A Summary of Outpatient Recommendations for COVID-19 Patients and Providers December 9, 2021

Richard A. Robbins MD¹

Stephen A. Klotz MD²

¹Phoenix Pulmonary and Critical Care Research and Education Foundation, Gilbert, AZ USA

²Division of Infectious Disease, Department of Medicine, University of Arizona College of Medicine, Tucson, AZ USA

We thought a follow-up to our original brief review of COVID-19 in February, 2020 might be useful. As we write this in early December 2021, we again caution that this area is rapidly changing and what is true today will likely be outdated tomorrow. We again borrowed heavily from the Centers for Disease Control (CDC)  CDC website and the NIH website which have extensive discussions over numerous pages covering COVID-19. Our hope is to condense those recommendations. We do not discuss inpatient care in any detail.

COVID-19 Variants

The initial steps of coronavirus infection involve the specific binding of the coronavirus spike (S) protein to the cellular entry receptors which are normally on a cell. These include human aminopeptidase N (APN; HCoV-229E), angiotensin-converting enzyme 2 (ACE2; HCoV-NL63, SARS-CoV and SARS-CoV-2) and dipeptidyl peptidase 4 (DPP4; MERS-CoV).

All viruses, but especially simple single-stranded RNA viruses like COVID-19, constantly change through mutation resulting in new variants (1). The variants vary in severity and infectivity. The CDC, World Health Organization (WHO), and other public health organizations monitor COVID-19 for emergence of new variants. Some variants emerge and disappear while others persist.

The Delta variant causes more infections and spreads faster than the original SARS-CoV-2 strain of the virus that cause COVID-19 (2). Delta is currently the predominant variant of the virus in the United States causing over 99% of infections (2). On November 24, 2021, a new variant of SARS-CoV-2, B.1.1.529, was reported to the World Health Organization (WHO). This new variant was first detected in specimens collected on November 11, 2021 in Botswana and on November 14, 2021 in South Africa. On November 26, 2021, WHO named the B.1.1.529 Omicron and classified it as a variant of concern because of the number of mutations on the spike protein. As of this yesterday morning (12/8/21), the first Omicron case was reported in Arizona (2). Omicron is also present in California, Utah and Colorado and probably several other states since there is a lag between the presence of the virus and detection.

Early reports have suggested the Omicron variant might cause milder disease more often in children, raising hopes that the variant might be less severe than some of its predecessors (3). Dr. Müge Çevik, an infectious-disease specialist at the University of St Andrews, UK cautions, “Everyone is trying to find some data that could guide us but it’s very difficult at the moment.”

Symptoms

People with COVID-19 have had a wide range of symptoms reported – from none to severe illness (2). Symptoms may appear 2-14 days after exposure to the virus. Symptoms of flu and COVID-19 may be very similar and it may be hard to tell the difference between them based on symptoms alone. Testing may be needed to help confirm a diagnosis. COVID-19 seems to spread more easily than flu and causes more serious illnesses in some people. It can also take longer before people show symptoms and people can be contagious for longer. Despite mild symptoms, people infected with COVID-19 can still infect others.

Testing

Two types of viral tests are used: nucleic acid amplification tests and antigen tests (2). A viral test checks specimens from the nose or mouth by first reverse transcribing the RNA to DNA and then amplifying the DNA by polymerase chain reaction. COVID-19 antigen tests are designed for the rapid diagnosis of active infection primarily by detecting the nucleocapsid protein antigen of the SARS-CoV-2 virus. People who develop symptoms or have come into close contact with someone with COVID-19 should be tested 5–7 days after their last exposure or immediately if symptoms develop.

Prevention

The CDC recommends several steps for prevention of COVID-19 (2).

1. Get Vaccinated. COVID-19 vaccines are protective against COVID-19, especially severe disease and death. Boosters should be administered as soon as possible.
2. Wear a mask. Everyone 2 years or older who is not fully vaccinated should wear a mask in indoor public places. In general, masks are unnecessary in outdoor settings.
3. However, in areas with high numbers of COVID-19 cases, consideration should be given to wearing a mask in crowded outdoor settings and for activities with close contact with others who are not fully vaccinated.
4. Stay 6 feet away from others. Whenever possible, people should stay 6 feet away from others especially those who are sick. If possible, patients should be advised to maintain 6 feet between sick family members.
5. Avoid crowds and poorly ventilated spaces. Crowded places like restaurants, bars, fitness centers, or movie theaters are high risk areas for spread of COVID-19. Indoor spaces that do not offer fresh air from the outdoors should be avoided.
6. Test to prevent spread to others. Testing provides information about the risk of spreading COVID-19. Over-the-counter self-tests can be used at home or anywhere, are easy to use, and produce rapid results.
7. Wash Hands Often. Hands should be washed often with soap and water after the patient blows their nose, coughs, sneezes, or is exposed to any public place.
8. Clean and disinfect. High touch surfaces should be cleaned and disinfected regularly or as needed. This includes tables, doorknobs, light switches, countertops, handles, desks, phones, keyboards, toilets, faucets, and sinks.

Specific Groups

Any immunocompromised group or group living in close contact is at increased risk for COVID-19 infection and complications of the infection (2). This includes asthma, pregnancy, the elderly (>65 years), nearly all chronic diseases and jails or prisons.

Holidays

With Holiday gatherings here, many are concerned about COVID-19 especially with an unvaccinated relative or guest. First, the CDC recommends they get vaccinated (2). Second follow the recommendations under prevention above.

COVID-19 Patients

Patients with COVID-19, should follow the steps under prevention above (2). In addition, they stay home for 10 days after symptoms appear except to get medical care. Patients should be advised to drink fluids, take over-the-counter medications for symptomatic relief, and go to the emergency room or a physician’s office if needed, but call ahead. They should tell their close contacts that they may have been exposed to COVID-19.

COVID-19 Exposure

Patients should quarantine if you have been in close contact (within 6 feet of someone for a cumulative total of 15 minutes or more over a 24-hour period) with someone who has COVID-19, unless they are fully vaccinated (2). People who are fully vaccinated do not need to quarantine after contact with someone who had COVID-19 unless they have symptoms.

Travel

At this time patients should delay travel by bus, train, plane or ship unless fully vaccinated.

Treatment

The NIH has convened a COVID-19 Treatment Guidelines Panel (4). They recommend*:

1. COVID-19 vaccination for everyone who is eligible according to the Advisory Committee on Immunization Practices (AI).
2. Using one of the following anti-SARS-CoV-2 monoclonal antibodies (as post-exposure prophylaxis (PEP) for people who are at high risk of progressing to severe COVID-19:
   • Bamlanivimab 700 mg plus etesevimab 1,400 mg administered as an intravenous (IV) infusion (BIII).
   • Casirivimab 600 mg plus imdevimab 600 mg administered as subcutaneous injections (AI) or an IV infusion (BIII).
3. Do not use hydroxychloroquine for SARS-CoV-2 PEP (AI).
4. Do not use of other drugs for SARS-CoV-2 PEP, except in a clinical trial (AIII).
5. Do not use any drugs for SARS-CoV-2 pre-exposure prophylaxis, except in a clinical trial (AIII).

*Rating of Recommendations: A = Strong; B = Moderate; C = Optional Rating of Evidence: I = One or more randomized trials without major limitations; IIa = Other randomized trials or subgroup analyses of randomized trials; IIb = Nonrandomized trials or observational cohort studies; III = Expert opinion

References

1. Yang H, Rao Z. Structural biology of SARS-CoV-2 and implications for therapeutic development. Nat Rev Microbiol. 2021 Nov;19(11):685-700. [CrossRef] [PubMed]
2. CDC. COVID-19. Available at: https://www.cdc.gov/coronavirus/2019-ncov/index.html (accessed 12-6-21).
3. Callaway E, Ledford H. How bad is Omicron? What scientists know so far. Nature. 2021 Dec 2. [CrossRef] [PubMed]
4. NIH. COVID-19 Treatment Guidelines. October 27, 2021. Available at: https://www.covid19treatmentguidelines.nih.gov/ (accessed 12/6/21).

Cite as: Robbins RA, Klotz SA. A Summary of Outpatient Recommendations for COVID-19 Patients and Providers December 9, 2021. Southwest J Pulm Crit Care. 2021;23(6):151-5. doi: https://doi.org/10.13175/swjpcc066-21 PDF 

December 2021 Pulmonary Case of the Month: Interstitial Lung Disease with Red Knuckles

Lewis J. Wesselius, MD

Department of Pulmonary Medicine

Mayo Clinic Arizona

Scottsdale, AZ USA

History of Present Illness

A 56-year-old man was referred for a second opinion on recent onset of diffuse parenchymal lung disease.  He had started noting mild dyspnea with yard work approximately in March 2021. His symptoms progressed over the next month with increasing shortness of breath and some fever. He presented to outside emergency department on April 17, 2021 and chest CT showing patchy ground-glass opacities with some areas of irregular consolidation (Figure 1).

Figure 1. Representative images from the thoracic CT in lung windows from outside emergency room visit.

He was subsequently seen by an outside pulmonologist and started empirically on prednisone (50 mg/day). An outside lung biopsy had been performed which showed nonspecific interstitial pneumonitis. There was some improvement in his symptoms and his prednisone dose was reduced to 20 mg/day; however, his symptoms subsequently worsened with saturations noted to drop to 85% with any ambulation. He also had swelling of his left face and a biopsy of the parotid gland with the findings suggestive of malignancy, possibly melanoma.

What should be done at this time? (Click on the correct answer to be directed to the second of seven pages)

1. History and physical examination
2. Repeat the open lung biopsy
3. Repeat the parotid biopsy
4. 1 and 3
5. All of the above

Cite as: Wesselius LJ. December 2021 Pulmonary Case of the Month: Interstitial Lung Disease with Red Knuckles. Southwest J Pulm Crit Care. 2021;23(6):144-8. doi: https://doi.org/10.13175/swjpcc063-21 PDF 

Alveolopleural Fistula In COVID-19 Treated with Bronchoscopic Occlusion with a Swan-Ganz Catheter

Nathaniel Hitt DO¹

Aleksey Tagintsev DO¹

Douglas Summerfield MD¹

Evan Schmitz MD² 

¹MercyOne North Iowa Medical Center, Des Moines, IA USA

²Airod Medical, Gainesville, FL USA

Abstract

Pneumothorax and pneumomediastinum are known complications of COVID-19 patients. They have been documented to occur both with and without mechanical ventilation. There are several reports of cases further complicated by alveolopleural or bronchopleural fistulas. However, there are no studies and only a few case reports on the treatment options used for alveolopleural fistulas in COVID-19 patients. To our knowledge, there is only one report of bronchoscopic treatment with endobronchial valves in a COVID-19 patient. We present the case of a 63-year-old male with COVID-19, pneumothorax, and an alveolopleural fistula that was successfully sealed using bronchoscopic occlusion with a Swan-Ganz catheter.

Abbreviation List

• COVID-19: Severe acute respiratory distress syndrome coronavirus-2
• PAL: Persistent air leak
• APF: Alveolopleural fistula
• PaO2: Partial pressure of arterial oxygen
• FiO2: Fraction of inspired oxygen

Background

Pneumothorax complicates 1% of COVID-19 hospital admissions and the risk increases with mechanical ventilation (1). There have been several reports of pneumothoraces in COVID-19 complicated by persistent air leaks (PAL) and alveolopleural fistulas (APFs) (1-3). APFs are a communication between the pulmonary parenchyma of the alveoli and the pleural cavity. The most common cause is lung reduction surgery, but it can also be present following spontaneous pneumothorax.  Less commonly it can be caused by pulmonary infection. Clinically, APFs present as a PAL on chest tube drainage with a PAL defined as a duration greater than 5 days. Complications include pleural infection and ventilation/perfusion mismatch with a loss of positive end expiratory pressure.  APFs in non-COVID patients have been associated with an increased duration of chest tube, prolonged hospital stay, and increased morbidity a drainage and mortality. Treatments in non-COVID patients have ranged from insertion of additional thoracostomy tubes, surgical intervention, and bronchoscopic intervention (2). There is one reported case of an APF in COVID-19 successfully treated with endobronchial valves (3). Here we present the case of an APF in COVID-19 treated with bronchoscopic occlusion with a Swan-Ganz catheter.

Case Presentation

The patient was a 63-year-old man diagnosed with COVID-19 who required intubation, mechanical ventilation, and admission to the critical care unit. On hospital day 2 chest x-ray revealed bilateral pneumothoraces requiring chest tube placement. Bilateral PAL was present and on hospital day 10 the patient developed a moderate sized right sided pneumothorax despite the adequately positioned chest tube. The initial thoracostomy tube was replaced with a large bore chest tube with immediate resolution of the pneumothorax. However, a moderate air leak persisted and by hospital day 14, the diagnosis of APF was suspected. Bronchoscopic occlusion using the balloon of a Swan-Ganz catheter was performed.

A Swan-Ganz catheter was inserted through the endotracheal tube and along-side of a bronchoscope. The balloon was sequentially inflated and deflated to occlude each lobe to assess for air leak resolution. The air leak was reduced, but not resolved with occlusion of the right lower lobe and right middle lobe individually. The balloon was inflated just enough to occlude the right bronchus intermedius with near complete resolution of the leak (Figure 1).

Figure 1. Chest radiograph showing Swan-Ganz catheter (yellow arrow) with its cuff inflated in the right bronchus intermedius to seal an alveolopleural fistula.

The patient was observed for ten minutes to ensure tolerability before concluding the procedure. He was kept paralyzed to reduce coughing. After 3 days the air leak resolved, the Swan-Ganz catheter was removed, and the air leak remained sealed. The PaO2:FiO2 ratio improved from 79 to 250. However, despite initial improvement and no air leak the patient's conditioned worsened in the setting of multisystem organ failure. Multisystem organ failure was attributed to a combination of severe acute respiratory distress syndrome, cytokine storm, and septic shock from a urinary tract infection. The patient's family made the decision to withdraw care on day 22.

Discussion

Despite several cases of refractory pneumothorax in COVID-19, the significance and optimal treatment remains unclear (1,3,4). There is one report of two COVID-19 patients treated with thoracoscopy, bleb resection, and pleurectomy(4) and a single report of endobronchial valves (3). Conservative management with prolonged chest tube remains the recommended treatment (2). The American College of Chest Physicians guidelines only recommend bronchoscopic treatment in refractory cases when surgery is not possible (2). This patient was not a surgical candidate due to his instability, endobronchial valves were unavailable at our facility, and at height of the COVID-19 pandemic, transfer to a tertiary care center was not possible. Bronchoscopic occlusion with a balloon catheter has been described previously in a case a of PAL secondary to polymicrobial pneumonia, pulmonary interstitial emphysema, and in a case of necrotic lung complicated by hydropneumothorax (2,5,6). Bronchoscopy in COVID-19 is associated with an increased risk of infection and its use should be limited if possible. In this case, it was determined that with proper personal protective equipment and lack of access to other treatments, bronchoscopic occlusion was the best option.

