Effect of moderate altitude with and without nocturnal oxygen therapy on the next-day cerebrovascular function in patients with chronic obstructive pulmonary disease -- A randomized, cross-over trial at 2048 m

Abstract

Background This study investigated whether nocturnal oxygen therapy (NOT) improves next-day cerebrovascular function in lowlanders with COPD staying at moderate altitude. Methods This randomized, placebo-controlled crossover trial was performed in stable patients with moderate to severe COPD (FEV1/FVC <0.7 and FEV1 30-80%predicted), living <800m and pulse oximetry (SpO2) ≥92%. Patients underwent assessments at 490m and during 2 stays of 2 days at 2048m while NOT or placebo (each at 3L min-1 through nasal cannula) were applied according to a randomized cross-over design. At both altitudes, SpO2, cerebral tissue oxygenation (CTO, near-infrared spectroscopy), mean arterial blood pressure (MAP, finger plethysmography) and middle cerebral artery systolic peak blood flow velocity (sMCAv, transcranial Doppler ultrasound) were assessed while patients were (0) quietly breathing FiO2 0.21; (i) quietly breathing FiO2 1.0, (ii) voluntarily hyperventilating, (iii) voluntarily hyperventilating under FiO2 1.0, and (iv) during head-up tilting. Indices of cerebrovascular responsiveness to changes in blood gases and blood pressure were computed. Results A total of 18 patients (8 women aged mean±SD 65±5y, FEV1 54.7±13.9%predicted) were analyzed. At 2048m under placebo, patients became hypoxemic, mean±SE SpO2 90.3±0.4% vs. 93.7±0.4% at 490m, while MAP, CTO and sMCAv remained unchanged compared to 490m. All ventilatory maneuvers at 2048 m induced greater increases in SpO2 compared to 490m while changes in MAP, CTO and sMCAv were similar. Head-up tilting induced a similar blood pressure fall at 2048m compared to 490m, whereas cerebral blood flow velocity changed less in response to systemic hypotension (mean±SE ΔsMCAv/ΔMAP 0.9±0.3 vs. 2.3±0.4cm s-1 mmHg-1) at 2048m. No alteration in cerebrovascular function as a treatment effect of NOT was observed in either maneuver. Conclusion This randomized clinical trial in moderate-to-severe COPD patients ascending to 2048m showed that moderate daytime systemic hypoxemia does not translate to cerebral hypoxia nor cerebrovascular autoregulatory impairments while at rest or under ventilatory or orthostatic challenges.

Competing Interest Statement

The authors have declared no competing interest.

Clinical Trial

NCT02150590

Funding Statement

The study was supported by the Swiss National Science Foundation (143875) and Lunge Zurich. Siemens Health Engineers provided some equipment for the study.

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Ethics committee of the University Hospital of Zurich gave ethical approval for this work (EK-2013-0088).

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Data Availability

All data produced in the present study are available upon reasonable request to the authors.

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