Changes In Lung Water Research Articles

Lung Ultrasound Reproducibly Outperforms Computed Tomography in the Detection of Extravascular Lung Water in Patients Undergoing Haemodialysis.

Lung ultrasound (LUS) is increasingly used as an extension of physical examination, informing clinical diagnosis, and decision making. There is particular interest in the assessment of patients with pulmonary congestion and extravascular lung water, although gaps remain in the evidence base underpinning this practice as a result of the limited evaluation of its inter-rater reliability and comparison with more established radiologic tests. 30 patients undergoing haemodialysis were prospectively recruited to an observational cohort study (NCT01949402). Patients underwent standardised LUS assessment before, during and after haemodialysis; their total LUS B-line score was generated, alongside a binary label of whether appearances were consistent with an interstitial syndrome. LUS video clips were recorded and independently scored by two blinded expert clinician sonographers. Low-dose non-contrast thoracic CT, pre- and post dialysis, was used as a "gold standard" radiologic comparison. LUS detected a progressive reduction in B-line scores in almost all patients undergoing haemodialysis, correlating with the volume of fluid removed once individuals with no or minimal B-lines upon pre-dialysis examination were discounted. When comparing CT scans pre- and post dialysis, radiologic evidence of the change in fluid status was only identified in a single patient. This is the first study to demonstrate that LUS detects changes in extravascular lung water caused by changing fluid status during haemodialysis using a blinded outcome assessment and that LUS appears to be more sensitive than CT for this purpose. Further research is needed to better understand the role of LUS in this and similar patient populations, with the aim of improving clinical care and outcomes.

Assessing fluid responsiveness with ultrasound in the neonatal intensive care setting: the mini-fluid challenge.

The mini-fluid challenge (MFC) can guide individualised fluid therapy and prevent fluid overload and associated morbidity in adult intensive care patients. This ultrasound test is based on the Frank-Starling principles to assess dynamic fluid responsiveness, but limited MFC data exists for newborns.This brief report describes the feasibility of the MFC in 12 preterm infants with late onset sepsis and 5 newborns with other pathophysiology. Apical views were used to determine the changes in left ventricular stroke volume before and after a 3ml/kg fluid bolus was given over 5min. Four out of the 17 infants were fluid responsive, defined as a post-bolus increase in stroke volume of 15% or more. Conclusion: The MFC was feasible and followed the physiological principles of stroke volume and extravascular lung water changes and 24% were fluid responsive. The MFC could enable future studies to examine whether adding fluid responsiveness to guide fluid therapy in newborns can reduce the risk of fluid overload. What is Known: • Fluid overload is associated with morbidity and mortality. • The mini-fluid challenge (MFC) provides a personalised approach to fluid therapy. What is New: • The MFC is feasible in newborns. • The MFC followed the physiological principles of stroke volume and extravascular lung water changes.

Evaluation of lung ultrasound to detect volume overload in children undergoing dialysis.

Lung ultrasound is a well-established technique to assess extravascular lung water, a proxy for volume status, in the adult population. Despite its utility, the data are limited supporting the use of ultrasound to evaluate fluid volume status among pediatric patients. Our study uses a simplified ultrasound protocol to evaluate changes in extravascular lung water, represented by b-lines, among pediatric patients undergoing hemodialysis. This prospective single-center study included children from birth to 18years of age. The number of b-lines per ml/kg of fluid removed was compared prior to, at the midpoint, and following termination of dialysis. An 8-zone protocol was utilized, and b-lines were correlated to hemoconcentration measured by the CRIT-LINE® hematocrit. Six patients with a total of 26 hemodialysis sessions were included in this study. The b-line measurements post-dialysis were 2.27 (p < 0.001; 94%CI -3.31, -1.22) lower relative to pre-dialysis. The number of b-lines was reduced by 1.69 (p < 0.001; -2.58, -0.80) between pre-dialysis and at the midpoint of dialysis and by 0.58 (p = 0.001; -0.90, -0.24) between the midpoint of dialysis and post-dialysis. A 1mL/kg fluid loss correlated to a decrease in the original b-lines by 0.079. An inverse relationship (r = -0.54; 95% CI: -0.72, -0.34; p < 0.001) was noted between the b-lines and the patients' hematocrit levels. A simplified 8-zone ultrasound protocol can assess fluid volume change in real time and correlates with hematocrit levels obtained throughout dialysis. This provides a valuable method for monitoring fluid status in volume overloaded patient populations. A higher resolution version of the Graphical abstract is available asSupplementary information.

