Department of Pulmonary Diseases and Tuberculosis, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
Groningen Research Institute of Asthma and COPD (GRIAC), University of Groningen, Groningen, Netherlands.
Cochrane Database Syst Rev. 2021 Aug 9;8(8):CD002878. doi: 10.1002/14651858.CD002878.pub3.
Chronic non-invasive ventilation (NIV) is increasingly being used to treat people with COPD who have respiratory failure, but the evidence supporting this treatment has been conflicting.
To assess the effects of chronic non-invasive ventilation at home via a facial mask in people with COPD, using a pooled analysis of IPD and meta-analysis.
We searched the Cochrane Airways Register of Trials, MEDLINE, Embase, PsycINFO, CINAHL, AMED, proceedings of respiratory conferences, clinical trial registries and bibliographies of relevant studies. We conducted the latest search on 21 December 2020.
We included randomised controlled trials (RCTs) comparing chronic NIV for at least five hours per night for three consecutive weeks or more (in addition to standard care) versus standard care alone, in people with COPD. Studies investigating people initiated on NIV in a stable phase and studies investigating NIV commenced after a severe COPD exacerbation were eligible, but we reported and analysed them separately. The primary outcomes were arterial blood gases, health-related quality of life (HRQL), exercise capacity (stable COPD) and admission-free survival (post-exacerbation COPD). Secondary outcomes for both populations were: lung function, COPD exacerbations and admissions, and all-cause mortality. For stable COPD, we also reported respiratory muscle strength, dyspnoea and sleep efficiency.
We used standard methodological procedures expected by Cochrane. After inclusion of a study, we requested the IPD. We analysed continuous and time-to-event data using linear- and cox-regression mixed-effect models with a random effect on study level. We analysed dichotomous IPD using generalised estimating equations. We adjusted all models for age and sex. We assessed changes in outcomes after three and 12 months. We also conducted a meta-analysis on aggregated trial data.
We included 14 new RCTs in this review update, in addition to the seven previously included. Seventeen studies investigated chronic NIV in stable COPD and four studies investigated chronic NIV commenced after a severe COPD exacerbation. Three studies compared NIV to sham continuous positive airway pressure (2 to 4 cmHO). Seven studies used a nasal mask, one study used an oronasal mask and eight studies used both interfaces. Five studies did not report the interface. The majority of trials (20/21) were at high risk of performance bias due to an unblinded design. We considered 11 studies to have a low risk of selection bias and 13 to have a low risk of attrition bias. We collected and analysed the IPD from 13 stable COPD studies (n = 778, 68% of the participants included) and from three post-exacerbation studies (n = 364, 96% of the participants