Noninvasive method to measure airway obstruction in nonanesthetized allergen-sensitized and challenged mice.
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BACKGROUND: Conventional methods used to measure bronchoconstriction are invasive, technically demanding and time consuming. OBJECTIVES: Our purpose was to evaluate a noninvasive method, by barometric whole-body plethysmography (WBP), to evaluate bronchoconstriction and bronchial hyperreactivity in mice induced by ovalbumin (OA) inhalation challenge in comparison with an invasive method. Enhanced pause (P(enh)) was used as an index of airway obstruction. METHODS: Eight mice were sensitized by OA (group I) and then challenged with OA. Twenty-four hours later, pulmonary function testing (PFT) was measured by WBP at baseline and after a methacholine (MCh) inhalation challenge. Eight weight-matched normal mice served as controls (group II). Four hours after PFT in a nonanesthetized condition, all animals were anesthetized and paralyzed. Baseline PFT was performed by the maximal forced expiratory maneuver (MFEM), and then the animals were given varying doses of acetylcholine (ACh; 25, 50, 75, 100 microg/kg) injected through the jugular vein. Five seconds after ACh injections, pulmonary functions were examined, including MFEM, peak airway pressure and total lung compliance. After completing PFT, bronchoalveolar lavage (BAL) was performed, the animals were sacrificed, and the lungs were examined histologically. RESULTS: Group I had increased P(enh) in response to MCh in the nonanesthetized condition and decreased flow in the anesthetized condition, characterized by greater decreases in MFEM flow rates MFEF 50% and MFEF 25% than the control group. The peak flows, MFEF 75%, MFEF 50% and MFEF 25%, for group I were lower than those for group II at doses of ACh higher than 25 microg/kg. There were concentration-dependent increases in P(enh) in response to aerosolized MCh in both groups, but the P(enh) in response to aerosolized MCh was significantly enhanced in group I when compared with controls. The doses of MCh required for 100% increases in P(enh) were significantly reduced for sensitized and challenged mice. There was a positive correlation between provocative doses PD200 P(enh) MCh, PD20 MFEF 50% ACh and PD20 MFEF 25% ACh. There was a negative correlation between the PD200 P(enh) MCh and the percentage of eosinophils in BAL fluid. There was an increased total cell count and an increased percentage and absolute number of eosinophils and lymphocytes in the BAL fluid of sensitized animals. OA-sensitized mice also had a severe inflammatory reaction of airway and lung tissue, characterized by congestion, edema and inflammatory cell infiltration and desquamation of bronchial epithelial cells. CONCLUSION: The noninvasive method of WBP can be used to evaluate airway obstruction and hyperreactivity induced in mice by allergen challenge. (+info)
Stress-induced attenuation of the hypercapnic ventilatory response in awake rats.
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To test the hypothesis that stress alters the performance of the respiratory control system, we compared the acute (20 min) responses to moderate hypoxia and hypercapnia of rats previously subjected to immobilization stress (90 min/day) with responses of control animals. Ventilatory measurements were performed on awake rats using whole body plethysmography. Under baseline conditions, there were no differences in minute ventilation between stressed and unstressed groups. Rats previously exposed to immobilization stress had a 45% lower ventilatory response to hypercapnia (inspiratory CO(2) fraction = 0.05) than controls. In contrast, stress exposure had no statistically significant effect on the ventilatory response to hypoxia (inspiratory O(2) fraction = 0.12). Stress-induced attenuation of the hypercapnic response was associated with reduced tidal volume and inspiratory flow increases; the frequency and timing components of the response were not different between groups. We conclude that previous exposure to a stressful condition that does not constitute a direct challenge to respiratory homeostasis can elicit persistent (> or =24 h) functional plasticity in the ventilatory control system. (+info)
The effect of ribavirin to treat previously healthy infants admitted with acute bronchiolitis on acute and chronic respiratory morbidity.
