Asthma

Chronic inflammatory airway disease causing bronchoconstriction, characterized by airway hyper responsiveness, mucosal edema and mucus production obstructing airways.

Interactions between susceptible genes and environmental factors play a role in development of asthma.

• Susceptible genes and mediators involved include
  • T-helper 1 and 2 (T_H1 and T_H2) cells, IgE, cytokines, GM-CSF
  • Tumor necrosis factor-α (TNF-α)
  • ADAM33 gene
• Environmental allergens include:
  • Mold, pollen, dust mite and fungi
  • Cockroaches and animal allergens
• Obesity (has been implicated)
• Work related asthma can be divided between
  • Occupational asthma
  • Work exacerbated asthma
• Allergic reactions to foods such as; peanuts, shellfish etc.
• Irritants: Such as household sprays, paint fumes, cigarette smoking, air quality (indoor and outdoor)
• Emotional factors or stress
• Perinatal factors: Pre-maturity, increased maternal age, maternal smoking and prenatal exposure to tobacco smoke

• Overall prevalence in Canadians
  • Approx. 15.6% in under 12 years of age
  • Approx. 8.3% in >12 years of age
• Asthma affects
  • Approx. 2.2 million in Canadians
  • Approx. 300 million persons worldwide
• Leading chronic illness in children
• Mortality rate of 20 children/year and 500 adults/year in Canada
• Leading cause of missed schools and third leading cause for sick day at work
• About 4000 asthma-related deaths annually in the US

Gross pathology of asthmatic airways displays:

• Submucosal inflammation
• Lung hyperinflation
• Smooth muscle hypertrophy
• Mucosal edema
• Epithelial cell sloughing
• Mucus gland hypersecretion

Airflow obstruction is associated with:

• Acute bronchoconstriction
• Airway edema
• Chronic mucous plug formation
• Airway remodeling is associated with structural changes

Mechanism(s) of Asthma

Inflammatory disorder of airways in which inflammation, airway remodeling and hypersensitivity ultimately lead to bronchoconstriction and respiratory distress.

Asthma is a variable disease in which the symptoms wax and wane. Attacks occur most commonly at night or in early morning hours (circadian variation).

Mild to moderate attacks:

• Cough, dyspnea, and wheezing (with or without mucus production)
• Shortness of breath (prolonged expiratory phase)
• Increased respiratory rate (with use of accessory muscles)
• Chest tightness
• Decreased breath sounds
• Increased heart rate
• Decreased exercise tolerance

Life threatening attacks: Include the above noted symptoms PLUS

• Peripheral cyanosis due to hypoxia as the attack progress
• Difficulty speaking
• Altered sensorium (with severe asthma attack)

Diagnosis:

Asthma can be diagnosed by history, physical exam and through objective measurements of pulmonary function in individuals ≥6 years and older.

Pulmonary function tests includes:

• Spirometry (preferred)
  • Measurements of lung function by spirometry, before and after administration of beta 2 agonists, should be used to confirm the clinical diagnosis of asthma (note, full pulmonary function testing is unnecessary)
  • The ratio FEV1/FVC is a measure of airflow obstruction. Diagnosis of asthma is supported when reversible airflow obstruction is present
• Alternative studies include:
  • Peak expiratory flow
  • Positive challenge tests

In children <6 years (spirometry unavailable at this age) the diagnosis is suggested by:

• Typical pattern of coughing, wheezing, dyspnea
• Nighttime cough
• Exercise-induced symptoms
• Response to asthma drugs
• Absence of other medical conditions that might account for symptoms

History

• History of presenting complaints: Breathlessness, wheezing, cough, sputum or chest tightness
• Exacerbation of attack
• Triggers, such as:
  • Smoking
  • Allergies (sudden exposure to dust, mites, fumes)
  • Psychosocial issues
• Current treatment such as; last steroid use
• ER/Hospital visits
• Family history
• Environmental history
• Occupational history
• Allergic history

Physical Examination:

• BP, pulse, temperature, respiratory rate, and oximetry
• Chest auscultation for wheeze, rhonchi and crepitations
• Breath sound reduction
• Nasal polyposis
• Cyanosis (peripheral and central)
• Any allergic rash or edema
• Accessory muscle use
• Hyperresponsiveness (assessed by the healthcare provider)
• Pulsus paradoxus

Ref: Kaplan AG, Balter MS, Bell AD, et al. Diagnosis of asthma in adults. CMAJ November 10, 2009 vol. 181 no. 10 E210-E220.

Laboratory Studies

Routine office/clinic visit may not require investigation if patient is stable.

Mild attack or at first presentation:

• Spirometry if >6 years

Consider ruling out concomitant issues or assessing triggers.

• CBC count with differential (eosinophilia >4% support asthma diagnosis)
• Chest radiography
• CT of sinuses (when chronic sinusitis a concern)
• Allergy testing

Moderate-severe exacerbations:

In addition to the work up for mild attacks, consider

• Blood cultures (if bacterial infection suspected)
• ABGs, if needed and concern for patient tiring in an acute attack
• Serum theophylline level, if taking theophylline
• Electrolytes with high dose B₂ agonist use to rule out hypokalemia

TREATMENT STRATEGIES:

CHRONIC ASTHMA:

A) Non-pharmacological measures

Education:

Goal:

• Enhance asthma knowledge to promote behavioral change, improve compliance and disease control

What is asthma?

