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. 2021 Apr 22;2021(4):CD013170. doi: 10.1002/14651858.CD013170.pub2

Del Amo Castrillo 2019.

Study characteristics
Methods Study design: randomised, open, single‐centre, cross‐over study comparing breathstacking and mechanical insufflation using VCM, both using a home ventilator
Study grouping: cross‐over
'Rescue' vs maintenance therapy: maintenance
Ethics: ethical clearance obtained. All participants or caregivers (or both) provided informed consent
Participants Baseline characteristics (n = 20)
Separate data were not available for group allocations in the first period of cross‐over. Data were presented for all participants who received all interventions.
  • Age in years, median: 32 (IQR 26–50)

  • Gender (male/female), n: 14/6

  • Diagnosis, n: DMD 7; SMA 6; Ulrich syndrome 1; vacuolar myopathy 1; poliomyelitis 1; gamma‐sarcoglycanopathy 2; BMD 1; acid maltase deficiency 1

  • Duration of mechanical ventilation in hours n = 18 (2 not determined); median: 8 (IQR 8–10)

  • Seated VC in %, median: 17 (IQR 14)

  • Maximum inspiratory pressure in cmH2O, median: 21 (IQR 15)

  • Maximum expiratory pressure in cmH2O, median: 21 (IQR 10)

  • PCF in L/min, median: 176 (IQR 68)


Inclusion criteria
  • Documented NMD

  • Using home NIV with a volumetric mode

  • No previous experience with cough‐assistance techniques

  • Aged > 18 years

  • Haemodynamic stability

  • Absence of acute respiratory tract infection in the past month

  • PCF < 270 L/min or maximum expiratory pressure < 45 cmH2O


Exclusion criteria
  • Concomitant lung disease

  • Respiratory infection on day of assessment

  • Tracheostomy

Interventions Intervention characteristics
Breathstacking
  • Position: seated in usual wheelchair

  • Duration: participants could rest between each cough, and total participation did not exceed 1 hour per person.

  • Technique description: using a ventilator equipped with VCM (Astral 150, Resmed, Saint‐Priest, France), a face‐mask interface (Laerdal Medical, Limonest, France), and volumetric mode, participants performed consecutive inspiratory‐hold insufflations until the lungs felt fully expanded, "producing a stretching sensation across the front of the chest, or until the insufflation pressure plateau was 50 cmH2O. The first exhalation after a single augmented insufflation was used to cough. Care was taken to avoid leaks around the face masks during tests, and during coughing participants received "strong verbal encouragement."

  • Repetitions: each test repeated ≥ 3 times


Mechanical insufflation using ventilator VCM
  • Position: seated in usual wheelchair

  • Duration: participants could rest between each cough, and total participation did not exceed 1 hour per person.

  • Technique description: using a ventilator equipped with VCM (Astral 150, Resmed, Saint‐Priest, France), a face‐mask interface (Laerdal Medical, Limonest, France), and using volumetric mode, lungs were intermittently inflated with a volume greater than participants' baseline tidal volume (hyperinflation cycle): the intermittent deep breath began at 110% of baseline tidal volume, and increased volitionally by 10% increments until the insufflated volume reached the highest tolerated value or 500% of baseline tidal volume or until maximum pressure reached 50 cmH2O. Care was taken to avoid leaks around the face masks during tests, and during coughing participants received "strong verbal encouragement."

  • Repetitions: hyperinsufflation cycle automatically repeated after 30 s of usual cycles. Each test was repeated ≥ 3 times.

Outcomes Separate first‐period data were not presented, precluding analysis.
Primary outcome measures
PCF
  • Outcome type: continuous

  • Reporting: not fully reported – data presented graphically only

  • Unit of measure: L/min

  • Technique description: PCF was measured during coughing after the participant was disconnected from the ventilator at the end of the augmented insufflation, to avoid resistance. The highest PCF value of 3 attempts was selected, if the difference did not exceed 10% of the other 2 values.


