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Principles of therapy
After the diagnosis
of asthma is made, it is recommended to initially start corticosteroids
(inhaled, low dose) as soon as possible for better outcomes. This depends on
the patient's presenting symptoms, risk factors, comorbidities, and treatment
preference.
Goals of Therapy
The goals of
therapy for long-term asthma control are effective
symptom control with minimal or no exacerbations, minimal or no daytime and
nocturnal symptoms, no limitations on activities including exercise, minimal or
no need for reliever treatment, no emergency visits, normal or near normal
pulmonary function, and minimal adverse effects of medication.
Therapeutic
Strategies
The
therapeutic strategies depend on a
control-based approach. Treatment is continuously adjusted depending on the
patient’s response to therapy. It involves a cycle of assessment, treatment,
and review of the patient response. Other strategies used include sputum-guided
treatment and fractional concentration of exhaled nitric oxide.
A specialist referral is
recommended for the following:
- The patient had a life-threatening asthma exacerbation
- Atypical clinical findings (eg clubbing, crackles, cyanosis, heart failure [HF], stridor, hemoptysis; and children with abnormal voice or cry, dysphagia, focal signs in the chest, inspiratory stridor)
- Excessive vomiting or possetting in children
- Persistent cough and/or sputum production; and children with persistent productive cough despite proper inhaler technique and good treatment adherence
- Persistent shortness of breath (not episodic and without associated wheeze)
- Spirometry or peak expiratory flow findings do not indicate asthma and requires additional testing (skin allergy testing, provocative challenge test)
- Symptoms present from birth or perinatal lung problem and have a family history of unusual chest disease
- Unilateral or fixed wheeze
- Weight loss
- Non-responsive to therapy after 3-6 months, needs step ≥4 care, or being considered for immunotherapy
COVID-19 and Asthma
Prescribed
asthma medications should be continued particularly inhaled corticosteroids.
For severe asthma, biologic therapy and oral corticosteroids should be
continued.
Strict
infection control procedures for aerosol-generating procedures (eg
nebulization, oxygen therapy, sputum induction, manual ventilation,
non-invasive ventilation, intubation) should be followed. Nebulizers should be
avoided if possible as it may increase risk of spreading the virus to other
patients and to healthcare professionals. The preferred treatment during severe
exacerbations is pressurized metered-dose inhaler via a spacer with mouthpiece
or tightly fitting face mask if needed.
Spirometry should be avoided in confirmed
or suspected COVID-19 patients and those with confirmed increased transmission
in the community. Vaccination against COVID-19 is recommended by the GINA
guidelines for asthma patients based on its risks and benefits.
Pharmacological therapy
Initial
Treatment of Asthma
| Recommended Options for Initial Treatment | ||
| Presenting Symptoms | Children 6-11 Years | Adults and Adolescents |
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Preferred |
| Alternative |
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Preferred |
| Alternative |
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Preferred |
| Alternative |
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Preferred |
| Alternative |
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| Reference: Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention: Updated 2024. 1As anti-inflammatory reliever (AIR) 2As maintenance and reliever therapy (MART) |
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Management Plans for Long-term Asthma Control
| Recommended Medications Based on Level of Control | ||
| Treatment Steps | Daily Controller Medications | |
| Children 6-11 Years |
Adults and Adolescents ≥12 Years | |
| Step 1 |
Preferred controller
Reliever (any of the following):
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Controller
Preferred reliever
Alternative reliever
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| Step 2 |
Preferred controller
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Controller
Preferred and alternative reliever, and other controller options same as Step 1 |
| Step 3 |
Preferred controller (any of the following):
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Controller
Other controller options (any of the following):
Preferred and alternative reliever options same as Step 13 |
| Step 4 |
Preferred controller (any of the following):
Other controller options (any of the following):
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Controller
Other controller options (any of the following):
Preferred and alternative reliever options same as Step 13 |
| Step 5 |
Preferred controller
Other controller option:
Preferred reliever options same as Step 1 |
Controller
Other controller options:
Preferred and alternative reliever options same as Step 13 |
| Reference: Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention: Updated 2024. 1As anti-inflammatory reliever (AIR) 2Low-dose inhaled corticosteroids may be used separately or in combination with short-acting inhaled beta2-agonists. 3Budesonide/Formoterol or Beclometasone dipropionate/Formoterol combination may be given as maintenance and reliever therapy (MART). 4Should not take >12 doses (>8 doses for children) of Budesonide/Formoterol or >8 doses of Beclometasone dipropionate/Formoterol per day. 5May be considered in sensitized adult patients with allergic rhinitis and FEV1 >70% predicted. 6Expert referral is recommended for patients 6-11 years old with disease progression despite good adherence and correct technique. 7Tiotropium by mist inhaler is only to be given to patients ≥6 years of age with a history of exacerbations. 8Contraindicated in patients <6 years of age. 9Contraindicated in patients <18 years of age. 10Contraindicated in patients <12 years of age. 11Approved for patients ≥12 years of age. |
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Stepwise Therapy Based on Control for Adults & Children ≥6 Years
Step 1 - Use of as-needed controller
In this step, medications on an “as necessary” basis are given. It is reserved for patients with controlled asthma (<2x/month occurrence of symptoms, absent exacerbation risk factors) and should address risk factors for exacerbation and symptom control. This step involves the use of as-needed low-dose inhaled corticosteroids plus Formoterol for symptom relief and the patient adherence to medication should be considered when prescribing corticosteroids.
