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

Chatwin 2003.

Study characteristics
Methods Study design: prospective randomised cross‐over trial, comparing MI‐E to other cough augmentation techniques*
Study grouping: cross‐over
'Rescue' vs maintenance therapy: maintenance
Ethics: local ethics committee approval. All participants, parents, or both, provided informed consent
Participants Baseline characteristics
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.
Neuromuscular disease group

  • Total sample size, n: 22

  • Age in years adult and paediatric population combined, mean: 25 (SD 13)

  • Age in years paediatric population, mean: 14 (SD 2)

  • Age in years adult population, mean: 32 (SD 13)

  • Gender (male/female), n: 16/6

  • Diagnosis paediatric population, n: SMA 3, DMD 3, CMD 2

  • Diagnosis adult population, n: SMA 7, DMD 3, CMD 1, poliomyelitis 3

  • Diagnosis total population, n: SMA 10, DMD 6, CMD 3, poliomyelitis 3

  • Nocturnal NIPPV, n: 17

  • Duration of nocturnal NIPPV in months, mean: 49 (SD 28)

  • Courses of antibiotics for respiratory tract infections in preceding 12 months, n range: 2–6

  • Poor cough, n (%): 22 (100)

  • Severe scoliosis (Cobb angle > 40°), n: 11

  • Spinal surgery, n: 11

  • SNIP in cmH2O for paediatric population, mean: 24.8 (SD 9.5)

  • SNIP in cmH2O for adult population, mean: 26.7 (SD 17.9)

  • SNIP in cmH2O for total population, mean: 26.0 (SD 14.8)

  • Pmo,w in cmH2O for paediatric population, mean: 21.5 (SD 10.0)

  • Pmo,w in cmH2O for adult population, mean: 31.2 (SD 30.5)

  • Pmo,w in cmH2O for total population, mean: 27.7 (SD 24.6)

  • MIP in cmH2O for paediatric population, mean: 22.7 (SD 14.3)

  • MIP in cmH2O for adult population, mean: 26.6 (SD 16.8)

  • MIP in cmH2O for total population, mean: 25.3 (SD 15.4)

  • MEP in cmH2O for paediatric population, mean: 19.7 (SD 12.2)

  • MEP in cmH2O for adult population, mean: 29.9 (SD 25.8)

  • MEP in cmH2O for total population, mean: 26.5 (SD 21.9)

  • FEV1 in L for paediatric population, mean: 0.5 (SD 0.4)

  • FEV1 in L for adult population, mean: 0.9 (SD 0.7)

  • FEV1 in L for total population, mean: 0.8 (SD 0.6)

  • FVC in L for paediatric population, mean: 0.7 (SD 0.5)

  • FVC in L for adult population, mean: 1.1 (SD 0.9)

  • FVC in L for total population, mean: 0.9 (SD 0.7)

  • FEV1/FVC in % for paediatric population, mean: 76.41 (SD 23.63)

  • FEV1/FVC in % for adult population, mean: 83.3 (SD 13.9)

  • FEV1/FVC in % for total population, mean: 80.7 (SD 17.3)

  • SpO2 in % for paediatric population, mean: 96 (SD 1)

  • SpO2 in % for adult population, mean: 96 (SD 2)

  • SpO2 in % for total population, mean: 96 (SD 1)

  • PETCO2 in kPa for paediatric population, mean: 5.6 (SD 0.4)

  • PETCO2 in kPa for adult population, mean: 5.7 (SD 0.9)

  • PETCO2 in kPa for total population, mean: 5.6 (SD 0.7)


Inclusion criteria (NMD group)

  • Adults and children (all ages)

  • History of recurrent chest infections or ineffective cough, or both

  • Clinically stable


Exclusion criteria (NMD group)

  • Use of antibiotics within 1 month prior to the research

  • Resting SpO2 < 90%

  • PETCO2 > 7 kPa

  • Presence of severe bulbar dysfunction

  • Previous history of pneumothorax


Age‐matched controls

  • Total sample size, n:19

  • Recruited from staff and families

  • Age in years adult and paediatric population combined, mean: 21 (SD 9)

  • Age in years paediatric population, mean: 13.6 (SD 2.4) (SD 2)

  • Age in years adult population, mean: 26(SD 8)

  • SNIP in cmH2O for paediatric population, mean: 95.8 (SD 19.2)

  • SNIP in cmH2O for adult population, mean: 92.3(SD 29.2)

  • SNIP in cmH2O for total population, mean: 93.8 (SD 24.9)

  • Pmo,w in cmH2O for paediatric population, mean: 113.3 (SD 41.0)

  • Pmo,w in cmH2O for adult population, mean: 145.2 (SD 51.)

