A Chart Review Assessing the Effects of Nebulised Hypertonic Saline on Respiratory-related Complications in Children and Young People With Neuromuscular Disease and Cerebral Palsy
Conditions: Neuromuscular Diseases
Sponsor: Imperial College London

Joint Research  
Compliance Office 
 
SOP Ref: JRCO/SOP/012  
V8.0 25 Oct 2017 
 
Page 1 of 20 
© Imperial College of Science, Technology and Medicine   
 
 
 
 
 
 
Nebulised HS in children and young people 
with NMD or CP 
 
 
 
 
A Chart Review assessing the effect of Nebulised Hypertonic Saline on 
Respiratory-related complications in children and young people with 
Neuromuscular Disease or Cerebral Palsy 
 
 
 
 
 
Version 2, 04/04/2018 
 
 
 
 
 
 
 
 
 
 
 
FUNDERS: This section does not apply 
 
IRAS Project ID: 243535 
REC reference: 18/YH/0103 
 
 
 
Protocol authorised by: 
 
Name & Role 
Date 
Signature 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Joint Research  
Compliance Office 
 
SOP Ref: JRCO/SOP/012  
V8.0 25 Oct 2017 
 
Page 2 of 20 
© Imperial College of Science, Technology and Medicine   
 
 
 
Study Management Group 
 
Chief Investigator: Hui-Leng Tan     
 
Co-investigators: Natalia Galaz Souza     
 
Statistician: Mark Rosenthal     
 
Study Management:       
 
Clinical Queries 
 
Clinical queries should be directed to Dr. Hui-Leng Tan who will direct the query to the appropriate 
person. 
 
 
Sponsor 
 
Imperial College London is the main research Sponsor for this study.  For further information 
regarding the sponsorship conditions, please contact the Head of Regulatory Compliance at: 
 
 
 
Joint Research Compliance Office 
Imperial College London  
Room 215, Level 2, Medical School Building 
Norfolk Place 
London, W2 1PG 
Tel: 0207 594 9459/ 0207 594 1862 
http://www3.imperial.ac.uk/clinicalresearchgovernanceoffice  
 
Funder 
 
[This section does not apply] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Joint Research  
Compliance Office 
 
SOP Ref: JRCO/SOP/012  
V8.0 25 Oct 2017 
 
Page 3 of 20 
© Imperial College of Science, Technology and Medicine   
This protocol describes the Nebulised Hypertonic Saline in children with Neuromuscular disease or Cerebral 
Palsy study and provides information about procedures for entering participants.  Every care was taken in its 
drafting, but corrections or amendments may be necessary. These will be circulated to investigators in the 
study.  Problems relating to this study should be referred, in the first instance, to the Chief Investigator.  
 
This study will adhere to the principles outlined in the NHS Research Governance Framework for Health and 
Social Care (2nd edition). It will be conducted in compliance with the protocol, the Data Protection Act and 
other regulatory requirements as appropriate.  
 
Table of Contents                                                             Page No 
1. 
INTRODUCTION 
6 
1.1 BACKGROUND 
6 
2.  STUDY OBJECTIVES 
7 
3.  STUDY DESIGN 
7 
3.1 STUDY OUTCOME MEASURES 
8 
4. 
PARTICIPANT ENTRY 
8 
4.1 PRE-REGISTRATION EVALUATIONS 
8 
4.2 INCLUSION CRITERIA 
8 
4.3 EXCLUSION CRITERIA 
8 
4.4 WITHDRAWAL CRITERIA 8 
5. 
ASSESSMENT AND FOLLOW-UP 
8 
6. 
STATISTICS AND DATA ANALYSIS 
8 
7. 
REGULATORY ISSUES 
9 
7.1 ETHICS APPROVAL 
9 
7.2 CONSENT 9 
7.3 CONFIDENTIALITY9 
7.4 INDEMNITY 
9 
7.5 SPONSOR 10 
7.6 FUNDING 10 
7.7 AUDITS 
10 
8. 
STUDY MANAGEMENT 
10 
9. 
PUBLICATION POLICY 
10 
10. 
REFERENCES 
10 
APPENDICES 
13 
 
 
 
GLOSSARY OF ABBREVIATIONS 

Joint Research  
Compliance Office 
 
SOP Ref: JRCO/SOP/012  
V8.0 25 Oct 2017 
 
Page 4 of 20 
© Imperial College of Science, Technology and Medicine   
AE 
Adverse Event 
CI 
Chief Investigator 
CRF 
Case Report Form 
DMC 
Data Monitoring Committee 
DOB 
Date of Birth 
GCP 
Good Clinical Practice 
HRA 
Health Research Authority 
ICF 
Informed Consent Form 
ID 
Identification number 
ISF 
Investigator Site File 
NHANES 
National Health and Nutrition 
Examination Survey 
PI 
Principal Investigator 
PIS 
Participant Information Sheet 
RB&HFT 
Royal Brompton and Harefield NHS 
Foundation 
REC 
Research Ethics Committee 
SAE 
Serious Adverse Event 
SOP 
Standard Operating Procedure 
SP 
Subject Patient 
VAS 
Visual Analogue Scale 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
KEYWORDS 
[Nebulised Hypertonic Saline, Neuromuscular disease, Cerebral Palsy, Children, Respiratory 
complications, Polygraphy] 
STUDY SUMMARY 