An 8.0 French Swan-Ganz catheter was selected for its balloon that connects to an integrated stopcock to maintain inflation and for its relative availability. We classified the PAL as an APF after the leak was revealed to be distal to the segmental bronchi. The average time to resolution is reported to be 4-7.5 days (2). The decision to maintain occlusion for 3 days was based on the above average, patient improvement, and the lack of drainage from the occluded lung. The risk of infection, in particular pneumonia and empyema, must be considered when using this technique.  Ideally, an endobronchial valve would have been available to allow a one-way valve to drain secretions (2). Our patient was closely monitored for developing pulmonary infection with daily chest radiography and, following the removal of the Swan-Ganz Catheter, a bacterial sputum culture which was negative.

Conclusion

There are no randomized controlled trials investigating which treatment of PALs is most effective or safe in COVID-19 patients or even in non-COVID-19 patients (2). Furthermore, pneumothorax and persistent air leaks in COVID-19 patients have not been universally shown to increase mortality (1). However, considering the known morbidity and mortality associated with PALs, we suggest it may be reasonable in cases refractory to thoracostomy tube to treat with a Swan-Ganz catheter when otherresources are not available.

Acknowledgement

Peter L. Larsen PhD for editorial and administrative support.

References

1. Martinelli AW, Ingle T, Newman J, et al. COVID-19 and pneumothorax: a multicentre retrospective case series. Eur Respir J. 2020 Nov 19;56(5):2002697. [CrossRef] [PubMed]
2. Sakata KK, Reisenauer JS, Kern RM, Mullon JJ. Persistent air leak - review. Respir Med. 2018 Apr;137:213-218. [CrossRef] [PubMed]
3. Pathak V, Waite J, Chalise SN. Use of endobronchial valve to treat COVID-19 adult respiratory distress syndrome-related alveolopleural fistula. Lung India. 2021 Mar;38(Supplement):S69-S71. [CrossRef] [PubMed]
4. Aiolfi A, Biraghi T, Montisci A, et al. Management of Persistent Pneumothorax With Thoracoscopy and Bleb Resection in COVID-19 Patients. Ann Thorac Surg. 2020 Nov;110(5):e413-e415. [CrossRef] [PubMed]
5. Ellis JH, Sequeira FW, Weber TR, Eigen H, Fitzgerald JF. Balloon catheter occlusion of bronchopleural fistulae. AJR Am J Roentgenol. 1982 Jan;138(1):157-9. [CrossRef] [PubMed]
6. Schmitz ED. A new interventional bronchoscopy technique for the treatment of bronchopleural fistula. Southwest J Pulm Crit Care. 2017;15(4):174-8. [CrossRef]

Cite as: Hitt N, Tagintsev A, Summerfield D, Schmitz E. Alveolopleural Fistula In COVID-19 Treated with Bronchoscopic Occlusion with a Swan-Ganz Catheter. Southwest J Pulm Crit Care. 2021;23(4):100-3. doi: https://doi.org/10.13175/swjpcc026-21 PDF 

Repeat Episodes of Massive Hemoptysis Due to an Anomalous Origin of the Right Bronchial Artery in a Patient with a History of Coccidioidomycosis

Blerina Asllanaj, MD

Elizabeth Benge MD

Yi McWhworter DO

Sapna Bhatia MD

Department of Internal Medicine

HCA Healthcare

Mountain View Hospital

Las Vegas, NV, USA

Abstract

Anomalous bronchial arteries originate outside the space bound by the T5 and T6 vertebrae at the major bronchi. Here, we highlight a case of a 37-year-old man with a past medical history of coccidioidomycosis and who presented with massive hemoptysis. A bronchial angiogram showed the patient had a right bronchial artery originating anomalously from the left subclavian artery. The patient ultimately underwent a bronchial artery embolization, after which he achieved symptomatic remission.

Introduction

Hemoptysis from primary coccioidomycosis is unusual and should prompt a search for other causes (1). These could include bronchitis, malignancy, or rarely, a fungus ball. Anomalous bronchial arteries have origins outside the space bound by the T5 and T6 vertebrae at the level of the major bronchi (2). Bronchial artery embolization is the standard treatment for patients with ruptured anomalous bronchial arteries and resultant hemoptysis (3). Here, we present a unique case of a 37-year-old male with a past medical history of coccidioidomycosis and previous episodes of massive hemoptysis who was found to have an anomalous right bronchial artery originating in his left subclavian artery. Symptomatic remission was achieved with bronchial artery embolization. To our knowledge, this is the only reported case of a patient with a history coccidioidomycosis and a ruptured anomalous right bronchial artery that was successfully treated with bronchial artery embolization.

Case Presentation

Our patient is a 37-year-old man with a past medical history significant for coccidioidomycosis (resolved nine years prior) and previous episodes of massive hemoptysis who presented to our emergency room with multiple episodes of hemoptysis over the course of one day. On admission, he reported a five-pack year smoking history. He denied hematemesis, dyspnea, and angina, a history venous thromboembolism and alcohol and recreational drug use.

In the emergency department, the patient was afebrile, his blood pressure was 177/119 mmHg, heart rate was 96 beats/min, respiratory rate was 16 breaths/minute, and his oxygen saturation was 95% on room air. The patient’s physical exam revealed diffuse rales throughout the right lung and decreased breath sounds in the right lower lobe. The remainder of the patient’s physical exam was negative for acute abnormalities.

His lab values on admission were significant only for an elevated D-dimer at 1.28 mcg/mL; his hemoglobin was 14.2 gm/dL and his INR was 0.93 sec/mL. His chest radiograph showed ill-defined patchy parenchymal densities over the bilateral lower lobes (Figure 1).

Figure 1. Chest x-ray reveals ill-defined patchy parenchymal densities over the lower lobes suggest evolving multifocal pneumonia or atypical viral pneumonia.

He experienced a witnessed episode of hemoptysis, expectorating 300 cc’s of blood, prompting an emergent bronchoscopy. During the bronchoscopy, bloody secretions were noted to in his right lower lobe. A five centimeter dark red gelatinous material was removed and sent for pathology studies alongside bronchoalveolar lavage washings. Two mL’s of 2% epinephrine were administered, after which no active oozing was noted. The patient was then intubated for airway protection and admitted to the intensive care unit.   

A repeat chest radiograph revealed opacification throughout the right lung with evidence of volume loss (Figure 2).

Figure 2. Chest x-ray showing interval development of opacification throughout the right lung with evidence of volume loss including rightward mediastinal shift. The left lung is clear.

The patient was empirically treated for atypical pneumonia with azithromycin, ceftriaxone, dexamethasone, and albuterol breathing treatments. A computed tomography angiogram (CTA) of the chest with contrast showed multifocal flocculent and nodular infiltrate posterolateral aspect right lower lobe as well as mild mucous plugging and bronchial edema. Bronchial angiography confirmed the branching of the right bronchial artery from the left subclavian artery (Figure 3) and evidence of shunting to the right lower lobe (Figure 4).

Figure 3. Bronchial angiography prior to embolization- right bronchial artery directly arising from the left subclavian artery and is unusually large in caliber.

Figure 4. Bronchial angiography confirms opacification of the right lower lobe.

After the aberrant artery was confirmed on bronchial angiogram, the patient underwent a right bronchial artery embolization. He was subsequently extubated. Pathology and bronchoalveolar lavage studies revealed blood; the patient’s infectious and autoimmune work-up were entirely negative. He was discharged home with self-care. To date, the patient has only experienced one episode of hemoptysis status-post embolization.

Discussion

Differential diagnoses for massive hemoptysis include pulmonary infections, such as coccidioidomycosis, invasive aspergillosis and Mycobacterium tuberculosis, and cardiovascular causes, including anomalous origin of bronchial arteries. A thorough diagnostic evaluation is needed to identify the causative underlying pathology, site of bleeding, and vascular anatomy, so that the appropriate treatment can be initiated (3).

Common origins of the bronchial arteries include the inferior aortic arch, distal descending thoracic aorta, subclavian artery, brachiocephalic trunk, thyrocervical trunk and coronary artery (5). A bronchial angiogram was pivotal in the evaluation of the anatomy of the bronchial arteries in our patient’s case, as it allowed for the optimal artery embolization due to the identification of an anomalous artery early in his treatment course.

The bronchial arteries can become dilated and tortuous due to chronic inflammatory diseases such as bronchiectasis, coccidioidomycosis and tuberculosis, and are prone to vascular remodeling; rendering them fragile (6). The new collateral vessels have thin walls, making them prone to rupture and bleeding. In our patient’s case, chronic inflammation related to his prior coccidioidomycosis infection contributed to the remodeling of his anomalous right bronchial artery, rendering it prone to rupture and therefore the likely culprit of his massive hemoptysis.

Conclusion

Overall, this case emphasizes the importance of recognizing the fragility of anomalous bronchial arteries. A history of previous episodes of hemoptysis can alert clinicians to the possibility of a congenital abnormality exacerbated by subsequent infection.   

References

1. Galgiani JN, Ampel NM, Blair JE, et al. 2016 Infectious Diseases Society of America (IDSA) Clinical Practice Guideline for the Treatment of Coccidioidomycosis. Clin Infect Dis. 2016 Sep 15;63(6):e112-46. [CrossRef] [PubMed]
2. Battal, B., Saglam M, Ors F et al. Aberrant right bronchial artery originating from right coronary artery–MDCT angiography findings. Br J Radiol. 2010;83(989): e101–e104. [CrossRef] [PubMed]
3. Keller FS, Rosch J, Loflin TG, Nath PH, McElvein RB. Nonbronchial systemic collateral arteries: significance in percutaneous embolotherapy for hemoptysis. Radiology. 1987 Sep;164(3):687-92. [CrossRef] [PubMed]
4. Ittrich H, Bockhorn M, Klose H, Simon M. The Diagnosis and Treatment of Hemoptysis. Dtsch Arztebl Int. 2017 Jun 5;114(21):371-381. [CrossRef] [PubMed]
5. Hartmann IJ, Remy-Jardin M, Menchini L, Teisseire A, Khalil C, Remy J. Ectopic origin of bronchial arteries: assessment with multidetector helical CT angiography. Eur Radiol. 2007 Aug;17(8):1943-53. [CrossRef] [PubMed]
6. Kathuria H, Hollingsworth HM, Vilvendhan R, Reardon C. Management of life-threatening hemoptysis. J Intensive Care. 2020 Apr 5;8:23. [CrossRef] [PubMed]

Cite as: Asllanaj B, Benge E, McWhworter Y, Bhatia S. Repeat Episodes of Massive Hemoptysis Due to an Anomalous Origin of the Right Bronchial Artery in a Patient with a History of Coccidioidomycosis. Southwest J Pulm Crit Care. 2021;23(3):89-92. doi: https://doi.org/10.13175/swjpcc037-21 PDF 

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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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

Association between Spirometric Parameters and Depressive Symptoms in New Mexico Uranium Workers

Shiva Sharma MD, MPH¹

Xin W. Shore MS²

Satyajit Mohite MD, MPH³

Orrin Myers PhD²

Denece Kesler MD, MPH¹

Kevin Vlahovich MD, MS¹

Akshay Sood MD, MPH⁴

¹Preventive Medicine Section, Department of Internal Medicine, University of New Mexico School of Medicine, Albuquerque, NM USA

²Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque, NM USA

³Department of Behavioral Health, Psychiatry & Psychology, Mayo Clinic Health System, Mankato, MN USA

⁴Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, University of New Mexico School of Medicine, Albuquerque, NM USA

Abstract

Background: Uranium workers are at risk of developing lung disease, characterized by low forced expiratory volume in one second (FEV1) and/or forced vital capacity (FVC). Previous studies have found an association between decreased lung function and depressive symptoms in patients with pulmonary pathologies, but this association has not been well examined in occupational cohorts, especially uranium workers.

Methods: This cross-sectional study evaluated the association between spirometric measures and depressive symptoms in a sample of elderly former uranium workers screened by the New Mexico Radiation Exposure Screening & Education Program (NM-RESEP). Race- and ethnicity-specific reference equations were used to determine predicted spirometric indices (predictor variable). At least one depressive symptom [depressed mood and/or anhedonia, as determined by a modified Patient Health Questionnaire-2 (PHQ-2)], was the outcome variables. Chi-square tests and multivariable logistic regression models were used for statistical analyses.

Results: At least one depressive symptom was self-reported by 7.6% of uranium workers. Depressed mood was reported over twice as much as anhedonia (7.2% versus 3.3%). Abnormal FVC was associated with at least one depressive symptom after adjustment for covariates. There was no significant interaction between race/ethnicity and spirometric indices on depressive symptoms.

Conclusions: Although depressive symptoms are uncommonly reported in uranium workers, they are an important comorbidity due to their overall clinical impact. Abnormal FVC was associated with depressive symptoms. Race/ethnicity was not found to be an effect modifier for the association between abnormal FVC and depressive symptoms. To better understand the mechanism underlying this association and determine if a causal relationship exists between spirometric indices and depressive symptoms in occupational populations at risk for developing lung disease, larger longitudinal studies are required. We recommend screening for depressive symptoms for current and former uranium workers as part of routine health surveillance of this occupational cohort. Such screening may help overcome workers’ reluctance to self-report and seek treatment for depression and may avoid negative consequences to health and safety from missed diagnoses.

Introduction

Uranium workers are at risk of pulmonary injury via two primary mechanisms: inhalation of radon daughters causing radiation-induced lung damage (1,2) and dust inhalation (3). Exposed workers are additionally at risk for developing cardiovascular pathology (4). Lung diseases can result in a clinically significant decline in pulmonary function and have been associated with various neuropsychiatric sequelae (5,6). Screening for and treatment of depression in interstitial lung disease (ILD) has been proposed to improve quality of life (6-8). Significant levels of depressive symptoms are described in patients with silicosis (8) and may adversely affect quality of life (9). In a study of patients with ILD, depressive symptoms correlate with dyspnea, forced vital capacity (FVC), sleep quality, and pain (7).

Presence of depressed mood or anhedonia, which is a significant decrease in deriving pleasure from the majority of one’s daily activities, on most days, is requisite for diagnosis of major depressive disorder (10). Individual inquiry of depressed mood has demonstrated 85-90% sensitivity for detection of depression; and addition of another question, specific for anhedonia, raises overall sensitivity to 95% for the two-question inquiry (11).

Our objective was to evaluate the prevalence of depressive symptoms in uranium workers, to examine their association with spirometric values, and examine race/ethnicity interaction with spirometry on depressive symptoms. We studied uranium workers enrolled in the New Mexico Radiation Exposure Screening and Education Program (NM-RESEP). New Mexico workers have been significantly impacted by uranium extraction activities and many are compensated through the Radiation Exposure Compensation Act (RECA) (12). The findings from this study may help elucidate the biopsychosocial impact of uranium-related lung abnormalities in New Mexico workers.

Methods

Study Design:

This is a cross-sectional analysis of baseline evaluation data from former New Mexico uranium workers (i.e., miners, millers, and ore transporters) voluntarily enrolled between 2004 and 2017 in NM-RESEP, a federally-funded health-screening and education program, located at the University of New Mexico (UNM) Health Sciences Center, serving Albuquerque and surrounding communities.