• Information about what is asthma including airway inflammation and bronchospasm

Provocative factors/prevention:

• Identify and eliminate allergens
  • Indoor: Animal fur/pets, house mites, cockroaches etc.
  • Outdoor: Pollen, mold, etc.
• Air pollutants/irritants:
  • Indoor: Smoking, carbon monoxide
  • Outdoor: Aerosol, weather (humidity, thunderstorms)
• Work related asthma
  • Work exacerbation asthma of preexisting disease
  • Occupational asthma should be considered and investigated especially in adults with new-onset asthma
• Remove possible causative substance from exposure such as
  • Certain foods and food additives
  • Remove pets if necessary especially cats
  • Old mattresses and pillow covers, if dust mite sensitive
• Emotional stress: May exacerbate asthma
• Drugs: Such as aspirin (and possible other NSAIDS) especially in those with nasal polyps
• Influenza vaccination: Does not protect against asthma exacerbations, but may prevent concomitant infections
• Pneumococcal vaccination: Literature is unclear on this, but there is a known higher risk of pneumococcal infections in those with asthma

Avoidance and adherence:

Patients should be made aware of

• Underlying provocative factors and need for avoidance
• Correct use and side effects of preventive medications and bronchodilators
• Correct use of inhaler technique, and the need for regular follow-up
• Increasing medication for asthma control is not accounted as avoidance strategy

Facilitation of asthma education and monitoring:

• Should be provided at each patient contact
• A written action plan for guided self-management (based on symptoms) should be provided to patients (e.g. www.AsthmaActionPlan.com; www.asthma-education.com)
• Communication and coordination between patients and health professionals is helpful to ensure the action plan is being followed

Home monitoring:

• Patients should be encouraged into self-monitoring of symptoms and/or use of PEF
• Symptom-based or PEF based monitoring appear to be similar in most cases
• Patients can also use diaries found at www.asthma-education.com to document their symptoms and PEF readings, especially who are poor perceivers of airflow obstruction

Physician office monitoring:

• Pattern and frequency of symptoms
• Nighttime attacks
• Exacerbations
• Monitoring the correct use of how and when to use medications
• Routine measurement of PEF

B) Pharmacological measures

• Relievers
• Controllers

Reliever medications

• Used to relieve acute asthma symptoms
• Short-acting β2-agonists (SABA), are bronchodilators used on demand at minimum required dose and frequency
• Fast-acting β2 agonists (FABA), are bronchodilators that includes fast acting medications with longer action e.g. formoterol
• For patients intolerant to Beta agonists, inhaled ipratropium bromide may be used as a reliever (less effective than SABA)

Controller medications

• Taken regularly to control asthma and prevent exacerbations
• Inhaled agents minimizes systemic absorption and hence improves therapeutic benefit to the potential side-effects ratio
• Inhaled glucocorticosteroids (ICS) are the most effective agents in this category
• Oral leukotriene antagonists not as effective as ICS, but is a non-inhaler alternative. It can be effective in exercise induced asthma; can also be used, as an add on to ICS

Note: If reliever use >3 times per week or any other indicator of poor control present then begin controller therapy (usually with low dose ICS) according to the recommended step wise approach, by age as suggested.

1. Control measures: Indicators of asthma control as assess by the Canadian Thoracic Society (CTS)
2. Recommended stepwise approach
3. Treatment according to the age

Follow-up and assessment is required in all patients:

Asthma is a chronic disease that requires regular follow up including:

• Assessing level of control; review of inhaler technique and effect on quality of life
• Frequency of follow up should be determined by the need to ensure good control of the disease
• Follow up 1-2 times per year may be adequate for those in good control
• Spirometry should be done to ensure diagnosis and then as a part of evaluation of asthma control, at least every 1-2 years
• On each assessment review inhaler technique or assign inhaler technique assessment to pharmacist and have pharmacist report back to physician

Considerations for special populations:

i) Elderly:

Asthma deaths in the elderly population account for more than 50% of asthma fatalities annually. Factors thought to contribute to such risk include:

• Delay in diagnosis and treatment
• Poor cardiorespiratory reserves
• Impaired perception of increasing air-way obstruction
• Blunted hypoxic ventilatory drive
• Psychosocial problems
• Cognitive problems
• Poor inhaler technique
• Poor coordination due to arthritis and other manipulation issues
• Expense of controller medications vs reliever medications

Treatment options:

Approach is similar to that in younger subjects however; an individualized approach may be required due to the existing comorbidities e.g.

• GERD is a common precipitant and mimic of asthma in elderly subjects
• Influenza and pneumococcal infections may complicate asthma exacerbations- vaccinations may help prevent infection-related to asthma exacerbations
• Use of spacers with inhalers or nebulizers may help improve drug delivery in the elderly

ii) Pregnancy:

• Treatment approach in pregnancy remains largely unaltered, however LTRAs should be avoided unless necessary
• Goal is to strive for excellent asthma control
• Poorly controlled asthma results in increased perinatal mortality, prematurity and low birth rate
• Acute exacerbations should be treated promptly and aggressively to avoid fetal hypoxia
• Budesonide is the ‘safest’ ICS, with a pregnancy risk category of B (all others are C)

TREATMENT STRATEGY FOR ACUTE EXACERBATIONS

Treatment would be directed by the extent of the exacerbation which could be mild, moderate or severe.

