Home-Based Physiological Monitoring of Patients with COVID-19

Akshay Warrier

Akshay Sood, MD, MPH

Division of Pulmonary, Critical Care and Sleep Medicine

Department of Internal Medicine

University of New Mexico School of Medicine

Albuquerque, NM USA

Abstract

The COVID-19 pandemic has necessitated the rise of telehealth modalities to relieve the incredible stress the pandemic has placed on the healthcare system. This rise has seen the emergence of new software, applications, and hardware for home-based physiological monitoring, leading to the promise of innovative predictive and therapeutic practices. This article is a literature-based review of the most promising technologies and advances regarding home-based physiological monitoring of patients with COVID-19. We conclude that the applications currently on the market, while helping stem the flow of patients to the hospital during the pandemic, require additional evidence related to improvement in patient outcomes. However, new devices and technology are a promising and successful venture into home-based monitoring with clinical implications reaching far into the future.

Abbreviations

• ARDS: Acute Respiratory Distress Syndrome
• CGM: Continuous Glucose Monitoring
• COVID-19: Coronavirus disease 2019
• EKG: Electrocardiogram
• FDA: Food and Drug Administration
• HIPAA: Health Insurance Portability and Accountability Act
• HR: Heart Rate
• HRV: Heart Rate Variability
• PP: Prone Positioning
• PPE: Personal Protective Equipment
• RHR: Resting Heart Rate
• RIP: Respiratory Inductive Plethysmograph
• SpO2: Peripheral Capillary Oxygen Saturation

Introduction

The severe acute respiratory syndrome coronavirus 2 (SARS-COV-2), which causes the novel coronavirus disease 2019 (COVID-19) infection, has been ravaging the globe. The number of infected cases worldwide has risen to 213 million and deaths beyond 4.4 million by August 2021 (1). Furthermore, healthcare workers are at nearly 12 times higher risk of becoming infected than the general community (2), exposing the dire need for a stronger "telemedicine" infrastructure for home-based patient care (1,3,4,5). Such a system not only needs to provide preventative information to users but also allow them to self-diagnose (using home-based testing kits) and self-triage (using real-time algorithms), thus telling patients when to seek emergency care (2). For the less severe cases, the "hospital-at-home" structure can provide acute care at low cost with coordinated telemedicine visits and necessary at-home treatment. For the hospitalized patients, this system allows an earlier discharge to receive post-illness care at home (2). This, in turn, decreases the burden on the hospitals during the pandemic.

Telemedicine, and the technology to support it, has been available for decades but had not become mainstream in the pre-pandemic era due to funding and licensing complications. The technology generally consists of three main functional units: general provision of information, provider-patient synchronous and asynchronous interactions, and remote monitoring (2). Virtual video-chat technologies and basic remote live monitoring algorithms and software were all ready to be used but had not been previously integrated into a fully functioning home-based health care system (5). However, as the pandemic began to spread, the focus on these specific technologies increased and recently have been implemented into several developing home-based systems. Most current remote monitoring programs have a few key features: scaled asynchronous entry, education and information videos/reports, standardized patient reports, real-time monitoring and modifications by a central platform, and enabled patient requests for feedback and assistance (2). "Digital personal protective equipment" or "digital PPE" such as wearable vital monitors, smart applications, and various other forms of medical monitoring have emerged so that COVID-19 monitoring can happen in real-time and assistance or advice can be algorithmically provided to patients.

Evolution of Smart Applications (Apps) for Home-based Monitoring

The foundation for remote monitoring during the pandemic has been provided by novel applications on smartphones (i.e., smart apps) and websites, and other innovative technologies and software hitting the App and Google Play stores, creating a unique opportunity in telemedicine for COVID-19 (7).

1. Application (App) Characteristics

Ideally, a developed application should be able to provide the following services: 1) symptom screening, 2) live updates and information about COVID-19, such as local test availability, 3) contact tracing and mapping of COVID-19 cases, 4) remote monitoring and patient surveillance, and 5) online chat/video consultation with a provider in a secure bidirectional network (6). In addition, the app characteristics should help ensure a streamlined and efficient system using a HIPAA verified data collection service for patients to use and allow big data capabilities for infection epidemiology (7).

2. Current App Developments

One of the earliest apps developed in Wuhan, China, using the popular WeChat platform, established bidirectional communication between a multidisciplinary medical team and quarantined patients through an eCounseling system. Using this app to triage patients, preliminary results show that continuous monitoring of changing symptoms helps in two ways: 1) reduces overcrowding in emergency rooms (ER); and 2) notifies those too afraid to present to the ER if their condition is critical enough to do so (8). 

Subsequently, the Cleveland Clinic at Cleveland, USA, put forth an app-based system for real-time monitoring of symptoms, facilitating physician advice and joint decision making, home-based physiological monitoring, and planning for advance directives and related discussions (9). The program used their MyChart Care Companion app, which focused on patient engagement to self-input symptoms and physiological signs (9). Although this app is an excellent first step towards remote patient monitoring, it does not provide patients with technology or equipment for home-based monitoring. Instead, it is an intermediary platform between the provider and the patient.

The GetWellLoop program at the University of Minnesota at Minneapolis, USA, implemented many of the same protocols, such as virtual triaging based on a combination of reported symptoms, conditions, and vital signs, and provision of immediate provider assistance, as needed. In addition, through the use of a smartphone app and basic bidirectional chat software, the program has quickly put in place an adequate but still limited roadmap for patient monitoring (10).

A review of these apps in the context of other more universal apps (Table 1) reveals that despite many desired features in disparate apps, comprehensive software has yet to be developed so far for the general public.

