Rolf Hubmayr - Academia.edu (original) (raw)

Papers by Rolf Hubmayr

Research paper thumbnail of Critical Care Perspective

The last two decades have brought new insights into mechanisms of lung injury. These insights hav... more The last two decades have brought new insights into mechanisms of lung injury. These insights have profoundly altered the ventilator management of patients with adult respiratory distress syndrome (ARDS). As recently as a few years ago, ventilator management focused on maintaining blood gas tensions. The recognition that airways and parenchyma can be injured by physical stress has redirected attention to lung mechanics and to the determinants of tissue damage, remodeling, and repair. Although it is difficult to assess the relative effects of ventilator-induced lung injury (VILI) compared with other disease mechanisms, a wealth of experimental and clinical data indicates that VILI indeed exists and that it contributes to the mortality of patients with ARDS (1–6). Some ventilator parameters, such as large tidal volumes, are firmly established as determinants of VILI. Others, such as low positive endexpiratory pressure (PEEP) or high inspiratory flow, remain controversial (7–12). In th...

Research paper thumbnail of Nonuniform expansion of constricted dog lungs

Journal of Applied Physiology

The parenchymal marker technique was used to measure regional tidal volumes of samples of lung pa... more The parenchymal marker technique was used to measure regional tidal volumes of samples of lung parenchyma in four open-chest supine dogs. Radiopaque markers that had been implanted in the lower lobe were tracked by biplane video fluoroscopy during sinusoidal volume oscillations at tidal volumes of approximately 20% of total lung capacity and frequencies of 1-40 breaths/min before and after methacholine was administered by aerosol. The volumes of tetrahedrons with apexes at four markers were computed, and sine waves were fit to the data for volume vs. time for each tetrahedron. The ratio of mean regional volume to mean airway pressure decreased by 10-45% after exposure to methacholine. Dynamic lung elastance and resistance of the constricted lungs were larger than control, and both were frequency dependent. Regional elastance and resistance varied considerably among tetrahedrons, and these were also frequency dependent. The data were fit by a model in which tissue elastance was unifo...

Research paper thumbnail of Inhaled TRIM72 Protein Protects Ventilation Injury to the Lung through Injury-guided Cell Repair

American journal of respiratory cell and molecular biology, Jan 29, 2018

[Rationale] Studies showed that TRIM72 is essential for repair of alveolar cell membrane disrupti... more [Rationale] Studies showed that TRIM72 is essential for repair of alveolar cell membrane disruptions, and exogenous TRIM72 protein (rhT72) demonstrated tissue-mending properties in animal models of tissue injury. [Objectives] To examine the mechanisms of rhT72-mediated lung cell protection in vitro and to test the efficacy of inhaled rhT72 in reducing tissue pathology in a mouse model of ventilator-induced lung injury (VILI). [Methods] In vitro lung cell injury was induced by glass beads and stretching. VILI was modeled by injurious ventilation at 30 ml/kg tidal volume. Affinity-purified rhT72 or control proteins were added into culture medium or applied through nebulization. Cellular uptake and in vivo distribution of rhT72 were detected by imaging and immunostaining. [Results] Exogenous rhT72 maintains membrane integrity of alveolar epithelial cells subjected to glass bead injury in a dose-dependent manner. Inhaled rhT72 decreases the number of fatally injured alveolar cells, and ameliorates tissue damaging indicators and cell injury markers following injurious ventilation. Using in vitro stretching assays, we reveal that rhT72 improves both cellular resilience to membrane wounding and membrane repair after injury. Image analysis detected rhT72 uptake by rat alveolar epithelial cells, which can be inhibited by a cholesterol disrupting agent. In addition, inhaled rhT72 distributes to the distal lungs, where it co-localizes with phosphatidylserine detection on non-permeabilized lung slices to label wounded cells. [Conclusions] Inhaled rhT72 accumulates in injured lungs and protects lung tissue from ventilator injury, the mechanisms of which include improving cell resilience to membrane wounding, localizing to injured membrane and augmenting membrane repair.

Research paper thumbnail of Plasma sRAGE is independently associated with increased mortality in ARDS: a meta-analysis of individual patient data

Intensive care medicine, Jan 26, 2018

The soluble receptor for advanced glycation end-products (sRAGE) is a marker of lung epithelial i... more The soluble receptor for advanced glycation end-products (sRAGE) is a marker of lung epithelial injury and alveolar fluid clearance (AFC), with promising values for assessing prognosis and lung injury severity in acute respiratory distress syndrome (ARDS). Because AFC is impaired in most patients with ARDS and is associated with higher mortality, we hypothesized that baseline plasma sRAGE would predict mortality, independently of two key mediators of ventilator-induced lung injury. We conducted a meta-analysis of individual data from 746 patients enrolled in eight prospective randomized and observational studies in which plasma sRAGE was measured in ARDS articles published through March 2016. The primary outcome was 90-day mortality. Using multivariate and mediation analyses, we tested the association between baseline plasma sRAGE and mortality, independently of driving pressure and tidal volume. Higher baseline plasma sRAGE [odds ratio (OR) for each one-log increment, 1.18; 95% con...