Data Collection:

Data were obtained from a self-reported questionnaire administered by a trained interviewer and confirmed by a physician/nurse practitioner. The questionnaire included demographics, severity of dyspnea via the modified Medical Research Council (mMRC) Dyspnea Scale (13), information on smoking history, cardiovascular status, and screening for depressive symptoms (using the modified Patient Health Questionnaire or PHQ-2) which includes two items on depressed mood and anhedonia (14). Body mass index (BMI) was calculated using measured height and weight. A prebronchodilator spirometry was obtained by trained technicians, utilizing standard guidelines from the American Thoracic Society and the European Respiratory Society (15). Test results were independently reviewed for quality by a pulmonologist. Gender- and race/ethnicity- specific reference equations were used to determine predicted normative values for spirometry (16). Abnormal values were defined by the lower limit of normal obtained from reference standards. Data was entered into a secure web-based Research Electronic Data Capture (REDCap) database.

Predictor and Outcome Variables:

The outcome included a positive response for PHQ-2 item on either depressive symptom, i.e., depressed mood or anhedonia. Predictor variables included spirometric parameters and race/ethnicity, including the absolute and percent-predicted values for FVC), forced expiratory volume in one second (FEV1), and the absolute value of the FEV1/FVC ratio. Lower limits of normal obtained from the reference standards from the Third National Health and Nutrition Examination Survey (NHANES III) were used to define abnormal spirometric values (16).

Statistical Methods:

Frequencies, percentages, means, and standard deviations in a univariate analysis were reported. For the purpose of analyses, the outcome variable was endorsement of either depressive symptom. Chi-Square tests were used to analyze categorical outcome variables and generate p-values to determine significance of the findings. In the multivariable logistic regression analysis, variables that were evaluated for potential confounding included smoking status and pack-years.

Ethical Approval and Funding:

This study was approved by the UNM Institutional Review Board or Human Resources Protections Office (14-058). The study was supported by NM-RESEP, which is funded by the Health Resources Services Administration (HRSA), and UNM Health Science Center CTSC Grant Number: UL1TR001449.

Results

Subject characteristics are shown in Table 1. Of the 570 uranium workers, 97.1% were men, 66.7% were of racial/ethnic minority with the largest group being American Indian (36.6%). Most workers were older (mean age of 68.5 ± 8.1 years) with BMI values in the overweight or obese categories (82.1%). 7.6% of workers reported at least one depressive symptom, with 7.2% and 3.3% reporting depressed mood and anhedonia, respectively. The prevalence of at least one depressive symptom in Hispanic, American Indian, and non-Hispanic White workers were 11.4%, 7.2%, and 4.1%, respectively (p=0.14 for all race/ethnicity group comparison) and post-hoc comparison between Hispanic and non-Hispanic White workers was significant (p=0.001) (not shown in Table 1). 66.9% of workers were either former or current smokers. With regards to previous pulmonary history, 15.3% and 10.0% of workers reported positive history of COPD and asthma, respectively.

Table 1. NM-RESEP Uranium Workers (2004-2017).

Both unadjusted univariate and adjusted multivariable analyses revealed that workers with abnormal FVC were at least 2.9 times more likely to endorse at least one depressive symptom. No associations were found between abnormal FEV1 or abnormal FEV1/FVC ratios and depressive symptoms (Table 2).

Table 2. Unadjusted and Adjusted Associations of the Presence of Depressive Symptoms on Spirometric Indices.

*Covariates in the above multivariable model using logistic regression analysis included: smoking status and smoking pack-years. **Further adjustment for the following covariates: age, gender, and race/ethnicity did not change results in the multivariable model (FVC OR: 2.86, 95% CI: 1.18-6.96, p=0.02).

Although the associations between spirometric indices and depressive symptoms appeared stronger among Hispanic workers than other race/ethnicity subgroups, this was not borne by a formal test of interaction between race/ethnicity and spirometric indices on either depressive symptom. However, interaction testing identified a trend towards significance for Hispanic workers between abnormal FEV1 and self-reporting of depressive symptoms (p=0.07) (Table 3).

Table 3: Interaction between Spirometric Indices and Race/Ethnicity on Depressive Symptoms.

*Logistic regression analysis was used.

Discussion

A minority of uranium workers sampled in this secondary analysis self-reported at least one depressive symptom (7.6%). Depressed mood was reported over twice as much as anhedonia was reported (7.2% vs 3.3%). Abnormal FVC on spirometry was found to be associated with depressive symptoms after adjustment for covariates. There was no significant interaction between race/ethnicity and spirometric indices on depressive symptoms.

Uranium ore extraction in New Mexico occurs in open pit or underground mines. Subsequently, uranium is isolated from ore via milling or heap leaching (17). Most of the workers in this study were subjected to hazardous working conditions marked by lack of provision of personal protective equipment (including respirators) to handle uranium and inhalational dust exposure. Inadequate ventilation in underground mines also led to increased radon and dust exposure and workers were not adequately informed of these occupational exposures by mining companies or federal agencies (i.e. US Atomic Energy Commission, Nuclear Regulatory Commission, US Department of Energy) (12).

Uranium enters the human body primarily via inhalation and ingestion (18). It deposits primarily in the lungs and skeleton (insoluble uranium) and kidneys (soluble uranium) (19) where it causes chemical and radiological damage to these organs (20). In a murine study, uranium was found to enter the central nervous system, crossing the blood-brain barrier and accumulating in the hippocampus, resulting in detrimental neurophysiological effects and changes in REM sleep patterns (21). A case study involving 81 American Indian uranium workers found anxiety and depression to be the most common mental health problems, and respiratory complaints and skin rashes were the most common physical health issues (22). Radon gas, a byproduct of the uranium decay process, attaches to dust particles and when inhaled into the lungs the alpha radiation released by radon daughters damages lung tissue. Like non-uranium industry workers engaged in other types of mining-related activities, uranium workers are at risk for occupational pneumoconiosis, presenting with features similar to silicosis (23), and chronic fibrotic ILD (3). Pneumoconiosis has been associated with increased risk of other pulmonary conditions, including pulmonary emboli (24), lung carcinoma (23), chronic obstructive pulmonary disease (COPD) (26), tuberculosis (27), and clinically significant decline in lung function (28).

Many chronic pulmonary conditions such as asthma, COPD (29), bronchiectasis (30), and lung cancer (31) are associated with depressive symptoms. In a prospective study of patients with bronchiectasis, low FEV1 values were observed among patients with depressive symptoms (30). In a study of French dairy farmers, Guillien (32) found depression was associated with lower FEV1. A 2013 systematic review and meta-analysis revealed that the relationship between COPD and depression is bidirectional (33). Our study did not contain information regarding history of a prior or current diagnosis of depression for enrolled patients, thus our secondary analysis is not a like-for-like comparison to existing literature on this topic. Our study involved individuals with mostly normal lung function, indicating that the association between abnormal FVC and depressive symptoms may be seen relatively early in the disease course.

Psychosocial factors may play a role in the development of workplace-associated disability in workers with respiratory impairment, but evidence-based guidance to address these psychosocial factors is limited (34). The low prevalence of depressive symptoms in our study may reflect the high proportion of men enrolled (97.1%), as overall prevalence of depression in men is approximately half that of women (35). Alternatively, men may under-report due to a lack of awareness and understanding of depression and fear of stigmatization for self-reporting amongst coworkers or wider society. Additionally, use of the standard PHQ-2 and DSM diagnostic criteria in American Indians may not produce reliable results due to potential cultural and linguistic differences (36). The rate of depression in American indigenous populations has found to be 8.9% (which is higher than all other racial/ethnic groups except biracial individuals) and can range from 10-30% (37), however, the prevalence of depressive symptoms in American Indian workers in our study was 7.2%. To the best of our knowledge, no validation studies have been performed for use of any version of the PHQ-2 in New Mexican American Indian populations. The PHQ-2 has been validated in English- and Spanish-speaking Hispanic Americans (38). Perini found ethnic minorities diagnosed with “chronic nonspecific lung disease” exhibited higher absolute prevalence of depressive symptoms than the ethnic majority (29). Our study findings partially agree with Perini’s findings in that Hispanic uranium workers were more likely to endorse depressed mood than non-Hispanic White workers.

Our study was a cross-sectional, secondary analysis of an occupational cohort of mostly elderly, former uranium workers enrolled in NM-RESEP. Longitudinal analysis of this association may further elucidate the direction of the association. Our study could benefit from culture-specific depression diagnostic criteria paired with spirometric measures to specific pulmonary diagnoses. While anhedonia has customarily been associated with loss of pleasure (10), the construct has recently expanded to include interest in activity, effort, and discrimination between anticipation and consummatory forms of pleasure. New approaches for anhedonia assessment are in development (39). Our assessment of anhedonia may have been limited and a more robust screening tool that screens for additional depressive symptoms beyond depressed mood and anhedonia, such as the PHQ-9 or Hospital Anxiety and Depression Scale (HADS) rather than the PHQ-2, could improve result validity. As depression has a complex nature, a more rigorous biopsychosocial assessment would help in determining the role pulmonary pathology plays in depression in this study sample. To the best of our knowledge, this is the first study to examine the association of spirometric indices with depressive symptoms in former uranium workers. The strengths of our study include the robust participation of minority workers due to use of a mobile screening unit, its clinical relevance in light of ongoing uranium-associated activity, and potential future impact on health. Further study on this topic is merited as untreated depression in workers poses potential risks to workplace safety. As industrial use of nuclear material continues in the United States and other countries such as Kazakhstan, Canada, and Australia, this area of study is relevant to occupational health on a global scale. We recommend screening for depressive symptoms in current and former uranium workers as part of routine health surveillance to better address reluctance to self-report and seek treatment for depression, as well as to avoid potential negative consequences to health and safety from a missed diagnosis.

Acknowledgments

Guarantor: Akshay Sood MD, MPH takes responsibility for the content of the manuscript, including the data and analysis.

Author contributions: All authors had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. All authors contributed substantially to the data analysis and interpretation and the writing of the manuscript.

Financial/non-financial disclosures: All authors report no conflict of interest.

Abbreviation List

• BMI: body mass index
• COPD: chronic obstructive pulmonary disease
• CTSC: Clinical and Translational Science Center
• DSM: Diagnostic and Statistical Manual of Mental Disorders
• FEV1: forced expiratory volume in one second
• FVC: forced vital capacity
• HADS: Hospital Anxiety and Depression Scale
• ILD: interstitial lung disease
• mMRC: modified Medical Research Council
• NHANES III: The Third National Health and Nutrition Examination Survey
• NM-RESEP: New Mexico Radiation Exposure Screening and Education Program
• PHQ-2/PHQ-9: Patient Health Questionnaire-2/Patient Health Questionnaire-9
• RECA: Radiation Exposure Compensation Act
• REDCap: Research Electronic Data Capture
• UNM: University of New Mexico

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Cite as: Sharma S, Shore XW, Mohite S, Myers O, Kesler D, Vlahovich K, Sood A. Association between Spirometric Parameters and Depressive Symptoms in New Mexico Uranium Workers. Southwest J Pulm Crit Care. 2021;21(2):58-68. doi: https://doi.org/10.13175/swjpcc015-20 PDF 

A Population-Based Feasibility Study of Occupation and Thoracic Malignancies in New Mexico

Claire R. Pestak, MPH ^1,2

Tawny W. Boyce, MS, MPH ¹

Orrin B. Myers, PhD ⁴

L. Olivia Hopkins^, MD ³

Charles L. Wiggins, PhD ^1,2,3

Bruce R. Wissore, JD, PhD, MA, MS, MS ^3,6

Akshay Sood, MPH, MD ^3,5

Linda S. Cook, PhD ^1,3

¹UNM Comprehensive Cancer Center, University of New Mexico, MSC 07-4025,
1 UNM, Albuquerque, NM, 87131, USA

²New Mexico Tumor Registry, University of New Mexico, MSC 11 6020, 1 UNM, Albuquerque, NM, 87131, USA

³Department of Internal Medicine, University of New Mexico School of Medicine, MSC 10 5550, 1 UNM, Albuquerque, NM, 87131, USA

⁴Department of Family and Community Medicine, University of New Mexico School of Medicine, MSC 09-5040, 1 UNM, Albuquerque, NM, 87131, USA

⁵Miners Colfax Medical Center, Raton, NM, 87740, USA

⁶Southwestern Illinois College, Belleville, IL, 62221, USA

Abstract

Background

Occupational exposures in mining and oil/gas extraction are known risk factors for thoracic malignancies (TMs). Given the relatively high proportion of these industries in New Mexico (NM), we conducted a feasibility study of adult lifetime occupational history among TM cases. We hypothesized a higher proportion of occupational TM in NM relative to the estimated national average of 10-14%.

Methods

We identified incident TM cases through the population-based New Mexico Tumor Registry (NMTR), from 2017- 2018. Cases completed a telephone interview. An adjudication panel reviewed case histories and classified cancers as probable, possible, or non-occupational related, taking into account the presence, duration, and latency of exposures. We characterized recruitment and describe job titles and exposures among those with occupational TMs. We also compared the distributions of industry between those with and without occupational TM.

Results

The NMTR identified 400 eligible TM cases, 290 of which were available to be recruited (n=285 lung/bronchial cancer; n=5 mesotheliomas). Of the latter, 60% refused and 18% were deceased, 9% had invalid addresses, 11% were unable to be reached by telephone, and 3% were too ill to participate. The 43 cases who completed an interview held 236 jobs. A total of 33% of cases were classified as probable occupational TM and 5% as possible occupational TM.

Conclusions

High rates of early mortality and refusals were significant barriers to study participation. Nonetheless, the proportion of probable occupational TMs greatly exceeded the estimated national average, highlighting the need for further study of occupational TM in the state.

Editor's Note: See The Best Laid Plans of Mice and Men for accompanying editorial.

Introduction

Lung cancer and mesothelioma are the most common thoracic malignancies (TMs). Lung cancer is the second most common cancer in the United States (US) and in New Mexico (NM) and the leading cause of cancer death (1). Mesothelioma is relatively rare but has a specific association with occupational exposure to asbestos. For this paper, lung cancer and pleural mesotheliomas are combined as TMs. Despite some treatment advances (2,3), five-year relative survival is less than 20% for all TM (4).

The strongest risk factor for lung cancer is cigarette smoking (5). Other established risk factors for TMs include exposure to asbestos, uranium, radon gas, and other cancer-causing agents in the workplace, radiation therapy to the lungs, and a family history of lung cancer (6-8). The importance of occupation in TMs is emphasized by the Global Burden of Disease (GBD) report indicating that the two main cancers caused by occupational exposures worldwide were lung cancer (274,000 deaths annually) and mesothelioma (27,000 deaths annually) (9). Various estimates attributing occupation to lung cancer include: a 1981 US estimate of 15% for men and 5% for women, or 10% overall (10), a 1987 NM estimate of 14% in men (11); and, a 2003 US estimate for deaths of 8.0%–19.2% for men and 2% for females, or 6.3%-13.0% overall (12,13). Thus we estimated that overall in the US, 10%-14% of TMs could be attributable to occupation.

Historic and current occupational exposures are of particular interest in NM. Mining, in particular uranium mining, was a major operation in NM from 1950-1970. Mining is still an important industry in this region: between 2011 and 2015, the NM mining industry saw a 20% increase in employment for all types of mining (14). NM also has significant employment in the Mining, Quarrying, and Oil and Gas Extraction industry relative to other parts of the Southwest (15). These industries have a greater share of local employment in NM than in the US overall (16). Additionally, NM was the ninth highest natural gas producer in the US in 2018, producing 1.49 million cubic feet of natural gas (17).

