An Animal Model for Lung Volume Reduction Therapy of Pulmonary Emphysema

Chen, John C.; Brenner, Matthew; Kafie, Fernando E.; Yoong, Benedid; Budd, Michael; Gassel, Adam; Waite, Teri A.; Millikan, Jeff; Huh, Joe; Wang, Nai‐San; McKenna, Robert J.; Gelb, Arthur F.; Wilson, Archie F.; Berns, Michael W.

doi:10.3109/08941939809032192

Cited by 9 publications

(8 citation statements)

References 6 publications

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“…This model is used to induce inflammatory responses to initiate and perpetuate the inflammatory response seen in COPD [12, 87, 88]. The major advantages of the elastase model are the technical ease of inducing the disease by a single instillation of the enzyme in the lung and the ability to control the disease severity by adjusting the amount of enzyme [9, 16, 89, 90]. However, the disadvantage of the elastase model is that the function of elastase in COPD emphysema depends on several pathophysiological mechanisms which again brings up the number of clinical events [12, 91, 92].…”

Section: Elastasementioning

confidence: 99%

Experimental animal models for COPD: a methodological review

Ghorani¹,

Boskabady²,

Khazdair³

et al. 2017

Tob. Induced Dis.

170

111

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IntroductionChronic obstructive pulmonary disease (COPD) is a progressive disorder that makes the breathing difficult and is characterized by pathological conditions ranging from chronic inflammation to tissue proteolysis. With regard to ethical issues related to the studies on patients with COPD, the use of animal models of COPD is inevitable. Animal models improve our knowledge about the basic mechanisms underlying COPD physiology, pathophysiology and treatment. Although these models are only able to mimic some of the features of the disease, they are valuable for further investigation of mechanisms involved in human COPD.MethodsWe searched the literature available in Google Scholar, PubMed and ScienceDirect databases for English articles published until November 2015. For this purpose, we used 5 keywords for COPD, 3 for animal models, 4 for exposure methods, 3 for pathophysiological changes and 3 for biomarkers. One hundred and fifty-one studies were considered eligible for inclusion in this review.ResultsAccording to the reviewed articles, animal models of COPD are mainly induced in mice, guinea pigs and rats. In most of the studies, this model was induced by exposure to cigarette smoke (CS), intra-tracheal lipopolysaccharide (LPS) and intranasal elastase. There were variations in time course and dose of inducers used in different studies. The main measured parameters were lung pathological data and lung inflammation (both inflammatory cells and inflammatory mediators) in most of the studies and tracheal responsiveness (TR) in only few studies.ConclusionThe present review provides various methods used for induction of animal models of COPD, different animals used (mainly mice, guinea pigs and rats) and measured parameters. The information provided in this review is valuable for choosing appropriate animal, method of induction and selecting parameters to be measured in studies concerning COPD.

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Section: Elastasementioning

confidence: 99%

Experimental animal models for COPD: a methodological review

Ghorani¹,

Boskabady²,

Khazdair³

et al. 2017

Tob. Induced Dis.

170

111

View full text Add to dashboard Cite

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“…Disease severity can be controlled by selection of enzyme dose. As opposed to smoke-induced emphysema, it is relatively easy to produce severe emphysema with elastase instillation, and this facilitates detection of pulmonary function abnormalities, particularly when evaluating the effects of an inhibitor or intervention such as lung volume reduction surgery or abnormalities in connective tissue elasticity (15,51). Biochemical and in situ hybridization studies have shown that over time there is increased synthesis of elastin and to a lesser extent collagen (77), making the model a candidate for studies on alveolar repair and regeneration [however, studies using all trans retinoic acid and/or bone marrow cell instillation or various colony-stimulating factors to attempt to drive repair are contradictory (49,50,76,102,164)].…”

Section: Elastase Emphysema Modelmentioning

confidence: 99%

Animal models of chronic obstructive pulmonary disease

Wright¹,

Cosio²,

Churg³

2008

American Journal of Physiology-Lung Cellular and Molecular Phys

379

326

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-The mechanisms involved in the genesis of chronic obstructive pulmonary disease (COPD) are poorly defined. This area is complicated and difficult to model because COPD consists of four separate anatomic lesions (emphysema, small airway remodeling, pulmonary hypertension, and chronic bronchitis) and a functional lesion, acute exacerbation; moreover, the disease in humans develops over decades. This review discusses the various animal models that have been used to attempt to recreate human COPD and the advantages and disadvantages of each. None of the models reproduces the exact changes seen in humans, but cigarette smoke-induced disease appears to come the closest, and genetically modified animals also, in some instances, shed light on processes that appear to play a role. chronic obstructive pulmonary disease CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) is an increasingly important cause of morbidity and mortality. COPD is now the fifth leading cause of death worldwide (109), and recent estimates suggest that the prevalence is as high as 9 -10% of adults over age 40 (38, 131). In the developed world, cigarette smoking is by far the most important risk factor for COPD. Exposure to air pollution particles, occupational exposures to dusts and fumes (39), and, in the developing world, exposure to biomass fuels used for cooking is also believed to be etiological agents of COPD (38).There are few animal models of COPD related to air pollution particles, dusts and fumes, and biomass fuels; most COPD models have either used cigarette smoke or other approaches, including genetic modifications to mice, believed to reproduce some of the mechanisms behind cigarette smoke. We have recently reviewed mechanistic studies of smoke-exposed animal models (16). In this paper, we will focus on the pros and cons of different COPD animal models.The first question to ask in this context is what would constitute a perfect model of human COPD. This is not a simple question because human COPD consists of at least four anatomic lesions (further defined below): emphysema, small airway remodeling (including goblet cell metaplasia), chronic bronchitis, and pulmonary hypertension; a given patient may have any or all of these lesions. In addition, COPD patients may develop acute exacerbations that are believed to have an infectious basis. To further complicate matters, no matter which lesions are present, COPD develops and is slowly progressive over many years.Because COPD is closely related to the underlying anatomy of the lung, a good animal model should have pulmonary anatomy similar to that of humans. The fundamental mechanisms behind COPD should be similar in animal models and humans. The ideal model would allow the investigator to produce the various different anatomic lesions just listed, all in a short period of time. Unfortunately, all of the known animal models meet only some of the above criteria, and even another human would probably not meet all of them, because, as noted above, there is considerable human to human variation in th...

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“…To evaluate the method's effectiveness in improving respiratory function, Chen et al 12 induced pulmonary emphysema in a rabbit model using aerosolized porcine elastase and performed stapled lung volume reduction. They observed that the static compliance decreased significantly immediately after the operation, and thereafter returned to its preoperative value at 1 week postoperatively; however, they also noted an increase in forced expiratory flow and a decrease in expiratory resistance.…”

Section: Discussionmentioning

confidence: 99%