All measurements were taken with the participant in a sitting position. The PCF measurements were made using a pneumotachograph (Fleisch No. 4, Lausanne, Switzerland). Flow increases were linear at 600 L/min, therefore the volume measured during calibration with a syringe was not influenced by flows of 30–600 L/min. The flow signal was sampled at 1000 Hz and recorded using an analogue‐numeric system (MP100, Biopac System, Goleta, California, USA) and its software (AcqKnowledge).
  • Direction: higher was better


Inspiratory capacity
  • Outcome type: continuous

  • Reporting: fully reported

  • Unit of measure: L

  • Technique description: calculated as tidal volume delivered by the ventilator multiplied by the number of stacked breaths during breathstacking and as the delivered volume during VCM.

  • Direction: higher was better


Secondary outcome measures
Subjective ratings of breathing comfort
  • Outcome type: ordinal, 10‐point VAS

  • Reporting: fully reported

  • Unit of measure: no units

  • Technique description: at the end of each intervention the participant was asked to rate their breathing comfort from 0 to 10

  • Direction: higher was better, scores range from 0 (I breathe very badly) to 10 (I breathe very well).


Subjective ratings of cough effectiveness
  • Outcome type: ordinal, 10‐point VAS

  • Reporting: fully reported

  • Unit of measure: no units

  • Technique description: at the end of each intervention the participant was asked to rate their cough effectiveness from 0 to 10

  • Direction: higher was better, scores ranged from 0, indicating a completely inefficient cough, to 10, indicating a fully effective cough.


Oxygen saturation and heart rate were recorded but not listed as primary or secondary outcome measures.
Adverse events: not reported
Identification Sponsorship source: not stated
Conflict of interest: the authors disclosed a relationship with ResMed France, the company who manufacture the VCM ventilator device. The exact nature of the relationship was unclear.
Country: France
Setting: home ventilation unit of the medical ICU of the Raymond Poincaré Teaching Hospital, Garxhes, France
Comments: authors disclosed a relationship with ResMed, France
First author name: Del Amo Castrillo
Institution: Ms Del Amo Castrillo, Mr Lacombe, and Mr Bore were affiliated with the ICU at Hôpital Raymond Poincaré, AP‐HP, Garches, France. Ms Vaugier and Dr Orlikowski were affiliated with Hôpital Raymond Poincaré, INSERM CIC 1429, Garches, France. Ms Falaize and Dr Prigent, and Dr Lofaso were affiliated with Service de Physiologie‐Explorations Fonctionnelles, Hôpital Raymond Poincaré, AP‐HP, Garches, France
Email: f.lofaso@rpc.aphp.fr
Address: Frédéric Lofaso MD PhD, Services de Physiologie et Explorations Fonctionnelles, Hôpital Raymond Poincaré, AP‐HP, 92380, Garches, France
Notes Study was approved by the French Ethics Committee (Comité de Protection des Personnes) of Saint‐Germain‐en‐Laye, France, on 3 September 2015 (NCPP15031) and registered on ClinicalTrials.gov as NCT02847299.
Attempts to contact the trial author for additional data were unsuccessful.
Risk of bias
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Unclear risk Quote: "We used a randomized, open, single‐center, crossover design…"
Comment: method of randomisation not described.
Allocation concealment (selection bias) Unclear risk Comment: allocation concealment not mentioned in the article.
Blinding of participants and personnel (performance bias)
All outcomes High risk Quote: "One physiotherapist and one technician carried out the tests, prevented leakage and performing measurements."
Comment: the same personnel conducted all interventions and measurements, and, therefore, it was highly unlikely that they would have been blinded. The nature of the interventions suggested that participants could not have been blinded to allocation.
Blinding of outcome assessment (detection bias)
All outcomes High risk Quote: "One physiotherapist and one technician carried out the tests, prevented leakage and performing measurements."
Comment: all outcome assessments were measured by the same technician, who could not feasibly have been blinded.
Incomplete outcome data (attrition bias)
All outcomes Low risk Comment: outcome measures were reported for all participants.
Selective reporting (reporting bias) Low risk Comment: all primary and secondary outcome measures were fully reported.
Other bias High risk Comment: the following factors placed this study at high risk of other sources of bias.
  • Short‐term cross‐over study design – this may not be the ideal study design for a condition such as NMD requiring long‐term follow‐up.

  • There was 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, precluding analysis.