Given the historic and current extraction activities in NM, we hypothesized that NM would have a higher proportion of occupational TMs than the estimated national average of 10%-14%. As an initial step in estimating this occupational TM cancer burden in NM, we conducted a feasibility study to obtain adult lifetime occupational histories for TM cases.

Methods

Recruitment and Data Collection 

This feasibility study was approved (#16-306) by the Human Research Review Committee at the University of New Mexico and cases provided signed, informed consent. We identified incident TM cases from February 1, 2017 to February 2, 2018 via the population-based New Mexico Tumor Registry (NMTR), a founding member of the National Cancer Institute’s (NCI) Surveillance Epidemiology and End Results (SEER) Program. Cases were identified by two methods: (1) rapid case ascertainment (RCA) via electronic pathology reports and (2) usual case ascertainment (UCA) via tumor registrars manually collecting data from around the state. Contact with eligible cases involved a three-step process. In step 1, the NMTR contacted treating physicians explaining the study and advising them of their patient’s eligibility allowing the physician to state any objection to patient contact. In step 2, the NMTR contacted the patient (letter and study brochure in English and Spanish) informing them about the study and allowing them to opt-out from further contact. In the special case of no physician of record, patients were contacted after a three month wait period. Patients who refused participation or were deceased were ineligible for study contact. In step 3, for the remainder, contact information was released to study personnel.

All potential cases in step 3 were mailed documents in both English and Spanish including: an introductory letter, a flyer about benefits counseling, a Frequently Asked Questions sheet, two copies of a Residence and Work History worksheet, a Life Events Calendar, showcards, and two copies of the consent form. One consent form was for the case to sign and keep and the other was signed and returned to the study, along with one copy of the Residence and Work History worksheet. Showcards functioned as a visual aid by listing possible answers to interview questions. The Life Events Calendar functioned as a memory aid to anchor major life events like marriages, births, deaths, relocations, job changes, and other historical events. The Residence and Work History Worksheet gave the cases a time frame to date their paid jobs and occupations, held for at least 6 months, during their adult life and was used for reference during the interview. Work did not have to occur in the state of NM. Study interviewers contacted cases by telephone to answer questions. Those who expressed a willingness to participate were asked to complete and return the worksheets/consent form and to schedule an interview.

Consenting cases completed the same structured telephone interview with an embedded script that obtained information on demographics, lifestyle factors, medical history, reproductive history (women only) and adult lifetime occupational history. For each and every job held for six months or longer from age 18 years onwards, the cases provided job title, city and country of job location, job status (full-time/part-time), job duties, exposure information on relevant agents (18) (a list of more than 30 relevant exposures was provided to cases) including the duration of each exposure, and age at start and end of the job. All cases were asked all job-related questions providing a detailed and specific work history for each individual. Data were recorded in Research Electronic Data Capture (REDCap) database (19). Cases received a small merchandise card in appreciation. All potential cases and surviving family members were given an optional referral to a benefits counselor regardless of their self-reported exposures or determination by the Data Adjudication Committee (DAC).

Determination of Occupational TM

De-identified occupational history summaries were reviewed by the DAC to determine if each case was attributable to occupational exposures, as summarized below. The DAC was composed of three voting members: a pulmonologist with expertise in occupational pulmonary diseases associated with the coal and uranium mining industries; a preventive medicine specialist with expertise in occupational health who works in the Center for Occupational Environmental Health Promotion; and, an attorney with expertise in the medicolegal definitions for causation in the occupational setting. A non-voting member (CRP) served as the committee Chair to tally votes and mediate further discussion if necessary.

This expert panel independently reviewed the de-identified individual job histories for each case, and considered exposures that had a latency of at least 10 years, exposure durations of at least one year, and exposure intensity through self-reported frequency of exposure on the job. To aid in assessment, each panel member was provided a summary table of the known strength of the association between relevant exposures and TM occurrence (available upon request) (20-27). After independent review, the panel would meet to discuss and vote on classification. If all three DAC members found sufficient evidence for relevant occupational exposure, the case was classified as a probable occupational TM. If at least one DAC member found insufficient evidence for relevant occupational exposure, the case was classified as a possible occupational TM. If all DAC members found insufficient evidence for relevant occupational exposure, the case was classified as non-occupational TM. Smoking history for each case was provided to the DAC, but occupational cancer was decided independent of smoking, except in the case of asbestos exposure where a synergistic relationship is well supported by the published literature (28). Because of the participant burden and the high likelihood of misclassification, we did not collect information on environmental tobacco smoke or biomass/coal smoke for each job reported in this study. A letter was sent to each case with the DAC’s determination.

Analysis

After the determination of occupational TM status by the DAC, each job title for each case was coded to an industry using the NIOSH Industry and Occupation Computerized Coding System (NIOCCS) (29). Each job title was submitted, and using the "Census 2010/NAICS 2007/SOC 2010" coding scheme, the most appropriate 2010 Industry Census Code provided by the industry and occupation output was selected. If the industry was unclear based on the job title alone, the work history was reviewed for the company name, job duties, or other relevant notes. In these situations, once an industry was selected, the industry was independently verified by another study team member. The possible 269 industry categories in the 2010 census system were further summarized into 20 North American Industry Classification System (NAICS) sectors (30).

Results

Of the 400 eligible cases initially identified via the NMTR, 110 (28%) were not released to study personnel for the following reasons: 33 (30%) refused to have their information released to investigators; 47 (43%) were deceased; 23 (21%) had no physician of record and were in the 3-month wait period; four (4%) had an invalid address; two (2%) were subsequently determined to be ineligible, and one case (1%) was determined to have a duplicate record in the NMTR. The remaining 290 eligible cases were invited to join the study, of which 285 had lung cancer and 5 had mesothelioma. Over-all, refusals (60%) and deaths (18%) were the two major reasons for non-participation in the interview, but cases also had invalid addresses (9%), were unable to be reached by telephone (11%), or were too ill to participate (3%). Of the 43 cases, 98% agreed to future tumor tissue testing and medical record reviews.

Demographic characteristics of cases are detailed in Table I.

Table I. Demographics of Thoracic Malignancies (TM) cases

Among the cases, 51% were women, 70% were Non-Hispanic White, 86% were >60 years of age, 19% reported a parent had lung cancer. In terms of insurance and benefits, 95% had some type of health insurance, but only 9% had sought compensation through Social Security Disability, Worker's Compensation, or the Veterans Administration before the study. Medical Histories of cases are detailed in Table II.

Table II. Medical History of Thoracic Malignancies (TM) cases.

Among the cases, 49% were overweight/obese. Both smoking (72% current/former cigarette smokers) and non-malignant respiratory diseases (40% reporting pulmonary fibrosis, COPD, or chronic bronchitis) were common.

Cases reported 236 jobs representing 20 NAICS sectors, and 14 (33%) were classified as probable and 2 (5%) as possible occupational TM. Among the probable occupational TM cases, 11 (79%) were men, and both the possible occupational TMs were men. The 14 cases with a probable occupational TM self-reported one or more of the following occupational exposures: aluminum production (n=1), arsenic (n=1), asbestos (n=7), cadmium (n=1), coal-tar (n=1), diesel (n=7), ether (n=5), nickel (n=2), paint (n=1), radiation (n=1), silica (n=9), and soot (n=2). The joint distribution of these cases by job title and exposure category is shown in Figure 1.

Figure 1. Relevant Self-Reported Exposures by Job Titles per Industry Sector for the Cases with Occupationally Related Thoracic Malignancies*

*Exposures deemed to be causal by the Data Adjudication Committee.

The study population only included those who were diagnosed and captured by the NMTR from February 1, 2017 to February 2, 2018 (n=400). Case identification at the NMTR, especially for cancers like TMs where there may not be a pathology report, may be ascertained more than a year after diagnosis. A NMTR query in March 2020 for diagnoses in the same time period noted above yielded more than double the number of TM cases (n=913). Thus we had the opportunity to compare those identified early (n=400) and up to two years later (n=513) as well as those released to the study for contact (n=290) with those whose names were not released for study contact (n=110) by selected demographic and histological characteristics (Table III).

Table III. Summary of the characteristics of the lung cancer and mesothelioma cases diagnosed between 2/1/17 – 2/2/18 for the OCTOPUS Study. Data source New Mexico Tumor Registry (NMTR).

There were differences in age between the 400 cases identified during the study period (50% for those 70 years and older) and the 513 cases identified later (57% for those 70 years and older) (p<0.05) and rurality between the 400 cases identified during the study period (23% rural) and the 513 cases identified later (44% rural) (p<0.001). Apart from the obvious difference in death as this was a criteria for not releasing contact to the study, a difference in histology was noted for those released to the study (77% non-small cell carcinoma) and those not released (66% non-small cell carcinoma) (p<0.05).

Discussion

This feasibility study was designed to obtain lifetime occupational histories from a population-based sample of TM cases and to determine the proportion of such cases that were likely attributable to occupational exposures. Despite our efforts to recruit these subjects in a timely manner, high rates of early mortality and refusals were significant barriers to study enrollment, indicating that a definitive study is not possible based on these methods. Among those who participated in the study, the proportion of cases with occupational TM (33%) was two to three times higher than prevailing national estimates (10-14%). While this result is intriguing and may warrant further study, we cannot say with certainty if this result is due to the low response percentage and the possible selection bias of having cases that were more likely to have relevant occupational exposures, or if this result truly reflects the occupational exposures in NM.

Recruiting TM cases via a population-based cancer registry is challenging. In total, 25% of eligible cases died before they could be recruited to the study via the NMTR or study personnel. An even higher proportion refused, 52% of eligible cases, in part due to poor health as cancer progressed and to the burden of treatment concurrent with study participation. Such a high refusal percentage could be a source of selection bias in which various occupations were under- or over-represented, but we had no data to address this bias directly. Additionally, the study only included those who were diagnosed and captured by the NMTR from February 1, 2017 to February 2, 2018 (n=400). We noted a substantial difference in rurality between the 400 cases identified for our study (23% rural) and the 513 cases identified later (44% rural). The majority of counties in NM are rural or frontier (26/33) (31). TM cases diagnosed among residents of these areas are less likely to receive health care in facilities that are served by pathology laboratories with electronic reporting; instead cancer registrars visit the facilities to manually abstract medical records leading to a longer reporting timeline. These results imply that rural TM cases were under-represented in our study, and since those with mining and other extraction occupations are more likely to reside and get health care in rural areas, our estimate of 33% occupational TM might be an underestimate.

From the list of more than 30 possible exposures that are known or suspected carcinogens for lung cancer (32), probable occupational TM cases reported exposures to aluminum production, arsenic, asbestos, cadmium, coal-tar, diesel fumes, ether, nickel, paint, radiation, silica, and soot. Limitations of these results include the difficulty of retrospective estimation of the intensity and duration of each of these exposures at each job, and the fact that the study did not have enough cases to conduct an analysis accounting for other exposures such as tobacco use, comorbidities, and socioeconomic factors (33). Further, we did not have information on exposures to indoor smoke in the home from, for example, wood burning stoves.

The U.S. does not have a comprehensive employment and exposure database or an occupational disease mortality surveillance system that could provide more objective and comprehensive occupational information than self-report. In some countries, researchers can link data from national cancer registries and occupational databases to help confirm associations between occupational exposures and cancers (34). Inclusion of an occupational history in medical records could also provide more objective data, but such practices are currently sporadic and non-uniform. While death certificates often record a decedent’s longest or lifetime occupation, no exposure details are included, and access to this minimal data is often restricted in an effort to maintain confidentiality (35). Thus, improvements to the evaluation of occupation and occupational exposures for cancers such as TMs on a population-basis remains a challenge.

Other strengths of our study not indicated above include: our success in ascertaining a detailed adult lifetime occupational history from lung cancer survivors using an English or Spanish interview; inclusion of racial/ethnic minorities; inclusion of both men and women (with 21% of women in our study having a probable occupational TM); no eligibility restriction to a specific industry or exposure; a rigorous procedure via the DAC to establish a probable-occupational, possible-occupational, or non-occupational classification for each case; and offering cases a referral for benefits counseling (65% accepted). The limitations of this study have been discussed above.

This feasibility study suggests that 33% of cases had a probable occupational TM, two to three times the national historical estimate, highlighting the importance of exposures and jobs in the NM population that can lead to occupational TMs. However, a more definitive study is not feasible based on the methods used in this study as the ability to overcome the above-described methodological and recruitment challenges remains a significant barrier to further population-based studies of occupation-related TM in NM and the US.

Acknowledgements: This research utilized the UNM Comprehensive Cancer Center (UNMCCC) Biostatistics Shared Resource, and the UNM Clinical & Translational Science Center, the Surveillance, Epidemiology and End Results Program (SEER) data for New Mexico, and REDCap (DHHS/NIH/NCRR #8UL1TR000041).

Funding: The grant sponsor was the UNM Foundation, a non-profit corporation, organized exclusively for charitable and educational purposes under Section 501(c)(3). CRP, TWB, and LSC and the Biostatistics Shared Resource received support from the UNM Comprehensive Cancer Center (NCI P30 CA118100). CRP and CLW received support by Contract HHSN261201800014I, Task Order HHSN26100001 from the National Cancer Institute.

Institution and Ethics approval and informed consent: The work was performed at the University of New Mexico and the Human Research Review Committee (Federal wide Assurance FWA00003255) approved this study. Study participants provided written informed consent.

Acknowledgements: This research utilized the UNM Comprehensive Cancer Center (UNMCCC) Biostatistics Shared Resource, and the UNM Clinical & Translational Science Center, the Surveillance, Epidemiology and End Results Program (SEER) data for New Mexico, and REDCap (DHHS/NIH/NCRR #8UL1TR000041).

Funding: The grant sponsor was the UNM Foundation, a non-profit corporation, organized exclusively for charitable and educational purposes under Section 501(c)(3). CRP, TWB, and LSC and the Biostatistics Shared Resource received support from the UNM Comprehensive Cancer Center (NCI P30 CA118100). CRP and CLW received support by Contract HHSN261201800014I, Task Order HHSN26100001 from the National Cancer Institute.

Institution and Ethics approval and informed consent: The work was performed at the University of New Mexico and the Human Research Review Committee (Federal wide Assurance FWA00003255) approved this study. Study participants provided written informed consent.

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Cite as: Pestak CR, Boyce TW, Myers OB, Hopkins LO, Wiggins CL, Wissore BR, Sood A, Cook LS. A Population-Based Feasibility Study of Occupation and Thoracic Malignancies in New Mexico. Southwest J Pulm Crit Care. 2021;22(1):23-35. doi: https://doi.org/10.13175/swjpcc057-20 PDF 

Adjunctive Effects of Oral Steroids Along with Anti-Tuberculosis Drugs in the Management of Cervical Lymph Node Tuberculosis

Adjunctive Effects of Oral Steroids Along with Anti-Tuberculosis Drugs in the Management of Cervical Lymph Node Tuberculosis

Babulal Bansiwal¹

Maneesha Jelia²

Ramesh Chand Meena²

Satyam Agarwal²

Shinu A²

Departments of ¹Respiratory Medicine and ²Anatomy

Government Medical College, Kota

Rajasthan 324010, India

Abstract

Background: Tuberculosis (TB) can infect both pulmonary and extra-pulmonary organs. In India pulmonary TB accounts for 80% of cases and extrapulmonary TB (EPTB) accounts for 20% cases. Cervical lymph nodes are the most location for EPTB.

