USF Health physician-scientist Dr. Juan Carlos Cardet was co-first author for the New England Journal of Medicine article reporting results of the long-awaited PREPARE trial

TAMPA, Fla (Feb. 26, 2022) — Black and Latinx patients suffer disproportionately from asthma, a chronic inflammatory disease with symptoms including shortness of breath, tightness in the chest, coughing, and wheezing. They experience more severe asthma, higher rates of asthma-related emergency department visits and hospitalizations, and approximately double the asthma death rates compared to white patients.

A new approach for managing moderate-to-severe asthma, known as single maintenance and reliever therapy, combines two medications in one inhaler for control of underlying inflammation and quick relief of acute symptoms. While this strategy has gained interest and led to updated guidelines for patients, no studies to date have focused on Black and Latinx populations.

To help address the lack of comparable data for these underrepresented populations, the PREPARE (PeRson EmPowered Asthma RElief) trial enrolled 1,201 Black and Latinx adults (ages 18 to 75)  with moderate-to-severe asthma. The study was conducted November 2017 to April 2021 at 19 sites in the U.S., including the USF Health Morsani College of Medicine, and Puerto Rico. Participants were randomized to one of two groups. In addition to continuing their usual asthma medications, half of the participants (intervention group) received one-time instruction on how to use inhaled corticosteroids whenever they dispensed airway-opening reliever medications via a nebulizer or rescue inhaler. The other half (control group) also continued their usual care (UC) but did not dispense inhaled corticosteroids as needed to treat asthma attacks along with quick-relief medications. All patients had one instructional visit followed by 15 monthly questionnaires.

The PREPARE study demonstrated that this new intervention, called Patient-Activated Reliever-Triggered Inhaled Corticosteroids (PARTICS), substantially reduced severe asthma attacks, improved asthma control and quality of life, and decreased lost days from work or school.

The study results were presented by USF Health physician-scientist Juan Carlos Cardet, MD, MPH, Feb. 26 at the 2022 Annual Meeting of the American Academy of Allergy, Asthma & Immunology (AAAAI) and simultaneously published in The New England Journal of Medicine.

“Despite decades spent trying to find effective solutions to address the health disparities in asthma care, we haven’t made a significant dent in the problem,” said Dr. Cardet, an assistant professor in the USF Health Division of Allergy and Immunology. “The patient-centered PARTICS intervention we investigated works in underrepresented populations with poorly controlled asthma. It’s feasible, low cost, and may be easy to implement and help reduce the burden of complications from asthma if we can bring it to the clinic.”

Dr. Juan Carlos Cardet of the USF Health Morsani College of Medicine’s Allergy and Immunology Division studies better ways to treat poorly controlled asthma, including in underserved populations.

Dr. Cardet was the PREPARE study’s co-first author along with Elliot Israel, MD, the Gloria M. and Anthony C. Simboli Distinguished Chair in Asthma Research and director of Clinical Research in the Pulmonary and Critical Care Division, Brigham and Women’s Hospital. Thomas Casale, MD, a professor of medicine and pediatrics in the USF Health Division of Allergy and Immunology, helped execute the study as the USF site principal investigator.

Among PREPARE’s key findings:

• The annualized rate of severe asthma exacerbations was 0.69 per patient for participants in the PARTICS+UC group; the rate was 0.82 for the control group.
• Participants in the PARTICS+UC group also showed improved scores for asthma control and quality of life compared to patients in the control group.
• Those in the PARTICS+UC group also missed fewer days of school, work or other usual activities compared to the control group (13.4 versus 16.8 days)

A distinctive aspect of the PREPARE trial was the degree of engagement by patients to help optimize the study. Researchers collaborated with Black and Latinx adults with asthma as well as asthma caregivers — called Patient Partners — who are among the NEJM paper’s coauthors.

Dr. Cardet, working with Dr. Israel worked with other collaborators, designed a symptom-driven treatment approach consistent with what patients wanted; that is, an intervention intended to help control the chronic inflammation of asthma (with an inhaled corticosteroid) at the same time an inhaled reliever medication is delivered to ease severe flare-ups of symptoms.

Many patients are prescribed complicated regimens of controller medications to be taken daily, even on days when they experience no need for a fast-acting medication to open their constricted airways,” Dr. Cardet said. “In real life, patients may or may not adhere to that regimen when they’re feeling OK, but they will use their medications when symptoms arise.”

This work was supported by a Patient-Centered Outcomes Research Institute (PCORI) Project Program Award (PCS-1504-30283), the Gloria M. and Anthony Simboli Distinguished Chair in Asthma Research Award, grant #K23AI125785 from the National Institute of Allergy and Infectious Diseases (NIAID) and grant #AI-835475 from the American Lung Association (ALA)/American Academy of Allergy, Asthma & Immunology (AAAAI).

