asthma
ASTHMA
Asthma is a chronic inflammatory disease of the airways in the lungs of children and adults.
The patient usually complains of shortness of breath, chest tightness and coughing with wheezing.
Goals of treatment are effective symptom control with minimal or no exacerbations, minimal or no nocturnal and daytime symptoms, no limitations on activities, minimal or no need for reliever treatment, and minimal adverse effects of medication.

Principles of Therapy

Goals of Therapy
  • Effective symptom control w/ minimal or no exacerbations
  • Minimal or no daytime & nocturnal symptoms
  • No limitations on activities, including exercise
  • Minimal or no need for reliever treatment
  • No emergency visits
  • Normal or near normal pulmonary function
  • Minimal adverse effects of medication

Therapeutic Strategies

  • Depends on a control-based approach
  • Treatment is continuously adjusted depending on patient’s response to therapy
  • Involves a cycle of assessment, treatment & review of patient response
  • Other strategies used include sputum-guided treatment & fractional concentration of exhaled nitric oxide
  • Beginning therapy at home avoids delay in treatment along w/ giving the patient a sense of control over their asthma
  • Degree of therapy administered at home will depend on the healthcare provider & the patient’s experience, availability of medicines & emergency care
  • Home PEF measurements may be part of the home management strategy
    • Degree of symptoms is generally a more sensitive predictor of early stages of asthma attack than PEF
  • If patient’s asthma continues to deteriorate or suddenly worsens, consider transferring to an acute care facility

Pharmacotherapy

Recommended Medications Based on Level of Control1
Treatment Steps Daily Controller Medications
  Children ≤5 years Adults & Children >6 years
Step 1
  • No daily medication required
Reliever
  • As needed beta2-agonist (inhaled, short-acting)
  • No daily medication required
Reliever
  • As needed beta2-agonist (inhaled, short-acting)2
Other controller options:
  • Consider corticosteroid (inhaled, low-dose)
Step 2

Preferred Controller

  • Corticosteroid (inhaled, low-dose)
Reliever
  • As needed beta2-agonist (inhaled, short-acting)
Other controller options:
  • Leukotriene modifier
  • Intermittent corticosteroid (inhaled)
Preferred Controller
  • Corticosteroid (inhaled, low-dose)
Reliever
  • As needed beta2-agonist (inhaled, short-acting)2
Other controller options:
  • Leukotriene modifier
  • Theophylline (low-dose)3
Step 3 Preferred Controller
  • Corticosteroid (inhaled, moderate-dose [doubled low-dose])
Reliever
  • As needed beta2-agonist (inhaled, short-acting)
Other controller options:
  • Corticosteroid (inhaled, low-dose) plus leukotriene modifier
Preferred Controller
  • Corticosteroid (inhaled, low-dose) plus beta2-agonist (inhaled, long-acting)3
Reliever (any of the following)
  • As needed beta2-agonist (inhaled, short-acting)3
  • Corticosteroid (inhaled, low-dose) plus Formoterol4
Other controller options (any one of the following):
  • Corticosteroid (inhaled, high- or medium-dose)
  • Corticosteroid (inhaled, low-dose)
    Plus any one of the following:
    - Leukotriene modifier
    - Theophylline (low-dose, extended-release)3
Step 4
  • Continue controller therapy
  • Specialist referral
Reliever
  • As needed beta2-agonist (short-acting)
Other controller options:
  • Plus any of the following:
  • - Leukotriene modifier
    - Increase corticosteroid (inhaled) frequency
    - Intermittent corticosteroid (inhaled)
Preferred Controller
  • Corticosteroid (inhaled, medium-/high-dose) plus beta2-agonist (inhaled, long-acting)
Reliever (any of the following)
  • As needed beta2-agonist (inhaled, short-acting)2
  • Corticosteroid (inhaled, low-dose) plus Formoterol4
Other controller options:
  • Tiotropium bromide5
  • Corticosteroid (inhaled, high-dose)
    Plus any one of the following:
    - Leukotriene modifier
    - Theophylline (extended-release, long-acting)3
Step 5   Step 4 therapy
Plus any one of the following:
    - Tiotropium bromide5
    - Corticosteroid (oral, lowest dose)
    - Anti-IgE/IL-5 (Omalizumab, Mepolizumab3, Reslizumab3)
1Adapted from: Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention 2017. pp. 43 & 111.
2Short-acting inhaled beta2-agonists should be used as required to relieve symptoms. These should not be taken >3-4 x/day. Other options for reliever medication are anticholinergic (inhaled), beta2-agonist (oral, short-acting) or Theophylline.
3Not recommended for children 6-11 years; for Step 3, increasing from low- to medium-dose corticosteroid is preferred.
4Preferred  for patients previously given low-dose Budesonide/Formoterol or low-dose Beclomethasone/Formoterol combination as maintenance & reliever regimen.
5Tiotropium by soft-mist inhaler is only to be given to patients ≥12 years of age with a history of exacerbations.