In general:

• Oxygen: Should be titrated to achieve oxygen saturation of at least 92% whenever required
  • Start high: FiO₂ 40-100% in adults and FiO₂ 100% in pediatrics patients
• Inhaled β2-agonist and anticholinergic: Are used with doses titrated to efficacy
• Systemic steroids should be utilized in the all but the mildest exacerbations, especially if:
  • The initial rapid acting inhaled β2-agonist therapy fails to achieve lasting improvement
  • Development of exacerbation even though the patient was already on oral glucocorticoid
  • Previous exacerbation required oral glucocorticoids

1. Therapeutic approach to adult patients with mild, moderate and severe presentations
2. Therapeutic approach to pediatric patients with mild, moderate and severe presentations

Follow-up management

Following acute exacerbation:

• Prescribe and encourage adequate regular SABA use for first 48 hrs then as required
• Oral steroid use for 7-14 days
• Reinforce patients’ knowledge about asthma and need for avoidance and compliance with their therapy
• Ensure patient is aware of acute signs and symptoms of an acute attack that may signify the need for urgent ED treatment
• Encourage regular follow-up visits with asthma clinic (where available), primary health care provider, as well as specialist (respirologist, pediatrician)

Outpatient monitoring (all asthmatics)

• The pattern of the symptoms (including nocturnal events and those with physical activity) should be documented
• Patient should diarize events including PEF, frequency and dose of beta-agonist; example of patient diary at www.asthma-education.com
• Use of the inhalation device should be observed and corrected (if required)
• Perform and document spirometry (FEV1 and FEV1/FVC); testing should be done pre and post (~15 mins) inhaled beta2-agonist

1) RELIEVER MEDICATIONS:

• ➢ Beta agonists:
  • Short-acting beta agonists (SABA)
  • Fast-acting beta agonists (FABA)
  • FABA/ICS combination therapy (SMART)
• ➢ Anticholinergic

Short/rapid-acting Beta agonists (SABA):

• Levalbuterol
• Salbutamol (Albuterol called in USA)
• Terbutaline

Budesonide/Formoterol combination in maintenance and reliever strategy.

Mechanisms:

• Relaxes bronchial smooth muscle by action on beta₂-receptors with little or no effect on a-adrenergic receptors

Dose:

Levalbuterol: not available in Canada

Adult:

Bronchospasm

• MDI: 2 puffs every 4-6 hrs
• Nebulizer: 0.63 mg TID at intervals of 6-8 hrs; may increase to 1.25 mg TID with close monitoring

Exacerbation of asthma

• MDI: 4-8 puffs every 20 mins for 4 hrs, then every 1-4hrs as needed
• Nebulizer: 1.25-2.5 mg every 20 min for 3 doses, then 1.25-5 mg every 1-4 hrs as needed

Pediatric:

Bronchospasm

• MDI: >4 years: Administer as in adults
• Nebulizer: <4 years: 0.31-1.25 mg every 4-6 hrs as needed; 5-11 years: 0.31 mg TID; Max. 0.63 mg TID

Exacerbation of asthma

• MDI: >4 years: 4-8 puffs every 20 mins for 3 doses, then every 1-4 hrs as needed prn
• Nebulizer: < 12 years: 0.075 mg/kg every 20 mins for 3 doses, then 0.075-0.15 mg/kg every 1-4 hrs as needed

Salbutamol (Albuterol in US):

Adult:

Bronchospasm

• Oral: 2-4 mg per dose divided in 2-3 doses/day: Max. 32 mg/day
• MDI: 2-3 puffs every 6 hrs. Max. 12 puffs/day; may use 2-4 puff every 20 min for 3 doses to treat an acute exacerbation
• Nebulizer: 2.5-5 mg every 4-6 hrs as needed, diluted in 2-5 ml sterile saline or water. Dilute 0.5 ml (2.5 mg) 0.5% inhalation solution in 1-2.5 ml of NS

Severe bronchospasm/Status asthmaticus:

• IV continuous infusion: Start 5 µg/min; may increase up to 10 µg/min & 20 µg/min at 5-30 ,minute intervals if needed
• Concentration should be reduced 50% before administration

Exacerbation of asthma

• MDI: 4-8 puffs every 20 min for upto 4hrs, then every 1-4 hrs as needed
• Nebulizer: 2.5-5 mg every 20 mins for 3 doses, then 2.5-10 mg every 1-4 hrs Or 10-15 mg/hr by continuous nebulization

Pediatric:

Bronchospasm

• Oral: 2-6 years: 0.1-0.2 mg/kg/dose PO TID daily; Max. 12 mg/day; age 6-12 years: 2 mg/dose PO TID or QID daily; Max. 24 mg/day
• MDI: <12 years: 2 puffs every 4-6 hrs; as needed with tube spacer; age >12 years: Same as above
• Nebulizer: 2-12 years: Nebulize 0.63-1.25 mg 3-4 times daily or as needed; age 12 years: Nebulize 2.5 mg 3-4 times daily as needed

Exacerbation of asthma

• MDI: <12 years: 4-8 puffs every 20 mins for 3 doses, then every 1-4hrs as needed; age ≥12 years: Administer as in adults
• Nebulizer: <12 years: 0.15 mg/kg every 20 mins for 3 doses, then 0.15-0.3 mg/kg every 1-4 hrs or 0.5 mg/kg/hour by continuous nebulization; age ≥12 years: Administer as in adults