However, the quick implementation of these apps during the pandemic was crucial for stemming the flow of patients into hospitals and in bidirectional home-based disease management in real-time and learning about the emerging disease from the front lines (9). These smart apps will continue to play a significant role in the medical system, greatly assisting, though perhaps not yet replacing, traditional home assessments and telemedicine visits. They offer a window into a secure, well-organized database and communication system as a focal point of remote care to streamline traditional modalities by avoiding significant parts of preliminary assessments and paperwork.  

Developments in Home-based Physiological Monitoring

As efforts for vaccination and curative measures continue, research on remote physiologic monitoring has increased (Table 2).

Powerful bioanalytical software coupled with innovative technologies and smart applications offers a pragmatic solution. Realizing the potential of these technologies, the U.S. Food and Drug Administration (FDA) has established a streamlined process for the research and use of home-monitoring devices through various medical platforms (11).

A. Cardiac Monitoring

SARS-COV-2 virus can cause myocarditis, acute coronary syndromes, and arrhythmias, while medications can prolong the corrected QT interval (QTc). Therefore, electrocardiographic (EKG) monitoring, which can help detect tachycardias, conduction defects, and other arrhythmias, and changes of myocardial injury (12), is critical to COVID-19 management (13). Remote single-lead EKG monitoring is considered less accurate than 12-lead telemetry, which is the gold standard. However, several companies now offer mobile solutions for real-time EKG monitoring. After a trial with COVID-19 patients, the FDA cleared one such device, a four-lead MCOT PATCH mobile cardiac telemetry path system for outpatient EKG monitoring (14). Another such device called KardiaMobile 6L by AliveCor offers a real-time QTc measurement service from remote EKG tracings (14). Apple Watches 4 and 5 also have certain EKG monitoring capabilities, modified for diagnostic purposes (15). Beyond EKG monitoring, heart rate (HR), resting heart rate (RHR), and heart rate variability (HRV) biometrics have the greatest predictive capacity (15). These devices illustrate the future of remote monitoring by tracking early heart damage or providing useful warning signs of cardiac status or recovery trajectories (16).

B. Respiratory Rate Monitoring

COVID-19 commonly presents as a lower-respiratory tract infection, necessitating respiratory rate monitoring (17, 18). Due to the relative consistency of an individual's resting respiratory rate, changes can be detected remotely (specifically greater than 27 breaths per minute) (17).  Home-based methods for monitoring respiratory rate utilize one of two techniques: 1) respiratory inductive plethysmograph (RIP), which uses belts to measure relative changes in circumference around the abdomen and ribcage, and 2) optoelectronic plethysmography, which uses cameras to map the topography of the torso using local markers. However, new technology has emerged, such as a wearable sensor around the size of a Band-Aid, which remotely monitors local chest wall strain and transmits information to a device through Bluetooth to health care providers (19).

C. Pulse Oximetry

Pulse oximeters, though traditionally used to measure the oxygen saturation of the peripheral blood (SpO2), can also measure heart rate.  Monitoring SpO2 is critical to managing the subset of asymptomatic or paucisymptomatic COVID-19 patients with severe hypoxemia (often referred to as "silent hypoxia"). There are generally two categories of pulse oximeters. The traditional method uses light transmission through cutaneous tissue (finger or earlobe). Varying in size, traditional pocket oximeters approved for clinical use can range in cost from 20-50 US dollars. The other major categories of oximeters use reflected light measured by apps that utilize smartphone hardware and software, like the Nellcor SpO2 forehead monitor (20).

An initiative at Cleveland University Hospitals promotes using a disposable wireless finger sensor for home-based SpO2 monitoring (21). Emerging as a costly but highly competitive alternative to others in its field is the Nonin Connect 3230 Bluetooth Smart Pulse Oximeter, which offers smartphone compatibility and alert generation linked with clinician databases, for unexpected SpO2 measurements below 94% (22). Differing branded alternatives have also quickly emerged on the market, providing a cheap and quick reading, albeit with significant and varying inaccuracies, which can be useful in especially urgent contexts.

D. Temperature Tracking

COVID-19 often presents with mild to moderate fever, making body temperature an important metric to track (23). Temperature monitoring has become standard at entry points to buildings to identify and triage those infected (24). In a home-based monitoring setting, fever can be a key warning sign of both the onset of COVID-19 as well as disease trajectory (25). Elevated body temperature is correlated with mortality - the mortality rate being more than 40% higher among those with a maximum body temperature over 40.0^° C than those with a lower temperature and increasing for every 0.5^° C elevation (26).

There are several modalities for temperature monitoring, the most common of which are electronic thermometers (placed into the mouth, rectum, or armpit); plastic strip surface thermometers which change color to indicate the temperature (limited by their low accuracy); electronic ear thermometers (commonly used but maybe less accurate due to external ear canal blockage); and non-contact forehead infrared thermometers (27). Wearable technology may be effective for frequently measuring and transmitting temperature information. HEATthermo is one such technology that can reliably measure body surface temperature and heart rate every 10 seconds with good reliability (28). The Taiwanese company iWEECARE has come out with the product Temp Pal. The device is the world's smallest thermometer that offers a 36-hour battery life. It sends secure body temperature data to an app and cloud dashboard through Bluetooth for centralized big data tracking (29). These apps and monitoring platforms make it easy for medical professionals to monitor patients and for the latter to seek advice on treatment from the former, using algorithm-based alert messages (30).

E. Glucose Monitoring

Patients with pre-existing diabetes are uniquely vulnerable to SARS-CoV-2 infection and its associated morbidity and mortality. The virus' inflammatory surge (dubbed "cytokine storm") can result in insulin resistance and new-onset diabetes mellitus and its complications. The systemic hyperglycemia can lead to greater viral replication in vivo coupled with a suppressed immune response (31). Continuous glucose monitoring may therefore be helpful in those infected. Recent developments in the field of Continuous Glucose Monitoring (CGM) devices offer a pragmatic solution. Low cost and small wearable devices, like Freestyle Libre, Dexcom, Medtronic, and Eversense, offer a variety of functions, like audio and visual alerts, automatic insulin injections, data confidentiality and integration, strong smartphone and app compatibility, blind data collection for big data studies, and bidirectional clinician interaction (32).

