Wheezing in Children

Difficulty breathing from wheezing is among the most common reasons people call an ambulance, or Emergency Medical Services (EMS), for a child. Acute wheezing is often caused by an asthma attack but can also be triggered by viral infections or allergies. Acute wheezing causes children to struggle to breathe. It can lead to low oxygen and, in rare cases, can cause death. Paramedics treat wheezing before the child gets to the hospital, though they often do not have all of the medications used in the hospital or do not use the medications the same way. These medications are considered standard in the hospital and generally have low side effects. Treating difficulty breathing from wheezing earlier has been shown to reduce the number of children who need to get admitted to the hospital or an intensive care unit. Our goal is to get the best treatment to the child as soon as possible.

How is wheezing treated?

The most common medication used to treat acute wheezing is albuterol, and most EMS agencies use it. It acts by opening up the airways. Ipratropium is used in the hospital to treat wheezing but is not used by most EMS agencies. Ipratropium helps the tubes that carry air through the lungs open up and improves airflow. Ipratropium is given by a nebulizer mist like albuterol and is breathed directly into the lungs. Dexamethasone is an anti-inflammatory steroid medication given orally or by injection. It is commonly used in the hospital Emergency Department for wheezing. It takes about 2 hours to take effect, reduces lung inflammation for an extended time, and helps children recover from wheezing.

How will T-RECS affect treatment for wheezing?

This study aims to test the implementation of ipratropium and dexamethasone for acute wheezing by paramedics. Currently, paramedics mostly rely on albuterol alone without using these other medications, either because they do not have access to them or are not using them often enough. EMS agencies participating in the T-RECS study will train paramedics to give ipratropium and dexamethasone using a standardized and simple protocol with a checklist.

The T-RECS pilot study will take place in 3 urban areas in the U.S. including; Charlotte, North Carolina, Buffalo, New York, and Salt Lake City, Utah. Participating EMS agencies will receive training on the new standardized treatment method before implementing it at a time designated by the study. Children aged 2 to 17 years who are transported by a participating EMS agency for wheezing will be enrolled in the study. Researchers will record information about whether or not the children enrolled in this study received medication and if they needed to be admitted to the hospital or not. We will also contact families 1 week after the EMS transport to see how the child is recovering.

What are the risks of study participation?

In this study, we will evaluate the impact of using bundled medications for treatment of life-threatening wheezing. Although these medications have been commonly used to treat respiratory emergencies in the hospital we do not know if using these medications as a part of bundled treatment during EMS care will increase or decrease any risks of the medications.

Ipratropium, albuterol, and dexamethasone are widely used medications with minimal side effects. However, like all medications, some side effects are possible. Adverse effects of the study medications, when used for short-term use are:

• Changes to pulse rate, blood pressure, other cardiovascular symptoms and/or ECG changes with or without cardiac symptoms
• Shakiness or agitation
• Allergic-type reactions
• Bronchospasm, dyspnea, or other respiratory problems
• Blurred vision, eye pain, temporary pupil dilation, or worsening of narrow-angle glaucoma (if eye exposure)
• Abdominal pain
• Nausea or vomiting
• Behavioral changes

Additional risks include accidental enrollment of ineligible subjects and accidental disclosure of private information.  There also may be risks that are unknown at this time.

Will the study affect any other part of a child’s treatment for wheezing?

No, after arrival at the emergency department, all decisions about how to treat a child with wheezing will be made by health professionals as they usually would for any child with difficulty breathing from wheezing.

What if I have questions or concerns about Exception from Informed Consent (EFIC)?

We encourage you to read the EFIC section below to learn more. You can provide your anonymous feedback about the TRECS study and the use of EFIC for emergency research by completing our survey at https://redcap.link/6zo829it.

Ethical standards require that researchers get permission before a person can be included in a study through a process called informed consent. However, severe difficulty breathing is an emergency condition that must be treated immediately. Although we will make every effort to gain consent prior to research participation, there may not be enough time to locate and talk to the person’s parent, guardian, or legal representative about the study. Patients enrolled in T-RECS will likely be enrolled before permission can be given. This is called “Exception from Informed Consent” (EFIC). Parents or guardians of children enrolled in this study will be notified about enrollment as soon as possible.