FAST-acting beta agonists (FABA):

• Formoterol

Mechanisms:

• These are the agents who have quick onset of action; and is effective for longer duration, so are often included in LABA

Dose:

• Adult: 6-12 µg/dose (1-2 inhalation of 6 µg dose) every 6 hr prn rescue (Canadian indication only)

FABA/ICS combination therapy:

• Budesonide/Formoterol SMART strategy (only indicated in Canada with turbuhaler)

Mechanisms:

• Formoterol relaxes bronchial smooth muscle by action on beta2-receptors with little or no effect on a-adrenergic receptors. It has a quick onset of action
• Budesonide acts as anti-inflammatory and immune modifier

Dose:

Adult

• 1- 2 inhalations BID plus prn rescue therapy; up to 8 puffs per day

Pediatric

• <12 years: Not established
• >12 years:1-2 inhalations BID plus prn rescue therapy (this is a second line therapy as data for children is much less than adults)

Anticholinergics:

• Ipratropium

Mechanisms:

• Inhibits cholinergic receptors in bronchial smooth muscle causing bronchodilator; local application to nasal mucosa inhibits secretions from glands lining the nasal mucosa

Dose:

Adult

• Nebulizer: 500 µg every 20 mins for 3 doses, then as needed for acute exacerbations
• MDI: 2 puffs QID; Max. 12 puffs/day

Pediatric

• Nebulizer: 250 µg TID
• MDI: 1-2 puffs TID; Max. 6 puffs/day

2) ORAL AND SYSTEMIC STEROIDS

• ➢ Methylprednisilone
• ➢ Hydrocortisone
• ➢ Prednisone

Mechanisms:

• Suppresses inflammation and the normal immune response, also suppresses adrenal function at high doses. It has minimal mineralocorticoid activity

Dose:

Methylprednisilone:

• Adults: 125 mg/day IV in 2 divided doses
• Pediatric: 1-2 mg/kg/day IV in 2 divided doses

Hydrocortisone

• Adults: 250-500 mg IV in 4 divided doses/day
• Pediatric: 5-7 mg/kg/day IV divided every 12-24 hrs

Prednisone

• Adult: 40-60 mg PO daily divided in 2-4 doses; taper over 2 weeks as symptoms resolve
• Pediatric: <11 years: 1-2 mg/kg/day PO divided in 2-4 doses; taper over 2 weeks as symptoms resolve

Note: In asthma oral steroids are always preferred.

3) LONG-TERM CONTROL MEDICATIONS:

• ➢ Inhaled corticosteroids
• ➢ Leukotriene modifiers
• ➢ Bronchodilators
• ➢ Long-acting beta agonists (LABAs)
• ➢ Combination inhalers

Inhaled corticosteroids

• Beclomethasone
• Budesonide
• Ciclesonide
• Fluticasone
• Mometasone
• Triamcinolone (not available in Canada)

Mechanisms:

• Acting as anti-inflammatory and immune modifier. May suppresses adrenal function at chronic high doses

Dose:

Beclomethasone

12 years of age and older

• Mild Asthma: 50 to 100 µg twice daily; Max. 100 µg twice daily
• Moderate Asthma: 100 to 250 µg twice daily; Max. 500 µg twice daily
• More Severe Cases: 300 to 400 µg twice daily; Max. 800 µg twice daily

5-11 years of age:

• 50-100 µg twice daily; Max. 100 µg twice daily

Budesonide

• Adult: 400-2400 µg/day inhalation in 2-4 divided doses; maintenance is 200-400 µg twice daily
  • Note: Patients taking only 400 µg/day may take it as a single daily dose
• Pediatric: Initially 200-400 µg/day inhalation in 2 divided doses; maintenance is individualized to lowest effective dose

Ciclesonide

12 years of age and older:

• Recommended initial dose 400 µg once daily; dose range 100-800 µg/day (1-2 puffs once daily either in the morning or evening); Max. 400 µg BID

6-11 years of age:

• Recommended initial dose 100-200 µg once daily; dose range 100-200 µg/day (1-2 puffs once daily either in the morning or evening); Max. 200 µg/day

Fluticasone

16 years of age and older:

• Mild Asthma: 100 to 250 µg BID
• Moderate Asthma: 250 to 500 µg BID
• Severe Asthma: 500 µg BID; may increase to 1000 µg BID to those patients currently requiring oral steroids

4-16 years of age:

• 50 or 100 µg BID daily; Max. 200 µg BID

12 months-4 years of age:

• 100 µg BID administered via a pediatric spacer device with a face mask

Mometasone:

12 years of age and older

• Usual recommended dose: 400 µg once daily in the morning or divided into BID; maintenance dose: 200-400 µg once daily in the morning
• Patients with severe asthma who may require oral corticosteroids: Starting dose: 400 µg twice daily; once reduction of oral steroid dose complete, titrate to the lowest effective dose

Triamcinolone

• Adult: 2 puffs 3-4 times a day or (400 µg) 4 sprays twice daily
• Pediatric: 6-12 years: 2 puffs 3-4 times a day or 2-4 puffs twice a day; >12 years: Administer as in adults

