Asthma – A Quick Review

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Course Purpose   

To provide healthcare professionals with an overview of asthma, symptoms, and treatment options.

Overview

Asthma is a chronic respiratory disease that is characterized by inflammation and narrowing of the airways. Symptoms of asthma often begin in childhood and often include cough, shortness of breath, and wheezing. This online learning activity provides an overview of asthma, diagnosis, and treatment and management options.

Objectives

Upon completion of the independent study, the learner will be able to:

  • Describe asthma in various populations
  • Describe exercise induced bronchospasm
  • Review tests and tools useful in diagnosing asthma
  • Identify physical presentations of asthma
  • Understand treatment and management options of asthma

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Fast Facts: Asthma – A Quick Review

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Asthma – A Quick Review Pretest

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Definitions

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AsthmaA chronic disease of the air passages that is characterized by hyper-responsiveness, reversible airway inflammation, and narrowing of the airways.
Exercise-Induced bronchoconstriction (EIB)Occurs during physical exertion and involves a narrowing of the airways.
Severe asthma (status asthmaticus)A severe form of asthma that is unresponsive treatment.
Introduction

Asthma is a chronic disease of the air passages that is characterized by hyper-responsiveness, reversible airway inflammation, and narrowing of the airways. ¹ Asthma occurs in episodes with symptom-free periods and acute exacerbations. Most asthma attacks are short-lived. Asthma is quite common and often presents in childhood. ¹It is associated with various conditions including allergies, hay fever, and eczema, and has a range of severity, from mild wheezing, cough, and shortness of breath to life-threatening airway closure. Asthma can be triggered by many factors, including: 

  • Chronic sinusitis
  • Environmental allergens
  • Exercise
  • Gastroesophageal reflux disease
  • Insects, plants, chemical fumes
  • Obesity
  • Respiratory tract infections
  • Stress
  • Tobacco smoke
  • Use of aspirin and beta-blockers

In asthma, a triggering agent causes bronchial hypersensitivity, inflammation of the airway, and an increased production of mucus, which leads to increased airway resistance that is most heard as wheezing on expiration. The increased airway resistance can lead to obstruction resulting from inflammation, formation of mucus plugs, and contraction of smooth muscles of the lungs. ² If not urgently treated, the increase in mucus production may prevent inhaled medications from reaching the bronchial mucosa, making asthma difficult to treat. When administered correctly and without delay, beta-2 agonists, (albuterol, salbutamol, and salmeterol) and muscarinic receptor antagonists (ipratropium bromide) are effective in reducing asthma symptoms by reducing the inflammation associated with it and relaxing the bronchial musculature, as well as reducing mucus production. ²

Because asthma is a common disease that often requires emergent medical intervention by healthcare professionals, it is important that the healthcare provider understand asthma symptoms, diagnosis, and treatment options. This independent learning activity provides a quick review of asthma considerations. 

Asthma Types

Childhood Asthma

In childhood asthma, the lungs and airways can become inflamed when they are triggered by certain factors, including environmental allergens, or respiratory tract infections. ³In children, asthma can cause daily symptoms that interfere with play, sports, school, and sleep. When it is uncontrolled, asthma can cause dangerous asthma attacks that can be life-threatening. Childhood asthma is no different than asthma in adults, but in children it is a leading cause of emergency department visits, hospitalizations and missed school days.

Common childhood asthma signs and symptoms include³:

  • Chest congestion or tightness
  • Frequent coughing that worsens with a viral infection, during sleep, or when exposed to cold air or during exercise
  • Shortness of breath
  • Wheezing on expiration

Factors that may increase the likelihood of being diagnosed with childhood asthma include:

  • A family history of asthma or allergies
  • Being Black or Puerto Rican
  • Being male
  • Exposure to tobacco smoke, including before birth
  • Gastroesophageal Reflux Disease
  • Living in an area with high pollution
  • Obesity
  • Previous allergic reactions, including skin reactions, food allergies or hay fever 
  • Respiratory conditions such as rhinitis, sinusitis, or pneumonia

Pregnancy Induced Asthma

Asthma is one of the most common chronic diseases in pregnancy. Asthma exacerbation in pregnancy represents a major clinical problem that can lead to maternal and fetal morbidity and mortality. ⁴

During pregnancy, asthma symptoms usually peak in the late second or early third trimester, but exacerbations are rare during labor and the peripartum period. 