Research paper thumbnail of Statement of the Fourth International Consensus Conference in Critical Care on ICU-Acquired Pneumonia

Research paper thumbnail of Reply: Transpulmonary Pressure Meaning: Babel or Conceptual Evolution?

American journal of respiratory and critical care medicine, May 15, 2017

Research paper thumbnail of Differentiating pulmonary transfusion reactions using recipient and transfusion factors

Transfusion, 2017

It is increasingly recognized that recipient risk factors play a prominent role in possible trans... more It is increasingly recognized that recipient risk factors play a prominent role in possible transfusion-related acute lung injury (pTRALI) and transfusion-associated circulatory overload (TACO). We hypothesized that both transfusion and recipient factors including natriuretic peptides could be used to distinguish TRALI from TACO and pTRALI. We performed a post hoc analysis of a case-control study of pulmonary transfusion reactions conducted at the University of California at San Francisco and Mayo Clinic, Rochester. We evaluated clinical data and brain natriuretic peptides (BNP) levels drawn after transfusion in patients with TRALI (n = 21), pTRALI (n = 26), TACO (n = 22), and controls (n = 24). Logistic regression and receiver operating characteristics curve analyses were used to determine the accuracy of clinical and biomarker predictors in differentiating TRALI from TACO and pTRALI. We found that pTRALI and TACO were associated with older age, higher fluid balance, and elevated B...

Research paper thumbnail of Quantitative assessment of lung stiffness in patients with interstitial lung disease using MR elastography

Journal of magnetic resonance imaging : JMRI, Jan 24, 2017

To investigate the use of magnetic resonance elastography (MRE) in the quantitative assessment of... more To investigate the use of magnetic resonance elastography (MRE) in the quantitative assessment of pulmonary fibrosis by comparing quantitative shear stiffness measurements of lung parenchyma in patients diagnosed with fibrotic interstitial lung disease (ILD) and healthy controls. A 1.5T spin-echo, echo planar imaging MRE (SE-EPI MRE) pulse sequence was utilized to assess absolute lung shear stiffness in 15 patients with diagnosed ILD and in 11 healthy controls. Data were collected at residual volume (RV) and total lung capacity (TLC). Spirometry data were obtained immediately prior to scanning. To test for statistical significance between RV and TLC shear stiffness estimates a two-sample t-test was performed. To assess variability within individual subject shear stiffness estimates, the intraclass correlation coefficient (ICC) and Krippendorff's alpha were calculated. Patients with ILD exhibited an average (±1 standard deviation) shear stiffness of 2.74 (±0.896) kPa at TLC and 1...

Research paper thumbnail of Plasma membrane wounding and repair in pulmonary diseases

American journal of physiology. Lung cellular and molecular physiology, Jan 6, 2017

Various pathophysiological conditions such as surfactant dysfunction, mechanical ventilation, inf... more Various pathophysiological conditions such as surfactant dysfunction, mechanical ventilation, inflammation, pathogen products, environmental exposures and gastric acid aspiration stress lung cells and the compromise of plasma membranes occur as a result. The mechanisms necessary for cells to repair plasma membrane defects have been extensively investigated in the last two decades, and some of these key repair mechanisms are also shown to occur following lung cell injury. As it was theorized that lung wounding and repair are involved in the pathogenesis of acute respiratory distress syndrome (ARDS) and idiopathic pulmonary fibrosis (IPF), in this review, we summarized the experimental evidence of lung cell injury in these two devastating syndromes, discuss relevant genetic, physical and biological injury mechanisms, as well as mechanisms utilized by lung cells for cell survival and membrane repair. Finally, we discuss relevant signalling pathways that may be activated by chronic or r...

Research paper thumbnail of Transpulmonary Pressure: The Importance of Precise Definitions and Limiting Assumptions

American journal of respiratory and critical care medicine, Dec 15, 2016

Recent studies applying the principles of respiratory mechanics to respiratory disease have used ... more Recent studies applying the principles of respiratory mechanics to respiratory disease have used inconsistent and mutually exclusive definitions of the term "transpulmonary pressure." By the traditional definition, transpulmonary pressure is the pressure across the whole lung, including the intrapulmonary airways, (i.e., the pressure difference between the opening to the pulmonary airway and the pleural surface). However, more recently transpulmonary pressure has also been defined as the pressure across only the lung tissue (i.e., the pressure difference between the alveolar space and the pleural surface), traditionally known as the "elastic recoil pressure of the lung." Multiple definitions of the same term, and failure to recognize their underlying assumptions, have led to different interpretations of lung physiology and conclusions about appropriate therapy for patients. It is our view that many current controversies in the physiological interpretation of dise...