Joint Research  
Compliance Office 
 
SOP Ref: JRCO/SOP/012  
V8.0 25 Oct 2017 
 
Page 5 of 20 
© Imperial College of Science, Technology and Medicine   
 
TITLE  A Chart Review assesing the effects of Nebulised Hypertonic Saline on 
Respiratory-related 
complications 
in 
children 
and 
young 
people 
with 
Neuromuscular Disease or Cerebral Palsy     
DESIGN  Chart Review and Questionnaire application     
AIMS  1)To explore whether treatment with 7% or 3% nebulised Hypertonic Saline in 
children and young people with Neuromuscular Disease or Cerebral Palsy 
decreases respiratory-related complications. 
2) Assess whether the use of 3% or 7% nebulised Hypertonic Saline improves 
ease of airway clearance in children and young people with Neuromuscular 
Disease or Cerebral Palsy    
OUTCOME MEASURES 1) Number of respiratory exacerbations requiring antibiotic treatment. 
2) Number of hospitalisations due to respiratory exacerbations, using NHANES 
2011 questionnaire for Hospitalisation and access to care HUQ.010. 
3) Nocturnal oximetry and polygraphy outcomes: BasalSpO2 (%), Minimum 
SpO2 (%),Maximum SpO2 (%), Average SpO2, Oxygen desaturation index 
(ODI), Snoring and End tidal CO2 (EtCO2). 
4) Rate of decline of pulmonary function. 
5) Score on the ease of airway clearance pictorial analogue scale from 
participants. 
6) Participants' perception of treatment. 
POPULATION Children and young people with Neuromuscular disease or Cerebral Palsy who 
are treated at Royal Brompton Hospital and their parents or legal guardians.     
ELIGIBILITY Inclusion cirteria: Children and young people 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. 
Exclusion criteria: Children or young people also diagnosed with Cystic 
Fibrosis.    
DURATION 6 months     
 
 
REFERENCE DIAGRAM 
 
[if appropriate] 
 
 
 
 
 
 
 
 
 

Joint Research  
Compliance Office 
 
SOP Ref: JRCO/SOP/012  
V8.0 25 Oct 2017 
 
Page 6 of 20 
© Imperial College of Science, Technology and Medicine   
1. 
INTRODUCTION  
 
1.1 
BACKGROUND 
In the UK, Neuromuscular diseases have a prevalence of 118 per 100,000 people amongst 
adults and children. About 70% are inherited, and 13% are muscular dystrophies (1). Worldwide, 
the prevalence of Cerebral Palsy is 2.11 per 1000 live births (2). 
The pathophysiology of neuromuscular diseases and cerebral palsy leads to restrictive 
pathology of the respiratory system. Children with neuromuscular diseases have several 
characteristics that may impair their respiratory function, such as weak bulbar and respiratory 
musculature, increased upper airway collapsibility and low lung compliance (3,4). Cerebral Palsy 
is defined as a group of disorders of the motor function, caused by a disturbance to the developing 
brain (5). Although pulmonary disease is not the primary diagnosis, some clinical characteristics 
may lead to respiratory failure. These include scoliosis, gastroesophageal reflux, and impaired 
swallowing, which leads to chronic aspiration, upper airway obstruction, recurrent infections, and 
possible bronchiectasis, developing lung disease (6). Bulbar musculature weakness impairs 
swallowing, which leads to chronic aspiration. Respiratory muscle weakness compromises the 
pump function and the effectiveness of cough. Upper airway collapsibility increases work of 
breathing and respiratory muscle fatigue. Low pulmonary compliance hinders the ability to expand 
the lung, which is exacerbated by respiratory muscle weakness, increasing the WOB. Low peak 
flow and decreased Vital Capacity (VC), which further decreases with progression of the disease 
(7), characterizes the pulmonary function of these patients. Consequently, cough may be impaired 
by low inspiration volumes, ineffective glottis closure and/or low expiratory force (4,8,9). Low Vital 
Capacity and ineffective cough in Neuromuscular disease has been associated with chronic 
airway inflammation and infection (9). Furthermore, children with Neuromuscular disease often 
have gastroesophageal reflux (GER) (10), which may cause airway inflammation (11). Chronic 
airway infection and colonisation of Pseudomonas aeruginosa and Gram-negative microorganisms 
have shown to increase morbidity of children with CP (12). GER, impaired swallowing and 
ineffective cough leads to chronic aspiration and contributes to recurrent pneumonias. Therefore, 
bronchiectasis and pulmonary fibrosis are commonly developed.  
 
