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

1. Summary of findings: cough augmentation therapy, short‐term outcomes – details of PCF by comparison.

Mean difference in PCF post intervention‐baseline (L/min)
Comparison (experimental vs control/alternative therapy/sham therapy)	Summary of results	Illustrative comparative risks		Relative effect (95% CI)	No of participants (studies)	Certainty of the evidence (GRADE)	Comments
	Summary of results	Control/comparator	Experimental	Relative effect (95% CI)	No of participants (studies)	Certainty of the evidence (GRADE)	Comments
Manual breathstacking vs mechanical breathstacking Follow‐up: < 1 day	No evidence of a difference between manual and mechanical breathstacking in the change of PCF.	The mean PCF difference in the comparison group was 67 (SD 73) L/min	The mean PCF difference in the experimental group was 61 (SD 72) L/min	MD 6.00 (–33.43 to 45.43)	52 (1)	⊕⊕⊝⊝ Low^a	Based on 1 short‐term RCT with high risk of performance and detection bias and unclear allocation concealment (Toussaint 2016).
Glossopharyngeal breathing vs manual breathstacking Follow‐up: < 1 day	No evidence of a difference between glossopharyngeal breathing and manual breathstacking in the change of PCF.	The mean PCF difference in the comparison group was 72.86 (SD 61.84) L/min	The mean PCF difference in the experimental group was 32.14 (SD 26.44) L/min	MD –40.72 (–90.54 to 9.10)	14 (1)	⊕⊝⊝⊝ Verylow^b	Based on first‐period data from 1 cross‐over RCT with unclear allocation concealment, very small sample size, imprecision of results (wide CI), and substantial risk of performance and detection bias (Torres‐Castro 2016).
Mechanical insufflation + MAC vs MI‐E Follow‐up: < 1 day	Mechanical insufflation + MAC produced a greater change in PCF compared to MI‐E alone.	The mean PCF difference in the comparison group was 53.4 (SD 51) L/min	The mean PCF difference in the experimental group was 124.8 (SD 38.4) L/min	MD 71.40 (18.08 to 124.72)	11 (1)	⊕⊝⊝⊝ Verylow^c	Based on first‐period data of 1 cross‐over RCT with very small sample size, imprecision of results (wide CIs), and substantial risk of performance and other biases (Lacombe 2014).
MI‐E + MAC vs MI‐E Follow‐up: < 1 day	No clear evidence of a difference between MI‐E + MAC compared to MI‐E alone in the change in PCF.	The mean PCF difference in the comparison group was 53.4 (SD 51) L/min	The mean PCF difference in the experimental group was 106 (SD 50.4) L/min	MD 52.80 (–0.32 to 105.92)	54 (2)	⊕⊝⊝⊝ Verylow^c	Analysis based on first‐period data of 1 randomised cross‐over study with very small sample size (n = 14), imprecision of results (wide CIs), and substantial risk of performance and other biases (Lacombe 2014).
MI‐E + MAC vs MI‐E Follow‐up: < 1 day		Study reported significantly higher PCF with MI‐E + MAC compared to MI‐E alone		N/A	54 (2)	⊕⊝⊝⊝ Verylow^c	The second study was a cross‐over RCT with high risk of performance, detection and other bias (Kim 2016). Separate period data were not reported, precluding analysis and assessment of precision.
MI‐E + MAC vs mechanical insufflation + MAC Follow‐up: < 1 day	There was no evidence of a difference in PCF change between MI‐E + MAC and mechanical insufflation + MAC.	The mean PCF difference in the comparison group was 124.8 (SD 38.4) L/min	The mean PCF difference in the intervention groups was 106 (SD 50.4) L/min	MD 18.60 (–34.46 to 71.66)	11 (1)	⊕⊝⊝⊝ Verylow^c	Based on the first‐period data of 1 randomised cross‐over study design with very small sample size, imprecision of results (wide CIs), and substantial risk of performance and other biases (Lacombe 2014).
MAC vs mechanical insufflation Follow‐up: < 1 day	We were unable to draw a conclusion.	Both studies reported no evidence of a difference in PCF between interventions.		N/A	26 (2)	⊕⊝⊝⊝ Verylow^c	Based on 2 cross‐over RCTs with small sample sizes (Chatwin 2003: n = 4; Sivasothy 2001: n = 22). Separate period data were not reported or available, precluding analysis and assessment of precision.
