Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Basic Science Article
  • Published:

Effort and work-of-breathing parameters strongly correlate with increased resistance in an animal model

Pediatric Research volume 94, pages 944–949 (2023)Cite this article

Abstract

Background

Effort of Breathing (EOB) calculations may be a reliable alternative to Work of Breathing (WOB) calculations in which Respiratory Inductance Plethysmography (RIP) replaces spirometry. We sought to compare EOB and WOB measurements in a nonhuman primate model of increasing extrathoracic inspiratory resistance simulating upper airway obstruction (UAO).

Methods

RIP, spirometry, and esophageal manometry were measured in spontaneously breathing, intubated Rhesus monkeys utilizing 11 calibrated resistors randomly applied for 2-min. EOB was calculated breath-by-breath as Pressure Rate Product (PRP) and Pressure Time Product (PTP). WOB was calculated from the Pressure-Volume curve based on spirometry (WOBSPIR) or RIP flow (WOBRIP).

Results

WOB, PRP and PTP showed similar linear increases when exposed to higher levels of resistive loads. When comparing WOBSPIR to WOBRIP, a similar strong correlation was seen for both signals as resistance increased and there were no statistically significant differences.

Conclusion

EOB and WOB parameters utilizing esophageal manometry and RIP, independent of spirometry, showed a strong correlation as a function of increasing inspiratory resistance in nonhuman primates. This allows several potential monitoring possibilities for non-invasively ventilated patients or situations where spirometry is not available.

Impact

  • EOB and WOB parameters showed a strong correlation as a function of increasing inspiratory resistance in nonhuman primates.

  • There was a strong correlation between spirometry-based WOB versus RIP-based WOB.

  • To date, it has remained untested as to whether EOB is a reliable alternative for WOB and if RIP can replace spirometry in these measurements.

  • Our results enable additional potential monitoring possibilities for non-invasively ventilated patients or situations where spirometry is not available.

  • Where spirometry is not available, there is no need to apply a facemask post extubation to a spontaneously breathing, non-intubated infant to make objective EOB measurements.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Calculation of Pressure Rate Product (PRP) and Pressure Time Product (PTP).
Fig. 2: Superimposed Work-of-breathing based on spirometry (WOBSPIR), Pressure Rate Product (PRP) and Pressure Time Product (PTP) against a range of resistors (0–1000 cmH2O/L/s).
Fig. 3: Superimposed Work-of-breathing based on spirometry (WOBSPIR) and Work of breathing based on Respiratory Inductance Plethysmography (WOBRIP) against a range of resistors (0–1000 cm H2O/L/s).
Fig. 4: Scatter plots of Work of Breathing based on Spirometry (WOBSPIR) versus Pressure Rate Product (PRP), Pressure Time Product (PRP) and Work of Breathing based on RIP (WOBRIP) of all data.

Similar content being viewed by others

References

  1. Argent, A. C., Newth, C. J. L. & Klein, M. The mechanics of breathing in children with acute severe croup. Intensive Care Med. 34, 324–332 (2008).

    Article  PubMed  Google Scholar 

  2. Graham, A. S., Chandrashekharaiah, G., Citak, A., Wetzel, R. C. & Newth, C. J. L. Positive end-expiratory pressure and pressure support in peripheral airways obstruction. Intensive Care Med. 33, 120–127 (2006).

    Article  PubMed  Google Scholar 

  3. Willis, B. C., Graham, A. S., Yoon, E., Wetzel, R. C. & Newth, C. J. L. Pressure-rate products and phase angles in children on minimal support ventilation and after extubation. Intensive Care Med. 31, 1700–1705 (2005).

    Article  PubMed  Google Scholar 

  4. Khemani, R. G. et al. Evaluating Risk Factors for Pediatric Post-extubation Upper Airway Obstruction Using a Physiology-based Tool. Am. J. Resp. Crit. Care. 193, 198–209 (2016).

    Article  Google Scholar 

  5. Klein, M. & Reynolds, L. G. Relief of sleep-related oropharyngeal airway obstruction by continuous insufflation of the pharynx. Lancet 1, 935–939 (1986).

    Article  CAS  PubMed  Google Scholar 

  6. Argent, A. C., Hatherill, M., Newth, C. J. L. & Klein, M. The effect of epinephrine by nebulization on measures of airway obstruction in patients with acute severe croup. Intensive Care Med. 34, 138–147 (2007).