Children with Neuromuscular disease show a decline of Forced Vital Capacity (FVC), which 
is steeper at younger ages (13). This is especially important because the age at which FVC 
reaches 1 Lt and the rate of decline of FVC are variables that can predict mortality (14).  
 
Pneumonia, respiratory exacerbations and failure are one of the most important causes of 
emergency admissions, hospitalisations and death in children with neuromuscular diseases and 
cerebral palsy (15-18). Physical health and the number of days spent outside home or hospitalised 
are important domains of life and predictor of Health-Related Quality of Life in children with 
Neuromuscular disease and children with Cerebral Palsy (19,20). In this context, it is of 
importance to research how to therapeutically aid airway clearance, decrease respiratory 
exacerbations and reduce the pulmonary function rate of decline. 
 
Hypertonic Saline is a solution of salt water used as a nebulized medication in many 
conditions. Its clinical benefits include mucus clearance, microbiological diagnosis, improvement of 
lung function, decrease in respiratory exacerbations, cough triggering and improvement of quality 
of life (21). It has mucolytic and expectorant effect, reduces biofilm formation by Pseudomonas 
Aeruginosa and increases antioxidative thiols in the airway liquid (22).   
 
 Retrospective studies and clinical trials have shown that inhaled Hypertonic Saline is well 
tolerated, reduces pulmonary exacerbations, improves lung function and Lung Clearance Index, 
reduces absenteeism, improves Health Related Quality of Life in patients with Cystic Fibrosis 
independent of rhDNase treatment (23-26), and has anti-inflammatory effect in sputum decreasing 

Joint Research  
Compliance Office 
 
SOP Ref: JRCO/SOP/012  
V8.0 25 Oct 2017 
 
Page 7 of 20 
© Imperial College of Science, Technology and Medicine   
IL-8 (27). In asthmatic and healthy subjects, inhaled Hypertonic Saline have shown to enhance 
mucociliary clearance (28). To date, studies investigating Hypertonic Saline in bronchiectasis have 
produced conflicting results (29).  
 
This study aims to assess the effectiveness of the use of nebulised Hypertonic Saline in 
respiratory outcomes in children and young people with Neuromuscular disease or with Cerebral 
Palsy.  
 
1.2 
RATIONALE FOR CURRENT STUDY 
[To our knowledge, there is currently no available data concerning the use of nebulised Hypertonic 
Saline in the management of children and young people with Neuromuscular Disease or with 
Cerebral Palsy. This study aims to assess whether the use of nebulised Hypertonic Saline in 
children and young people with Neuromuscular disease or Cerebral Palsy is effective in the 
management and prevention of respiratory-related complications. 
 
Hypothesis: Nebulised Hypertonic Saline in children and young people with Neuromuscular 
disease or Cerebral Palsy decreases respiratory-related complications.] 
 
 
2.  STUDY OBJECTIVES 
 
[Primary Objective: To explore whether treatment with 3% and 7% Nebulised Hypertonic Saline in 
children and young people with Neuromuscular Disease or Cerebral Palsy decreases respiratory-
related complications. 
 
Secondary Objectives: 
- Assess the effect of the treatment with nebulised hypertonic saline in children and young people 
with Neuromuscular disease or Cerebral Palsy on the number of courses of antibiotic prescribed 
compared to year before starting treatment. 
- Determine whether the use of nebulised Hypertonic Saline in children and young people with 
Neuromuscular Disease or Cerebral Palsy reduces the frequency of hospitalisations due to 
respiratory exacerbations compared to year before commencing treatment. 
- Explore the impact of the treatment with hypertonic saline on nocturnal oxygenation and 
ventilation in children and young people with Neuromuscular disease or with Cerebral Palsy. 
- Evaluate whether the treatment with nebulised hypertonic saline in children and young people 
with neuromuscular disease or cerebral palsy improves the ease of airway clearance. 
- In the subgroup of participants with neuromuscular disease who can perform spirometry, assess 
whether the use of Hypertonic Saline decreases rate of decline of pulmonary function compared to 
year before commencing treatment. 
- Explore how parents of children and young people with Neuromuscular disease or with Cerebral 
Palsy perceive the treatment with nebulised hypertonic saline compared to previous management.  
] 
 
3.  STUDY DESIGN 
 
[Chart review of children and young people with Neuromuscular disease or with 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. Children and young people who are also diagnosed with 
Cystic Fibrosis will be excluded.  
 
Parents or legal guardians will be asked to complete two questionnaires to further complement 
data from hospital records. 

Joint Research  
Compliance Office 
 
SOP Ref: JRCO/SOP/012  
V8.0 25 Oct 2017 
 
Page 8 of 20 
© Imperial College of Science, Technology and Medicine   
 
Participants between 10 and 18 years old will be asked to complete one questionnaire to 
complement hospital records.] 
 