Leukotriene modifiers:

• Montelukast
• Zafirlukast
• Zileuton (not available in Canada)

Mechanisms:

• Selective leukotriene receptor antagonist → inhibits the cysteinyl leukotriene receptor
• Have been correlated with the pathophysiology of asthma, including airway edema, smooth muscle contraction

Dose:

Montelukast

Prophylaxis and chronic treatment of asthma

• 15 years of age and older: 10 mg tablet once daily taken at evening time
• 6 to 14 Years of Age: 5 mg chewable tablet once daily at evening time
• 2 to 5 Years of Age: 4 mg chewable tablet or granules once daily at evening time

Zafirlukast

• ≥12 years of age: 20mg PO BID empty stomach; Max. 40 mg/day

Zileuton: (not available in Canada)

15 years of age and older:

• Immediate release: 600 mg four times/day
• Extended release: 1200 mg twice daily

Bronchodilators

• Theophylline

Mechanisms:

• It increases tissue concentrations of cyclic adenosine monophosphate (cAMP), this in turns results in bronchodilation, CNS stimulation, positive inotropic and chronotropic effects, diuresis, and gastric acid secretion

Dose:

Theophylline

Adult:

• Initially 5-8 mg/kg/d IV to maintain concentration in the range of 5-15 µg/ml; then 5.6 mg/kg loading dose (based on aminophylline) IV over 20 min; followed by maintenance infusion of 0.1-1.1 mg/kg/hr

Pediatric:

• <6 weeks: Not established
• 6 weeks-to-6 months: 0.5 mg/kg/hr loading dose IV in first 12 hrs (based on aminophylline); followed by maintenance infusion of 12 mg/kg/d
• 6 months to 1 year: 0.6-0.7 mg/kg/hr loading dose IV in first 12 hrs; followed by maintenance infusion of 15 mg/kg/d
• >1 year: Administer as in adults

Long-acting beta agonists (LABA)

• Formoterol
• Salmeterol

Mechanisms:

• Long acting control of reversible airway obstruction. It Relaxes bronchial smooth muscle by action on beta₂-receptors with little or no effect on a-adrenergic receptors

Dose:

Formoterol

• Adult: 12 µg/day (1 inhalation) every 12 hr; Max. 48 µg/day
• Pediatric: <6 years: Not established; 6-16 years: Administer as in adults; Max. 24 µg/day

Salmeterol

• Adult: 1 inhalation (50 µg) BID ~12 hrs apart
• Pediatric: 4-12 years: 1 puff (50 µg) every 12 hrs; >12 years: Administer as in adults

Combination inhalers

• Budesonide/Formoterol
• Mometasone/Formoterol
• Salmeterol/Fluticasone

Mechanisms:

• Formoterol, salmeterol relaxes bronchial smooth muscle by selective action on beta ₂ receptors with little effect on heart rate
• Formoterol has both a long acting and rapid acting effect
• Fluticasone, budesonide and mometasone are corticosteroid which controls the rate of protein synthesis, depresses the migration of polymorphonuclear leukocytes/fibroblasts, and reverses capillary permeability and lysosomes stabilization at the cellular level to prevent or control inflammation

Dose:

Budesonide/Formoterol (100 µg/6 mcg per dose, 200 µg/6 µg per dose)

Only available as a turbuhaler in Canada and as MDI in USA.

Maintenance and reliever therapy

• 12 years and older: 1-2 inhalations twice daily or 2 inhalations once daily; may use additional 1 dose after every few minutes as needed up to maximum of 6 inhalations on any single occasion; Max. 8 inhalations total daily dose

Maintenance therapy

• Adults: 1-2 inhalations twice daily; Maximum recommended daily maintenance dose is 4 inhalations
• Pediatric: <12 years: Not established; >12 years: 1-2 inhalations once or twice daily

Note: In case of worsening asthma, may increase the dose temporarily up to 4 inhalations BID

Mometasone/Formoterol:

Maintenance treatment of asthma where combination therapy is indicated.

Mometasone 50 µg/formoterol 5 µg:

• 2 puffs twice daily; in patients previously on inhaled low dose corticosteroids; Max daily dose 200/20 µg (4 puffs)

Mometasone100 µg/formoterol 5 µg:

• 2 puffs twice daily; in patients previously on inhaled medium dose corticosteroids; Max daily dose 400/20 µg (4 puffs)

Mometasone 200 µg/formoterol 5 µg:

• 2 puffs twice daily; in patients previously on inhaled high dose corticosteroids; Max daily dose 800/20 µg (4puffs)

Salmeterol/Fluticasone (also available in an MDI in Canada)

• ➢ Diskus type is available in 3 strengths:
  • Fluticasone/Salmeterol: 100 µg/50 µg, 250 µg/50 µg, 500 µg/50 µg
• ➢ Metered-dose inhaler (MDI) type is available in 2 strengths:
  • Fluticasone/Salmeterol: 125 µg/25 µg, 250 µg/25 µg

Adult and Adolescents (≥12 years of age):

• Diskus (all strengths): One inhalation twice daily
• MDI (all strengths): Two inhalations twice daily

Note: If Diskus is used 2 puffs BID salmeterol overdose will ensue.