Step 2 - Use of daily or as-needed controller
This step is for patients who require controller medications daily to maintain control of their asthma. It may be used as initial therapy for treatment-naive patients with persistent symptoms. It involves the use of daily low-dose inhaled corticosteroid with long-acting beta2-agonist as an initial maintenance controller treatment as an option for patients ≥12 years who are being given controller medications for the first time. Daily inhaled corticosteroids or as-needed inhaled corticosteroids plus Formoterol is a treatment option for patients with purely seasonal allergic asthma. Other controller options include the addition of oral leukotriene modifiers or house dust mite SLIT.
Step 3 - Use of daily controller and reliever, plus as-needed reliever
This step is for patients who require controller medications daily to maintain control of their asthma. For patients ≥12 years of age, low-dose inhaled corticosteroids with Formoterol may be used as both maintenance and reliever treatment. The addition of oral leukotriene modifiers or Theophylline to low-dose corticosteroids may be considered. For children, increasing the dose of the corticosteroid from low to medium is preferred over adding a long-acting beta2-agonist. The addition of house dust mite SLIT may also be considered in patients ≥12 years of age sensitized to house dust mites with allergic rhinitis and FEV1 of >70% predicted.
Step 4 - Daily controller and reliever therapy, plus as-needed reliever treatment continued
This therapy usually requires multiple daily controller medications. The treatment choice will depend upon what was previously used in Step 3. Consider expert referral if increasing the dose of inhaled corticosteroids fails or if symptom control remains poor and/or flare-ups persist.
The addition of house dust mite SLIT may also be considered in patients ≥12 years of age sensitized to house dust mites with allergic rhinitis and FEV1 of >70% predicted. The addition of oral leukotriene modifiers or Tiotropium for patients ≥6 years old with a history of exacerbations or increasing the dose of inhaled corticosteroids given with long-acting inhaled beta2-agonist may be considered if symptoms are still not controlled in step 3. For patients being considered for high-dose inhaled corticosteroids, advice should be given about the increased risk of side effects. Tiotropium via mist inhaler may be considered for patients with a history of exacerbations despite combination therapy in step 3. Long-acting muscarinic antagonists may be considered as an add-on therapy for patients ≥6 years old or in patients ≥18 years as a combination inhaler if asthma is persistently uncontrolled despite medium- or high-dose of inhaled corticosteroid with long-acting beta2-agonist. If symptoms are not controlled by step 3 medications, the patient may be referred to a specialist for further diagnostic evaluation.
Step 5 - Add-on treatment & expert referral
This step is for patients with persistent symptoms or exacerbations despite optimization of existing therapy, correct inhaler technique, and good compliance. Oral low-dose corticosteroids may be added to other controller medications. This step may be effective in reducing the symptoms, especially in some adults with severe asthma, however, it may be associated with severe side effects, hence, should only be given to patients with uncontrolled symptoms and/or frequent exacerbations despite step 4 medications.
Long-acting muscarinic antagonists may be considered an add-on therapy for patients ≥6 years old or in patients ≥18 years as a combination inhaler if asthma is persistently uncontrolled despite medium- or high-dose inhaled corticosteroid with long-acting beta2-agonist.