Stroke volume versus stroke volume variations as guidance for fluid therapy in major abdominal surgery

Background: The aim of the present study was for comparison of stroke volume versus stroke volume variations as guidance for fluid management under guide directions of electrical cardiometry, during major abdominal surgeries. The primary outcome was to compare between two fluid infusion protocols, regarding the haemodynamic changes, whereas secondary outcomes were to evaluate the impact of each protocol on extravascular lung water and oxygenation changes in the post-operative periods, study the effect of each of the adopted method on postoperative complications, incidence of acute kidney injury and intensive care unit staying duration. Settings and Design: This study was a prospective randomized controlled clinical trial. Methods: The study was carried out on 60 patients scheduled for major abdominal surgery. 30 patients, whose intraoperative fluid administration was managed by stroke volume optimization, were compared with 30 patients who received intraoperative fluid therapy guided by stroke volume variation optimization. Results: There was no difference regarding haemodynamic changes in terms of mean heart rate, mean blood pressure, stroke volume, stroke volume variation, and cardiac index. The first group showed a significant incidence of postoperative pulmonary edema which affected oxygentation process till 24 hours postoperatively.

Volume Assessment in Hemodialysis: A Comparison of Present Methods in Clinical Practice with Sonographic Lung Comets.

Dry weight assessment in dialysis patients remains a challenging endeavor owing to the limitations of the available methods for volume assessment. Lung ultrasound is emerging as an invaluable tool to assist in the appropriate assessment and assignment of dry weight. The objectives of this study are (1) to determine the reliability of clinical signs and symptoms for volume assessment, (2) to compare lung ultrasound with High Resolution Computed Tomography (HRCT) chest-A noninvasive gold standard tool for detecting pulmonary congestion and with inferior vena cava diameter (IVCD) – another time-tested volume assessment method, and (3) to analyze if lung ultrasound could detect dialysis induced fluid status variations. The cross-sectional study involves 50 patients on maintenance hemodialysis. Lung ultrasound for B line estimation and ultrasonographic measurement of IVCD performed before and after hemodialysis by a nephrologist trained in ultrasonography. Limited HRCT was obtained just before hemodialysis. Edema, crackles, and dyspnea had a poor sensitivity of 37.9%, 11.5%, and 52.6%, respectively, to detect clinically significant pulmonary congestion by lung ultrasound. A highly significant correlation was obtained between B-line score and HRCT signs of pulmonary congestion (P < 0.001) before dialysis. B lines showed statistically significant reduction with dialysis. The absolute reduction of B lines showed significant correlation with ultrafiltration volume and weight loss. Bedside lung ultrasound appears a sensitive tool for evaluating real-time changes in extravascular lung water and would serve to optimize volume status in dialysis patients.

Subclinical pulmonary congestion is prevalent in nephrotic syndrome.

In patients with nephrotic syndrome (NS), the lung is considered an organ protected from the risk of edema. However, data on objectively measured lung water in NS patients is lacking. Here we measured lung water by an ultrasound (US) technique as well as by transthoracic impedance in 42 asymptomatic patients with active NS, in 14 stage G5D CKD patients on chronic hemodialysis, and in 21 healthy individuals. In patients with active NS, the median number of US-B lines (a metric of lung water) after 5 min in a supine position was significantly higher (12; interquartile range: 7-25) compared with that in healthy individuals (4; 2-9) but similar to that in hemodialysis patients (23; 10-39). The difference between NS patients and healthy individuals was significantly amplified (16; 10-35 vs. 4; 2-9) after 60 min of supine resting and significantly attenuated after 5 min of standing (10; 7-25 vs. 3; 1-6). Posture-dependent changes in lung water in patients with active NS were significantly accentuated compared with both hemodialysis patients and healthy individuals. After NS remission, the number of US-B lines was significantly reduced to 5 (4-18) at 5 min and to 6 (5-22) at 60 min approaching the normal range. Lung congestion in patients with active NS was confirmed by transthoracic impedance. Thus, asymptomatic pulmonary congestion is pervasive in patients with NS. A clinical trial is needed to assess the utility of lung US for the management of patients with NS.

