Aero was founded in December 2019 by Yale faculty member Dr. Anjelica Gonzalez to provide respiratory solutions for patients in low-and-middle income countries. The first medical device we developed aims to provide a solution for premature babies. It was developed to be rugged, sustainable, and affordable as to provide treatment options in areas with no supply chain or clean water available. We are also in the process of modifying the device to function as a traditional ventilator; without modification, it could help on the frontlines of the current coronavirus pandemic.

 

There are two areas where our high-flow device could fit in COVID patient care of adults without modification:

1 ) Patients who are not intubated and have less than severe respiratory support needs.

2 ) Patients who are transitioning off a traditional invasive closed-loop ventilator.

 

Our device is comparable to commercially available devices in many aspects: it delivers airflows between 0-10 liters per minute, warms to 32 degrees Celsius, humidifies between 90-95%, and oxygenates between 21-100% oxygen concentration. The device delivers air that can be supplemented with concentrated oxygen, allowing operator control of oxygen delivery. Our device’s mobile and resilient design could help meet demand as we repurpose surgical suites, parking lots, local school gymnasiums, etc. We also designed it to be fixed with local parts. Housed within the device itself is an automated UV sterilization component kills bacteria and viruses. The choice of non-biofouling air delivery tubing also prevents colonization by pathogenic bacteria.

By mimicking physiological conditions, humidified air warmed to body temperature decreases the metabolic cost of gas conditioning and nasopharyngeal drying, reducing the risk of hypothermia and infection. Per the WHO: these devices do not create wide-spread dispersion of exhaled air and therefore should be associated with low risk of transmission of respiratory viruses. High-flow devices have been used successfully during the current pandemic, as well as during the SARs epidemic.

We are nearly ready to make the initial batch of clinical-grade units for patients and intend to test the first batch of devices in Addis Ababa, Ethiopia and across several states in India.

Contact: Jamison.Langguth@Yale.edu

Respiratory Distress in Adult/Child COVID Patients (High Income Countries / LMIC)

The device we developed can provide support for adult patients, particularly those who need non-invasive respiratory support of high-flow up to 10 L/min. The use of non-invasive ventilation for patients with infectious diseases like COVID-19 is incredibly controversial (Namendys-Silva, 2020). Clinicians at the Massachusetts General Hospital have suggested high-flow nasal cannulas could be used for non-intubated patients who presented to the clinic while the virus was still active and did not need an invasive ventilator for respiratory support (MGH, 2020). Some clinics in high-income countries are hesitant to use high-flow technologies in their wards due to a fear of aerosolization putting frontline workers at risk. The stark contrast between these two decisions is common. The literature surrounding potential aerosolization is mixed as mathematicians and engineers argue that it is safe with precautions, however, expert clinical opinion tends to argue that it is not safe due to unavailability of said precautions.

 

Arguments For HFNC Use in COVID Patients

WHO guidance proffers that non-invasive ventilators like high-flow nasal cannulas do not create wide-spread dispersion of exhaled air and therefore should be associated with low risk of transmission of respiratory viruses. WHO recommends wearing a standard medical face mask if the healthcare worker is within 2 meters of the patient and there is a physical bed separation of at least 1 meter. (Loh, 2020). High-flow devices were deployed successfully during the 2003 SARs epidemic, as more than one-third of all the SARs patients required high-flow oxygen therapy (Lau, 2004). Exhaled air dispersion during HFNC and CPAP via different interfaces is limited provided there is good mask interface fitting (Hui, 2019). HFNC supplies gas at a rate of ~40-60 liters/minute, whereas a normal cough achieves flow rates of ~400 liters/minute, therefore, it's doubtful that a patient on HFNC is more contagious than a patient on standard nasal cannula who is coughing (Mellies 2014). One COVID19 case series from China suggested that HFNC was associated with higher rates of survival than either other noninvasive option or invasive ventilation options (Yang, 2020). A management strategy for COVID19 by a French group used HFNC preferentially instead of BiPAP (Bouadma, 2020). Some in the west believe it should be used for patients who have fully cleared their viral load (Namendys-Silva, 2020). Others argue it could be used while a COVID patient is viral and if it does not improve within 2 hours they should be put on an invasive mechanical ventilator instead (Hui, 2019; Cascella, 2020).