[Duration: 6 months.] 
 
[We aim to review all charts of participants recruited that meet criteria between December 2011 
and May 2018. We aim to recruit 40 participants from each group, including children, young 
people, and parents or legal guardians,  as this will be a pilot study. Only participants recruited will 
have their charts reviewed] 
 
 
3.1 
STUDY OUTCOME MEASURES 
Primary Endpoints: 
- Number of respiratory exacerbations requiring antibiotic treatment. 
- Number of hospitalsiations due to respiratory exacerbations, using NHANES 2011 questionnaire 
for Hospitalisation and access to care HUQ.010. 
- Nocturnal oximetry and polygraphy outcomes: Basal SpO2 (%), Minimum SpO2 (%), Maximum 
SpO2 (%), Average SpO2 (%), Oxygen desaturation index (ODI), Snoring and End tidal CO2 
(EtCO2). 
- Rate of decline of pulmonary function. 
 
Secondary Endpoints: 
- Score on the ease of airway clearance pictorial analogue scale from all participants. 
- Participants' perception of treatment. 
 
4. 
PARTICIPANT ENTRY  
 
4.1 
PRE-REGISTRATION EVALUATIONS  
[This section does not apply]  
 
4.2 
INCLUSION CRITERIA 
[Children and young people under 18 years old with Neuromuscular disease or with Cerebral 
Palsy treated with nebulised Hypertonic Saline for at least 12 months and their parents or legal 
guardians.] 
 
4.3 
EXCLUSION CRITERIA 
[Children or young people who are also diagnosed with Cystic Fibrosis, as the effectiveness of 
nebulised Hypertonic Saline have already been studied extensively in this group.] 
 
4.4 
WITHDRAWAL CRITERIA 
[This section does not apply.] 
 
5. 
ASSESSMENT AND FOLLOW-UP  
 
[This section does not apply] 
 
6. 
STATISTICS AND DATA ANALYSIS 
 
[Sample Size:  
 

Joint Research  
Compliance Office 
 
SOP Ref: JRCO/SOP/012  
V8.0 25 Oct 2017 
 
Page 9 of 20 
© Imperial College of Science, Technology and Medicine   
We aim to recruit 40 participants for each group, including children and young people and their 
parents or legal guardians, as this is a pilot study. 
 
Statistical Analysis Plan: 
 
Primary endpoint analysis: 
- Univariate X2 analysis for categorical variables to investigate Courses of antibiotic treatment. 
- Univariate X2 analysis for categorical variables to investigate Number of hospitalisations.  
- Student t testing will be used to analyse nocturnal oxygenation and ventilation outcomes 
comparing one year before and after starting treatment with Hypertonic Saline. 
- Independent t testing and Mann-Whitney U test to analyse Rate of decline in pulmonary 
function.  
- Cox proportional hazard model to test differences in primary endpoints for different baseline 
FVC. 
Secondary enpoint analysis: 
- Univarate analysis to analyse Ease of airway clearance. 
- Univariate analysis on perception of treatment. ] 
 
Data and all appropriate documentation will be stored for a minimum of 10 years after the 
completion of the study, including the follow-up period.   
 
7. 
REGULATORY ISSUES 
 
7.1 
ETHICS APPROVAL 
The Study Coordination Centre has obtained approval from the Yorkshire & The Humber - Leeds 
West Research Ethics Committee (REC) and Health Regulator Authority (HRA). The study must 
also receive confirmation of capacity and capability from each participating NHS Trust before 
accepting participants into the study or any research activity is carried out. The study will be 
conducted in accordance with the recommendations for physicians involved in research on human 
subjects adopted by the 18th World Medical Assembly, Helsinki 1964 and later revisions. 
 
7.2 
CONSENT  
Consent to enter the study must be sought from each participant only after a full explanation has 
been given, an information leaflet offered, and time allowed for consideration.  Signed participant 
consent should be obtained.  The right of the participant to refuse to participate without giving 
reasons must be respected.  After the participant has entered the study the clinician remains free 
to give alternative treatment to that specified in the protocol at any stage if he/she feels it is in the 
participant’s best interest, but the reasons for doing so should be recorded.  In these cases, the 
participants remain within the study for the purposes of follow-up and data analysis.  All 
participants are free to withdraw at any time from the protocol treatment without giving reasons 
and without prejudicing further treatment. 
 
7.3 
CONFIDENTIALITY 
The Chief Investigator will preserve the confidentiality of participants taking part in the study and is 
registered under the Data Protection Act. 
 
7.4 
INDEMNITY 
Imperial College London holds negligent harm and non-negligent harm insurance policies which 
apply to this study. 

Joint Research  
Compliance Office 
 
SOP Ref: JRCO/SOP/012  
V8.0 25 Oct 2017 
 
Page 10 of 20 
© Imperial College of Science, Technology and Medicine   
7.5 
SPONSOR 
Imperial College London will act as the main Sponsor for this study.  Delegated responsibilities will 
be assigned to the NHS trusts taking part in this study.   
 
