Early‐ and late‐phase bronchoconstriction, airway hyper‐reactivity and cell influx into the lungs, after 5′‐adenosine monophosphate inhalation: comparison with ovalbumin

Smith, Nicola J.; Johnson, Frederick J.

doi:10.1111/j.1365-2222.2005.02211.x

Cited by 14 publications

(13 citation statements)

References 30 publications

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“…Inhaled AMP acts through A2B receptors and is thought to result in bronchoconstriction via mast-cell degranulation that releases histamine and other cytokines [16]. Inhaled AMP increased the eosinophil count in the lungs in a sensitized animal model [17]. Recruited eosinophils may reflect an overall increased inflammatory activity, increasing the production of cytokines that stimulate mast cells directly and indirectly.…”

Section: Discussionmentioning

confidence: 99%

Exhaled Nitric Oxide and Airway Hyperresponsiveness to Adenosine 5′-monophosphate and Methacholine in Children with Asthma

Perzanowski

Yoo²

2015

Int Arch Allergy Immunol

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Background: There is increasing interest in the role of indirect bronchial challenges because clinical studies have shown that indirect airway hyperresponsiveness (AHR) reflects underlying airway inflammation better than direct AHR. Fractional exhaled nitric oxide (FeNO) appears to be a useful clinical tool for assessing airway inflammation noninvasively. We examined whether FeNO is more closely related to AHR to indirect stimuli than AHR to direct stimuli in children with mild to moderate asthma. Methods: Fifty-nine asthmatic children aged 6-16 years without rhinitis, underwent spirometry, FeNO measurement and blood tests for serum total IgE, blood eosinophil count and serum eosinophil cationic protein (ECP). All subjects underwent methacholine and adenosine 5-monophosphate (AMP) challenge tests at intervals of 3 days. Results: In a univariate linear regression analysis, FeNO was significantly associated with both PC₂₀ AMP (R² = 0.341, p < 0.001) and PC₂₀ methacholine (R² = 0.188, p = 0.001). After adjustment for age, sex, serum total IgE and blood eosinophil count, the association between FeNO and PC₂₀ AMP (β = -1.98, p = 0.001) was more robust than that between FeNO and PC₂₀ methacholine (β = -0.87, p = 0.081). The significant correlation between FeNO and PC₂₀ AMP was observed in the steroid-naïve group (β = -2.48, p = 0.001), but not in the steroid-treated group (β = 0.88, p = 0.463). Conclusions: FeNO levels were more closely associated with PC₂₀ AMP than with PC₂₀ methacholine. This relationship could only be seen in the steroid-naïve subjects. These results suggest that FeNO levels in children with asthma may be more closely related to indirect AHR than to direct AHR.

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Section: Discussionmentioning

confidence: 99%

Exhaled Nitric Oxide and Airway Hyperresponsiveness to Adenosine 5′-monophosphate and Methacholine in Children with Asthma

Perzanowski

Yoo²

2015

Int Arch Allergy Immunol

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“…Despite this enormous variation, the general technique for inducing 'asthma' in laboratory animals involves sensitizing their immune system to a previously unseen antigen and subsequently challenging the airways with the same antigen in order to study the cascade of events or a distant outcome parameter of interest that occurs some time after the challenge. There are an enormous number of techniques for achieving this and it is not possible to provide a comprehensive list but a good starting point is the general OVA protocol that is the most common and is used primarily in the smaller species including mice [41], rats [72] and guinea-pigs [84]. This technique usually involves sensitizing the animal systemically via intraperitoneal injection with the antigen and an adjuvant, usually aluminium hydroxide (alum), to prime the immune system to respond in the desired way [103].…”

Section: Extrapolating To Humansmentioning

confidence: 99%

Animal models of asthma

Zosky

Sly

2007

Clin Experimental Allergy

261

195

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SummaryAnimal models of asthma are a tool that allows studies to be conducted in the setting of an intact immune and respiratory system. These models have highlighted the importance of T-helper type 2 driven allergic responses in the progression of asthma and have been useful in the identification of potential drug targets for interventions involving allergic pathways. However, a number of drugs that have been shown to have some efficacy in animal models of asthma have shown little clinical benefit in human asthmatics. This may be due to a number of factors including the species of animal chosen and the methods used to induce an asthmatic phenotype in animals that do not normally develop a disease that could be characterized as asthma. The range of animal models available is vast, with the most popular models being rodents (inbred mice and rats) and guinea-pigs, which have the benefit of being easy to handle and being relatively cost effective compared with other models that are available. The recent advances in transgenic technology and the development of species-specific probes, particularly in mice, have allowed detailed mechanistic studies to be conducted. Despite these advances in technology, there are a number of issues with current animal models of asthma that must be recognized including the disparity in immunology and anatomy between these species and humans, the requirement for adjuvant during senitization in most models, the acute nature of the allergic response that is induced and the use of adult animals as the primary disease model. Some larger animal models using sheep and dogs have been developed that may address some of these issues but they also have different biology from humans in many ways and are extremely costly, with very few probes available for characterizing allergic responses in the airway in these species. As research in this area continues to expand, the relative merits and limitations of each model must be defined and understood in order to evaluate the information that is obtained from these models and to extrapolate these findings to humans so that effective drug therapies can be developed. Despite these issues, animal models have been, and will continue to be, vital in understanding the mechanisms that are involved in the development and progression of asthma.

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“…For example, asthma is characterized by a biphasic bronchospasm response, consisting of an earlyphase asthmatic response and a late-phase asthmatic response (LAR) Smith and Johnson, 2005). The previously introduced HDM animal model is able to mimic both early-phase asthmatic response and LAR (Hatzivlassiou et al, 2010), contributing to its popularity in the field.…”

Section: Mechanism Of Eosinophilia In Asthmamentioning

confidence: 98%