 

DIFFERENTIATING FEATURES - Respiratory Distress in Premature Neonates (LMIC)

We have arrived at our current design thanks to generous grants from USAID and the Gates Foundation. Our development so far has taken place in iterations on the ground with input from low-resource Ethiopian clinics, and it is ready to be tested in the field.

Our device oxygenates, warms, humidifies, and sterilizes air before it is delivered in a single, compact, and mobile enclosure. By integrating design input from providers in Addis we designed it to be rugged yet able to be maintained and serviced with locally sourced parts, operate without needing distilled water to clean it, and perform at levels consistent with commercial cannulas while remaining low-cost. HHFNC systems prevent airway desiccation and discomfort, allowing infants to be kept under support for longer periods of time. By mimicking physiological conditions, humidified air warmed to body temperature decreases the newborn’s metabolic cost of gas conditioning and nasopharyngeal drying, reducing the risk of hypothermia and infection.

 

Existing HHFNC respiratory aid devices are largely immobile and impractical for patients who are in transport or reside in difficult-to-reach, resource-poor settings. Other treatment options for these patients are ventilators, including CPAPs. Ventilators offer unacceptable side effects stemming from their use of cold dry air and need to maintain pressure: their invasiveness induces at-minimum nasal trauma, an increased risk of hypothermia and infection, conditions to decrease appetite leading to malnutrition, and they make it harder for vital skin-to-skin contact. Overall, the competition is just too costly, their side effects are unacceptable and their devices do not clean themselves. The closest competitor to us in LMIC is the Pumani CPAP device and beyond their side effects they have had trouble scaling at their price. Our HHFNC breathing support device has decreased in cost of goods sold (COGS) from $800 to <$400 over the lifespan of its development. We are currently finalizing minor changes to the device with an engineer, and prepping a set of 10 units for a clinical trial in Ethiopia followed by India.

 

If our device were to be deployed at-scale it could put a significant dent in the global neonatal yearly death rate.

 

FEATURES - EXTENDED

Respiratory therapy has been particularly important for neonatal and infant patients up to one year of age, as they tend to be especially vulnerable and rely on respiratory aids to keep their airways open, regulate blood oxygen content, and maintain lung pressure to promote recovery. Currently, without access to appropriate respiratory devices, low-income hospitals must improvise care or attempt to operate a limited number of donated or purchased respirators designed for resource-rich clinical settings. Respiratory therapy in Ethiopian hospitals often consists of devices cobbled together from locally available materials - including Coca-Cola bottles and reused IV tubing - to deliver 100% oxygen in simulated continuous positive airway pressure (CPAP) or low-flow therapy. This delivery of 100% oxygen to newborn patients, however, can cause severe complications such as blindness and chronic lung conditions like asthma and bronchopulmonary dysplasia. Recently, low-cost commercial CPAP devices have also been developed to address the resource constraints of low-income settings like the Pumani device. However, CPAP devices do not warm or humidify airflow, which has been clinically demonstrated to be critical in reducing comorbidities and increasing patient comfort, and they are still too costly for uptake in these areas. The all in one nature of our device provides an advantage over CPAPs, as opposed to having external pieces for the oxygen mixing unit, warming and sterilization. No other device on market currently sterilizes air that is delivered, our technology eliminates the need for distilled water to clean the devices.

 

Our prototype delivers airflows between 0-10 liters per minute, warmed to 32 degrees Celsius, humidified between 90-95%, and oxygenated between 21-100% oxygen concentration. The device delivers air that can be supplemented with concentrated oxygen, allowing operator control of oxygen delivery. Housed within the device itself, an automated UV sterilization component kills bacteria and viruses. The choice of non-biofouling air delivery tubing also prevents colonization by pathogenic bacteria.

