Description of the condition
Improvement in neonatal and paediatric care in recent decades has resulted in the survival of increasing numbers of children with multiple and profound impairment. Babies born early or in frail condition are being successfully treated and surviving into childhood. Young children suffering serious neurological impairment as a result of infection, illness or trauma are also surviving longer, as are children with various genetic, neuromuscular and metabolic disorders (Blucker 2011).
While some of these children go on to lead normal lives, others are left with severe impairment in all aspects of functioning. While the causes of these impairments are varied, these children bear the illness burden of profound and multiple disabilities, and for research purposes may be grouped under the label of 'severe global developmental delay' (SGDD).
SGDD is therefore an umbrella term, broadly capturing a population of children with severe intellectual disability and severe motor impairment, most of whom will be extremely limited in their functional movement, and are dependent upon others for all activities of daily living.
Their physical handicap and associated musculoskeletal deformities lead to high levels of respiratory morbidity as a consequence of the combination of several factors which may include; excessive salivation (sialorrhoea), swallowing problems (dysphagia), gastro-oesophageal reflux (GOR), ineffective cough, immobility, chest wall deformity, weakness of respiratory muscles, small airways collapse (atelectasis), damaged lung tissue (bronchiectasis), sleep disordered breathing (nocturnal hypoventilation),aspiration and respiratory failure.
Description of the intervention
The respiratory problems experienced by this patient group are often multi-faceted and complex, and a myriad of interventions are applied in clinical practice, including chest physiotherapy, suction, mechanical insufflation-exsufflation (MIE), non-invasive ventilation (NIV), postural management and tracheostomy.
How the intervention might work
The rationale by which these interventions may decrease respiratory morbidity broadly include improved ventilation, enhanced ventilation-perfusion (V/Q) matching, and assistance in mobilisation and expectoration of secretions.
Why it is important to do this review
Patients with SGDD do not share a specific diagnosis and some have no definitive diagnosis - representative statistics are difficult to obtain. As a result of the heterogeneity of these patients and the breadth of factors impacting upon their respiratory health, comprehensive review of the literature exists.
Current research into paediatric respiratory care tends to focus on very specific groups of patients, such as those with cystic fibrosis, spinal muscular atrophy or Duchenne's muscular dystrophy, with consensus guidelines published for the respiratory care of some of these groups (Finder 2004; Hull 2012; Wang 2007). The available literature reflects that respiratory compromise is a major, if not the largest, cause of mortality for individuals with cerebral palsy (Augustine 2010; Fitzgerald 2009; Healy 2010; Littleton 2011; Somerville 2008; Sullivan 2006), neuromuscular disorders (Katz 2004; Panitch 2009; Simonds 2006) and severe developmental disability (Mestrovic 2006; O'Loughlin 2009). It is also a major cause of morbidity (Chatwin 2003; Fitzgerald 2009; Healy 2010; Seddon 2003; Yuan 2010) requiring hospital admissions and impacting upon quality of life.
In the United Kingdom (UK), children with SGDD often end up in costly acute care for prolonged periods of time. In the current economic and political climate, there is a drive toward community-based care for long-term conditions. Improved access to specialist equipment and trained staff would allow treatment of sub-acute and chronic respiratory conditions in the community, facilitate timely discharge and prevent hospital readmissions. A systematic review that brings together the range of management options in a way which can inform best practice is therefore timely.
Quality research is necessary to ensure that this growing population of vulnerable children receive equity of care and that treatment is safe and effective and enhances quality of life for them and their families.
To assess the effects of non-pharmaceutical management of respiratory morbidity in children with severe global developmental delay.
Criteria for considering studies for this review
Types of studies
We will include randomised controlled trials (RCTs), controlled trials and cohort studies provided that data from a comparison group is reported.
The rationale for including non-randomised studies (NRS) is that RCTs are rarely available for this patient group but other types of studies may be available. Where such a paucity of evidence exists we consider it preferable to report other types of studies, provided that rigorous risk of bias assessment is applied, in order to provide a summary of available evidence as opposed to returning an empty review.
Types of participants
We will include children aged up to 18 years of age with a diagnosis of severe neurological impairment and with respiratory morbidity. We will include children with severe neurological impairment who do not have severe cognitive impairment, and exclude studies on children only if cognitive impairment would make the intervention studied impracticable in a wider group.