F. Adapting Existing Wearable Biometric Technology

The most logical response to the need for home-based monitoring involves repurposing existing wearable technology to generate useful multimodal biometric data. One-fifth of Americans currently wear some smartwatch or activity tracker, and most of them can give baseline resting heart rate, sleep data, and activity data (33). Duke University investigated the role of an app that tracks smartwatches and fitness trackers in mapping and diagnosing the disease (34,35) through their DETECT program. Recently, new research with larger population input has come to light due to collaborative studies from Stanford, Fitbit, and Scripps, among others, corroborating the use of smartwatches as a predictive tool for disease (15). A recent study of 30,529 people using Fitbit, Apple Health Kit, and Google Fit data showed that individuals' changes in physiological metrics (like HRV, respiratory rate, temperature, oxygen saturation, blood pressure, cardiac output, etc.) tracked by these devices could significantly improve the detection of COVID-19 days before symptoms (33). In a retrospective study sponsored by Stanford University, researchers determined that 63% of COVID-19 cases could have been detected before symptom onset in real-time (36), using smartwatches to generate resting heart rate (RHR) difference data based on standardized values and using anomalies in "heart rate over steps" data (36). Other studies have also bolstered the use of RHR data to detect COVID-19 with smartwatches (37).

G. Emerging Multimodal Biometric Technologies

As the necessity for home-based monitoring grows, wearable multimodal monitoring technologies are being developed. One of the most promising wearable devices is the Oura ring, an aesthetic piece of jewelry that tracks multimodal data. Its use with Smart apps is being investigated (38,39). Northwestern University has invented a wireless sensor, the size of a postage stamp, that rests on the suprasternal notch to monitor cough intensity and patterns, chest wall movements, and vital signs (40,41). Mayo Clinic has started its own project, offering an albeit bulkier device yielding multimodal data, including patient self-reporting of symptoms, lung function (spirometry), and vital signs including oxygen saturation (42,5). Two powerful technology companies, Lenovo and Motorola, have joined efforts to begin certification of their Vital Moto Mod product for multimodal monitoring of vital signs, though not in a continuous or wearable fashion (43). A Chinese company KoKo LLC has agreed to distribute the Belun Technology's system (including the popular Belun ring) for monitoring vital signs. The device, called BLR-1000, uses a SIM (subscriber identification module) card and a HIPAA (Health Insurance Portability and Accountability Act) secured cloud-based system with secure protocols for data transmission to clinicians through a centralized platform (44).

More innovative research is coming in continuous respiratory rate monitoring through the modulation of radio waves and Wi-Fi signals caused by respiration-related thoracic movements, as well as smart garments and mattress pressure sensors (10), combined with cloud-based analytics. Moreover, technologies are being disseminated even as they are developed: Oakland University, California, USA, started handing out skin temperature tracking devices (BioButtons) to its students; employees in Plano, Texas, and football players at the University of Tennessee are already using proximity detectors; Kinexon from Munich is distributing SafeZone proximity trackers to many companies; and GlaxoSmithKline began manufacturing a virus tracking system with Microshare (45).

Although the devices listed above may greatly facilitate home-based physiological monitoring, physical interaction with the provider is still necessary and reassuring for patients. A recent 2020 survey of SWJPCC readership showed that despite the reduced need for documentation, greater overall efficiency, and decreased virus exposure with remote monitoring, patients valued interpersonal interactions associated with physical visits (63). Of course, considerations must be taken into account of those without easy access to technology and the Internet and those requiring additional services such as translation, interpretation, and further testing. Thus, although televisits may have increased out of necessity during the pandemic, they will likely decrease post-pandemic. However, the developed platforms may positively affect harder-to-reach communities if supplemented with the necessary resources, long after the pandemic abates (64).

Promising Home-based Lung Monitoring, Diagnosis, and Treatment Modailities

Lung ultrasound, useful in the point-of-care diagnosis and management of patients with acute respiratory failure, may be helpful in the diagnosis and management of COVID-19 pneumonia (46-49, 62). However, the lack of robust evidence and the need for technology and training renders this option currently not feasible for use in the home setting (62).

Patients at risk for atelectasis use an incentive spirometer to encourage deep, slow breaths (50,51). Although useful for atelectasis, there is little role for incentive spirometry in the treatment of COVID-19. Used in the investigation of asthma, peak expiratory flow rate measures the speed of exhalation (52,53), but its role in the home-based monitoring of COVID-19 is not known. Patients with COVID-19 pneumonia with hypoxia managed at home can be encouraged to use electronically timed treatments of prone-positioning (PP) sessions (54,55).

There still exist other developing investigations into the field of lung testing and early diagnosis. For example, one innovative study delves into machine learning with existing smartphone software and hardware to review breathing sounds. Although not specific to COVID-19 pneumonia, the acoustic technology may help classify subjects with and without pneumonia (56). Another area of investigation is the outpatient use of lung compliance measurements for COVID-19 pneumonia tracking and diagnosis (57, 58). However, the use of lung compliance for this purpose is limited by the normal lung compliance noted in some patients despite severe hypoxemia (58-60).  