Aims and Objectives: To study the efficacy of treatment with oral steroids along with anti-tuberculosis treatment in cervical lymph node tuberculosis.

Methods: A total of 60 patients were enrolled in the study all with EPTB and cervical lymphadenitis. These 60 study patients were randomised into two groups. Group-I consisted of 30 patients given anti-tuberculosis therapy along with prednisolone 1mg/kg body weight for 4 weeks followed by tapering at 0.5 mg/kg body weight over 4 weeks. Group-II was comprised of 30 patients given antituberculosis treatment plus placebo

Results: After completion of treatment 27 patients in Group 1 (90%) showed complete resolution and 3 patients (10%) had residual evidence of lymphadenitis with no change. In contrast, only 19 patients (63.3%) showed complete resolution in Group 2 and 11 patients (36.7%) had residual lymphadenitis present (10 had no change, 1 had increase in size).

Conclusion: We conclude that steroids given with antituberculosis treatment to patients with cervical lymphadenitis led to faster and earlier resolution of tuberculous lymphadenitis.

Introduction

Tuberculosis (TB) is an ancient disease that affects both pulmonary and extra-pulmonary organs. In India most TB cases are pulmonary (80%) but extrapulmonary TB (EPTB) accounts for a substantial proportion (20%) (1). Peripheral lymph node tuberculosis is observed in about 5% of all TB patients and 30-55% of extra-pulmonary TB cases (2). Cervical lymph nodes are the most common lymph nodes affected, classically termed as “scrofula”, although supraclavicular, axillary, inguinal nodes may also be involved (3-5). Lymphadenopathy may lead to complications by compression of adjacent structures, organs, and blood vessels or fistula formation (6-10). Multiple studies have shown better outcomes with addition of steroids to anti-tuberculosis treatment in extrapulmonary tuberculosis including pleural effusion, pericardial effusion, tubercular meningitis, and mediastinal lymphadenopathy (11,12). However, the safety and efficacy of this approach remains largely unproven except in cases of intrathoracic obstruction where it was found to relieve the pressure on the compressed bronchus (13).

Aims and Objectives

To study the efficacy of treatment with oral steroids along with anti-tuberculosis treatment in cervical lymph node tuberculosis.

Materials and Methods

Patients: Sixty patients with cervical lymph node tuberculosis seen from 1st October 2013 to 30^th September 2014 in the Department of Respiratory Medicine, Government Medical College, Kota, India participated in the study. All cases of cervical lymph node tuberculosis found to have cyto-pathological, histo-pathological, immunological and/or bacteriological evidence of TB and who had not received any anti- tuberculosis therapy in the past, were included in the study. Patients were excluded if they were pregnant or had a chronic disease such as diabetes mellitus, hypertension, peptic ulcer disease, alcoholism, or HIV-AIDS. Patients were also excluded if they had a detectable abscess.

Study Design: The study was an open label, randomized, prospective and placebo-controlled interventional study comparing the efficacy of the addition of two months treatment with oral corticosteroids along with Revised National Tuberculosis Control Programme (RNTCP) recommended anti-TB therapy.

Sixty patients were randomised into two groups by a computer-generated random table. All patients were given category I anti-tuberculosis therapy (ATT) consisting of INH 600 mg and rifampicin 450 mg daily for 6 months with pyrazinamide 1500 mg daily for the first 2 months. Group-I consisted of 30 patients given category I RNTCP-recommended therapy along with prednisolone 1mg/kg body weight for 4 weeks followed by tapering at 0.5mg/kg body weight for 4 weeks. Group-II was comprised of 30 patients given category I RNTCP-recommended therapy plus placebo.

All the study cases were monitored clinically by visits after 1, 2 and 6 months.

Statistical Analysis: Pearson’s x² test or Fisher’s exact test was used to evaluate correlations between categorical variables, as appropriate. Relationships among continuous variables was evaluated using Student’s t- test. All tests of significance are two-tailed, and p < 0.05 was considered to reflect significance.

Results

The patients were well matched between groups in age (27.5 + 12.9 years vs. 26.3 + 11.7 years, p=0.612) and sex (12M/18F vs. 11M/19F). The groups were well-matched in other clinical characteristics (Table 1).

Table 1. Clinical characteristics of patients at beginning of therapy.

In addition to the above, the patients were well-matched by the extent of both upper and lower lymphadenopathy (Group I, 25/30; Group 2, 28/30), absence of chest lesions (Group I, 1/30; Group 2, 2/30), and positive histopathology on needle aspiration (Group I, 27/30; Group 2, 26/30). Out of 26 patients of Group II, 4 (13.3%) patients were diagnosed by AFB smear of the needle aspirate as well as cytopathological examination, 2(6.7%) had only AFB smear positivity and 22 (86.7%) had only cytopathological confirmation. None had a positive sputum smear.

Most of the patients in Group-I had earlier lymph node resolution compared to Group-II (Table 2).

Table 2. Initial lymph node status and after varying durations of treatment.

This table shows the status of the lymph node initially and after varying duration of treatment. After completion of treatment 27 patients (90%) showed complete resolution and only 3 patients (10%) had no change in Group-I. In contrast, only 19 patients (63.3%) in Group-II showed complete resolution and 11 patients (36.7%) had residual lymph nodes (10 with no change, 1 with an increase in size). Most patients had a negative AFB smear from the needle aspirate after 6 months in both Group-I (27 patients) and group-II (26 patients).

Only 2 patients in Group-I (6.67%) had complications as compared to 09 (30.0%) in Group-II (p<0.001). The complications were in the form of abscess, sinus and/or new lymph node/s. All these patients needed surgical exploration during the course of treatment. Sequelae in form of residual lymph node was also higher in Group II patients (10 out of 30 patients) as compared to Group I (3 out of 30, p<0.001).

Overall, the incidence of side effects was greater in Group-II. This difference was mostly due to a higher occurrence of joints pain and skin rashes in Group-II than Group-I, (8 and 4 patients vs. 1 and 1 patients respectively).

Discussion

The present study was done to determine the role of steroids in the management of cervical lymph node tuberculosis. In contrast to 20 patients (66.67%) in the non-steroid group-II who had complete resolution after 6 months, 27 patients (90%) in the steroid group had complete resolution. Blaikely et al. (14) reported complete resolution in 82% of their non-steroid study patients which was similar to results of our study.

In the present clinical study, only 2 patients (6.66%) in the steroid group had complications as compared to 9 (30.0%) in the non-steroid group. The complications were in the form of abscess, sinus and/or new lymph node/s. In Group II, fresh lymph nodes appeared in 4, existing lymph node increased in 1, abscess formation occurred in 3 while 2 patients developed sinuses. Sequela in the form of residual lymph node was also higher in the non-steroid patients (10 out of 30, 33.33%) as compared to the steroid treated patients (3 out of 30 patients, 5%, p<0.001). Results were comparable to other studies (15).

We used a moderate dose of steroids for 2 months. The major concern against the use of steroids when given along with anti-TB treatment in tubercular lymphadenitis are adverse systemic effects. However, the overall incidence of side effects with anti-TB treatment were more in the non-steroid group in the form of joint pains and skin rashes, (8 and 4 patients v/s 1 and 1 patients respectively). Gastro-intestinal side effects i.e. nausea/vomiting and pain abdomen, were slightly higher in the steroid-treated patients.

Conclusion

We conclude that steroids when given along with anti-tubercular treatment led to faster and earlier resolution of tuberculous lymphadenitis. Complication and sequela in form of residual lymph node are also less in steroid group as compared to non-steroid group. It is unclear if long-term outcomes are affected. However, this data suggests that justification for routine use of corticosteroids could be made in tubercular cervical lymphadenitis.

References

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Cite as: Bansiwal B, Jelia M, Chand Meena RC, Agarwal S, A S. Adjunctive Effects of Oral Steroids Along with Anti-Tuberculosis Drugs in the Management of Cervical Lymph Node Tuberculosis. Southwest J Pulm Crit Care. 2021;22(1):16-20. doi: https://doi.org/10.13175/swjpcc067-20 PDF 

Respiratory Papillomatosis with Small Cell Carcinoma: Case Report and Brief Review

Priya Sharma

Anish Kumar

Bharath Janapati

Anil Kumar Jain

Department of Respiratory Medicine

National Institute of Tuberculosis and Respiratory Diseases

New Delhi 110030, India

Abstract

Respiratory Papillomatosis is a rare disease in which multiple exophytic squamous wart-like lesions occur within the respiratory tract. Recurrent Respiratory Papillomatosis (RRP) has the potential for malignant transformation to squamous lung cell carcinoma with a dismal prognosis. Most of the prior literature has shown malignant transformation of respiratory papillomatosis into squamous cell carcinoma. Here, we report a rare presentation of respiratory papillomatosis coexisting with small cell carcinoma and a review of relevant literature.

Introduction

RRP is a rare disease in which multiple exophytic squamous wart-like lesions occur within the respiratory tract. RRP has the potential for malignant transformation to squamous lung cell carcinoma with a dismal prognosis. The cases of squamous cell carcinomas developing within lung papillomas have been reported and these are usually associated with HPV 11 DNA (1,2). Here we present a rare case of respiratory papillomatosis coexisting with small cell carcinoma.  

Case Report

A 47-year-old woman presented with right sided chest pain and cough for 8 months. She had history of two episodes of blood streaked sputum four months ago. She also complained of loss of appetite and weight loss. She was a former smoker (1-2 cigarettes per day for 2-3 years quitting 5 years ago) and had a history of exposure to biomass fuel while working as a farmer. On examination pallor and clubbing was noted. Chest x-ray was suggestive of hilar enlargement (Figure 1).

Figure 1. Initial chest radiography.

Contrast-enhanced CT of the chest showed homogeneously enhancing soft tissue density central lung mass that is narrowing and circumferentially encasing right main bronchus. The mass was abutting arch of aorta and the ascending aorta and circumferentially encasing and narrowing the superior vena cava and right main pulmonary artery. Subsegmental collapse of superior segment of right lower lobe was also seen with right paratracheal and pretracheal lymph node enlargement (Figure 2).

Figure 2. Representative axial image from thoracic CT scan in soft tissue windows showing the right lung mass.

Flexible optic bronchoscopy showed an endoluminal irregular mass invading distal end of trachea along with carina and right main bronchus (Figure 3).

Figure 3. Photograph taken at bronchoscopy of the endobronchial mass in the distal trachea and right main bronchus.

Endobronchial biopsy showed papillary structures with fibro vascular cores lined with cell with moderate amount of cytoplasm with enlarged nuclei with granular chromatin and inconspicuous nuclei suggestive of RPR on histopathological examination. The patient was lost to follow up. Two months later she presented with increased breathlessness. Chest x-ray showed unilateral opaque right hemithorax with mediastinum slightly shifted to right (Figure 4).

Figure 4. Repeat chest radiography taken 2 months after initial presentation.

Hyponatremia was seen on routine blood investigation. CECT chest showed a well-defined heterogeneously enhancing soft tissue mass lesion with irregular margins involving the upper and middle lobe of right lung (Figure 5).

Figure 5. Coronal view of repeat thoracic CT in soft tissue windows.

The mass was encasing the right main bronchus and distal trachea, abutting large vessel, shifting trachea towards right side with moderate pleural effusion. Sputum analysis for acid-fast bacteria and malignant cells was negative. Ultrasound of abdomen showed no abnormality. Pleural fluid analysis showed paucicellular smear on cytology with ADA 20.5U/l, Protein 2.4 mg/dl and glucose 95.1 mg/dl. The patient refused bronchoscopy but consented to an ultrasound guided trans-thoracic biopsy. Histopathology showed pulmonary tissue with infiltrating tumor and the tumor was made up of sheets of small round cells with irregular contours suggestive of small cell carcinoma. Patient refused further management and left against medical advice. She passed away 11 days later.

Discussion

The incidence of RRP is bimodal, with the juvenile-onset form typically first occurring in children aged 2 to 4 years and adult-onset RRP typically occurring in adults aged 20 to 40 years. Juvenile-onset RRP is thought to be caused from peripartum exposure through an infected birth canal (3). Risk factors for adult-onset RRP include multiple lifetime sexual partners as well as a high frequency of oral sex. There was no statistically significant difference in illicit drug use between patients with adult-onset RRP vs a control group in a study by Ruiz et al. (4). RRP affects, from the most common site to the least common site, the true vocal cord, oral cavity, trachea, bronchi, and esophagus. Only 5% of the patients had the distal involvement of the trachea, and the involvement of the lung parenchyma is very rare, which is seen in, 1% of all cases (5). Therefore, patients present most commonly with hoarseness followed by stridor, cough, and dyspnea. Risk factor for malignant conversion includes smoking, prior irradiation, HPV-6. A recent study showed the presence of E6 and E7 oncogenes and their transcripts in HPV-positive lung cancer cases that are prerequisite for cancer development, thus reinforcing further the hypothesis that HPV could be a co-factor in bronchial carcinogenesis (6).Our patient had history of smoking as the only risk factor for malignant conversion.

Progressively increased expression of p53 and pRb proteins along with a reduced expression of p21^WAF1 protein appears to be significant subsequent events in the progression to carcinoma (7). Talierco et al. (8) reported 100% of patients with adult onset RRP had concurrent HPV infection of the oral cavity; however, our patient had no evidence of oral cavity HPV infection on physical examination. Bronchoscopic pictures were suggestive of papillary lesion although association with HPV can’t be commented upon as patient refused for further testing. A literature review of RRP case reports revealed that patients usually have the diagnosis of RRP many years before evidence of malignant transformation (9-12). In contrast, our patient had evidence of malignant transformation about six months after diagnosis of respiratory papillomatosis.

DiMarco et al. (13) were the first to report the presence of the multiple RRP of the tracheobronchial tree with malignant degeneration, in 1978. One other case report showing coexistence of multiple squamous cell papilloma and carcinoma in the upper trachea with severe airway obstruction has been reported (14). A case study done in Taiwan suggests that HPV infection is an important risk factor for lung cancer among women (15).

Surgical excision of RRP is the current standard of care with objective of preserving adequate voice quality and airway patency (16). Lasers can also be employed for surgical excision of RRP. Either cutting/ablating lasers (CO2 and thallium lasers), or photoangiolytic lasers such as pulsatile (PDL) and potassium- titanil-phosphate lasers (KTP) can be used. Both KTP and PDL lasers are safe and effective for in office treatment of RRP (17). Microdebriders have distinct advantages over lasers and cold instruments because of their shorter operating time and absence of thermal injury (18). Adjuvant therapies for RRP include the usage of immunomodulators such as IFN, antivirals such as Cidofovir, Angiogenesis inhibitor (Bevacizumab) and PDL-1 inhibitor (19). The development of HPV- 1 vaccination is perhaps the most important modality in the management of RRP, by preventing infection with papilloma virus.

Conclusion

To the best of our knowledge, this is the first case report of coexisting respiratory papillomatosis with small cell carcinoma lung. Thus, coexistence of malignancy or malignant degeneration of respiratory papillomatosis is although unusual but can still occur without the associative factors. Patients with RRP should be radiographically monitored at regular intervals for pulmonary involvement and further evaluation actively pursued if any suspicion of malignancy arises.

