Update: Non-Invasive Positive Pressure Ventilation in Chronic Respiratory Failure Due to COPD

Figures & data

Table 1. Studies employing LI-NPPV; showing benefit of NPPV

Prospective randomized studies
First author year (reference)	Mean IPAP cmH2O	Mean EPAP cmH2O	Study design	Study Length	Number of patients	Outcomes
Garrod et al. 2000 (16)	16	4	NPPV+ E.T vs. E.T alone	8 weeks	55	Significant Improvement in mean shuttle walk test, chronic respiratory disease questionnaire, and PaO2 in NPPV+E.T group.
Diaz et al. 2002 (17)	18	2	NPPV vs. Sham NPPV	3 weeks	36	Day time PaCO2 and PaO2 and also PFT improved in NPPV group
Sin et al. 2007 (18)	20	4	NPPV vs. Sham NPPV	3 months	23	Blood gasses, 6 MWD, HRV were improved and natriuretic peptide was reduced in NPPV group however FEV1 was not different between groups.
Duiverman et al. 2008 (19)	20	6	NPPV + rehabilitation vs. rehabilitation	3 months	72	Day time PaCO2, cognition domain, fatigue domain and SRI summary score, minute ventilation, tidal volume were improved in NPPV group.
Prospective crossover studies
Ambrosino 1992 (20)	22	0	NPPV vs. standard treatment sequentially	<1 week	8	Significant improvement in pH, PaCO2, PaO2, minute ventilation and tidal volume in NPPV group.
Meecham et al. 1995 (21)	18	2	NPPV+LTOT vs. LTOT sequentially	3 months	14	Day time PaO2 and PaCO2, overnight PaCO2 total sleep time, sleep efficiency, HRQL were improved in favor of NPPV group.

LI-NPPV, Low intensity non-invasive positive pressure ventilation; IPAP, inspiratory positive airway pressure; EPAP, expiratory positive airway pressure; E.T, exercise training; vs,versus; LTOT, long-term oxygen therapy; PFT, pulmonary function test; HRQL, health-related quality of life; SRI, The severe respiratory insufficiency questionnaire; HRV, heart rate variability; 6 MWD, 6-minute walk distance.

Table 2. Studies employing LI-NPPV showing non-benefit of NPPV

Prospective randomized studies
First author Date (reference)	Mean IPAP cmH2O	Mean EPAP cmH2O	Study design	Study length	Number of patients	Outcomes
Renston et al. 1994 (22)	15-20	2	NPPV vs. Sham NPPV	<1 week	9	No difference on PaCO2 and PFT in both groups however improved exercise capacity and Borg dyspnea score in NPPV group.
Gay et al. 1996 (23)	10	2	NPPV vs. Sham NPPV	3 months	13	Lung function, nocturnal oxygen saturation, and sleep efficiency remained unchanged in both groups.
Casanova 2000 (24)	13	4	NPPV+LTOT vs. LTOT	1 year	52	Acute COPD exacerbations, hospital admissions, intubations, mortality rates, gas exchange, pulmonary function, cardiac function did not change in either group. However Borg dyspnea score dropped from 6 to 5 and one of the neuropsychological performance was improved in NPPV group.
Clini et al. 2002 (25)	14	2	NPPV+LTOT vs. LTOT	2 years	90	Lung function, inspiratory muscle function, exercise tolerance, sleep quality score, hospital admissions and survival rates did not change in either group. However dyspnea and HRQL, day time PaCO2 were improved in NPPV group.
McEvoy et al. 2009 (26)	13	5	NPPV+LTOT vs LTOT	28 months	144	FEV1 and PaCO2 measured at 6 and 12 months were not different between groups. However nocturnal NPPV improved survival in stable hypercapnic COPD, but this was at the cost of worsening quality of life.
Prospective crossover studies
Strumpf et al. 1991 (27)	15	2	NPPV vs. standard care sequentially.	6 months	7	NPPV revealed no improvements in pulmonary function, respiratory muscle strength, gas exchange, exercise endurance, sleep efficiency, quality of oxygenation or dyspnea ratings.
Lin 1996 (28)	12	2	O2 monotherapy vs. NPPV sequentially.	6 week	12	NPPV did not improve nocturnal oxygenation and also sleep efficiency was poorer in NPPV group.
Krachman et al. 1997 (29)	22	3	NPPV vs. Sham NPPV sequentially.	< 1 week	6	PaCO2 was not different during NREM and REM sleep in both groups. Sleep efficiency increased by 14% with NPPV. However Sleep architecture was not changed.
Highcock et al. 2003 (30)	12–15	-	Walking with 3 different types of NPPVs vs. unencumbered walking sequentially.	<1 week	8	NPPV did not improve exercise capacity however it increased ventilation.

