The severity of the 2017-2018 influenza season has been one of the most prominent stories of 2018, so far.  It has been a difficult time for patients and a busy one for doctors.  Thankfully, the end of peak season is near!  Although cases can occur as early as October and as late as May, peak influenza season runs annually from December to March.  The Centers for Disease Control and Prevention (CDC) declared this season an epidemic due to the significantly elevated death rates of influenza and pneumonia.  One of the most common reasons for hospitalization and death from influenza is the development of pneumonia ⁶. 

By mid-February, every state in the continental U.S. had experienced extensive influenza activity for the first time since the CDC began monitoring it 13 years ago.³  Many attribute this epidemic to less effective influenza vaccines, as they are performing at about 10-20% effectiveness due to mutations in the virus strain.^4,7  Despite low efficacy, the CDC encourages patients to have the vaccine as it can lessen symptoms if influenza is contracted and potentially reduce pneumonia risk. 

There are multiple forms of pneumonia, and not all instances of it develop from influenza.  However, the two most common types, bacterial and viral, typically develop when the immune system is weakened by other illnesses.⁵  Populations at greater risk for developing pneumonia include those who are over the age of 65 or under age two, are immunocompromised, have pre-existing respiratory conditions, and smoke or abuse alcohol.⁵ 

Although vaccines aid in prevention, about one million people are hospitalized in the United States for pneumonia annually with approximately 50,000 deaths.¹  Because pneumonia often develops from influenza, the annual vaccine helps to protect people who are generally healthy.  For higher risk patients, a pneumonia vaccine is available.  Treatment for pneumonia is limited and most cases are treated at home.⁵  Antibiotics can treat bacterial pneumonia, but viral types do not have a specific treatment.

Pneumonia researchers use DSI equipment to learn more about the disease – its causes, progression, and to evaluate potential treatments.  Below are five DSI systems used to study various aspects of pneumonia followed by a selection of publications citing use.

1. Plethysmography - Whole Body and Head Out

   Plethysmography can be used to monitor pulmonary function and collect various respiratory endpoints, such as respiratory rate, inspiration/expiration, and tidal volume.  These assessments allow researchers to study the progression of pneumonia and its effect on lung function.  It can also be used to evaluate symptom improvement related to various treatment compounds.  A nebulizer can be attached to the chamber to aerosolize compounds. 

   Whole body plethysmography allows animals to move freely and breathe naturally.  Head out plethysmography restrains the animal with a special Allay™ collar which induces less stress than traditional restraining methods and allows the animal to breathe naturally.  The Allay™ also ensures consistent positioning of animals resulting in high-quality data.  As a result, compared with alternative methods, studies performed with the Allay™ restraint are more reproducible and superior for animal welfare.

2. Non-Invasive Airway Mechanics (NAM)

   The Buxco® FinePointe NAM system can be used to study airway resistance, therefore allowing researchers to assess pneumonia development, progression, and symptom improvement from treatment compounds without anesthesia.  Using this system, animals are awake and breathing naturally, providing a realistic representation of the disorder.  A nebulizer can be attached to deliver and control aerosolization of treatment compounds.

3. Resistance and Compliance (RC)

   The Buxco® FinePointe RC system can be used to measure invasive resistance, dynamic compliance, and elastance data.  The subject is anesthetized and instrumented to directly measure their respiratory flow and lung pressure.  This system can be used with either tracheostomized or intubated animals.  Intubation provides the ability to perform longitudinal studies.  An intelligent ventilator supports protocol-driven deep inflations, breath holds and PEEP, allowing researchers to study specific types of breaths rather than simply evaluating the animal’s natural breathing.  The RC system includes an option to incorporate heart rate and blood pressure measurements or a nebulizer for aerosolization to study additional effects of the disorder and evaluate treatment compounds.

4. Pulmonary Function Test (PFT)

   The Buxco® PFT system provides comprehensive PFT data for pre-clinical applications, similar to spirometry in cooperative humans.  This system provides researchers a direct measurement of various aspects of lung function in relation to pneumonia symptoms and progression.  Tests can be performed on anesthetized animals breathing naturally, such as the functional residual capacity (FRC) test.  Ventilators can also be used when necessary.  The PFT system is capable of performing many tests, and additional examples include forced expiratory volume (FEV), forced expiratory flow (FEF). 

5. Inhalation Tower

DSI’s Buxco® Inhalation Tower can be used to aerosolize a virus, such as influenza, to study the progression and development of pneumonia.  It can also be used to aerosolize treatment compounds for evaluation.

