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Research letter

Nasal high ow oxygen have the potential for domiciliary use. oxygen (FiO2) to a total ow of 30 L/min
NHF delivers heated and humidied air/ from an AIRVO through an Optiow nasal
therapy in patients with COPD oxygen with ows up to 60 L/min. NHF interface (Fisher & Paykel Healthcare,
reduces respiratory rate and produces pharyngeal pressures of 28 cm Auckland, New Zealand). Data collected
H2O2, which transmit to the alveoli, con- included transcutaneous oxygen (TcO2) and
tissue carbon dioxide while tributing to lung recruitment and upper transcutaneous carbon dioxide (TcCO2);
increasing tidal and airway splinting.3 Nasopharyngeal dead pulse oximetry; tidal volume (Vt) and
end-expiratory lung volumes: space washout has been proposed to minute volume (MV), respiratory rate (RR)
reduce CO2 rebreathing, thus providing a and I:E ratio via respiratory inductance
a randomised crossover trial fresh reservoir of oxygen from which to plethysmography; end-expiratory lung
breathe.4 The observed clinical effects of impedance (EELI) via electrical impedance
Abstract high gas ows in patients with COPD tomography; heart rate (HR) via standard
Patients with COPD using long-term oxygen include improvements in exercise toler- ECG monitoring; subjective dyspnoea and
therapy (LTOT) over 15 h per day have ance, oxygenation and reduced dys- comfort scores (0=no dyspnoea/discomfort
improved outcomes. As inhalation of dry cold pnoea.5 6 NHF has been demonstrated to to 10=maximum dyspnoea/discomfort);
gas is detrimental to mucociliary clearance, increase tidal volumes in a number of and videography of the patients torso to
humidied nasal high ow (NHF) oxygen may cohorts,7 while reducing work of breath- identify inconsistencies during data analysis
reduce frequency of exacerbations, while ing by lowering inspiratory resistance and such as coughing and sneezing.
improving lung function and quality of life in generating positive expiratory pressure.5 Patients remained on LTOT during the
this cohort. In this randomised crossover study, NHF has been shown to be non-inferior 20 min set-up period while baseline
we assessed short-term physiological responses to non-invasive ventilation in the preven- recordings were taken. Patients received
to NHF therapy in 30 males chronically treated tion of treatment failure in patients with the rst randomised therapy (LTOT or
with LTOT. LTOT (24 L/min) through nasal acute respiratory failure postcardiac NHF) for 20 min, followed by a 20 min
cannula was compared with NHF at 30 L/min surgery8 and reduce mortality (both in the washout period of LTOT, after which they
from an AIRVO through an Optiow nasal intensive care unit and at 90 days) in crossed over to the second therapy (LTOT
interface with entrained supplemental oxygen. patients with acute respiratory failure.9 or NHF) for 20 min.
Comparing NHF with LTOT: transcutaneous A randomised crossover study was com-
carbon dioxide (TcCO2) (43.3 vs 46.7 mm Hg, menced to assess the short-term physio- RESULTS
p<0.001), transcutaneous oxygen (TcO2) (97.1 logical effects of NHF oxygen in patients Details regarding the numbers of patients
vs 101.2 mm Hg, p=0.01), I:E ratio (0.75 vs with chronic stable COPD. screened and subsequently excluded are
0.86, p=0.02) and respiratory rate (RR) (15.4
contained in the online repository. Thirty
vs 19.2 bpm, p<0.001) were lower; and tidal METHODS patients were included in the study (see
volume (Vt) (0.50 vs 0.40, p=0.003) and end- The online repository for this research tables in online repository for patient
expiratory lung volume (EELV) (174% vs 113%, letter contains details on study inclusion characteristics). Results are contained in
p<0.001) were higher. EELV is expressed as and exclusion criteria, study procedures table 1.
relative change from baseline (%). Subjective and statistical analysis. When comparing NHF with LTOT,
dyspnoea and interface comfort favoured LTOT.
TcO2, TcCO2, RR and I:E ratio were sig-
NHF decreased TcCO2, I:E ratio and RR, with a
Study protocol nicantly lower when using NHF. On
concurrent increase in EELV and Vt compared
A randomised crossover design was used to NHF, Vt and EELI were signicantly
with LTOT. This demonstrates a potential
study subjects on their own LTOT (low higher than on LTOT. Figure 1 illustrates
mechanistic rationale behind the improved
ow oxygen, 24 L/min through nasal the decrease in TcCO2 and RR. No signi-
outcomes observed in long-term treatment with
cannula) and NHF using air supplemented cant difference between groups was found
NHF in oxygen-dependent patients.
with the equivalent fraction of inspired in SpO2, MV or HR.
Trial registration number
ACTRN12613000028707.