As with children and those in the general population, symptoms of pregnancy induced asthma may include chest tightness, wheezing, shortness of breath, and cough. These symptoms are characterized by the following⁴:

  • Episodic with fluctuations in time and in intensity
  • Often are worse at night or in the early morning
  • Symptoms that are triggered by allergens, exercise, viral infections, and weather changes 

Exercise-Induced Bronchoconstriction

Exercise-Induced bronchoconstriction (EIB) occurs during physical exertion and involves a narrowing of the airways. ⁵ It occurs in 40% to 90% of people with asthma and up to 20% of those without asthma. The benefits of regular exercise are well established, however, people with EIB may avoid physical exertion due to symptoms of chest tightness, cough, shortness of breath, and wheezing. Although EIB occurs because of physical exertion, exercise has also been shown to improve the severity of exercise induced bronchospasm, pulmonary function, and reduce airway inflammation in people with asthma. ⁵˒⁶Early detection, diagnosis that is evidenced by changes in lung function during exercise, treatment, and management allows people with EIB to exercise without limitations and can improve their quality of life. 

Symptoms of exercise-induced bronchoconstriction can include mild to moderate symptoms of chest tightness, wheezing, coughing, and dyspnea that occurs within 15 minutes after 5 to 8 minutes of high-intensity exercise. ⁶These symptoms may occur more frequently in environments with cold, dry air or high concentrations of respiratory irritants such as allergens. Symptoms of EIB usually resolve spontaneously within 30 to 90 minutes. 

 Risk factors for exercise induced bronchospasm include:

  • A personal or family history of asthma
  • A personal history of allergic rhinitis
  • Exposure to cigarette smoke 
  • Participating in high-risk sports 
  • Living and practicing in areas with elevated levels of pollution 
  • Female gender

Severe Asthma

Severe asthma (status asthmaticus) is a severe form of asthma that is unresponsive treatment. It is the extreme form of asthma exacerbation and is characterized by hypercarbia, hypoxemia, and secondary respiratory failure. ⁷ It is a medical emergency that requires immediate recognition and treatment. Everyone with asthma is at risk of developing an acute asthma attack with a severity that does not respond well to standard therapeutic measures. Most often, severe asthma is caused by an upper respiratory infection. ⁸Other causes include nonadherence to treatment regimens, nonsteroidal anti-inflammatory exposure to those allergic to aspirin, exposure to environmental irritants, and exercise. When assessing the asthmatic person, the healthcare professional should focus on a history that includes⁷˒⁸: 

  • Current medications or illicit drug use
  • Emergency room visits and intubations
  • Exercise intolerance
  • Exposure to allergens
  • Frequency of albuterol use
  • Number of hospitalizations related to asthma
  • Presence of nighttime symptoms

 Severe airflow obstruction may be evidenced by accessory muscle use, pulsus paradoxus, refusal to recline below 30°, a pulse greater than 120 beats per minute, and decreased breath sounds. ¹˒⁷

Clinically, an exacerbation of asthma may appear as⁸:

  • Arrhythmias
  • Bradycardia
  • Coma
  • Confusion
  • Cyanosis
  • Feeble respiratory effort
  • Hypotension
  • Oxygen saturation less than 92%
  • Peak expiratory flow less than 33% of personal best
  • Respiratory exhaustion
  • Silent or severely decreased lung sounds

People with severe asthma should be managed with high flow oxygen, steroids, continuous nebulization treatments consisting of short-acting beta 2 agonists and short-acting muscarinic antagonists, and intravenous magnesium sulfate. In cases of asthma attacks where respiratory failure is predicted, early intubation and mechanical ventilation is required. 