Research paper thumbnail of Entrainment of Respiration in Humans by Periodic Lung Inflations Effect of State and CO 2

Lack of synchrony between a patient and the mechanical ventilator occurs when the respiratory rhy... more Lack of synchrony between a patient and the mechanical ventilator occurs when the respiratory rhythm of the patient fails to entrain to machine inflations. Entrainment implies a resetting of the respiratory rhythm such that a fixed temporal relationship exists between the onset of inspiratory ac- tivity and the onset of a mechanical breath. We examined the entrainment response to mechanical

Research paper thumbnail of 14-Hour Shift Schedule for Medical ICU Interns

Chest, 2006

We report here on an alternate version of the 14-h shift model for ICU residents that was describ... more We report here on an alternate version of the 14-h shift model for ICU residents that was described by Afessa and colleagues (December 2005). 1 Shift schedules limit resident hours and shift duration; however, these undermine the intern's traditional role of knowing ...

Research paper thumbnail of The control of breathing during weaning from mechanical ventilation

Chest Journal, Sep 1, 1991

Using the recruitment threshold technique, we measured the CO2 responsiveness of the unloaded res... more Using the recruitment threshold technique, we measured the CO2 responsiveness of the unloaded respiratory pump in 14 mechanically ventilated patients prior to weaning. The CO2 recruitment threshold (CO2RT) was compared with the arterial CO2 tension during unassisted breathing (CO2SB) and with the PaCO2 during mechanical ventilation (CO2MV) at machine settings determined by the primary physician. Based on these comparisons, we tested the hypotheses that (1) patients without weaning-induced respiratory distress (group 1) maintain CO2SB near CO2RT, (2) patients with weaning-induced respiratory distress (group 2) retain CO2SB above CO2RT, thereby manifesting incomplete load compensation, and (3) CO2MV is ventilator setting dependent and provides insufficient information about the ventilatory requirement during weaning. Respiratory distress was prospectively defined as sustained tachypnea (rate greater than or equal to 30) or intense dyspnea (Borg scale rating) and limited weaning in nine of 14 patients. The average CO2RT was 40 mm Hg in both groups. All patients in group 1 maintained CO2SB near CO2RT (p greater than 0.1). Seven of nine patients in group 2 retained CO2 by greater than or equal to 3 mm Hg above CO2RT (p less than 0.01). There was no significant difference between CO2MV and CO2SB in either group. We conclude that CO2RT provides a better reference of the adequacy of ventilatory load compensation during weather than CO2MV.

Research paper thumbnail of Intraoperative Tidal Volume as a Risk Factor for Respiratory Failure after PneumonectomyFernández-Pérez ER, Keegan MT, Brown DR, et al (Mayo Clinic, Rochester, Minn) Anesthesiology 105:14–18, 2006§

The Journal of the American Society of Anesthesiologists, Jul 1, 2007

Research paper thumbnail of Lung Stress and Strain in Acute Respiratory Distress Syndrome

American Journal of Respiratory and Critical Care Medicine, Dec 20, 2012

bronchodilator component and not to the inhaled corticosteroid component (6, 8). Moreover, inhale... more bronchodilator component and not to the inhaled corticosteroid component (6, 8). Moreover, inhaled corticosteroids alone or in combination have been associated with increased risks of glaucoma and possibly osteoporotic fractures (9-11), and have been shown to increase the risk of cataract and pneumonia, particularly with the high doses currently in use (12-16). On the whole, this study offers two major advances that benefit the patient with COPD. It provides the first possible evidence that lung function decline can be slowed with medications. It also provides further evidence that the use of inhaled corticosteroids, alone or in combination, in COPD is unnecessary and thus inappropriate.

Research paper thumbnail of Epithelial to mesenchymal transition: A new twist to biotrauma?