Stepwise Therapy Based on Control

Step 1 - Use of Reliever, as Needed

  • Only reliever medications on an “as necessary” basis are given
  • Reserved for patients with controlled asthma
  • Additional low-dose inhaled corticosteroid may be considered for patients with increased risk of exacerbations

Step 2 - Use of Reliever, as Needed & a Single Controller

  • For patients who require controller medications everyday in order to maintain control of their asthma
  • May be used as initial therapy for treatment-naive patients with persistent symptoms

Step 3 - Use of Reliever, as Needed & 1 or 2 Controllers

  • For patients who require controller medications everyday in order to maintain control of their asthma
  • If symptoms are not controlled by step 3 medications, patient may be referred to a specialist for further diagnostic evaluation
  • For children, increasing the dose of the corticosteroid from low to medium is preferred than adding a long-acting beta2-agonist

Step 4 - Use of Reliever, as Needed & ≥2 Controllers

  • Consider expert referral
  • Therapy usually requires multiple daily controller medications
  • Treatment choice will depend upon what was previously used in step 2 or 3
  • For adult & adolescent patients, low-dose inhaled corticosteroid combined with Formoterol used as both maintenance & reliever treatment is preferred than increasing the dose of inhaled corticosteroids

Step 5 - Use of Reliever, as needed & Additional Controller Options

  • Oral corticosteroids may be added to other controller medications
    • May be effective in reducing the symptoms esp in some adults with severe asthma
    • Associated with severe side effects, hence, should only be given to patients with uncontrolled symptoms &/or frequent exacerbations despite step 4 medications
  • Addition of anti-IgE may be considered for asthma with allergic component when control is not achieved despite combination of other controllers
  • Additional anti-IL5 (Mepolizumab) may be considered for patients >12 year of age with severe uncontrolled eosinophilic asthma despite adherence to step 4 regimen
  • Treatment may be reassessed based on the patient’s eosinophilia seen during sputum exam
    • May be applied if with previous history of high-dose inhaled corticosteroid or inhaled corticosteroid with long-acting beta2-agonist therapy

Maintaining Control of Asthma

  • Step-wise approach to therapy is the advancement to the next step of therapy if control is not reached or obtained w/ the current treatment
  • Treatment should be individualized based on the availability of antiasthmatic medications, resources of healthcare system, individual patient circumstances & cost

Step Down

  • Once control is achieved & maintained for 3 months, gradual step-wise reduction in treatment may be attempted
  • Not applicable for patients at risk of exacerbations & fixed airflow limitation
  • Patients currently on Step 2:
    • Inhaled low-dose corticosteroids may be reduced to once-daily dosing
    • Addition of leukotriene modifiers may be considered when stepping down inhaled corticosteroids dose
    • May consider stopping controller treatment when non-symptomatic for 6-12 months & without risk factors
  • Patients currently on Step 3:
    • Shift to once-daily dosing of low-dose inhaled corticosteroid-long-acting beta2-agonist combination
    • Moderate-high dose inhaled corticosteroid step down at 25-50% in 3 month intervals is suggested
  • Patients currently on Step 4:
    • May reduce dose of inhaled corticosteroids by 50% for patients on inhaled corticosteroid-/long-acting beta2-agonist combination
    • Continue as needed low-dose corticosteroid/Formoterol reliever regimen
  • Patients currently on Step 5:
    • Oral corticosteroids may be reduced or may be replaced with inhaled forms

Step Up

  • Consider step-up if control is not maintained (review patient medication techniques, compliance & non-pharmacological control)
  • Sustained step-up of 2-3 months duration may be considered in patients who are not responding to initial treatment regimen despite good treatment adherence & removal of modifiable risk factors
  • Short-term step up 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

Exercise-Induced Bronchoconstriction

  • Reliever medication 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 to those in whom exercise-induced bronchoconstriction is the only symptom