  • Pmo,w in cmH2O for total population, mean: 131.7 (SD 48.6)

  • MIP in cmH2O for paediatric population, mean: 102.3 (SD 33.0)

  • MIP in cmH2O for adult population, mean: 103.5 (SD 33.2)

  • MIP in cmH2O for total population, mean: 103.0 (SD 32.2)

  • MEP in cmH2O for paediatric population, mean: 94.1 (SD 39.6)

  • MEP in cmH2O for adult population, mean: 121.1 (SD 39.0)

  • MEP in cmH2O for total population, mean: 109.7 (SD 40.5)

  • FEV1 in L for paediatric population, mean: 2.8 (SD 1.3)

  • FEV1 in L for adult population, mean: 3.5 (SD 0.7)

  • FEV1 in L for total population, mean: 3.2 (SD 1.0)

  • FVC in L for paediatric population, mean: 3.5 (SD 1.7)

  • FVC in L for adult population, mean: 4.4 (SD 1.2)

  • FVC in L for total population, mean:4.0 (SD 1.5)

  • FEV1/FVC in % for paediatric population, mean: 79.9 (SD 7.6)

  • FEV1/FVC in % for adult population, mean: 80.8 (SD 9.2)

  • FEV1/FVC in % for total population, mean: 80.4 (SD 8.4)

  • SpO2 in % for paediatric population, mean: 97 (SD 1)

  • SpO2 in % for adult population, mean: 98 (SD 1)

  • SpO2 in % for total population, mean: 98 (SD 1)

  • PETCO2 in kPa for paediatric population, mean: 5.3 (SD 0.4)

  • PETCO2 in kPa for adult population, mean: 5.1 (SD 0.5)

  • PETCO2 in kPa for total population, mean: 5.2 (SD 0.5)


Inclusion criteria (controls)

  • None provided


Exclusion criteria (controls)

  • None provided


Pretreatment: no separate data were provided for the first period of cross‐over, or for separate intervention order groups.
Interventions For all participants, baseline unassisted cough was compared, in random order: to standard physiotherapy and assisted cough; cough after inspiration supported by NIPPV (BiPAP); exsufflation‐assisted cough, with negative pressure initiated manually at end of inspiration; insufflation‐assisted cough; and exsufflation‐assisted cough with negative pressure delivered immediately preceding the cough effort.
Baseline unassisted cough

  • Participant positioning: participant's preferred position, "usually seated."

  • Technique description: 6 maximal unaided coughs, with rest periods in between. Primary outcomes of PCF and patient comfort were measured, as described above, after the intervention.


Standard "physiotherapy assisted cough"

  • Participant positioning: participant's preferred position, "usually seated."

  • Technique description: not described. Primary outcomes of PCF and patient comfort were measured, as described, after the intervention.


Cough after inspiration supported by a non‐invasive positive pressure ventilator

  • Participant positioning: participant's preferred position, "usually seated."

  • Technique description: non‐invasive positive pressure ventilator (BiPAP) used to support inspiration (Respironics Inc, Murraysville, Pennsylvania, USA or PV401, Breas Medical, Moinlucke, Sweden). Pressures titrated to patient comfort. Primary outcomes of PCF and patient comfort were measured, as described, after the intervention.


Exsufflation‐assisted cough, with negative pressure initiated manually at end inspiration

  • Participant positioning: participant's preferred position, "usually seated."

  • Technique description: using the mechanical in‐exsufflator, described for PCF measurement, and a face mask interface ("Cough‐Assist;" JH Emerson Co.; Cambridge, Massachusetts, USA); exsufflation pressure titrated for patient comfort and the negative (exsufflation) pressure initiated manually at the end of inspiration. Primary outcomes of PCF and patient comfort were measured, as described, after the intervention.


Insufflation‐exsufflation‐assisted cough

  • Participant positioning: participant's preferred position, "usually seated."

  • Technique description: using the mechanical in‐exsufflator and a face mask interface ("Cough‐Assist;" JH Emerson Co.; Cambridge, Massachusetts, USA). Insufflation was given using the manual mode during the inspiratory phase. Insufflation pressure was titrated for patient comfort. Negative exsufflation pressure was delivered immediately preceding the cough effort. Primary outcomes of PCF and patient comfort were measured, as described above, after the intervention.


Exsufflation‐assisted cough with negative pressure delivered immediately preceding the cough effort

  • Participant positioning: participant's preferred position, "usually seated."

