Nasal high ﬂow therapy and PtCO
in stable COPD: A randomized
controlled cross-over trial
VAN DE HEI,
Medical Research Institute of New Zealand, Wellington;
School of Biological Sciences, Victoria University of Wellington,
Capital and Coast District Health Board, Wellington;
School of Medicine and Health Sciences, University of
Otago Wellington, Wellington, New Zealand;
University of Groningen, Groningen, The Netherlands
Background and objective: Hypercapnia is associated
with worse clinical outcomes in exacerbations of COPD.
The present study aimed to determine the effects of nasal
high ﬂow (NHF) therapy on transcutaneous partial pres-
sure of carbon dioxide (PtCO
) in stable COPD patients.
Methods: In a single-blind randomized controlled cross-
over trial, 48 participants with COPD were allocated in
random order to all of four 20 min interventions: NHF at
15 L/min, 30 L/min and 45 L/min or breathing room air
with each intervention followed by a washout period of
15 min. The primary outcome measure was PtCO
20 min, adjusted for baseline PtCO
. Secondary outcomes
included respiratory rate at 20 min, adjusted for baseline.
Results: The mean (95% CI) change in PtCO
at 20 min
was −0.6 mm Hg (−1.1 to 0.0), P = 0.06; −1.3 mm Hg
(−1.9 to 0.8), P < 0.001; and −2.4 mm Hg (−2.9 to −1.8),
P < 0.001; for NHF at 15 L/min, 30 L/min and 45 L/min
compared with room air, respectively. The mean (95%
CI) change in respiratory rate at 20 min was −1.5 (−2.7
to −0.3), P = 0.02; −4.1 (−5.3 to −2.9), P < 0.001; and
−4.3 (−5.5 to −3.1), P < 0.001; breaths per minute com-
pared with room air, respectively.
Conclusion: NHF results in a small ﬂow-dependent
reduction in PtCO
and respiratory rate in patients with
Clinical trial registration:
ACTRN12615000471583 at anzctr.
arterial partial pressure, carbon dioxide, chronic
obstructive respiratory disease, nasal high ﬂow, randomized
, forced expiratory volume in 1 s; FVC,
forced vital capacity; NHF, nasal high ﬂow; NIV, non-invasive
, partial pressure of arterial carbon dioxide;
, transcutaneous partial pressure of carbon dioxide; RIP,
Respiratory Inductance Plethysmography; StO
In acute exacerbations of COPD, hypercapnia is associ-
ated with worse clinical outcomes including death.
invasive ventilation (NIV) is recommended to provide
respiratory support to patients with exacerbations of
COPD who have hypercapnic respiratory failure despite
optimal medical therapy.
Tolerability of NIV may be a
barrier to effective use
and an alternative to NIV is a prior-
ity for the management of acute exacerbations of COPD.
Nasal high ﬂow (NHF) therapy may cause a modest
reduction in the partial pressure of arterial carbon diox-
) in both stable and acute COPD.
ever, the interpretation of studies of NHF, and their
applicability to clinical practice, remains variably limited
by the confounding effect of concomitant oxygen ther-
apy, absence of randomized controlled treatments and
a lack of data on the dose–response relationship across
the range of ﬂows used in clinical practice.
The present study is a randomized controlled cross-
over trial of the effect of three different ﬂow rates of
NHF therapy compared with a control intervention of
room air, in patients with stable COPD who do not
need concomitant oxygen therapy. The main objective
of the present study was to determine the ﬂow-
response relationship of NHF therapy and PaCO
stable COPD. The hypothesis was that NHF therapy
would cause a ﬂow-dependent reduction in PaCO
respiratory rate in stable COPD.
In this single-blind, randomized, controlled, four-way
cross-over trial, 48 participants with a doctor’s diagno-
sis of COPD, aged at least 40 years and with a tobacco
Correspondence: Steven McKinstry, Medical Research
Institute of New Zealand, Private Bag 7902, Wellington 6242,
New Zealand. Email: email@example.com
Received March 23 2017; revised July 6 2017; accepted
September 4 2017 (Associate Editor: Maarten van den Berge;
Senior Editor: Phan Nguyen).
SUMMARY AT A GLANCE
In patients with stable COPD, the administration of
nasal high ﬂow results in ﬂow-dependent reduc-
tions in transcutaneous partial pressure of carbon
dioxide and respiratory rate.
© 2017 Asian Paciﬁc Society of Respirology Respirology (2018) 23, 378–384