We will exclude children with a primary respiratory pathology such as cystic fibrosis and those receiving palliative or end of life care.
Types of interventions
Airways clearance techniques, postural drainage, suction, mechanical insufflator- exsufflator, non-invasive ventilation, tracheostomy, postural drainage, sleep systems, postural management.
Types of outcome measures
- Respiratory parameters, e.g. VT, RR, PETC0
2, PCF, SaO 2, PaCO 2, Pa0 2(as defined by study authors)
- Number of hospital admissions
- Number of respiratory infections requiring antibiotics
- Length of hospital stay
- Quality of life measures (as defined by study authors)
- Length of survival
- Adverse outcomes for each intervention, for example pain, pneumothorax
Search methods for identification of studies
We will search: the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library); MEDLINE (Ovid); EMBASE (Ovid); AMED (EBSCOHost); and CINAHL (EBSCOHost). See Appendix 1 for the proposed MEDLINE strategy. This will be adapted for use in other databases.
We will search all databases from their inception to the present and there will be no restriction on language of publication. We will manage references using EndNote.
Searching other resources
We will search Web of Science for grey literature such as conference proceedings.
We will check the reference lists of all primary included studies and review articles for relevant additional references. We will contact authors of identified trials, if necessary, for identification of other relevant published and unpublished studies. We will also contact experts in the field.
Data collection and analysis
Selection of studies
Two review authors will independently screen titles and abstracts generated by the electronic and manual searches to ascertain if they meet the inclusion criteria. Potentially-relevant articles will be reviewed independently by two authors to assess eligibility based on the pre-specified inclusion criteria. We will resolve disagreement by discussion and consensus; discrepancies will be re-evaluated by a third independent review author if required.
Data extraction and management
Two review authors will independently extract data from the eligible studies and we will resolve disagreement by consensus or through the input of a third review author. When necessary, we will contact authors of included studies to obtain important missing data.. All relevant data including demographics of participants, study methodology, outcome measures and results of each of the included studies will be extracted and documented in a data extraction form. We will then convert the extracted data to the desired format and enter it into RevMan 5.2 software for analysis.
Assessment of risk of bias in included studies
Two review authors will independently assess risk of bias for each study using the criteria outlined in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). Any disagreement will be resolved by discussion. We will assess the risk of bias according to the following domains:
- random sequence generation.
- allocation concealment.
- blinding of participants and personnel.
- blinding of outcome assessment.
- incomplete outcome data.
- selective outcome reporting.
- other bias.
We will grade each potential source of bias as high, low, or unclear risk of bias.
Measures of treatment effect
We will express results for continuous variables using mean difference (MD) or standardised mean difference (SMD) with 95% confidence interval (CI). Results for pooled outcomes with dichotomous variables will be expressed using odds ratios (OR) with 95% CI. We will consider a P value of less than 0.05 statistically significant.
The OR will be used for dichotomous data and presented along with the absolute difference. The risk ratio will be calculated for events presenting 'bad' outcomes, for example increased exacerbations, development of antibiotic resistance, worsened quality of life.
For ease of communication and clarity, the risk difference (RD) will be calculated and the number needed to treat (NNT) will be derived.
Unit of analysis issues
For continuous data, we will prefer the mean difference based on change from baseline over mean difference based on absolute.
For cross-over trials we will report data where it is presented with results from a paired t-test if available. If we encounter cluster randomised trials we will analyse data in consultation with a statistician and using methods recommended in the Cochrane Handbook.
Dealing with missing data
We will contact the original investigators to verify the study characteristics and obtain missing numerical outcome data. We will adopt the intention-to-treat principle while analysing the outcomes or use 'imputation methods' to impute standard deviations. We will perform sensitivity analyses to assess the effects of missing data on the overall results and conclusions. The potential impact of missing data (if any) on the findings of the review will be discussed thoroughly.
Assessment of heterogeneity
We will use the I
Assessment of reporting biases
Where we suspect reporting bias, we will attempt to contact study authors and ask them to provide missing outcome data. Where this is not possible, and the missing data are thought to introduce serious bias, we will explore the impact of including such studies in the overall assessment of results by a sensitivity analysis.