 

We have completed bench testing development, piloting, and refinement of clinical materials as well as training curriculum with end-users at Yale and in LMIC settings in Ethiopia; our current final prototype is a result of iterative testing and design improvements based on those outcomes with user feedback assumptions on device design, market approaches, and service delivery through end-user and partner feedback. Developments in the design of the device ranged from refined circuit architecture to considerations for a more efficient heating system that were integrated into the device, as a result of the analysis of data from device testing. Most notable, the water heating system now includes direct heating and a magnetic warming blanket for maintenance of optimal temperature and humidity over extended periods. In addition, the interior of the design now includes detailed operational flow patterns to highlight water flow (inlet and outlet), airflow (inlet and outlet) and electrical wiring patterns for ease of maintenance and part replacement. Additional considerations for improvements to the device’s heating and sterilization systems were discussed in the report as was a preliminary timeline of the design for manufacturability work to be completed.

COVID Specific References

  1. Bhatraju, P et al. (2020). Covid-19 in Critically Ill Patients in the Seattle Region — Case Series. New England Journal of Medicine. Published online March 30, 2020, at NEJM.org. DOI: 10.1056/NEJMoa2004500

  2. Bouadma, L. (2020). Severe SARS-CoV-2 infections: practical considerations and management strategy for intensivists. Intensive Care Med. 46:579–582 https://doi.org/10.1007/s00134-020-05967-x

  3. Bourouiba L. (2020). Turbulent Gas Clouds and Respiratory Pathogen Emissions: Potential Implications for Reducing Transmission of COVID-19. JAMA. Published online March 26, 2020. doi:10.1001/jama.2020.4756

  4. Cascella M, Rajnik M, Cuomo A, et al. Features, Evaluation and Treatment Coronavirus (COVID-19) [Updated 2020 Mar 20]. In: StatPearls [Internet]. Treasure Island (FL):

  5. Guan, L et al. (2020) More awareness is needed for severe acute respiratory syndrome coronavirus 2019 transmission through exhaled air during non-invasive respiratory support: experience from China. European Respiratory Journal. 55: 2000352; DOI: 10.1183/13993003.00352-2020

  6. Hui DS, Chow BK, Lo T, Tsang OTY, Ko FW, Ng SS, Gin T, Chan MTV. Exhaled air dispersion during high-flow nasal cannula therapy versus CPAP via different masks. Eur. Respir. J. 2019 Apr;53(4) [PubMed]

  7. ICNARC. (2020). Report on 775 patients crucially ill with COVID-19. Report published online March 27th 2020. https://www.icnarc.org/DataServices/Attachments/Download/b5f59585-5870-ea11-9124-00505601089b

  8. Lau, A. C., Yam, L. Y., & So, L. K. (2004). Management of Critically Ill Patients with Severe Acute Respiratory Syndrome (SARS). International journal of medical sciences, 1(1), 1–10. https://doi.org/10.7150/ijms.1.1

  9. Loh, N.W., Tan, Y., Taculod, J. et al. The impact of high-flow nasal cannula (HFNC) on coughing distance: implications on its use during the novel coronavirus disease outbreak. Can J Anesth/J Can Anesth (2020). https://doi.org/10.1007/s12630-020-01634-3

  10. Massachusetts General Hospital. (2020). Grand Rounds: Pathogenesis and Management of Respiratory Failure in COVID-19: What we know so far. Presented live and posted to the web on March 26th, 2020. http://healthcare.partners.org/streaming/Live/MGH/2020COVID_MedicalGrandRounds.html?fbclid=IwAR1WPLsuj-pbI5Q3HJbdRQqL8A3Y3kYhNf8APMNejfWgHJ2S4SAGf0a83CU

  11. Mellies U & Goebel C. (2014). Optimum Insufflation Capacity and Peak Cough Flow in Neuromuscular Disorders Annals of the American Thoracic Society. Vol 11:10. https://doi.org/10.1513/AnnalsATS.201406-264OC.       PubMed: 25384211

  12. Namendys-Silva S. (2020) Respiratory support for patients with COVID-19 infection. The Lancet. Published online March 05,2020 ttps://doi.org/10.1016/S2213-2600(20)30110-7

  13. StatPearls Publishing; 2020 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK554776/

  14. Yang, X et al. (2020). Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. The Lancet Respiratory Medicine. Published Online February 21, 2020 https://doi.org/10.1016/ S2213-2600(20)30079-5

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