References

1. Magid MS, Chen YT, Soslow RA, Boulad F, Kernan NA, Szabolcs P. Juvenile-onset recurrent respiratory papillomatosis involving the lung: A case report and review of the literature. Pediatr Dev Pathol. 1998 Mar-Apr;1(2):157-63. [CrossRef] [PubMed]
2. Kramer SS, Wehunt WD, Stocker JT, Kashima H. Pulmonary manifestations of juvenile laryngotracheal papillomatosis. AJR Am J Roentgenol. 1985 Apr;144(4):687-94. [CrossRef] [PubMed]
3. Kashima HK, Shah F, Lyles A, Glackin R, Muhammad N, Turner L, Van Zandt S, Whitt S, Shah K. A comparison of risk factors in juvenile-onset and adult-onset recurrent respiratory papillomatosis. Laryngoscope. 1992 Jan;102(1):9-13. [CrossRef] [PubMed]
4. Ruiz R, Achlatis S, Verma A, Born H, Kapadia F, Fang Y, Pitman M, Sulica L, Branski RC, Amin MR. Risk factors for adult-onset recurrent respiratory papillomatosis. Laryngoscope. 2014 Oct;124(10):2338-44. Epub 2014 Jun 10. [CrossRef] [PubMed].
5. Cook JR, Hill DA, Humphrey PA, Pfeifer JD, El-Mofty SK. Squamous cell carcinoma arising in recurrent respiratory papillomatosis with pulmonary involvement: emerging common pattern of clinical features and human papillomavirus serotype association. Mod Pathol. 2000 Aug;13(8):914-8. [CrossRef] [PubMed]
6. Giuliani L, Favalli C, Syrjanen K, Ciotti M. Human papillomavirus infections in lung cancer. Detection of E6 and E7 transcripts and review of the literature. Anticancer Res. 2007 Jul-Aug;27(4C):2697-704. [PubMed]
7. Lele SM, Pou AM, Ventura K, Gatalica Z, Payne D. Molecular events in the progression of recurrent respiratory papillomatosis to carcinoma. Arch Pathol Lab Med. 2002 Oct;126(10):1184-8. [CrossRef] [PubMed]
8. Taliercio S, Cespedes M, Born H, Ruiz R, Roof S, Amin MR, Branski RC. Adult-onset recurrent respiratory papillomatosis: a review of disease pathogenesis and implications for patient counseling. JAMA Otolaryngol Head Neck Surg. 2015 Jan;141(1):78-83. [CrossRef] [PubMed]
9. Martina D, Kurniawan A, Pitoyo CW. Pulmonary papillomatosis: a rare case of recurrent respiratory papillomatosis presenting with multiple nodular and cavitary lesions. Acta Med Indones. 2014 Jul;46(3):238-43. [PubMed]
10. Azadarmaki R, Lango MN. Malignant transformation of respiratory papillomatosis in a solid-organ transplant patient: case report and literature review. Ann Otol Rhinol Laryngol. 2013 Jul;122(7):457-60. [CrossRef] [PubMed]
11. Hasegawa Y, Sato N, Niikawa H, Kamata S, Sannohe S, Kurotaki H, Sasaki T, Ebina A. Lung squamous cell carcinoma arising in a patient with adult-onset recurrent respiratory papillomatosis. Jpn J Clin Oncol. 2013 Jan;43(1):78-82. Epub 2012 Oct 30. [CrossRef] [PubMed]
12. Lin HW, Richmon JD, Emerick KS, de Venecia RK, Zeitels SM, Faquin WC, Lin DT. Malignant transformation of a highly aggressive human papillomavirus type 11-associated recurrent respiratory papillomatosis. Am J Otolaryngol. 2010 Jul-Aug;31(4):291-6. Epub 2009 Jul 10.  [CrossRef] [PubMed].
13. DiMarco AF, Montenegro H, Payne CB Jr, Kwon KH. Papillomas of the tracheobronchial tree with malignant degeneration. Chest. 1978 Oct;74(4):464-5. [CrossRef] [PubMed].
14. Paliouras D, Gogakos A, Rallis T, Chatzinikolaou F, Asteriou C, Tagarakis G, Organtzis J, Tsakiridis K, Tsavlis D, Zissimopoulos A, Kioumis I, Hohenforst-Schmidt W, Zarogoulidis K, Zarogoulidis P, Barbetakis N. Coexistence of squamous cell tracheal papilloma and carcinoma treated with chemotherapy and radiotherapy: a case report. Ther Clin Risk Manag. 2015 Dec 21;12:1-4. [CrossRef] [PubMed]
15. Lin FC, Huang JY, Tsai SC, Nfor ON, Chou MC, Wu MF, Lee CT, Jan CF, Liaw YP. The association between human papillomavirus infection and female lung cancer: A population-based cohort study. Medicine (Baltimore). 2016 Jun;95(23):e3856. Erratum in: Medicine (Baltimore). 2016 Jul 18;95(28):e0916. [CrossRef] [PubMed]
16. Kim HT, Baizhumanova AS. Is recurrent respiratory papillomatosis a manageable or curable disease? Laryngoscope. 2016 Jun;126(6):1359-64. [CrossRef] [PubMed] Epub 2015 Nov 26.
17. Yan Y, Olszewski AE, Hoffman MR, Zhuang P, Ford CN, Dailey SH, Jiang JJ. Use of lasers in laryngeal surgery. J Voice. 2010 Jan;24(1):102-9. Epub 2009 May 31.  [CrossRef] [PubMed]
18. Holler T, Allegro J, Chadha NK, Hawkes M, Harrison RV, Forte V, Campisi P. Voice outcomes following repeated surgical resection of laryngeal papillomata in children. Otolaryngol Head Neck Surg. 2009 Oct;141(4):522-6. [CrossRef] [PubMed]
19. Ivancic R, Iqbal H, deSilva B, Pan Q, Matrka L. Current and future management of recurrent respiratory papillomatosis. Laryngoscope Investig Otolaryngol. 2018 Jan 14;3(1):22-34. [CrossRef] [PubMed]

Cite as: Sharma P, Kumar A, Janapati B, Jain AK. Respiratory papillomatosis with small cell carcinoma: case report and brief review. Southwest J Pulm Crit Care. 2020;21:141-6. doi: https://doi.org/10.13175/swjpcc064-20 PDF

December 2020 Pulmonary Case of the Month: Resurrection or Medical Last Rites?

Lewis J. Wesselius, MD

Department of Pulmonary Medicine

Mayo Clinic Arizona

Scottsdale, AZ USA

History of Present Illness

An 88-year-old man who has been short of breath and febrile up to 101.5° F for the past day presented on October 20, 2020. He has no known sick contacts or exposure to COVID-19.

PMH, SH, and FH

• No reported pulmonary history although he had a Xopenex MDI which he rarely used.
• Coronary artery disease with prior coronary artery bypass grafting (1978); multiple subsequent stents; chronic atrial fibrillation; pacemaker (Micra)
• Stage 3-4 CKD (creatinine 1.95)
• Chronically on warfarin

Physical Examination

• Temp 37.3, Sat 92% on RA, 95% on 2 lpm,
• Lungs: Few crackles in right upper chest
• CV: regular, no murmur
• Ext: 1 to 2+ edema (chronic, uses TED hose)

Which of the following is/are the most likely diagnosis? (Click on the correct answer to be directed to the second of seven pages)

1. Community-acquired pneumonia
2. Congestive heart failure
3. COVID-19
4. 1 and 3
5. Any of the above

Cite as: Wesselius LJ. December 2020 Pulmonary Case of the Month: Resurrection or Medical Last Rites? Southwest J Pulm Crit Care. 2020;21(6):128-37. doi: https://doi.org/10.13175/swjpcc065-20 PDF

Results of the SWJPCC Telemedicine Questionnaire

Richard A. Robbins, MD

Julene R. Robbins, PhD, NCSP

Phoenix Pulmonary and Critical Care Research and Education Foundation

Gilbert, AZ USA

Abstract

As the COVID-19 crisis puts pressure on outpatient providers to facilitate remote care, some have set aside their skepticism and opened telemedicine clinics as an alternative to the traditional office visit. In these visits, the provider and patient usually are able to visually and verbally interact. However, interactions that require contact such as a physical examination are not possible. We conducted a voluntary, anonymous, on-line survey of the Southwest Journal of Pulmonary and Critical Care (SWJPCC) readership to determine their experience and attitudes toward telemedicine. Of the 84 respondents we surveyed, most were favorable towards telemedicine visits with two-thirds of respondents being very or mostly satisfied with telemedicine. However, some (30%) estimated that over 50% of their time was spent with documentation and a significant portion (55%) noted reduced reimbursement. These data support the Center for Medicare and Medicaid’s (CMS) decision to expand telemedicine beyond the present COVID-19 pandemic.

Introduction

The COVID-19 pandemic has created new challenges for patient care. The risk for severe illness from COVID-19 increases with age (1). Many patients and some providers are elderly and at risk for more severe disease. According to the Centers for Disease Control and Prevention (CDC), the best protection is to limit interactions with other people as much as possible (1).

One potential solution which avoids contraction of COVID-19 by face-to-face exposure is telemedicine. Telemedicine is the remote diagnosis and treatment of patients by means of telecommunications technology usually employing both visual and audio interaction. Telemedicine has been around for some time and its use has increasing (2). However, telemedicine is not without limitations including the obvious concerns of reimbursement, regulatory issues, privacy, the need for access to telemedicine devices (e.g., smartphone, tablet, computer), comfort levels with the technology by both healthcare providers and patients, and cultural acceptance of conducting virtual visits in lieu of in-person visits (3). Furthermore, other fundamental issues such as selection of patients and outcomes are largely unknown.

To discover the experiences with and the attitudes toward telemedicine, we posted an on-line questionnaire and solicited the Southwest Journal of Pulmonary and Critical Care (SWJPCC) readership to fill out the questionnaire The results suggest that telemedicine usage has increased with the COVID-19 pandemic, and despite the short time of implementation, is generally acceptable to providers.

Methods

Questionnaire

A questionnaire was constructed with the goals of determining healthcare providers experience and attitudes towards telemedicine.  An additional goal was to keep the survey brief, since previous experience was that long surveys usually have a poor response. A series of 11 questions was developed (Appendix 1).

Data Collection and Statistical Analysis

Data was collected August 9, 2020 through August 31, 2020. The data was collected on the Southwest Journal of Pulmonary and Critical Care website using Excel.

Results

Demographics

There were 84 respondents. Eighty-one answered yes to offering telemedicine but 3 no’s appeared to have prior experience with telemedicine (Appendix 2). Although we did not question which were physicians, nurse practitioners, physician assistants, etc., the vast majority of respondents to previous SWJPCC surveys have been pulmonary and critical care physicians (4).

Sixty-eight of the eighty-four respondents (81%) did not offer telemedicine before the COVID-19 pandemic. The majority of these 64/84 (76%) offered telemedicine to both new and established patients. Only 20/84 (24%) offered telemedicine to established patients only.

Telemedicine platform

There were 90 responses from the 84 respondents to which telemedicine platform was being used. Some respondents apparently used more than one platform.

Table 1. Telemedicine platforms used.

The most common reason cited for using a platform was that the telemedicine platform was offered with the electronic healthcare record currently in use (30 of 84, 36%). An almost an equal number (29/84, 35%) did not know the basis of choosing the platform and presumably had not been involved in the selection process. Only 4 said the platform was chosen on the basis of reviews.

Connectivity

A major concern of telemedicine has been the ability of some patients and providers to use the technology (3). This would likely be reflected in a low number of patients and providers to establish a connection. The results of the questionnaire suggest connectivity is not a major problem (Figure 1).

Figure 1. Connectivity of telemedicine visits. Number of respondents is on the vertical axis and their responses are on the horizontal axis.

There was no consistent pattern in those who had problems with connections (Appendix 2).

Satisfaction

Two-thirds of the respondents were either very or mostly satisfied with their current telemedicine platform (Figure 2).

Figure 2. Satisfaction with current telemedicine system.

There was no consistent pattern to telemedicine satisfaction although other than only one of the seven respondents who used eVisit (Banner Healthcare system) or the VA system was satisfied (Appendix 3).

Disadvantages of Telemedicine

The five most common disadvantages of telemedicine as viewed by the respondents are listed in Table 2.

Table 2. Most common disadvantages of telemedicine.

No other pattern of responses was discerned other than four noting the obvious lack of vitals and physical exams possible with telemedicine.  The questionnaire also asked specifically about time for documentation and reimbursement because one of the authors (RAR) noted high documentation time and low reimbursement in his practice. Documentation time did tend to be high (Appendix 2). Twenty-five respondents (30%) noted that over half the time of a telemedicine visits was spent in documentation and/or billing. Many respondents (35 out of 84, 42%) did not know the reimbursement for the telemedicine visits compared to a face-to-face office visit. One respondent claimed a higher reimbursement with telemedicine; 21 (25%) claimed reimbursement was about the same; and the remainder (74%) claimed lower reimbursement (Appendix 2).

Advantages of Telemedicine

Some advantages of telemedicine are obvious such as decreased exposure to COVID-19. This was noted by a majority of our respondents (80 out of 84 (95%), Table 3).

Table 3. Advantages of telemedicine. 

Other advantages cited included patient preference (42 respondents, 50%); more efficient time utilization (29 respondents, 35%); provider time savings (25 respondents, 30%); and reduced documentation (22 respondents, 26%). There were 11 other responses but none listed by more than 2 respondents.

Discussion

To our knowledge this is the first survey of healthcare providers providing telemedicine since the beginning of the COVID-19 pandemic. Although the sample-size of respondents is not large, it is adequate when compared to relatively smaller number of pulmonary and critical care providers in the Southwest United States. Most (67%) were satisfied with telemedicine. However, 30% noted high documentation times and 55% decreased reimbursement.

Our study is consistent with previous observations that patients are mostly satisfied with telemedicine[HD1] . Gustke et al. (5) reported an extraordinarily high patient satisfaction rate of 98.3% from a telemedicine center. Review articles and meta-analysis suggest that telemedicine is acceptable to most patients in a variety of circumstances (6,7). However, many studies have methodological deficiencies such as low sample sizes, context, and study designs which limit generalizability (6,7). Studies clearly defining “when” and “for what” telemedicine should be utilized are needed. Data demonstrating outcomes will be necessary but at the present time such data is lacking.

Telemedicine has been around for some time but has never been fully utilized. In 2019, only 12% of pulmonologists were using telemedicine although its use has slowly been increasing over the past 20 years (7). Telemedicine usage appears to have been markedly accelerated by the COVID-19 pandemic (8). According to The Physicians Foundation’s 2018 Survey of America’s Physicians conducted by Merritt Hawkins, approximately 18% of physicians indicated they were using telemedicine to treat patients in 2018 (9). That number had increased to 48% by April, 2020 according to a new survey (10). In this rush to establish telemedicine if and how much training the providers receive is unclear.

In a survey conducted by American Well physicians several reasons were listed for choosing telemedicine including: 1. Improved patient access to care (93%); 2. More efficient use of time (77%); 3. Reduced healthcare costs (71%); 4. High-quality communications with patients (71%); and  5. Enhanced doctor-patient relationship (60%) (7). Almost certainly contributing to the increase in telemedicine usage has been the relaxation of the Centers for Medicare & Medicaid Services (CMS) rules regarding reimbursement for telemedicine (11). CMS is now proposing changes to expand telemedicine permanently (12).

