RATIONALE: People with cystic fibrosis (pwCF) may experience mucus retention, increased breathlessness, and decreased respiratory muscle strength. Non-invasive positive pressure ventilation (NIPPV) is used to treat acute and chronic respiratory symptoms in people. Studies have investigated the effects of NIPPV on airway clearance during sleep and exercise, as strategies to optimize the treatment of cystic fibrosis (CF).
OBJECTIVES: To assess the effects, acceptability and individual preference of NIPPV for pwCF.
SEARCH METHODS: On 2 April 2025, we conducted searches in the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register. Additionally, we consulted clinical trial registry databases and checked the reference lists of included studies.
ELIGIBILITY CRITERIA: We included randomized controlled trials (RCTs) of parallel and cross-over designs that compared NIPPV with no NIPPV or other treatments in pwCF.
OUTCOMES: Our outcomes were mortality, quality of life (QoL), sleep symptoms and sleep quality, lung function, respiratory symptoms, sputum production, resource use, acceptability, and serious adverse events.
RISK OF BIAS: Two reviewers independently assessed the risk of bias using the Risk of Bias 2.0 (RoB 2.0); for cross-over studies, we used the adapted version.
SYNTHESIS METHODS: Two independent authors selected studies based on the inclusion criteria, extracted data, and assessed the certainty of the evidence using the GRADE system. We were only able to combine results for one outcome measure, for which we used the restricted maximum likelihood (REML) method random-effects analysis. We did not perform further meta-analyses because most outcomes were reported by a single study.
INCLUDED STUDIES: Of the 14 studies included, 11 had a cross-over design and three were parallel RCTs, with a total of 261 participants. Studies lasted a maximum of three months. Two studies included only children, four included mixed populations (adults and children), and eight focused exclusively on adults. Nine studies included pwCF in stable condition and five studies included pwCF with an acute exacerbation. Most included few participants and did not assess our critical outcomes, in addition to limited data on important outcomes such as treatment adherence and adverse events.
SYNTHESIS OF RESULTS: NIPPV for pwCF experiencing a pulmonary exacerbation The evidence is very uncertain regarding the acute effects of BiPAP (bilevel positive airway pressure), both in comparison to the PEP (positive expiratory pressure) mask (mean difference (MD) -0.06, 95% confidence interval (CI) -0.46 to 0.34) and to directed coughing (MD -0.09, 95% CI -0.56 to 0.38) on the amount of dry sputum expectorated. Regarding patient-reported tiredness, participants reported feeling less tired after BiPAP than after the PEP mask (limited data for analysis). Evidence is also very uncertain regarding the short-term effects of BiPAP combined with airway clearance techniques on length of hospital stay (MD -0.5, 95% CI -3.06 to 2.06) and on adverse events. Similarly, the evidence is very uncertain about the acute effect of BiPAP compared to oxygen therapy on patient-reported comfort (MD 1.00, 95% CI -0.75 to 2.75). NIPPV for people with stable CF The evidence is very uncertain regarding the acute effect of BiPAP compared to the PEP mask on FEV₁ (forced expiratory volume in the first second) and FEF25-75 (forced expiratory flow between 25% and 75% of FVC) (limited data for analysis). The evidence is also very uncertain regarding adverse events (limited data for analysis). In the short term, the evidence is very uncertain about the effect of BiPAP combined with other treatments compared to PEP with the same treatments on predicted FEV₁ % (MD -13.00, 95% CI -21.32 to -4.68) and predicted FVC (forced vital capacity) % (MD -17.00, 95% CI -26.80 to -7.20). The same applies to CPAP (continuous positive airway pressure) combined with airway clearance techniques compared to techniques alone, with very low certainty of evidence for predicted FEV₁ % (MD -0.90, 95% CI -17.41 to 15.61), predicted FVC % (MD 0.40, 95% CI -13.46 to 14.26) and predicted FEF25-75 % (MD -6.00, 95% CI -28.03 to 16.03). Also in the short term, the evidence is very uncertain regarding the effect of BiPAP compared to room air on sleep quality (MD -1.0, 95% CI -4.04 to 2.04), predicted FEV₁ % (MD 1.00, 95% CI -8.62 to 10.62), predicted FVC % (MD 4.00, 95% CI -10.32 to 18.30) and patient-reported acceptability (withdrawal due to mask). Similarly, the evidence is also very uncertain regarding the effect of BiPAP compared to oxygen therapy on sleep quality (MD 0.0, 95% CI -2.62 to 2.62), predicted FEV₁ % (MD 1.00, 95% CI -8.13 to 10.13), predicted FVC % (MD 4.00, 95% CI -11.22 to 19.22) and acceptability (withdrawal due to mask). And the evidence is very uncertain regarding the medium-term effect of BiPAP combined with oxygen therapy compared to oxygen therapy alone on sleep quality (MD 1.00, 95% CI -1.77 to 3.77), predicted FEV₁ % (MD 2.00, 95% CI -7.52 to 11.52) and predicted FVC % (MD -1.00, 95% CI -19.11 to 17.11). The risk of bias limitations involved period and carryover effects (from cross-over), deviations from interventions, outcome measurement, and outcome selection. All outcomes presented very low certainty of the evidence due to methodological limitations, limited data for analysis, and imprecision. The other prespecified outcomes that were considered priorities in this review were not assessed in the included studies.
AUTHORS' CONCLUSIONS: Current evidence on the effects of NIPPV in patients with CF, both in people experiencing a pulmonary exacerbation and in stable conditions, is still uncertain. The studies included few participants, assessed few critical outcomes, and presented methodological limitations, resulting in substantial uncertainties. High-quality studies with longer interventions are needed to better estimate the effects of NIPPV on airway clearance, during nocturnal ventilation, during exercise, or for other applications in patients with CF.
FUNDING: The authors of the 2025 update did not receive financial support. This review was previously supported by the National Institute for Health & Care Research, via Cochrane Infrastructure funding to the Cochrane Cystic Fibrosis and Genetic Disorders Group.
REGISTRATION: This is an update of a Cochrane Review previously published in 2003, 2007, 2011, 2013 and 2017.