The addition of Azithromycin may be considered if symptoms are still not controlled. Add-on anti-IgE (Omalizumab) may be considered for asthma patients aged ≥6 years old with the allergic components when control is not achieved despite the combination of other controllers. An add-on anti-IL5 (Mepolizumab, Reslizumab) and anti-IL5 receptor (Benralizumab) may be considered for patients with severe uncontrolled eosinophilic asthma despite adherence to step 4 regimen. Add-on anti-IL4α receptor (Dupilumab) may be considered in patients aged ≥6 years old with severe eosinophilic or type 2 asthma or in patients aged ≥12 years old in need of oral corticosteroid maintenance therapy. Add-on anti-thymic stromal lymphopoietin (anti-TSLP) (Tezepelumab) may be considered for patients aged ≥12 years old with severe asthma. Add-on Azithromycin may be considered for eosinophilic and non-eosinophilic asthma patients with persistent symptomatic asthma despite the reduction of exacerbations and improved quality of life with moderate- to high-dose inhaled corticosteroid-long-acting beta2-agonist combination therapy. Add-on low-dose oral corticosteroids may only be used on patients with severe asthma if with poor symptom control and/or frequent exacerbations despite good inhaler technique and adherence to step 4 regimen, and after other contributory factors and add-on treatments have been excluded.
If symptoms are not controlled by step 4 medications, the patient should be referred to a specialist for further diagnostic evaluation including assessment of phenotype and additional treatment. Treatment may be reassessed based on the patient’s eosinophilia seen during the sputum exam and may be applied if with a previous history of high-dose inhaled corticosteroid or inhaled corticosteroid with long-acting beta2-agonist therapy.
Maintaining Control of Asthma
A stepwise approach to therapy is the advancement to the next step of therapy if control is not reached or obtained with the current treatment. Treatment should be individualized based on the availability of antiasthmatic medications, resources of the healthcare system, individual patient circumstances, and cost.
Step Down
Once control is achieved and maintained and the patient has achieved stable lung function for 2-3 months, a gradual step down or stepwise reduction in treatment may be attempted. Nonetheless, stepping down is not applicable for patients at risk of exacerbations or persistent airflow limitation.
Patients currently on step 2 may reduce inhaled low-dose corticosteroids to once-daily dosing, may switch to as-needed low-dose inhaled corticosteroid-Formoterol, and may switch to inhaled corticosteroids whenever short-acting beta2-agonist is taken. Discontinuation of inhaled corticosteroid therapy is not advised for patients on this step.
Patients currently on step 3 may shift to once-daily dosing of low-dose inhaled corticosteroid-long-acting beta2-agonist combination, may shift to once-daily dosing of inhaled corticosteroid-Formoterol maintenance dose, and continue as-needed low-dose inhaled corticosteroid-Formoterol reliever, and may reduce moderate-high dose inhaled corticosteroid dose by 50%. The addition of leukotriene modifiers may be considered when stepping down an inhaled corticosteroid dose.
Patients currently on step 4 or patients on moderate-high dose inhaled corticosteroid-long-acting beta2-agonist combination maintenance regimen may reduce dose of inhaled corticosteroids by 50%, may switch to a lower maintenance dose inhaled corticosteroid-Formoterol as MART, may reduce inhaled corticosteroid-Formoterol therapy from medium-dose to low-dose then continue as-needed low-dose corticosteroid-Formoterol reliever regimen, and may reduce high-dose inhaled corticosteroids by 50% and continue the second controller.
Patients currently on step 5 may continue the high-dose inhaled corticosteroid-long-acting beta2-agonist combination. They may reduce the dose of oral corticosteroids wherein they may use a sputum-guided approach or may switch to alternate-day treatment or replace with inhaled forms. Patients may replace oral corticosteroids with high-dose inhaled corticosteroids or add biologic therapy if T2 high severe asthma. Patients on high-dose inhaled corticosteroid-long-acting beta2-agonist combination with other add-on agents should be referred for expert advice. Lastly, the patient’s inflammatory type based on sputum eosinophil count or FENO should be identified to assess eligibility to various add-on treatments.
Step Up
Consider step-up if control is not maintained upon reviewing the patient’s medication techniques, compliance, and non-pharmacological control. A sustained step-up of 2-3 months duration may be considered in patients who are not responding to the initial treatment regimen despite good treatment adherence and removal of modifiable risk factors. A short-term step-up of 1-2 weeks involved increasing the dose of inhaled corticosteroid for 1-2 weeks for special situations such as in the presence of viral infections or seasonal allergens. A day-to-day adjustment of as-needed inhaled corticosteroid-Formoterol doses based on symptoms should be considered in patients given Budesonide-Formoterol or Beclometasone-Formoterol combination as maintenance or reliever therapy.
Exercise-Induced Bronchoconstriction
In patients experiencing exercise-induced bronchoconstriction, reliever medications should be given prior to exercise or to relieve post-exercise symptoms. Treatment is reserved for patients with controlled asthma who develop exercise-induced symptoms or for those in whom exercise-induced bronchoconstriction is the only symptom.
Controller Medications
Preferred Therapy
Corticosteroids (Inhaled)
Inhaled corticosteroids are the most effective anti-inflammatory medications used for asthma and are the preferred controller medications for patients with persistent asthma of all levels of severity. Discontinuation of corticosteroids is followed by the deterioration of control within weeks to months in some patients.