Critical Care Medicine, Feb 1, 2012

Research paper thumbnail of Bronchoscopy in Ventilator-associated Pneumonia

American Journal of Respiratory and Critical Care Medicine, Dec 20, 2012

Rationale: Although the serial dilution technique for quantitative culture of bronchoalveolar flu... more Rationale: Although the serial dilution technique for quantitative culture of bronchoalveolar fluid is considered to be the gold standard for the diagnosis of ventilatorassociated pneumonia, it is more labor intensive than the calibrated loop technique. Objective: We sought to determine the agreement between the calibrated loop and serial dilution techniques in the diagnosis of ventilator-associated pneumonia. Methods: We prospectively measured bacterial colony counts by the serial dilution and calibrated loop techniques in 121 bronchoalveolar lavage samples of 104 patients with suspected ventilator-associated pneumonia. Measurements and Main Results: At the time of bronchoscopy, patients had received mechanical ventilation for a median of 8 days. Patients were receiving antibiotics when 90 of the 121 (74.4%) bronchoalveolar samples were obtained. The colony counts of 13 bacterial isolates were too numerous to count by the calibrated loop technique; by serial dilution technique, their counts ranged from 4.70 log10 to 6.74 log10 colony forming unit (CFU)/mL. Fifty other bacteria had paired colony counts measured by each of the two techniques: the bias (95% confidence interval) between the two techniques was-0.380 (-0.665 to-0.095) log10 CFU/mL with precision of 1.002 log10 CFU/mL and 95% limits of agreement-2.344 to 1.584 log10 CFU/mL. Using the threshold of 4 log10 CFU/mL as a criterion for the diagnosis of ventilator-associated pneumonia, there was discordance only for one bacterial organism between the two techniques. Conclusions: The calibrated loop technique can be used for the diagnosis of ventilatorassociated pneumonia using bronchoalveolar fluid.

Research paper thumbnail of Bronchoscopy in Ventilator-associated Pneumonia Agreement of Calibrated Loop and Serial Dilution

American Journal of Respiratory and Critical Care Medicine, Jul 1, 2006

Rationale: Although the serial dilution technique for quantitative culture of bronchoalveolar flu... more Rationale: Although the serial dilution technique for quantitative culture of bronchoalveolar fluid is considered to be the gold standard for the diagnosis of ventilatorassociated pneumonia, it is more labor intensive than the calibrated loop technique. Objective: We sought to determine the agreement between the calibrated loop and serial dilution techniques in the diagnosis of ventilator-associated pneumonia. Methods: We prospectively measured bacterial colony counts by the serial dilution and calibrated loop techniques in 121 bronchoalveolar lavage samples of 104 patients with suspected ventilator-associated pneumonia. Measurements and Main Results: At the time of bronchoscopy, patients had received mechanical ventilation for a median of 8 days. Patients were receiving antibiotics when 90 of the 121 (74.4%) bronchoalveolar samples were obtained. The colony counts of 13 bacterial isolates were too numerous to count by the calibrated loop technique; by serial dilution technique, their counts ranged from 4.70 log10 to 6.74 log10 colony forming unit (CFU)/mL. Fifty other bacteria had paired colony counts measured by each of the two techniques: the bias (95% confidence interval) between the two techniques was-0.380 (-0.665 to-0.095) log10 CFU/mL with precision of 1.002 log10 CFU/mL and 95% limits of agreement-2.344 to 1.584 log10 CFU/mL. Using the threshold of 4 log10 CFU/mL as a criterion for the diagnosis of ventilator-associated pneumonia, there was discordance only for one bacterial organism between the two techniques. Conclusions: The calibrated loop technique can be used for the diagnosis of ventilatorassociated pneumonia using bronchoalveolar fluid.

Research paper thumbnail of Early nutritional support is associated with improved outcomes in respiratory failure

Acta Medica Academica, May 23, 2010

Objective. To evaluate early feeding as a predictor of outcome in critically ill patients receivi... more Objective. To evaluate early feeding as a predictor of outcome in critically ill patients receiving prolonged mechanical ventilation. Patients and methods. A retrospective cohort study in four medical, surgical and multidisciplinary intensive care units (ICU) in a tertiary referral center of adult patients requiring at least 48 hours of mechanical ventilation. Early feeding was defined as any nutritional support (enteral or parenteral) for at least 6 hours, started within 48 hours of mechanical ventilation. The primary endpoint was hospital mortality. The secondary endpoints were length of stay, and duration of mechanical ventilation. Univariate and multivariate analysis were used as appropriate. Results. 394 out of 4,546 patients admitted to the ICU were studied. Age (mean: 95% confidence interval was 62 (60-63); female gender 43%; APACHE III 72 (70-75); APACHE III predicted hospital mortality 36 % (33-39); ICU mortality 19%, hospital mortality 28%, ventilation-free days 41 (39-44). Only 11% (3% enteral, 8% parenteral) were fed on day 1, 55% (30% enteral, 25% parenteral) on day 4, and 88% (51% enteral, 37% parenteral) on day 7. Early feeding was associated with a reduced Standardized Mortality Ratio (number of observed hospital deaths/number of expected hospital deaths) of 0.53. When adjusted for various confounding factors such as severity of illness, trauma, route of feeding, post-operative state or the use of vasopressors, early feeding remained independently associated with decreased hospital mortality (Odd Ratio 0.51; 95% confidence interval 0.26-0.98; p = 0.042). Conclusion. Early nutrition is associated with decreased hospital mortality in patients receiving prolonged (more than 48 hours) invasive mechanical ventilation.

Research paper thumbnail of The Times Are A-Changin???: Should We Hang Up the Stethoscope?

