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Uncovering the mechanisms of exertional dyspnoea in combined pulmonary fibrosis and emphysema

Camila M. Costa, J. Alberto Neder, Carlos G. Verrastro, Marcelle Paula-Ribeiro, Roberta Ramos, Eloara M. Ferreira, Luiz E. Nery, Denis E. O'Donnell, Carlos A.C. Pereira, Jaquelina Ota-Arakaki
European Respiratory Journal 2020 55: 1901319; DOI: 10.1183/13993003.01319-2019
Camila M. Costa
1Pulmonary Vascular Disease and Interstitial Lung Disease Services, Division of Respirology, Federal University of Sao Paulo, Sao Paulo, Brazil
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J. Alberto Neder
2Laboratory of Clinical Exercise Physiology and Respiratory Investigation Unit, Queen's University and Kingston General Hospital, Kingston, ON, Canada
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  • For correspondence: alberto.neder@queensu.ca
Carlos G. Verrastro
3Division of Imaging, Federal University of Sao Paulo, Sao Paulo, Brazil
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Marcelle Paula-Ribeiro
1Pulmonary Vascular Disease and Interstitial Lung Disease Services, Division of Respirology, Federal University of Sao Paulo, Sao Paulo, Brazil
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Roberta Ramos
1Pulmonary Vascular Disease and Interstitial Lung Disease Services, Division of Respirology, Federal University of Sao Paulo, Sao Paulo, Brazil
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Eloara M. Ferreira
1Pulmonary Vascular Disease and Interstitial Lung Disease Services, Division of Respirology, Federal University of Sao Paulo, Sao Paulo, Brazil
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Luiz E. Nery
1Pulmonary Vascular Disease and Interstitial Lung Disease Services, Division of Respirology, Federal University of Sao Paulo, Sao Paulo, Brazil
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Denis E. O'Donnell
2Laboratory of Clinical Exercise Physiology and Respiratory Investigation Unit, Queen's University and Kingston General Hospital, Kingston, ON, Canada
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Carlos A.C. Pereira
1Pulmonary Vascular Disease and Interstitial Lung Disease Services, Division of Respirology, Federal University of Sao Paulo, Sao Paulo, Brazil
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Jaquelina Ota-Arakaki
1Pulmonary Vascular Disease and Interstitial Lung Disease Services, Division of Respirology, Federal University of Sao Paulo, Sao Paulo, Brazil
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Abstract

The prevailing view is that exertional dyspnoea in patients with combined idiopathic pulmonary fibrosis (IPF) and emphysema (CPFE) can be largely explained by severe hypoxaemia. However, there is little evidence to support these assumptions.

We prospectively contrasted the sensory and physiological responses to exercise in 42 CPFE and 16 IPF patients matched by the severity of exertional hypoxaemia. Emphysema and pulmonary fibrosis were quantified using computed tomography. Inspiratory constraints were assessed in a constant work rate test: capillary blood gases were obtained in a subset of patients.

CPFE patients had lower exercise capacity despite less extensive fibrosis compared to IPF (p=0.004 and 0.02, respectively). Exertional dyspnoea was the key limiting symptom in 24 CPFE patients who showed significantly lower transfer factor, arterial carbon dioxide tension and ventilatory efficiency (higher minute ventilation (V′E)/carbon dioxide output (V′CO2) ratio) compared to those with less dyspnoea. However, there were no between-group differences in the likelihood of pulmonary hypertension by echocardiography (p=0.44). High dead space/tidal volume ratio, low capillary carbon dioxide tension emphysema severity (including admixed emphysema) and traction bronchiectasis were related to a high V′E/V′CO2 ratio in the more dyspnoeic group. V′E/V′CO2 nadir >50 (OR 9.43, 95% CI 5.28–13.6; p=0.0001) and total emphysema extent >15% (2.25, 1.28–3.54; p=0.01) predicted a high dyspnoea burden associated with severely reduced exercise capacity in CPFE

Contrary to current understanding, hypoxaemia per se is not the main determinant of exertional dyspnoea in CPFE. Poor ventilatory efficiency due to increased “wasted” ventilation in emphysematous areas and hyperventilation holds a key mechanistic role that deserves therapeutic attention.

Abstract

Exertional dyspnoea is related to poor ventilatory efficiency rather than hypoxaemia or inspiratory constraints in CPFE. Lessening patients' excessive ventilation might prove particularly beneficial to mitigate the burden of this disabling symptom. http://bit.ly/2MRn6az

Footnotes

  • This article has supplementary material available from erj.ersjournals.com

  • Support statement: Camila M. Costa received a Doctoral Fellowship from Brazil's Coordenadoria de Aperfeicoamento do Pessoal de Nivel Superior (CAPES). J. Alberto Neder has been funded by a New Clinician Scientist Program from the Southeastern Ontario Academic Medical Association (SEAMO), Canada. The funders had no role in the study design, data collection and analysis, or preparation of the manuscript.

  • Conflict of interest: C.M. Costa has nothing to disclose.

  • Conflict of interest: J.A. Neder has nothing to disclose.

  • Conflict of interest: C.G. Verrastro has nothing to disclose.

  • Conflict of interest: M. Paula-Ribeiro has nothing to disclose.

  • Conflict of interest: R. Ramos has nothing to disclose.

  • Conflict of interest: E.M. Ferreira has nothing to disclose.

  • Conflict of interest: L.E. Nery has nothing to disclose.

  • Conflict of interest: D.E. O'Donnell has nothing to disclose.

  • Conflict of interest: C.A.C. Pereira has nothing to disclose.

  • Conflict of interest: J. Ota-Arakaki has nothing to disclose.

  • Received April 30, 2019.
  • Accepted October 12, 2019.
  • Copyright ©ERS 2020
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Uncovering the mechanisms of exertional dyspnoea in combined pulmonary fibrosis and emphysema
Camila M. Costa, J. Alberto Neder, Carlos G. Verrastro, Marcelle Paula-Ribeiro, Roberta Ramos, Eloara M. Ferreira, Luiz E. Nery, Denis E. O'Donnell, Carlos A.C. Pereira, Jaquelina Ota-Arakaki
European Respiratory Journal Jan 2020, 55 (1) 1901319; DOI: 10.1183/13993003.01319-2019

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Uncovering the mechanisms of exertional dyspnoea in combined pulmonary fibrosis and emphysema
Camila M. Costa, J. Alberto Neder, Carlos G. Verrastro, Marcelle Paula-Ribeiro, Roberta Ramos, Eloara M. Ferreira, Luiz E. Nery, Denis E. O'Donnell, Carlos A.C. Pereira, Jaquelina Ota-Arakaki
European Respiratory Journal Jan 2020, 55 (1) 1901319; DOI: 10.1183/13993003.01319-2019
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