HI-NPPV, High intensity non-invasive positive pressure ventilation; IPAP, inspiratory positive airway pressure; EPAP, expiratory positive airway pressure; E.T., exercise training; vs, versus; LTOT, long-term oxygen therapy; PFT, pulmonary function test; HRQL, health-related quality of life; COPD, chronic obstructive pulmonary disease.

Table 3a. Studies employing HI-NPPV prospective randomized studies

First author date (reference)	Mean IPAP cmH2O	Backup rate	Study design	Study length	Number of patients	Outcomes
Windisch et al.2006 (40)	31	21	Randomized controlled Trial Half of the patients with COPD; received HI-NPPV other half received symptomatic treatment and physiologic parameters were compared.	2 months	24**	PaCO2 decreased by 13 mm Hg, PO2 increased by 18 mm Hg FEV1 increased by 0.3 L in patients with COPD after 2 months of HI-NPPV. And there was a significant stepwise decrease of PaCO2 during the following 3 h after cessation of nocturnal NPPV in the early morning in HI-NPPV group whereas no change was observed in control group.
Dreher et al. 2007 (34)	29	20	Randomized controlled Trial Patients with COPD (GOLD stage 4), who used nocturnal HMV for 35 months, underwent two 6 MWT with oxygen or oxygen plus NPPV with help of walking rollator. Physiologic parameters and walking distances were measured.	35 months	20	PaCO2 increased by 0.4 kPa during the 6MWT when supplemental oxygen was used, but did not significantly change when NPPV was used in addition to supplemental oxygen. PaO2 significantly increased by after walking with NPPV, but significantly decreased by without NPPV. Dyspnea, as assessed by the BDS, significantly decreased from 6 to 4 and walking distance significantly increased from 209 m to 252 m when walking was NPPV-aided.
Dreher et al. 2009 (52)	29	19	Randomized crossover study. Patients with COPD (GOLD stage 4) used nocturnal HMV for mean of 27 months, underwent 12 MWT with oxygen or oxygen plus NPPV without help of walking rollator. NPPV replaced backpack of patients.	27 months	11	After 12MWT; PaO2 decreased by 8 mm Hg in oxygen group whereas 6 mm Hg increased in NPPV group. PCO2 increased in both study arms. BDS increased in both groups. FEV1 increased 0.1 L in NPPV group whereas 1.4 L decreased in O2 group. However, walking distance was 64 m shorter in the NPPV group than oxygen group. Authors think it is due to the burden of carrying the NPPV in a backpack.
Dreher et al. 2010 (41)	29 vs 15	18 vs assist controlled	Randomized controlled crossover study. Compared 6 weeks of HI-NPPV using controlled ventilation with LI-NPPV in patients with stable COPD.	12 weeks	17	Nighttime PCO2, HCO3 decreased in Hi-NPPV group. After the walking test, BDS score was improved in HI-NPPV group. There were no significant treatment effects between LI-NPPV and HI-NPPV in terms of SRI subscales.
Dreher et al. 2011 (61)	29 vs 14	19 vs assist controlled	Randomized crossover study. Assessed the difference in sleep quality in HI-NPPV and LI-NPPV.	42 months	17	In both group there were no changes in terms of slow wave sleep, sleep quality, sleep stages and arousal rates.
Murphy et al. 2012 (37)	29	16 vs 6	Crossover randomized controlled study. Compared high-intensity (high IPAP pressure with back up rate) and high-pressure (high IPAP pressure without back-up rate) ventilation groups.	12 week	12	There were no between-group differences in health-related quality of life, mean nocturnal ventilator usage, gas exchange, objective sleep quality and subjective sleep quality. However the respiratory domain of the Severe Respiratory Insufficiency questionnaire was higher in the high-intensity group.
Ekkernkamp et al. 2014 (42)	25	18	Minute ventilation measured in patients who received for a median 22 months HI-NPPV compared with spontaneous breathing.	22 months	27	Long-term HI-NPPV increased minute ventilation by an average of 26% compared with spontaneous breathing in stable hypercapnic COPD patients.
Köhnlein et al. 2014 (77)	22	16	COPD GOLD stage IV patients were randomly assigned either to optimized standard COPD treatment (control group) or to standard COPD treatment plus NPPV (intervention group) for at least 12 months.	Approximately 7 years	195	31 (33%) of 93 patients in the control group, and 12 (12%) of 102 patients in the intervention group died within 1 year after randomization (log rank p=0.0004). PaCO2, pH, SaO, HCO–, and FEV were significantly increased in intervention group. HRQL significantly improved with NPPV treatment. However PaO2, FVC, 6-minute walk distance and residual volume/total lung capacity were not statistically different between groups.