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The role of ribavirin in the treatment of acute bronchiolitis is controversial. It has been suggested that the use of ribavirin may be of benefit during the acute illness and may reduce subsequent recurrent respiratory morbidity. This randomized, double-blind, placebo-controlled study was designed to determine whether ribavirin administered during the acute illness would have an influence on respiratory morbidity during both the acute illness and during the following year. Bronchial reactivity 6 months after the acute illness was also assessed. Forty previously well infants with moderately severe acute bronchiolitis were recruited during three winter epidemics. Subjects received study medication for 18 h a day. Management was otherwise unaltered. Subjects were evaluated daily by the investigator and subsequently assessed at 6 weeks, 6 months and 1 year following the acute illness. Assessment of bronchial hyper-responsiveness was assessed at 6 months of age using total body plethysmography and an established ultra-sonically nebulized distilled water challenge. A total of 40 patients (21 ribavirin, 19 placebo) were entered into the study. The two groups did not differ with respect to age, gender or clinical severity on entry to the trial. No significant differences were identified in the rate of clinical improvement over the first 24 h, the time to discharge, bronchial responsiveness at 6 months of age, frequency of significant respiratory symptoms over the first year of life and the frequency of prescribed bronchodilators and inhaled steroids during the year of follow-up. This study was unable to demonstrate any clinical benefit from the use of ribavirin in the acute illness or during subsequent follow-up for 1 year. (+info)
Plethysmographic measurements of lung volume and airway resistance. ERS/ATS Task Force on Standards for Infant Respiratory Function Testing. European Respiratory Society/ American Thoracic Society.
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Functional residual capacity (FRC) is the only static lung volume that can be measured routinely in infants. It is important for interpreting volume-dependent pulmonary mechanics such as airway resistance or forced expiratory flows, and for defining normal lung growth. Despite requiring complex equipment, the plethysmographic method for measuring FRC is very simple to apply and, unlike the gas dilution techniques, enables repeat measures of lung volume to be obtained within a few minutes. This method has the further advantage that with suitable adaptations to the equipment, simultaneous measurements of airway resistance can also be obtained. The aim of this paper is to provide recommendations pertaining to equipment requirements, study procedures and reporting of data for plethysmographic measurements in infants. Implementation of these recommendations should help to ensure that such measurements are as accurate as possible and that meaningful comparisons can be made between data collected in different centres or with different equipment. These guidelines cover numerous aspects including terminology and definitions, equipment, data acquisition and analysis and reporting of results and also highlight areas where further research is needed before consensus can be reached. (+info)
Hyperoxia-induced changes in mouse lung mechanics: forced oscillations vs. barometric plethysmography.
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Hyperoxia-induced lung damage was investigated via airway and respiratory tissue mechanics measurements with low-frequency forced oscillations (LFOT) and analysis of spontaneous breathing indexes by barometric whole body plethysmography (WBP). WBP was performed in the unrestrained awake mice kept in room air (n = 12) or in 100% oxygen for 24 (n = 9), 48 (n = 8), or 60 (n = 9) h, and the indexes, including enhanced pause (Penh) and peak inspiratory and expiratory flows, were determined. The mice were then anesthetized, paralyzed, and mechanically ventilated. Airway resistance, respiratory system resistance at breathing frequency, and tissue damping and elastance were identified from the LFOT impedance data by model fitting. The monotonous decrease in airway resistance during hyperoxia correlated best with the increasing peak expiratory flow. Respiratory system resistance and tissue damping and elastance were unchanged up to 48 h of exposure but were markedly elevated at 60 h, with associated decreases in peak inspiratory flow. Penh was increased at 24 h and sharply elevated at 60 h. These results indicate no adverse effect of hyperoxia on the airway mechanics in mice, whereas marked parenchymal damage develops by 60 h. The inconsistent relationships between LFOT parameters and WBP indexes suggest that the changes in the latter reflect alterations in the breathing pattern rather than in the mechanical properties. It is concluded that, in the presence of diffuse lung disease, Penh is inadequate for characterization of the mechanical status of the respiratory system. (+info)
Assessment of an infant whole-body plethysmograph using an infant lung function model.