    Article  PubMed  Google Scholar 

  7. Khemani, R. G. et al. Respiratory inductance plethysmography calibration for pediatric upper airway obstruction: an animal model. Pediatr. Res. 77, 75–83 (2015).

    Article  PubMed  Google Scholar 

  8. Harrison, V. C., Heese Hde, V. & Klein, M. The significance of grunting in hyaline membrane disease. Pediatrics 41, 549–559 (1968).

    Article  CAS  PubMed  Google Scholar 

  9. Asher, M. I., Coates, A. L., Collinge, J. M. & Milic-Emili, J. Measurement of pleural pressure in neonates. J. Appl Physiol. 52, 491–494 (1982).

    Article  CAS  PubMed  Google Scholar 

  10. Coates, A. L., Davis, G. M., Vallinis, P. & Outerbridge, E. W. Liquid-filled esophageal catheter for measuring pleural pressure in preterm neonates. J. Appl. Physiol. 67, 889–893 (1989).

    Article  CAS  PubMed  Google Scholar 

  11. Hammer, J. & Newth, C. Influence of endotracheal tube diameter on forced deflation flow-volume curves in rhesus monkeys. Eur. Respir. J. 10, 1870–1873 (1997).

    Article  CAS  PubMed  Google Scholar 

  12. Cabello, B. & Mancebo, J. Work of breathing. Intensive Care Med. 32, 1311–1314 (2006).

    Article  PubMed  Google Scholar 

  13. Khemani, R. G. et al. Pediatric extubation readiness tests should not use pressure support. Intensive Care Med. 42, 1214–1222 (2016).

    Article  PubMed  Google Scholar 

  14. Sivan, Y., Deakers, T. W. & Newth, C. J. L. Thoracoabdominal asynchrony in acute upper airway obstruction in small children. Am. Rev. Respir. Dis. 142, 540–544 (1990).

    Article  CAS  PubMed  Google Scholar 

  15. Stocks, J. Respiratory physiology during early life. Monaldi Arch. Chest Dis. 54, 358–364 (1999).

    CAS  PubMed  Google Scholar 

  16. Verma, R. P. Respiratory Distress Syndrome of the Newborn Infant. Obstet. Gynecol. Surv. 50, 542–555 (1995).

    Article  CAS  PubMed  Google Scholar 

  17. de Vries, H., Jonkman, A., Shi, Z. H., Spoelstra-de Man, A. & Heunks, L. Assessing breathing effort in mechanical ventilation: physiology and clinical implications. Ann. Transl. Med. 6, 387 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors acknowledge the financial support of the National Institutes of Health/National Institutes of Child Health and Development 1K23HL103785 (R.G.K.), Bethesda, MD, and Novartis Pharmaceutical Grant-in-Aid for facilities (C.J.L.N.), Basel, Switzerland.

Author information

Authors and Affiliations

  1. Department of Neonatology, Emma Children’s Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands

    Rutger C. Flink, Frans H. de Jongh & Anton. H. van Kaam

  2. Department of Anesthesiology & Critical Care Medicine, Children’s Hospital Los Angeles, Los Angeles, CA, USA

    Christopher J. L. Newth, Justin C. Hotz, Patrick A. Ross & Robinder G. Khemani

  3. Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

    Christopher J. L. Newth, Justin C. Hotz & Robinder G. Khemani

  4. Department of Paediatrics, Division of Paediatric Critical Care Medicine, Beatrix Children’s Hospital Groningen, University Medical Center Groningen, The University of Groningen, Groningen, The Netherlands

    Martin C. J. Kneyber

Authors
  1. Rutger C. Flink
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Christopher J. L. Newth
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Justin C. Hotz
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Martin C. J. Kneyber
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Patrick A. Ross
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Frans H. de Jongh
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Anton. H. van Kaam
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Robinder G. Khemani
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Conception and design: R.F., R.K., C.N. Analysis and interpretation: R.F., J.H., M.K., F.d.J., C.N., A.v.K., R.K. Drafting the paper for important intellectual content: R.F., A.v.K., F.d.J., M.K., C.N., R.K.

Corresponding author

Correspondence to Rutger C. Flink.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Flink, R.C., Newth, C.J.L., Hotz, J.C. et al. Effort and work-of-breathing parameters strongly correlate with increased resistance in an animal model. Pediatr Res 94, 944–949 (2023). https://doi.org/10.1038/s41390-023-02576-4

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41390-023-02576-4

Search

Advanced search

Quick links