**Half of the subjects were patients with restrictive lung disease.

GOLD, Global initiative for chronic obstructive lung disease; 6 MWT, 6-minute walking test; HMV, home mechanical ventilation; SF-36, Medical Outcome Survey 36-Item Short-form Health Status Survey; BDS, Borg Dyspnea Scale; SRI, the Severe Respiratory Insufficiency Questionnaire; CRF, chronic respiratory failure; IPAP, inspiratory positive airway pressure; EPAP, expiratory positive airway pressure; NPPV, non-invasive positive pressure ventilation; ET, exercise training; vs, versus; LTOT, long-term oxygen therapy; PFT, pulmonary function test; HRQL, health-related quality of life.

Table 3b. Studies employing HI-NPPV non-randomized cohort studies

First author Date (reference)	Mean IPAP cmH2O	Mean EPAP cmH2O	Study design	Study length	Number of patients	Outcomes
Windisch et al. 2002 (67)	30	23	Non-RCT; HI-NPPV was given in GOLD stage 4 COPD patients and physiologic parameters were measured	6 months	14	Normocapnia was achieved in mean of 9 days. PCO2 decreased by 20 mm Hg, HCO3 decreased by 7 mmol/l, PO2 increased by 25 mm Hg.
Windisch 2005 (39)	28	21	Retrospective non-RCT, Nocturnal HI-NPPV was given in GOLD stage 4 patients and physiologic parameters were measured	6 years	34	In a 2 month-period; PaCO2 decreased by 7 mm Hg,HCO3 decreased by 3 mmol/l,PO2 increased by 6 mm Hg, FEV1 increased by 0.14 L.
Windisch et al. 2008 (65)	25	18	Non-RCT; patients received HI-NPPV for 12 months and HRQL and physiologic parameters were measured in the 1^st and 12^th month.	12months	27	In the first month; PaCO2 decreased by 13 mmHg, PaO2 increased by 13 mmHg,HCO3 decreased by 4 mmHg In the 12^th month; PaCO2 decreased by 14 mmHg, PaO2 increased by 12 mmHg, HCO3 decreased by 5 mmHg. General and condition-specific aspects of HRQL which was measured by SF-36 and SRI increased following NPPV establishment.
Windisch et al. 2009 (36)	29	21	Retrospective non-RCT Physiologic parameters, exacerbation rates, long-term survival rates were evaluated in patients with COPD	9 years	73	After one year, PCO2 decresed by 7 mm Hg, PO2 increased by 12 mmHg, Hematocrit levels were improved and hospitalization rates were decreased. Two- and 5-year survival rates of all patients were 82% and 58%, respectively.

GOLD, Global initiative for chronic obstructive lung disease; 6 MWT, 6-minute walking test; HMV, home mechanical ventilation; SF-36, Medical Outcome Survey 36-Item Short-form Health Status Survey; SRI, the Severe Respiratory Insufficiency Questionnaire; CRF, chronic respiratory failure; IPAP, inspiratory positive airway pressure; EPAP, expiratory positive airway pressure; NPPV, non-invasive positive pressure ventilation; ET, exercise training; vs, versus; LTOT, long-term oxygen therapy; PFT, pulmonary function test; HRQL, health-related quality of life.

Figure 1. A chronic obstructive pulmonary disease patient during a 6-minute walking test while walking with a rollator [Reproduced by permission of Dr. Wolfram Windisch from Dreher et al. (34)).

Figure 2. Changes in arterial oxygen tension (PaO₂) before and after 6-minute walking test while on a) supplemental oxygen and b) non-invasive positive-pressure ventilation in addition to supplemental oxygen. [Reproduced by permission of Dr. Wolfram Windisch from Dreher et al. (34)].

Figure 3. A chronic obstructive pulmonary disease patient during a 6-minute walking test while walking with a backpack [Reproduced by permission of Dr. Wolfram Windisch from Dreher et al. (52)].

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