Transpulmonary Thermodilution Enables to Detect Small Short-Term Changes in Extravascular Lung Water Induced by a Bronchoalveolar Lavage

To take the opportunity of a bronchoalveolar lavage to challenge the transpulmonary thermodilution for detecting the time course of changes in extravascular lung water. Observational study. Medical ICU. Mechanically ventilated patients in whom a bronchoalveolar lavage by bronchoscopy was performed. Transpulmonary thermodilution before and after bronchoalveolar lavage. Before and at different times after bronchoalveolar lavage, transpulmonary thermodilution was performed to record the value of indexed extravascular lung water. For each measurement, the values of three thermodilution measurements were averaged at the following steps: before bronchoalveolar lavage, after bronchoalveolar lavage, and 1 hour, 2 hours, 4 hours, and 6 hours after bronchoalveolar lavage. The amount of saline infusion left in the lungs after bronchoalveolar lavage was also recorded. Twenty-five patients with suspicion of pneumonia were included. Twenty-eight bronchoalveolar lavages were finally analyzed. On average, 200 mL (180-200 mL) of saline were injected and 130 mL (100-160 mL) were left in the lungs. Between before and immediately after bronchoalveolar lavage, indexed extravascular lung water significantly increased from 12 ± 4 to 15 ± 5 mL/kg, respectively, representing a 169 ± 166 mL increase in nonindexed extravascular lung water. After bronchoalveolar lavage, the value of indexed extravascular lung water was significantly different from the baseline value until 2 hours after bronchoalveolar lavage and became similar to the baseline value thereafter. Transpulmonary thermodilution enabled to detect small short-term changes of indexed extravascular lung water secondary to bronchoalveolar lavage.

Extravascular Lung Water, B-Type Natriuretic Peptide, and Blood Volume Contraction Enable Diagnosis of Weaning-Induced Pulmonary Edema*

We tested whether the changes in extravascular lung water indexed for ideal body weight could detect weaning-induced pulmonary edema. We also studied the diagnostic value of blood volume contraction indices and B-type natriuretic peptide variations. Prospective study. Twenty-one patients who failed a first spontaneous breathing trial. None. We performed a second 60-minute T-tube spontaneous breathing trial. Before and at the end of spontaneous breathing trial, we recorded pulmonary artery occlusion pressure, the extravascular lung water indexed for ideal body weight, plasma B-type natriuretic peptide level, hemoglobin, and plasma protein concentrations. Weaning-induced pulmonary edema was defined by the association of signs of clinical intolerance and a pulmonary artery occlusion pressure greater than or equal to 18 mm Hg at the end of spontaneous breathing trial. Because some patients performed several spontaneous breathing trial, a primary analysis included all spontaneous breathing trial and a secondary analysis included only the first spontaneous breathing trial of each patient. In primary analysis, 36 spontaneous breathing trials were analyzed, 21 spontaneous breathing trial with weaning-induced pulmonary edema and 15 without. During spontaneous breathing trial, extravascular lung water indexed for ideal body weight increased only in cases with weaning-induced pulmonary edema (25% ± 23%). Plasma protein concentration, hemoglobin concentration, and B-type natriuretic peptide also significantly increased only in cases with weaning-induced pulmonary edema (9% ± 3%, 9% ± 4%, 21% ± 23%, respectively). The areas under the receiver operating characteristics curves to detect weaning-induced pulmonary edema were 0.89 (95% CI, 0.78-0.99) for extravascular lung water indexed for ideal body weight, 0.97 (0.93-1.01) for spontaneous breathing trial-induced changes in plasma protein concentration, 0.96 (0.90-1.01) for changes in hemoglobin concentration, and 0.76 (0.60-0.93) for changes in B-type natriuretic peptide. An increase in extravascular lung water indexed for ideal body weight greater than or equal to 14% diagnosed weaning-induced pulmonary edema with a sensitivity of 67% (95% CI, 43-85%) and a specificity of 100% (95% CI, 78-100%). The secondary analysis confirmed these results. Spontaneous breathing trial-induced increases in extravascular lung water indexed for ideal body weight, plasma protein concentrations, hemoglobin concentration, and B-type natriuretic peptide are reliable alternatives to the pulmonary artery catheter for diagnosing weaning-induced pulmonary edema.