To minimize its side effects, inhaler technique should be optimized to minimize systemic medication absorption. The patient should also rinse their mouth after use of inhaled corticosteroids or use a spacer to reduce topical adverse effects. Upon achievement of control, corticosteroids should be titrated carefully to lowest effective dose to maintain control and if need to increase dose, it is advisable to add another agent first (ie long-acting beta2-agonist or leukotriene receptor antagonist) rather than increasing the dose of inhaled corticosteroids.
Combination with Formoterol as initial treatment is preferred over daily inhaled corticosteroid monotherapy due to issues with treatment adherence. In patients taking short-acting beta2-agonists, inhaled low-dose corticosteroid therapy may be given without Formoterol, considering the patient's history of treatment adherence. The addition of long-acting inhaled beta2-agonist is preferred when daily low-dose inhaled corticosteroid fails. This addition may improve lung function and symptoms, reduce exacerbations, decrease the need of short-acting beta2-agonists, achieve faster clinical control of asthma, and may also be used to prevent exercise-induced asthma.
Alternative or Add-on Therapy
Anticholinergic (Inhaled)
Example drugs: Ipratropium bromide, Tiotropium bromide
Inhaled anticholinergic drugs are considered as alternative to short-acting inhaled beta2-agonists because they may have a slower onset of action and/or higher risk for side effects. They have an additive effect when nebulized together with a short-acting beta2-agonists for exacerbations of asthma. These drugs may be considered in patients who experience adverse effects (eg tachycardia, arrhythmia, tremor) from short-acting beta2-agonists. In general, they help improve lung function and increase the interval to the next asthma exacerbation. Ipratropium bromide may only be considered for exacerbations and not for long-term therapy.
Azithromycin
Azithromycin may be considered as an alternative add-on off-label therapy for uncontrolled or severe asthma. Sputum exam for atypical mycobacteria should be conducted prior to therapy initiation.
Beta2-Agonists (Inhaled, Long-acting)
Inhaled, long-acting beta2-agonists have no effect on airway inflammation, hence are not used as monotherapy. They are considered most efficacious when given together with inhaled corticosteroids. They achieve rapid clinical control of asthma than when inhaled glucocorticosteroids are given alone. Studies have shown an increased mortality risk when given alone and should not be used as a substitute for corticosteroids. They cause improved symptom scores, decreased nocturnal asthma symptoms, improved lung function, decreased use of short-acting beta2-agonists, and reduced number of exacerbations.
Beta2-Agonist (Oral, Long-acting)
Oral, long-acting beta2-agonists may be considered as alternative add-on therapy and should always be given with inhaled corticosteroids. They are only used on rare occasions when more bronchodilation is needed. However, they are considered less effective than inhaled beta2-agonists and pose increased risk of side effects.
Corticosteroids (Oral)
Based on Global Initiative for Asthma (GINA) 2023, low-dose oral corticosteroids (≤7.5 mg/day Prednisone equivalent) may be considered as a last resort treatment for adults with severe asthma. They should only be considered for adults with poor symptom control and/or frequent exacerbation despite good inhaler technique and adherence with step 5 treatment, and after exclusion of other contributory factors and availability of add-on treatments (eg anti-IgE, anti-IL5/IL5R, anti-IL4R, anti-TSLP). Long-term use (>2 weeks) may be required for severely uncontrolled asthma.
Leukotriene Modifiers (Oral)
Oral leukotriene modifiers may be used as an alternative for adult patients with mild persistent and Aspirin-sensitive asthma who are not able to tolerate inhaled corticosteroids or those who respond well to leukotriene modifiers. When used as add-on therapy, they may reduce the required dose of inhaled corticosteroid for patients with moderate to severe symptoms. When used as monotherapy for control of asthma, leukotriene modifiers are less effective than low-dose inhaled corticosteroids.
Monoclonal Antibodies
Example drugs: Benralizumab, Dupilumab, Mepolizumab, Omalizumab, Reslizumab, Tezepelumab
Monoclonal antibodies reduce exacerbations in patients with severe, uncontrolled asthma and improves lung function, asthma control, and health-related quality of life.
Omalizumab is indicated for patients ≥6 years of age with moderate to severe asthma with an allergic component, and allergic and nonallergic severe eosinophilic asthma not controlled by inhaled corticosteroids.
Subcutaneous (SC) Mepolizumab, SC Dupilumab, SC Benralizumab, and IV Reslizumab may be considered for severe eosinophilic asthma not controlled by inhaled corticosteroids. Dupilumab may also be considered in severe T2 asthma not controlled by medium- to high-dose inhaled corticosteroids plus ≥2 additional controller medications.
