Infectious Respiratory Diseases
Infectious respiratory diseases are caused by pathogenic microorganisms that can affect the upper (e.g. common cold, sinusitis) and lower (e.g. bronchitis, pneumonia) airways in an acute or a chronic manner. Not only do respiratory infections produce symptoms like sneezing, runny nose, cough or excess mucus production, they may also exacerbate existing respiratory conditions including asthma or Chronic Obstructive Pulmonary Disorder (COPD), leading to airway hyperresponsiveness, airflow obstruction or alterations in gas exchanges. Lower respiratory tract infections (e.g. pneumonia) can result in hospitalization, respiratory failure, or manifestation of Acute Respiratory Distress Syndrome (ARDS). Further preclinical studies are required to investigate the pathophysiology of infectious diseases.
ACCURATE CHALLENGES, DETAILED MEASUREMENTS
The flexiVent’s unique ability to measure central vs. peripheral airways resistance, combined with a delivered dose estimator and an automated dose-response feature permits unique and novel insights into inflammatory responses and evolution of lung function throughout the progression of infectious respiratory diseases.
As respiratory infection induces airway hyperresponsiveness and mucus hypersecretion, the flexiVent can be used to both deliver aerosol challenges to a subject’s lungs and follow the developing bronchoconstriction through automated data collection. The software calculates and displays an estimate of the dose delivered to the subject’s airway opening. Furthermore, detailed dose-response curves demonstrating airway hyperresponsiveness are computed and graphed in real-time. Learn what Dr. Davis, a researcher at the forefront of pulmonary viral infection research, has to say about working with the flexiVent.
REFERENCES
- Halstead, E.S. et al. (2018). GM-CSF overexpression after influenza A virus infection prevents morality and moderates M1-like airway monocyte/macrophage polarization. Respiratory Research, 19(3)
- Coates, B.M., et al. (2018). Inflammatory Monocytes Drive Influenza A Virus-Mediated Lung Injury in Juvenile Mice. The Journal of Immunology, 201(11)
- Wang, H., et al. (2018). CSF3R/CD114 mediates infection-dependent transition to severe asthma. Journal of Allergy and Clinical Immunology, in Press
- Shrestha, B., et al. (2017). IL-4a on Dendritic Cells in Neonates and Th2 Immunopathology in Respiratory Syncytial Virus Inflection. Journal of Leukocyte Biology, 102(5)
- Shibata M., et al. (2017). A Critical Role of Gas6/Axl Signal in Allergic Airway Responses During RSV Vaccine-enhanced Disease. Immunology and Cell Biology, 95; 906-915
- The Antibacterial and Anti-inflammatory Activity of Chicken Cathelicidin-2 combined with Exogenous Surfactant for the Treatment of Cystic Fibrosis-Associated Pathogens – Banaschewski, B. J. H., et al. Scientific Reports, 7(1). 2017.
- Pregnancy preserves pulmonary function following influenza virus infection in C57BL/6 mice – Vermillion, M. S. et al. American Journal of Physiology-Lung Cellular and Molecular Physiology. 315(4), pp. L517–L525. 2018.
- Non-lytic clearance of influenza B virus from infected cells preserves epithelial barrier function – Dumm, R. E. et al. Nature Communications. 10(1), p. 779. 2019.
STANDARDIZED PROCESSES
The administration of drugs or novel therapeutic carriers through inhalation is a desirable route for many preclinical models of respiratory infection. The large surface area and high vascularization of the lung can provide a fast and effective delivery of substances either locally or systemically, via the blood. When considering inhalation as the route for drug delivery, the inExpose standardizes experimental conditions providing reproducible and relevant animal models. Integrated with the Aeroneb nebulizer, the inExpose provides sophisticated computer control which enables automated, precise, and repeatable aerosol exposure sessions to small laboratory animals. Furthermore, the inExpose offers small internal volumes, reducing exposure ramp-up times and minimizing the need for large quantities of material.
REFERENCES
- Aerosol administration increases the efficacy of oseltamivir for the treatment of mice infected with influenza viruses. Leyva-Grado, V. H., & Palese, P. (2017). Antiviral Research, 142, 12–15. 2017.
- Levya-Grado, V.H., & Palese, P. (2017). Aerosol administration increases the efficacy of oseltamivir for the treatment of mice infected with influenza viruses. Antiviral Research, 142: 12-15
- Aeffner, F., et al. (2012). Postinfection A77-1726 Treatment Improves Cardiopulmonary Function in H1N1Influenza-Infected Mice. American Journal of Respiratory Cell and Molecular Biology, 47(4)
- Patterson, C.M., et al. (2012). Inhaled fluticasone propionate impairs pulmonary clearance of Klebsiella Pneumonaie in mice. Respiratory Research, 13(4)
- Levya-Grado, V.H., et al. (2015). Direct Administration in the Respiratory Tract Improves Efficacy of Broadly Neutralizing Anti-Influenza Virus Monoclonal Antibodies. Antimicrobial Agents and Chemotherapy, 59(7) :4162-4172
SYMPTOM SCREENING
In preclinical disease models, the analysis of ventilatory patterns in conscious subjects could prove to be useful for continuous tracking of the progression of infectious respiratory diseases over time.
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) following respiratory infection. Additionally, enhanced pause (Penh) is an indicator of airway obstruction and morbidity, that quantifies changes in the shape of the breathing waveform. Events such as coughing and apneas can also be detected and monitored.
REFERENCES
- Hurst, B.L., et al. (2019). Evaluation of antiviral therapies in respiratory and neurological disease models of Enterovirus D68 infection in mice. Virology, 526(2): 146-154
- Luo, B., et al. (2019). Cold stress provokes lung injury in rats co-exposed to fine particulate matter and lipopolysaccharide. Ecotoxicology and Environmental Safety, 168: 9-16
- Park, S., et al. (2018). Vaccination by microneedle pathc with inactivated respiratory syncytial virus and monophosphoryl lipid A enhances the protective efficacy and diminishes inflammatory disease after challenge. PLOS one
- Hwang, H.S., et al. (2017). Virus-like particle vaccines containing F or F and G proteins confer protection against respiratory syncytial virus without pulmonary inflammation in cotton rats. Human Vaccines & Immunotherapeutics, 13(5): 1031-1039
- Chandler, J.D., et al. (2016). Metabolic pathways of lung inflammation revealed by high-resolution metabolomics (HRM) of H1N1 influenza virus infection in mice. Respiration, 311(5): 906-916
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