Pediatric (4-11 years of age):

• Fluticasone/Salmeterol (100 µg/50 µg): One inhalation twice daily

4) Treatment for allergy-induced asthma:

• ➢ Monoclonal antibodies
• ➢ Mast cell stabilizers

Monoclonal antibodies

• Omalizumab

Mechanisms:

• Inhibits IgE binding to receptors on mast cells and basophiles. Prevents the release of mediators of the allergic response

Dose:

Omalizumab

• Adult: 150-375 mg SC every 3-4 weeks; inject slowly over 5-10 seconds due to viscosity. Not to exceed 150 mg/injection site
• Pediatric: <12 years: Not established; >12 years: Administer as in adults

Mast cell stabilizers (MCS)

• Cromolyn
• Nedocromil

Mechanisms:

• Inhibits activation and release of mediators (e.g., histamine) from cells involved in hypersensitivity reactions (including mast cells). It inhibits the development of early and late bronchoconstriction responses to inhaled antigen

Dose:

Cromolyn

• Adult: 2 puffs 15-60 min prior to exercise or exposure
• Pediatric: <12 years: Not established; ≥12 years: Administer as in adults

Nedocromil

• 2 inhalations 4 times/day; may reduce dosage to 2-3 times/day once desired clinical response to initial dose is observed

Diagnosis:

• Airway obstruction and shortness of breath due to
  • Bronchoconstriction
  • Excessive mucus production
  • Bronchial infections
  • Airway irritants
• Impaired gas exchange due to inadequate perfusion
• Limited activity due to breathlessness
• Incomplete knowledge of the disease
• Show signs of not being able to cope up with the disease

Potential complications:

• Status asthmaticus
• Respiratory failure
• Pneumonia

Goals:

• To improve airway obstruction and shortness of breath
• Promote smoking cessation
• To improve limited activity
• Encourage self management
• Compliance with the therapeutic regimen
• Should be able to cope up with the disease

Improving gas exchange:

Monitor for:

• Dyspnea and signs of hypoxemia
• Decreased breath sound
• Correct administration of medication as prescribed
• Relief of spam by assessing improvement in expiratory flow rates by flow meter

Achieving airway clearance:

• Pulmonary irritants should be removed from the patients surrounding
• Cigarette smoke is a persistent irritant, hence advise to quit
• Controlled coughing is taught to the patient to be more effective and reduces unnecessary fatigue
• Chest physiotherapy with postural drainage (to clear the lungs) – technique is taught to the patients and caregivers

Promote smoking cessation:

Strategies to quit smoking are to be discussed at length and should include

• Counseling referrals
• Formalized programme available within the community
• Nicotine replacement prescriptions
• Reminding the smoker very subtly, at each visit, to quit smoking
• Patients who don’t smoke remind them second hand smoke is also injurious

Improve breathing:

• Improving inspiratory muscle performance by restraining them
• Diaphragmatic breathing will decrease respiratory rate, which increase expiration
• Purse lip breathing will help decrease dyspnea, fatigue and panic by control rate and depth

Improve activity tolerance:

• Develop strategies according to the limitations, to conserve energy by using supportive devices
• Physical, occupational and rehabilitation therapy may be considered

Self care strategies:

• If the patient has limited activity in daily life, the goal is to relieve symptoms and improve activity
• Avoid extreme heat cold
• Avoid pollutants such as fumes, smoke, lint
• High altitudes aggravate hypoxia due to lack of O₂ in air

Lifestyle modification:

• Avoid circumstances leading to stress
• Advise for smoking cessation with reinforcement as required
• Behavioral modification techniques

Individual coping strategies:

• Identify and develop strategies to cope with psychological, social, emotional and functional issues
• Provide health care referrals for above mentioned issues if required

Monitor and manage complications:

• Monitor and report increased:
  • Dyspnea/tachypnea
  • Tachycardia/cyanosis
  • Cognitive changes(behavioral and memory impairment)
  • Pulse oximetry results periodically
  • Signs of infection (fever, differentials)

All the above symptoms could lead to respiratory failure and/or intubation and mechanical ventilation and so should be recognized and treated promptly.

Promote home and community based care:

• Teach patient and family self management strategies
• They should be aware of all the medications and their side effects
• Should be able to recognize early signs and triggers to avoid them or seek help to avoid complications
• Should be able to perform correct administration of medication
• Home care referrals should be provided for continuing care, to reinforce information

Expected outcomes:

• Smoking is a major hazard, and quitting improves outcome
• Feels comfortable and is not agitated or restless
• Maintaining stable pulse oximetry, with improved gas exchange
• Have achieved good airway clearance by quitting smoking and avoiding irritants
• Able to perform postural drainage if required
• Avoiding extreme heat/cold exposure
• Is able to improve breathing by utilizing different techniques like diaphragmatic breathing and purse lip breathing etc.
• Improved level of activity by applying strategies to conserve energy

– Inhaler types and use

– How to use metered-dose inhaler (MDI)

• Hypoxemia stimulates respiration which increases blood O₂ → decrease respiratory drive → leading to CO2 retention requiring close monitoring
• Be aware of the clinical signs of impending respiratory failure
  • Respiratory distress/breathlessness/tachypnea
  • Engaged accessory muscles
  • Diaphoresis/tachycardia
  • Cyanosis/hypoxemia

Core Resources:

