Acute Asthma Exacerbation – Introduction
Chronic asthma is characterized by hypersensitivity to environmental stimuli and sporadic respiratory symptoms. According to estimates, 300 million people worldwide suffer from asthma (1), with 20 million of the people living in the United States (2). About 11 million individuals in the US experience an acute asthma exacerbation each year as a result of a respiratory virus infection or exposure to allergens or irritants in the environment (3). Although the majority of asthma exacerbations are treated in an outpatient setting, more serious exacerbations may necessitate hospitalization, which accounts for a sizable amount of asthma healthcare costs. Over 400,000 hospitalizations due to severe acute asthma exacerbations occur annually in the United States, accounting for nearly one-third of the $11.5 billion in annual healthcare costs associated with asthma (4).
For this claim, an asthma exacerbation is characterized as an acute or subacute decrease in symptom control that results in distress or poses a health risk to the point when seeking medical attention. Acute asthma exacerbations need medical attention, and that term includes every treatment available according to the severity of exacerbation. Viral respiratory tract infections are the most frequent cause of asthma exacerbations in both younger and older children. Other prevalent causes include allergen exposure and inadequate asthma control at baseline [ 5,6].
A common reason for people to visit the emergency room (ED) is acute exacerbations. According to Guttmann and colleagues , between 3% and 7% of all pediatric ED visits in Ontario were for asthma exacerbations, and over 9% of children with asthma had visited the ED at least once in the previous two years. Preschool age (5 years) accounts for more than 50% of children who present to the ED with an asthma exacerbation. According to a recent study, Rosychuk et al , showed that one child died in every 25,000 visits to the emergency department in Alberta hospital.
For the assessment and management of acute asthma exacerbations, numerous healthcare facilities across Canada and a variety of national and international health organizations have created their practice recommendations [9,10]. Children with asthma may fare better if evidence-based asthma guidelines are followed . The management of acute asthma exacerbations in pediatric patients with a known diagnosis of asthma is specifically addressed in this statement. Preschoolers with early, transient wheezing, whose pattern of symptoms and history of atopy suggest a high risk for persistent asthma, are the focus of this statement .
Acute Asthma Exacerbation Definition
The most recent National Asthma Education and Prevention Guidelines from the NIH define asthma exacerbations as acute or subacute episodes of shortness of breath, cough, wheezing, and chest tightness, or some combination of these symptoms, that get worse over time and are accompanied by decreases in expiratory airflow and objective measures of lung function (spirometry and peak flow) . Patients find these episodes upsetting, and as a result, a significant amount of healthcare resources are used, as well as lost productivity at work and in the classroom. The majority of exacerbations are treated outside of the hospital. There were 14.7 million visits to doctors’ offices and hospital outpatient departments in the US in 2004 for acute asthma, but 1.4 million people still needed emergency room treatment for an asthma exacerbation.
Epidemiology of Acute Asthma Exacerbation
Hospitalization is the outcome of more severe exacerbations, and it accounts for nearly one-third ( $14.7 billion) in yearly US healthcare costs associated with asthma . The Nationwide Inpatient Sample (NIS), the largest all-payer source of data on hospitalized patients in the United States, is sponsored by the Agency for Healthcare Research and Quality. According to statistics from 2000, there were 65381 hospitalizations for asthma (ages > 5 years) . There were 2770 intubations among them for respiratory failure linked to acute, severe asthma (Table 1). Additional information from the NIS shows that hospitalization rates were equal across all age categories, with a slight preference for those between the ages of 35 and 54, who accounted for 31.7% of hospitalizations for asthma. The NIS, however, demonstrates that mortality rises sharply as age increases. The death rate from asthma is lowest in children and adolescents (0.02%), and highest in the elderly (1.9% for those over 75). Notably, the majority (about 2/3) of the 4210 asthmatic individuals who die from acute asthma each year in the United States still happen outside of hospitals .