Predictors of pulmonary edema formation during fluid loading in the critically ill with presumed hypovolemia*

It is largely unknown why extravascular lung water may increase during fluid loading in the critically ill with presumed hypovolemia. In this study we evaluated the hemodynamic predictors of such an increase. A prospective observational study. Sixty-three presumed hypovolemic mechanically ventilated patients (22 septic and 41 nonseptic patients). Fluid loading with saline or colloid fluids guided by (changes in) cardiac filling pressures. Before and after fluid-loading, hemodynamic and respiratory variables were recorded, including variables obtained by transpulmonary dilution such as cardiac index, pulmonary blood volume index, and extravascular lung water. Baseline parameters and change in parameters were compared between patients with a change in extravascular lung water <10% and patients with a change in extravascular lung water ≥ 10%. Predictive values for change in extravascular lung water ≥ 10% were evaluated. Baseline cardiac index and pulmonary blood volume index were higher, whereas change in cardiac index, change in pulmonary blood volume index, and change in PaO2/FIO2 ratio were lower in patients with a change in extravascular lung water ≥ 10% than in patients with a change in extravascular lung water <10%. The change in extravascular lung water correlated to baseline cardiac index (r = 0.17; p = .001), baseline pulmonary blood volume index (r = 0.15; p = .001), change in pulmonary blood volume index (r = 0.16; p < .001), and change in PaO2/FIO2 ratio (r = 0.13; p = .004). In multiple logistic regression analysis baseline cardiac index, baseline pulmonary blood volume index, the change in cardiac index, change in pulmonary blood volume index, and change in PaO2/FIO2 ratio individually contributed to prediction of a change in extravascular lung water ≥ 10%, independent of the presence of sepsis, pulmonary vascular permeability, and cardiac filling pressures. A change in extravascular lung water ≥ 10% was predicted by baseline cardiac index (77% sensitivity, 98% specificity) and pulmonary blood volume index (92% sensitivity, 68% specificity), and by change in cardiac index (69% sensitivity, 59% specificity), change in pulmonary blood volume index (77% sensitivity, 82% specificity), and change in PaO2/FIO2 ratio (77% sensitivity, 66% specificity). Extravascular lung water increase during fluid loading in the critically ill is predicted by a plateau of cardiac function and pulmonary vascular filling at baseline, rather than by pulmonary vascular permeability and filling pressures. Increasing extravascular lung water is further reflected by a decrease of PaO2/FIO2 ratio. These observations may help preventing pulmonary fluid overloading.

Digitalized acoustic monitoring of lung congestion

Changes in lung water are known to change breath sound acoustics [1]. Using two pig models, we observed that continuous elevation of lung sound amplitude may indicate an increase in total lung water content [2]. Here we report three cases of ventilated patients in whom continuous acoustic monitoring was done during extravascular lung water (EVLW) measurements.

Continuous elevation of lung sound amplitudes, recorded at fixed flow rate, may indicate an increase in lung water content

Vibration response imaging (VRI) is a bedside lung sound monitoring system. We previously reported that vibration intensity can be significantly elevated in patients with congestion, as opposed to pleural effusion, atelectasis, or normal lung [1]. We hypothesized that changes in lung water content (that is, pulmonary edema) may influence breath sound amplitude and explored the possibility of using continuous digitalized lung sound monitoring as a means to track changes in extravascular lung water (EVLW).

Salbutamol up-regulates matrix metalloproteinase-9 in the alveolar space in the acute respiratory distress syndrome

Acute respiratory distress syndrome (ARDS) is characterized by alveolar-capillary barrier damage. Matrix metalloproteinases (MMPs) are implicated in the pathogenesis of ARDS. In the Beta Agonists in Acute Lung Injury Trial, intravenous salbutamol reduced extravascular lung water (EVLW) in patients with ARDS at day 4 but not inflammatory cytokines or neutrophil recruitment. We hypothesized that salbutamol reduces MMP activity in ARDS. MMP-1/-2/-3/-7/-8/-9/-12/-13 was measured in supernatants of distal lung epithelial cells, type II alveolar cells, and bronchoalveolar lavage (BAL) fluid from patients in the Beta Agonists in Acute Lung Injury study by multiplex bead array and tissue inhibitors of metalloproteinases (TIMPs)-1/-2 by enzyme-linked immunosorbent assay. MMP-9 protein and activity levels were further measured by gelatin zymography and fluorokine assay. BAL fluid MMP-1/-2/-3 declined by day 4, whereas total MMP-9 tended to increase. Unexpectedly, salbutamol augmented MMP-9 activity. Salbutamol induced 33.7- and 13.2-fold upregulation in total and lipocalin-associated MMP-9, respectively at day 4, compared with 2.0- and 1.3-fold increase in the placebo group, p < 0.03. Salbutamol did not affect BAL fluid TIMP-1/-2. Net active MMP-9 was higher in the salbutamol group (4222 pg/mL, interquartile range: 513-7551) at day 4 compared with placebo (151 pg/mL, 124-2108), p = 0.012. Subjects with an increase in BAL fluid MMP-9 during the 4-day period had lower EVLW measurements than those in whom MMP-9 fell (10 vs. 17 mL/kg, p = 0.004): change in lung water correlated inversely with change in MMP-9, r = -.54, p = 0.0296. Salbutamol up-regulated MMP-9 and down-regulated TIMP-1/-2 secretion in vitro by distal lung epithelial cells. Inhibition of MMP-9 activity in cultures of type II alveolar epithelial cells reduced wound healing. Salbutamol specifically up-regulates MMP-9 in vitro and in vivo in patients with ARDS. Up-regulated MMP-9 is associated with a reduction in EVLW. MMP-9 activity is required for alveolar epithelial wound healing in vitro. Data suggest MMP-9 may have a previously unrecognized beneficial role in reducing pulmonary edema in ARDS by improving alveolar epithelial healing.