• Balter MS, Bell AD, Kaplan AG et al. Management of asthma in adults. CMAJ. 2009 8; 12:915-22
• Chapman KR, McIvor A. Asthma that is unresponsive to usual care. CMAJ 2010 182:45-52
• Compendium of Pharmaceuticals and Specialties (CPS). Canadian Pharmacist association. Toronto: Webcom Inc. 2012
• Day RA, Paul P, Williams B, et al (eds). Brunner & Suddarth’s Textbook of Canadian Medical-Surgical Nursing. 2^nd ed. Philadelphia: Lippincott Williams and Wilkins; 2010
• FitzGerald JM, Boulet L-P, McIvor RA, et. Al. Asthma control in Canada remains suboptimal: The Reality of Asthma Control (TRAC) study Can Respir J. 2006 Jul-Aug; 13(5): 253-259
• Foster C, Mistry NF, Peddi PF, Sharma S, eds. The Washington Manual of Medical Therapeutics. 33^rd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2010
• Gray J, ed. Therapeutic Choices. Canadian Pharmacists Association. 6^th ed. Toronto: Webcom Inc. 2011
• Guidelines for the Diagnosis and Management of Asthma. National Asthma Education and Prevention Programme Expert Panel Report 3. NIH Publication Number 08-5846. 2007
• Hodder R, Lougheed MD, Rowe BH et al. Management of acute asthma in adults in the emergency department: nonventilatory management. A.CMAJ. 2009
• DOI:10.1503/cmaj.080072
• Horne R, Price D, Cleland J, et al. Can asthma control be improved by understanding the patient’s perspective. BMC Pulmonary Medicine 2007, 7:8
• DOI:10.1186/1471-2466-7-8
• Kaplan A. Action Plans in Asthma. The (Canadian) Family Physician, August 2002
• Kaplan AG, Balter MS, Bell AD, et al. Diagnosis of asthma in adults. CMAJ 2009;181(10):E210-E220
• Katzung BG, Masters SB, Trevor AJ, eds. Basic and Clinical Pharmacology. 11^th ed. New York: McGraw-Hill; 2009
• Kovesi T, Schuh S, Spier S et al. Achieving control of asthma in preschoolers .CMAJ 2010; 4:E175
• Longo D, Fauci A, Kasper D, et al (eds). Harrison’s Principles of Internal Medicine. 18 ^th ed. New York: McGraw-Hill; 2011
• Lougheed MD, Lemiere C, Dell SD et al, Canadian Thoracic Society asthma management continuum-2010 consensus summary for children six years of age and over, and adults. Can Respir J 2010 17:15-24
• Lougheed MD, Lemiere C, Ducharme FM et al. Canadian Thoracic Society 2012 guideline updates: Diagnosis and management of asthma in preschoolers, children and adults. Can Respir J 2012; 19:127-164
• McPhee SJ, Papadakis MA, eds. Current Medical Diagnosis & Treatment. 49^th ed. New York: McGraw-Hill; 2010
• Pagana KD, Pagana TJ eds. Mosby’s Diagnostic and Laboratory Test Reference. 9^th ed. St. Louis: Elsevier-Mosby; 2009
• Skidmore-Roth L. ed. Mosby’s drug guide for nurses. 9^th ed. St. Louis: Elsevier-Mosby; 2011
• Skidmore-Roth L, ed. Mosby’s nursing drug reference. 24^th ed. St. Louis: Elsevier-Mosby; 2011
• Online resource/weblinks:
  • The Children’s Asthma Education Centre (CAEC)
  • The Family Physicians Airway Group of Canada (FPAGC)
  • The National Heart, Lung, and Blood Institute (NHLBI)

Online Pharmacological Resources:

• e-Therapeutics
• Lexicomp
• RxList
• Epocrates
• National Heart, Blood, and Lung Institute Expert Panel Report 3 (EPR 3)
• Guidelines for the Diagnosis and Management of Asthma. NIH Publication no. 08-4051, 2007

Journals/Clinical Trials:

