Methacholine-induced pulmonary gas trapping in guinea pigs, hamsters, mice, and rats

Stengel, Peter W.; Yiamouyiannis, Carmen A.; Obenchain, Robert L.; Silbaugh, Steven A.

doi:10.1152/jappl.1995.79.6.2148

Cited by 16 publications

(17 citation statements)

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“…Relative to other small mammalian species, guinea pigs are far more susceptible to gas trapping during bronchospasm. Figure modified from [308]. Table 2 Cloned and characterized guinea pig genes: autacoid and nerve related genes relevant to asthma and COPD…”

Section: Discussionmentioning

confidence: 99%

“…There is no comparable respiratory maneuver in guinea pigs. Relative to other species, the guinea pig is considered "hyperresponsive" even at baseline, given their tendency to constrict excessively, leading to airway closure, gas trapping and ultimately collapse [308]. In vitro studies of guinea pig airway smooth muscle responsiveness do not support the notion that the guinea pig is uniquely responsive to contractile agonists.…”

Section: Airways Hyperresponsivenessmentioning

confidence: 99%

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Using guinea pigs in studies relevant to asthma and COPD

Canning

Chou

2008

Pulmonary Pharmacology & Therapeutics

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The guinea pig has been the most commonly used small animal species in preclinical studies related to asthma and COPD. The primary advantages of the guinea pig are the similar potencies and efficacies of agonists and antagonists in human and guinea pig airways and the many similarities in physiological processes, especially airway autonomic control and the response to allergen. The primary disadvantages to using guinea pigs are the lack of transgenic methods, limited numbers of guinea pig strains for comparative studies and a prominent axon reflex that is unlikely to be present in human airways. These attributes and various models developed in guinea pigs are discussed.

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Section: Discussionmentioning

confidence: 99%

Section: Airways Hyperresponsivenessmentioning

confidence: 99%

Using guinea pigs in studies relevant to asthma and COPD

Canning

Chou

2008

Pulmonary Pharmacology & Therapeutics

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“…The lungs and trachea were removed and trimmed of nonpulmonary tissue. ELGV was measured as previously described 26 and compared with values in control, unexposed mice.…”

Section: Measurement Of Airway Hyperreactivity: Excised Lung Gas Volumementioning

confidence: 99%

Shifts in Lung Lymphocyte Profiles Correlate with the Sequential Development of Acute Allergic and Chronic Tolerant Stages in a Murine Asthma Model

Yiamouyiannis

Schramm

Puddington

et al. 1999

The American Journal of Pathology

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T lymphocytes have a central regulatory role in the pathogenesis of asthma. We delineated the participation of lymphocytes in the acute allergic and chronic tolerant stages of a murine model of asthma by characterizing the various subsets of lymphocytes in bronchoalveolar lavage and lung tissue associated with these responses. Acute (10-day) aerosol challenge of immunized C57BL/6J mice with ovalbumin resulted in airway eosinophilia , histological evidence of peribronchial and perivascular airway inflammation, clusters of B cells and TCR␥␦ cells in lung tissue, increased serum IgE levels , and airway hyperresponsiveness to methacholine. In mice subjected to chronic (6-week) aerosol challenge with ovalbumin, airway inflammation and serum IgE levels were significantly attenuated and airway hyperresponsiveness was absent. The marked increases in lung B and T cell populations seen in the acute stage were also significantly reduced in the chronic stage of this model. Thus , acute ovalbumin challenge resulted in airway sensitization characteristic of asthma, whereas chronic ovalbumin challenge elicited a suppressed or tolerant state. The transition from antigenic sensitization to tolerance was accompanied by shifts in lymphocyte profiles in the lung and bronchoalveolar lavage fluid. Asthma is the most common chronic illness in developed countries. Our current understanding of the pathophysiology of allergic asthma is that it occurs from a breakdown of the normal tolerance to inhaled antigens, as a result of complex interactions between host and environmental factors. Emerging evidence suggests that the development of clinical sensitivity versus normal tolerance to inhaled antigens involves the establishment of a dominant population of CD4 ϩ T lymphocytes that are either classified as Th2-like (sensitization) or Th1-like (tolerance).1 Th2 responses are characterized by secretion of the cytokines interleukin (IL)-4 and IL-13, which induce the production of IgE by B cells, 2-5 and IL-5, which regulates the growth, differentiation, and activation of eosinophils.6 Conversely, Th1 responses are characterized by secretion of IL-2, tumor necrosis factor (TNF)-␤, and interferon (IFN)-␥. IFN-␥ has been shown to stimulate low-level IgG production and to potently inhibit IL-4-mediated IgE responses both in vivo and in vitro.7 The mechanisms that control CD4 ϩ T lymphocyte polarization into either Th1 or Th2 phenotypes are incompletely understood but appear to involve genetic predispositions, local factors such as existing cytokine concentrations and inflammation, and antigenic factors such as the potency, dose, and duration of exposure of the eliciting antigen. In susceptible individuals, antigen sensitization results in specific local and systemic IgE production and airway eosinophilia, which in turn induce the airway inflammation, airway hyperresponsiveness, and reversible airway obstruction characteristic of asthma.The factors influencing antigen sensitization or tolerance can be better studied in mice, given their well defined...