Conclusion

COVID-19 has radically shifted the healthcare infrastructure; however, depending on how we utilize this system, it may open more doors than close them. The age of telehealth and telemonitoring, and the necessary implications of interactions with the Internet of things, are sure to raise privacy and security questions. Many of the companies and institutions developing smart apps and technologies above prioritize the safety of medical information. From HIPAA-secured clouds to centralized operating databases and governmentally approved/sponsored applications, patients and their security are paramount. A deep and critical analysis of the role that these apps will hold over our healthcare system is not only important but necessary.

The use of remote home-based monitoring to decrease hospital stay is the new future of the medical system. While these technologies are increasing in number and versatility, they are not empirically improving patient outcomes significantly at this time, mainly due to their novelty. The technology’s usefulness and predicted applicability, however, is undeniable in several areas as they become both more intuitive and multifaceted. Using such technological modalities to target rural, underprivileged, and underserved communities could be the stepping-stone to a universal healthcare system. Furthermore, such devices and continuous data streaming to clinician platforms also offer critical benefits to patients with varying conditions outside COVID-19. This system of remote monitoring has changed the healthcare system permanently and will change patient-physician interaction during the pandemic and post-pandemic.

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51. Eltorai AEM, Szabo AL, Antoci V Jr, Ventetuolo CE, Elias JA, Daniels AH, Hess DR. Clinical Effectiveness of Incentive Spirometry for the Prevention of Postoperative Pulmonary Complications. Respir Care. 2018 Mar;63(3):347-352. [CrossRef] [PubMed]
52. Ruffin R. Peak expiratory flow (PEF) monitoring. Thorax. 2004 Nov;59(11):913-4. [CrossRef] [PubMed]
53. Iwasawa T, Sato M, Yamaya T, Sato Y, Uchida Y, Kitamura H, Hagiwara E, Komatsu S, Utsunomiya D, Ogura T. Ultra-high-resolution computed tomography can demonstrate alveolar collapse in novel coronavirus (COVID-19) pneumonia. Jpn J Radiol. 2020 May;38(5):394-398. [CrossRef] [PubMed] Erratum in: Jpn J Radiol. 2020 Apr 22.
54. Pugliese F, Babetto C, Alessandri F, Ranieri VM. Prone Positioning for ARDS: still misunderstood and misused. J Thorac Dis. 2018 Jun;10(Suppl 17):S2079-S2082. [CrossRef] [PubMed]
55. Restrepo RD, Wettstein R, Wittnebel L, Tracy M. Incentive spirometry: 2011. Respir Care. 2011 Oct;56(10):1600-4. [CrossRef] [PubMed]
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57. Woods AD. COVID-19 – Not Your "Typical" ARDS [Internet]. COVID-19 – Not Your "Typical" ARDS | Lippincott NursingCenter. Lippincott Nursing Center; 2020 [cited 2021Jan5]. Available from: https://www.nursingcenter.com/ncblog/april-2020/covid-19-not-your-typical-ards
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60. Gargani L, Soliman-Aboumarie H, Volpicelli G, Corradi F, Pastore MC, Cameli M. Why, when, and how to use lung ultrasound during the COVID-19 pandemic: enthusiasm and caution. Eur Heart J Cardiovasc Imaging. 2020 Sep 1;21(9):941-948. [CrossRef] [PubMed]
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Disclosures

No disclosures of any personal or financial support or author involvement with organization(s) with financial interest in the subject matter, or any actual or potential conflict of interest.

Cite as: Warrier A, Sood A. Home-Based Physiological Monitoring of Patients with COVID-19. Southwest J Pulm Crit Care. 2021;23(3):76-88. doi: https://doi.org/10.13175/swjpcc005-21 PDF 

September 2021 Pulmonary Case of the Month: A 45-Year-Old Woman with Multiple Lung Cysts

Lewis J. Wesselius, MD

Department of Pulmonary Medicine

Mayo Clinic Arizona

Scottsdale, AZ USA

History of Present Illness

A 45-year-old woman presented with increasing dyspnea on exertion and a history of recurrent pneumothoraces. In March 2018 she had laparoscopic ovarian cyst removal and noted some subsequent shortness of breath. In August 2018 she developed a right pneumothorax requiring chest tube placement. In September 2018 she had recurrent right pneumothorax and had video-assisted thoracoscopic surgery (VATS) with a right pleurodesis. The operative note from the outside VATS indicates a RUL bleb was removed and a wedge biopsy was done from posterior segment of the RUL. Pathology from the wedge biopsy reported “minimal emphysematous disease without other diagnostic abnormality”. She continued to be short of breath after the operation.

PMH, SH, and FH

• In 1975 she reportedly had pulmonary tuberculosis.  
• In 2018 the pneumothoraces, pleurodesis and the right ovarian cyst resection noted above.  
• She is a never smoker and has no family history of lung disease or pneumothoraces.

Medications

• Advair 115-21
• Hydroxyzine

Review of Systems

• In addition to her dyspnea she also reported a dry mouth.

Physical Examination

• Vital Signs: BP 143/93, afebrile, SpO2 99% at rest, Body Mass Index (BMI) 25.9
• Chest:  breath sounds diminished, no crackles
• CV: regular, no murmur
• Ext:  no clubbing or edema

Radiography

Prior outside CT scans are available from January 2019 (Figure 1) and December 2020.

Figure 1. Representative images from January 2019 high resolution thoracic CT scan in lung windows.

