Chatwin 2009.

Study characteristics
Methods	Study design: 2‐day randomised controlled cross‐over trial comparing standard chest physiotherapy with and without MI‐E Study grouping: cross‐over 'Rescue' vs maintenance therapy: rescue Ethics: ethical clearance obtained. All participants, caregivers, or both, provided informed consent
Participants	Baseline characteristics Separate period data for the cross‐over trial were not available, therefore, overall baseline data were presented for the entire sample only. Overall Sample size, n: 8 Age in years, median: 21.5 (range 4–44) Gender (male/female) n: 6/2 Diagnosis, n: DMD 4, SMA II 3, congenital myopathy 1 C‐reactive protein level in mg/L, median: 113 (range 13–321) White cell count in × 109 cells/L, median: 14 (range 7–25) NIV use, n: 8 (nocturnal 4, occasional 1, > 23 hours/day 2, 20 hours/day 1) Difficulty clearing secretions, n: 8 Duration NIV use in months, median: 19.5 (range 1–130) Inclusion criteria Participants aged > 3 years admitted to Royal Brompton Hospital (adult and paediatric wards) with confirmed NMD and an acute respiratory infection. Acute respiratory tract infection determined by a participant presenting with ≥ 3 of the following: decreased oxygen saturation < 94%; sputum production (patient producing yellow or green secretions when normally has none); increased shortness of breath (subjectively reported or increase in resting respiratory rate of > 5 breaths/min); pyrexia (temperature > 38 °C); signs of infection on chest x‐ray (collapse or consolidation) or auscultation (presence of crackles in lung fields); elevated C‐reactive protein (> 5 mg/L) or white‐cell count (> × 109 cells/L). All participants used nocturnal NIV. Exclusion criteria Pneumothorax Tracheostomy Severe bulbar weakness Severe uncontrolled asthma Rapidly progressive chest infection with failure to control arterial blood gas tension using NIV Patients referred for weaning of NIV after intubation. Pretreatment: cross‐over study. Separate data were not provided for allocation groups at baseline or for the first period of cross‐over. Sputum growth/culture: 3 sputum cultures were positive Chest x‐ray: at baseline 5 participants presented with changes on chest x‐ray
Interventions	Intervention characteristics Participants received MI‐E for 1 treatment session and no MI‐E for the second treatment session, in a randomly assigned order, with reverse cross‐over the following day. Standard airway clearance therapy without in‐exsufflation Technique description: modified ACBT on NIV with manual assisted cough (abdominal thrust): ACBT comprised: breathing control, 4 or 5 thoracic expansion exercises by changing settings on NIV to increase tidal volume and for preinsufflation part of cough, with or without manual chest physiotherapy techniques (clapping, shaking), breathing control, forced expiration technique. Expiration was performed with MAC. Patient position: not specified Frequency: twice a day (morning and afternoon). If evening treatments were required, conventional physiotherapy was provided. If treatment time was required "earlier" than standardised treatment, this was provided and further treatment times adjusted accordingly. Duration: minimum 30 min, after which participants were reassessed. If treatment was considered incomplete at 30 min (on reassessment), the session was continued (until fatigue or effective airway clearance or no more secretions). Additional time after 30 min was recorded. Standard airway clearance therapy with in‐exsufflation Technique description: similar to non‐MI‐E intervention ("standard care"), but with MI‐E added (CoughAssist, Philips Respironics, Murrysville, Pennsylvania, USA) during the cough manoeuvre (manual mode), together with MAC. Settings were: +20 cmH2O (range 15–35 cmH2O) and exsufflation: –20 cmH2O (range –20 cmH2O to –40 cmH2O). Insufflation time 2–4 s, exsufflation time: 4̫–5 s. A face mask interface was used for MIE. Patient position: not specified Frequency: twice a day (morning and afternoon). If evening treatments were required, conventional physiotherapy was provided. If treatment time was required "earlier" than standardised treatment, this was provided and further treatment times adjusted accordingly. Duration: minimum of 30 min, then reassessed. If treatment was incomplete at 30 min (reassessment), session was continued (until fatigue or effective airway clearance or no more secretions). Additional time after 30 min was recorded.
