Lacombe 2014.

Study characteristics
Methods	Design: randomised controlled cross‐over trial comparing mechanical insufflation + MAC, MI‐E, and MI‐E + MAC Group: cross‐over 'Rescue' vs maintenance therapy: maintenance Ethics: approved by hospital's ethics committee. Patients provided written informed consent before participating. Registered on ClinicalTrials.gov (NCT01518439). Time frame: March 2012 to June 2013 Additional comments on methodology: open, single‐centre, randomised (block size of 6) cross‐over study
Participants	The author provided baseline separate group allocation data for the first period of cross‐over on request. Baseline characteristics Entire sample Sample size, n: 18 Age in years, median: 28.5 (IQR 24.0–38.0) Gender (male/female), n: 13/5 Diagnosis, n: DMD 9; BMD 1; acid maltase deficiency 2; SMA 2; congenital MD 1; gamma‐sarcoglycanopathy 2; Ulrich syndrome 1 Duration of mechanical ventilation during the day in hours/day, median: 10 (IQR 8–13.5) VC, in %, median: 11.5 (IQR 8–22) MIP in cmH2O, mean: 15.05 (SD 6.06) MEP in cmH2O, median: 12 (IQR 10–16) PCF in L/min, mean: 124.2 (SD 60.6) IPPB pressure in cmH2O, median: 39 (IQR 35–840) Mechanical insufflation + MAC Sample size, n: 4 Age in years, median: 30.5 (IQR 4.25) Gender (male/female), n: 2/2 Diagnosis, n: DMD 2; congenital MD 1; gamma‐sarcoglycanopathy 1 Mechanical ventilation duration in hour/day, median: 16.5 (IQR 13.5) VC seated in %, mean: 18.5 (SD 5) MIP in cmH2O, mean: 14.5 (SD 7.75) MEP in cmH2O, mean: 9 (SD 7) PCF in L/min, mean: 100.8 (SD 69.0) IPPB pressure in cmH2O, mean: 37.5 (SD 6.25) MI‐E pressure in cmH2O, mean (SD): N/A MI‐E Sample size, n: 7 Age in years, median: 31 (IQR 18.5) Gender (male/female), n: 5/2 Diagnosis, n: DMD 3; BD 1; SMA 1; gamma‐sarcoglycanopathy 1; acid maltase deficiency 1 Mechanical ventilation duration in hour/day, median: 8 (IQR 1.5) VC seated in %, mean: 22 (SD 16) MIP in cmH2O, mean: 20 (SD 8) MEP in cmH2O, mean: 16 (SD 29.5) PCF in L/min, mean: 157.2 (SD 64.2) IPPB pressure in cmH2O, mean (SD): N/A MI‐E pressure in cmH2O, mean: +33 (SD 4.5)/–38 (SD 3) MI‐E + MAC Sample size, n: 7 Age in years, median: 25 (IQR 7.5) Gender (male/female), n: 6/1 Diagnosis, n: DMD 4; SMA 1; acid maltase deficiency 1; Ulrich syndrome 1 Mechanical ventilation duration in hour/day, mean: 10 (SD 2.25) VC seated in %, mean: 8 (SD 2.5) MIP in cmH2O, mean: 15 (SD 4.5) MEP in cmH2O, mean: 11 (SD 3.5) PCF in L/min, mean: 104.4 (SD 41.4) IPPB pressure in cmH2O, mean (SD): N/A MI‐E pressure in cmH2O, mean: +35 (SD 6.5)/–40 (SD 3.5) Inclusion criteria Confirmed/documented NMD Cough assist naive (inexperienced) Aged > 18 years Haemodynamically stable Absence of acute respiratory infection (bronchial congestion) 1 month prior to study PCF < 3 L/sec (180 L/min) (threshold for statutory healthcare insurance coverage in France and Belgium) or MEP < 45 cmH2O Presence of NIV Exclusion criteria None specified Pretreatment Baseline VC was considerably different among participant groups, with the lowest value recorded in the MI‐E + MAC group. This suggests there may have been baseline differences in participant groups, which may have influenced the outcomes.