The thoracic CT scan in Figure 1 shows which of the following. (Click on the correct answer to be directed to the second of six pages)

1. Pleural thickening and scarring
2. A subpleural pulmonary nodule in the RUL
3. Multiple lung cysts
4. 1 and 3
5. All of the above

Cite as: Wesselius LJ. September 2021 Pulmonary Case of the Month: A 45­-Year-Old Woman with Multiple Lung Cysts. Southwest J Pulm Crit Care. 2021;23(3):64-72. doi: https://doi.org/10.13175/swjpcc036-21 PDF

A Case Series of Electronic or Vaping Induced Lung Injury

Ronald Ferrer Espinosa DO¹

Abdirahman Hussein MD²

Matthew Sehring DO¹

Mohamad Rachid MD¹

Ryan Dunn MD¹

Deepak Taneja MD¹

Department of Pulmonary and Critical Care Medicine¹

Department of Internal Medicine²

University of Illinois College of Medicine at Peoria

Peoria, Illinois 

Abstract

Introduction: Since their introduction, electronic cigarette use has increased and was even proposed as an alternative to traditional tobacco use. Recently, a series of patients with acute respiratory failure due electronic cigarette, or vaping, associated lung injury (EVALI) in 2019 has been described which has largely been attributed to tetrahydrocannabinol (THC) containing vaporizer itself, as well as vitamin E acetate. Several case series have been published regarding the acute presentation, diagnosis and management. In addition to diagnosis and management of EVALI, we sought to describe potential long-term effects of lung parenchyma in these patients.

Methods: A retrospective review was performed on 16 patients with clinically diagnosed EVALI at OSF St Francis Medical Center between August 01 2019 and February 1 2020. Relevant demographic and clinical data were collected in patients diagnosed with EVALI.

Results: Of the 16 patients in the study the median age (IQR) age was 25.25 (20-29) and 94% were male. The predominant presenting symptoms were dyspnea (94%), cough (56%), nausea 63%), vomiting (63%), abdominal pain (50%), diarrhea (50%), and fever (63%). 2 (13%) patients required endotracheal intubation. Common features of computerized tomography (CT) scan were bilateral diffuse ground glass opacity (93%), septal thickening (53%), and subpleural sparing (47%). Bronchoalveolar lavage (BAL) was obtained in 3 patients and all demonstrated neutrophil predominance of 69% (56-90). One BAL was significant for hemosiderin laden macrophages. Post hospital follow up pulmonary function tests were obtained in 3 and 2 of these were significant for obstructive lung disease.

Conclusions: In this case series of patients diagnosed with vaping associated lung injury, obstructive lung disease may be seen on pulmonary function testing and surveillance of these patients should occur regardless of duration.

Keywords: CT scan, EVALI, bronchoalveolar lavage, electronic cigarette, pulmonary function testing, respiratory failure, tetrahydrocannabinol, vaping, vaping associated lung injury, vitamin E,

Introduction

The first cases of vaping associated lung injury (EVALI) were reported in Wisconsin and Illinois in the summer of 2019 which reached its peak in the fall of 2019 (1). This sudden epidemic of respiratory failure in patients who used tetrahydrocannabinol (THC) containing vaporizing devices lead the Food and Drug Administration (FDA), Center for Disease Control (CDC) and local public health departments to initiate investigations and research into the causative mechanisms of this disease. Currently, it is postulated that vitamin E acetate plays a role in the pathogenesis of VALI, as this substance was found in samples of vaping cartridges and in the bronchoalveolar fluid of patients with the disease (2,3). These pathological pathways are still being elucidated. Little is known about the long-term damage to the respiratory system in patients with EVALI. In this study, we sought to describe the diagnostic commonalities in patients with EVALI and describe potential long-term complications.

Methods

The study was a retrospective cohort analysis. Institutional Review Board (IRB) approval (1593746-1) was obtained through the University of Illinois College of Medicine at Peoria IRB. Data was collected for consecutive patients over 18 years of age who were diagnosed with EVALI between the dates of August 1, 2019 and February 1, 2020. The diagnosis of EVALI was consistent with the outbreak case surveillance definition. A confirmed case required the following to satisfy criteria: e-cigarette or dabbing in 90 days before symptom onset, pulmonary infiltrate, absence of infection, and no evidence of alternative plausible causes. A presumptive case definition included the above definition except for possibility of another cause of the patient’s symptoms such as infection. Data were extracted from the electronic medical record. The recorded data included the following: age, gender, co-morbidities, tobacco and electronic cigarette use history, need for endotracheal intubation, symptoms on presentation to the emergency department, computerized tomography findings, pulmonary function test values, bronchoalveolar lavage fluid studies, and discharge treatment plans. Obstructive lung disease is based on the American Thoracic Society/European Respiratory Society criteria that recommends the fifth percentile of the distribution in a population of healthy lifelong nonsmokers as the lower limit of normal. One patient described in this study has been previously described (4). Continuous variables are presented at median and interquartile range (IQR) with 95% CI. Categorical variables are described as number of patients (percentage).

Results

From August 1, 2019 to February 1, 2020, a total of 16 patients with either confirmed or presumptive vaping associated lung injury were reviewed. Table 1 shows the demographic data obtained from these patients.

 

The median age was 25.25 (IQR, 20-29) and the majority of patients were male 94% (n=15). Only 13% (n=2) of patients had previously diagnosed lung conditions, both of which were asthma. Of the reported THC brands, Dank© was the most commonly reported occurring in 25% (n=4) of patients (Table 2).

However, 50% (n=8) of THC products were not clearly stated in the patient’s medical record. Tobacco cigarette and tobacco electronic cigarette use were also documented, occurring in 63% (n=10) and 44% (n=7) of patients, respectively. Of those reporting tobacco use, the median pack years was 1.5 (IQR, 0.5-4.25). 7 patients reported no prior tobacco use. 13% (n=2) of patients required endotracheal intubation
 

Patients' symptoms are summarized in Table 3.

