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Assessment of murine lung mechanics outcome measures: alignment with those made in asthmatics.

Walker JK, Kraft M, Fisher JT - Front Physiol (2013)

Bottom Line: Murine models of allergic inflammatory airway disease have been widely used to gain mechanistic insight into the pathogenesis of asthma; however, several aspects of murine models could benefit from improvement.A brief description of techniques available to measure murine lung mechanics is provided along with a methodological consideration of their utilization.How murine lung mechanics outcome measures relate to pulmonary physiology measures conducted in humans is discussed and we recommend that, like human studies, outcome measures be standardized for murine models of asthma.

View Article: PubMed Central - PubMed

Affiliation: Division of Pulmonary, Allergy and Critical Care Medicine, Duke University Medical Center Durham, NC, USA.

ABSTRACT
Although asthma is characterized as an inflammatory disease, recent reports highlight the importance of pulmonary physiology outcome measures to the clinical assessment of asthma control and risk of asthma exacerbation. Murine models of allergic inflammatory airway disease have been widely used to gain mechanistic insight into the pathogenesis of asthma; however, several aspects of murine models could benefit from improvement. This review focuses on aligning lung mechanics measures made in mice with those made in humans, with an eye toward improving the translational utility of these measures. A brief description of techniques available to measure murine lung mechanics is provided along with a methodological consideration of their utilization. How murine lung mechanics outcome measures relate to pulmonary physiology measures conducted in humans is discussed and we recommend that, like human studies, outcome measures be standardized for murine models of asthma.

No MeSH data available.


Related in: MedlinePlus

Examples of routine methods of Respiratory mechanics Measurements for AHR: each panel illustrates animal instrumentation, airway measurement (s) and presence of mechanical or spontaneous ventilation. (A) Airway Pressure Time Index: APTI measures the tracheal pressure response to MCh in a mouse to calculate an aggregate change in respiratory system impedance (Levitt and Mitzner, 1988). (B) Flow Plethysmography: Flow and tracheal pressure (Ptr) signals derived from a flow-plethysmograph and tracheal cannula are used to calculate Rrs or RL depending on whether transrespiratory or transpulmonary pressure is measured (Amdur and Mead, 1958; Waldron and Fisher, 1988). (C) End-Inflation Occlusion: This technique relies on a purpose built ventilator to deliver and hold known inflation volumes and measure the resultant pressure peak and plateau pressures to calculate Rrs and Crs (Ewart et al., 1995; Volgyesi et al., 2000). Ventilators may be lab constructed or use a commercial product (Volgeysi ventilator). (D) Forced Oscillation Technique: The FOT method relies on a purpose built ventilator requiring sophisticated software for the control of volume perturbations and analysis of generated pressure, volume and flow signals. In brief, ventilator housed pistons generate a complex frequency perturbation in the volume signal administered to mice. The lung response is measured as pressure from which lung impedance and other variables are calculated. Current use applications in the literature appear to be restricted to a commercially built ventilator (Scireq®flexivent).
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Figure 1: Examples of routine methods of Respiratory mechanics Measurements for AHR: each panel illustrates animal instrumentation, airway measurement (s) and presence of mechanical or spontaneous ventilation. (A) Airway Pressure Time Index: APTI measures the tracheal pressure response to MCh in a mouse to calculate an aggregate change in respiratory system impedance (Levitt and Mitzner, 1988). (B) Flow Plethysmography: Flow and tracheal pressure (Ptr) signals derived from a flow-plethysmograph and tracheal cannula are used to calculate Rrs or RL depending on whether transrespiratory or transpulmonary pressure is measured (Amdur and Mead, 1958; Waldron and Fisher, 1988). (C) End-Inflation Occlusion: This technique relies on a purpose built ventilator to deliver and hold known inflation volumes and measure the resultant pressure peak and plateau pressures to calculate Rrs and Crs (Ewart et al., 1995; Volgyesi et al., 2000). Ventilators may be lab constructed or use a commercial product (Volgeysi ventilator). (D) Forced Oscillation Technique: The FOT method relies on a purpose built ventilator requiring sophisticated software for the control of volume perturbations and analysis of generated pressure, volume and flow signals. In brief, ventilator housed pistons generate a complex frequency perturbation in the volume signal administered to mice. The lung response is measured as pressure from which lung impedance and other variables are calculated. Current use applications in the literature appear to be restricted to a commercially built ventilator (Scireq®flexivent).

Mentions: Current methods that assess murine pulmonary function can be categorized broadly into invasive (Figures 1A–D) and non-invasive (Figure 2) techniques. Invasive techniques directly measure respiratory system (including chest-wall) or pulmonary (lung only) mechanics and typically rely on tracheal cannulation or orotracheal intubation to measure airflow and pressure across the respiratory system or across the lung (transpulmonary pressure). Based on physiological principles these methods provide reproducible, consistent, and meaningful data with respect to RL and elastance, which are sufficiently sensitive to reveal subtle changes in lung mechanics induced by allergen-exposure models (Irvin and Bates, 2003; Glaab et al., 2007). Thus, invasive techniques are valuable tools for assessing AHR in murine models of asthma.


