Home noninvasive ventilation in severe COPD: in whom does it work and how?

Tim Raveling^{1

2}, Judith M Vonk^{2

3}, Nicholas S Hill⁴, Peter C Gay⁵, Ciro Casanova⁶, Enrico Clini⁷, Thomas Köhnlein⁸, Eduardo Márquez-Martin^{9

10}, Tessa Schneeberger^{11

12}, Patrick B Murphy¹³, Fransien M Struik¹, Huib A M Kerstjens^{1

2}, Marieke L Duiverman^{1

2}, Peter J Wijkstra^{1

2}

Affiliations

¹ Department of Pulmonary Diseases and Home Mechanical Ventilation, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
² Groningen Research Institute of Asthma and COPD, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
³ Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
⁴ Division of Pulmonary, Critical Care and Sleep Medicine, Tufts University Medical Center Boston, Boston, MA, USA.
⁵ Department of Pulmonary and Critical Care Medicine and the Center for Sleep Medicine, Mayo Clinic, Rochester, MN, USA.
⁶ Department of Pulmonary, Research Unit, Hospital Universitario La Candelaria, Universidad de La Laguna, Tenerife, Spain.
⁷ Respiratory Diseases Unit, Dept of Medical and Surgical Sciences SMECHIMAI, University Hospital of Modena Policlinico, University of Modena Reggio-Emilia, Modena, Italy.
⁸ Pneumological Specialist Center, Teuchern, Germany.
⁹ Medical-Surgical Unit of Respiratory diseases, University Hospital Virgen del Rocío, Seville, Spain.
¹⁰ CIBER-ES, Instituto de Salud Carlos III, Madrid, Spain.
¹¹ Department of Pulmonary Rehabilitation, Philipps-University of Marburg, Marburg, Germany.
¹² Institute for Pulmonary Rehabilitation Research, Schoen Klinik Berchtesgadener Land, Schoenau am Koenigssee, Germany.
¹³ Lane Fox Clinical Respiratory Physiology Research Unit, Guy's and St Thomas' NHS Foundation Trust, London, UK.

PMID: 38348241
PMCID: PMC10860207
DOI: 10.1183/23120541.00600-2023

Home noninvasive ventilation in severe COPD: in whom does it work and how?

Tim Raveling et al. ERJ Open Res. 2024.

. 2024 Feb 12;10(1):00600-2023.

doi: 10.1183/23120541.00600-2023. eCollection 2024 Jan.

Authors

Affiliations

¹ Department of Pulmonary Diseases and Home Mechanical Ventilation, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
² Groningen Research Institute of Asthma and COPD, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
³ Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
⁴ Division of Pulmonary, Critical Care and Sleep Medicine, Tufts University Medical Center Boston, Boston, MA, USA.
⁵ Department of Pulmonary and Critical Care Medicine and the Center for Sleep Medicine, Mayo Clinic, Rochester, MN, USA.
⁶ Department of Pulmonary, Research Unit, Hospital Universitario La Candelaria, Universidad de La Laguna, Tenerife, Spain.
⁷ Respiratory Diseases Unit, Dept of Medical and Surgical Sciences SMECHIMAI, University Hospital of Modena Policlinico, University of Modena Reggio-Emilia, Modena, Italy.
⁸ Pneumological Specialist Center, Teuchern, Germany.
⁹ Medical-Surgical Unit of Respiratory diseases, University Hospital Virgen del Rocío, Seville, Spain.
¹⁰ CIBER-ES, Instituto de Salud Carlos III, Madrid, Spain.
¹¹ Department of Pulmonary Rehabilitation, Philipps-University of Marburg, Marburg, Germany.
¹² Institute for Pulmonary Rehabilitation Research, Schoen Klinik Berchtesgadener Land, Schoenau am Koenigssee, Germany.
¹³ Lane Fox Clinical Respiratory Physiology Research Unit, Guy's and St Thomas' NHS Foundation Trust, London, UK.

PMID: 38348241
PMCID: PMC10860207
DOI: 10.1183/23120541.00600-2023

Abstract

Background: Not all hypercapnic COPD patients benefit from home noninvasive ventilation (NIV), and mechanisms through which NIV improves clinical outcomes remain uncertain. We aimed to identify "responders" to home NIV, denoted by a beneficial effect of NIV on arterial partial pressure of carbon dioxide (P_aCO₂), health-related quality of life (HRQoL) and survival, and investigated whether NIV achieves its beneficial effect through an improved P_aCO₂.

Methods: We used individual patient data from previous published trials collated for a systematic review. Linear mixed-effect models were conducted to compare the effect of NIV on P_aCO₂, HRQoL and survival, within subgroups defined by patient and treatment characteristics. Secondly, we conducted a causal mediation analysis to investigate whether the effect of NIV is mediated by a change in P_aCO₂.