Any respiratory symptom occurred in 94% (n=15) of patients which included dyspnea 94% (n=15), cough 56% (n=9), chest pain 25% (n=4), and hemoptysis 19% (n=3). Abdominal symptoms were common and occurred in 75% (n=12) of patients. The most common gastrointestinal symptom were both nausea and vomiting 63% (n=10). These were followed by abdominal pain and diarrhea 50% (n=8). Fever was the most common constitutional symptom occurring in 63% (n=10) of patients. Less common constitutional symptoms included fatigue and chills both of which occurred in 13% (n=2) of patients. 

Chest computerized tomography (CT) scans were available in 94% (n=15) of patients. The findings are summarized in Table 4.

The most common radiographic feature was bilateral diffuse ground glass opacity (GGO), which occurred in 93% (n=14) of patients. Septal thickening and subpleural sparing were the next most common radiographic findings, occurring in 53% (n=8) and 47% (n=7) patients, respectively. Less common features that were described on chest CT scan were centrilobular nodular consolidations occurring in 27% (n=4) and reverse haloing occurring in 7% (n=1, Figure 1).

Figure 1.  Reverse halo sign in a patient with EVALI.

Three patients diagnosed with EVALI underwent bronchoscopy with bronchoalveolar lavage which are summarized in table 5.

Bronchoscopy was performed when the outbreak case definition was not met or there was a clinical concern for a secondary pathological process. The “typical” bronchoalveolar lavage (BAL) differential was neutrophilic predominant (56%-90%) with elevated macrophage and/or monocyte counts (4-19%, 0-23%). The lymphocyte count was typically low (0-4%) as well as the eosinophil count (0-1%). All the microbiologic data from these lavage samples were negative and included the following tests: aerobic and anaerobic bacterial cultures, fungal cultures, silver stain, acid fast bacilli smear and culture, varicella zoster polymerase chain reaction (PCR), histoplasma antigen and galactomannan. The results of cytology were different in all three BAL samples and were significant fore alveolar macrophages, atypical glandular cells and hemosiderin laden macrophages. At the time of bronchoscopy, only 1 or 3 patients was on or received systemic steroids therapy.

A few complications occurred in our cohort which included pneumothorax, pneumorrhachis, pulmonary embolism and Takutsubo cardiomyopathy. The case of Takusubo cardiomyopathy has been reported in the literature (4). The rate of pneumothorax was 13% (n=2). The pneumorrhachis 6% (n=1) occurred in a patient with pneumothoraces. Pulmonary embolism was only seen in 1 patient.

The discharge treatment course involved mainly systemic corticosteroids which were given in 81% (n=13) of patients. Antibiotics were continued at discharge in a minority of patients 38% (n=6). The majority of patients (94%) recovered and were asymptomatic at a later clinic visit. One patient remained symptomatic with persistent dyspnea.

Full pulmonary function tests were obtained in 3 patients (Table 6).

The timing of the pulmonary function tests occurred 3-4 weeks post hospital discharge. THC vape duration for these patients ranged from 4-12 weeks and tobacco pack years ranged from 0-2. Forced expiratory volume in 1 second to forced vital capacity (FEV1/FVC) ratios were 70%, 71%, and 86%. FEV1% ranged from 70 to 119%. FVC ranged from 81% to 119%. The total lung capacity in these three patients ranged from 85% to 109%. Diffusing capacity of carbon monoxide (DLCO) ranged from 60% to 100%. The flow volume loops of two patients demonstrate coving of the expiratory limb (Figure 2).

Pre-EVALI pulmonary function testing was not available for review in any of the patients.

Discussion

In this case series of patients with vaping associated lung injury of 16 patients in Central Illinois from August 1 2019 through February 1, 2020 the majority were younger men with respiratory and gastrointestinal symptoms. The symptomatology was consistent with previously published data (1,5,6,7). The exact pathophysiologic mechanisms implicated in vaping associated lung injury are currently still under investigation, but vitamin E acetate has recently been implicated possibly through the transition of tocopherols induced transition of phosphatidiylcholines from gel to liquid crystalline, causing surfactant dysfunction (2). The same authors proposed an alternative mechanism whereby ketene, created while heating e-cigarette products, causes direct lung irritation. However, many branded vaping products are not commercially produced and the heterogenous ingredients such as propylene glycol and other flavoring ingredients in these products may reflect its informal creation, which may influence the development of different disease mechanisms, clinical phenotypes and imaging findings (8,9).

A growing body of EVALI cases demonstrate predominant features on computerized tomography which include basilar predominant centrilobular nodular ground glass opacities and ground glass opacities with subpleural sparing. An initial study proposed four imaging patterns which included acute eosinophilic pneumonia, diffuse alveolar damage, organizing pneumonia and lipoid pneumonia and predicted the dominant CT scan findings (10). Later in a small case series of pediatric patients, centrilobular ground glass opacities were present in 92% and ground glass opacities with subpleural sparing were present in 75% of patients (11). The importance of recognizing these patterns is essential, especially in the adolescent and young adult populations where disclosure of medical history may prove to be difficult. Our findings support the cases in literature, with 93% of patients having bilateral diffuse basilar predominant GGO (93%), some associated with subpleural sparing (47%) and to a lesser degree centrilobular nodular consolidation (27%).

The role of bronchoscopy in patients with vaping associated lung injury has waned with as the characterization of clinical and radiographic findings has matured. Importantly, there is no finding on bronchoscopy that is specific for diagnosis of EVALI. Recently, the role of bronchoscopy with bronchoalveolar lavage (BAL) has been suggested to be performed in cases with a high pretest probability of EVALI with atypical features that cannot be attributed to vaping (5).  Lipid laden macrophages (LLM) are a non-specific finding in many different illnesses such as infection, aspiration, drug reactions, lipoid pneumonia, pulmonary alveolar proteinosis and autoimmune disorders, but the absence of LLM, argued by Aberegg, would be an atypical finding in EVALI (5,12). Our BAL fluid differentials are consistent with the published data, with elevations in neutrophils and/or monocytes and macrophages, with scant lymphocytes and eosinophils. In our institution, staining for lipid laden macrophages was not routinely performed. However, in one of our cytologic BAL samples hemosiderin macrophages were identified. The inconsistent cytologic findings on BAL in our series supports the notion of heterogenous underlying pathophysiologic mechanisms involved in EVALI.