Obtaining the History and Physical

People suspected of asthma will usually have a history of coughing or wheezing that is exacerbated by allergens, exercise, cold, or viral infections. ¹˒²They also may have a history of eczema or hay fever and may experience increased symptoms at night and decreased symptoms during the day. When acute exacerbations occur, chest pain may be present. 

The physical exam findings will depend on whether an individual is currently experiencing any symptoms of asthma or acute exacerbation of asthma. During an acute exacerbation, there may some respiratory distress that is reflective of their posture; people will lean forward when sitting to open their airways. On auscultation, a bilateral expiratory wheeze will be heard in asthma. In asthma exacerbation and status asthmaticus, lungs sounds may be severely diminished or absent because of the lack of air movement the lungs. There may also be signs of systemic hypoxia, including pulse oximeter readings less than 92%, tachycardia, diaphoresis, cyanosis, and accessory muscle use.

In children, systemic hypoxia may be life-threatening, and cardiac arrest may be imminent. ³These children may appear confused, cyanotic, drowsy, or unresponsive. Wheezing may be absent because of the lack of air movement in the lungs. Bradycardia may occur, indicating severe respiratory muscle fatigue.

Making the Diagnosis

Obtaining a detailed history as well as a thorough examination helps to diagnose asthma. ⁹The healthcare professional may conduct some tests to confirm the diagnosis and to exclude other lung conditions. The following provides a brief overview of tests and tools to assess for and confirm an asthma diagnosis. ⁹˒¹⁰˒¹¹

Asthma Control Test 

An ACT can be used to assess asthma control during pregnancy. The ACT is a five-item questionnaire with a 4-week recall of symptoms and daily functioning. The scores range from 5 indicating poor asthma control, to 25 indicating complete control. A score of less than 20 on the ACT indicates uncontrolled asthma. 

Blood Gas

The arterial blood gas (ABG) provides vital information in acute asthma. This test may reveal dangerous levels of hypoxemia or hypercarbia secondary to hypoventilation and respiratory acidosis. Although respiratory acidosis may be revealed in acute asthma attacks, respiratory alkalosis may be the initial findings in the beginning stages of the attack.

Exercise Challenge Testing

Exercise challenge testing is an effective means of diagnosing exercise induced bronchoconstriction (EIB). The test should be performed in a controlled, dry environment. Exercise testing parameters include recommendations on ventilation level, heart rate, time at maximal capacity, and medications to hold before testing. Serial measurements of spirometry, specifically FEV1, are recorded during exercise at 5,10,15, and 30 minutes. A decrease in FEV1 of 10% or more is diagnostic of EIB.

Methacholine Challenge Test

A methacholine challenge test is a type of bronchoprovocation test used to help diagnose asthma. Methacholine is an inhaled drug that causes mild narrowing of the airways in the lungs. The test should not be performed in women who are pregnant or nursing, or in those who have an aortic or brain aneurysm, uncontrolled blood pressure, heart attack or stroke in the last three months, or have extremely low lung function on the baseline spirometry test. The test begins with a baseline spirometry evaluation to check lung function, including a Forced Expiratory Volume (FEV1). Progressively larger doses of inhalation methacholine are administered by a nebulizer. Spirometry is performed before and after every dose of inhaled methacholine to measure the amount of airway narrowing. The test stops once the lung function (FEV1) drops by 20% or more from baseline or the maximum dose of methacholine is reached. A methacholine challenge test is considered positive if methacholine causes the lung function (FEV1) to drop by 20% or more. 

Peak Flow Measurement

Peak flow measurement is a quick test to measure air flowing out of the lungs. The measurement is also called the peak expiratory flow rate (PEFR) or the peak expiratory flow (PEF). Peak flow measurement can show the amount and rate of air that can be forcefully breathed out of the lungs and can help show the narrowing of the airways well before an asthma attack happens. The measurement should begin after a full lung inhalation. An important part of peak flow measurement is noting peak flow zones, areas of measurement on a peak flow meter. The goal of the peak flow zones is to show early symptoms of uncontrolled asthma. The green zone is 80% to 100% of one’s highest peak flow reading, or personal best. This is the zone one with asthma should be in every day as it shows that air is moving well through the large airways in the lungs. The yellow zone is 50% to 80% of one’s personal best and is also a sign that the large airways are starting to narrow. The red zone is less than 50% of one’s personal best and shows that one with asthma has severe narrowing of the large airways. 