7.6 
FUNDING 
This section does not apply.   
 
7.7 
AUDITS  
The study may be subject to inspection and audit by Imperial College London under their remit as 
sponsor and other regulatory bodies to ensure adherence to GCP and the NHS Research 
Governance Framework for Health and Social Care (2nd edition).  
 
8. 
STUDY MANAGEMENT 
 
The day-to-day management of the study will be co-ordinated through Hui-Leng Tan.    
 
9. 
PUBLICATION POLICY 
 
[ Data ownership rights will lie with the institution. Findings of this study will be presented as a 
Dissertation and will be available through Open Access. We aim to publish findings in peer-review 
journals. Dr. Hui-Leng Tan will take the lead in the publication and dissemination.] 
 
10. 
REFERENCES 
 
(1) Pohlschmidt M, Meadowcroft R. Muscle disease: the impact. Incidence and Prevalence of 
Neuromuscular Conditions in the UK. Muscular Dystrophy Campaign: Report number: 1, 2010.  
(2) Oskoui M, Coutinho F, Dykeman J, Jetté N, Pringsheim T. An update on the prevalence of 
cerebral palsy: a systematic review and meta-analysis. Developmental Medicine & Child 
Neurology. 2013;55(6): 509-519.  
(3) Allen J. Pulmonary complications of neuromuscular disease: A Respiratory mechanics 
perspective. Paediatric Respiratory Reviews. 2010;11(1): 18-23. . Available from: doi: 
https://doi.org/10.1016/j.prrv.2009.10.002. 
Available 
from: 
http://www.sciencedirect.com/science/article/pii/S1526054209000700. 
(4) Lo Mauro A, Aliverti A. Physiology of respiratory disturbances in muscular dystrophies. Breathe. 
2016;12(4): 318-327.  
(5) Rosenbaum P, Paneth NF, Leviton AF, Goldstein MF, Bax MF, Damiano DF, et al. A report: the 
definition and classification of cerebral palsy April 2006. Developmental medicine and child 
neurology.Supplement JID - 0006762. 2007;1098-14.  
(6) Fitzgerald DA, Follett J, Van Asperen PP. Assessing and managing lung disease and sleep 
disordered breathing in children with cerebral palsy. Paediatric Respiratory Reviews. 2009;10(1): 
18-24. . Available from: doi: https://doi.org/10.1016/j.prrv.2008.10.003. Available from: 
http://www.sciencedirect.com/science/article/pii/S1526054208000729. 

Joint Research  
Compliance Office 
 
SOP Ref: JRCO/SOP/012  
V8.0 25 Oct 2017 
 
Page 11 of 20 
© Imperial College of Science, Technology and Medicine   
(7) Bushby K, Finkel R, Birnkrant DJ, Case LE, Clemens PR, Cripe L, et al. Diagnosis and 
management of Duchenne muscular dystrophy, part 1: diagnosis, and pharmacological and 
psychosocial management. The Lancet Neurology. 2010;9(1): 77-93.  
(8) Boitano LJ. Management of Airway Clearance in Neuromuscular Disease. Respiratory care. 
2012;51(8): 913-924. . Available from: http://rc.rcjournal.com/content/51/8/913.abstract. 
(9) Stehling F, Pieper N, Bouikidis A, Steinmann J, Rath P, Mellies U. Upper airway microbial 
colonization in patients with neuromuscular disorders. Respirology. 2016;21(7): 1285-1291.  
(10) Skalsky AJ, Dalal PB. Common Complications of Pediatric Neuromuscular Disorders. Physical 
Medicine and Rehabilitation Clinics of North America. 2015;26(1): 21-28. . Available from: doi: 
https://doi.org/10.1016/j.pmr.2014.09.009 
". 
Available 
from: 
http://www.sciencedirect.com/science/article/pii/S1047965114001065. 
(11) Carpagnano GE, Resta O FAU - Ventura,,M.T., FAU VM, FAU AA, Di Gioia GF, Giliberti TF, et 
al. Airway inflammation in subjects with gastro-oesophageal reflux and gastro-oesophageal reflux-
related asthma. Journal of internal medicine. 2006;259(3): 323-331.  
(12) Gerdung CA, Tsang A, Yasseen AS, Armstrong K, McMillan HJ, Kovesi T. Association Between 
Chronic Aspiration and Chronic Airway Infection with Pseudomonas aeruginosa and Other Gram-
Negative Bacteria in Children with Cerebral Palsy. Lung. 2016;194(2): 307-314.  
(13) Kohler M, Clarenbach CF, Böni L, Brack T, Russi EW, Bloch KE. Quality of Life, Physical 
Disability, and Respiratory Impairment in Duchenne Muscular Dystrophy. Am J Respir Crit Care 
Med. 2005;172(8): 1032-1036.  
(14) Phillips MF, Quinlivan RCM, Edwards R , Calverley PM . Changes in Spirometry Over Time as 
a Prognostic Marker in Patients with Duchenne Muscular Dystrophy. Am J Respir Crit Care Med. 
2001;164(12): 2191-2194.  
(15) Bell CF, Kurosky SK, Candrilli SD. Muscular dystrophy-related hospitalizations among male 
pediatric patients in the United States. Hospital practice. 2015;43(3): 180-185.  
(16) Van Ruiten HJA, Marini Bettolo C, Cheetham T, Eagle M, Lochmuller H, Straub V, et al. Why 
are some patients with Duchenne muscular dystrophy dying young: An analysis of causes of death 
in North East England. European Journal of Paediatric Neurology. 2016;20(6): 904-909. . Available 
from: 
doi: 
https://doi.org/10.1016/j.ejpn.2016.07.020. 
Available 
from: 
http://www.sciencedirect.com/science/article/pii/S109037981630126X. 
(17) Meehan E, Reid SM, Williams K, Freed GL, Sewell JR, Vidmar S, et al. Hospital admissions in 
children with cerebral palsy: a data linkage study. Developmental medicine and child neurology. 
2017;59(5): 512-519.  
(18) Meehan E, Reid SM, Williams K, Freed GL, Babl FE, Sewell JR, et al. Tertiary paediatric 
emergency department use in children and young people with cerebral palsy. Journal of 
paediatrics and child health. 2015;51(10): 994-1000.  