Dr. Cardet is a co-investigator for the Precision Interventions for Severe and/or Exacerbation-Prone Asthma Network (PrecISE) sponsored by the National Heart, Lung, and Blood Institute (NHLBI). This multisite clinical study, which aims to identify biomarkers to guide development of targeted treatments for severe asthma, is also seeking participants from underrepresented populations.

USF Health’s Dr. Thomas Casale leads one of only two academic allergy-research centers in Florida participating in the national trial

TAMPA, Fla. (April 14, 2021) — USF Health is participating in a National Institutes of Health (NIH) clinical trial to determine whether highly allergic people or those with mast cell disorders are at greater risk for severe, immediate allergic reactions to the Moderna or Pfizer-BioNTech COVID vaccines.  A mast cell disorder is caused by a type of white blood cell that is abnormal, overly active or both, predisposing a person to life-threatening reactions that resemble allergic reactions.

USF Health allergist Thomas Casale, MD, is the USF site principal investigator for the Systemic Allergic Reactions to SARS-CoV-2 Vaccination clinical trial, sponsored by the National Institute of Allergy, Immunology and Infectious Diseases, part of NIH. | Photo by Torie Doll

The USF Health Asthma, Allergy and Immunology Clinical Research Unit is one of only two academic allergy-research centers in the state, and up to 35 centers nationwide, enrolling adults who have not yet received a COVID vaccine in this Phase 2 randomized, placebo-controlled trial funded by NIH’s National Institute of Allergy and Infectious Diseases (NIAID). The USF site will enroll 120 participants, ages 18 to 69, in the study; two-thirds must have a history of severe allergic reactions or diagnosis of a mast cell disorder, and one-third must have no history of allergies. Nationwide, 3,400 adults are expected to complete the 17-week NIAID trial called Systemic Allergic Reactions to SARS-CoV-2 Vaccination.

The Moderna and Pfizer-BioNTech COVID-19 vaccines were the first two COVID-19 vaccines authorized by the Food and Drug Administration for emergency use and have already been given to millions of Americans.

Rare, severe allergic reactions to both messenger RNA (mRNA) COVID vaccines have occurred more commonly in women and primarily in people with a history of allergies to foods, insect bites, or medications. A large number had previously experienced anaphylaxis, a potentially life-threatening allergic reaction with serious symptoms, such as  hives, swelling, low blood pressure, difficulty breathing and severe diarrhea. Reversing anaphylaxis requires treatment with autoinjectible epinephrine, and/or an emergency room visit.

“Defining the causes of acute allergic reactions to these two mRNA vaccines will be critical to enhance safety of potentially required booster mRNA vaccinations, or different mRNA vaccine platforms, used for COVID or other infectious diseases,” said USF site principal investigator Thomas Casale, MD, a professor of medicine and pediatrics in the Division of Allergy and Immunology, USF Health Morsani College of Medicine.

Severe allergic reactions to the two mRNA COVID-19 vaccines  — made by Pfizner-BioNtech and by Moderna  — have been rare, but higher than incidences reported for other vaccines in general. | Photo by Allison Long

Anaphylaxis has been reported at a rate of about 10 to 12 people per every 1 million Pfizer-BioNTech COVID-19 vaccine doses administered, and 2.5 per 1 million Moderna vaccine doses,

“These incidences have been rare, but still higher than what we see with typical vaccines, such as those for influenza; measles, mumps and rubella; tetanus; and hepatitis. With vaccines in general, severe allergic reactions occur at a rate of about 1.3 people per 1 million injections,” Dr. Casale said. “I would emphasize that nothing contained in these two mRNA COVID vaccines has yet been identified as the culprit triggering the allergic reactions reported.”

Study participants will be divided into groups and assigned at random to receive either the Pfizer-BioNTech vaccine (one-third), the Moderna vaccine (one-third), a placebo followed by the Pfizer-BioNTech vaccine (one sixth); or a placebo followed by the Moderna vaccine (one sixth). Initially, neither the participants nor the study team will know who receives a vaccine or the placebo, or which vaccine is being administered. All participants ultimately will receive a full two-dose course of either the Pfizer-BioNTech vaccine or the Moderna vaccine.

The Centers for Disease Control and Prevention currently recommends a 30-minute on-site observation period after COVID-19 vaccination for people with any history of severe or sudden allergic reactions. Those in the NIAID trial will be closely monitored for at least 90 minutes after each injection by allergists trained to recognize and treat anaphylaxis, and armed with emergency medications, oxygen, and medical equipment.

“It’s important to allay some of the vaccine hesitancy concerns among this higher-risk population,” Dr. Casale said. “We’re vaccinating people in a very controlled environment. So, if anyone does experience an acute allergic reaction, we’re right there to immediately treat them and get them safely through it.”