included). In the stable COPD group, NIV probably results in a minor benefit on the arterial partial pressure of oxygen (PaO) after three months (adjusted mean difference (AMD) 0.27 kPa, 95% CI 0.04 to 0.49; 9 studies, 271 participants; moderate-certainty evidence), but there was little to no benefit at 12 months (AMD 0.09 kPa, 95% CI -0.23 to 0.42; 3 studies, 171 participants; low-certainty evidence). The arterial partial pressure of carbon dioxide (PaCO) was reduced in participants allocated to NIV after three months (AMD -0.61 kPa, 95% CI -0.77 to -0.45; 11 studies, 475 participants; high-certainty evidence) and persisted up to 12 months (AMD -0.42 kPa, 95% CI -0.68 to -0.16; 4 studies, 232 participants; high-certainty evidence). Exercise capacity was measured with the 6-minute walking distance (minimal clinical important difference: 26 m). There was no clinically relevant effect of NIV on exercise capacity (3 months: AMD 15.5 m, 95% CI -0.8 to 31.7; 8 studies, 330 participants; low-certainty evidence; 12 months: AMD 26.4 m, 95% CI -7.6 to 60.5; 3 studies, 134 participants; very low-certainty evidence). HRQL was measured with the Severe Respiratory Insufficiency and the St. Georges's Respiratory Questionnaire and may be improved by NIV, but only after three months (3 months: standardised mean difference (SMD) 0.39, 95% CI 0.15 to 0.62; 5 studies, 259 participants; very low-certainty evidence; 12 months: SMD 0.15, 95% CI -0.13 to 0.43; 4 studies, 200 participants; very low-certainty evidence). Lastly, the risk for all-cause mortality is likely reduced by NIV (adjusted hazard ratio (AHR) 0.75, 95% CI 0.58 to 0.97; 3 studies, 405 participants; moderate-certainty evidence). In the post-exacerbation COPD group, there was little to no benefit on the PaO after three months, but there may be a slight decrease after 12 months (3 months: AMD -0.10 kPa, 95% CI -0.65 to 0.45; 3 studies, 234 participants; low-certainty evidence; 12 months: -0.27 kPa, 95% CI -0.86 to 0.32, 3 studies; 170 participants; low-certainty evidence). The PaCO was reduced by NIV at both three months (AMD -0.40 kPa, 95% CI -0.70 to -0.09; 3 studies, 241 participants; moderate-certainty evidence) and 12 months (AMD -0.52 kPa, 95% CI -0.87 to -0.18; 3 studies, 175 participants; high-certainty evidence). NIV may have little to no benefit on HRQL (3 months: SMD 0.25, 95% CI -0.01 to 0.51; 2 studies, 219 participants; very low-certainty evidence; 12 months: SMD 0.25, 95% -0.06 to 0.55; 2 studies, 164 participants; very low-certainty evidence). Admission-free survival seems improved with NIV (AHR 0.71, 95% CI 0.54 to 0.94; 2 studies, 317 participants; low-certainty evidence), but the risk for all-cause mortality does not seem to improve (AHR 0.97, 95% CI 0.74 to 1.28; 2 studies, 317 participants; low-certainty evidence).
