who are cared for in the Royal Brompton Hospital and that have been treated with nebulised hypertonic saline for at least 12 months. Charts that meet criteria will be reviewed until May 2018. \n\nStudy duration: 6 months.\n\nInclusion criteria: Children with Neuromuscular disease or Cerebral Palsy who have their care at the Royal Brompton Hospital and are on treatment with nebulised Hypertonic Saline for at least 12 months.\n\nExclusion criteria: Children also diagnosed with Cystic Fibrosis. \n\nTo further complement data from hospital records, two questionnaires will be applied. Parents of children who meet criteria will be asked to complete the following questionnaires: 1) The National Health and Nutrition Examination Survey (NHANES) for Hospitalisation and access to are – HUQ.010; and 2) Questionnaire on Hypertonic Saline treatment. Children from 10 – 18 years will be asked to complete the Questionnaire on Hypertonic Saline treatment.\n\nAims:\n1) Explore whether treatment with nebulised Hypertonic Saline in children with Neuromuscular disease or Cerebral Palsy decreases respiratory-related complications.\n2) Evaluate whether the treatment with nebulised hypertonic saline in children with neuromuscular disease or cerebral palsy improves the ease of airway clearance. \n3) Explore how parents of children with Neuromuscular disease and children with Cerebral Palsy perceive the treatment with nebulised hypertonic saline compared with previous management. \n

  Lay Summary of Results:

  1) What was this study about?
  Children with neuromuscular disease (conditions that affect the muscles and the nerves controlling them, such as muscular dystrophy or spinal muscular atrophy) and cerebral palsy (a condition affecting movement and posture caused by brain injury in early life) often struggle with chest problems. Their weak muscles make it hard to cough effectively, which means mucus builds up in their airways, leading to chest infections, hospital admissions, and in some cases, early death.
  Hypertonic saline is a salty water solution (either 3%, 5%, 6% or 7% salt, compared to the 0.9% in normal body fluids). When breathed in as a fine mist using a nebuliser (a machine that turns liquid medicine into a mist), it is thought to help thin and loosen mucus, making it easier to cough up and clear from the airways.
  This treatment is well established for cystic fibrosis (CF) — a genetic condition that causes thick, sticky mucus in the lungs — but until this study, there was no evidence about whether it worked in children with neuromuscular disease or cerebral palsy.

  How was the study carried out?
  Children and young people with neurodisability aged 1 to 18 years who had been prescribed nebulised saline (at concentrations of 0.9%, 3%, 6%, and/or 7%) for use daily or as needed for at least 12 months, between 2011 and 2019, were included in the review. These children had been prescribed nebulised saline because they had thick, sticky secretions and recurrent chest infections. The study was carried out at Royal Brompton Hospital in London. Medical records were reviewed to compare what happened to each child in the year before they started the treatment versus the year after. Parents and, where possible, the children themselves also completed questionnaires about how they found the treatment and whether clearing mucus felt easier.

  2) What did the study find?
  - Fewer hospital admissions: Starting nebulised saline was associated with a fall in the number of hospitalisations per year. Before treatment, the typical (median) number of hospital admissions per year was 1; after starting treatment, this fell to 0. This result was statistically significant (p=0.001), meaning it is very unlikely to be due to chance. Even after accounting for factors such as age, sex, use of home breathing support, and whether children were on regular antibiotics, the association remained strong.
  - Fewer courses of antibiotics: Starting nebulised saline was associated with a marked reduction in the total number of courses of antibiotics given for chest infections per year. Before treatment, the typical (median) number of antibiotic courses per year was 4; after starting treatment, this fell to 1. This was a statistically significant result (95% CI −4.0 to −1.5; p < 0.001).
  The overall finding held firm even after the researchers accounted for other factors that might have influenced results, such as age, sex, and whether children were already on regular antibiotics for preventive reasons.
  - Ease of clearing the airways: Children and parents reported that clearing mucus from the airways felt easier after starting treatment. This was measured using a simple pictorial scale, and the improvement was also statistically meaningful.
  - Lung function testing: A small number of children who were able to cooperate with formal lung function testing had measurements of breathing capacity (forced vital capacity, or FVC — and forced expiratory volume in one second, or FEV1) before and after treatment. There was no significant change in these measurements over time.
  - What patients and families thought: The prescription of nebulised saline in children and young people with neurodisability was associated with improved respiratory outcomes and was favourably received by patients and their caregivers.

  3) Were there any limitations?
  This was an exploratory study — meaning it was designed to gather initial evidence and inform future research, rather than to prove that the treatment definitely works. It was a chart review (looking back at existing medical records) rather than a randomised controlled trial (where children are randomly assigned to receive either the treatment or a dummy treatment for comparison). Because of this design, it is possible that some of the improvement seen could be explained by other changes happening at the same time or by the fact that children who were already doing better were more likely to continue on the treatment.
  Most patients used combinations of treatments with different concentrations of saline, so it was not possible to determine whether one concentration worked better than another.

  4) What does this mean for the future?
  This study provides data that will serve for future power calculations — that is, it helps researchers work out how large a future trial would need to be to reliably test the treatment. A randomised controlled trial of nebulised saline in children and young people with neuromuscular disorder is now needed to confirm benefit, determine the optimum treatment regimens, and understand how the treatment works. Such a trial is now underway.