The Journal of the American Society of Anesthesiologists, 2004

Research paper thumbnail of Critical Care Perspective

The last two decades have brought new insights into mechanisms of lung injury. These insights hav... more The last two decades have brought new insights into mechanisms of lung injury. These insights have profoundly altered the ventilator management of patients with adult respiratory distress syndrome (ARDS). As recently as a few years ago, ventilator management focused on maintaining blood gas tensions. The recognition that airways and parenchyma can be injured by physical stress has redirected attention to lung mechanics and to the determinants of tissue damage, remodeling, and repair. Although it is difficult to assess the relative effects of ventilator-induced lung injury (VILI) compared with other disease mechanisms, a wealth of experimental and clinical data indicates that VILI indeed exists and that it contributes to the mortality of patients with ARDS (1–6). Some ventilator parameters, such as large tidal volumes, are firmly established as determinants of VILI. Others, such as low positive endexpiratory pressure (PEEP) or high inspiratory flow, remain controversial (7–12). In th...

Research paper thumbnail of Nonuniform expansion of constricted dog lungs

Journal of Applied Physiology

The parenchymal marker technique was used to measure regional tidal volumes of samples of lung pa... more The parenchymal marker technique was used to measure regional tidal volumes of samples of lung parenchyma in four open-chest supine dogs. Radiopaque markers that had been implanted in the lower lobe were tracked by biplane video fluoroscopy during sinusoidal volume oscillations at tidal volumes of approximately 20% of total lung capacity and frequencies of 1-40 breaths/min before and after methacholine was administered by aerosol. The volumes of tetrahedrons with apexes at four markers were computed, and sine waves were fit to the data for volume vs. time for each tetrahedron. The ratio of mean regional volume to mean airway pressure decreased by 10-45% after exposure to methacholine. Dynamic lung elastance and resistance of the constricted lungs were larger than control, and both were frequency dependent. Regional elastance and resistance varied considerably among tetrahedrons, and these were also frequency dependent. The data were fit by a model in which tissue elastance was unifo...

Research paper thumbnail of Inhaled TRIM72 Protein Protects Ventilation Injury to the Lung through Injury-guided Cell Repair

American journal of respiratory cell and molecular biology, Jan 29, 2018

[Rationale] Studies showed that TRIM72 is essential for repair of alveolar cell membrane disrupti... more [Rationale] Studies showed that TRIM72 is essential for repair of alveolar cell membrane disruptions, and exogenous TRIM72 protein (rhT72) demonstrated tissue-mending properties in animal models of tissue injury. [Objectives] To examine the mechanisms of rhT72-mediated lung cell protection in vitro and to test the efficacy of inhaled rhT72 in reducing tissue pathology in a mouse model of ventilator-induced lung injury (VILI). [Methods] In vitro lung cell injury was induced by glass beads and stretching. VILI was modeled by injurious ventilation at 30 ml/kg tidal volume. Affinity-purified rhT72 or control proteins were added into culture medium or applied through nebulization. Cellular uptake and in vivo distribution of rhT72 were detected by imaging and immunostaining. [Results] Exogenous rhT72 maintains membrane integrity of alveolar epithelial cells subjected to glass bead injury in a dose-dependent manner. Inhaled rhT72 decreases the number of fatally injured alveolar cells, and ameliorates tissue damaging indicators and cell injury markers following injurious ventilation. Using in vitro stretching assays, we reveal that rhT72 improves both cellular resilience to membrane wounding and membrane repair after injury. Image analysis detected rhT72 uptake by rat alveolar epithelial cells, which can be inhibited by a cholesterol disrupting agent. In addition, inhaled rhT72 distributes to the distal lungs, where it co-localizes with phosphatidylserine detection on non-permeabilized lung slices to label wounded cells. [Conclusions] Inhaled rhT72 accumulates in injured lungs and protects lung tissue from ventilator injury, the mechanisms of which include improving cell resilience to membrane wounding, localizing to injured membrane and augmenting membrane repair.

Research paper thumbnail of Plasma sRAGE is independently associated with increased mortality in ARDS: a meta-analysis of individual patient data

Intensive care medicine, Jan 26, 2018

The soluble receptor for advanced glycation end-products (sRAGE) is a marker of lung epithelial i... more The soluble receptor for advanced glycation end-products (sRAGE) is a marker of lung epithelial injury and alveolar fluid clearance (AFC), with promising values for assessing prognosis and lung injury severity in acute respiratory distress syndrome (ARDS). Because AFC is impaired in most patients with ARDS and is associated with higher mortality, we hypothesized that baseline plasma sRAGE would predict mortality, independently of two key mediators of ventilator-induced lung injury. We conducted a meta-analysis of individual data from 746 patients enrolled in eight prospective randomized and observational studies in which plasma sRAGE was measured in ARDS articles published through March 2016. The primary outcome was 90-day mortality. Using multivariate and mediation analyses, we tested the association between baseline plasma sRAGE and mortality, independently of driving pressure and tidal volume. Higher baseline plasma sRAGE [odds ratio (OR) for each one-log increment, 1.18; 95% con...