The use of Benralizumab and Dupilumab are contraindicated in patients <12 years of age; Mepolizumab in patients <6 years of age; and Reslizumab in patients <18 years of age. Tezepelumab was recently approved as an add-on maintenance treatment of severe asthma for patients ≥12 years of age.
Theophylline (Oral, Extended-release)
Theophylline is a bronchodilator, which at low dose, has anti-inflammatory effects but with known adverse effects, thus is not recommended for routine use. Monitoring of serum level is needed.
Reliever Medications
Preferred Therapy
Corticosteroids (Inhaled) with Formoterol
The combination of steroid with Formoterol is the preferred reliever medication previously given Budesonide-Formoterol or Beclometasone-Formoterol maintenance and reliever therapy. It is known to reduce the risk for severe exacerbation in adults and adolescents with mild asthma compared to short-acting beta2-agonist monotherapy.
Alternative Therapy
Beta2-agonists (Inhaled, Short-acting)
Inhaled, short-acting beta2-agonists are treatment option for relief of bronchoconstriction during acute episodes of asthma and are useful for pretreatment prior to exercise, to be used concomitantly with inhaled corticosteroids. Reliever-only initial treatment such as as-needed short-acting inhaled beta2-agonist is no longer recommended due to accumulated reports of increased risk of exacerbations and lower lung function with short-acting inhaled beta2-agonist monotherapy.
They may be used only when necessary, increased use indicates that management should be reassessed. Concomitant use with corticosteroid is recommended with every intake of a short-acting inhaled beta2-agonist to prevent side effects of short-acting inhaled beta2-agonist monotherapy. Overuse (≥3 dispensing of 200-dose canister/year) increases risk for asthma exacerbation.
Beta2-agonists (Oral, Short-acting)
Oral, short-acting beta2-agonists are alternatives to short-acting inhaled beta2-agonists but with slower onset of action and higher risk for side effects, more than the inhalation route.
Difficult-to-Treat Asthma
Difficult-to-treat asthma is defined as asthma with persistent symptoms and/or exacerbations despite adherence to high-dose asthma regimens (eg steps 4-5 of the management plan for long-term asthma, high-dose inhaled corticosteroids in adults or medium-dose inhaled corticosteroids in children with a long-acting inhaled beta2-agonist or leukotriene modifier, continuous or frequent therapy with oral corticosteroids). Risk factors include incorrect inhaler technique, poor adherence, comorbidities, exacerbation triggers, over-use of a long-acting inhaled beta2-agonist, psychosocial factors, and adverse effects of medications.
In order to optimize management, the steps include checking, reviewing, correcting, and demonstrating inhaler technique every visit; confirming if the patient has a written asthma action plan, and if the patient understands what is included; treating comorbidities and modifiable risk factors; considering lifestyle modifications, avoidance of triggers, influenza vaccination, and other non-pharmacologic treatments; considering nonbiologic therapies (eg Tiotropium bromide, Azithromycin, long-acting beta2-agonist, leukotriene modifiers) or high-dose inhaled corticosteroids if not previously given.
To manage difficult-to-treat asthma, it is important to assess the patient's inflammatory phenotype if unresponsive to the optimized management strategies and to consider add-on biologic treatments (eg Mepolizumab, Dupilumab, Benralizumab, etc) once severe asthma phenotype has been identified. The recommended biologic type-2 targeted treatments include the following:
- Omalizumab for patients aged ≥6 years old with sensitization to inhaled allergens on skin prick testing or specific IgE, total serum IgE, and body weight within specified dosing range, number of exacerbations within the last year considered under severe allergic asthma and/or with childhood-onset asthma.
- Mepolizumab (for patients aged ≥6 years old), Benralizumab (for patients aged ≥12 years old), or Reslizumab (for patients aged ≥18 years old) in patients with blood eosinophils above specified level, with number of exacerbations within the last year considered under severe eosinophilic asthma, with adult-onset asthma, with nasal polyposis, who are on oral corticosteroid maintenance therapy at baseline and/or with low lung function (eg FEV1 <65%).
- Dupilumab for patients aged ≥6 years old with severe type 2 inflammation characterized by raised eosinophils and/or raised FENO, or for patients aged ≥12 years old who require maintenance therapy with oral corticosteroids or for patients with concomitant moderate or severe atopic dermatitis.
- Tezepelumab may be considered for patients aged ≥12 years old without elevated type 2 markers characterized by raised eosinophils and/or raised FENO.