We will use fixed effects models when pooling data. We will present the findings of our primary outcomes in a 'Summary of findings' table using the recommendations in the Cochrane Handbook for Systematic Reviews of Interventions and GRADEPro software (Higgins 2011).
Where data are not suitable for meta-analysis, we will describe the results for the relevant outcomes narratively. We will describe results from cohort studies narratively.
Subgroup analysis and investigation of heterogeneity
We we analyse the data in subgroups according to type of intervention, for example, interventions to manage sleep disordered breathing, and interventions to manage sputum retention.
We will perform sensitivity analyses to examine the effect on results of excluding trials at high risk of bias.
We would like to acknowledge the support from the following people: Elizabeth Gillen, academic librarian at Cardiff University; Mala Mann, academic librarian at Cardiff University; Elspeth Webb, Dissertation Supervisor, Cardiff Univeristy; Airways Group editorial team, The Cochrane Collaboration. Anne Holland was the editor for this review.
Appendix 1. MEDLINE search strategy
1. exp Respiratory Therapy/
2. exp Physical Therapy Modalities/
4. Patient Positioning/
5. exp Posture/
7. Mucociliary Clearance/
9. ((chest$ or respiratory$) adj3 (physiotherap$ or physical$)).tw.
10. (postur$ adj3 (drain$ or manage$)).tw.
11. (CPAP or "continuous positive airway*" or "nasal continuous positive airway pressure" or NCPAP or PPR or "positive pressure respiration" or "Positive end-expiratory pressureOR PEEP" or "inspiratory positive-pressure breathing" or IPB or IPPB).tw.
13. (mechanical$ adj3 (insufflat$ or exsufflat$)).tw.
14. (cough$ adj3 assist$).tw.
15. (percussi$ or oscillat$ or vibrat$).tw.
17. "sleep system$".tw.
19. Developmental Disabilities/
20. exp Intellectual Disability/
21. exp Child Development Disorders, Pervasive/
22. exp Learning Disorders/
23. Cerebral Palsy/
24. exp Communication Disorders/
25. Disabled Children/
26. (development$ adj3 (disabiliti$ or delay$)).tw.
27. (mental$ adj3 retard$).tw.
29. "cerebral palsy".tw.
31. neurological disabilit$.tw.
32. (multiple adj3 disabilit$).tw.
33. exp Neuromuscular Diseases/
34. exp Muscular Diseases/
37. (muscular adj3 dystroph$).tw.
39. exp Respiratory Tract Diseases/
44. (secretion$ or sputum or mucus).tw.
46. ((respiratory or airway$ or pulmonary) adj3 (problem$ or infection$ or condition$ or disease$ or disorder$)).tw.
48. exp Child/
49. exp Pediatrics/
50. exp infant/
51. exp adolescent/
52. (paediatric$ or paediatric$ or child$ or adolescen$ or infant$ or young$ or preschool$ or pre-school$ or newborn$ or new-born$ or neonat$ or neo-nat$).tw.
54. 18 and 38 and 47 and 53
55. (clinical trial or controlled clinical trial or randomised controlled trial).pt.
56. (randomised or randomised).ab,ti.
62. exp Cohort Studies/
64. (follow-up adj3 (study or studies)).tw.
65. meta analysis.pt.
68. (systematic$ adj3 (review$1 or overview$1)).tw.
73. 71 not (71 and 72)
74. 70 not 73
75. 54 and 74
/=search all subheadings
Contributions of authors
Naomi Winfield (NW) conceived, designed and drafted the protocol and will co-ordinate the review.
Esme Turner (ET), Nicola Barker (NB), Gemma Quinn (GQ) provided input to the protocol.
NW will take a lead role in data collection, designing search strategies, undertaking searches and organising retrieval of papers.
ET, NB, GQ and NW will jointly screen search results, appraise quality of papers and extract data.
NW will take a lead role in writing to the authors of papers for additional information, obtaining additional data about papers and obtaining and screening data on unpublished studies.
NW, ET, NB and GQ will jointly undertake analysis and interpretation of data.
NW and ET will provide a clinical perspective.
NW will take a lead role in writing the review.
Declarations of interest
Sources of support
- Cardiff University, UK.Access to dissertation supervisor and support from academic librarians. Library assistance in obtaining references not available online.
- No sources of support supplied