AUTHORS' CONCLUSIONS: Regardless of the timing of initiation, chronic NIV improves daytime hypercapnia. In addition, in stable COPD, survival seems to be improved and there might be a short term HRQL benefit. In people with persistent hypercapnia after a COPD exacerbation, chronic NIV might prolong admission-free survival without a beneficial effect on HRQL. In stable COPD, future RCTs comparing NIV to a control group receiving standard care might no longer be warranted, but research should focus on identifying participant characteristics that would define treatment success. Furthermore, the optimal timing for initiation of NIV after a severe COPD exacerbation is still unknown.
慢性无创通气（NIV）越来越多地被用于治疗呼吸衰竭的 COPD 患者，但支持这种治疗的证据存在冲突。
通过汇总个人资料和荟萃分析，评估 COPD 患者在家中使用面罩进行慢性 NIV 的效果。
我们检索了 Cochrane 气道试验注册库、MEDLINE、Embase、PsycINFO、CINAHL、AMED、呼吸会议记录、临床试验注册处和相关研究的参考文献。我们于 2020 年 12 月 21 日进行了最新检索。
我们纳入了比较至少每晚使用 NIV 进行 3 周或更长时间（除标准治疗外）与单独使用标准治疗的随机对照试验（RCT），纳入人群为 COPD 患者。我们纳入了在稳定期开始接受 NIV 治疗和在 COPD 加重后开始接受 NIV 治疗的研究，但我们分别对其进行了报告和分析。主要结局为动脉血气、健康相关生活质量（HRQL）、运动能力（稳定期 COPD）和无住院生存率（加重期 COPD）。对于稳定期 COPD，我们还报告了呼吸肌力量、呼吸困难和睡眠效率。次要结局为肺功能、COPD 加重和住院以及全因死亡率。对于稳定期 COPD，我们还报告了呼吸肌力量、呼吸困难和睡眠效率。我们还对汇总试验数据进行了荟萃分析。
我们使用了 Cochrane 预期的标准方法学程序。纳入研究后，我们请求了个人资料。我们使用线性和协方差混合效应模型，以研究水平的随机效应分析连续和时间至事件数据。我们使用广义估计方程分析二分类个人资料。我们调整了所有模型以考虑年龄和性别。我们还分析了 3 个月和 12 个月后的结局变化。
本综述更新纳入了 14 项新的 RCT，此外还包括之前纳入的 7 项 RCT。17 项研究调查了稳定期 COPD 中的慢性 NIV，4 项研究调查了 COPD 加重后开始的慢性 NIV。3 项研究比较了 NIV 与假连续气道正压通气（2 至 4 cmHO）。7 项研究使用鼻罩，1 项研究使用口鼻面罩，8 项研究同时使用了这两种面罩。5 项研究未报告面罩类型。由于设计不设盲，大多数试验（20/21）存在高度的偏倚风险。我们认为 11 项试验具有低偏倚风险，13 项试验具有低失访偏倚风险。我们从 13 项稳定期 COPD 研究（n = 778，纳入参与者的 68%）和 3 项加重后 COPD 研究（n = 364，纳入参与者的 96%）中收集和分析了个人资料。在稳定期 COPD 组中，NIV 可能在 3 个月时对动脉血氧分压（PaO）有轻微益处（调整平均差异（AMD）0.27 kPa，95% CI 0.04 至 0.49；9 项研究，271 名参与者；中等确定性证据），但在 12 个月时几乎没有益处（AMD 0.09 kPa，95% CI -0.23 至 0.42；3 项研究，171 名参与者；低确定性证据）。参与者接受 NIV 治疗后，动脉血二氧化碳分压（PaCO）在 3 个月时降低（AMD -0.61 kPa，95% CI -0.77 至 -0.45；11 项研究，475 名参与者；高确定性证据），并持续到 12 个月（AMD -0.42 kPa，95% CI -0.68 至 -0.16；4 项研究，232 名参与者；高确定性证据）。6 分钟步行距离（最小临床重要差异：26 米）测量了运动能力。NIV 对运动能力没有明显的临床影响（3 个月：AMD 15.5 m，95% CI -0.8 至 31.7；8 项研究，330 名参与者；低确定性证据；12 个月：AMD 26.4 m，95% CI -7.6 至 60.5；3 项研究，134 名参与者；非常低确定性证据）。HRQL 采用严重呼吸衰竭和圣乔治呼吸问卷进行测量，NIV 可能会改善 HRQL，但仅在 3 个月时（SMD 0.39，95% CI 0.15 至 0.62；5 项研究，259 名参与者；非常低确定性证据；12 个月：SMD 0.15，95% CI -0.13 至 0.43；4 项研究，200 名参与者；非常低确定性证据）。最后，NIV 可能降低全因死亡率的风险（调整后的危险比（AHR）0.75，95% CI 0.58 至 0.97；3 项研究，405 名参与者；中等确定性证据）。在加重后 COPD 组中，3 个月时 PaO 几乎没有改善，但 12 个月时可能会略有下降（3 个月：AMD -0.10 kPa，95% CI -0.65 至 0.45；3 项研究，234 名参与者；低确定性证据；12 个月：AMD -0.27 kPa，95% CI -0.86 至 0.32，3 项研究；170 名参与者；低确定性证据）。NIV 在 3 个月和 12 个月时均降低了 PaCO（3 个月：AMD -0.40 kPa，95% CI -0.70 至 -0.09；3 项研究，241 名参与者；中等确定性证据；12 个月：AMD -0.52 kPa，95% CI -0.87 至 -0.18；3 项研究，175 名参与者；高确定性证据）。NIV 对 HRQL 可能几乎没有益处（3 个月：SMD 0.25，95% CI -0.01 至 0.51；2 项研究，219 名参与者；非常低确定性证据；12 个月：SMD 0.25，95% CI -0.06 至 0.55；2 项研究，164 名参与者；非常低确定性证据）。入院无生存率似乎因 NIV 而改善（AHR 0.71，95% CI 0.54 至 0.94；2 项研究，317 名参与者；低确定性证据），但全因死亡率的风险似乎没有改善（AHR 0.97，95% CI 0.74 至 1.28；2 项研究，317 名参与者；低确定性证据）。
无论起始时间如何，慢性 NIV 均可改善日间高碳酸血症。此外，在稳定期 COPD 中，生存似乎得到改善，可能有短期 HRQL 获益。在 COPD 加重后持续存在高碳酸血症的患者中，慢性 NIV 可能延长无住院生存率，而对 HRQL 无有益作用。在稳定期 COPD 患者中，比较 NIV 与单独接受标准治疗的 RCT 可能不再需要，但研究应侧重于确定治疗成功的患者特征。此外，加重后 COPD 患者中开始 NIV 的最佳时机仍不清楚。
