House dust mite models: Will they translate clinically as a superior model of asthma?

Phillips, Jonathan E.; Peng, Ruoqi; Harmatz, Paul; Burns, Lisa; Renteria, Lorena; Lundblad, Lennart K. A.; Fine, Jay S.; Bauer, Carla M. T.; Stevenson, Christopher S.

doi:10.1016/j.jaci.2012.12.1571

Cited by 13 publications

(12 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, models extending re‐exposure past four challenges have reported LAR in mice [Nabe et al, ], although there is a small window before tolerance to ovalbumin occurs. In the HDM model, an EAR is evident following 3 weeks of challenge but not following 1 week, despite elevated airway inflammation at both time points [Phillips et al, ]. To the best of our knowledge we are unaware of any studies which have investigated the LAR in HDM models of asthma.…”

Section: Evaluating the Mouse In Models Of Asthmamentioning

confidence: 99%

Animal Models of Allergic Airways Disease: Where Are We and Where to Next?

Chapman

Tully

Nolin

et al. 2014

J of Cellular Biochemistry

View full text Add to dashboard Cite

In a complex inflammatory airways disease such as asthma, abnormalities in a plethora of molecular and cellular pathways ultimately culminate in characteristic impairments in respiratory function. The ability to study disease pathophysiology in the setting of a functioning immune and respiratory system therefore makes mouse models an invaluable tool in translational research. Despite the vast understanding of inflammatory airways diseases gained from mouse models to date, concern over the validity of mouse models continues to grow. Therefore the aim of this review is two-fold; firstly, to evaluate mouse models of asthma in light of current clinical definitions, and secondly, to provide a framework by which mouse models can be continually refined so that they continue to stand at the forefront of translational science. Indeed, it is in viewing mouse models as a continual work in progress that we will be able to target our research to those patient populations in whom current therapies are insufficient.

show abstract

Section: Evaluating the Mouse In Models Of Asthmamentioning

confidence: 99%

Animal Models of Allergic Airways Disease: Where Are We and Where to Next?

Chapman

Tully

Nolin

et al. 2014

J of Cellular Biochemistry

View full text Add to dashboard Cite

show abstract

“…For example, intraperitoneal injection of crude extracts of house dust mite (HDM) from Dermatophagoides pteronyssinus in guinea pigs elicits Th2 sensitization and antigen challenge-induced bronchoconstriction (23), whereas bronchial anaphylactic reactions have been observed in sensitized Sprague Dawley rats following intravenous challenge with OVA (14). We recently demonstrated similar effects in mice that were subjected to sensitization inhalation exposure to HDM (39). In addition, allergic sheep exposed to inhaled tryptase, a mast cell serine protease released during mast cell activation, exhibit both bronchoconstriction and AHR, further implicating a role for mast cellderived mediators (34).…”

mentioning

confidence: 99%

Antigen-induced mast cell expansion and bronchoconstriction in a mouse model of asthma

Aliyeva

Daphtary

et al. 2014

American Journal of Physiology-Lung Cellular and Molecular Phys

Self Cite

View full text Add to dashboard Cite

Lung mastocytosis and antigen-induced bronchoconstriction are common features in allergic asthmatics. It is therefore important that animal models of asthma show similar features of mast cell inflammation and reactivity to inhaled allergen. We hypothesized that house dust mite (HDM) would induce mastocytosis in the lung and that inhalation of HDM would trigger bronchoconstriction. Mice were sensitized with intranasal HDM extract, and the acute response to nebulized HDM or the mast cell degranulating compound 48/80 was measured with respiratory input impedance. Using the constant-phase model we calculated Newtonian resistance (Rn) reflecting the conducting airways, tissue dampening (G), and lung elastance (H). Bronchoalveolar lavage fluid was analyzed for mouse mast cell protease-1 (mMCP-1). Lung tissue was analyzed for cytokines, histamine, and α-smooth muscle actin (α-SMA), and histological slides were stained for mast cells. HDM significantly increased Rn but H and G remained unchanged. HDM significantly expanded mast cells compared with control mice; at the same time mMCP-1, α-SMA, Th2 cytokines, and histamine were significantly increased. Compound 48/80 inhalation caused bronchoconstriction and mMCP-1 elevation similarly to HDM inhalation. Bronchoconstriction was eliminated in mast cell-deficient mice. We found that antigen-induced acute bronchoconstriction has a distinct phenotype in mice. HDM sensitization caused lung mastocytosis, and we conclude that inhalation of HDM caused degranulation of mast cells leading to an acute bronchoconstriction without affecting the lung periphery and that mast cell-derived mediators are responsible for the development of the HDM-induced bronchoconstriction in this model.

show abstract

“…The first group of 8 mice was removed from the inhalation unit after 5 min, the second group after 15 min, and the third group after 45 min. Bronchoconstriction 32 was measured as the increase in respiratory system resistance (Rrs) to a single nebulized dose of methacholine (30 mg/mL) delivered 2 h after dosing ipratropium using the rodent respirator 33 . The percent increase in Rrs for each animal, calculated as the maximum Rrs over the 3-min interval after nebulized methacholine (Rmax) minus the Rrs value of the baseline measurement before methacholine (Rbase) divided by Rbase (% increase in Rrs = (Rmax-Rbase)/Rbase), was used to quantitate the bronchoconstriction.…”

Section: Representative Resultsmentioning

confidence: 99%

Dry Powder and Nebulized Aerosol Inhalation of Pharmaceuticals Delivered to Mice Using a Nose-only Exposure System

Phillips

Zhang

Johnston

2017

JoVE

Self Cite

View full text Add to dashboard Cite

Obstructive respiratory diseases like asthma and chronic obstructive pulmonary disease (COPD) are currently treated by inhaled anti-inflammatory and bronchodilator drugs. Despite the availability of multiple treatments, both diseases are growing public health concerns. The majority of asthma patients are well controlled on current inhaled therapies but a substantial number of patients with severe asthma are not. Asthma affects an estimated 300 million people worldwide and approximately 20 percent have a severe form of the disease. In contrast to asthma, there are few effective therapies for COPD. An estimated 10% of the population has COPD and the trend in death rates is increasing for COPD while decreasing for other major diseases. Although developing drugs for inhaled delivery is challenging, the nose-only inhalation unit enables direct delivery of novel drugs to the lung of rodents for pre-clinical efficacy and safety/toxicology studies. Inhaled drug delivery has multiple advantages for respiratory diseases, where high concentration in the lung improves efficacy and minimizes systemic side effects. Inhaled corticosteroids and bronchodilators benefit from these advantages and inhaled delivery may also hold potential for future biologic therapies. The inhalation unit described herein can generate, sample for characterization, and uniformly deposit a drug aerosol in the lungs of rodents. This enables the pre-clinical determination of the efficacy and safety of drug doses deposited in the lungs of rodents, key data required before initiating clinical development.

show abstract

House dust mite models: Will they translate clinically as a superior model of asthma?

Cited by 13 publications

References 7 publications

Animal Models of Allergic Airways Disease: Where Are We and Where to Next?

Animal Models of Allergic Airways Disease: Where Are We and Where to Next?

Antigen-induced mast cell expansion and bronchoconstriction in a mouse model of asthma

Dry Powder and Nebulized Aerosol Inhalation of Pharmaceuticals Delivered to Mice Using a Nose-only Exposure System

Contact Info

Product

Resources

About