Alveolar Fluid Clearance in Patients With ARDS: Does It Make a Difference?

doi:10.1378/chest.122.6_suppl.340S

Chest

Volume 122, Issue 6, Supplement, December 2002, Pages 340S-343S

https://doi.org/10.1378/chest.122.6_suppl.340S Get rights and content

Experimental methods to quantify alveolar fluid clearance have been adapted for our studies in patients with acute lung injury (ALI) or ARDS. We recently completed a study of 79 patients with ALI/ARDS that was designed to examine alveolar fluid clearance in the setting of alveolar epithelial injury from ALI/ARDS. Pulmonary edema fluid and plasma were sampled serially in the first 4 h after endotracheal intubation and the initiation of positive-pressure ventilation. Net alveolar fluid clearance was calculated from sequential edema fluid protein measurements. Patients with maximal alveolar fluid clearance had a significantly lower mortality rate and a shorter duration of mechanical ventilation. Several mechanisms may account for the decrease in the rate of alveolar fluid clearance in ALI/ARDS patients, including hypoxia, reactive oxygen species, reactive nitrogen species, and the loss of an intact epithelial barrier in the distal airspaces of the lung. Despite the epithelial injury in patients with ALI/ARDS, some experimental studies have suggested that alveolar fluid clearance could be increased with therapy using cyclic adenosine monophosphate agonists or other pharmacologic agents.

Section snippets

Alveolar Fluid Clearance in Patients

For several years, our research group has measured the rate of fluid clearance from the airspaces of the lung by measuring protein concentrations in sequential samples of undiluted edema fluid obtained from patients.⁶⁷⁸ This method was adapted from validated measures of airspace fluid clearance in several experimental studies in small and large animals.³ The collection of sequential samples of undiluted edema fluid from the distal airspaces of the lung is performed with a standard suction

Mechanisms That Impair Epithelial Fluid Clearance in Clinical Lung Injury

What are the mechanisms that may impair alveolar fluid clearance in patients with clinical lung injury? Experimentally, severe injury to the endothelial barrier can result in persistent alveolar flooding and can prevent any net alveolar fluid clearance. For example, severe acid-induced lung injury in rabbits can result in relentless alveolar flooding and a markedly impaired alveolar fluid clearance.⁹¹⁰ On the other hand, experimental evidence indicates that ALI with severe increased

Strategies to Augment the Rate of Alveolar Fluid Clearance in Clinical Lung Injury

There are several experimental models in which endogenous or exogenous cAMP stimulation has resulted in an up-regulation of alveolar fluid clearance. For example, in the setting of septic or hypovolemic shock, the marked rise in plasma epinephrine levels increases the rate of alveolar fluid clearance in rats.²¹²² Also, the exogenous administration of cAMP agonists has been shown to increase the resolution of alveolar and lung edema in a model of hydrostatic pulmonary edema in rats,²³ and

Summary

In conclusion, there is excellent evidence that impaired alveolar epithelial fluid clearance early in the course of clinical lung injury correlates well with a poor clinical outcome. The mechanisms for altered epithelial barrier transport include the loss of type I and type II cells by apoptosis or necrosis, as well as cellular dysfunction induced by hypoxia and reactive oxygen species and reactive nitrogen species. It is conceivable that an increase in net alveolar fluid clearance and the

ACKNOWLEDGMENT

I appreciate the assistance of Rebecca Cleff in the preparation of this manuscript.

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Hypoxemia and pulmonary bilateral infiltrate are the clinical characteristic of ALI/ARDS, therefore, it is important to effectively clear the edema fluid in the alveoli to guarantee effective gas exchange for patients with ALI/ARDS to survive. Therefore, alveolar fluid clearance (AFC) is an important factor for the treatment of ALI/ARDS, and those patients with maximal AFC have lower mortality [51]. During the AFC process, the alveolar epithelium plays a primary role with epithelial sodium channels (ENaCs), Na+/K+-ATPase, aquaporin (AQP), cystic fibrosis transmembrane regulator (CFTR), K+ channels and other channels also actively involved.
Acute lung injury (ALI) and its more severe form, acute respiratory distress syndrome (ARDS) as common life-threatening lung diseases with high mortality rates are mostly associated with acute and severe inflammation in lungs. With increasing in-depth studies of ALI/ARDS, significant breakthroughs have been made, however, there are still no effective pharmacological therapies for treatment of ALI/ARDS. Especially, the novel coronavirus pneumonia (COVID-19) is ravaging the globe, and causes severe respiratory distress syndrome. Therefore, developing new drugs for therapy of ALI/ARDS is in great demand, which might also be helpful for treatment of COVID-19. Natural compounds have always inspired drug development, and numerous natural products have shown potential therapeutic effects on ALI/ARDS. Therefore, this review focuses on the potential therapeutic effects of natural compounds on ALI and the underlying mechanisms. Overall, the review discusses 159 compounds and summarizes more than 400 references to present the protective effects of natural compounds against ALI and the underlying mechanism.
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: This research was supported by National Institutes of Health grants HL51854 and HL51856.

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Alveolar Fluid Clearance in Patients With ARDS*: Does It Make a Difference?

Section snippets

Alveolar Fluid Clearance in Patients

Mechanisms That Impair Epithelial Fluid Clearance in Clinical Lung Injury

Strategies to Augment the Rate of Alveolar Fluid Clearance in Clinical Lung Injury

Summary

ACKNOWLEDGMENT

Chest

The acute respiratory distress syndrome

N Engl J Med

Sodium channels in alveolar epithelial cells: molecular characterization, biophysical properties, and physiological significance

Annu Rev Physiol

Lung epithelial fluid transport and the resolution of pulmonary edema

Physiol Rev

Adrenergic stimulation of Na +transport across alveolar epithelial cells involves activation of apical Cl −channels

Am J Physiol

Novel role for CFTR in fluid absorption from the distal airspaces of the lung

J Gen Physiol

Intact epithelial barrier function is critical for the resolution of alveolar edema in humans

Am Rev Respir Dis

Alveolar epithelial fluid transport and the resolution of clinically severe hydrostatic pulmonary edema

J Appl Physiol

Alveolar fluid clearance is impaired in the majority of patients with acute lung injury and the acute respiratory distress syndrome

Am J Respir Crit Care Med

Acid aspiration induced lung injury in rabbits is mediated by interleukin-8 dependent mechanisms

J Clin Invest

Acid induced lung injury: protective effect of anti-interleukin-8 pretreatment on alveolar epithelial barrier function in rabbits

Am J Respir Crit Care Med

The relationship of pleural effusions to increased permeability pulmonary edema in anesthetized sheep

J Clin Invest

Hypoxia reduces alveolar epithelial sodium and fluid transport in rats: reversal by beta-2 adrenergic agonist treatment

Am J Respir Cell Mol Biol

Hypoxia and beta-2 agonists regulate cell surface expression of the epithelial sodium channel in native alveolar epithelial cells

J Biol Chem

Reactive nitrogen species inhibit alveolar epithelial fluid transport after hemorrhagic shock in rats

J Immunol

Inhibition of β-adrenergic-dependent alveolar epithelial clearance by oxidant mechanisms after hemorrhagic shock

Am J Physiol

Alveolar Fluid Clearance in Patients With ARDS^*: Does It Make a Difference?

Adrenergic stimulation of Na ⁺transport across alveolar epithelial cells involves activation of apical Cl ⁻channels