Chest
Animal Models of Cigarette Smoke-Induced COPD*
Section snippets
Emphysema Types
There is much literature detailing the descriptions of emphysematous lung destruction in cigarette smokers.1 In general, the majority of the emphysema produced by smoke is of the centriacinar type, although panacinar emphysema may occur in conjunction with centriacinar emphysema.
There is also no doubt that chronic exposure of animals to cigarette smoke will produce emphysema, as defined by the National Heart, Lung, and Blood Institute.2 The length of time required to produce emphysema varies
Epithelial Cell Alterations
Goblet cell metaplasia is a frequent finding in the large and small airways of cigarette smokers,2627 but it has been difficult to find consistent results, probably due to sampling difficulties because the metaplastic cells are not randomly distributed, but occur in clusters. Metaplasia is also a frequent feature in asthmatic large and small airways.
In animals, secretory cell metaplasia as a response to cigarette smoke appears to be of greater intensity than that found in humans. Workers have
Airway Wall Alterations
In humans, the structure of the larger airways has been examined, with evidence of muscle thickening, particularly in those subjects with airflow obstruction, although there was a wide degree of variation in any group examined and there may also be variation from site to site.32 In examining biopsy specimens from the larger airways of cigarette smokers, it appears that when both chronic bronchitis and airflow obstruction exists, there are increases in the overall T-cell population,3334 with
Alterations of the Pulmonary Vasculature
In humans, 6% of subjects with COPD will acquire pulmonary hypertension and, ultimately, cor pulmonale. Morphometric examination of the pulmonary vascular tree has demonstrated intimal and medial thickening of the muscular arteries, and muscularization of the small arteries/arterioles, which appeared to have a progressive increase in severity from nonsmokers to smokers without COPD to smokers with COPD.41
To our knowledge, the only model in which the vasculature has been examined is the guinea
Alterations of Cytokines
The cytokine profile in smokers has recently become of great interest to investigators, largely because of the differentiation of the cytokine secretion profiles by the subset of CD4 lymphocytes that become activated. These subsets have been termed T-helper (Th)-1 and Th-2, and each has its characteristic cytokine secretion pattern.45 When bronchial biopsy samples were obtained in current and ex-smokers with chronic bronchitis, and compared with data from nonsmokers, there were increased
Evidence of Cell Proliferation or Induction of Apoptosis
There are few data in humans in regards to the balance between cell proliferation and cellular apoptosis in cigarette smokers. Kasahara et al51 demonstrated an increase in apoptotic cells in the lungs of smokers with emphysema, while there was no difference between the numbers of cells in nonemphysematous smokers and nonsmokers. Interestingly, however, Yasuda and colleagues52 measured plasma sFas, which is an inhibitor of apoptosis and found an increase in those subjects with severe COPD.
In
Systemic Effects
Human smokers, particularly those with COPD, often have significant weight loss, and those patients who lose larger amounts of weight appear to have a greater mortality than those with stable weight.55 Almost all of the models that have evaluated this parameter have demonstrated a failure of smoke-exposed animals to gain weight.692940 We know of no study that has been constructed to determine whether the animals actually lose weight. In our guinea pig model, the smoke-exposed animals weighed
Conclusion
This article has reviewed data from a wide variety of animal models of cigarette smoke-induced lung disease, and compared these results to the information available from human smokers. There is a basic degree of similarity among the studies, although certainly they differ in the degree of abnormalities produced, and the length of exposure time and protocols used to induce the lesions. The lesions of the lung parenchyma are not an absolute mimic of human emphysema, except perhaps in the dog
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2017, Pulmonary Pharmacology and TherapeuticsCitation Excerpt :The release of these inflammatory mediators might lead to further endothelial cell activation, amplified inflammation, and to impaired epithelial barrier function potentially increasing the susceptibility to viral/bacterial infections and subsequent exacerbations [2,7,8]. Pre-clinical models employing cigarette smoke (CS)-exposure are widely used to mimic aspects of airway inflammation [9,10] and have been used previously to link the IL-1 pathway to CS-induced airway inflammation [3,4,11]. Increased IL-1α and IL-1β levels have been detected separately in CS-treated animals and inhibition of the respective signaling pathways resulted in anti-inflammatory activity.
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Supported by grants from the Heart and Stroke Foundation of British Columbia and Yukon, Canadian Institutes of Health Research, and the British Columbia Lung Association.