Joint Research  
Compliance Office 
 
SOP Ref: JRCO/SOP/012  
V8.0 25 Oct 2017 
 
Page 12 of 20 
© Imperial College of Science, Technology and Medicine   
(19) Davis E, Reddihough D, Murphy N, Epstein A, Reid SM, Whitehouse A, et al. Exploring quality 
of life of children with cerebral palsy and intellectual disability: What are the important domains of 
life? Child: Care, Health and Development. 2017;43(6): 854-860.  
(20) Otto C, Steffensen BF, Højberg A, Barkmann C, Rahbek J, Ravens-Sieberer U, et al. Predictors 
of Health-Related Quality of Life in boys with Duchenne muscular dystrophy from six European 
countries. Journal of neurology. 2017;264(4): 709-723.  
(21) Rogers DF. Mucoactive agents for airway mucus hypersecretory diseases. Respiratory care: 
the official journal of the American Association for Respiratory Therapy. 2007;52(9): 1176-1197.  
(22) Elkins MR, Bye PT. Mechanisms and applications of hypertonic saline. J R Soc Med. 
2011;104(1): 2-5.  
(23) Dmello D, Nayak RP, Matuschak GM. Stratified assessment of the role of inhaled hypertonic 
saline in reducing cystic fibrosis pulmonary exacerbations: a retrospective analysis. BMJ Open. 
2011;1(1): 1-4. . Available from: doi: 10.1136/bmjopen-2010-000019. Available from: 
http://bmjopen.bmj.com/content/1/1/e000019. 
(24) Elkins MR, Robinson M, Rose BR, Harbour C, Moriarty CP, Marks GB, et al. A Controlled Trial 
of Long-Term Inhaled Hypertonic Saline in Patients with Cystic Fibrosis. N Engl J Med. 
2006;354(3): 229-240.  
(25) Amin R, Subbarao P, Jabar A, Balkovec S, Jensen R, Kerrigan S, et al. Hypertonic saline 
improves the LCI in paediatric patients with CF with normal lung function. Thorax. 2010;65(5): 
379-383. 
. 
Available 
from: 
doi: 
10.1136/thx.2009.125831. 
Available 
from: 
http://thorax.bmj.com/content/65/5/379.abstract. 
(26) Donaldson SH, Bennett WD, Zeman KL, Knowles MR, Tarran R, Boucher RC. Mucus clearance 
and lung function in cystic fibrosis with hypertonic saline. The New England journal of medicine. 
2006;354241-250.  
(27) Reeves EP, Williamson M, O'Neill SJ, Greally P, McElvaney NG. Nebulized Hypertonic Saline 
Decreases IL-8 in Sputum of Patients with Cystic Fibrosis. Am J Respir Crit Care Med. 
2011;183(11): 1517-1523.  
(28) Daviskas E, Anderson S, Gonda I, Eberl S, Meikle S, Seale J, et al. Inhalation of hypertonic 
saline aerosol enhances mucociliary clearance in asthmatic and healthy subjects. European 
Respiratory 
Journal. 
1996;9(4): 
725-732. 
Available 
from: 
http://erj.ersjournals.com/content/9/4/725.abstract. 
(29) Hart A, Sugumar K FAU - Milan, Stephen, J., FAU MS, FAU FS, Crossingham I. Inhaled 
hyperosmolar agents for bronchiectasis. The Cochrane database of systematic reviews JID - 
100909747. 1996;9(4): 725-732.  
 
