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Boaz A Markewitz - One of the best experts on this subject based on the ideXlab platform.
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evaluation of a co2 partial rebreathing functional residual capacity measurement method for use during mechanical ventilation
Journal of Clinical Monitoring and Computing, 2011Co-Authors: Lara Brewer, Earl Fulcher, Boaz A MarkewitzAbstract:Objective There is a need for an automated bedside functional residual capacity (FRC) measurement method that does not require a step change in inspired oxygen fraction. Such a method can be used for patients who require a high inspired oxygen fraction to maintain arterial oxygenation and for patients ventilated using a circle breathing system commonly found in operating rooms, which is not capable of step changes in oxygen. We developed a CO2 rebreathing method for FRC measurement that is based on the change in partial pressure of end-tidal carbon dioxide and volume of CO2 eliminated at the end of a partial rebreathing period. This study was designed to assess the accuracy and precision of the proposed FRC measurement system compared to Body Plethysmography and nitrogen washout FRC.
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measurement of functional residual capacity by modified multiple breath nitrogen washout for spontaneously breathing and mechanically ventilated patients
BJA: British Journal of Anaesthesia, 2011Co-Authors: Lara Brewer, Joseph A Orr, M R Sherman, Earl Fulcher, Boaz A MarkewitzAbstract:Background There is a need for a bedside functional residual capacity (FRC) measurement method that performs well in intensive care patients during many modes of ventilation including controlled, assisted, spontaneous, and mixed. We developed a modified multiple breath nitrogen washout method for FRC measurement that relies on end-tidal gas fractions and alveolar tidal volume measurements as inputs but does not require the traditional measurements of volume of nitrogen or oxygen. Using end-tidal measurements, not volume, reduces errors from signal synchronization. This study was designed to assess the accuracy, precision, and repeatability of the proposed FRC system in subjects with variable ventilation patterns including some spontaneous effort. Methods The accuracy and precision of measurements were assessed by comparing the novel N2 washout FRC values to the gold standard, Body Plethysmography, in 20 spontaneously breathing volunteers. Repeatability was assessed by comparing subsequent measurements in 20 intensive care patients whose lungs were under controlled and assisted mechanical ventilation. Results Compared with Body Plethysmography, the accuracy (mean bias) of the novel method was −0.004 litre and precision [1 standard deviation ( sd )] was 0.209 litre [mean ( sd )] [−0.1 (5.9)% of Body Plethysmography]. The difference between repeated measurements was 0.009 (0.15) litre [mean ( sd )] [0.4 (6.4)%]. The coefficient of repeatability was 0.31 litre (12.7%). Conclusions The modified multiple breath nitrogen washout method for FRC measurement provides improved precision and equivalent accuracy and repeatability compared with existing methods during ventilation with variable ventilation patterns. Further study of the novel N2 washout method is needed.
Lara Brewer - One of the best experts on this subject based on the ideXlab platform.
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evaluation of a co2 partial rebreathing functional residual capacity measurement method for use during mechanical ventilation
Journal of Clinical Monitoring and Computing, 2011Co-Authors: Lara Brewer, Earl Fulcher, Boaz A MarkewitzAbstract:Objective There is a need for an automated bedside functional residual capacity (FRC) measurement method that does not require a step change in inspired oxygen fraction. Such a method can be used for patients who require a high inspired oxygen fraction to maintain arterial oxygenation and for patients ventilated using a circle breathing system commonly found in operating rooms, which is not capable of step changes in oxygen. We developed a CO2 rebreathing method for FRC measurement that is based on the change in partial pressure of end-tidal carbon dioxide and volume of CO2 eliminated at the end of a partial rebreathing period. This study was designed to assess the accuracy and precision of the proposed FRC measurement system compared to Body Plethysmography and nitrogen washout FRC.