Table 1. Epidemiology of acute asthma exacerbations in the USA
|Hospital Mortality rate||0.5|
|Hospital Admission (Age older than 5)||65 381|
|Length of Hospital Stay (Mean)||2.7 days|
|Hospital Charge (Mean)||9078 USD|
|Total Hospital Days||1.1millions|
|Total costs||2.9 billion USD|
Females are twice as likely as males to be hospitalized for asthma, and they experience asthma exacerbations more frequently . The higher rates of adult females seeking care for acute asthma are mostly explained by the fact that asthma prevalence is higher in post-pubertal females than post-pubertal boys [17, 18]. Contrasting with the higher frequency of asthma in male children is the higher prevalence of asthma in adult females . This gender-specific differential in susceptibility to asthma in adults as opposed to childhood is probably due to the complex roles played by sex hormones in the development of asthma. Observations of an increase in asthma exacerbations after menstruation  provide evidence for an estrogen-related function in asthma. Women using hormone replacement treatment had a higher prevalence of adult-onset asthma , as do animal models .
Race and ethnicity are significant factors in asthma exacerbation risk. Patients with asthma who are African American, or Hispanic are more likely than Caucasians to need hospital admission for the treatment of an exacerbation . Differences in socioeconomic status, asthma severity, or asthma therapy variations cannot account for these correlations. Although African Americans have significantly higher total asthma mortality rates than Caucasians, this is due to factors that affect out-of-hospital mortality because in-hospital mortality is similar between both groups. These out-the-hospital variables may include disparities in access to medical care, inadequate preventative care, and delays in seeking treatment [24,25]. Puerto Rican Americans have a disproportionately high rate of self-reported asthma exacerbations in the United States, compared to other Hispanic subgroups like Mexican Americans, who experience asthma exacerbations less frequently . Uncertain societal, environmental, or genetic factors could be the cause of an elevated exacerbation risk. Even though there has been tremendous progress in finding potential genetic factors connected to the onset of asthma in Puerto Ricans , exacerbation risk genetic susceptibility factors have not been investigated.
Asthma is characterized by episodes of exacerbation interspersed with stable disease. Airway inflammation is a typical feature of exacerbations, but the current understanding of the mechanisms at play is poor, and treatments for exacerbations are insufficient .
Environmental factors like ozone, nitrogen dioxide, living near roadways, and allergies are linked to exacerbations; nevertheless, most exacerbations are linked to viral infection, mainly rhinoviruses .
About 80% of exacerbations are linked to viral infections of the respiratory system, with rhinoviral infection accounting for nearly two-thirds of cases. When infected with the rhinovirus, asthmatic participants experience substantially more severe lower respiratory tract disease than healthy control subjects. Experimental studies have shown that Asthmatic participants experienced more symptoms of the lower respiratory tract, less lung function, and more bronchial hyperresponsiveness than non-asthmatic subjects in a human experimental model of rhinoviral infection. The severity of the infection was identified as the primary driver of the severity of the exacerbation based on the substantial correlation between viral load and asthma symptoms and hyperresponsiveness. It is unknown if asthmatic people are more prone to contracting other viral illnesses [29-32].
Interferons in Virus-Induced Acute Asthma exacerbations
The susceptibility of asthmatic individuals to rhinovirus may be brought on by a problem with interferon (IFN) synthesis. Asthmatic patients have been found to have inadequate interferon responses to rhinoviruses and other viruses in a variety of cells. Interferons are antiviral proteins that play a crucial role in the innate response to infection.
The asthmatic bronchial epithelium has been shown to produce less IFN-B in response to rhinoviral infection ex vivo, which reduces an infected cell’s capacity to undergo apoptosis and promotes virus reproduction. In vivo indicators of the degree of the exacerbation were likewise correlated with the IFN- response. This faulty innate immune response involves two separated types of cells (type I and II pneumocytes), type I and type III interferons, and peripheral blood mononuclear cells (PBMCs). As a result, it is an interesting target for further research and raises the possibility of a novel interferon-based treatment or preventative method.
In addition, there have been reports of diminished type III, or IFN-, responses in ex vivo bronchial epithelial cells and airway macrophages as well as lower IFN- responses in PBMCs from asthmatic subjects [30-32].
Virus-induced Asthma Exacerbation
Uncertainty surrounds the ways by which rhinovirus causes exacerbations. Through increased mRNA expression and translation of IL-6, IL-8, IL-16, eotaxin, IFN-induced protein 10 (IP-10), RANTES, and other proinflammatory cytokines, infection causes inflammation and raises numbers of neutrophils, eosinophils, CD4+ cells, CD8+ cells, and mast cells. For instance, IL-16 is a potent lymphocyte chemoattractant that also elicits the activation of macrophages and eosinophils. Eosinophils and lymphocytes are drawn to RANTES by its chemoattractant properties, and their release, together with that of other proinflammatory cytokines, can result in airway hyperresponsiveness, inflammation, and mucus secretion [33,34].
