Mechanisms of impaired alveolar fluid clearance

doi:10.1002/ar.25166

Review

. 2025 Apr;308(4):1026-1039.

doi: 10.1002/ar.25166. Epub 2023 Jan 23.

Mechanisms of impaired alveolar fluid clearance

Hiroki Taenaka^{1

2

3}, Michael A Matthay^{1

2}

Affiliations

¹ Department of Medicine, Cardiovascular Research Institute, University of California, San Francisco, California, USA.
² Department of Anesthesia, Cardiovascular Research Institute, University of California, San Francisco, California, USA.
³ Department of Anesthesiology and Intensive Care Medicine, Osaka University Graduate School of Medicine, Suita, Japan.

PMID: 36688689
PMCID: PMC10564110 (available on 2025-04-01)
DOI: 10.1002/ar.25166

Review

Mechanisms of impaired alveolar fluid clearance

Hiroki Taenaka et al. Anat Rec (Hoboken). 2025 Apr.

. 2025 Apr;308(4):1026-1039.

doi: 10.1002/ar.25166. Epub 2023 Jan 23.

Authors

Hiroki Taenaka^{1

2

3}, Michael A Matthay^{1

2}

Affiliations

¹ Department of Medicine, Cardiovascular Research Institute, University of California, San Francisco, California, USA.
² Department of Anesthesia, Cardiovascular Research Institute, University of California, San Francisco, California, USA.
³ Department of Anesthesiology and Intensive Care Medicine, Osaka University Graduate School of Medicine, Suita, Japan.

PMID: 36688689
PMCID: PMC10564110 (available on 2025-04-01)
DOI: 10.1002/ar.25166

Abstract

Impaired alveolar fluid clearance (AFC) is an important cause of alveolar edema fluid accumulation in patients with acute respiratory distress syndrome (ARDS). Alveolar edema leads to insufficient gas exchange and worse clinical outcomes. Thus, it is important to understand the pathophysiology of impaired AFC in order to develop new therapies for ARDS. Over the last few decades, multiple experimental studies have been done to understand the molecular, cellular, and physiological mechanisms that regulate AFC in the normal and the injured lung. This review provides a review of AFC in the normal lung, focuses on the mechanisms of impaired AFC, and then outlines the regulation of AFC. Finally, we summarize ongoing challenges and possible future research that may offer promising therapies for ARDS.

Keywords: acute lung injury; acute respiratory distress syndrome; alveolar fluid clearance.

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References

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1. Azzam ZS, Dumasius V, Saldias FJ, Adir Y, Sznajder JI, Factor P. 2002. Na,K-ATPase overexpression improves alveolar fluid clearance in a rat model of elevated left atrial pressure. Circulation 105:497–501. - PubMed
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[1] Abraham A, Krasnodembskaya A. 2020. Mesenchymal stem cell-derived extracellular vesicles for the treatment of acute respiratory distress syndrome. Stem Cells Transl Med 9:28–38. - PMC - PubMed

[2] Abraham A, Krasnodembskaya A. 2020. Mesenchymal stem cell-derived extracellular vesicles for the treatment of acute respiratory distress syndrome. Stem Cells Transl Med 9:28–38. - PMC - PubMed

[3] Amato MBP, Barbas CSV, Medeiros DM, Magaldi RB, Schettino GP, Lorenzi-Filho G, Kairalla RA, Deheinzelin D, Munoz C, Oliveira R, Takagaki TY, Carvalho CRR. 1998. Effect of a Protective-Ventilation Strategy on Mortality in the Acute Respiratory Distress Syndrome. New England Journal of Medicine 338:347–354. - PubMed

[4] Amato MBP, Barbas CSV, Medeiros DM, Magaldi RB, Schettino GP, Lorenzi-Filho G, Kairalla RA, Deheinzelin D, Munoz C, Oliveira R, Takagaki TY, Carvalho CRR. 1998. Effect of a Protective-Ventilation Strategy on Mortality in the Acute Respiratory Distress Syndrome. New England Journal of Medicine 338:347–354. - PubMed

[5] Asmussen S, Ito H, Traber DL, Lee JW, Cox RA, Hawkins HK, McAuley DF, McKenna DH, Traber LD, Zhuo H, Wilson J, Herndon DN, Prough DS, Liu KD, Matthay MA, Enkhbaatar P. 2014. Human mesenchymal stem cells reduce the severity of acute lung injury in a sheep model of bacterial pneumonia. Thorax 69:819–825. - PMC - PubMed

[6] Asmussen S, Ito H, Traber DL, Lee JW, Cox RA, Hawkins HK, McAuley DF, McKenna DH, Traber LD, Zhuo H, Wilson J, Herndon DN, Prough DS, Liu KD, Matthay MA, Enkhbaatar P. 2014. Human mesenchymal stem cells reduce the severity of acute lung injury in a sheep model of bacterial pneumonia. Thorax 69:819–825. - PMC - PubMed

[7] Azzam ZS, Dumasius V, Saldias FJ, Adir Y, Sznajder JI, Factor P. 2002. Na,K-ATPase overexpression improves alveolar fluid clearance in a rat model of elevated left atrial pressure. Circulation 105:497–501. - PubMed

[8] Azzam ZS, Dumasius V, Saldias FJ, Adir Y, Sznajder JI, Factor P. 2002. Na,K-ATPase overexpression improves alveolar fluid clearance in a rat model of elevated left atrial pressure. Circulation 105:497–501. - PubMed

[9] Bai C, Fukuda N, Song Y, Ma T, Matthay MA, Verkman AS. 1999. Lung fluid transport in aquaporin-1 and aquaporin-4 knockout mice. The Journal of clinical investigation 103:555–561. - PMC - PubMed

[10] Bai C, Fukuda N, Song Y, Ma T, Matthay MA, Verkman AS. 1999. Lung fluid transport in aquaporin-1 and aquaporin-4 knockout mice. The Journal of clinical investigation 103:555–561. - PMC - PubMed

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Mechanisms of impaired alveolar fluid clearance

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Mechanisms of impaired alveolar fluid clearance

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