Interventions	Mechanical insufflation + MAC Position: seated in wheelchair Technique description: insufflation was provided by an Alpha 200 C ventilator (Air Liquide, Antony, France). Participants started IPPB insufflation with an inspiratory effort, then allowed the insufflation to continue passively until the selected inspiratory pressure was reached in about 5 s. The lowest inspiratory trigger was chosen to facilitate the start of insufflation. Inspiratory pressure (insufflation) with IPPB was increased gradually to the highest tolerated value, or 40 cmH2O. Inspiratory flow was set to maximise participant comfort. Once target inspiratory pressure was reached, 1 physiotherapist removed the IPPB circuit to avoid resistance while coughing. At the same time, MAC (compression to the abdomen, thorax, or both, participant and on cough efficiency as perceived by the participant and physiotherapist. Interface: IPPB was applied using a face mask, chosen to fit each participant individually. MI‐E Participant position: seated in wheelchair Technique description: MI‐E was performed using the CoughAssist device (JH Emerson Co., Cambridge, Massachusetts, USA) in manual mode. After each insufflation, a physiotherapist delivered the exsufflation while simultaneously asking the participant to cough. Inspiratory and expiratory pressures were increased/decreased gradually to the highest/lowest tolerated values, up to +40 cmH2O for inspiratory pressure and down to –40 cmH2O for expiratory pressure. Insufflation flow adjustment (high or low insufflation flow) was set according to participant comfort. Interface: MI‐E was applied using a face mask, chosen to fit each participant individually. MI‐E + MAC MI‐E and MAC interventions as described above.
Outcomes	Separate first‐period data were not presented, precluding analysis. Primary objective outcome PCF Outcome type: continuous Unit of measure: L/min Measurement: unassisted cough effort. All tests were repeated ≥ 3 times. The highest PCF value was used for analysis (if the difference did not exceed 10% of the other 2 values). Flow was measured making use of a Fleisch No. 4 Pneumotachograph First‐period data fully reported on request Secondary objective outcomes Effective cough time: time with PCF > 3 L/s or 180 L/min Outcome type: continuous Unit of measure: ms Not fully reported (presented graphically only) Inspiratory capacity Outcome type: continuous Unit of measure: L Not fully reported (presented graphically only) Secondary subjective outcomes Comfort ratings Outcome type: ordinal Unit of measure: VAS (0 – "I breathe very badly" to 10 – "I breathe very well") Fully reported Subjective cough effectiveness Outcome type: ordinal Unit of measure: VAS (0 – completely inefficient cough to 10 – fully effective cough) Fully reported Adverse events: not reported
Identification	Sponsorship source: no declaration of funding source Conflict of interest: not declared Country: France Setting: home ventilation unit of the medical ICU, Raymond Poincare Teaching Hospital, Garches Comments: registered on ClinicalTrials.gov (NCT01518439) Author name: Matthieu Lacombe was the primary author; Prof F Lofaso is the contact author Institution: Hôpital Raymond Poincaré Email: f.lofaso@rpc.aphp.fr Address: Réanimation Médicale, Physiologie – Explorations Fonctionnelles, Centre d’Innovations Technologiques UMR 805, Hôpital Raymond Poincaré, AP‐HP, Garches; EA 4497, Université de Versailles Saint‐Quentin‐en‐Yvelines, Versailles, France"
Notes	Separate baseline data and postintervention data for first‐period group allocation were provided by author on request.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Comment: cross‐over trial during which cough assist techniques were applied in random order; however, it was unclear how randomisation was performed.
Allocation concealment (selection bias)	Unclear risk	Comment: insufficient information was provided to determine if participants/physiotherapists involved in the study could have foreseen the cough augmentation technique allocated.
Blinding of participants and personnel (performance bias) All outcomes	High risk	Comment: it would not be possible for participants and those implementing the cough augmentation techniques to be blinded to the cough augmentation used. 3 physiotherapists (MLa, LDAC, and AB) were involved in interventions and assessments. For each participant, 2 physiotherapists were needed for the intervention: 1 for using the device and 1 for MAC manoeuvres. The same physiotherapist performed the different cough techniques for a single participant. In addition, the same technician (MLe) performed the measurements.
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Comment: unclear whether the outcome assessor was blinded to group allocation, but seems likely that blinding would not have been possible.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Comment: no incomplete data in the study report.
Selective reporting (reporting bias)	Unclear risk	Comment: primary outcome measure of PCF and secondary outcomes of effective cough time and inspiratory capacity were only presented graphically, with no specific values provided. Subjective secondary outcome measures of comfort and cough effectiveness (VAS) were fully reported.
Other bias	High risk	Comment: the following factors placed the study at high risk of other bias. Cross‐over study design, which may not be appropriate for a condition such as NMD, which requires long‐term follow‐up. Undetermined carry‐over effect. Learning effect, fatigue, and the variety of NMD included could have affected outcomes (potential confounders). Standardisation of interventions were not ensured, with techniques adapted for participant comfort.