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

Kim 2016.

Study characteristics
Methods Study design: randomised controlled cross‐over trial comparing unassisted cough and cough augmentation using MAC, MIE, and MIE + MAC.
Study grouping: cross‐over
'Rescue' vs maintenance therapy: maintenance
Ethics: all 40 participants provided written informed consent. Ethical approval was obtained from the local ethics committee (no reference number provided).
Participants Baseline characteristics
Separate period data were not provided for the cross‐over trial; therefore, only overall sample data were reported.

  • Total sample size, n: 40

  • Age in years, mean: 20.9 (SD 7.2)

  • Gender (male/female), n: 37/3

  • FVC in mL, mean: 667.4 (SD 313.4)

  • FVC % predicted value, mean: 17.9 (SD 10.2)

  • MIP in cmH2O, mean: 19.5 (SD 10.2)

  • MIP% predicted value, mean: 19.1 (SD 10.3)

  • MEP in cmH2O, mean: 25.3 (SD 19.6)

  • MEP% predicted value, mean: 16.0 (SD 12.7)

  • Diagnosis, n: DMD 20, SMA 13, progressive muscular dystrophy 5, myasthenia gravis 1, congenital myopathy 1


Inclusion criteria

  • Stable NMD

  • Receiving NIV

  • Familiar with the use of MIE device at time of enrolment


Exclusion criteria

  • Pneumonia or another intercurrent respiratory infection

  • Cognitive impairment

  • Severe bulbar dysfunction

  • Tracheostomy status
Interventions Intervention characteristics
Unassisted cough

  • Participant positioning: semi‐recumbent or sitting (60° to 90° from supine)

  • Technique description: participants were asked to cough as forcefully as possible through the CoughAid (at the same time the pushing bar was pressed to allow air flow through the device)

  • Washout after intervention: 10 min


Manual thrust (MAC) following manual breathstacking

  • Participant positioning: semi‐recumbent or sitting (60–90° from supine)

  • Technique description: maximal breathstacking was performed with an Ambu‐bag (attached to the connection part of the CoughAid) up to MIC. Thereafter, the participant was asked to cough (while pushing bar was pressed) and MAC (abdominal thrust) was applied.

  • Washout after intervention: 10 min


MI‐E

  • Participant positioning: semi‐recumbent or sitting (60° to 90° from supine)

  • Technique description: MI‐E device (CoughAssist, Respironics) was connected to the CoughAid, insufflation pressure of +40 cmH2O and exsufflation pressure of –40 cmH2O were applied. 5 cycles were performed using the manual mode (to correlate with patient's inspiratory and cough efforts). Insufflation time 3 s, exsufflation time 2 s, with a 3 s pause between cycles. On the 5th application, the participant was asked to perform a maximal voluntary cough into the CoughAid. A face mask interface was used.

  • Washout after intervention: 10 min


MI‐E + manual thrust

  • Participant positioning: semi‐recumbent or sitting (60° to 90° from supine)

  • Technique description: similar to MI‐E technique, with the addition of an abdominal thrust (MAC) being applied during the cough manoeuvre.

  • Washout after intervention: 10 min
Outcomes Separate first‐period data were not presented, precluding analysis.
PCF

  • Outcome type: continuous

  • Units: L/min

  • Measurement technique: the Cough Aid technique was used to measure PCF, using a 1‐way valve connected to the MI‐E or Ambu‐bag; and a "pushing bar" which is pressed manually during cough to allow air to exit through the device. A commercial flow analyser test system with the Cough Aid device (Certifier FA, TSI Inc, Shoreview, Minnesota, USA) was used to measure PCF.

  • Fully reported


Adverse events: not reported. All 3 cough augmentation techniques were reported to be "well tolerated."
Identification Sponsorship source: none mentioned
Conflict of interest: declared no financial conflicts of interests, but other interests were not declared.
Country: Korea
Setting: not specifically stated
Comments: seemed to have been in an outpatient setting; however, the exact setting was unclear.
First author name: Sun Mi Kim
Corresponding author: Dr Seong‐Woong Kang
Institution: Yonsei University College of Medicine
Email: kswoong@yuhs.ac
Address: Department of Rehabilitation Medicine, Gangnam Severance Hospital, Rehabilitation Institute of Neuromuscular Disease, Yonsei University College of Medicine, 211 Eonju‐ro, Gangnam‐gu, Seoul 06273, Korea
Notes Attempts to contact authors for first‐period data were unsuccessful.
A new device was used for measurement of PCF (CoughAid), and authors indicated that it accurately measured PCF in people with ALS. However, the article referred to the effectiveness of the CoughAid as a cough augmentation device, not as a measurement device for PCF. Therefore, the validity of this device was unclear.
Risk of bias
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Unclear risk Quote: "…following an MIC maneuver, MI‐E, and MI‐E in combination with manual thrust, with a 10‐minute washout period between conditions. The order of the PCF measurements was randomized."
Quote: "randomized crossover single‐center controlled trial,"
Comment: randomised cross‐over trial with randomisation of order of cough augmentation techniques. However, the method of randomisation was unclear.
Allocation concealment (selection bias) Unclear risk Comment: insufficient information to allow judgement (method of concealment not described).
Blinding of participants and personnel (performance bias)
All outcomes High risk Comment: neither participants nor personnel could feasibly be blinded to cough augmentation intervention allocation.
Blinding of outcome assessment (detection bias)
All outcomes High risk Comment: same staff performing the cough intervention also performed the assessment; there was no attempt to blind outcome measurement.
However, it noted that inter‐rater (0.98) and intra‐rater (0.99) reliability for measuring the primary outcome of PCF was high.
Incomplete outcome data (attrition bias)
All outcomes Low risk Comment: there were no attritions, and all participants performed all interventions. There were no dropouts or loss to follow‐up.
Selective reporting (reporting bias) Low risk Comment: the primary outcome measure of PCF was fully reported. No secondary outcome measures were defined.
Other bias High risk Comment: the following factors placed the study at high risk for other bias.

  • Short‐term 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.

  • The authors acknowledged the following limitation: some participants individually showed better PCF values with MAC following MIC, than with MI‐E alone. Presenting aggregated mean values may have obscured individual variation. It would have reduced bias to present between subject variability.

  • The use of NIV (diurnal, nocturnal, or both) was not specified, which is a potential confounder.

  • Mean change in PCF was not compared among different interventions, rather the absolute values obtained with the interventions were reported.

  • The CoughAid device was reported to be valid and reliable in ALS; however, the cited study was not aimed at determining validation/accuracy of measurement, and the population (ALS vs other NMD), also differed. Therefore, the validity of the device in measuring PCF in the general NMD population was unclear.

  • The results sections and descriptions of statistical analytical methods were limited.

  • No separate data were available for each period of cross‐over study, and data were, therefore, unable to be pooled for meta‐analysis.

  • Unclear if patients were treated equally between the different arms of the study, in terms of standard management.

  • No distinction could be made between the various conditions (DMD, SMA, etc.) or age groups (adolescents and adults).

  • No washout period was described.

  • Learning effect may have influenced the results.