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Potential confounders for the effect of high-flow nasal cannula oxygen therapy

The Original Article was published on 02 August 2018

To the Editor:

We read with considerable interest the article published in a recent issue of Critical Care by Di Mussi and colleagues [1], who investigated the physiological effects of high-flow nasal canula (HFNC) compared with conventional O2 therapy after extubation in patients with chronic obstructive pulmonary disease (COPD) receiving mechanical ventilation. The authors demonstrated that postextubation HFNC significantly decreased neuroventilatory drive and the work of breathing compared with conventional O2 therapy. However, several factors that might potentially affect their results should be discussed.

First, although the authors discussed one of the mechanisms related to the decreased work of breathing using HFNC compared with conventional O2 therapy, which was associated with the flow-dependent CO2 wash-out effect, they did not directly assess the relationship between the variables of work of breathing and the flow rate of HFNC. Various flow rates ranging from 20 to 60 L/min were used in this study, which are inconsistent with previous studies, where the flow rates of HFNC were fixed [2, 3]. A higher flow rate of HFNC potentially increases the CO2 wash-out effect and consequently decreases the respiratory effort [4].

Second, the reasons for reintubation in this study were unclear. The authors failed to show a correlation between the work of breathing and the requirement of reintubation; more significant risk factors of reintubation could include other clinical conditions. Shock or disturbed consciousness, masking the effect of HFNC, might be potential confounders in this study.

Finally, we would like to know the differences in clinical characteristics between the patients who benefited from HFNC and those who did not. The authors demonstrated that several patients showed almost no change in neuroventilatory drive and work of breathing independent of the use of HFNC or conventional O2 therapy. We speculate that the strength of respiratory drive or the severity of COPD affected these parameters.

In conclusion, we believe that clarification of these issues by the authors would be helpful for a better understanding of the benefit of postextubation HFNC in patients with COPD.



Chronic obstructive pulmonary disease


High-flow nasal canula


  1. Di Mussi R, Spadaro S, Stripoli T, Volta CA, Trerotoli P, Pierucci P, Staffieri F, Bruno F, Camporota L, Grasso S. High-flow nasal cannula oxygen therapy decreases postextubation neuroventilatory drive and work of breathing in patients with chronic obstructive pulmonary disease. Crit Care. 2018;22:180.

    Article  Google Scholar 

  2. Maggiore SM, Idone FA, Vaschetto R, Festa R, Cataldo A, Antonicelli F, Montini L, De Gaetano A, Navalesi P, Antonelli M. Nasal high-flow versus Venturi mask oxygen therapy after extubation. Effects on oxygenation, comfort, and clinical outcome. Am J Respir Crit Care Med. 2014;190:282–8.

    Article  Google Scholar 

  3. Rittayamai N, Tscheikuna J, Rujiwit P. High-flow nasal cannula versus conventional oxygen therapy after endotracheal extubation: a randomized crossover physiologic study. Respir Care. 2014;59:485–90.

    Article  Google Scholar 

  4. Mauri T, Alban L, Turrini C, Cambiaghi B, Carlesso E, Taccone P, Bottino N, Lissoni A, Spadaro S, Volta CA, Gattinoni L, Pesenti A, Grasselli G. Optimum support by high-flow nasal cannula in acute hypoxemic respiratory failure: effects of increasing flow rates. Intensive Care Med. 2017;43:1453–63.

    Article  CAS  Google Scholar 

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We thank Edanz Group ( for editing a draft of this manuscript.


This work was supported by KAKENHI Grants from the Japan Society for the Promotion of Science (JSPS) (numbers JP 16K09541, 17K11573 and 18K16540), and by the Strategic Information and Communications R&D Promotion Programme (SCOPE), and the Japan Agency for Medical Research and Development (AMED).

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SY drafted the manuscript. SO and NS revised the manuscript. All authors read and approved the final manuscript.

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Correspondence to Shinichiro Ohshimo.

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See related research by Di Mussi et al.,

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Yamaga, S., Ohshimo, S. & Shime, N. Potential confounders for the effect of high-flow nasal cannula oxygen therapy. Crit Care 23, 17 (2019).

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