Effect of Home Noninvasive Ventilation With Oxygen Therapy vs Oxygen Therapy Alone on Hospital Readmission or Death After an Acute COPD Exacerbation: A Randomized Clinical Trial

Abstract

Importance: Outcomes after exacerbations of chronic obstructive pulmonary disease (COPD) requiring acute noninvasive ventilation (NIV) are poor and there are few treatments to prevent hospital readmission and death.

Objective: To investigate the effect of home NIV plus oxygen on time to readmission or death in patients with persistent hypercapnia after an acute COPD exacerbation.

Design, setting, and participants: A randomized clinical trial of patients with persistent hypercapnia (Paco2 >53 mm Hg) 2 weeks to 4 weeks after resolution of respiratory acidemia, who were recruited from 13 UK centers between 2010 and 2015. Exclusion criteria included obesity (body mass index [BMI] >35), obstructive sleep apnea syndrome, or other causes of respiratory failure. Of 2021 patients screened, 124 were eligible.

Interventions: There were 59 patients randomized to home oxygen alone (median oxygen flow rate, 1.0 L/min [interquartile range {IQR}, 0.5-2.0 L/min]) and 57 patients to home oxygen plus home NIV (median oxygen flow rate, 1.0 L/min [IQR, 0.5-1.5 L/min]). The median home ventilator settings were an inspiratory positive airway pressure of 24 (IQR, 22-26) cm H2O, an expiratory positive airway pressure of 4 (IQR, 4-5) cm H2O, and a backup rate of 14 (IQR, 14-16) breaths/minute.

Main outcomes and measures: Time to readmission or death within 12 months adjusted for the number of previous COPD admissions, previous use of long-term oxygen, age, and BMI.

Results: A total of 116 patients (mean [SD] age of 67 [10] years, 53% female, mean BMI of 21.6 [IQR, 18.2-26.1], mean [SD] forced expiratory volume in the first second of expiration of 0.6 L [0.2 L], and mean [SD] Paco2 while breathing room air of 59 [7] mm Hg) were randomized. Sixty-four patients (28 in home oxygen alone and 36 in home oxygen plus home NIV) completed the 12-month study period. The median time to readmission or death was 4.3 months (IQR, 1.3-13.8 months) in the home oxygen plus home NIV group vs 1.4 months (IQR, 0.5-3.9 months) in the home oxygen alone group, adjusted hazard ratio of 0.49 (95% CI, 0.31-0.77; P = .002). The 12-month risk of readmission or death was 63.4% in the home oxygen plus home NIV group vs 80.4% in the home oxygen alone group, absolute risk reduction of 17.0% (95% CI, 0.1%-34.0%). At 12 months, 16 patients had died in the home oxygen plus home NIV group vs 19 in the home oxygen alone group.

Conclusions and relevance: Among patients with persistent hypercapnia following an acute exacerbation of COPD, adding home noninvasive ventilation to home oxygen therapy prolonged the time to readmission or death within 12 months.

Trial registration: clinicaltrials.gov Identifier: NCT00990132.

Conflict of interest statement

Conflict of Interest Disclosures: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. The Lane Fox Clinical Respiratory Physiology Research Centre has received unrestricted research grants from ResMed, Philips Respironics, Fisher & Paykel Healthcare, and B&D Electromedical. Dr Murphy reported receiving reimbursement for expenses for travel to conferences and lecture fees from Philips Respironics, ResMed, Fisher & Paykel, and B&D Electromedical. Dr Bourke reported receiving unrestricted research grant funding from Philips Respironics and Pfizer Open Air; and personal fees from Pfizer. Dr Hughes reported receiving reimbursement for travel expenses to scientific meetings from ResMed, Philips Respironics, and B&D Electromedical. Dr Lewis reported receiving speakers fees and institutional grant funding from Philips Respironics for an unrelated study. Dr Mukherjee reported receiving nonfinancial support from ResMed and Breas (before it was incorporated into B&D Electromedical). Dr Patout reported receiving personal fees from Fisher & Paykel and ResMed; nonfinancial support from Antadir; and grant funding from B&D Electromedical. Dr Pepperell reported receiving personal fees and nonfinancial support from ResMed for lecturing and serving on an advisory panel; and travel reimbursement and speakers fees from Philips Respironics, ResMed, Fisher & Paykel, B&D Electromedical, and Weinmann. Dr Smith reported receiving unrestricted research grant funding from B&D Electromedical. Dr Stradling reported receiving consultant fees from ResMed. Dr Wedzicha reported receiving personal fees from Novartis, GlaxoSmithKline, Pfizer, Takeda, AstraZeneca, Boehringer Ingelheim, Johnson & Johnson, Vifor Pharma, Bayer, Chiesi, and Napp; receiving grants from GlaxoSmithKline, Takeda, Johnson & Johnson, and Vifor Pharma; and receiving nonfinancial support from Novartis, GlaxoSmithKline, Takeda, AstraZeneca, and Boehringer Ingelheim. Dr Polkey reported receiving personal fees from Philips Respironics for serving as a consultant that were paid to his institution; and his institution is currently negotiating a consultancy position between Royal Brompton and Harefield Hospital Foundation Trust and Philips Respironics for which his trust will be remunerated. Dr Elliott reported receiving personal fees from ResMed, Philips Respironics, Curative Medical, and Agir a Dom. Dr Hart reported receiving personal fees from Fisher & Paykel; grant funding for other trials from Philips Respironics, ResMed, B&D Electromedical, and Fisher & Paykel; and having a patent pending for a myotrace technology. No other disclosures were reported.

Figures

Figure 1.. Participant Flow Diagram

aDefined as absence of hypercapnia (Paco2 <53 mm Hg), hypoxemia (Pao2 >60 mm Hg), or both. bCalculated as weight in kilograms divided by height in meters squared. cDefined as an arterial pH of less than 7.30 when morning arterial blood gas measured after use of oxygen therapy alone. dSeventeen patients received home noninvasive ventilation after hospital readmission (consistent with trial protocol) and, at the discretion of the treating clinician, 1 patient received home noninvasive ventilation prior to reaching the primary outcome.

Figure 2.. Kaplan-Meier Survival Plot of Time to Readmission or Death From Randomization to the End of Trial Follow-up at 1 Year

The median follow-up times were 8.1 months (interquartile range, 2.3-12.6 months) for the home oxygen therapy alone group and 12.2 months (interquartile range, 8.9-12.9 months) for the home oxygen therapy plus home noninvasive ventilation (NIV) group. aAdjusted for number of chronic obstructive pulmonary disease readmissions within past year, prior use of long-term oxygen therapy, age, and body mass index.