Pulse Oximetry

Pulse oximetry can be useful in assessing the severity of an asthma attack or monitoring for deterioration of one who is experiencing the attack. The pulse oximeter attaches to the skin and uses light wavelengths to measure the percentage of hemoglobin molecules carrying oxygen. It is important to note that there is a lag in pulse oximetry readings, and a low oxygen level on pulse oximetry is a late finding, indicating a severely unwell or individual who is imminent of cardiac arrest.

Radiography

A chest x-ray is an important test in asthma, especially if it is believed that an infection is present. In addition, a chest CT scan may be performed in individuals with recurrent asthma symptoms that do not respond to therapy.

Spirometry

Spirometry can help diagnose asthma in the general population and in pregnancy by detecting reversible airway obstructive patterns and helping to monitor response to asthma treatment. Spirometry is the diagnostic method of choice and should be done before initiating treatment to determine the severity of asthma. A reduced ratio of forced expiratory volume (FEV1) to forced vital capacity (FVC) is indicative of airway obstruction, which is reversible with treatment. Reversibility testing is done by administering an inhaled short-acting beta 2 agonists, followed by a repeated spirometry test. If there is a 12% or 200ml improvement in FEV1 from the previous value, then it shows reversibility and is diagnostic of asthma. 

Treatment and Management Options

When a person is diagnosed with asthma, they initially will have a treatment plan developed that manages their asthma symptoms and prevents asthma attacks. ¹⁰ The treatment usually depends on their age, severity of asthma, and responses to any previous treatments. Their treatment plan should be adjusted based on these findings. In addition, any environmental factors should be considered, and be removed from the environment to reduce exposure to triggering substances such as tobacco, dust mites, animals, and pollen.

Most often, people with asthma are treated with a short-term relief medication when symptoms develop, and a long-term daily medication to control asthma. These medications may be the only ones needed for those with mild asthma symptoms or exercise induced bronchospasm.

Short term medications include¹⁰:

  • Short-acting anticholinergics in combination with short-acting beta2-agonists – Ipratropium bromide/albuterol
  • Short-acting beta2-agonists  

Long-term control medicines may be taken daily to prevent asthma symptoms by reducing airway narrowing and inflammation. The treatment regimen is individualized and varies by age. 

Long-term control medications include¹⁰:

  • Corticosteroids
  • Leukotriene Receptor Antagonists
  • Long-acting beta2-agonists
  • Mast Cell Stabilizing Agents 

The following provides a brief overview of medications to be considered when treating asthma. ¹⁰˒¹¹

Short Acting Beta 2 Agonists

Anyone who is diagnosed with asthma should be prescribed a short-acting beta-2 agonist (SABA) rescue inhaler. The SABA most often prescribed is an albuterol metered-dose inhaler (MDI). Short acting beta-2 agonist medications function by relaxing the airway smooth muscles. The bronchodilation effect of albuterol is rapid and can last 2 to 4 hours. Short-acting beta-2 agonists are the first line treatment for symptomatic asthma and have minimal side effects.

Long-Acting Beta 2 Agonists

The long-acting beta2-agonists most used are salmeterol and formoterol. These medications function similarly to short-acting beta 2 agonists, except the half-life is much longer, which leads to a slower onset and a longer duration of action. Long-acting beta-agonists should not be used alone to treat asthma because of the federal drug administration’s black-box warning regarding the occurrence of severe asthma exacerbation. Adverse side effects are reduced when long-acting beta agonists are combined with anticholinergic or corticosteroid medications. 

