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

Brito 2009.

Study characteristics
Methods Study design: prospective randomised cross‐over trial comparing MAC, breathstacking, and MAC + breathstacking
Study grouping: cross‐over
'Rescue' vs maintenance therapy: maintenance
Ethics: ethical clearance provided by Federal University of São Paulo (UNIFESP) Research Ethics Committee (CEP 0775/06)
Participants Baseline characteristics
Separate data were not documented for group allocations in the first period of cross‐over. Data were presented for all participants, who received all interventions.
  • Sample size, n: 28

  • Age in years, mean: 20 (SD 4)

  • FVC % predicted, mean: 29 (SD 12)

  • Bodyweight in kg, mean: 56 (SD 17)

  • Pronounced kyphoscoliosis, n: 17


Inclusion criteria
  • DMD

  • Aged > 10 years

  • Receiving NIV (BiPAP)

  • FVC < 60% of predicted

  • Intellectual level sufficient to perform the manoeuvres


Exclusion criteria
  • Current acute infection

  • Other NMDs

  • Presence of nasogastric tube


Pretreatment
  • Not applicable

  • All participants randomly received the various cough augmentation techniques

Interventions Intervention characteristics
Baseline spontaneous MEE
  • Participant positioning: sitting

  • Technique description: participants were asked to take a deep inhalation, after which PCF for spontaneous (unassisted) MEE was measured.


Manual chest compression (MAC)
  • Participant positioning: sitting

  • Technique description: therapist placed external pressure on the rib cage by placing 1 hand over the posterosuperior region of the chest and 1 hand supported the anterior region of the chest at the inferior third of the sternum. The participant was instructed to inhale deeply (spontaneous maximal inspiratory effort), close their glottis and on exhalation therapist applied chest compression in the direction of the abdomen (down and inwards).


Breathstacking using a manual resuscitation bag
  • Participant positioning: sitting. Participant's head was supported (to avoid hyperextension)

  • Technique description: sequential insufflations were delivered using a manual resuscitation bag, with closed unidirectional valve (Moriya, São Paulo, Brazil) and a face‐mask interface. The mask was fitted firmly to the participant's face to avoid air leaks. With each compression of the manual resuscitation bag, the participant was instructed to take a deep breath and hold it. With each subsequent compression of the manual resuscitation bag, the participant inhaled again, without releasing the air inhaled previously. 1 complete air stacking manoeuvre consisted of 3 insufflations without exhalation. After the third insufflation, the participant made a forced exhalation, and the PCF with maximal expiratory effort was measured.


Chest compressions (MAC) + breathstacking
  • Participant positioning: sitting

  • Technique description: breathstacking as described above followed by manual chest compression (MAC) as described above.

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

  • Reporting: fully reported

  • Unit of measure: L/min

  • Technique description: all measurements were taken by the same examiner and with the participant in a sitting position. The PCF measurements were determined using a disposable cardboard mouthpiece attached to a peak flow meter (Mini‐Wright AFS; Clement Clarke International, Essex, England), on MEE.

  • Direction: higher was better


Adverse events: not reported
Identification Funding source: financial support was provided by the Associação Fundo de Incentivo à Psicofarmacologia (AFIP, Association for the Incentive Funding of Psychopharmacology).
Conflict of interest statement: funding source declared and unlikely to constitute a conflict of interest.
Country: Brazil
Setting: outpatient clinic: Pediatric Sector of the Noninvasive Mechanical Ventilation Outpatient Clinic of the Psychobiology Department of the Sleep Institute at UNIFESP, Federal University of São Paulo
Author name: Magneide Fernandes Brito (corresponding author)
Institution: Sleep Medicine and Biology Division of the Psychobiology Department; Federal University of São Paulo
Email: magneide@gmail.com
Address: Rua Marselhesa, 500, 14° andar, Vila Clementino, CEP 04020‐060, São Paulo, SP, Brazil
Notes Attempts to contact the corresponding author for additional data were unsuccessful.
Risk of bias
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Unclear risk Quote: "To avoid the influence of the order of the maneuvers and minimize patient fatigue, the sequence of the time points (other than, obviously, baseline) was random."
Comment: there was no intervention and control group, each participant acted as their own control in a cross‐over design. All participants had baseline measurements, which were compared to various cough augmentation interventions. Although there was random allocation of intervention order, there was no indication of how randomisation was done. Separate group/period data were not provided so baseline imbalances could not be determined.
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: although not stated in the study, this was likely not achieved, as both participants and personnel performing the interventions would have been aware of allocation.
Blinding of outcome assessment (detection bias)
All outcomes High risk Quote: "the PCF measurements were taken during a spontaneous MEE accompanied by chest compression…"
Quote: "For the air stacking‐only time point, the PCF measurements were made after air stacking…"
Quote: "…after the third insufflation, the patient made a forced exhalation, and the PCF with MEE was measured."
Quote: "For the combined technique time point, the PCF was measured after the use of air stacking with a manual resuscitation bag followed by chest compression with MEE."
Comment: PCF values were measured while performing the cough assist techniques and, therefore, assessment could not have been performed blinded. This leads to potential detection bias. The same examiner performed all measurements.
Incomplete outcome data (attrition bias)
All outcomes Low risk Quote: "We excluded 2 patients for not having the intellectual capacity to understand and perform the maneuvers involved in the spirometry and PCF measurements."
Comment: 2 participants were excluded with reasons provided; there were no other missing data or dropouts reported. All 28 participants' data were presented in Figure 2 of the publication.
Selective reporting (reporting bias) High risk Comment: not all the prespecified outcome measures were reported in the results, e.g. SpO2, expired CO2, and all spirometric measures. Of the last‐mentioned, only FVC was reported (mean FVC% predicted 29% (SD 12%)); no other spirometry or bio‐demographic values were provided. Data for the primary outcome measure, PCF, were presented; however, separate period data were not provided, precluding the possibility of meta‐analysis.
Other bias High risk Comment: the following factors placed the study at high risk of other bias.
  • Study design (cross‐over trial) with undetermined carry‐over effect

  • Potential learning effect regarding techniques and improved co‐ordination with performance of assessment techniques was not considered, and may have been a confounder.

  • No washout period or time was mentioned.

  • Comorbid conditions were not reported (potential confounding factors).

  • No mention of standard therapy (how groups were treated throughout the study besides the intervention).

  • Separate data for the first period of cross‐over were not provided, and data could, therefore, not be included in meta‐analysis.