Outcomes	Separate first‐period data were not presented, precluding analysis. Transcutaneous oxygen saturation (SpO2) Outcome type: continuous Reporting: not fully reported Unit of measure: % Direction: higher was better PtcCO2 Outcome type: continuous Reporting: not fully reported Unit of measure: % Direction: higher was worse Treatment time after 30 min Outcome type: continuous Reporting: fully reported Unit of measure: min Direction: lower was better Auscultation score Outcome type: ordinal, subjective (VAS) Reporting: fully reported Direction: lower was better VAS for comfort, mood, breathlessness, fatigue, and presence of sputum Outcome type: ordinal, subjective (VAS) – separate scores for each item listed above Reporting: not fully reported – some data presented in figures only, no values or significance levels provided Direction: lower was better Evaluated 1–2 min before and 1–2 min after intervention Adverse events: fatigue based on VAS; no other adverse events reported on.
Identification	Sponsorship source: partly sponsored by the Jennifer Trust for Spinal Muscular Atrophy, UK Conflict of interest statement: disclosed a relationship with a healthcare company (Breas Medical) that manufactures ventilation equipment, although the nature of the relationship and the relevance to this study was unclear. Country: UK Setting: Royal Brompton Hospital (adult and paediatric wards), London Comments: M Chatwin disclosed a relationship with Breas Medical, Molnlycke, Sweden; A Simonds had no conflicts of interest. First author name: Michelle Chatwin Institution: Royal Brompton Hospital Email: m.chatwin@rbht.nhs.uk Address: Sleep and Ventilation Unit; Royal Brompton Hospital; Sydney street, London, UK
Notes	Author was contacted for first‐period baseline and outcome data; however, these data were not available.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "2‐day randomized crossover treatment program." Quote: "Patients were randomized to group 1 or group 2." Comment: 2‐day randomised cross‐over trial; however, unclear how randomisation was performed.
Allocation concealment (selection bias)	Unclear risk	Comment: no information provided. Unclear whether or how allocation concealment was maintained.
Blinding of participants and personnel (performance bias) All outcomes	High risk	Comment: participants and therapists performing the interventions could not feasibly have been blinded to treatment allocation.
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Comment: the assessor performing the auscultation and determining the auscultation score was blinded to allocation. No information provided regarding blinding of other outcome assessors. Potential high level of assessor bias for the outcome measure "treatment time."
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Comment: unclear whether outcome data on all 8 included participants were presented. This was not explicitly mentioned in the text.
Selective reporting (reporting bias)	High risk	Comment: data were not presented for the primary physiological outcome measures of SpO2, heart rate, and PtcCO2. Other prespecified outcome measures were reported. VAS scores for comfort, breathlessness, and mood were only presented as graphs and data could not be extracted precisely.
Other bias	High risk	Quote: "Airway clearance sessions were standardized to prevent treatment bias. Individuals had their randomized treatment at standardized times, as in other airway clearance studies." Quote: "Patients then continued to have treatment until they were fatigued or there were no longer any secretions produced." Comment: the following factors placed the study at high risk for other bias: Cross‐over study design – this may not be the ideal study design for a condition such as NMD requiring long‐term follow‐up. Sampling method used: purposive sampling, inclusion of all eligible participants at 1 centre or hospital. No mention of whether order of group allocation influenced results (carry‐over effect). Separate data for the 2 periods of cross‐over were not available, therefore, data could not be pooled in meta‐analysis. Treatment standardisation was in place, but this was not further defined. A minimum duration of intervention was described, but the stopping rule of 'fatigue' was unclear and could have introduced bias for this outcome measure. Discrepancy between decrease in secretions (depicted in Figure 2 of publication) with in‐exsufflation after intervention and what was stated in the text on page 1477.