Side effects of short and long-acting beta-agonist medications include:

Allergic reactionBronchitisBronchospasm
ChillsChronic obstructive pulmonary disease (COPD) exacerbationCough
DizzinessDry mouthDyspepsia
FeverHeadacheIncreased nervousness
Insomnia in childrenNauseaPain
SweatingTremorUrinary retention
VomitingSinusitis 

Beta-2 agonist medications (albuterol) can be used independently, however, they are often used in combination with anticholinergics for a combined increased efficacy over individual use of either medication. For example, Ipratropium bromide/albuterol is a common combination of medications that are used to effectively treat asthma. Simultaneous administration of both an anticholinergic and a beta-2 agonist produce a greater bronchodilation effect than either drug can achieve alone.

Inhaled Corticosteroids 

If symptoms are not well controlled with the SABA or an individual is using short-acting beta-agonists more than twice a week, additional medications can be added after adherence and proper use of medications is confirmed. A daily inhaled corticosteroid (ICS) is often the first line medication for maintenance of asthma symptoms. Inhaled corticosteroids include beclomethasone, budesonide nebules, flunisolide, fluticasone, and mometasone. These medications work by decreasing the inflammatory response of an overactive immune system and effectively decrease the airway’s hyperresponsiveness. Dosages can vary from minimal as a monotherapy to remarkably high in combination therapy with either beta-2 agonists or anticholinergics. Common combination therapy medications include fluticasone and salmeterol, budesonide, and formoterol, mometasone and formoterol, and fluticasone and vilanterol. Daily use of inhaled corticosteroids may take 2 to 4 weeks to show effects in treating asthma. 

Side effects that may occur with the use of inhaled corticosteroids include:

Abdominal painBack painBronchitis
CoughDysphoniaHeadache
Influenza NasopharyngitisOral candidiasis
Oropharyngeal candidiasisOropharyngeal painPharyngitis 
Procedural painRespiratory tract infectionrhinitis
SinusitisThroat irritationToothache
Viral gastroenteritis  

Leukotriene Receptor Antagonists

Leukotriene receptor antagonists (LTRA) include montelukast, zafirlukast, and zileuton. These medications are often prescribed for exercise induced bronchospasm and work by decreasing inflammation and decreasing responsiveness of the airways to immune triggers. These medications provide long-lasting bronchodilation and are not associated with tolerance; however, they may take 2 to 4 weeks to see maximal benefits.

Some side effects that may occur with LTRAs include: 

Abdominal painAggressive behaviorAllergic granulomatous angiitis (Churg Strauss syndrome)
BronchitisCholestatic hepatitis, and rarelyCough
Dental painDizzinessDyspepsia
EczemaElevated liver function testsFever
GastroenteritisHeadacheInfluenza
LaryngitisNasal congestionOtitis
PharyngitisRashSinusitis
Suicidal thoughtsUpper respiratory tract infectionUrticaria
viral infectionWheezing 

Methylxanthine

Theophylline is a methylxanthine drug that causes smooth muscle relaxation and dilation of the bronchioles, thereby reducing airway obstruction. Theophylline has a narrow window between therapeutic and toxic ranges, and therefore requires close monitoring of serum levels.

Side effects associated with theophylline include:

Acute myocardial infarctionCardiac flutterCentral nervous system excitement
DiarrheaDifficulty urinatingDiuresis
Exfoliative dermatitisHeadacheHypercalcemia
Insomnia IrritabilityNausea
RestlessnessSeizureSeizures
Skeletal muscle tremorsTachycardiaUrinary retention
Vomiting  

Mast Cell Stabilizing Agents 

Mast cell stabilizing agents (MCSA) cromolyn and zileuton are effective in reducing the risk of exercise induced bronchospasm. Cromolyn works by reducing histamine release. Zileuton effectively decreases the inflammatory response of the immune system. Mast cell stabilizing agents are less effective than short-acting beta-agonists and are not widely available in the United States.

Side Effects of mast cell stabilizing agents include:

Chest painCoughDysphagia
Esophagus spasmFatigueFlushing
MigraineNasal congestionNausea
PalpitationPancytopeniaPharyngitis
PolycythemiaPruritusPsychosis
SneezingTinnitusWheezing

Monoclonal Antibody Immune-Modulating Medications

Monoclonal antibody immune-modulating medications can be used in certain situations when people with asthma do not respond well to inhaled corticosteroid treatment and are found to have eosinophilia (white blood cells that destroy substances in the body). Monoclonal antibody immune-modulating medications include omalizumab, mepolizumab, and reslizumab. These medications work by decreasing the immune response to a triggering agent, resulting in decreased eosinophilia.