The function of bacterial infection in asthma exacerbations is less clear than that of viral infection, while historically being significant. Due to their increased risk of developing invasive pneumococcal disease, increased frequency of Chlamydophila pneumonia detection in stable asthma, and impaired interferon production in response to LPS stimulation, recent data suggests that asthmatic subjects may also be more susceptible to bacterial infection. The potential contribution of an atypical bacterial infection to asthma exacerbations is consequently receiving more and more attention [35-37].
Nitrogen Dioxide, particulates, Sulphur Dioxide and Ozone.
Physical Examination and Clinical Presentationin Acute Asthma Exacerbation
Clinical assessment of disease severity based on a physical examination and interview; an audible wheeze is typically a marker of moderate asthma, whereas no wheezing can be a symptom of severe airflow restriction.
The severity of acute asthma exacerbation symptoms can vary from person to person and can range from mild to severe.
Mild asthma symptoms can include:
O’Byrne, Paul M., Helen K. Reddel, and Richard Beasley. “The management of mild asthma.” European Respiratory Journal 57.4 (2021).
- Coughing, especially at night or after exercising.
- Shortness of breath or difficulty breathing.
- Chest tightness or discomfort.
- Wheezing or a whistling sound when a patient breathes out.
Mild attacks may be relieved with over-the-counter or prescription bronchodilator medications, such as albuterol or levalbuterol. It is important to do a follow-up on the patient’s adherence to medical treatment.
Symptoms of moderate asthma may include:
- Shortness of breath: This is a common symptom of asthma and may be worse with physical activity or during an asthma attack.
- Chest tightness: This sensation may feel like a band is tightening around the chest and may be accompanied by coughing and wheezing.
- Coughing: A persistent cough, especially at night or after physical activity, can be a symptom of asthma.
- Wheezing: This is a high-pitched whistling sound that occurs when air is forced through narrowed airways.
- Fatigue: Asthma can cause difficulty breathing, which can lead to fatigue and a lack of energy.
Severe asthma symptoms can be life-threatening and require immediate medical attention. They can include:
- Difficulty speaking or walking due to shortness of breath
- Chest pain or tightness
- Bluish color to the lips or face
- Rapid pulse
- Frequent asthma attacks: People with severe asthma may experience frequent asthma attacks, even when taking medications as prescribed.
- Decreased lung function: Severe asthma can cause a decline in lung function, as measured by spirometry tests.
It’s important to note that the symptoms of asthma can vary from person to person and may not always be present. If you think you may have asthma, it’s important to see a healthcare provider for an accurate diagnosis and treatment plan. Severe attacks may not be relieved with bronchodilator medications, and you may need additional medications, such as corticosteroids, to control these symptoms.
In addition to the above-mentioned symptoms, patients may experience feelings of air hunger, inability to lie comfortably, insomnia, and extreme exhaustion are all signs of severe asthma. The employment of accessory muscles of breathing, hyperinflation of the chest, tachypnea, tachycardia, diaphoresis, obtundation, anxious demeanor, wheezing, inability to finish phrases, and difficulties lying down are all indications of severe asthma. Whether there is cyanosis or not, altered mental status is a warning indication that necessitates rapid hospitalization and emergency care. A thorough examination should involve checking for indications of pneumonia, a pneumothorax, or a pneumomediastinum. The last condition can be checked by palpating for subcutaneous crepitations, especially in the supraclavicular regions of the chest wall. The patient’s respiration rate, pulse, and blood pressure should all be closely monitored. A moderate-to-severe exacerbation can be indicated by tachycardia and tachypnea, whereas approaching respiratory arrest might be indicated by bradycardia. The frequency and the potential relationship between pulsus paradoxus and the degree of aggravation .
Differential Diagnosis of Acute Asthma Exacerbation
Acute asthma has several other conditions in its differential diagnosis [40,41] such as:
- Vocal cord dysfunction.
- Foreign bodies.
- Extrathoracic or intrathoracic tracheal obstruction.
- Cardiogenic pulmonary edema.
- Noncardiogenic pulmonary edema.