Telemedicine visits may require less efforts on the part of the support staff. For example, no vitals are needed. No show rates might also improve. Once telemedicine established and up and running, it can also reduce the size of office space required per provider in the clinic. This could help compensate for lower reimbursement by reducing overhead expenses.

It seems likely that telemedicine will persist in some form after the COVID-19 pandemic. What is unclear is which patients should be seen and what reimbursement should be provided. For example, doing an office visit to check on CPAP compliance for a patient with sleep-apnea is probably appropriate and can probably be done efficiently by telemedicine. However, a more complex patient and especially one where a physical examination is important, might require a face-to-face office visit. Further investigation is needed to determine both appropriateness and optimal reimbursement for telemedicine rather than a one telemedicine fits all approach.

References

1. Centers for Disease Control and Prevention. Older adults and COVID-19. August 16, 2020. Available at: https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/older-adults.html#:~:text=As%20you%20get%20older%2C%20your,than%20people%20in%20their%2050s. (accessed 9/14/20).
2. Health and Human Services. HHS Issues New Report Highlighting Dramatic Trends in Medicare Beneficiary Telehealth Utilization amid COVID-19.  July 28. 2020. Available at: https://www.hhs.gov/about/news/2020/07/28/hhs-issues-new-report-highlighting-dramatic-trends-in-medicare-beneficiary-telehealth-utilization-amid-covid-19.html (accessed 9/14/20).
3. Centers for Disease Control and Prevention. Using Telehealth to Expand Access to Essential Health Services during the COVID-19 Pandemic. June 10, 2020. Available at: https://www.cdc.gov/coronavirus/2019-ncov/hcp/telehealth.html (accessed 9/14/20).
4. Robbins RA, Gotway MB, Robbins JR, Wesselius LJ. Results of the SWJPCC healthcare survey. Southwest J Pulm Crit Care. 2020;20(1):9-15. [CrossRef]
5. Gustke SS, Balch DC, West VL, Rogers LO. Patient Satisfaction with Telemedicine. Telemedicine Journal. 2004;6(1):5-13. [CrossRef]
6. Mair F, Whitten P. Systematic review of studies of patient satisfaction with telemedicine. BMJ. 2000;320(7248):1517-1520. [CrossRef] [PubMed]
7. Kruse CS, Krowski N, Rodriguez B, Tran L, Vela J, Brooks M. Telehealth and patient satisfaction: a systematic review and narrative analysis. BMJ Open. 2017;7(8):e016242. Published 2017 Aug 3. [CrossRef] [PubMed]
8. Zarefsky M. 5 huge ways the pandemic has changed telemedicine. AMA Practice Management. August 26, 2020. Available at: https://www.ama-assn.org/practice-management/digital/5-huge-ways-pandemic-has-changed-telemedicine?gclid=Cj0KCQjwqfz6BRD8ARIsAIXQCf0iteUTWx7lZpFS_uqgkRYc9c4Sjm6iRq9mflmInb-L1H_jvWMszW4aAnsAEALw_wcB (accessed 9/14/20).
9. The Physicians Foundation. 2018 Survey of America’s Physicians. Available at: https://physiciansfoundation.org/wp-content/uploads/2018/09/physicians-survey-results-final-2018.pdf (accessed 9/14/20).
10. Miliard M. CMS relaxes more rules around telehealth, allowing care across state lines. Healthcare IT News. April 10, 2020. Available at: https://www.healthcareitnews.com/news/cms-relaxes-more-rules-around-telehealth-allowing-care-across-state-lines (accessed 9/14/20).
11. Centers for Medicare & Medicaid Services. Trump Administration Proposes to Expand Telehealth Benefits Permanently for Medicare Beneficiaries Beyond the COVID-19 Public Health Emergency and Advances Access to Care in Rural Areas. August 3, 2020. Available at: https://www.cms.gov/newsroom/press-releases/trump-administration-proposes-expand-telehealth-benefits-permanently-medicare-beneficiaries-beyond.

Cite as: Robbins RA, Robbins JR. Results of the SWJPCC Telemedicine Questionnaire. Southwest J Pulm Crit Care. 2020;21:66-72. doi: https://doi.org/10.13175/swjpcc049-20 PDF 

September 2020 Pulmonary Case of the Month: An Apeeling Example

Lewis J. Wesselius, MD

Department of Pulmonary Medicine

Mayo Clinic Arizona

Scottsdale, AZ USA

History of Present Illness

A 67-year-old woman who developed a chronic nonproductive cough beginning in October 2019. After 4 weeks, she consulted her primary care physician.

PMH, SH, and FH

• She had a history of several prior pneumonias, including respiratory syncytial virus in 2018
• Irritable bowel syndrome
• Hypertension
• Prior smoker: 28 pack years, none since 1999
• FH negative

Physical Examination

Her physical examination is recorded as unremarkable other than decreased nasal flow.

Which of the following is/are common cause(s) of a chronic cough? (Click on the correct answer to be directed to the second of seven pages)

1. Cough-variant asthma
2. Gastroesophageal reflux disease
3. Upper airway cough syndrome (UACS) secondary to rhinosinus diseases
4. 1 and 3
5. All of the above

Cite as: Wesselius LJ. September 2020 pulmonary case of the month: an apeeling example. Southwest J Pulm Crit Care. 2020;21(3):56-63. doi: https://doi.org/10.13175/swjpcc048-20 PDF

June 2020 Pulmonary Case of the Month: Twist and Shout

Lewis J. Wesselius, MD¹

Staci E. Beamer, MD² 

¹Departments of Pulmonary Medicine and ²Thoracic Surgery

Mayo Clinic Arizona

Scottsdale, AZ USA

History of Present Illness

An 83-year-old man presented with a left upper lobe lung nodule. The nodule was noted on a routine follow-up chest radiograph obtained after a radical cystectomy and left nephro-ureterectomy done 9 months earlier for invasive bladder cancer as well clear cell carcinoma of left kidney. He had symptoms of a mild chronic cough but denied shortness of breath with activities of daily living.

PMH, SH, FH

• Prostate cancer, post prostatectomy in 2009. 
• Bladder cancer and left renal cell cancer resected in Jan 2019
• Post-op chemotherapy after bladder and left kidney resections
• Non-ischemic cardiomyopathy, possibly due to            chemotherapy, EF 45%
• Chronic atrial fibrillation
• Smoking history: 60 pack years, no occupational exposures

Physical Examination

Other than an irregular pulse, his physical examination was unremarkable.

Medications

• Warfarin
• Atorvastatin
• Hydrochlorothiazide
• Ramipril
• Atenolol

Radiography

The initial chest radiograph is shown in Figure 1.

Figure 1. Initial chest x-ray.

Which of the following should be done at this time? (Click on the correct answer to be directed to the second of eight pages)

1. Chest CT scan
2. Left upper lobectomy
3. Comparison to old chest x-rays
4. 1 and 3
5. All of the above

Cite as: Wesselius LJ, Beamer SE. June 2020 pulmonary case of the month: twist and shout. Southwest J Pulm Crit Care. 2020;20(6):179-87. doi: https://doi.org/10.13175/swjpcc038-20 PDF 

Case Report: The Importance of Screening for EVALI

Vanessa Josef MD, MS

George Tu, MD, FCCP

Department of Internal Medicine and Lung Center of Nevada

HCA MountainView Hospital

Las Vegas, Nevada, USA

Abstract

E-cigarette or vaping product use associated lung injury (EVALI) is an epidemic that has swept the United States by storm starting in Sept 2019. E-cigarettes or vaping was initially advertised as a “safer” alternative to smoking cigarettes when they entered the market in 2007. Only now are we are starting to see the complications of a not so harmless behavior. Many times, EVALI can present similar to community acquired pneumonia (CAP), which can cause a clinical conundrum when despite adequate antibiotic coverage, patients’ respiratory status tend to decline. Through our case report, we demonstrate and stress the importance of early screening for e-cigarette and vaping use in social history to increase clinical suspicion of EVALI and provide early intervention if a patient does not respond to CAP treatment, in hopes of identifying more cases of EVALI and igniting future research. 

Introduction

The recent outbreaks of E-cigarette or vaping product use associated lung injury (EVALI) in Sept 2019, has placed the spotlight on the dangers of vaping. EVALI is a form of acute or subacute lung injury whose pathogenesis is unknown and is thought to be a spectrum of disease, rather than a single process. It has many findings such as organizing pneumonia, diffuse alveolar damage or acute fibrinous pneumonitis that are bronchiocentric and accompanied by bronchiolitis (1). If not identified quickly, EVALI has led to non-invasive ventilation, intubation and mechanical ventilation and even death in, otherwise, healthy young adults (1). The CDC confirmed 57 deaths and 2,602 reported cases of EVALI throughout the United States from Aug 2019 to Jan 2020, all of whom were between the ages of 18-34 (2,3). The paucity of knowledge within the medical community with regards to the disease, its pathogenesis and targeted treatment puts clinicians at a disadvantage. We report a case of a 30-year-old male who presented to our hospital with complaints of flu-like symptoms who was initially thought to have community acquired pneumonia but was later diagnosed with EVALI in order to raise awareness, illustrate how crucial screening can affect patient outcome and the need for further investigations of this severe respiratory illness. 

Case Presentation

A 30-year-old Hispanic male with significant past medical history of intracranial hemorrhage secondary to arteriovenous malformation and craniotomy (2016) was admitted to our hospital in December 2019 after experiencing productive cough, subjective fevers, malaise, night sweats, dizziness, and fatigue for 3 days. He denied having any sick contacts or obtaining the flu vaccine, or any recent hospitalization. His admitting diagnosis was sepsis due to community acquired pneumonia and he was found to have acute renal failure which was pre-renal in nature.

Clinical findings on admission were as follows: body temperature 37°C, blood pressure 116/75mmHg, heart rate 129 beats/min, respiratory rate 18 breaths/min and oxygen saturation 99% on room air. Physical examination revealed diminished breath sounds on the right lower lobe upon auscultation. The patient’s breathing did not appear labored and he was able to speak full sentences. Laboratory tests revealed: white blood cell count of 13,000 x 10⁹/L with 88.8% neutrophils, BUN/creatinine was 29/1.59 (elevated compared to last admission in 2016), urine toxicology was positive for cannabinoids, urinalysis showed proteinuria of 100 and the rest of the biochemical testing were within normal ranges.

The initial chest x-ray (Figures 1 and 2) was read as interval development of interstitial type infiltrates in the perihilar and lower lobe distribution bilaterally, favoring pneumonia, compared to his pervious chest x-ray from 2016 which had no evidence of acute cardiopulmonary process (Figure 3).

Figures 1 and 2. Chest radiography (PA and lateral views) from the day of admission.

Figure 3. Chest radiograph from a previous admission in 2016 showing no acute cardiopulmonary process.

Sepsis bolus was given in the emergency department, blood cultures were drawn, and patient was started on ceftriaxone and azithromycin for community acquired pneumonia. Overnight, The patient spiked fever twice of 39°C at 2am and 4am the next morning. Antibiotics were broadened to vancomycin and piperacillin-tazobactam and blood cultures were repeated. Patient endorsed dyspnea and increased work of breathing requiring 2L nasal cannula. He remained tachycardic with his heart rate in the 110s despite adequate fluid resuscitation and antibiotic coverage. He also spiked an additional fever of 39.3°C at 8am. Arterial blood gas obtained showed pH 7.49, pCO₂ 33, pO₂ 70, HCO₃ 25 on 2L nasal cannula indicating acute hypoxic respiratory failure and respiratory alkalosis. Since renal function normalized, CT angiogram of the chest (Figure 4) was obtained. Although negative for pulmonary embolism, it showed extensive bilateral ground-glass lung opacities characteristic of pulmonary edema or pneumonia, noted predominantly in the lower and middle lung zones with sparing of the periphery.

Figure 4. CT angiography of the chest in lung windows, almost 24hrs after presentation to the emergency department.

Pulmonology was consulted. Upon further questioning it was discovered the patient has been vaping CBD oil and THC for about 5 years. He vapes approximately 1-2 dabbed cartridges per week which he normally obtains from a dispensary and his friends. The last time he vaped was 3 days prior to admission. He denied smoking tobacco, having a history of childhood asthma. He was started on methylprednisolone 40mg IV BID. Because his temperature became mildly elevated at 37.9°C in the afternoon, it was decided to take him for a bronchoalveolar lavage (BAL) the following day.

Respiratory viral panel, urine Legionella and urine Streptococcus pneumoniae, HIV 4^th generation screen, sputum culture and blood cultures were all negative. Procalcitonin was 3.88 ng/ml. BAL cytology revealed non-specific pulmonary macrophages, benign bronchial epithelial cells, and mucus. It was negative for fungal organisms, cytomegalovirus, Mycoplasma, tuberculosis, Pneumocystis jirovecii, Legionella, and malignant cells. Gram stain was negative as well. 

No other events occurred during the rest of his hospital course. Extensive counseling provided regarding cessation of vaping, which the patient expressed he will no longer do. His respiratory symptoms improved with the start of steroids and he was discharged on hospital day 6 with Augmentin and a 10-day prednisone taper.

Discussion

Currently, EVALI is a diagnosis of exclusion, rather than part of the initial screening for patients who present to the hospital with respiratory complaints. During our team’s initial assessment of the patient, vaping was not asked based off the reported history, imaging studies, and labs obtained by the emergency department because it appeared to be a straightforward case of sepsis secondary to community acquired pneumonia (CAP). However, despite adequate antibiotic coverage with ceftriaxone and azithromycin our patient continued to spike high fevers overnight. He did not have any risk factors for MRSA or Pseudomonas that would call for broad empiric coverage when he was first admitted based off the IDSA 2019 guidelines for treating CAP (7).

Despite sepsis fluid resuscitation, our patient remained tachycardic where his heart rate ranged between 110-120s. CT angiogram of the chest to rule out pulmonary embolism could not be done when he was admitted due to acute renal failure. A ventilation-perfusion scan would not be an appropriate study at the time due to patient’s abnormal chest x-ray. Thus, the details of the lung parenchyma could not be appreciated at the time of admission. With his continual fever spikes, we ordered the following labs to try and identify the type of infection, the possibility of a superimposed infection or resistance to the current antimicrobial regimen and if the patient was immunocompromised: flu antigens, urine Legionella and Streptococcus pneumoniae, respiratory viral panel (adenovirus, human metapneumovirus, influenza A & B, parainfluenza 1, 2 & 3, RSV, rhinovirus), HIV 4^th generation screen, sputum culture, procalcitonin and repeat blood cultures. That same morning, his antibiotics were broadened to vancomycin and piperacillin-tazobactam.