Omalizumab may be an option for adults and adolescents 12 years of age and older who have moderate to severe asthma and symptoms not controlled by inhaled corticosteroids. 

Side effects of Omalizumab include:

Alopecia AnaphylaxisArm pain
ArthralgiabronchitisDermatitis 
DizzinessEaracheEdema 
Epistaxis FatigueFracture
HeadacheInjection site reactionsleg pain
NasopharyngitisOtitis media Pain
PharyngitisPruritus Pyrexia
Sinusitis Streptococcal pharyngitisUpper abdominal pain
Upper respiratory infection UrticariaViral gastroenteritis 
Viral infections  

Mepolizumab is an add-on treatment that is indicated for people 12 years of age and older with severe asthma and high eosinophil levels. This medicine works by preventing the proliferation of eosinophils in the bone marrow. 

Side effects of Mepolizumab include:

Allergic reactionsBack painFatigue
HeadacheInfluenzaInjection site reactions
Muscle spasmsPruritus, eczemaUpper abdominal pain
Urinary tract infection  

Reslizumab is an add-on therapy for people 18 years and older with severe asthma and eosinophilia. This medication works by preventing the proliferation of eosinophils in the bone marrow.

Side effects of Reslizumab include:

AnaphylaxisElevated creatine phosphokinase 
MyalgiasOropharyngeal pain

Short-Acting Muscarinic Antagonists

Inhaled anticholinergic agents are rarely recommended as monotherapy. Short-acting muscarinic antagonists (SAMA) are less effective than short-acting beta-2 agonists (albuterol), however, they can be used in combination when tolerance to SABA develops. For instance, SAMA such as ipratropium are given as a high dose nebulized therapy in acute severe asthma and is taken in conjunction with a short-acting beta-2 agonist. 

Side effects of Short-acting muscarinic antagonists include:

Blurred visionConfusionConstipation
CycloplegiaDeliriumDry mouth
HallucinationsIncreased intraocular pressureMydriasis
RestlessnessTachycardiaUrinary retention

Long-Acting Muscarinic Antagonists 

Long-acting muscarinic receptor antagonists (LAMA) reverse airflow obstruction in the airways. They do not create immediate relief of symptoms, instead of having a slower onset and lasting for 12 hours. Typically, they are not used to treat asthma, and are more effective in treating chronic obstructive pulmonary disease (COPD). 

Bronchial Thermoplasty

Bronchial thermoplasty is an option for people with severe, persistent asthma that is unresponsive to treatment. In bronchial thermoplasty, a controlled therapeutic radiofrequency energy in infused into the airway wall, heating and destroying bronchial tissue. Most of what makes up the bronchial tissue (epithelium, blood vessels, mucosa, and nerves) will regenerate over time, but the airway smooth muscle will not, and instead will be replaced with connective tissue. The result is a decrease in bronchoconstriction due to loss of musculature within the bronchial tissue.

Conclusion

Despite advances in medical management and access to early diagnosis and treatment, asthma remains one of the most common causes of emergency department visits. When an exacerbation of asthma occurs, the healthcare professional should urgently assess the signs and symptoms, airflow and blood gas readings, in addition to rapid intervention to treat acute symptoms. Once acute symptoms are resolved, the asthmatic should be placed on a long-term treatment regimen to prevent asthma exacerbations. In addition to pharmacologic therapy to reduce asthma, the individual should also be provided with education on the importance of compliance and adherence to the treatment regimen. The education should include types of medications, dosing, and how to use inhalers, nebulizers and injectables, learning about warning signs and how to manage acute attacks, and ways to identify asthma triggers. With treatment regimen adherence and reductions in exposure to triggering causes of acute asthma attacks, complications related to asthma can be reduced. 

References
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