Assessment of murine lung mechanics outcome measures: alignment with those made in asthmatics.

Walker JK, Kraft M, Fisher JT - Front Physiol (2013)

Examples of routine methods of Respiratory mechanics Measurements for AHR: each panel illustrates animal instrumentation, airway measurement (s) and presence of mechanical or spontaneous ventilation. (A) Airway Pressure Time Index: APTI measures the tracheal pressure response to MCh in a mouse to calculate an aggregate change in respiratory system impedance (Levitt and Mitzner, 1988). (B) Flow Plethysmography: Flow and tracheal pressure (Ptr) signals derived from a flow-plethysmograph and tracheal cannula are used to calculate Rrs or RL depending on whether transrespiratory or transpulmonary pressure is measured (Amdur and Mead, 1958; Waldron and Fisher, 1988). (C) End-Inflation Occlusion: This technique relies on a purpose built ventilator to deliver and hold known inflation volumes and measure the resultant pressure peak and plateau pressures to calculate Rrs and Crs (Ewart et al., 1995; Volgyesi et al., 2000). Ventilators may be lab constructed or use a commercial product (Volgeysi ventilator). (D) Forced Oscillation Technique: The FOT method relies on a purpose built ventilator requiring sophisticated software for the control of volume perturbations and analysis of generated pressure, volume and flow signals. In brief, ventilator housed pistons generate a complex frequency perturbation in the volume signal administered to mice. The lung response is measured as pressure from which lung impedance and other variables are calculated. Current use applications in the literature appear to be restricted to a commercially built ventilator (Scireq®flexivent).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3569663&req=5

Figure 1: Examples of routine methods of Respiratory mechanics Measurements for AHR: each panel illustrates animal instrumentation, airway measurement (s) and presence of mechanical or spontaneous ventilation. (A) Airway Pressure Time Index: APTI measures the tracheal pressure response to MCh in a mouse to calculate an aggregate change in respiratory system impedance (Levitt and Mitzner, 1988). (B) Flow Plethysmography: Flow and tracheal pressure (Ptr) signals derived from a flow-plethysmograph and tracheal cannula are used to calculate Rrs or RL depending on whether transrespiratory or transpulmonary pressure is measured (Amdur and Mead, 1958; Waldron and Fisher, 1988). (C) End-Inflation Occlusion: This technique relies on a purpose built ventilator to deliver and hold known inflation volumes and measure the resultant pressure peak and plateau pressures to calculate Rrs and Crs (Ewart et al., 1995; Volgyesi et al., 2000). Ventilators may be lab constructed or use a commercial product (Volgeysi ventilator). (D) Forced Oscillation Technique: The FOT method relies on a purpose built ventilator requiring sophisticated software for the control of volume perturbations and analysis of generated pressure, volume and flow signals. In brief, ventilator housed pistons generate a complex frequency perturbation in the volume signal administered to mice. The lung response is measured as pressure from which lung impedance and other variables are calculated. Current use applications in the literature appear to be restricted to a commercially built ventilator (Scireq®flexivent).
Mentions: Current methods that assess murine pulmonary function can be categorized broadly into invasive (Figures 1A–D) and non-invasive (Figure 2) techniques. Invasive techniques directly measure respiratory system (including chest-wall) or pulmonary (lung only) mechanics and typically rely on tracheal cannulation or orotracheal intubation to measure airflow and pressure across the respiratory system or across the lung (transpulmonary pressure). Based on physiological principles these methods provide reproducible, consistent, and meaningful data with respect to RL and elastance, which are sufficiently sensitive to reveal subtle changes in lung mechanics induced by allergen-exposure models (Irvin and Bates, 2003; Glaab et al., 2007). Thus, invasive techniques are valuable tools for assessing AHR in murine models of asthma.

Bottom Line: Murine models of allergic inflammatory airway disease have been widely used to gain mechanistic insight into the pathogenesis of asthma; however, several aspects of murine models could benefit from improvement.A brief description of techniques available to measure murine lung mechanics is provided along with a methodological consideration of their utilization.How murine lung mechanics outcome measures relate to pulmonary physiology measures conducted in humans is discussed and we recommend that, like human studies, outcome measures be standardized for murine models of asthma.

View Article: PubMed Central - PubMed

Affiliation: Division of Pulmonary, Allergy and Critical Care Medicine, Duke University Medical Center Durham, NC, USA.

ABSTRACT
Although asthma is characterized as an inflammatory disease, recent reports highlight the importance of pulmonary physiology outcome measures to the clinical assessment of asthma control and risk of asthma exacerbation. Murine models of allergic inflammatory airway disease have been widely used to gain mechanistic insight into the pathogenesis of asthma; however, several aspects of murine models could benefit from improvement. This review focuses on aligning lung mechanics measures made in mice with those made in humans, with an eye toward improving the translational utility of these measures. A brief description of techniques available to measure murine lung mechanics is provided along with a methodological consideration of their utilization. How murine lung mechanics outcome measures relate to pulmonary physiology measures conducted in humans is discussed and we recommend that, like human studies, outcome measures be standardized for murine models of asthma.

No MeSH data available.


Related in: MedlinePlus