Table 1 Two-way (paired) comparisons between the long-term oxygen therapy (LTOT) and
INTRODUCTION nasal high flow (NHF) groups
The burden of COPD is increasing glo- Variable LTOT NHF p Value
bally, and its physiological, economical
Oxygen saturation (%)* 95.8 (94.6 to 96.9) 95.7 (93.1 to 97.1) 0.06
and mortality costs are enormous, with
Transcutaneous O2 (mm Hg) 101.2 (22.5) 97.1 (24.2) 0.01
>65 million people affected by
Transcutaneous CO2 (mm Hg) 46.7 (9.4) 43.3 (9.5) <0.001
moderate-to-severe COPD.
Respiratory rate (breaths/min) 19.2 (6.3) 15.4 (4.8) 0.001
Long-term oxygen therapy (LTOT)
Inspiratory:expiratory ratio 0.86 (0.20) 0.75 (0.25) 0.02
improves health outcomes and reduces
Tidal volume (L)* 0.40 (0.34, 0.46) 0.50 (0.41, 0.54) 0.003
mortality.1 However, further optimisation
Minute volume (L/min)* 6.20 (4.84, 8.18) 6.18 (4.75, 7.69) 0.88
of respiratory support may diminish
Heart rate (beats/min) 70.1 (59.1, 79.3) 69.8 (61.3, 79.8) 0.21
symptomatic breathlessness, ameliorate
End-expiratory lung impedance (%)* 113 (98, 128) 174 (161, 187) <0.001
COPD-associated cachexia, reduce hyper-
carbia, improve right ventricular function A p value <0.05 was considered significant. Normally distributed data are presented as mean (SD) while non-normal
data are presented as median (IQR). End-expiratory lung impedance data are presented as percentage change from
and provide psychological benets. baseline (%). All variables returned to baseline values during the washout periods and subsequently during the
Nasal high ow (NHF) oxygen, an recovery period.
emerging therapy developed for acute *A paired t test was used for the normally distributed data while a Wilcoxon signed rank test was used for the
non-normal data.
care areas for respiratory support, may
Thorax August 2016 Vol 71 No 8 759
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Research letter

Figure 1 Observed decreases in respiratory rate and transcutaneous carbon dioxide level between the long-term oxygen therapy (LTOT) group and
the nasal high ow (NHF) group. Data are presented as mean and vertical 95% CI bars.

Median subjective dyspnoea scores reduced RR and increased EELV and Vt, patient, short-term NHF use results in
were signicantly higher during NHF combined with adequate oxygen to reductions in TcCO2 and RR, with
compared with LTOT (LTOT: median 0.5 prevent hypoxia and pulmonary hyperten- increased Vt and EELV, when compared to
[range 03.5]; NHF: 2.005, p<0.001). sion, is unknown, indicating the need for LTOT. However, this cohort rated their
Similarly with interface comfort, LTOT a long-term study in the domiciliary LTOT interface more comfortable and
was more comfortable than NHF (LTOT: setting. This reduction in TcCO2 corre- providing more dyspnoea relief than
9;710 NHF: 8 [2.510], p<0.02). lates with the consistent rise in Vt, and we NHF. This short-term study demonstrates
believe this increase may be accompanied adequate physiological rationale to
by dead space and subsequent CO2 proceed with trialling these devices in the
DISCUSSION washout, as seen in preceding COPD long-term management of COPD, with
In this study, NHF in patients with stable studies.6 the hope of reducing further physiological
oxygen-dependent COPD led to a signi- The ability of NHF to reduce RR is decay, improving quality of life and redu-
cant reduction in TcCO2 levels. NHF use consistent with a reduction in work of cing hospital admissions.
also resulted in increases in Vt, end- breathing. The mechanism is most likely
expiratory lung volume (EELV) and I:E the reduced anatomical dead space
ratio with corresponding decreases in RR, John F Fraser,1 Amy J Spooner,1
assisted by the positive expiratory pres- Kimble R Dunster,1,2 Chris M Anstey,1,3
without changes to MV. These short-term sure effect of NHF, which allows for Amanda Corley1
ndings, if conrmed over a longer dur- improved ventilation and perfusion 1
Critical Care Research Group, The Prince Charles
ation in subsequent studies, could imply a matching. Additionally, matching the Hospital and University of Queensland, Brisbane,
role for NHF in the domiciliary manage- inspiratory ow demands with NHF Australia
2
ment of patients with COPD dependent overcomes nasopharyngeal inspiratory Biomedical Engineering and Medical Physics, Science
on LTOT. and Engineering Faculty, Queensland University of
resistance, thereby diminishing resistive Technology, Brisbane, Australia
Hypercarbia, respiratory acidosis and work of breathing.5 3
Intensive Care Unit, Nambour General Hospital,
failure are all associated with increased In this NHF-naive cohort, higher dys- Nambour, Australia
risk of acute deterioration and poor out- pnoea and lower comfort scores were Correspondence to Amanda Corley, Critical Care
comes for patients with COPD. Home observed during NHF, perhaps due to Research Group, Level 5 CSB, The Prince Charles
NHF use with titrated or low-level supple- commencing a new treatment in a cohort Hospital, Rode Rd, Chermside, Brisbane, QLD 4032,
mental oxygen may assist in avoiding known to suffer from anxiety. Australia; amanda.corley@health.qld.gov.au
these problems. How long patients should This study has some limitations that are Additional material is published online only. To view
be maintained on this strategy for the ben- contained in the online repository. please visit the journal online (http://dx.doi.org/10.
ets of NHF to be sustained is unclear; 1136/thoraxjnl-2015-207962).
however, in a recent study of long-term
Acknowledgements The authors would like to
domiciliary use of NHF, the actual expos- CONCLUSIONS acknowledge the Respiratory Physicians for their
ure time to NHF was 1.6 h/day.10 The This study demonstrates that in the stable support and Lisa McCarthy for her encouragement and
supplemental benet of reduced TcCO2, home-oxygen-dependent male COPD assistance throughout the project.