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measurement of functional residual capacity by modified multiple breath nitrogen washout for spontaneously breathing and mechanically ventilated patients
BJA: British Journal of Anaesthesia, 2011Co-Authors: Lara Brewer, Joseph A Orr, M R Sherman, Earl Fulcher, Boaz A MarkewitzAbstract:Background There is a need for a bedside functional residual capacity (FRC) measurement method that performs well in intensive care patients during many modes of ventilation including controlled, assisted, spontaneous, and mixed. We developed a modified multiple breath nitrogen washout method for FRC measurement that relies on end-tidal gas fractions and alveolar tidal volume measurements as inputs but does not require the traditional measurements of volume of nitrogen or oxygen. Using end-tidal measurements, not volume, reduces errors from signal synchronization. This study was designed to assess the accuracy, precision, and repeatability of the proposed FRC system in subjects with variable ventilation patterns including some spontaneous effort. Methods The accuracy and precision of measurements were assessed by comparing the novel N2 washout FRC values to the gold standard, Body Plethysmography, in 20 spontaneously breathing volunteers. Repeatability was assessed by comparing subsequent measurements in 20 intensive care patients whose lungs were under controlled and assisted mechanical ventilation. Results Compared with Body Plethysmography, the accuracy (mean bias) of the novel method was −0.004 litre and precision [1 standard deviation ( sd )] was 0.209 litre [mean ( sd )] [−0.1 (5.9)% of Body Plethysmography]. The difference between repeated measurements was 0.009 (0.15) litre [mean ( sd )] [0.4 (6.4)%]. The coefficient of repeatability was 0.31 litre (12.7%). Conclusions The modified multiple breath nitrogen washout method for FRC measurement provides improved precision and equivalent accuracy and repeatability compared with existing methods during ventilation with variable ventilation patterns. Further study of the novel N2 washout method is needed.
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measurement of functional residual capacity of the lung by nitrogen washout carbon dioxide rebreathing and Body Plethysmography in healthy volunteers
2009Co-Authors: Lara Brewer, Joseph A OrrAbstract:Background: We measured Functional Residual Capacity (FRC) of the lungs with three methods in healthy volunteers. The three techniques included a CO2 partial rebreathing technique, nitrogen washout technique, and the reference technique for ambulatory patients, Body Plethysmography. Materials and Methods: After granting consent to an IRB-approved protocol, each of the 20 healthy volunteers participated in FRC measurement by three methods, including Body Plethysmography, carbon dioxide (CO2) rebreathing, and nitrogen washout. Gas concentration and volume data were collected from the distal side of a mouthpiece during spontaneous ventilation for the washout and rebreathing measurements. The FRC was measured twice with a nitrogen washout measurement technique and then signals from five partial CO2 rebreathing measurement cycles were collected. Finally, the nitrogen washout FRC measurements were repeated twice. We compared the average CO2 rebreathing FRC measurements and the average nitrogen washout FRC measurements to the Body Plethysmography FRC measurements for each subject through statistical methods of linear regression analysis and BlandAltman Analysis. Results: The squared correlation coefficient for the linear regression between nitrogen washout and Body Plethysmography measurements was r = 0.91 (n = 35). The bias ± Standard Deviation was 0.054 ± 0.373 L. Conclusion: These results indicate FRC measurement by nitrogen washout correlate well with the Body Plethysmography reference standard in ambulatory, spontaneously breathing subjects. This method could possibly be used in space to monitor lung function. Introduction Functional Residual Capacity (FRC) measurements may be useful as a guide for ventilation management or as a way to follow disease progression for patients with acute lung injury and ARDS. While traditional methods of FRC measurement are valuable for researching disease progression and for monitoring ambulatory patients, they have been of limited utility at the bedside due to difficulty of use, high expense, and impracticality during mechanical ventilation. FRC measurement at the bedside for mechanically and spontaneously ventilated patients has recently been reported by several researchers, who evaluated systems based on nitrogen washout and Electrical Impedance Tomography. The nitrogen washout and CO2 rebreathing methods have previously been validated by our research group with the use of a bench lung model. We also previously evaluated both methods in an animal study. The aim of this study was to evaluate the accuracy of the two FRC measurement systems compared to the clinical gold standard for ambulatory patients, Body Plethysmography, in healthy, spontaneously breathing volunteers.
