Antigen-induced Bronchial Hyperresponsiveness in the Rabbit is not Dependent on M2-receptor Dysfunction

Patel, Hema J; Douglas, Garry J.; Herd, Caroline M.; Spina, Domenico; Giembycz, Mark A.; Barnes, Peter J.; Belvisi, Maria G.; Page, Clive

doi:10.1006/pupt.1999.0204

Cited by 6 publications

(3 citation statements)

References 39 publications

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“…Our data are partially supported by previous in vitro studies, where bronchoconstrictive responses were totally abolished in mice lacking M 3 receptors (26). Additionally, the pathogenesis of airway hyperresponsiveness is related to excessive effect of M 3 muscarinic receptors on the airway smooth muscle (27) and, finally, antigen-induced bronchial hyperresponsiveness does not appear to depend upon M 2 -receptor dysfunction (28). The absence of significant differences after the inhalation of placebo further confirms our hypothesis.…”

Section: Discussionsupporting

confidence: 91%

Isocapnic Cold Air Challenge in Patients with COPD: Are There any Predisposing Factors?

Κostikas

Koutsoumbou

Karamanis³

et al. 2008

COPD: Journal of Chronic Obstructive Pulmonary Disease

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Cold air hyperventilation is an indirect challenge (cold air challenge, CACh) with high specificity and low sensitivity in defining asthmatic subjects. A small proportion of chronic obstructive pulmonary disease (COPD) patients present with positive CACh. The aim of this prospective study was to investigate the presence of factors related to cold air challenge (CACh) in COPD patients. Factors examined were FEV(1), FEV(1)/FVC, reversibility after bronchodilation, eosinophils in induced sputum, bronchial hyperresponsiveness to methacholine and the spirometric response to tiotropium compared to placebo. We studied 92 consecutive COPD patients in order to retrieve 15 CACh positive + patients. Fifteen COPD patients with negative CACh [CACh(-)], randomly selected from the initial group, were added in order to retrieve a group of 30 patients. Spearman's correlation coefficient was used in order to evaluate possible significant correlations between CACh values and study parameters. Sixteen percent of our subjects presented CACh+. CACh values were repeatable with an intraclass correlation coefficient between the two measurements 0.980 (95% CI 0.940-0.993). The only significant correlation observed was between Delta FEV(1) after CACh [Delta(C)FEV(1)] and trough FEV(1) values post tiotropium inhalation (r(2) = 0.62, p < 0.0001). When we analyzed the response to tiotropium in the 2 separate groups we found that patients with CACh+ presented significantly lower values of trough FEV(1) compared to those with CACh(-). In conclusion, a small proportion of COPD patients present with bronchial hyperresponsiveness to CACh. The only parameter related to CACh + in our study was a smaller bronchodilating effect of tiotropium.

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Section: Discussionsupporting

confidence: 91%

Isocapnic Cold Air Challenge in Patients with COPD: Are There any Predisposing Factors?

Κostikas

Koutsoumbou

Karamanis³

et al. 2008

COPD: Journal of Chronic Obstructive Pulmonary Disease

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“…Recent findings demonstrate that GPCR-mediated contraction of ASM strips ex vivo is augmented by various "sensitization" strategies [ 165 ]. These strategies include sensitization to allergen in vivo [ 68 , 112 , 166 , 167 ] or prior exposure of ASM strips ex vivo to cytokines, serum from atopic asthmatics, or immune complexes [ 113 , 168 - 172 ]. Studies of ASM cells suggest that the observed ASM hyperreactivity results in part from an increased calcium flux mediated by sensitized Gq- or Gi-coupled receptor transmembrane signaling.…”

Section: Aberrant Gpcr Signaling and Airway Hyperreactivitymentioning

confidence: 99%

Untitled

Billington¹,

Penn²

2003

Respir Res

183

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Signaling through G protein-coupled receptors (GPCRs) mediates numerous airway smooth muscle (ASM) functions including contraction, growth, and "synthetic" functions that orchestrate airway inflammation and promote remodeling of airway architecture. In this review we provide a comprehensive overview of the GPCRs that have been identified in ASM cells, and discuss the extent to which signaling via these GPCRs has been characterized and linked to distinct ASM functions. In addition, we examine the role of GPCR signaling and its regulation in asthma and asthma treatment, and suggest an integrative model whereby an imbalance of GPCR-derived signals in ASM cells contributes to the asthmatic state.

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“…Furthermore, the route of sensitization influences the immune response. The intraperitoneal route is the route of choice in allergic rabbit models [20,43]. It induces a stronger immune response than the intra-gastric, respiratory, or cutaneous route [44,45] and is also less similar to reallife routes.…”

Section: Plos Onementioning

confidence: 99%

Early exposure to farm dust in an allergic airway inflammation rabbit model: Does it affect bronchial and cough hyperresponsiveness?

et al. 2023

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Introduction Over the past 50 years, the prevalence of allergic respiratory diseases has been increasing. The Hygiene hypothesis explains this progression by the decrease in the bio-diversity of early microbial exposure. This study aims to evaluate the effect of early-life farm exposure on airway hyperresponsiveness and cough hypersensitivity in an allergic airway inflammation rabbit model. Method A specific environment was applied to pregnant rabbits and their offspring until six weeks after birth. Rabbits were housed in a pathogen-free zone for the control group and a calf barn for the farm group. At the end of the specific environmental exposure, both groups were then housed in a conventional zone and then sensitized to ovalbumin. Ten days after sensitization, the rabbit pups received ovalbumin aerosols to provoke airway inflammation. Sensitization to ovalbumin was assessed by specific IgE assay. Cough sensitivity was assessed by mechanical stimulation of the trachea, and bronchial reactivity was assessed by methacholine challenge. The farm environment was characterized by endotoxin measurement. Results A total of 38 rabbit pups were included (18 in the farm group). Endotoxin levels in the farm environment varied from 30 to 1854 EU.m-3. There was no significant difference in specific IgE values to ovalbumin (p = 0.826) between the two groups. The mechanical threshold to elicit a cough did not differ between the two groups (p = 0.492). There was no difference in the number of cough (p = 0.270) or the intensity of ventilatory responses (p = 0.735). After adjusting for age and weight, there was no difference in respiratory resistance before and after methacholine challenge. Conclusion Early exposure to the calf barn did not affect cough sensitivity or bronchial reactivity in ovalbumin-sensitized rabbits. These results suggest that not all farm environments protect against asthma and atopy. Continuous exposure to several sources of microbial diversity is probably needed.

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Antigen-induced Bronchial Hyperresponsiveness in the Rabbit is not Dependent on M2-receptor Dysfunction

Cited by 6 publications

References 39 publications

Isocapnic Cold Air Challenge in Patients with COPD: Are There any Predisposing Factors?

Isocapnic Cold Air Challenge in Patients with COPD: Are There any Predisposing Factors?

Untitled

Early exposure to farm dust in an allergic airway inflammation rabbit model: Does it affect bronchial and cough hyperresponsiveness?

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