  • Technique description: using the mechanical in‐exsufflator, described for PCF measurement, and a face mask interface ("Cough‐Assist;" JH Emerson Co.; Cambridge, Massachusetts, USA); exsufflation pressure titrated for patient comfort and the negative (exsufflation) pressure applied immediately before the cough effort. Primary outcomes of PCF and patient comfort were measured, as described, after the intervention.
Outcomes Separate first‐period data were not presented, precluding analysis.
PCF

  • Outcome type: continuous outcome

  • Reporting: fully reported

  • Unit of measure: L/min

  • Direction: higher was better

  • Participant position: seated

  • Technique description: measured by coughing into a tight‐fitting, full‐face mask (Mirage Full‐face mask; ResMed, Abingdon, UK), connected by plastic tubing to a 41 cm long (3.5 cm internal diameter) metal tube, which was, in turn, connected to a Fleisch No. 4 pneumotachograph head (Fleisch, Lausanne, Switzerland) and an electrospirometer (GM Instruments, Kilwinning, UK). The pneumotachograph head was connected via ventilator tubing to a mechanical insufflator‐exsufflator ("Cough‐Assist;" JH Emerson Co.; Cambridge, Massachusetts, USA). Mask pressure was measured from a side port, with the mask secured to the participant's face to minimise air leak.


VAS comfort, distress, and perceived cough strength

  • Outcome type: ordinal

  • Reporting: individual VAS scores not presented, only mean overall VAS

  • Unit of measure: ordinal scale 0–10

  • Direction: higher was better


Adverse events: no adverse events reported and participants were reported to tolerate all interventions well.
Identification Funding source: Jennifer Trust for Spinal Muscular Atrophy,UK (M Chatwin); Brompton Breathers Trust Fund, UK (patient expenses support); Cystic Fibrosis Trust, UK (E Ross); British Lung Foundation, UK (AH Nickol); Association Française Contre Les Myopathies, France (N Hart)
Conflict of interest: funding sources identified and unlikely to constitute a conflict of interests.
Country: UK
Setting: Sleep and Ventilation Unit, Royal Brompton Hospital
Comments: no conflict of interest mentioned
First author name: M Chatwin
Institution: Sleep and Ventilation Unit, Royal Brompton Hospital, London, UK
Email: M.Chatwin@rbh.nthames.nhs.uk
Address: Sleep and Ventilation Unit, Royal Brompton Hospital, Sydney Street, London, UK
Notes *The study was designed as a parallel non‐randomised clinical trial comparing participants with NMD to 19 healthy, age‐matched controls (parallel grouping). Only data from the prospective randomised cross‐over trial within the NMD participant group was eligible for inclusion in this review.
We contacted the author who was unable to provide additional data.
Risk of bias
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Unclear risk Quote: "…random order by coughs assisted by physiotherapy, noninvasive ventilation, insufflation and exsufflation, and exsufflation alone."
Quote: "Initial assessment consisted of at least six maximal unaided coughs followed in random order by the cough intervention techniques;"
Comment: the interventions in the NMD arm of the study were performed in random order to reduce bias. However, it is unclear how randomisation was performed and whether there were baseline differences between groups.
Allocation concealment (selection bias) Unclear risk Comment: no information was provided. Unclear whether or how allocation concealment was maintained.
Blinding of participants and personnel (performance bias)
All outcomes High risk Comment: participants and personnel would have been aware of group allocation, given the nature of the interventions. Those performing the interventions could not be blinded.
Blinding of outcome assessment (detection bias)
All outcomes Unclear risk Comment: PCF was assessed during the cough assist and, therefore, was likely done by a non‐blinded outcome assessor; however, this is not clear from the article. The outcome "comfort" was rated on a VAS scale by the participants, who were aware of the intervention they were given. There was no mention of whether the same assessor performed all measurements.
Incomplete outcome data (attrition bias)
All outcomes Low risk Comment: there were no missing data.
Selective reporting (reporting bias) Unclear risk Quote: "Following each intervention, the subjects rated comfort of intervention, distress and strength of cough produced (0: least; 10: most)."
Comment: separate VAS scores for patient comfort, distress, and strength of cough were not reported; only 1 VAS result was presented, and it is unclear how this was calculated. It was stated that there was no significant change from baseline in results for comfort or distress of intervention on the VAS.
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 with improved co‐ordination and oral control when performing PCF measurements could be a confounder. No information about attempts to minimise the learning effect was provided.

  • Unclear whether groups were treated equally.

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