Preferred Inhaler Device for Asthmatic Children

  • 0-3 years old: Pressurized metered-dose inhaler plus dedicated spacer with face mask
    • Nebulizer with face mask may be an alternative
  • 4-5 years old: Pressurized metered-dose inhaler plus dedicated spacer with mouthpiece
    • Pressurized metered-dose inhaler plus dedicated spacer with face mask or nebulizer with mouthpiece or face mask is an alternative
  • ≥6 years old: Dry powder inhaler, or breath-actuated pressurized metered-dose inhaler, or pressurized metered-dose inhaler with spacer & mouthpiece
    • Nebulizer with mouth piece may be an alternative for children 4 years old & above

Reliever Medications

Preferred Therapy

  • Beta2-Agonists (Inhaled, Short-Acting)
    • Most effective bronchodilator
    • Agents of choice for relief of bronchoconstriction during acute episodes of asthma & are useful for pretreatment prior to exercise with effects lasting for 0.5 to 2 hours
    • Used only when necessary; increased use indicates that management should be re-assessed

Alternative Therapy

  • Beta2-Agonists (Oral, Short-Acting) 
    • Reserved for children in whom inhaled therapy is not well-tolerated
    • More side effects than inhalation route
  • Corticosteroids (Inhaled) + Formoterol
    • May be used for patients unresponsive to inhaled short-acting beta2-agonist as reliever treatment

Controller Medications

Preferred Therapy

  • Corticosteroids (Inhaled)
    • These are the most effective anti-inflammatory medications used for asthma & are the preferred controller medications for patients with persistent asthma of all levels of severity
    • Discontinuation is followed by deterioration of control within weeks to months in some patients
    • To minimize side effects, upon achievement of control, corticosteroids should be titrated carefully to lowest effective dose to maintain control
      • Ciclesonide, a prodrug activated only in the lungs, may be an alternative with decreased oropharyngeal side effect
    • Addition of long-acting inhaled beta2-agonist is preferred when medium-dose inhaled corticosteroid fails
      • Improves lung function & symptoms, reduces exacerbations, decreases need of short-acting beta2-agonists, achieves faster clinical control of asthma, & may also be used to prevent exercise-induced asthma
    • Combination inhalers are available which may increase compliance 

Alternative or Add-On Therapy

  • Anticholinergic (Inhaled)
    • Eg Tiotropium bromide, Ipratropium bromide 
    • Considered alternative to short-acting inhaled beta2-agonists because they may have a slower onset of action &/or higher risk for side effects
    • Have an additive effect when nebulized together with a short-acting beta2-agonists for exacerbations of asthma
    • Considered in patients who experience adverse effects (eg tachycardia, arrhythmia, tremor) from short-acting beta2-agonists
    • Tiotropium by mist inhaler may be considered for patients >12 years of age with a history of exacerbations 
    • Not for long term management of asthmatic children
  • Beta2-Agonists (Inhaled, Long-acting)
    • Has no effect on airway inflammation, hence not used as a monotherapy
    • Most efficacious when given together with inhaled corticosteroids
      • Rapid clinical control of asthma is achieved than when inhaled glucocorticosteroids are given alone
      • Studies have shown increased mortality risk when given alone; should not be used as a substitute for corticosteroids
      • Causes improved symptom scores, decreased nocturnal asthma symptoms, improved lung function, decreased use of short-acting beta2-agonists, & reduced number of exacerbations
  • Beta2-Agonist (Oral, Long-acting)
    • May be considered as an alternative add-on therapy & should always be given with inhaled corticosteroids
    • Only used on rare occasions when more bronchodilation is needed
    • Less effective than inhaled beta2-agonists & poses increased risk of side effects
  • Corticosteroids (Oral)
    • Long-term use (>2 week) may be required for severely uncontrolled asthma
    • Long-term use should be used at the lowest possible dose
  • Cromones (Inhaled)
    • Limited use in long-term treatment of asthma
    • May be used for patients with mild persistent asthma & exercise-induced bronchoconstriction
    • Weak anti-inflammatory effect, less effective than low-dose inhaled corticosteroids
  • Leukotriene Modifiers (Oral)
    • May be used as an alternative for adult patients with mild persistent & 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, 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 (Mepolizumab, Omalizumab, IV Reslizumab)
    • Reduces asthma symptoms and exacerbations, and the need for rescue medications
    • Omalizumab is indicated for moderate to severe asthma with allergic component not controlled by inhaled corticosteroids
    • Mepolizumab & Reslizumab may be considered for severe eosinophilic asthma not controlled by inhaled corticosteroids
      • Use of Reslizumab in patients <18 years of age with asthma has not been established
  • Theophylline (Oral, Extended-Release)
    • Bronchodilator, which at low dose, has anti-inflammatory effects
    • Monitoring of serum level is needed
      • Side effects are more common at doses ≥10 mg/kg body weight/day