Research paper thumbnail of Statement of the Fourth International Consensus Conference in Critical Care on ICU-Acquired Pneumonia

Research paper thumbnail of Reply: Transpulmonary Pressure Meaning: Babel or Conceptual Evolution?

American journal of respiratory and critical care medicine, May 15, 2017

Research paper thumbnail of Differentiating pulmonary transfusion reactions using recipient and transfusion factors

Transfusion, 2017

It is increasingly recognized that recipient risk factors play a prominent role in possible trans... more It is increasingly recognized that recipient risk factors play a prominent role in possible transfusion-related acute lung injury (pTRALI) and transfusion-associated circulatory overload (TACO). We hypothesized that both transfusion and recipient factors including natriuretic peptides could be used to distinguish TRALI from TACO and pTRALI. We performed a post hoc analysis of a case-control study of pulmonary transfusion reactions conducted at the University of California at San Francisco and Mayo Clinic, Rochester. We evaluated clinical data and brain natriuretic peptides (BNP) levels drawn after transfusion in patients with TRALI (n = 21), pTRALI (n = 26), TACO (n = 22), and controls (n = 24). Logistic regression and receiver operating characteristics curve analyses were used to determine the accuracy of clinical and biomarker predictors in differentiating TRALI from TACO and pTRALI. We found that pTRALI and TACO were associated with older age, higher fluid balance, and elevated B...

Research paper thumbnail of Quantitative assessment of lung stiffness in patients with interstitial lung disease using MR elastography

Journal of magnetic resonance imaging : JMRI, Jan 24, 2017

To investigate the use of magnetic resonance elastography (MRE) in the quantitative assessment of... more To investigate the use of magnetic resonance elastography (MRE) in the quantitative assessment of pulmonary fibrosis by comparing quantitative shear stiffness measurements of lung parenchyma in patients diagnosed with fibrotic interstitial lung disease (ILD) and healthy controls. A 1.5T spin-echo, echo planar imaging MRE (SE-EPI MRE) pulse sequence was utilized to assess absolute lung shear stiffness in 15 patients with diagnosed ILD and in 11 healthy controls. Data were collected at residual volume (RV) and total lung capacity (TLC). Spirometry data were obtained immediately prior to scanning. To test for statistical significance between RV and TLC shear stiffness estimates a two-sample t-test was performed. To assess variability within individual subject shear stiffness estimates, the intraclass correlation coefficient (ICC) and Krippendorff's alpha were calculated. Patients with ILD exhibited an average (±1 standard deviation) shear stiffness of 2.74 (±0.896) kPa at TLC and 1...

Research paper thumbnail of Plasma membrane wounding and repair in pulmonary diseases

American journal of physiology. Lung cellular and molecular physiology, Jan 6, 2017

Various pathophysiological conditions such as surfactant dysfunction, mechanical ventilation, inf... more Various pathophysiological conditions such as surfactant dysfunction, mechanical ventilation, inflammation, pathogen products, environmental exposures and gastric acid aspiration stress lung cells and the compromise of plasma membranes occur as a result. The mechanisms necessary for cells to repair plasma membrane defects have been extensively investigated in the last two decades, and some of these key repair mechanisms are also shown to occur following lung cell injury. As it was theorized that lung wounding and repair are involved in the pathogenesis of acute respiratory distress syndrome (ARDS) and idiopathic pulmonary fibrosis (IPF), in this review, we summarized the experimental evidence of lung cell injury in these two devastating syndromes, discuss relevant genetic, physical and biological injury mechanisms, as well as mechanisms utilized by lung cells for cell survival and membrane repair. Finally, we discuss relevant signalling pathways that may be activated by chronic or r...

Research paper thumbnail of Transpulmonary Pressure: The Importance of Precise Definitions and Limiting Assumptions

American journal of respiratory and critical care medicine, Dec 15, 2016

Recent studies applying the principles of respiratory mechanics to respiratory disease have used ... more Recent studies applying the principles of respiratory mechanics to respiratory disease have used inconsistent and mutually exclusive definitions of the term "transpulmonary pressure." By the traditional definition, transpulmonary pressure is the pressure across the whole lung, including the intrapulmonary airways, (i.e., the pressure difference between the opening to the pulmonary airway and the pleural surface). However, more recently transpulmonary pressure has also been defined as the pressure across only the lung tissue (i.e., the pressure difference between the alveolar space and the pleural surface), traditionally known as the "elastic recoil pressure of the lung." Multiple definitions of the same term, and failure to recognize their underlying assumptions, have led to different interpretations of lung physiology and conclusions about appropriate therapy for patients. It is our view that many current controversies in the physiological interpretation of dise...