Investigators will assess the proportion of study participants in each group who have a severe allergic reaction within 90 minutes after injection with the first or second doses of either the Pfizer-BioNTech vaccine or the Moderna vaccine. Results are expected in late summer 2021.

The USF Health Asthma, Allergy and Immunology Clinical Research Unit stocks stocks auto-injectable epinephrine that can be quickly administered to counteract severe and immediate allergic reactions. | Photo by Torie Doll

If a significant number of severe allergic reactions to either or both mRNA COVID vaccines occur during the trial, researchers will analyze blood and urine samples collected before and after each injection to identify possible biological mechanisms for the reactions. They will examine whether certain genetic patterns or other factors can predict which individuals are most susceptible to adverse effects, Dr. Casale said.

For more information on the clinical trial, or to speak to a USF Health coordinator, please call 813-631-4024.

Tampa, FL (June 8, 2016) — The American Lung Association’s Airways Clinical Research Centers (ACRC) network has expanded the national reach of its clinical trials to enhance the quality of life for patients with asthma and chronic obstructive pulmonary disease (COPD). The University of South Florida (USF) — a continuous member of the Lung Association ACRC since its inception in 1999 — is among 17 centers across the country and one of only two centers in Florida.

The non-profit national network studies patients with airways diseases, specifically asthma and COPD, the latter of which includes emphysema and chronic bronchitis.

Asthma affects a high rate of Florida’s population, 8 percent of adults and 10 percent of children, and nearly 8 percent of Floridians have COPD, said Thomas Casale, MD, who assumes the role of principal investigator for USF’s Lung Association ACRC on July 1.

“Finding how best to treat these patients is a primary goal of the American Lung Association’s ACRC,” said Dr. Casale, professor of medicine and pediatrics in the Division of Allergy and Immunology, Department of Internal Medicine, USF Health Morsani College of Medicine.

                              Dr. Thomas Casale, left, and Dr. Richard Lockey

“Participation in this network gives our patients the opportunity to enroll in clinical studies designed to study these disorders and define optimal care for patients with asthma or COPD.  They can also expect to learn a lot about their disease and how best to manage their symptoms.”

Many studies published by investigators in the highly competitive Airways Clinical Research Centers network have been published in the New England Journal of Medicine or the Journal of the American Medical Association.

Richard Lockey, MD, director of the USF Health Division of Allergy and Immunology, has been USF’s ACRC principal investigator since the group began and will continue to collaborate on studies. Under his leadership, USF has participated in a variety of ACRC network clinical trials in which outcomes are helping shape the nature of care, including the:

• Anxiety and COPD Evaluation (ACE Trial) examining the relationship between anxiety, health status and prognosis to inform appropriate treatment strategies. Open at USF through June 30, 2016.
• Resistant Airway Obstruction in Children (REACH) study, investigating whether or not anti-inflammatory medications normally prescribed for children with asthma can help in the management of children with fixed airflow obstruction. Open at USF through June 30, 2017.
• Long-acting Beta Agonist Step-Down Study (LASST), investigating the best way to reduce treatment in well-controlled asthmatic patients.

• Continuous Positive Airway Pressure (CPAP) on Reducing Airway Reactivity in Asthmatics, a trial evaluating whether CPAP, an effective treatment for sleep apnea, can improve asthma control.

“Breathing is essential to life, and it’s vital for those suffering from lung disease to have access to the best treatment options available, and we get there through research,” said Harold P. Wimmer, National President and CEO of the American Lung Association.

“The Airways Clinical Research Centers Network attracts some of the best investigators nationwide, and by adding significantly to the expertise of the ACRC network, we will advance research to improve the quality of life for those living with both COPD and asthma.”

For more information on the American Lung Association’s ACRC, visit http://www.lung.org/our-initiatives/research/airways-clinical-research-centers/

About USF Health
USF Health’s mission is to envision and implement the future of health. It is the partnership of the USF Health Morsani College of Medicine, the College of Nursing, the College of Public Health, the College of Pharmacy, the School of Physical Therapy and Rehabilitation Sciences, the Biomedical Sciences Graduate and Postdoctoral Programs, and the USF Physicians Group. The University of South Florida is a Top 50 research university in total research expenditures among both public and private institutions nationwide, according to the National Science Foundation. For more information, visit www.health.usf.edu

About the American Lung Association
The American Lung Association is the leading organization working to save lives by improving lung health and preventing lung disease, through research, education and advocacy. The work of the American Lung Association is focused on four strategic imperatives: to defeat lung cancer; to improve the air we breathe; to reduce the burden of lung disease on individuals and their families; and to eliminate tobacco use and tobacco-related diseases. For more information about the American Lung Association, a holder of the Better Business Bureau Wise Giving Guide Seal, or to support the work it does, call 1-800-LUNGUSA (1-800-586- 4872) or visit: Lung.org.