Effects of High-Frequency Oscillatory Ventilation on Oleic Acid-Induced Lung Injury in Sheep

High-frequency oscillatory ventilation (HFOV) is a possible mechanical method for open lung strategies. The aim of this study was to examine whether HFOV has a beneficial effect on oleic acid-induced lung injury, with emphasis on changes in extravascular lung water. Thirteen anesthetized sheep prepared with a lung lymph fistula and vascular catheters for monitoring were randomly allocated to two experimental groups. In experiment 1, sheep (n = 6) were ventilated using conventional mechanical ventilation [CMV; 10 ml/kg of tidal volume, 70% oxygen, and positive end-expiratory pressure (PEEP) of 6 cmH(2)O after oleic acid administration (0.08 ml/kg)]. In experiment 2, sheep (n=7) were ventilated using HFOV (frequency=15 Hz, stroke volume=120 ml, mean airway pressure=15 cmH(2)O) after administration of the same dose of oleic acid as in experiment 1. Observation was continued for 4 h after oleic acid administration, then bronchoalveolar lavage (BAL) was performed and the lung wet-to-dry weight ratio was determined. Compared with CMV, HFOV significantly improved the deteriorated oxygenation during the late phase (2-4 h) of oleic acid-induced lung injury without any deterioration effects on pulmonary or systemic hemodynamics. HFOV showed significantly reduced lung lymph protein clearance, which paralleled significant decreases in wet-to-dry ratios and neutrophil counts in BAL fluid in the HFOV group. These findings suggest that HFOV could contribute to decreased lung lymph filtration in pulmonary microcirculation and improved oxygenation following oleic acid-induced lung injury in sheep.

Measurement of extravascular lung water in patients with pulmonary edema

measurement of extravascular lung water has been a topic of major interest for more than two decades ([1][1], [5][2], [19][3]). In the recent article by Effros et al. ([2][4]), they provide a review of current and past efforts to measure extravascular lung water with thermal and osmotic dilution

In vivo and in vitro effects of salbutamol on alveolar epithelial repair in acute lung injury

Background: Acute lung injury is an important cause of respiratory failure in the critically ill patient. It is caused by damage to the alveolar barrier with subsequent alveolar flooding leading...

Extravascular lung water after pneumonectomy and one-lung ventilation in sheep

To compare the single thermodilution and the thermal-dye dilution techniques with postmortem gravimetry for assessment of changes in extravascular lung water after pneumonectomy and to explore the evolution of edema after injurious ventilation of the left lung. Experimental study. University laboratory. A total of 30 sheep weighing 35.6 +/- 4.6 kg. The study included two parts: a pneumonectomy study (n = 18) and an injurious ventilation study (n = 12). Sheep were anesthetized and mechanically ventilated with an FiO2 of 0.5, tidal volume of 6 mL/kg, and positive end-expiratory pressure of 2 cm H2O. In the pneumonectomy study, sheep were assigned to right-sided pneumonectomy (n = 7), left-sided pneumonectomy (n = 7), or lateral thoracotomy only (sham operation, n = 4). In the injurious ventilation study, right-sided pneumonectomy was followed by ventilation with a tidal volume of 12 mL/kg and positive end-expiratory pressure of 0 cm H2O (n = 6) or by ventilation with a tidal volume of 6 mL/kg and positive end-expiratory pressure of 2 cm H2O for 4 hrs (n = 6). Volumetric variables, including extravascular lung water index (EVLWI), were measured with single thermodilution (STD; EVLWI(STD)) and thermal-dye dilution (TDD; EVLWI(TDD)) techniques. We monitored pulmonary hemodynamics and respiratory variables. After the sheep were killed, EVLWI was determined for each lung by gravimetry (EVLWI(G)). In total, the study yielded strong correlations of EVLWI(STD) and EVLWI(TDD) with EVLWI(G) (n = 30; r = .83 and .94, respectively; p < .0001). After pneumonectomy, both the left- and the right-sided pneumonectomy groups displayed significant decreases in EVLWI(STD) and EVLWI(TDD). The injuriously ventilated sheep demonstrated significant increases in EVLWI that were detected by both techniques. The mean biases (+/-2 SD) compared with EVLWI(G) were 3.0 +/- 2.6 mL/kg for EVLWI(STD) and 0.4 +/- 1.6 mL/kg for EVLWI(TDD). After pneumonectomy and injurious ventilation of the left lung, TDD and STD displayed changes in extravascular lung water with acceptable accuracy when compared with postmortem gravimetry. Ventilator-induced lung injury seems to be a crucial mechanism of pulmonary edema after pneumonectomy.