760 Thorax August 2016 Vol 71 No 8


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Research letter
Contributors JFF contributed to study design, Attribution Non Commercial (CC BY-NC 4.0) license, end-expiratory lung volume and reduce respiratory
manuscript preparation, data interpretation and which permits others to distribute, remix, adapt, build rate in post-cardiac surgical patients. Br J Anaesth
manuscript review. KRD, AJS and AC contributed to study upon this work non-commercially, and license their 2011;107:9981004.
design, data collection, cleaning and interpretation, derivative works on different terms, provided the 4 Dysart K, Miller TL, Wolfson MR, et al. Research in
manuscript preparation and manuscript review. CMA original work is properly cited and the use is non- high ow therapy: mechanisms of action. Respir Med
contributed to data cleaning, analysis and interpretation, commercial. See: http://creativecommons.org/licenses/ 2009;103:14005.
manuscript preparation and manuscript review. by-nc/4.0/ 5 Chatila W, Nugent T, Vance G, et al. The effects of
high-ow vs low-ow oxygen on exercise in
Competing interests JFF has received a research
advanced obstructive airways disease. Chest
fellowship from Queensland Health Ofce of Health
2004;126:110815.
and Medical Research. JFF received an unrestricted
6 Okuda M, Kashio M, Tanaka N, et al. Nasal
grant from Fisher & Paykel Healthcare in support of the
high-ow oxygen therapy system for improving
current study. JFF and AC have received assistance from
To cite Fraser JF, Spooner AJ, Dunster K R, et al. sleep-related hypoventilation in chronic obstructive
Fisher & Paykel Healthcare to support travel and
Thorax 2016;71:759761. pulmonary disease: a case report. J Med Case Rep
accommodation costs to attend research meetings;
2014;8:341.
neither has received honoraria or consultancy fees from Received 18 October 2015 7 Brunlich J, Beyer D, Mai D, et al. Effects of nasal
Fisher & Paykel; Revised 22 February 2016 high ow on ventilation in volunteers, COPD and
Patient consent Obtained. Accepted 26 February 2016 idiopathic pulmonary brosis patients. Respiration
Published Online First 25 March 2016 2013;85:31925.
Ethics approval Institutional Human Research and
Ethics Committee (HREC/11/QPCH/152). Thorax 2016;71:759761. 8 Stphan F, Barrucand B, Petit P, et al. High-ow
doi:10.1136/thoraxjnl-2015-207962 nasal oxygen vs noninvasive positive airway pressure
Provenance and peer review Not commissioned; in hypoxemic patients after cardiothoracic surgery.
externally peer reviewed. A randomized clinical trial. JAMA 2015;313:23319.
REFERENCES 9 Frat JP, Thille AW, Mercat A, et al. High-ow oxygen
1 Kent BD, Mitchell PD, McNicholas WT. Hypoxemia in through nasal cannula in acute hypoxemic respiratory
patients with COPD: cause, effects, and disease failure. N Engl J Med 2015;372:218596.
progression. Int J Chron Obstruct Pulmon Dis 10 Rea H, McAuley S, Jayaram L, et al. The clinical
2011;6:199208. utility of long-term humidication therapy in chronic
2 Parke RL, McGuinness SP. Pressures delivered by airways disease. Respir Med 2010;104:52533.
nasal high ow oxygen during all phases of the
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Open Access This is an Open Access article 3 Corley A, Caruana LR, Barnett AG, et al. Oxygen
distributed in accordance with the Creative Commons delivery through high-ow nasal cannulae increase

Thorax August 2016 Vol 71 No 8 761


Downloaded from http://thorax.bmj.com/ on September 13, 2017 - Published by group.bmj.com

Nasal high flow oxygen therapy in patients


with COPD reduces respiratory rate and
tissue carbon dioxide while increasing tidal
and end-expiratory lung volumes: a
randomised crossover trial
John F Fraser, Amy J Spooner, Kimble R Dunster, Chris M Anstey and
Amanda Corley

Thorax 2016 71: 759-761 originally published online March 25, 2016
doi: 10.1136/thoraxjnl-2015-207962

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References This article cites 10 articles, 1 of which you can access for free at:
http://thorax.bmj.com/content/71/8/759#BIBL
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permits others to distribute, remix, adapt, build upon this work
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