Media contact:
Anne DeLotto Baier, USF Health Communications
abaier@health.usf.edu or (813) 974-3303

Tampa, FL (April 10, 2014) — Patients with severe allergies to stings from bees, wasps, hornets, fire ants and other insects should seriously consider immunotherapy, the recommended standard treatment that can prevent life-threatening reactions, concludes an article co-authored by internationally-recognized allergists/immunologists from the University of South Florida (USF) and the University of North Carolina (UNC) at Chapel Hill. 

The clinical practice article, featured in today’s New England Journal of Medicine, also recommends learning to carry and self-administer an auto-injectable syringe containing epinephrine, which counteracts the allergic reaction to insect venom, at the earliest signs of an acute response.

The paper was written by lead author Thomas B. Casale, MD, professor of medicine in the Division of Allergy and Immunology, USF Health Morsani College of Medicine, and A. Wesley Burks, MD, chairman of the Department of Pediatrics, UNC School of Medicine.

It describes the case of 24-year-old woman who reported being stung on her upper lip while drinking from a can of soda at a picnic, and within 5 minutes experiencing a cascade of reactions including swollen lips, light-headedness, difficulty swallowing, flushing and hives. She was rushed to a local emergency department, where she was treated, observed and discharged with injectable epinephrine.  The article provides a review of strategies for managing allergies to stinging insects.

“Stinging insects are the number one cause of venomous deaths in the United States,” Dr. Casale said. With snakes the venom itself kills, but with stinging insects you can die from anaphylaxis, the severe systemic allergic reaction to the venom.”

When most people are stung by an insect, the reaction is typically localized – some redness, itching and swelling at the site of the sting.  Cold compresses, cortisone cream and/or oral antihistamines can help ease these bothersome symptoms.

However, up to about 4 percent of the population is allergic to the venom of a stinging insect. For these adults and children, the more rapid the onset of symptoms of anaphylaxis, the more severe the reaction tends to be.

“So, if you are stung by an insect and develop any acute symptoms, especially getting lightheaded, short of breath or breaking out in hives, immediately seek emergency treatment,” Dr. Casale said.  “The sooner you treat acute symptoms, the less likely you are to have a catastrophic event like death.”

Lead author Dr. Thomas Casale is a professor in the USF Health Morsani College of Medicine Division of Allergy and Immunology.

Adults or children who have had a severe allergic reaction to an insect sting should be referred to an allergist/immunologist for diagnostic testing and consideration of immunotherapy, the authors say.  Immunotherapy involves a series of injections that expose the patient in a medically-controlled environment to tiny amounts of venom.   The therapy is intended to stimulate the immune system to build up tolerance over time to the venom, helping to prevent severe allergic reactions to a future insect sting. Immunotherapy is a process that takes several years, although for those at higher risk, maintenance doses may need to continue indefinitely.

Immunotherapy for insect stings “reduces the risk of having another severe systemic allergic reaction from more than 60 percent to about 5 percent,” Dr. Casale said.

With spring pollination in bloom and summertime heat approaching, it’s prime time for stinging insects to encroach on outdoor activities.  The allergy experts provide some prevention strategies for those with venom allergies, including:

–         Avoid gardens and keep outdoor areas free of exposed garbage that draws insects.

–         Wear closed-toe shoes and avoid going barefoot when outdoors.   Yellow jackets may build nests in the ground and fire ant mounds are popping up underfoot.

–         Don’t wear brightly colored clothing, perfumes, lotions or scented soaps that make you a more attractive target.

–         Cover food and drink at picnics.  The case scenario of the woman being stung while drinking from a soda can is not uncommon. “Yellow jackets, especially, will fly inside the can and sting when a person drinks,” Dr. Casale said. “It’s better to drink from a cup, where you can see what you’re drinking.”

–         Make sure you or a child’s caregiver is educated about how and when to use an epinephrine auto-injector, and bring it with you whenever there is a chance of a sting. Don’t leave the auto-injector on car dashboards or other hot places, because heat and sunlight breaks down the epinephrine.

                                                                                                  -USF Health-
USF Health’s mission is to envision and implement the future of health. It is the partnership of the USF Health Morsani College of Medicine, the College of Nursing, the College of Public Health, the College of Pharmacy, the School of Biomedical Sciences and the School of Physical Therapy and Rehabilitation Sciences; and the USF Physician’s Group. The University of South Florida is a Top 50 research university in total research expenditures among both public and private institutions nationwide, according to the National Science Foundation. For more information, visit www.health.usf.edu