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In order to facilitate international multicentre studies and improve the quality control of infant pulmonary function measurements, the European Respiratory Society-American Thoracic Society Task Force for infant lung function testing has recently developed specifications for standardized infant lung function equipment and software. A mechanical infant lung model analogue has been developed to assess whether infant lung function equipment is able to meet these requirements. However, the practical testing of infant lung function equipment using such models is highly complex because of the need to use very small pressure and flow changes, and the numerous potentially confounding factors associated with both the design of the device and the testing procedure. The aim of this study was to determine whether the infant lung model is capable of assessing the overall function of an whole-body infant- plethysmograph, using the only infant plethysmograph that was commercially available at the time as an example. The mechanical characteristics of the model such as vibrations or noise did not disturb the delicate plethysmographic measurements and thereby allowed a reliable assessment of the system. A series of tests revealed that the plethysmograph was able to measure airway resistance 1-3.5 kPa.L(-1).s with an accuracy of +/-2.5% and lung volumes 75-300 mL with an accuracy of +/-2.5% under in vitro conditions. To conclude, the infant lung model is a useful means of assessing the overall in vitro performance of infant whole-body plethysmographs, but thermal, mechanical and frequency response characteristics of such a device must be taken into account when interpreting the results of such assessments. (+info)
Evaluation of impulse oscillation system: comparison with forced oscillation technique and body plethysmography.
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The impulse oscillation system (IOS) has been developed recently to measure respiratory system resistance (Rrs) and reactance (Xrs) at different frequencies up to > or = 25 Hz. IOS has, however, not been validated against established techniques. This study compared IOS with the classical pseudorandom noise forced oscillation technique (FOT) and body plethysmographic airway resistance (Raw) in 49 subjects with a variety of lung disorders and a wide range of Raw (0.10-1.28 kPa x L(-1) x s). Rrs,IOS was slightly greater than Rrs,FOT, especially at lower frequencies, with a mean +/- SD difference at 5-6 Hz of 0.14 +/- 0.09 kPa x L(-1) x s. Comparisons with the wave-tube technique applied on two analogues indicated an overestimation by IOS. Xrs,IOS and Xrs,FOT were very similar, with a slightly higher resonant frequency with IOS than with FOT (mean difference +/- SD 1.35 +/- 3.40 Hz). Raw was only moderately correlated with Rrn,FOT and Rrs-IOS; although the mean differences were small (0.04 +/- 0.14 kPa x L(-1)s for Rrs6,FOT and -0.10 +/- 0.14 kPa x L(-1) x s for Rrs5,IOS), IOS and FOT markedly underestimated high resistance values. In conclusion, the impulse oscillation system yields respiratory system resistance and reactance values similar, but not identical to those provided by the forced oscillation technique. (+info)
Genes other than TLR4 are involved in the response to inhaled LPS.
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For several decades, the mouse strains C3H/HeJ and C57BL/10ScNCr have been known to be hyporesponsive to endotoxin or lipopolysaccharide (LPS). Recently, mutations in Toll-like receptor (TLR) 4 have been shown to underlie this aberrant response to LPS. To further determine the relationship between TLR4 and responsiveness to LPS, we genotyped 18 strains of mice for TLR4 and evaluated the physiological and biological responses of these strains to inhaled LPS. Of the 18 strains tested, 6 were wild type for TLR4 and 12 had mutations in TLR4. Of those strains with TLR4 mutations, nine had mutations in highly conserved residues. Among the strains wild type for TLR4, the inflammatory response in the airway induced by inhalation of LPS showed a phenotype ranging from very sensitive (DBA/2) to hyporesponsive (C57BL/6). A broad spectrum of airway hyperreactivity after inhalation of LPS was also observed among strains wild type for TLR4. Although the TLR4 mutant strains C3H/HeJ and C57BL/10ScNCr were phenotypically distinct from the other strains with mutations in the TLR4 gene, the other strains with mutations for TLR4 demonstrated a broad distribution in their physiological and biological responses to inhaled LPS. The results of our study indicate that although certain TLR4 mutations can be linked to a change in the LPS response phenotype, additional genes are clearly involved in determining the physiological and biological responses to inhaled LPS in mammals. (+info)