It is essential to review patient response after 3-4 months. Advise the patient to follow up after 3-6 months to assess the patient's response to treatment changes. Referral to a specialist or to a severe asthma clinic is recommended if asthma is still uncontrolled even with modifications and optimization of treatment. If with uncontrolled symptoms and/or exacerbations after treatment step-down, return to previous regimen and refer to a specialist or to a severe asthma clinic.
Nonpharmacological
Patient Education
The goal of patient education among asthmatic patients includes
increasing the patient’s understanding, skills, satisfaction, and
confidence to increase compliance and self-management of asthma, and developing
partnerships between healthcare professionals, the patient, and the patient’s
family. Patient education is a continual process to provide the patient and
their family with appropriate information (eg asthma is a chronic condition) and
training to allow the patient to remain well. It modifies therapy according to a
predetermined medication plan which includes monitoring, a written asthma
action plan containing specific information about medication, and the dosage
changes based on symptoms and/or peak expiratory flow, when and how to access
medical care, and regular follow-up. It should be provided over
several visits and ensure inquiry about the patient’s compliance with the
treatment plan and their ways of avoiding risk factors.
To improve compliance, the patient is more likely to be compliant with medicine
regimens if the diagnosis is accepted and the patient realizes that asthma can
be dangerous or can be a problem, the patient believes the treatment is safe,
or the patient feels in control and there is good communication between the
patient and the provider.
Healthcare
professionals should help patients to recognize deterioration in asthma control
and should educate patients to seek medical attention if there is a severe
asthma attack and respiratory distress (ie severe dyspnea, difficulty talking).
Reliever medication is needed more than every 4 hours and symptoms are still
not improving.
Self-monitoring
If possible, self-monitoring should be done based on
the resources of the healthcare system. On the initial visit, the concept of peak
expiratory flow monitoring may be introduced to the motivated patient. Patients
with more than mild disease should receive training on how to measure and
record peak expiratory flow. If peak expiratory flow monitoring is not an
option, patients should be educated to assess their status based on symptoms. Nonetheless,
self-monitoring is not reliable in children.
Written
Asthma Action Plan
A written asthma action plan may help patients
recognize and respond appropriately to an asthma attack. It should include
specific and individualized instructions about medications and medical care
access. Changes to medications may include increasing as-needed inhaled
low-dose corticosteroid-Formoterol doses, the use of an inhaler containing
rapid-onset long-acting beta2-agonist with a low-dose corticosteroid,
other inhaled corticosteroids and inhaled corticosteroid-long-acting beta2-agonist
maintenance controlled regimens, and short-course oral corticosteroids for
patients unresponsive to increased doses of reliever and controller
medications, rapid deterioration, peak expiratory flow or FEV1
<60% of personal best, or a history of sudden severe exacerbations.
Other Management
Allergen Immunotherapy
Allergen immunotherapy serves as a treatment option
after strict avoidance of triggers and medical intervention have failed. It may
reduce symptoms and medication use, improve allergen-specific and non-specific
airway hyperresponsiveness, and can possibly prevent asthma development in
children with allergic rhinoconjunctivitis.
It may be given as
subcutaneous immunotherapy (SCIT) or SLIT. House dust mite SCIT and SLIT are
recommended as add-on treatment in patients with controlled house dust
mite-driven allergic asthma. In children, SCIT has a higher efficacy than SLIT though
the latter has a better safety profile than the former. SLIT may be considered
in adults with asthma and allergic rhinitis whose triggers include house dust
mites whose exacerbations are not relieved by inhaled corticosteroids and with
FEV1 of >70% predicted.
SLIT has been associated with mild oral and
gastrointestinal symptoms. Life-threatening anaphylactic reactions have been
reported with SCIT use. Benefits must be weighed against adverse effects and
inconvenience of length of therapy. Efficacy of extracts or regimens based on
clinical trials should be put into consideration before initiating therapy.
Bronchial
Thermoplasty
Bronchial thermoplasty is a treatment option for adult
patients with severe asthma unresponsive to step 5 of the recommended
medications for asthma control and even with specialist referral, preferably
under a board-approved clinical trial. It is a procedure that utilizes
radiofrequency pulse during bronchoscopies to reduce bronchial smooth muscle
mass, thereby decreasing the capacity for bronchoconstriction.
Asthma Exacerbations
Asthma exacerbations are
events characterized by increased dyspnea, cough, wheezing, or chest tightness,
and progressive decrease in lung function. It is described as having a
reduction in expiratory airflow that is measured and monitored by lung function.
It may occur in patients previously diagnosed with asthma or as first
presentation of asthma.
During asthma exacerbation, the goal of management
is to immediately relieve airflow obstruction and hypoxemia, and to prevent
further deterioration of the patient.
