Chronic Obstructive Pulmonary Disease
Chronic obstructive pulmonary disease (COPD) is a term used to refer to a set of chronic lung diseases with pulmonary manifestations (e.g. emphysema, chronic bronchitis, or a combination of both) resulting from exposure to inhaled irritants such as cigarette smoke and environmental pollutants. The pulmonary aspects of COPD typically include characteristic lesions, chronic inflammation, excessive mucus production, and a degree of fixed airflow limitation associated with disease severity. This disease is one of the major causes of morbidity and mortality worldwide. In the clinical setting, physicians rely heavily on spirometry and its outcome parameters (e.g. FEV1 and FVC) for diagnosis and monitoring as well as for the assessment of disease severity, as defined by the GOLD scale. Other lung function measurements, such as pressure-volume curves, forced oscillations, or thoracic imaging, are used in addition to bronchoprovocation tests to establish a diagnosis or evaluate disease progression.
COMPREHENSIVE AND INTEGRATED ASSESSMENT
In preclinical research, the challenge is often to link structural changes (e.g. cigarette-smoke induced alveolar destruction) to altered lung function measurements, such as resistance, compliance or spirometry outcomes. The flexiVent is a comprehensive tool allowing an integrated assessment of various disease determinants (e.g. extent and pattern of induced damage) on lung function decline. It measures the mechanical properties of the lungs with high sensitivity and reproducibility. In addition, it reliably evaluates COPD-diseased lungs through pressure-volume curves, changes in lung volume (e.g. inspiratory or forced vital capacities), or forced expiration outcomes, providing clinically relevant information.
- α1-Antitrypsin Determines the Pattern of Emphysema and Function in Tobacco Smoke–exposed Mice – Takubo et al. Am J Respir Crit Care Med., 166: 1596, 2002.
- The development of emphysema in cigarette smoke-exposed mice is strain dependent. – Guerassimov et al. Am J Respir Crit Care Med., 170: 974, 2004.
- Combined forced oscillation and forced expiration measurements in mice for the assessment of airway hyperresponsiveness. – Shalaby et al. Respir Res., 11: 82, 2010.
- Superiority of PC-SOD to other anti-COPD drugs for elastase-induced emphysema and alteration in lung mechanics and respiratory function in mice. – Tanaka et al. Am J Physiol Lung Cell Mol Physiol., 302: L1250, 2012.
- Effects of lecithinized superoxide dismutase and/or pirfenidone against bleomycin-induced pulmonary fibrosis. – Tanaka et al. Chest, 142: 1011, 2012.
COMPACT, REPRODUCIBLE, AUTOMATED
The inExpose is a compact, computer controlled system and can integrate with several smoke generation devices and adapters to suit a wide range of specific smoke applications. Its low internal volume allows desired concentrations to be reached with minimal tobacco quantities. The pumps are specifically designed to deliver standard and customized puff profiles. Industry standards such as the commonly used ISO standard or the Massachusetts or Canadian profiles are often used to generate COPD models.
Smoke composition will be influenced by a number of technical factors. For example, the constituents of smoke will differ whether the smoke is drawn from side-stream, main-stream, or environmental tobacco smoke. Different brands of cigarettes, water filtered smoke (hookah), cigars, or other tobacco smoke preparations will result in different compositions. In addition, the choice of the puff profile will influence cigarette yields. It is therefore important, when studying the impacts of tobacco smoke, to consistently and reproducibly be able to introduce the same smoke composition at each experimental session.
To date, this versatility and programmability of the inExpose system has been employed in a variety of exposure studies, both in vivo and in vitro, to evaluate the effects of smoke.
- SCIREQ Application Note: Reproducible Respiratory Research.
- Identification of differentially expressed proteins in blood plasma of control and cigarette smoke-exposed mice by 2-D DIGE/MS. – Tewari et al. Proteomics, 11: 2051, 2011.
- Early pulmonary events of nose-only water pipe (shisha) smoking exposure in mice. – Nemmar et al. Physiol Rep., 3.3: E12258, 2015.
- Evaluation of the pulmonary effects of short-term nose-only cigarette smoke exposure in mice. – Nemmar et al. Exp Biol Med (Maywood), 237: 1449, 2012.
- Chronic cigarette smoking causes hypertension, increased oxidative stress, impaired NO bioavailability, endothelial dysfunction, and cardiac remodeling in mice. – Talukder et al. Am J Physiol Heart Circ Physiol., 300: H388, 2011.
- Enhancement between environmental tobacco smoke and arsenic on emphysema-like lesions in mice. – Wang et al. J Hazard Mater., 221– 222: 256, 2012.
- Acute secondhand smoke-induced pulmonary inflammation is diminished in RAGE knockout mice. – Wood et al. Am J Physiol Lung Cell Mol Physiol., 307.10: L758-L764, 2014.
- Cystic fibrosis transmembrane conductance regulator activation by roflumilast contributes to therapeutic benefit in chronic bronchitis. – Lambert et al. Am J Respir Cell Mol Biol., 50(3):549-58, 2014.
Symptoms of COPD include dyspnea, chronic cough, and chronic sputum production. Plethysmography, as a non-invasive technique, offers a powerful means of rapidly screening subjects based on changes in ventilatory parameters (e.g. breathing frequency, tidal volume, peak inspiratory or expiratory flows). Events such as coughing can also be detected and monitored.
- Effects of cigarette smoke and chronic hypoxia on airways remodeling and resistance. Clinical significance. – Olea et al. Respir Physiol Neurobiol., 15;179(2-3):305-13, 2011.
- Extracellular matrix defects in aneurysmal Fibulin-4 mice predispose to lung emphysema. – Ramnath et al. PLOS ONe, 9(9):e106054, 2014.
- Use of cyclodextrin for treatment and prevention of bronchial inflammatory diseases. – Cataldo, Didier. Patent application US 13/804,626.