- Pulmonary embolism.
- Chemical pneumonitis.
- Hyperventilation syndrome.
Management of Acute Asthma Exacerbation
The fundamentals of acute asthma inpatient therapy are the same as those described for treatment in the emergency room. According to several studies, the use of structured care plans and observation units has been linked to lower rates of hospital admission and shorter lengths of stay.
Referrals to asthma specialists should be made for patients who need to be admitted to the hospital due to an asthma exacerbation because they have demonstrably poor asthma control. The objectives of such a referral are to increase the possibility that self-management education will involve creating a written action plan, successfully examining any obstacles to asthma control, and increasing the likelihood of adherence with follow-up. Such advice ought to be obtained if possible before the patient is discharged.
Primary Treatments for Acute Asthma Exacerbation: [42,43]
- 100% Oxygen.
- Short-acting Beta-agonists inhalation (SABAs). e.g., Albuterol.
- Anticholinergic inhaler.
Some patients may not react to initial therapy and display asthma symptoms that are getting worse. These patients may also require other therapies, such as:
- Adrenaline. Intramuscular or subcutaneous administration, while experts prefer a slow intravenous infusion.
- heliox-driven albuterol nebulization,
- IV Magnesium sulfate,
- (NIV) Non-Invasive Ventilation (e.g., CPAP),
- Intubation and mechanical ventilation.
Short-Acting Beta Agonists (SABAs)
The potential of cardiotoxicity, particularly in older asthmatic patients, makes the use of only selective SABAs in high dosages (i.e., albuterol and levalbuterol) highly recommended. Albuterol should be given as the first course of treatment, either using a nebulizer or an metered-dose inhaler (MDI) with a spacer device or mask (for children under 4 years old).
Treatment should continue until the patient has stabilized or a choice to hospitalize is reached. According to studies, a nebulizer or an MDI can be used to give.
A quaternary derivative of atropine sulfate called ipratropium bromide is available as a nebulizer solution. The muscarinic cholinergic receptor is competitively inhibited, which relaxes the smooth muscle of the big central airways when acetylcholine is present. Although it is not a first-line treatment, it may be added in individuals with severe asthma, especially if albuterol is not working as well as it should. It can be used for up to three hours in the initial administration when combined with albuterol or levalbuterol.
Selected patients may begin receiving high-dose intravenous corticosteroids (ICSs). There is evidence that oral corticosteroids (OCSs) are equally effective in treating minor asthma exacerbations. High-dose ICSs should be saved for patients with moderate asthma and those who refuse or are unable to tolerate OCSs due to insufficient data, nevertheless. The recommended dose of ICS should be at least quadrupled, according to guidelines.
However, 10% to 20% of people with acute asthma who were treated in the hospital would relapse within two weeks of being discharged. This could be the result of untreated asthma-related inflammation. To lessen the likelihood of a recurrence, ICS therapy should be restarted. short- or long-term ICS therapy should be started. In order to maintain an asymptomatic state once the patient’s asthma is stable, the ICS dose should be gradually decreased.
Both a rapid bronchodilator and a modest anti-inflammatory action are produced by magnesium sulfate. Patients who report severe, life-threatening asthma exacerbations (FEV1 25% of anticipated value) and those who are still in the severe category after an hour of intensive conventional treatment may be candidates for intravenous magnesium therapy.
Heliox-driven albuterol nebulization
It’s debatable whether heliox-driven albuterol should be used to treat acute exacerbations. Despite these doubts, heliox-driven albuterol can be used to treat both children and adults who have severe, life-threatening exacerbations and who continue to fall under the severe category after receiving an hour of rigorous conventional therapy.
Hospitalization and Refractory Respiratory Distress
Hospitalization is necessary if the patient does not respond to treatment. It is important to evaluate the patient’s fluid status and, if necessary, offer oral or intravenous hydration therapy. Young infants and children may require special attention when it comes to hydration because of their greater risk of dehydration due to poor oral intake and rapid breathing rates. If a nasal cannula or mask is more tolerable, oxygen can be given at a rate of 2 to 4 L/min.
Patients who are more likely to experience respiratory failure, are able to safely cooperate with noninvasive positive-pressure ventilation (NPPV) treatment and do not require emergency intubation can try NPPV for the treatment of severe acute asthma.
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