Baseline Level and Reduction in PaCO2 are Associated with the Treatment Effect of Long-Term Home Noninvasive Positive Pressure Ventilation in Stable Hypercapnic Patients with COPD: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Abstract

Purpose

The evidence of long-term home noninvasive positive pressure ventilation (LTHNIPPV) in patients with stable hypercapnic chronic obstructive pulmonary disease (COPD) is controversial. In this meta-analysis study, we sought to establish whether a baseline level and reduction in partial pressure of arterial carbon dioxide (PaCO2) were associated with the treatment effect of LTHNIPPV in these patients.

Patients and Methods

Six electronic databases were comprehensively searched from January 1980 until June 2020. Randomized clinical trials (RCTs) comparing LTHNIPPV with control treatment were included. Two authors independently extracted data, assessed the study quality, and used the GRADE approach to evaluate evidence quality. The main outcome was mortality.

Results

Nineteen studies involving 1482 patients (LTHNIPPV, n = 730; control, n = 752) were included. LTHNIPPV significantly reduced mortality (relative risk [RR] = 0.76; 95% confidence interval [CI]: 0.61–0.95; p = 0.02; I² = 14%), the frequency of hospital admissions, PaCO2, and improved partial pressure of oxygen (PaO2) compared to control treatment. LTHNIPPV also relieved dyspnea and improved exercise capacity and health-related quality of life (HRQL) but showed no significant benefit for improving the forced expiratory volume in one second in predicted (FEV1% pred). Subgroup analysis revealed that the baseline level and reduction in PaCO2 were associated with decreased mortality (baseline PaCO2 ≥ 55 mmHg RR = 0.69, P = 0.02; vs baseline PaCO2 < 55 mmHg RR = 0.87, P = 0.32; and higher dPaCO2 RR = 0.42, P < 0.0001; vs lower dPaCO2 RR = 0.91, P = 0.38).

Conclusion

LTHNIPPV significantly reduced mortality. The baseline level and reduction in PaCO2 were associated with the treatment effect of LTHNIPPV in patients with stable hypercapnic COPD. Large-scale, multicenter RCTs are needed to confirm our results.

Keywords:

• COPD
• long-term home noninvasive positive pressure ventilation
• mortality
• meta-analysis study
• RCTs
• stable hypercapnic

Abbreviations

LTHNIPPV, long-term home noninvasive positive pressure ventilation; COPD, chronic obstructive pulmonary disease; PaCO2, partial pressure of arterial carbon dioxide; RCT, randomized clinical trial; GRADE, Grading of Recommendations Assessment, Development, and Evaluation; RR, relative risk; CI, confidence interval; WMD, weighted mean difference; PaO2, partial pressure of oxygen; HRQL, health-related quality of life; FEV1% pred, forced expiratory volume in one second in predicted; 6-MWD, 6-min walk distance; dPaCO2 = (NIPPV group baseline PaCO2 - NIPPV group endpoint PaCO2) - (control group baseline PaCO2 - control group endpoint PaCO2); GOLD, global initiative for chronic obstructive lung disease; Df, degrees of freedom; LTOT, long-term oxygen therapy; NR, not reported; PR, pulmonary rehabilitation; IPAP, intermittent positive airway pressure; EPAP, expiratory positive airway pressure; FEV1 (L), forced expiratory volume in first second; MRC-dyspnea scale, Medical Research Council scale; SGRQ, St. George’s Respiratory Questionnaire; W, weeks; M, month, Y, year; h, hour; SD, standard deviation; WMD, weighted mean difference; SE, standard error; ARF, acute respiratory failure.

Acknowledgments

The study was supported by the National Key Research and Development Program of China (2019YFC0121700), Beijing Hospitals Authority Clinical Medicine Development of Special Funding Support (XMLX201709), Beijing Municipal Commission of Science and Technology Cultivation Research Program of Biomedicine and Life Science Innovation (Z171100000417057), and Beijing Hospitals Authority Youth Program (QML20180303).

Author Contributions

All authors have contributed toward this paper. YMM, ZXC, ZPW, and ZJL proposed the concepts and designed the study. ZPW and ZJL performed the acquisition, analysis, and interpretation of data and statistical analysis. All authors contributed to data analysis, drafting or revising the article, have agreed on the journal to which the article was submitted, gave final approval of the version to be published, and agree to be accountable for all aspects of the work.

Disclosure

The authors declare no conflicts of interest in this work.