 

Joint Research  
Compliance Office 
 
SOP Ref: JRCO/SOP/012  
V8.0 25 Oct 2017 
 
Page 13 of 20 
© Imperial College of Science, Technology and Medicine   
 
APPENDICES 
 
• 
Appendix 1   Questionnaire on Hypertonic Saline treatment for parents and legal guardians. 
• 
Appendix 2   Questionnaire on Hypertonic Saline treatment for participants 16 – 18 years. 
• 
Appendix 3   Questionnaire on Hypertonic Saline treatment for participants 10 – 15 years. 
• 
Appendix 4   Consent form 
• 
Appendix 5   Consent form 
• 
Appendix 6   Assent form 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Joint Research  
Compliance Office 
 
SOP Ref: JRCO/SOP/012  
V8.0 25 Oct 2017 
 
Page 14 of 20 
© Imperial College of Science, Technology and Medicine   
Hypertonic saline treatment questionnaire 
PARENTS/LEGAL GUARDIAN 
 
 
 
Participant ID:                                                                    
Date: ____/_____/____ 
 
1)Overall, do you feel that nebulised hypertonic saline your child / young person has 
had has been 
 
___Useful 
___Not useful 
___I don’t know 
 
  
What have you found most useful about it? 
 
 
 
 
What have you found most difficult/ troublesome about it?  
 
 
 
 
2)Please score how easy you think it has been  to clear sputum from your child’s 
airway 
 
Before starting Hypertonic Saline 
 
After starting Hypertonic Saline 
 
 
 
 
 
 
 
 

Joint Research  
Compliance Office 
 
SOP Ref: JRCO/SOP/012  
V8.0 25 Oct 2017 
 
Page 15 of 20 
© Imperial College of Science, Technology and Medicine   
Participant ID:  
Date: ____/_____/____ 
 
 
In the 12 months before starting Hypertonic saline, how many courses of antibiotics 
did your child need? If you don’t remember, please leave it blank. 
 
 
 
 
 
         Oral  
 
 
 
 
 
 
 
 
 IV 
 
 
In the 12 months after starting Hypertonic saline, how many courses of antibiotics did 
your child need? If you don’t remember, please leave it blank. 
 
 
 
 
 
        Oral  
 
 
 
 
 IV 
 
 
In the 12 months before starting Hypertonic saline, how many times did you have to 
take your child to see a doctor because s/he was unwell with a chest infection? If you 
don’t remember, please leave it blank. 
 
 
 
 
         
 
In the 12 months after starting Hypertonic saline, how many times did you have to 
take your child to be seen by a doctor because s/he was unwell with a chest infection? 
If you don’t remember, please leave it blank. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Joint Research  
Compliance Office 
 
SOP Ref: JRCO/SOP/012  
V8.0 25 Oct 2017 
 
Page 16 of 20 
© Imperial College of Science, Technology and Medicine   
Hypertonic saline questionnaire 
Ages 16 to 18 years  
 
 
 
Participant ID:    
Date: ____/_____/____ 
  
 
1)Overall, do you feel that nebulised hypertonic saline has been 
 
___Useful 
___Not useful 
___ I don’t know 
 
  
What have you found most useful about it? 
 
 
 
 
What have you found most difficult/ troublesome about it?  
 
 
 
2)Please score your perception of how easy it is to clear sputum.  
 
Before starting Hypertonic Saline 
 
 
 
 
 
After starting Hypertonic Saline 
 
 
 
 
 
 
 
 
 

Joint Research  
Compliance Office 
 
SOP Ref: JRCO/SOP/012  
V8.0 25 Oct 2017 
 
Page 17 of 20 
© Imperial College of Science, Technology and Medicine   
Hypertonic saline questionnaire 
AGES 10 to 15 YEARS 
 
 
Participant ID: 
Date: ____/_____/____ 
  
 
1) Do you feel that nebulised hypertonic saline has been 
 
___Useful 
___Not useful 
___I don’t know 
 
  
What do you like about it? 
 
 
 
 
What do you not like about it?  
 
 
2) Please point on the line below, between EXTREMELY EASY and EXTREMELY HARD, 
to show how easy it is to clear your sputum. 
 
Before starting Hypertonic Saline 
 
 
 
 
 
 
 
After starting Hypertonic Saline 
 
 
 
 
 
 
 
 

Joint Research  
Compliance Office 
 
SOP Ref: JRCO/SOP/012  
V8.0 25 Oct 2017 
 
Page 18 of 20 
© Imperial College of Science, Technology and Medicine   
 
 
Imperial College London 
 
St Mary’s Campus 
Praed St., Paddington, London 
W2 1NY 
Tel: +44 02033126666  
www.imperial.ac.uk 
 
A Chart Review assessing the effect of Nebulised Hypertonic Saline on 
Respiratory-related complications in children and young people with 
Neuromuscular Disease or Cerebral Palsy 
 
IRAS Project ID: 243535 
 
CONSENT FORM 
(16 - 18 years) 
 
 
Participant Identification Number for this trial: 
Name of Researcher: 
   
 
 
 
 
 
 
 
           Please initial box if you agree
 
 
 
 
 
 
 
 
1. I confirm that I have read and understood the information sheet version n°2 date 
04/04/2018, for the above study. I have had the opportunity to consider the 
information, ask questions and have these answered satisfactorily.  
  