What is Exception From Informed Consent (EFIC)?

The U.S. Food and Drug Administration (FDA) is an agency of the federal government that oversees human research protection involving medicines. The FDA has created a set of special rules, called Exception from Informed Consent (EFIC), for clinical trials that apply to critically ill patients who require emergency treatment when obtaining consent in advance is not possible or may put the patient at risk for increased harm by delaying potentially life-saving therapies. Under some circumstances, there may not be time to obtain consent in advance from every eligible patient. In some cases, discussing a possible option to enroll in a study may cause dangerous delays in a person’s care. Nonetheless, many critically ill patients could benefit from enrollment in an appropriate clinical trial. Therefore, to ensure that clinical trials can be conducted for patients in emergencies, the FDA established rules for EFIC that require special safeguards to ensure that most people would consider the study ethical and appropriate. These special rules allow research studies in certain emergencies to be conducted without obtaining consent in advance.

EFIC can only be used when:

• The person’s life is at risk, AND
• The best treatment is not known, AND
• The study might help the person, AND
• It is not possible to get permission:
  • From the person because of their medical condition NOR
  • From the person’s guardian, because there is a very short amount of time required to treat the medical problem

Before researchers start a study using EFIC, they must provide information about the study to the community and get their feedback. If you would like to fill out a short online survey to provide your thoughts about this study, please click HERE. (insert survey link)

Delays in treating respiratory distress from life-threatening wheezing can lead to worsening symptoms which can be less responsive to medications. Respiratory distress can also lead to low oxygen levels and sometimes require more invasive assistance of breathing. Further, acute wheezing can be a significant burden to patients since 20-50% of children who have a 9-1-1 call for acute wheezing will require hospital admission for ongoing treatment. Early treatment with the best medications has the chance to reduce the rate of hospitalization along with the need for more invasive treatments. Sometimes, patients experience delays of up to an hour after hospital arrival to receive ipratropium and dexamethasone, so giving the medications in the EMS system can facilitate significantly earlier treatment.

Paramedics currently rely on albuterol to treat acute wheezing but do not often use ipratropium or dexamethasone. These medications, when given early, can reduce the need for hospital admission and the severity of symptoms.

The TRECS study is a multi-center, before-and-after pilot trial to compare the current standard treatment to a new protocol, including the early use of ipratropium and dexamethasone. Participants will be enrolled at 3 locations across the country over a one-year study period. Data will be collected on children aged 2 to 17 years who experience life-threatening wheezing and are transported to the hospital before and after implementing the standardized protocol. The study is funded by the National Heart, Lung, and Blood Institute (NHLBI) at the National Institutes of Health (NIH).

This study is a pilot study designed to be conducted at a limited number of sites. This pilot study aims to test our ability to collect all of the data needed. One of the outcomes we are using is the PROMIS asthma impact scale which is uncommonly used in emergency care research. We will be collecting this information approximately 7 days after the EMS encounter to determine how early treatment of severe acute wheezing in the EMS setting impacted the child's quality of life over a one-week period.

Because difficulty breathing requires immediate treatment, we anticipate that in most cases, it will not be possible to obtain informed consent from patients before they are enrolled. Therefore, eligible patients will be enrolled in this trial under the U.S. Food and Drug Administration’s exception from informed consent (EFIC) requirements for emergency research (21 CFR 50.24). These special rules allow research studies in certain emergency situations to be conducted without consent. EFIC can be used only when the person’s life is at risk, the best treatment is not known, the study might help the person, and it is not possible to obtain informed consent from the patient or a legally authorized representative. 

The study will not modify the way life-threatening wheezing is managed by providers in the emergency department; it will only modify how wheezing is managed by EMS before hospital arrival. All hospital-based care will be standard and determined by the treatment team per routine.

We believe that this study may help paramedics optimally treat difficulty breathing from acute severe wheezing in the future by implementing medications that are proven to be effective in the hospital.