The long-term effects of EVALI on lung parenchyma are unknown. Prior studies evaluating the effects of electronic cigarette use prior to the EVALI epidemic have suggested airway hyper responsiveness and an obstructive pattern on spirometry. In mice, it has been previously demonstrated that aerosolized nicotine induced airway hyperreactivity (13). A human study of 30 electronic cigarette users with at least 6 months of use compared with matched controls, demonstrated PFTs consistent with peripheral obstruction (14). A different study comparing vaping asthmatics versus healthy controls demonstrated acute declines in the FEV1/FVC ratio (15). Additionally, a few recent reports of pulmonary function testing have been documented in patients diagnosed with EVALI in late 2019 and early 2020. One study of intubated adults reported one follow-up PFT that was significant for only a low DLCO (16). A case series of pediatric patients describes two patients with 6 week follow up PFT’s that were significant for obstructive lung disease, and one of these patients had a low DLCO (11). Our study contributes 3 full PFT’s in adult patients diagnosed with EVALI performed at either 3 or 4 weeks following hospital discharge. Two of these PFT’s demonstrated obstructive lung disease, of which one had a low DLCO. The duration of vaping in these two abnormal cases were 8 and 12 weeks, and the pack years of tobacco use were 2 and 1.25 years. This small data set suggests that patients who participate in electronic cigarette use, or vaping, may be at higher risk for developing obstructive lung disease regardless of the duration of use. It is also important to take into account that a fixed FEV1/FVC ratio may underestimate young patients with obstructive lung disease (17). Using the lower limit of normal in this younger patient population is likely to be more sensitive in detecting obstructive physiology. It is plausible that vaping may cause an accelerated obstructive lung pattern due to the many potential pathways for lung injury. Full pulmonary function testing in any patient who was diagnosed with EVALI or continues to use electronic cigarettes, or vaping, products should be considered.

This study has several limitations. First, this was a retrospective study of patients at a single center in one geographic location. Second, our sample size was relatively small. Third, our clinical follow up rate was only 50%, of which only 37% completed PFT’s.

Conclusions

In our case series of 16 patients, predominantly male, diagnosed with EVALI there was a high incidence of gastrointestinal symptoms on presentation and follow up pulmonary function tests suggested there may be an increased risk for obstructive lung disease. Avoidance of vaping products, especially “Dank” and other similarly formulated products, is strongly recommended.

References

1. Layden JE, Ghinai I, Pray I, et al. Pulmonary Illness Related to E-Cigarette Use in Illinois and Wisconsin - Final Report. N Engl J Med. 2020 Mar 5;382(10):903-916. [CrossRef] [PubMed] 
2. Blount BC, Karwowski MP, Shields PG, et al. Vitamin E Acetate in Bronchoalveolar-Lavage Fluid Associated with EVALI. N Engl J Med. 2020 Feb 20;382(8):697-705. [CrossRef] [PubMed] 
3. Taylor J, Wiens T, Peterson J, et al. Characteristics of E-cigarette, or Vaping, Products Used by Patients with 18 and 2019. MMWR Morb Mortal Wkly Rep. 2019 Nov 29;68(47):1096-1100. [CrossRef] [PubMed]
4. Rachid M, Yin J, Mier N, et al. Reversed Takutsubo Cardiomyopathy in a young patient with vaping induced acute lung injury. ATS International Conference Abstract Presentation. 2020 May 15-20. Philadelphia, PA. Abstract nr A1839.
5. Aberegg SK, Maddock SD, Blagev DP, Callahan SJ. Diagnosis of EVALI: General Approach and the Role of Bronchoscopy. Chest. 2020 Aug;158(2):820-827. [CrossRef] [PubMed]
6. Blagev DP, Harris D, Dunn AC, Guidry DW, Grissom CK, Lanspa MJ. Clinical presentation, treatment, and short-term outcomes of lung injury associated with e-cigarettes or vaping: a prospective observational cohort study. Lancet. 2019 Dec 7;394(10214):2073-2083. [CrossRef] [PubMed]
7. Kalininskiy A, Bach CT, Nacca NE, et al. E-cigarette, or vaping, product use associated lung injury (EVALI): case series and diagnostic approach. Lancet Respir Med. 2019 Dec;7(12):1017-1026. [CrossRef] [PubMed]
8. Heinzerling A, Armatas C, Karmarkar E, et al. Severe Lung Injury Associated With Use of e-Cigarette, or Vaping, Products-California, 2019. JAMA Intern Med. 2020 Jun 1;180(6):861-869. [CrossRef] [PubMed]
9. Puebla Neira D, Tambra S, Bhasin V, Nawgiri R, Duarte AG. Discordant bilateral bronchoalveolar lavage findings in a patient with acute eosinophilic pneumonia associated with counterfeit tetrahydrocannabinol oil vaping. Respir Med Case Rep. 2020 Feb 3;29:101015. [CrossRef] [PubMed]
10. Henry TS, Kanne JP, Kligerman SJ. Imaging of Vaping-Associated Lung Disease. N Engl J Med. 2019 Oct 10;381(15):1486-1487. [CrossRef] [PubMed]
11. Thakrar PD, Boyd KP, Swanson CP, Wideburg E, Kumbhar SS. E-cigarette, or vaping, product use-associated lung injury in adolescents: a review of imaging features. Pediatr Radiol. 2020 Mar;50(3):338-344. [CrossRef] [PubMed]
12. Larsen BT, Butt YM, Smith ML. More on the Pathology of Vaping-Associated Lung Injury. Reply. N Engl J Med. 2020 Jan 23;382(4):388-390. [CrossRef] [PubMed]
13. Larcombe AN, Janka MA, Mullins BJ, Berry LJ, Bredin A, Franklin PJ. The effects of electronic cigarette aerosol exposure on inflammation and lung function in mice. Am J Physiol Lung Cell Mol Physiol. 2017 Jul 1;313(1):L67-L79. [CrossRef] [PubMed]
14. Meo SA, Ansary MA, Barayan FR, Almusallam AS, Almehaid AM, Alarifi NS, Alsohaibani TA, Zia I. Electronic Cigarettes: Impact on Lung Function and Fractional Exhaled Nitric Oxide Among Healthy Adults. Am J Mens Health. 2019 Jan-Feb;13(1):1557988318806073. [CrossRef] [PubMed]
15. Kotoulas SC, Pataka A, Domvri K, et al. Acute effects of e-cigarette vaping on pulmonary function and airway inflammation in healthy individuals and in patients with asthma. Respirology. 2020 Oct;25(10):1037-1045. [CrossRef] [PubMed]
16. Choe J, Chen P, Falk JA, Nguyen L, Ng D, Parimon T, Ghandehari S. A Case Series of Vaping-Associated Lung Injury Requiring Mechanical Ventilation. Crit Care Explor. 2020 Jan 29;2(1):e0079. [CrossRef] [PubMed]
17. Cerveri I, Corsico AG, Accordini S, et al. Underestimation of airflow obstruction among young adults using FEV1/FVC <70% as a fixed cut-off: a longitudinal evaluation of clinical and functional outcomes. Thorax. 2008 Dec;63(12):1040-5. [CrossRef] [PubMed]