 
2. I understand that participation is voluntary and that I am free to withdraw at any time, 
without giving any reason, without my medical care or legal rights being affected. 
 
 
3. I understand that the study research team will review relevant sections of my medical 
records and data. 
 
 
4. I understand that data collected during the study may be looked at by responsible 
individuals, from regulatory authorities, Imperial College London or from the NHS 
Trust, where it is relevant to my taking part in this research. I give permission for 
these individuals to have access to my records.   
 
 
5. I agree to fill in the study questionnaires. 
 
 
 
6. I agree to my parents completing the study questionnaires. 
 
 
 
________________________ 
________________ 
____________________ 
Name of Participant 
Date 
Signature  
 
 
_________________________ 
________________ 
____________________ 
Name of Person taking consent 
Date 
Signature 
 
When completed, 1 for participant; 1 for researcher site file; 1 (original) to be kept in medical notes 
 

Joint Research  
Compliance Office 
 
SOP Ref: JRCO/SOP/012  
V8.0 25 Oct 2017 
 
Page 19 of 20 
© Imperial College of Science, Technology and Medicine   
 
 
Imperial College London 
 
St Mary’s Campus 
Praed St., Paddington, London 
W2 1NY 
Tel: +44 02033126666  
www.imperial.ac.uk 
 
A Chart Review assessing the effect of Nebulised Hypertonic Saline on 
Respiratory-related complications in children and young people with 
Neuromuscular Disease or Cerebral Palsy 
 
IRAS Project ID: 243535 
 
CONSENT FORM 
Participant Identification Number for this trial: 
Name of Researcher: 
   
 
 
 
 
 
 
 
           Please initial box if you agree 
 
1. I confirm that I have read and understood the information sheet version n°2 
date 04/04/2018, for the above study. I have had the opportunity to consider 
the information, ask questions and have these answered satisfactorily.  
 
 
2. I understand that participation is voluntary and that I am free to withdraw my 
child at any time, without giving any reason, without affecting my child’s 
medical care or legal rights being affected. 
 
 
3. I understand that the study research team will review relevant sections of my 
child’s medical records and data. 
 
 
4. I understand that data collected during the study may be looked at by 
responsible individuals, from regulatory authorities, Imperial College London 
or from the NHS Trust, where it is relevant to my child taking part in this 
research. I give permission for these individuals to have access to my child’s 
records.   
 
 
5. I agree to my child completing the study questionnaire. 
 
 
 
 
 
      
  
________________________ 
________________ 
____________________ 
Name of Parent 
Date 
Signature 
 
 
________________________ 
________________ 
____________________ 
Name of Participant 
Date 
Signature (if appropriate) 
 
 
_________________________ 
________________ 
____________________ 
Name of Person taking consent 
Date 
Signature 
 
When completed, 1 for participant; 1 for researcher site file; 1 (original) to be kept in medical notes 
 

Joint Research  
Compliance Office 
 
SOP Ref: JRCO/SOP/012  
V8.0 25 Oct 2017 
 
Page 20 of 20 
© Imperial College of Science, Technology and Medicine   
 
 
Imperial College London 
 
St Mary’s Campus 
Praed St., Paddington, London 
W2 1NY 
Tel: +44 02033126666  
 
www.imperial.ac.uk 
 
A Chart Review assessing the effect of Nebulised Hypertonic Saline on 
Respiratory-related complications in children and young people with 
Neuromuscular Disease or Cerebral Palsy 
 
IRAS Project ID: 243535 
 
INFORMED ASSENT FORM 
 
Participant Identification Number for this trial: 
Name of Researcher: 
   
 
 
 
 
 
 
 
           Please circle all that you 
agree  
 
 
 
 
 
 
1. Do you understand what this study is about? 
  
Yes/No 
2. Have you asked all the questions you want? 
 
Yes/No 
3. Have you had your questions answered in a way you understand? 
 
Yes/No 
4. Do you want to take part?   
 
Yes/No 
If any answer is “No”, don’t sign your name. 
 
 
 
 
 
 
________________________ 
________________ 
____________________ 
Name of Participant 
Date 
Signature  
 
 
_________________________ 
________________ 
____________________ 
Name of Person taking assent 
Date 
Signature 
 
 
 
When completed, 1 for participant; 1 for researcher site file; 1 (original) to be kept in medical notes