Research paper thumbnail of Entrainment of Respiration in Humans by Periodic Lung Inflations Effect of State and CO 2

Lack of synchrony between a patient and the mechanical ventilator occurs when the respiratory rhy... more Lack of synchrony between a patient and the mechanical ventilator occurs when the respiratory rhythm of the patient fails to entrain to machine inflations. Entrainment implies a resetting of the respiratory rhythm such that a fixed temporal relationship exists between the onset of inspiratory ac- tivity and the onset of a mechanical breath. We examined the entrainment response to mechanical

Research paper thumbnail of 14-Hour Shift Schedule for Medical ICU Interns

Chest, 2006

We report here on an alternate version of the 14-h shift model for ICU residents that was describ... more We report here on an alternate version of the 14-h shift model for ICU residents that was described by Afessa and colleagues (December 2005). 1 Shift schedules limit resident hours and shift duration; however, these undermine the intern's traditional role of knowing ...

Research paper thumbnail of The control of breathing during weaning from mechanical ventilation

Chest Journal, Sep 1, 1991

Using the recruitment threshold technique, we measured the CO2 responsiveness of the unloaded res... more Using the recruitment threshold technique, we measured the CO2 responsiveness of the unloaded respiratory pump in 14 mechanically ventilated patients prior to weaning. The CO2 recruitment threshold (CO2RT) was compared with the arterial CO2 tension during unassisted breathing (CO2SB) and with the PaCO2 during mechanical ventilation (CO2MV) at machine settings determined by the primary physician. Based on these comparisons, we tested the hypotheses that (1) patients without weaning-induced respiratory distress (group 1) maintain CO2SB near CO2RT, (2) patients with weaning-induced respiratory distress (group 2) retain CO2SB above CO2RT, thereby manifesting incomplete load compensation, and (3) CO2MV is ventilator setting dependent and provides insufficient information about the ventilatory requirement during weaning. Respiratory distress was prospectively defined as sustained tachypnea (rate greater than or equal to 30) or intense dyspnea (Borg scale rating) and limited weaning in nine of 14 patients. The average CO2RT was 40 mm Hg in both groups. All patients in group 1 maintained CO2SB near CO2RT (p greater than 0.1). Seven of nine patients in group 2 retained CO2 by greater than or equal to 3 mm Hg above CO2RT (p less than 0.01). There was no significant difference between CO2MV and CO2SB in either group. We conclude that CO2RT provides a better reference of the adequacy of ventilatory load compensation during weather than CO2MV.

Research paper thumbnail of Intraoperative Tidal Volume as a Risk Factor for Respiratory Failure after PneumonectomyFernández-Pérez ER, Keegan MT, Brown DR, et al (Mayo Clinic, Rochester, Minn) Anesthesiology 105:14–18, 2006§

The Journal of the American Society of Anesthesiologists, Jul 1, 2007

Research paper thumbnail of Lung Stress and Strain in Acute Respiratory Distress Syndrome

American Journal of Respiratory and Critical Care Medicine, Dec 20, 2012

bronchodilator component and not to the inhaled corticosteroid component (6, 8). Moreover, inhale... more bronchodilator component and not to the inhaled corticosteroid component (6, 8). Moreover, inhaled corticosteroids alone or in combination have been associated with increased risks of glaucoma and possibly osteoporotic fractures (9-11), and have been shown to increase the risk of cataract and pneumonia, particularly with the high doses currently in use (12-16). On the whole, this study offers two major advances that benefit the patient with COPD. It provides the first possible evidence that lung function decline can be slowed with medications. It also provides further evidence that the use of inhaled corticosteroids, alone or in combination, in COPD is unnecessary and thus inappropriate.

Research paper thumbnail of Epithelial to mesenchymal transition: A new twist to biotrauma?