Since the patient endorsed increased work of breathing and required 2L nasal cannula when he was initially on room air when he first arrived, pulmonary embolism (PE) had to be ruled out. With his renal function back to normal, we were able to get the CT angiogram of the chest which was negative for PE but showed the largely affected parenchyma. Pulmonology was consulted because of the irregular findings and sudden decline. Based off the peripheral sparing which is characteristic for EVALI and his urine toxicology testing positive for cannabinoids, further questioning about his social history was obtained. The patient’s admission to vaping THC and CBD oil for several years and that he obtains his cartridges from dispensaries and his friends, increased the suspicion for EVALI. Based on the current literature and reports from the CDC, EVALI is largely associated with the use of THC and products obtained from informal sources such as family/friends, dealers or online sellers (1). Many times, these unregulated products contain vitamin E acetate, which is currently thought to be the culprit ingredient igniting the destruction of lung parenchyma (4). The answer remains unclear if the cause of EVALI is an inhalation injury and/or is there an intrinsic reaction sparked by the chemical reactions between the various products that causes tissue injury.

He was immediately started on methylprednisolone 40mg IV BID, based on the recommended dosing of intravenous steroids of 1mg/kg (6). However, the patient’s temperature started to rise again despite the initiation of empiric antibiotics and steroids on the same day. BAL was performed the next morning to rule out infection, malignancy or any other structural issues and only revealed non-specific pulmonary macrophages, benign bronchial epithelial cells, and mucus. The patient clinically improved with the continued regimen of vancomycin, piperacillin-tazobactam and methylprednisolone IV.

There have been notable case reports with regards to EVALI that illustrate its various presentations and some of the barriers that make it difficult to diagnose. Salzman et al. (8) presented a case of a 27-year-old Caucasian female who developed acute eosinophilic pneumonia associated with electronic cigarettes. CBC at the time of admission showed WBC of 24,400 with 47% eosinophils. Although she admitted to vaping both nicotine and THC products for at least three years, three months prior to admission, she was vaping exclusively JUUL pods with nicotine blueberry and mint flavors. Her symptoms were severe enough that she required a one day stay in the ICU. She was treated with oral prednisone 50mg daily for a total of 5 days and oral doxycycline 100mg BID with improvement in her symptoms. This brings up the question whether her prior vaping history already jeopardized her lung parenchyma thus putting her at higher risk for developing EVALI.

In Schmitz’ (9) case report of a 38-year-old obese female with fibromyalgia on chronic prednisone (20mg daily), she admits to having started vaping CBD oil one month prior to admission. On BAL she was found to have diffuse upper and lower airway erythema with significant coughing, elevated eosinophil count (59%) and foamy macrophages which is associated with EVALI. She was started on methylprednisolone 1000mg daily, without antibiotics and experienced rapid improvement within a couple of days.

Works and Stack (5) discussed the case of a 20-year-old male who had several hospital admissions due to complaints of productive cough, high grade fever, gastrointestinal symptoms of diarrhea/nausea and 20lb unintentional weight loss over 3 weeks. The patient initially was treated at another hospital with ceftriaxone, levofloxacin and azithromycin and did not complete the course of antibiotics because they left against medical advice since they did not experience any improvement. On admission, the patient was found to have a very high leukocytosis with WBC of 44,800 and was not started immediately on empiric antibiotics. Instead, he was started on prednisone 1mg/kg and Bactrim after the BAL failed to yield an infectious cause. The patient was also noted to have obtain his THC cartridges from an outside source, like our patient.

Panse’s (10) case of a 25-year-old male who previously smoked 1-2packs per day and quit 6 months prior to admission was not forthcoming about vaping. Both CT scans showed multifocal ground-glass opacities with features of small airway obstruction. He underwent bronchoscopy and transbronchial biopsy which did not provide enough information to make a diagnosis. A video-assisted thorascopic lung biopsy was performed and showed acute and organized lung injury with interstitial edema, type II pneumocyte hyperplasia, alveolar fibrin deposition, acute fibrinous pneumonitis, lipid-laden macrophages and foci of organizing pneumonia consistent with EVALI. This is a prime example of how omission of vaping history delays diagnosis, leads to invasive procedures and although it did not happen in this particular situation, can result in death (10). Unlike the patient in Panse’s case, our patient easily admitted to vaping. Non-disclosure of medically relevant information such as vaping, is a problem clinicians will run into especially since it is a key piece of information needed to diagnose EVALI. Many patients withhold information from their doctors, especially those that they may find embarrassing, feel that they will be judge or lectured, or not wanting to hear about associated harm. Quantifying how many patients are withholding information or how many cases are not being accounted for because the person does not want to admit they are vaping would be difficult.

Formal diagnostic criteria for EVALI has not been agreed upon which can be attributed to the various forms of lung injury. We were able to diagnose our patient based of the suggested criteria of e-cigarette or vaping in the previous 90 days, lung opacities on chest x-ray or CT, exclusion of infection, and the absence of alternative diagnosis (cardiac, neoplastic or rheumatologic) (1). In a case series by Kalininskiy et al. (12), the University of Rochester Medical Center (Rochester, New York, USA) created a clinical practice algorithm to allow for the rapid identification of suspected EVALI based on history, clinical presentation and chest imaging, which is similar to the CDC however it focuses on vaping activity from the past 30 days rather than 90 days.

Currently, the treatment of EVALI is empiric antibiotics for community acquired pneumonia, systemic glucocorticoids in those with worsening symptoms, and supportive therapy with supplemental oxygen (6). In our case, the patient improved with the combination of vancomycin, piperacillin-tazobactam and methylprednisolone. The efficacy of systemic glucocorticoids is still unknown (1). However, it still remains unclear whether it was the combination of those specific antibiotics in conjunction with steroids, the combination of vancomycin and piperacillin-tazobactam only or solely systemic glucocorticoids. Since CAP is more common, it should not be overlooked and go untreated. Further investigation needs to be done for more targeted therapy.

The long-term effects of EVALI in those who were treated are still not well known. It is currently recommended for repeat imaging to determine if the treatment regimen was successful. However, many patients are lost to follow-up, as was the case for our patient due to lack of insurance.

Our case report illustrates how crucial early identification of EVALI affects patient care. It is imperative clinicians screen for the disease to prevent further complications. We recommend the following screening criteria: although the population greatly affected by the EVALI epidemic have been predominantly males between the ages of 18-34 (37% of the cases reported to the CDC as of Jan 14, 2020 are age 18-24, and 24% are 25-34, with a 66% male predominance) it should include all those who vape or use e-cigarettes regardless of age or gender as illustrated with the aforementioned case reports (13). Patients who presents with respiratory symptoms, especially if they are similar to pneumonia, such as dyspnea, increased work of breathing, fevers/chills, productive cough, chest pain, pleurisy, hemoptysis, and noted hypoxemia should be asked more than just smoking history with regards to cigarettes. They should be asked about prior E-cigarettes usage or vaping in the past, when was the last use, what kind of products were used and were they concentrated/dabbed and where it was obtained. Clinical suspicion should be increased if patients admit to THC or CBD use, but nicotine, flavorings and additives should not be disregarded. Urine drug screen should be ordered if there is a strong clinical suspicion, and the patient is denying prior THC use. EVALI has also been associated with gastrointestinal symptoms of abdominal pain, diarrhea, and nausea/vomiting. It is important to rule out infectious causes, by asking about sick contacts, recent hospitalizations, history of HIV and use of immunologic agents that can cause one to be immunocompromised. Patients should be screened about airway diseases such as asthma, COPD, and interstitial lung disease since they could have already caused chronic changes to lung parenchyma. There is still so much that the medical community does not know about EVALI. Further investigations still need to be pursued to improve the medical community’s diagnosis and treatment of this serious respiratory epidemic.

Disclaimer

This research was supported (in whole or in part) by HCA and/or an HCA affiliated entity. The views expressed in this publication represent those of the author(s) and do not necessarily represent the official views of HCA or any of its affiliated entities.

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):903-16. [CrossRef] [PubMed]
2. Centers for Disease Control. Outbreak of lung injury associated with the use of e-cigarette, or vaping, products. January 17, 2020.Available at: https://www.cdc.gov/tobacco/basic_information/e-cigarettes/severe-lung-disease.html#key-facts (accessed 3/10/20).
3. Ellington S, Salvatore PP, Ko J, et al. Update: product, substance-use, and demographic characteristics of hospitalized patients in a nationwide outbreak of e-cigarette, or vaping, product use-associated lung injury - United States, August 2019-January 2020. MMWR Morb Mortal Wkly Rep. 2020 Jan 17;69(2):44-9. [CrossRef] [PubMed]
4. 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]
5. Works K, Stack L. E‐cigarette or vaping product‐use‐associated lung injury (EVALI): A case report of a pneumonia mimic with severe leukocytosis and weight loss. JACEP Open. 2020;1-3. [CrossRef]
6. Triantafyllou GA, Tiberio PJ, Zou RH, et al. Vaping-associated acute lung injury: a case series. Am J Respir Crit Care Med. 2019 Dec 1;200(11):1430-1. [CrossRef] [PubMed]
7. Metlay JP, Waterer GW, Long AC, et al. Diagnosis and treatment of adults with community-acquired pneumonia. an official clinical practice guideline of the American Thoracic Society and Infectious Diseases Society of America. Am J Respir Crit Care Med. 2019 Oct 1;200(7):e45-e67. [CrossRef] [PubMed]
8. Salzman GA, Alqawasma M, Asad H. Vaping associated lung injury [EVALI]: an explosive United States epidemic. Mo Med. 2019 Nov-Dec;116(6):492-6. [PubMed]
9. Schmitz ED. Severe respiratory disease associated with vaping: a case report. Southwest J Pulm Crit Care. 2019;19[3]:105-9.[CrossRef]
10. Panse PM, Feller FF, Butt YM, Gotway MB. February 2020 imaging case of the month: an emerging cause for infiltrative lung abnormalities. Southwest J Pulm Crit Care. 2020;20(2):43-58. [CrossRef]
11. Levy AG, Scherer AM, Zikmund-Fisher BJ, Larkin K, Barnes GD, Fagerlin A. Prevalence of and factors associated with patient nondisclosure of medically relevant information to clinicians. JAMA Netw Open. 2018 Nov 2;1(7):e185293. [CrossRef] [PubMed]
12. Kalininskiy A, Bach CT, Nacca NE, Ginsberg G, Marraffa J, Navarette KA, McGraw MD, Croft DP. E-cigarette, or vaping, product use associated lung injury (EVALI): case series and diagnostic approach. Lancet Respir Med. 2019 Dec;7(12):1017-26. [CrossRef] [PubMed]
13. Centers for Disease Control. Outbreak of lung injury associated with the use of e-cigarette, or vaping, products. February 5, 2020. Available at:  https://www.cdc.gov/tobacco/basic_information/e-cigarettes/severe-lung-disease.html#map-cases (accessed 3/10/20).

Cite as: Josef V, Tu G. Case report: the importance of screening for EVALI. Southwest J Pulm Crit Care. 2020;20(3)87-94. doi: https://doi.org/10.13175/swjpcc012-20 PDF 

March 2020 Pulmonary Case of the Month: Where You Look Is Important

Richard A. Robbins, MD

Anselmo Garcia, MD

Arizona Chest and Sleep Medicine

Phoenix, AZ USA

History of Present Illness

A 47-year-old woman was seen for the first time in our clinic. She had approximately a two-year history of gradually increasing shortness of breath to the point where she could only climb one flight of stairs. In addition, she has a history of a cough sometimes productive and sometimes nonproductive. She did hear herself wheeze intermittently.

PMH, SH, and FH

She has a past medical history of gastroesophageal reflux disease (GERD). She was a nonsmoker and had no occupational exposure. Her aunt has a history of asthma.

Physical Examination

Her physical examination was normal and her lungs were clear.

Which of the following is appropriate at this time?

1. Reassurance
2. Treat empirically for post-nasal drip
3. Treat empirically with albuterol
4. Treat empirically with omeprazole
5. None of the above

Cite as: Robbins RA, Garcia A. March 2020 pulmonary case of the month: where you look is important. Southwest J Pulm Crit Care. 2020;20(3):76-83. doi: https://doi.org/10.13175/swjpcc013-20 PDF

Brief Review of Coronavirus for Healthcare Professionals February 10, 2020

Richard A. Robbins, MD¹

Stephen A. Klotz, MD²

¹Phoenix Pulmonary and Critical Care Research and Education Foundation, Gilbert, AZ USA

²Division of Infectious Diseases, Department of Internal Medicine, University of Arizona, Tucson, AZ USA

The epidemic of coronavirus (2019-nCoV) near Wuhan City and the surrounding Hubei Province in China has received extensive news coverage. Some have predicted the virus will cause a worldwide pandemic (1). The CDC has an extensive website discussing over numerous pages whom to suspect, how to diagnose and how to treat 2019-nCoV. 2019-nCoV represents the most recent of the severe coronaviral infections. Severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) are also caused by coronaviruses that have jumped from animals to humans like 2019-nCoV. It should be remembered that there are only 12 confirmed cases of 2019-nCoV in the US and the mortality rate appears to be only about 3% which is lower than SARS or MERS (2,3). This could be offset by a greater infectiousness of 2019-nCoV resulting in more aggregate infectious, and hence, deaths.

Anyone with a fever who has recently visited the epidemic area in China or been exposed to someone with known 2019-nCoV should be quarantined (2). The only reliable symptom has been fever (98%) (4). Cough (76%), myalgia/fatigue (44%), sputum production (28%), headache (8%), hemoptysis (5%), and diarrhea (3%) were much less common. The clinical course was characterized by the development of dyspnea in 55% of patients and lymphopenia in 66%.

Persons suspected of 2019-nCoV should be quarantined and reported to their local state health departments. The incubation period appears about 2-14 days and is spread by person-to-person transmission based on the previous MERS epidemic (2). There is no need to wear masks in the US where the incidence is low and they are likely ineffective (2).

Diagnosis is made real-time reverse transcription polymerase chain reaction (rRT-PCR) assay. This was only available from the CDC but very recently the CDC has made kits available to state health departments (2).

At present the treatment for 2019-nCoV is supportive in appropriate respiratory isolation to protect healthcare workers. A randomized, controlled trial of Gilead’s antiviral drug remdesivir used to treat Ebola is currently underway in China in hopes that it will be an effective treatment for 2019-nCoV (5).

Please be aware that this information is current as of February 10, 2020. It is likely to change.

References

1. McNeil DG Jr. Wuhan coronavirus looks increasingly like a pandemic, experts say. New York Times. February 2, 2020. Available at: https://www.nytimes.com/2020/02/02/health/coronavirus-pandemic-china.html (accessed 2/10/20).
2. Centers for Disease Control. 2019 Novel Coronavirus (2019-nCoV) in the U.S. February 10, 2020. Available at: https://www.cdc.gov/coronavirus/2019-ncov/cases-in-us.html (accessed 2/10/20).
3. Worldometer. Novel coronavirus (2019-nCoV) mortality rate. Available at: https://www.worldometers.info/coronavirus/coronavirus-death-rate/ (accessed 2/10/20).
4. Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020 Jan 24. pii: S0140-6736(20)30183-5. [Epub ahead of print] [CrossRef] [PubMed]
5. Wetsman N. An experimental antiviral medication might help fight the new coronavirus. The Verge. Feb 4, 2020. Available at: https://www.theverge.com/2020/2/4/21122327/coronavirus-experimental-medication-treatment-wuhan-china-gilead-hiv (accessed 2/10/20).

Cite as: Robbins RA, Klotz SA. Brief review of coronavirus for healthcare professionals February 10, 2020. Southwest J Pulm Crit Care. 2020;20(2):69-70. doi: https://doi.org/10.13175/swjpcc011-20 PDF