The inhalation tower features a “flow past” concentric design, delivering the same exposure to all animals and eliminating re-breathing.  The tower also incorporates the Allay™ restraint to ensure animals are all positioned correctly, are less stressed than with alternative methods, and each animal’s thorax is not compressed.  All of these variables can affect exposure levels.  When positioned properly, animals receive the same exposure throughout the tower.

Pneumonia publications citing DSI technology:

• Hsieh T, Vaickus MH, Stein TD, Lussier BL, Kim J, Stepien DM, Duffy ER, Chiswick EL, Remick DG. (2016). “The Role of Substance P in Pulmonary Clearance of Bacteria in Comparative Injury Models.” The American Journal of Pathology. 186(12); 3236-3245. https://doi.org/10.1016/j.ajpath.2016.08.014
• Kling H, Shipley T, Guyach S, Tarantelli R, Morris A, Norris K. (2014). “Trimethoprim-Sulfamethoxazole Treatment Does Not Reverse Obstructive Pulmonary Changes in Pneumocystis-Colonized Non-Human Primates with SHIV Infection.” Journal of Acquired Immune Deficiency Syndromes. 65(4):381-389. doi: 10.1097/QAI.0000000000000007
• Tavares LP, Garcia CC, Vago JP, Queiroz-Junior CM, Galvão I, David BA, Rachid MA, Silva PMR, Russo RC, Teixeira MM, Sousa LP. (2016). “Inhibition of Phosphodiesterase-4 during Pneumococcal Pneumonia Reduces Inflammation and Lung Injury in Mice.” American Journal of Respiratory Cell and Molecular Biology. 55(1). https://doi.org/10.1165/rcmb.2015-0083OC
• Wonderlich ER, Swan ZD, Bissel SJ, Hartman AL, Carney JP, O’Malley KJ, Obadan AO, Santos J, Walker R, Sturgeon TJ, Frye Jr. LJ, Maiello P, Scanga CA, Bowling JD, Bouwer AL, Duangkhae PA, Wiley CA, Flynn JL, Wang J, Cole KS, Perez DR, Reed DS, Barratt-Boyes SM. (2017). “Widespread Virus Replication in Alveoli Drives Acute Respiratory Distress Syndrome in Aerosolized H5N1 Influenza Infection of Macaques.” The Journal of Immunology. 198(4); 1616-1626. https://doi.org/10.4049/jimmunol.1601770
• Zhang ZQ, Wang J, Hoy Z, Keegan A, Bhagwat S, Gigliotti F, Wright TW. (2015). “Neither classical nor alternative macrophage activation is required for Pneumocystis clearance during immune reconstitution inflammatory syndrome.” Infection and Immunology. 83:4594-603. doi: 10.1128/IAI.00763-15.

References

¹Centers for Disease Control and Prevention. Pneumonia Can Be Prevented—Vaccines Can Help. https://www.cdc.gov/features/pneumonia/index.html. Accessed 13 Feb 2018.

²Centers for Disease Control and Prevention. Frequently Asked Flu Questions 2016-2017 Influenza Season. https://www.cdc.gov/flu/about/season/flu-season-2016-2017.htm. Accessed 13 Feb 2018.

³Ducharme J., Johnson D. (2018). The Flu Map Shows How the Biggest Influenza Outbreak in Years Spread Across the U.S. Time Health. http://time.com/5108077/2018-flu-map/. Accessed 15 Feb 2018.

⁴Gale, J. (2018). How Effective Is the 2018 Flu Shot? Here's What You Should Know. Time Health. http://time.com/5138100/how-effective-is-the-2018-flu-shot/. Accessed 13 Feb 2018.

⁵Johns Hopkins Medicine. Pneumonia. https://www.hopkinsmedicine.org/healthlibrary/conditions/respiratory_disorders/pneumonia_85,P01321. Accessed 13 February 2018.

⁶Scutti, S. (2018). How the Flue Turns Deadly. CNN. https://www.cnn.com/2018/01/24/health/how-flu-kills/index.html. Accessed 22 February 2018.

⁷Skowronski DM, Chambers C, De Serres Ga, Dickinson JA, Winter AL, Hickman R, Chan T, Jassem AN, Drews SJ, Charest H, Gubbay JB, Bastien N, Li Y, Krajden M. (2018). “Early season co-circulation of influenza A(H3N2) and B(Yamagata): interim estimates of 2017/18 vaccine effectiveness.” Euro Surveillance. 23(5):pii=18-00035. https://doi.org/10.2807/1560-7917.ES.2018.23.5.18-00035