Allergen-Specific Immunotherapy

  • Treatment option after strict avoidance of triggers & medical intervention have failed
  • May be given as subcutaneous immunotherapy (SCIT) or sublingual immunotherapy (SLIT) 
    • SLIT may be considered in adults with asthma & allergic rhinitis whose triggers include house dust & mites whose exacerbations are not relieved by inhaled corticosteroids & with FEV1 of >70% predicted 
    • Life-threatening anaphylactic reactions have been reported with SCIT use
    • Sublingual immunotherapy (SLIT) has been associated with mild oral and GI symptoms
  • May reduce symptoms, medication use, improve allergen-specific & non-specific airway hyperresponsiveness & can possibly prevent asthma development in children with allergic rhinoconjunctivitis
  • Benefits must be weighed against adverse effects & inconvenience of length of therapy

Bronchial Thermoplasty

  • Treatment option for patients with severe asthma unresponsive to Step 5 of the recommended medications for asthma control & even with specialist referral
  • A procedure that utilizes radiofrequency pulse during bronchoscopies 
Managing Asthma Exacerbations
  • Beginning therapy at home avoids delay in treatment along with giving the patient a sense of control over their asthma
  • Degree of therapy administered at home will depend on the healthcare provider & the patient’s experience, availability of medicines & emergency care
  • Home PEF measurements may be part of the home management strategy
    • Degree of symptoms is generally a more sensitive predictor of early stages of asthma attack than PEF
  • If patient’s asthma continues to deteriorate or suddenly worsens, consider transferring to an acute care facility

Treatment

First Line

  • Oxygen
    • O2 should be administered via nasal cannula, mask or if required, head box (for some infants), to achieve arterial O2 saturation 93-95% (94-98% in children)
    • If O2 monitoring is not available, supplemental O2 is recommended
    • Good physiological outcomes were observed w/ controlled O2 therapy using pulse oximetry to maintain O2 saturation at 93-95% compared to high flow 100% O2 therapy
    • O2 therapy should be titrated against pulse oximetry to maintain a satisfactory oxygen saturation
      • However, O2 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
      • Onset is more rapid, fewer side effects & less time in the emergency department
    • Inhalation via nebulizer may be easier for children
    • Should use continuous inhaled therapy initially, then followed by intermittent on-demand therapy
  • Epinephrine
    • May be considered in severe exacerbations associated with anaphylaxis & angioedema, if inhaled or parenteral beta2-agonists are not available or patient is not responsive to inhaled short-acting beta2-agonists
    • Not routinely used in asthma exacerbation

Additional Bronchodilators

  • Anticholinergics (Inhaled)
    • Eg Ipratropium bromide
    • When nebulized with beta2-agonist, may achieve better bronchodilatation than either drug alone
    • This combination should be used before considering xanthines
  • Xanthines
    • Eg Theophylline, Aminophylline
    • Bronchodilator effect is less than that of beta2-agonist
    • Should only be considered as an alternative agent because of the risk of adverse effects
  • Corticosteroids (Systemic)
    • Considered a fundamental part in the treatment of all exacerbations except in the mildest form
    • Especially recommended when:
      • Initial short-acting beta2-agonist dose has not achieved a lasting improvement
      • Exacerbation occurred even though patient is receiving oral corticosteroids or high-dose inhaled steroids
      • Exacerbation is prolonged for >36-48 hours
      • Previous life-threatening exacerbations requiring oral corticosteroids
    • Oral doses are usually as effective as IV
      • IV may be considered if GI absorption is questionable or if an IV line needs to be established
      • IM may be used if the patient is being discharged from the emergency room & compliance is an issue
  • Corticosteroids (Inhaled)
    • Effective as part of combination therapy for asthma exacerbations
    • High dose of inhaled corticosteroid can give the same effect as 40 mg oral Prednisone, but cost may be an inhibiting factor
  • Magnesium (Mg)
    • IV Mg should not be used routinely in exacerbations but may be considered in adults w/ FEV1 <25-30% predicted at presentation, adults & children who do not respond to initial treatment with persistent hypoxemia & children whose FEV1 does not improve above 60% of predicted after 1 hour of care
      • Usual dose: 2 g IV over 20 minutes (Max dose: 2 g)
      • In children: 40-50 mg/kg slow IV over 20-60 minutes (Max dose: 2 g)
    • For children ≤2 year with severe exacerbations, nebulized isotonic Magnesium may be combined with inhaled Salbutamol & Ipratropium during the initial stages of therapy
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