Evaluation
Primary
Care Management Assessment
Patients with mild-moderate exacerbations talk in
phrases, prefer to sit, are calm, with increased respiratory rate, pulse rate
of 100-120 bpm, O2 saturation of 90-95%, and peak expiratory flow of
>50% predicted/personal best.
Patients suspected with severe exacerbations
manifesting with a respiratory rate of >30/min, pulse rate of >120 bpm, O2
saturation of <90%, peak expiratory flow of ≤50% predicted/best, accessory
muscles in use, talk in words, hunched forward while sitting, and agitated require
immediate hospital transfer.
Emergency
Department Assessment
A brief history and physical exam should be
conducted while therapy is initiated.
History
and Physical Examination
The following are the important components of medical history in
patients suspected with asthma exacerbations:
- Symptom severity
- Time of onset and cause
- Risks for possible
asthma-related death, which necessitates closer medical supervision
- History of asthma attack that needed intubation and mechanical ventilation
- Hospitalized or emergency visit in the past year
- Using oral or inhaled corticosteroid currently or recently stopped
- Using >1 canister of inhaled rapid-acting beta2-agonists monthly
- With psychiatric or psychosocial problem
- Noncompliant to management plan
- Food allergy
- Any symptoms indicative of anaphylaxis
- All current medications including doses, devices, adherence pattern, changes in regimen, and treatment response
During the physical examination, it is important to assess
and classify the severity of exacerbation. It is also important to examine for
other factors that may complicate the condition (eg pneumonia, pneumothorax,
atelectasis).
Patients with mild-moderate exacerbations prefer to
sit, talk in phrases, without accessory muscles being used, no agitated, with
increased respiratory rate, pulse rate of 100-120 bpm, O2 saturation
of 90-95%, and peak expiratory flow of >50% predicted or best.
Patients with severe
exacerbations manifest with a respiratory rate of >30/min, pulse rate of
>120 bpm, O2 saturation of <90%, peak expiratory flow of ≤50%
predicted/best, accessory muscles in use, talk in words, hunched forward while
sitting, and agitated.
Functional
Assessments
If possible, obtain a baseline peak expiratory flow
or FEV1 prior to treatment without unduly delaying therapy, and
until improvement is observed. In addition, O2 saturation which is
preferably obtained by pulse oximetry is also helpful in children where lung
function measurement is not reliable.
Imaging such as a chest X-ray is requested only if
there are suspected complicating factors, the patient is for admission, and not
responding to treatment.
An arterial blood gas is recommended in patients with
peak expiratory flow of <50% predicted, unresponsive to treatment, and signs
of deterioration. Respiratory failure is indicated if results show a partial
arterial pressure of oxygen (PaO2) of <60 mmHg, and normal or increased partial arterial carbon dioxide pressure
(PaCO2) of >45 mmHg.
Assessment
of Patient’s Response After Initial Emergency Department Therapy
Lung function should be
measured after 1 hour, after administration of first 3 bronchodilators, and
in patients with disease progression despite intensive bronchodilator and
steroid therapy, to evaluate the need for intensive care unit transfer.
For patients with
moderate exacerbation, the patient response may include an FEV1 or peak
expiratory flow of >60-80% predicted or personal best and with improved
symptoms. Hence, consideration for discharge should be made.
For patients with severe exacerbation, the patient
response may include an FEV1 or peak expiratory flow of <60%
predicted or personal best and the symptoms may not be improving. Hence, continuation
of treatment with reassessment at regular intervals should be done.
Assessment
of Patient’s Response After Hospital Admission
Consider
admission to intensive care unit if the patient is having severe asthma and
there is no response to initial therapy in the emergency department or there is
worsening asthma despite therapy. Other indications for admission to intensive
care unit include patients with signs of imminent respiratory arrest (eg confusion,
drowsiness, loss of consciousness) or in patients showing signs hypoxemia
despite supplemental oxygen which is indicative of impending respiratory arrest
showing a PaO2 of <60 mmHg (8 kPa) and/or a PaCO2 of
>45 mmHg (6 kPa), or oxygen saturation by oximetry of 90% in children.
Intubation is considered if there is continued
deterioration despite optimal therapy. Intubation may also be considered in exhausted
patients and/or if the partial arterial carbon dioxide pressure is increasing.
Consider home discharge in
patients with peak expiratory flow of >60-80% predicted/personal best, an
oxygen saturation of >94% room air, and is sustained on oral or inhaled
medication.