  Summary: This study found promising early evidence that nebulised saline may reduce hospital admissions and the need for antibiotics in children with neuromuscular disease and cerebral palsy and that it was well tolerated and viewed positively by families. A larger, properly controlled trial is now needed to confirm these findings.
  Has the registry been updated to include summary results?: Yes
  If yes - please enter the URL to summary results: https://gbr01.safelinks.protection.outlook.com/?url=https%3A%2F%2Ftrack.pstmrk.it%2F3ts%2Fclinicaltrials.gov%252Fstudy%252FNCT03623698%253Ftab%253Dresults%2526a%253D2%2FNBTI%2FnObFAQ%2FAQ%2Ffacd1bde-d665-43dc-8d64-741b3c883b48%2F3%2F1KIZ1hU7eZ&data=05%7C02%7Cleedswest.rec%40hra.nhs.uk%7Cc1ef5a91b1574c80c75008dec55b8362%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C639165194020683577%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=k1ugNZBE3%2BbZF7%2F3meopqPJEhfebwgfTQwcQvGd4q4k%3D&reserved=0
  If no – why not?:
  Did you follow your dissemination plan submitted in the IRAS application form (Q A51)?: Yes
  If yes, describe or provide URLs to disseminated materials: doi: 10.1183/13993003.01407-2020
  If pending, date when dissemination is expected:
  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: Results were shared verbally on a one-to-one basis
  If pending, date when feedback is expected:
  If no, explain why they haven't:
  Have you enabled sharing of study data with others?: No
  If yes, describe or provide URLs to how it has been shared:
  If no, explain why sharing hasn't been enabled: The study has been completed, and the findings have been published in a peer-reviewed journal (European Respiratory Journal, 2021; DOI: 10.1183/13993003.01407-2020), where the results are freely accessible in the public domain via open access. Formal data sharing infrastructure has not been enabled on ClinicalTrials.gov; however, the underlying anonymised dataset is available to researchers upon reasonable request to the corresponding author (Dr Hui-Leng Tan, Imperial College London). This approach ensures that participant confidentiality and data protection obligations are maintained in accordance with the Data Protection Act, while still enabling access for legitimate research purposes. There are no plans to restrict data sharing, and any reasonable request from interested researchers or communities will be considered.

  Have you enabled sharing of tissue samples and associated data with others?: No
  If yes, describe or provide a URL:
  If no, explain why: There were no tissue samples in the study
  Captcha: 0cAFcWeA7xDbWIOEWRjkX1oIMrR7Rxegvmnm4Nt4XeZgNQA8cqJ53ZssJNiZip1W2kZ1hiKjS0cZw5RMZuFMARVrD75kQi2Xgb-wwaCewTtazCrF0nR4MvwhuLlblx-pMHvdIrAlRXJUuB06Ovv1MI11-wbYv8BFp_TbCNxrZZnrROaJAwB8DmRBFehahDeDY_guf0DB0ers_71NONefVj4KgF4CK1EpvuSjma_jggLjjsVysvBcARtdJM5dTDC6AR4dHbEv-m27L9afttev_dRqA1DdNGwcF_Hw0Hzes50eKYiVXgFQkNOTkwODmOGUICmUuecYBPEI6MavUkGbI0M8ok-QqJsBpCv2KphhUpMV5bEuEcWV3KVoNrw6CMM-VT5_idrv4vcg5rj5RCJzpKVqUk636S9e8wGUp61IPx_RJZcDk7dCPNrJiljeIa1SECmUat4wkzUBvqAcNT5X5MChlAzV_oApOAir3pLR8Fueb-n2hbcSfh3P1jNZIUMHXuwRipS6F6zKw7rjM70CdzfvGmRqevnRpU51rJiDd5Y_qtEVcHHcNH1LIR5PRM_x2g5vkY_UEKIxagGyiAWSn-LtiQDrLlGQ5PTIWmQoLYzebofcOD64z6ZhgaZv0z5U89G78I5bte8HKiMy0eNY7wveHC0SNHBAwQ5bMwXlcGtt-Wu_rC3-lgpIaHhJRcq2BWuDDDjBSsVjcSo_v4GC9OaTE9v0yzqUgZBLYn_nPEP1Mp3tijcsMfflDJA6o-qNrmicsGNaIZ9oLshqivB8i8T2p1rkR6SP3G7c86Mxarxmf-FWeSF9ZviSaEH5DLECPoOgwm-f15SlPER_LtNjKrnNkjdSvnq0BDwxK4eg9gFMXyBwgtfqvU4fEMtWw3arQrBsTd7mTB9G89w5eNb5ajIwPoNp_2ZwdklmsfWzkNDuewsaIzzEgRCMcuPtnzgPA7Y8S5mdqm-jKoi1Gm47G9OtyAQetKC41Hy4gmD2TUOjtvgZ_chz9T4tIuOrKIhI6XyuJfA2YtNpPSzqWV07OBKKSBAv_ojVIqjyIQlJZE3jGxij3qfM0FDCN0Ke1hR8aVecnD2aFdp8qRtb68t6dANf-OeJSlIMQ7KB0DzVKk5FZea8lrE5P9npSgso1g_DtED2POuusNExPd

• REC name

  Yorkshire & The Humber - Leeds West Research Ethics Committee

• REC reference

  18/YH/0103

• Date of REC Opinion

  1 Jun 2018

• REC opinion

  Further Information Favourable Opinion