Providing Detailed Insight Into Lung Inflammatory Responses
The emergence of novel zoonotic outbreaks such as the 2019-nCoV coronavirus continue to result in high mortality rates, as seen in previous epidemics (i.e SARS & MERS). Coronaviruses are a family of viruses that can cause severe respiratory illnesses and infections, leading to impaired lung function and respiratory failure manifestations such as Acute Respiratory Distress Syndrome (ARDS). Current treatment includes antibiotics, corticosteroids and oxygen support via mechanical ventilation, but no effective vaccines have been developed. Further preclinical and clinical studies are required to investigate the pathophysiology of these diseases, which remains poorly understood.
Providing a detailed insight into lung inflammatory responses and function throughout the progression or treatment of infectious respiratory diseases, the flexiVent can help researchers advance our understanding surrounding the mechanisms of host response and pathogenesis of viruses. These insights will allow for fastest countermeasure developments, with hopes of preventing the rapid spread of current viruses such as the 2019-nCoV, and those of possible future zoonotic events.
Airway Hyperresponsiveness Assessement Upon Infection
During the 2009 Swine Flu pandemic, a subset of asthmatic patients showed significant resistance to influenza morbidity which drove researchers to develop preclinical models to try and recapitulate these findings. In the study referenced below, Palipane, M. et al. investigated the host-pathogen mechanisms in asthma and influenza co-morbidity, specifically the role of CD14 in macrophage’s immune response. The flexiVent system was used to assess airway hyperresponsiveness (AHR) through airway resistance measurements following dose response challenges in five groups (Naïve, Flu-control, Asthma-control, and AA + Flu). Their results showed a decrease in AHR in the asthma-influenza co-occurrence group (AA + Flu), while the asthma and flu-control groups showed elevated resistance, suggesting a pro-inflammatory role of CD14 which contributes to enhanced immune protection.
- Palipane, M. et al. (2019). Macrophage CD14 impacts immune defenses against influenza virus in allergic hosts. Microbial Pathogenesis Volume 127, February 2019, Pages 212-219
Lung Physiology Assessement Upon Infection
As opposed to Influenza A Virus (IVA) which has been extensively studied by researchers, Influenza B Virus (IVB) remains under investigated. In an effort of further elucidating the host-response pathways following IVB infection, Dumm, R. E. et al investigated the hypothesis that certain epithelial cells can survive IVB infection and confer lung barrier protection. The flexiVent system was used to measure compliance in mice either harboring or depleted from survivor cells. Their results showed that mice depleted from the survivor cell population had decreased compliance, suggesting that these cells contribute to preservation of the epithelial barrier and thus help maintain lung function following infection.
- Dumm, R. E. et al. (2019). Non-lytic clearance of influenza B virus from infected cells preserves epithelial barrier function. Nature Communications. 10(1), p. 779. 2019.
Drug Delivery And Therapeutics Assessment.
In a recently published study, Umstead et al. used the flexiVent as an intervention tool to develop a mouse model of inhaled recombinant GM-CSF through nebulization. Subsequent evaluation of the therapeutic potential conferred by this treatment was performed after secondary challenge with pneumococcus during influenza A virus (IAV) infection.
- Umstead, T. M., et al. (2020). Lower Respiratory Tract Delivery, Airway Clearance, and Preclinical Efficacy of Inhaled GM-CSF in a Post-influenza Pneumococcal Pneumonia Model. American Journal of Physiology-Lung Cellular and Molecular Physiology. doi: 10.1152/ajplung.00296.2019
More Pulmonary Solutions
The inExpose administers drugs and novel therapeutic carriers through
the inhalation pathway, a preferential route for preclinical models.
It standardizes experimental conditions providing reproducible
and relevant animal model.
The vivoFlow whole-body plethysmograph tracks changes in ventilatory parameters
throughout the progression of a respiratory infection. This technique provides
continuous high-fidelity respiratory recordings including measures of
respiratory rate, estimated tidal volumes and minute ventilation.