Changes in extravascular lung water determined with single transpulmonary thermodilution after pneumonectomy and lung resection

Changes in extravascular lung water determined with single transpulmonary thermodilution after pneumonectomy and lung resection

Flat beer vs. physiological improvement: effect of acetazolamide during hypoxic exercise

Flat beer <i>vs.</i> physiological improvement: effect of acetazolamide during hypoxic exercise

How important is the measurement of extravascular lung water?

Accurate quantification of extravascular lung water is an important issue in the management of patients with pulmonary edema. The single transpulmonary thermal indicator method has been available since the late 1990s. Its simplicity and easy application make it clinically attractive. Several experimental studies have confirmed the accuracy of the single transpulmonary thermal indicator technique in comparisons with postmortem gravimetric method. Whereas changes in extravascular lung water of less than 100-200% are undetectable by other clinically applicable methods of lung injury assessment (chest radiograph and oxygenation), the single transpulmonary indicator has proven highly sensitive to small (10-20%) increases and is therefore useful to detect incipient pulmonary edema. In patients with sepsis or acute respiratory distress syndrome, extravascular lung water measurement offers information unobtainable by other means. Extravascular lung water can be considered a relevant parameter that contributes to rational management of fluid and vasoactive therapy of many critically ill patients and offers a fuller picture of their overall lung function.

Short-term hypoxic exposure at rest and during exercise reduces lung water in healthy humans

Hypoxia and hypoxic exercise increase pulmonary arterial pressure, cause pulmonary capillary recruitment, and may influence the ability of the lungs to regulate fluid. To examine the influence of hypoxia, alone and combined with exercise, on lung fluid balance, we studied 25 healthy subjects after 17-h exposure to 12.5% inspired oxygen (barometric pressure = 732 mmHg) and sequentially after exercise to exhaustion on a cycle ergometer with 12.5% inspired oxygen. We also studied subjects after a rapid saline infusion (30 ml/kg over 15 min) to demonstrate the sensitivity of our techniques to detect changes in lung water. Pulmonary capillary blood volume (Vc) and alveolar-capillary conductance (D(M)) were determined by measuring the diffusing capacity of the lungs for carbon monoxide and nitric oxide. Lung tissue volume and density were assessed using computed tomography. Lung water was estimated by subtracting measures of Vc from computed tomography lung tissue volume. Pulmonary function [forced vital capacity (FVC), forced expiratory volume after 1 s (FEV(1)), and forced expiratory flow at 50% of vital capacity (FEF(50))] was also assessed. Saline infusion caused an increase in Vc (42%), tissue volume (9%), and lung water (11%), and a decrease in D(M) (11%) and pulmonary function (FVC = -12 +/- 9%, FEV(1) = -17 +/- 10%, FEF(50) = -20 +/- 13%). Hypoxia and hypoxic exercise resulted in increases in Vc (43 +/- 19 and 51 +/- 16%), D(M) (7 +/- 4 and 19 +/- 6%), and pulmonary function (FVC = 9 +/- 6 and 4 +/- 3%, FEV(1) = 5 +/- 2 and 4 +/- 3%, FEF(50) = 4 +/- 2 and 12 +/- 5%) and decreases in lung density and lung water (-84 +/- 24 and -103 +/- 20 ml vs. baseline). These data suggest that 17 h of hypoxic exposure at rest or with exercise resulted in a decrease in lung water in healthy humans.