Findings: Data of 1142 participants from 16 studies were used. Participants treated with lower pressure support (<14 versus ≥14 cmH₂O) and with lower adherence (<5 versus ≥5 h·day^-1) had less improvement in P_aCO₂ (mean difference (MD) -0.30 kPa, p<0.001 and -0.29 kPa, p<0.001, respectively) and HRQoL (standardised MD 0.10, p=0.002 and 0.11, p=0.02, respectively), but this effect did not persist to survival. P_aCO₂ improved more in patients with severe dyspnoea (MD -0.30, p=0.02), and HRQoL improved only in participants with fewer than three exacerbations (standardised MD 0.52, p=0.03). The results of the mediation analysis showed that the effect on HRQoL is mediated partially (23%) by a change in P_aCO₂.

Interpretation: With greater pressure support and better daily NIV usage, a larger improvement in P_aCO₂ and HRQoL is achieved. Importantly, we demonstrated that the beneficial effect of home NIV on HRQoL is only partially mediated through a reduction in diurnal P_aCO₂.

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Conflict of interest statement

Conflict of interest: T. Raveling reports a travel grant from Breas Medical. N.S. Hill reports consulting fees from Philips, consulting fees and payments from Fisher & Paykel, and participates in boards of Breas and Philips. C. Casanova reports consulting fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Menarini and Novartis, and participates in boards of AstraZeneca and GlaxoSmithKline. E. Clini reports consulting fees from Chiesi Italia and Novartis, payments from AstraZeneca, Boehringer Ingelheim and GaxoSmithKline, and meeting/travel support from Boehringer Ingelheim and Chiesi. T. Köhnlein reports support from Grifols Deutschland GmbH. P.B. Murphy reports grants and payments from Fisher & Paykel, Resmed, Breas Medical and Philips Respironics, and payments from Chiesi and Genzyme. M.L. Duiverman reports grants from Resmed, Philips, Lowenstein, Vivisol, Sencure and Fisher & Paykel, and payments from Chiesi and Breas Medical. P.J. Wijkstra reports grants from Resmed, and grants and consulting fees from Philips.

Figures

**FIGURE 1**
Subgroup analysis on the 3-month change in diurnal arterial partial pressure of carbon dioxide (P_aCO₂). Results are adjusted for age, sex and timing of initiation of noninvasive ventilation (NIV) (stable disease *versus* after an episode of acute respiratory failure), and are presented as the mean difference (95% CI); the vertical dashed line indicates no effect. aeCOPD: acute exacerbation of COPD; BMI: body mass index; FEV₁: forced expiratory volume in 1 s; HRQoL: health-related quality of life; mMRC: modified Medical Research Council dyspnoea scale; PS: pressure support (the difference between the inspiratory and expiratory positive airway pressure). ^#: z-scores (a value of 0 indicates the mean of all participants, and a negative value indicates worse HRQoL).

**FIGURE 2**
Subgroup analysis on the 3-month change in health-related quality of life (HRQoL) (z-scores of the Severe Respiratory Insufficiency and St George's Respiratory Questionnaire combined). Results are adjusted for age, sex and timing of initiation of noninvasive ventilation (NIV) (stable disease *versus* after an episode of acute respiratory failure), and are presented as the standardised mean difference (SMD) (95% CI); the vertical dashed line indicates no effect. aeCOPD: acute exacerbation of COPD; BMI: body mass index; FEV₁: forced expiratory volume in 1 s; P_aCO₂: arterial partial pressure of carbon dioxide; mMRC: modified Medical Research Council dyspnoea scale; PS: pressure support (the difference between the inspiratory and expiratory postive airway pressure). ^#: z-scores (a value of 0 indicates the mean of all participants, and a negative value indicates worse HRQoL).

**FIGURE 3**
Subgroup analysis on all-cause mortality. Results are adjusted for age, sex and timing of initiation of noninvasive ventilation (NIV) (stable disease *versus* after an episode of acute respiratory failure), and are presented as the hazard ratio (95% CI); the vertical dashed line indicates a hazard ratio of zero (no effect). aeCOPD: acute exacerbation of COPD; BMI: body mass index; FEV₁: forced expiratory volume in 1 s; P_aCO₂: arterial partial pressure of carbon dioxide; HRQoL: health-related quality of life; mMRC: modified Medical Research Council dyspnoea scale; PS: pressure support (the difference between the inspiratory and expiratory postive airway pressure). ^#: z-scores (a value of 0 indicates the mean of all participants, and a negative value indicates worse HRQoL).

**FIGURE 4**
Results of the causal mediation analysis estimating the average direct effect (ADE) and the average causal mediation effect (ACME), with 95% confidence intervals, of treatment with home noninvasive ventilation (NIV) and change in arterial partial pressure of carbon dioxide (P_aCO₂) on the change in health-related quality of life (HRQoL) among COPD patients (five studies, 428 participants).

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References

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Home noninvasive ventilation in severe COPD: in whom does it work and how?

Affiliations

Home noninvasive ventilation in severe COPD: in whom does it work and how?

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

LinkOut - more resources

Full Text Sources