Mechanical insufflation + MAC vs MAC Follow‐up: < 1 day	We were unable to draw a conclusion.	Reported no evidence of a difference in PCF between interventions.		N/A	4 (1)	⊕⊝⊝⊝ Verylow^c	Based on 1 cross‐over RCT with 4 participants eligible for this review (Sivasothy 2001). Separate period data were not reported or available, precluding analysis and assessment of precision.
MI‐E vs MAC Follow‐up: < 1 day	We were unable to draw a conclusion.	MI‐E reported to produce a higher PCF than MAC.		N/A	22 (1)	⊕⊝⊝⊝ Verylow^c	Based on 1 cross‐over RCT with 22 participants (Chatwin 2003). Separate period data were not reported or available, precluding analysis and assessment of precision.
MI‐E vs mechanical exsufflation Follow‐up: < 1 day	We were unable to draw a conclusion.	MI‐E reported to produce a higher PCF than mechanical exsufflation.		N/A	22 (1)	⊕⊝⊝⊝ Verylow^c	Based on 1 cross‐over RCT with 22 participants (Chatwin 2003). Separate period data were not reported or available, precluding analysis and assessment of precision.
MI‐E vs mechanical insufflation Follow‐up: < 1 day	We were unable to draw a conclusion.	PCF reported to be higher with MI‐E than with mechanical insufflation.		N/A	22 (1)	⊕⊝⊝⊝ Verylow^c	Based on 1 cross‐over RCT with 22 participants (Chatwin 2003). Separate period data were not reported or available, precluding analysis and assessment of precision.
Manual breathstacking + MAC vs MI‐E Follow‐up: < 1 day	We were unable to draw a conclusion.	PCF reported to be higher with MI‐E than with MAC + breathstacking.		N/A	40 (1)	⊕⊝⊝⊝ Verylow^c	Based on 1 cross‐over RCT with 40 participants (Kim 2016). Separate period data were not reported or available, precluding analysis and assessment of precision.
MI‐E + MAC vs manual breathstacking + MAC Follow‐up: < 1 day	We were unable to draw a conclusion.	PCF reported to be higher with MI‐E + MAC than with MAC + breathstacking.		N/A	40 (1)	⊕⊝⊝⊝ Verylow^c	Based on 1 cross‐over RCT with 40 participants (Kim 2016). Separate period data were not reported or available, precluding analysis and assessment of precision.
MAC vs manual breathstacking + MAC Follow‐up: < 1 day	We were unable to draw a conclusion.	PCF reported to be higher with manual breathstacking + MAC than with MAC alone.		N/A	28 (1)	⊕⊝⊝⊝ Verylow^c	Based on 1 cross‐over RCT with 28 participants (Brito 2009). Separate period data were not reported or available, precluding analysis and assessment of precision.
Manual breathstacking vs manual breathstacking + MAC Follow‐up: < 1 day	We were unable to draw a conclusion	PCF reported to be higher with manual breathstacking + MAC than with manual breathstacking alone.		N/A	28 (1)	⊕⊝⊝⊝ Verylow^c	Based on 1 cross‐over RCT with 28 participants (Brito 2009). Separate period data were not reported or available, precluding analysis and assessment of precision.
Mechanical breathstacking vs mechanical insufflation Follow‐up: < 1 day	We were unable to draw a conclusion.	PCF reported to be higher with mechanical insufflation compared to mechanical breathstacking. Not quantitatively reported.		N/A	20 (1)	⊕⊝⊝⊝ Verylow^c	Based on 1 cross‐over RCT with 20 participants (Del Amo Castrillo 2019). Data were presented graphically only and could not be precisely extracted from figures provided. Separate period data were not reported or available, precluding analysis and assessment of precision.
CI: confidence interval; MD: mean difference; MAC: manually assisted cough; MI‐E: mechanical insufflation‐exsufflation; min: minute; n: number of participants; N/A: not available; PCF: peak cough flow; RCT: randomised controlled trial; SD: standard deviation.

^aDowngraded twice because results come from a single short‐term RCT at high risk of bias. ^bDowngraded three times based on a single randomised cross‐over study design with very small sample size, imprecision of results (wide CIs), and high risk of performance and detection bias. ^cDowngraded three times based on a single randomised cross‐over study design with very small sample size, imprecision of results (wide CIs), and substantial risk of performance and other biases.