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“…The lung weight values reflect lung inflammatory oedema while the values for ELGV reflect the severity of bronchoconstriction, mucus plugging, and also to a certain extent, oedema [8]. We have also observed that the inflammatory as compared to 5% decrease (p=0.97) by conventional best practice therapy (based on maintenance dosing) [12].…”

Section: Discussionmentioning

confidence: 54%

“…We evaluated the effects of dosing regimens on two different parameters: excised lung gas volume (ELGV), a measure of gas trapped by bronchoconstriction [7,8] and lung weight, an indicator of oedema and inflammation. The initial two studies …”

Section: Introductionmentioning

confidence: 99%

Sensitivity of disease parameters to flexible budesonide/formoterol treatment in an allergic rat model

Brange

Smailagic

Jansson

et al. 2009

Pulmonary Pharmacology & Therapeutics

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Rationale: Clinical studies show that flexible dosing (maintenance and symptom-driven dose adjustments) of budesonide and formoterol (BUD/FORM) improves control of asthma exacerbations as compared to fixed maintenance dosing protocols (maintenance therapy) even when the latter utilize higher BUD/FORM doses. This suggests that dose-response relationships for certain pathobiologic mechanisms in asthma shift over time.Here, we have conducted animal studies to address this issue. Objectives: 1)To test in an animal asthma-like model whether it is possible to achieve the same or greater pharmacological control over bronchoconstriction and airway/lung inflammation, and with less total drug used, by flexible BUD/FORM dosing (upward adjustment of doses) in association with allergen challenges. 2) To determine whether the benefit requires adjustment of both drug components. Methods: Rats sensitized on day 0 and 7 were challenged intratracheally with ovalbumin on day 14 and 21. On days 13 through 21, rats were treated intratracheally with fixed maintenance or flexible BUD/FORM combinations. On day 22, rats were challenged with methacholine and lungs were harvested for analysis. Results: A flexible BUD/FORM dosing regimen (using 3.3 times less total drug than the fixed maintenance high dose regimen), delivered the same or greater reductions of excised lung gas volume (a measure of gas trapped in lung by bronchoconstriction) and lung weight (a measure of inflammatory oedema). When either BUD or FORM alone was increased on days of challenge, the benefit of the flexible dose upward adjustment was lost. Conclusions: Flexible dosing of the BUD/FORM combination improves the pharmacological inhibition of allergen-induced bronchoconstriction and an inflammatory oedema in an allergic asthma-like rat model.

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Methacholine-induced pulmonary gas trapping in guinea pigs, hamsters, mice, and rats

Cited by 16 publications

References 0 publications

Using guinea pigs in studies relevant to asthma and COPD

Using guinea pigs in studies relevant to asthma and COPD

Shifts in Lung Lymphocyte Profiles Correlate with the Sequential Development of Acute Allergic and Chronic Tolerant Stages in a Murine Asthma Model

Sensitivity of disease parameters to flexible budesonide/formoterol treatment in an allergic rat model

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