Ubaldo J Martin - One of the best experts on this subject based on the ideXlab platform.
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onset of effect changes in airflow obstruction and lung volume and health related quality of life improvements with benralizumab for patients with severe eosinophilic asthma phase iiib randomized controlled trial solana
Journal of Asthma and Allergy, 2020Co-Authors: Reynold A Panettieri, Peter Barker, Richard F Olsson, Stephanie Korn, Tobias Welte, Kartik Shenoy, Margret Jandl, Edward Kerwin, Rosa Feijoo, Ubaldo J MartinAbstract:Objective In the SOLANA trial, we sought to physiologically characterize benralizumab's onset of effect and maintenance of that effect for patients with severe eosinophilic asthma. Methods SOLANA (NCT02869438) was a multicenter, randomized, double-blind, parallel-group, placebo-controlled, Phase IIIb study conducted at 49 centers in six countries (Chile, Germany, Hungary, the Philippines, South Korea, and the United States). Eligible patients with baseline blood eosinophil counts ≥300 cells/µL were randomized to subcutaneous benralizumab (30 mg) or placebo administered at Days 0, 28, and 56. The primary endpoint was the average change from baseline in prebronchodilator forced expiratory volume in 1 s (pre-BD FEV1) during the Day 28‒Day 84 period for benralizumab vs placebo. Secondary endpoints included patient-reported outcomes (PROs). A subset of patients participated in a whole-Body Plethysmography substudy. Safety was also assessed. Results In total, 233 patients were randomized to benralizumab (n=118) or placebo (n=115). Improvement from baseline in pre-BD FEV1 with benralizumab 30 mg was not statistically significant compared with placebo (least-squares mean change difference [95% confidence interval] 57 mL [-22 to 135]; p=0.16). Compared with placebo, benralizumab demonstrated early (Day 7) nonstatistically significant improvements in whole-Body Plethysmography assessments of hyperinflation and clinically meaningful improvements in PRO measures (Asthma Control Questionnaire 6 at Day 14 and St. George's Respiratory Questionnaire at Day 28), which were maintained over the treatment period. Benralizumab's safety profile was commensurate with previously reported studies. Conclusion The observed early changes in lung volume despite relatively small improvements in airflow obstruction suggest that the anti-inflammatory effect of benralizumab may be manifested as deflation over time for patients with hyperinflation, who potentially have a greater degree of airway remodeling. This early effect could partially explain the rapid PRO improvements observed for certain patients.
Philippe Brabet - One of the best experts on this subject based on the ideXlab platform.
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pituitary adenylate cyclase activating peptide receptor 1 mediates anti inflammatory effects in allergic airway inflammation in mice
Clinical & Experimental Allergy, 2011Co-Authors: Hansdieter Lauenstein, David Quarcoo, L Plappert, Carsten Schleh, Matthias Nassimi, C Pilzner, Sabine Rochlitzer, Philippe BrabetAbstract:Cite this as: H. D. Lauenstein, D. Quarcoo, L. Plappert, C. Schleh, M. Nassimi, C. Pilzner, S. Rochlitzer, P. Brabet, T. Welte, H. G. Hoymann, N. Krug, M. Muller, E. A. Lerner, A. Braun and D. A. Groneberg, Clinical & Experimental Allergy, 2011 (41) 592–601. Summary Background Bronchial asthma is characterized by airway inflammation and reversible obstruction. Since the gold standard of therapy, a combination of anti-inflammatory corticosteroids and bronchodilatory β2 agonists, has recently been discussed to be related to an increased mortality, there is a need for novel therapeutic pathways. Objective A new experimental concept that encompasses the vasoactive intestinal peptide/pituitary adenylate cyclase activating peptide (PACAP) family of receptors by demonstrating the anti-inflammatory effects of the PACAP receptor 1 (PAC1R) in a murine model of allergic asthma is described. Methods