Management
Beginning therapy at
home avoids delay in treatment along with giving the patient a sense of control
over their asthma. The degree of therapy administered at home will depend on
the healthcare provider and the patient’s experience, availability of medicines,
and emergency care. Home peak expiratory flow measurements may be part of the
home management strategy. The degree of symptoms is generally a more sensitive
predictor of early stages of asthma attack than peak expiratory flow. If the patient’s
asthma continues to deteriorate or suddenly worsens, consider transferring to
an acute care facility.
First-Line
Treatment
Oxygen
(O2)
Oxygen should be administered via nasal cannula,
mask or if required, head box (for some infants), to achieve an arterial oxygen
saturation of 93-95% (94-98% in children). Good physiological outcomes were
observed with controlled oxygen therapy using pulse oximetry to maintain oxygen
saturation at 93-95% compared to high flow 100% oxygen therapy. It should be
titrated against pulse oximetry to maintain a satisfactory oxygen saturation. However,
oxygen should not be withheld if oximetry is not available.
Beta2-Agonists
(Inhaled, Short-Acting)
Bronchodilatation equivalent to nebulizer can be
achieved using a metered dose inhaler (MDI) with a spacer. The onset is more
rapid, with fewer side effects, and achieves lesser time in the emergency
department. Inhalation via nebulizer may be easier for children. Patients should
use continuous inhaled therapy initially, then followed by intermittent
on-demand therapy. Studies showed that high-dose inhaled Budesonide/Formoterol
combination is comparable to high-dose inhaled short-acting beta2-agonists
for the treatment of acute asthma exacerbation in the emergency department
setting.
Epinephrine
Epinephrine may be considered in severe exacerbations
associated with anaphylaxis and angioedema, if inhaled or parenteral beta2-agonists
are not available, or the patient is not responsive to inhaled short-acting
beta2-agonists. It is not routinely used in asthma exacerbation.
Other
Treatments
Anticholinergics
(Inhaled)
Example drug: Ipratropium bromide
When nebulized with a beta2-agonist, anticholinergics
may achieve better bronchodilatation than either drug alone. This combination
should be used before considering xanthines.
Xanthines
Example drugs: Theophylline, Aminophylline
The bronchodilator effect of xanthines is less than
that of beta2-agonist drugs. It should only be considered as an
alternative agent if other agents do not work and because of the risk of side
effects.
Corticosteroids
(Systemic)
Systemic corticosteroids are considered a
fundamental part in the treatment of all exacerbations except in the mildest
form. It is especially recommended when the initial short-acting beta2-agonist
dose has not achieved a lasting improvement, the exacerbation occurred even
though patient is receiving oral corticosteroids, or when previous
exacerbations required oral corticosteroids.
Oral doses are usually as effective as the
intravenous route. The intravenous route may be considered if gastrointestinal
absorption is questionable, if the patient cannot tolerate oral preparations,
very dyspneic to swallow, vomiting, or requiring intubation or non-invasive
ventilation. Intramuscular route may be used if the patient is being discharged
from the emergency room and compliance is an issue.
Corticosteroids
(Inhaled)
Inhaled corticosteroids are an effective part of
combination therapy for asthma exacerbations. High-dose inhaled corticosteroid
may reduce the need for hospitalization when given within the first hour after
presentation in the emergency room. It may reduce hospital admission and the
need for systemic corticosteroids in children if administered with or without
systemic corticosteroids within the first hour in the emergency room. High dose
of inhaled corticosteroid can give the same effect as 40 mg oral Prednisone,
but cost may be an inhibiting factor.
Treatment containing inhaled corticosteroids should
be prescribed upon discharge to reduce future exacerbations and the risk of
asthma-related death or hospitalization. Patients admitted to the hospital due
to asthma exacerbation should continue on or be prescribed with inhaled
corticosteroid therapy.
Magnesium
(Mg)
Intravenous magnesium should not be used routinely in exacerbations but
may be considered in adults with FEV1 of <25-30% predicted at
presentation, adults and children who do not respond to initial treatment with
persistent hypoxemia, and children whose FEV1 does not improve above
60% of predicted after 1 hour of care. The usual dose is 2 g IV over
20 minutes (Max dose: 2 g), and in children, the usual dose is 40-50 mg/kg slow
IV over 20-60 minutes (Max dose: 2 g).
Considerations
Prior to Discharge
For patients with good response to treatment being
considered for discharge, ensure that the patient has adequate resources at
home and advise the patient to contact the clinician urgently if with worsening
of symptoms. Make sure to provide a guided self-management plan to all patients
with asthma. Educate the patients about significant symptoms that should be
monitored and a written asthma action plan* and stress the importance of
adherence to prescribed medications, preventive strategies for exacerbations, and
follow-ups. Arrangements for follow-up after 2-7 days should be made.
*Please see Patient Education section for further information.