Critical Care Medicine, Feb 1, 2012

Research paper thumbnail of Bronchoscopy in Ventilator-associated Pneumonia

American Journal of Respiratory and Critical Care Medicine, Dec 20, 2012

Rationale: Although the serial dilution technique for quantitative culture of bronchoalveolar flu... more Rationale: Although the serial dilution technique for quantitative culture of bronchoalveolar fluid is considered to be the gold standard for the diagnosis of ventilatorassociated pneumonia, it is more labor intensive than the calibrated loop technique. Objective: We sought to determine the agreement between the calibrated loop and serial dilution techniques in the diagnosis of ventilator-associated pneumonia. Methods: We prospectively measured bacterial colony counts by the serial dilution and calibrated loop techniques in 121 bronchoalveolar lavage samples of 104 patients with suspected ventilator-associated pneumonia. Measurements and Main Results: At the time of bronchoscopy, patients had received mechanical ventilation for a median of 8 days. Patients were receiving antibiotics when 90 of the 121 (74.4%) bronchoalveolar samples were obtained. The colony counts of 13 bacterial isolates were too numerous to count by the calibrated loop technique; by serial dilution technique, their counts ranged from 4.70 log10 to 6.74 log10 colony forming unit (CFU)/mL. Fifty other bacteria had paired colony counts measured by each of the two techniques: the bias (95% confidence interval) between the two techniques was-0.380 (-0.665 to-0.095) log10 CFU/mL with precision of 1.002 log10 CFU/mL and 95% limits of agreement-2.344 to 1.584 log10 CFU/mL. Using the threshold of 4 log10 CFU/mL as a criterion for the diagnosis of ventilator-associated pneumonia, there was discordance only for one bacterial organism between the two techniques. Conclusions: The calibrated loop technique can be used for the diagnosis of ventilatorassociated pneumonia using bronchoalveolar fluid.

Research paper thumbnail of Bronchoscopy in Ventilator-associated Pneumonia Agreement of Calibrated Loop and Serial Dilution

American Journal of Respiratory and Critical Care Medicine, Jul 1, 2006

Rationale: Although the serial dilution technique for quantitative culture of bronchoalveolar flu... more Rationale: Although the serial dilution technique for quantitative culture of bronchoalveolar fluid is considered to be the gold standard for the diagnosis of ventilatorassociated pneumonia, it is more labor intensive than the calibrated loop technique. Objective: We sought to determine the agreement between the calibrated loop and serial dilution techniques in the diagnosis of ventilator-associated pneumonia. Methods: We prospectively measured bacterial colony counts by the serial dilution and calibrated loop techniques in 121 bronchoalveolar lavage samples of 104 patients with suspected ventilator-associated pneumonia. Measurements and Main Results: At the time of bronchoscopy, patients had received mechanical ventilation for a median of 8 days. Patients were receiving antibiotics when 90 of the 121 (74.4%) bronchoalveolar samples were obtained. The colony counts of 13 bacterial isolates were too numerous to count by the calibrated loop technique; by serial dilution technique, their counts ranged from 4.70 log10 to 6.74 log10 colony forming unit (CFU)/mL. Fifty other bacteria had paired colony counts measured by each of the two techniques: the bias (95% confidence interval) between the two techniques was-0.380 (-0.665 to-0.095) log10 CFU/mL with precision of 1.002 log10 CFU/mL and 95% limits of agreement-2.344 to 1.584 log10 CFU/mL. Using the threshold of 4 log10 CFU/mL as a criterion for the diagnosis of ventilator-associated pneumonia, there was discordance only for one bacterial organism between the two techniques. Conclusions: The calibrated loop technique can be used for the diagnosis of ventilatorassociated pneumonia using bronchoalveolar fluid.

Research paper thumbnail of Early nutritional support is associated with improved outcomes in respiratory failure

Acta Medica Academica, May 23, 2010

Objective. To evaluate early feeding as a predictor of outcome in critically ill patients receivi... more Objective. To evaluate early feeding as a predictor of outcome in critically ill patients receiving prolonged mechanical ventilation. Patients and methods. A retrospective cohort study in four medical, surgical and multidisciplinary intensive care units (ICU) in a tertiary referral center of adult patients requiring at least 48 hours of mechanical ventilation. Early feeding was defined as any nutritional support (enteral or parenteral) for at least 6 hours, started within 48 hours of mechanical ventilation. The primary endpoint was hospital mortality. The secondary endpoints were length of stay, and duration of mechanical ventilation. Univariate and multivariate analysis were used as appropriate. Results. 394 out of 4,546 patients admitted to the ICU were studied. Age (mean: 95% confidence interval was 62 (60-63); female gender 43%; APACHE III 72 (70-75); APACHE III predicted hospital mortality 36 % (33-39); ICU mortality 19%, hospital mortality 28%, ventilation-free days 41 (39-44). Only 11% (3% enteral, 8% parenteral) were fed on day 1, 55% (30% enteral, 25% parenteral) on day 4, and 88% (51% enteral, 37% parenteral) on day 7. Early feeding was associated with a reduced Standardized Mortality Ratio (number of observed hospital deaths/number of expected hospital deaths) of 0.53. When adjusted for various confounding factors such as severity of illness, trauma, route of feeding, post-operative state or the use of vasopressors, early feeding remained independently associated with decreased hospital mortality (Odd Ratio 0.51; 95% confidence interval 0.26-0.98; p = 0.042). Conclusion. Early nutrition is associated with decreased hospital mortality in patients receiving prolonged (more than 48 hours) invasive mechanical ventilation.

Research paper thumbnail of The Times Are A-Changin???: Should We Hang Up the Stethoscope?

The Journal of the American Society of Anesthesiologists, 2004