PAC1R expression was investigated in lung tissue and isolated dendritic cells (DCs) via real-time PCR. Ovalbumin (OVA)-induced asthma models were used in PAC1R-deficient mice and BALB/c mice treated with PAC1R agonist maxadilan (MAX). Bronchoalveolar lavages have been performed and investigated at the cellular and cytokine levels. Fluorescence staining of a frozen lung section has been performed to detect eosinophil granulocytes in lung tissue. Plasma IgE levels have been quantified via the ELISA technique. Lung function was determined using head-out Body Plethysmography or whole-Body Plethysmography. Results Increased PAC1R mRNA expression in lung tissue was present under inflammatory conditions. PAC1R expression was detected on DCs. In OVA-induced asthma models, which were applied to PAC1R-deficient mice (PAC1R−/−) and to BALB/c mice treated with the specific PAC1R agonist MAX, PAC1R deficiency resulted in inflammatory effects, while agonistic stimulation resulted in anti-inflammatory effects. No effects on lung function were detected both in the gene-depletion and in the pharmacologic studies. In summary, here, we demonstrate that anti-inflammatory effects can be achieved via PAC1R. Conclusion PAC1R agonists may represent a promising target for an anti-inflammatory therapy in airway diseases such as bronchial asthma.
C Pilzner - One of the best experts on this subject based on the ideXlab platform.
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pituitary adenylate cyclase activating peptide receptor 1 mediates anti inflammatory effects in allergic airway inflammation in mice
Clinical & Experimental Allergy, 2011Co-Authors: Hansdieter Lauenstein, David Quarcoo, L Plappert, Carsten Schleh, Matthias Nassimi, C Pilzner, Sabine Rochlitzer, Philippe BrabetAbstract:Cite this as: H. D. Lauenstein, D. Quarcoo, L. Plappert, C. Schleh, M. Nassimi, C. Pilzner, S. Rochlitzer, P. Brabet, T. Welte, H. G. Hoymann, N. Krug, M. Muller, E. A. Lerner, A. Braun and D. A. Groneberg, Clinical & Experimental Allergy, 2011 (41) 592–601. Summary Background Bronchial asthma is characterized by airway inflammation and reversible obstruction. Since the gold standard of therapy, a combination of anti-inflammatory corticosteroids and bronchodilatory β2 agonists, has recently been discussed to be related to an increased mortality, there is a need for novel therapeutic pathways. Objective A new experimental concept that encompasses the vasoactive intestinal peptide/pituitary adenylate cyclase activating peptide (PACAP) family of receptors by demonstrating the anti-inflammatory effects of the PACAP receptor 1 (PAC1R) in a murine model of allergic asthma is described. Methods PAC1R expression was investigated in lung tissue and isolated dendritic cells (DCs) via real-time PCR. Ovalbumin (OVA)-induced asthma models were used in PAC1R-deficient mice and BALB/c mice treated with PAC1R agonist maxadilan (MAX). Bronchoalveolar lavages have been performed and investigated at the cellular and cytokine levels. Fluorescence staining of a frozen lung section has been performed to detect eosinophil granulocytes in lung tissue. Plasma IgE levels have been quantified via the ELISA technique. Lung function was determined using head-out Body Plethysmography or whole-Body Plethysmography. Results Increased PAC1R mRNA expression in lung tissue was present under inflammatory conditions. PAC1R expression was detected on DCs. In OVA-induced asthma models, which were applied to PAC1R-deficient mice (PAC1R−/−) and to BALB/c mice treated with the specific PAC1R agonist MAX, PAC1R deficiency resulted in inflammatory effects, while agonistic stimulation resulted in anti-inflammatory effects. No effects on lung function were detected both in the gene-depletion and in the pharmacologic studies. In summary, here, we demonstrate that anti-inflammatory effects can be achieved via PAC1R. Conclusion PAC1R agonists may represent a promising target for an anti-inflammatory therapy in airway diseases such as bronchial asthma.