Cite as: Espinosa RF, Hussein A, Sehring M, Rachid M, Dunn R, Taneja D. A Case Series of Electronic or Vaping Induced Lung Injury. Southwest J Pulm Crit Care. 2021;23(2):62-9. doi: https://doi.org/10.13175/swjpcc032-21 PDF 

June 2021 Pulmonary Case of the Month: More Than a Frog in the Throat

Michael B. Gotway, MD

Department of Radiology, Mayo Clinic Arizona

Phoenix, Arizona 85054

A 66-year-old woman with a history of GERD and previous renal transplant due to lithium toxicity was seen in the clinic complaining of a shortness of breath and nonproductive cough. She was on immunosuppression due to her renal transplant done about 5 months ago. These include daily trimethoprim (TMP) – sulfamethoxazole (SMX). She also had asthma and was on a long-acting bronchodilator with an inhaled corticosteroid. Because of a previous history of oropharyngeal candidiasis (thrush), she was doing nystatin swish and swallow four times a day.

Which of the following should be included in your differential diagnosis in this clinical setting? (Click on the correct answer to be directed to the second of 5 pages. Multiple guesses are allowed.)

1. Candida esophagitis
2. COVID-19 Infection
3. Cytomegalovirus esophagitis
4. Group A Streptococcus infection
5. All of the above

Cite as: Gotway MB. June 2021 Pulmonary Case of the Month: More Than a Frog in the Throat. Southwest J Pulm Crit Care. 2021;22(6):109-13. doi: https://doi.org/10.13175/swjpcc017-21 PDF 

March 2021 Pulmonary Case of the Month: Transfer for ECMO Evaluation

Nicholas G. Blackstone, MD

April Olson, MD

Angela Gibbs, MD

Bhupinder Natt, MD

Janet Campion, MD

University of Arizona College of Medicine – Tucson

Tucson, AZ USA

History of present illness

A 31-year-old male fire fighter with a history of recurrent “atypical pneumonia”, environmental and drug allergies, nasal polyps, asthma, and Crohns disease (not on immunosuppressants) was transferred from an outside hospital for management of acute hypoxic respiratory failure with peripheral eosinophilia. Prior to admission he reported a 2-week history of worsening dyspnea, productive cough and wheezing, prompting an urgent care visit where he was prescribed amoxicillin-clavulanate for suspected community acquired pneumonia. Despite multiple days on this medication, his symptoms significantly worsened until he was unable to lie flat without coughing or wheezing. He was ultimately admitted to an outside hospital where his labs were notable for a leukocytosis to 22,000 and peripheral eosinophilia with an absolute eosinophil count of 9700 cells/microL. His blood cultures and urine cultures were negative, and a radiograph of the chest demonstrated bilateral nodular infiltrates. With these imaging findings combined with the peripheral eosinophilia there was a concern for Coccidioidomycosis infection and he was subsequentially started on empirical fluconazole in addition to ceftriaxone and azithromycin. Bronchoalveolar lavage (BAL) was performed revealing 80% eosinophils, 14% polymorphic nuclear cells (PMNs), 4% monocytes and 2% lymphocytes, no pathogens were identified. The patient’s clinical status continued to decline despite antimicrobial therapy, and he was intubated for refractory hypoxia. At this point, the patient was transferred to our hospital for further care.

What is the most likely diagnosis in this patient? (Click on the correct answer to be directed to the second of four pages.)

1. Acute asthma exacerbation
2. Bacterial pneumonia
3. Coccidioidomycosis pneumonia
4. Eosinophilic pneumonia
5. Rocky Mountain Spotted Fever

Cite as: Blackstone NG, Olson A, Gibbs A, Natt B, Campion J. March 2021 Pulmonary Case of the Month: Transfer for ECMO Evaluation. Southwest J Pulm Crit Care. 2021;22(3):69-75. doi: https://doi.org/10.13175/swjpcc069-20 PDF