• Abramson MJ, Puy RM, Weiner JM. Is allergen immunotherapy effective in asthma? A meta-analysis of randomized controlled trials. Am J Respir Crit Care Med. Apr 1995; 151:969-74
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• Bailey WC, Richards JM Jr, Brooks CM, Soong SJ, Windsor RA, Manzella BA. A randomized trial to improve self-management practices of adults with asthma. Arch Intern Med. Aug 1990;150(8):1664-8
• Barnes PJ. Inhaled glucocorticoids for asthma. N Engl J Med. Mar 30 1995;332(13):868-75
• Burrows B, Barbee RA, Cline MG, Knudson RJ, Lebowitz MD. Characteristics of asthma among elderly adults in a sample of the general population. Chest. Oct 1991;100(4):935-42
• Busse WW, Calhoun WF, Sedgwick JD. Mechanism of airway inflammation in asthma. Am Rev Respir Dis. Jun 1993;147(6 Pt 2):S20-4
• Camargo CA Jr, Weiss ST, Zhang S, Willett WC, Speizer FE. Prospective study of body mass index, weight change, and risk of adult-onset asthma in women. Arch Intern Med. Nov 22 1999;159(21):2582-8.
• Castro M, Rubin AS, Laviolette M, et al. Effectiveness and safety of bronchial thermoplasty in the treatment of severe asthma: a multicenter, randomized, double-blind, sham-controlled clinical trial. Am J Respir Crit Care Med. Jan 15 2010;181(2):116-24
• Cates CJ, Lasserson TJ, Jaeschke R. Regular treatment with formoterol and inhaled steroids for chronic asthma: serious adverse events. Cochrane Database Syst Rev. Apr 15 2009;CD006924
• Centers for Disease Control and Prevention. Asthma–United States, 1982-1992. MMWR Morb Mortal Wkly Rep. Jan 6 1995;43(51-52):952-5
• Chan-Yeung M. 2003 Christie Memorial lecture. Occupational asthma–the past 50 years. Can Respir J. Jan-Feb 2004; 11(1):21-6
• Chan-Yeung M. Assessment of asthma in the workplace. ACCP consensus statement. American College of Chest Physicians. Chest. Oct 1995;108(4):1084-117
• Coffman JM, Cabana MD, Yelin EH. Do school-based asthma education programs improve self-management and health outcomes?. Pediatrics. Aug 2009;124(2):729-42
• Crapo RO, Casaburi R, Coates AL, et al. Guidelines for methacholine and exercise challenge testing-1999. This official statement of the American Thoracic Society was adopted by the ATS Board of Directors, July 1999. Am J Respir Crit Care Med. Jan 2000;161(1):309-29
• Dell S, To T, Breastfeeding and Asthma in Young Children: Title and subTitle BreakFindings From a Population-Based Study. Arch Pediatr Adolesc Med. 2001;155:1261-1265
• Djukanovic R, Wilson JW, Britten KM, et al. Effect of an inhaled corticosteroid on airway inflammation and symptoms in asthma. Am Rev Respir Dis. Mar 1992;145(3):669-74
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• Enright PL, Lebowitz MD, Cockroft DW. Physiologic measures: pulmonary function tests. Asthma outcome. Am J Respir Crit Care Med. Feb 1994;149(2 Pt 2):S9-18; discussion S19-20
• Expert Panel Report 3 (EPR 3): Guidelines for the Diagnosis and Management of Asthma. National Heart, Blood, and Lung Institute. NIH Publication no. 08-4051, 2007
• Green RH, Brightling CE, McKenna S, et al. Asthma exacerbations and sputum eosinophil counts: a randomised controlled trial. Lancet. Nov 30 2002;360(9347):1715-21
• Hamilos DL. Gastroesophageal reflux and sinusitis in asthma. Clin Chest Med. Dec 1995;16(4):683-97
• Harding SM, Guzzo MR, Richter JE. The prevalence of gastroesophageal reflux in asthma patients without reflux symptoms. Am J Respir Crit Care Med. Jul 2000;162(1):34-9
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• Horwitz RJ, Busse WW. Inflammation and asthma. Clin Chest Med. Dec 1995;16(4):583-602
• Ignacio-Garcia JM, Gonzalez-Santos P. Asthma self-management education program by home monitoring of peak expiratory flow. Am J Respir Crit Care Med. Feb 1995;151(2 Pt 1):353-9
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• Juniper EF, Buist AS, Cox FM, Ferrie PJ, King DR. Validation of a standardized version of the Asthma Quality of Life Questionnaire. Chest. May 1999;115(5):1265-70
• Kiljander TO, Salomaa ER, Hietanen EK, Terho EO. Gastroesophageal reflux in asthmatics: A double-blind, placebo-controlled crossover study with omeprazole. Chest. Nov 1999;116(5):1257-64
• Kingston HG, Hirshman CA. Perioperative management of the patient with asthma. Anesth Analg. Sep 1984;63(9):844-55
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• Lahdensuo A, Haahtela T, Herrala J, et al. Randomised comparison of guided self-management and traditional treatment of asthma over one year. BMJ. Mar 23 1996;312(7033):748-52
• Laitinen LA, Laitinen A, Haahtela T. A comparative study of the effects of an inhaled corticosteroid, budesonide, and a beta 2-agonist, terbutaline, on airway inflammation in newly diagnosed asthma: a randomized, double-blind, parallel-group controlled trial. J Allergy Clin Immunol. Jul 1992;90(1):32-42
• McFadden ER Jr. Exercise-induced airway obstruction. Clin Chest Med. Dec 1995;16(4):671-82
• Martin AJ, Landau LI, Phelan PD. Lung function in young adults who had asthma in childhood. Am Rev Respir Dis. Oct 1980;122(4):609-16
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• Nair P, Pizzichini MM, Kjarsgaard M, et al. Mepolizumab for prednisone-dependent asthma with sputum eosinophilia. N Engl J Med. Mar 5 2009;360(10):985-93
• Nathan RA, Sorkness CA, Kosinski M, et al. Development of the asthma control test: a survey for assessing asthma control. J Allergy Clin Immunol. Jan 2004;113(1):59-65
• National Asthma Education and Prevention Program. Expert Panel Report 2: Guidelines for the diagnosis and management of asthma. NIH Publication No. 97-4051. NIH Publication. 1997
• National Asthma Education and Prevention Program. Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma. NIH Publication No. 07-4051. 2007
• National Asthma Education and Prevention Program Expert Panel Report 3, Guidelines for the Diagnosis and Management of Asthma. No. 08-5846 Washington DC: NIH, Oct 2007
• National Heart, Lung, and Blood Institute. Global Strategy for Asthma Management and Prevention. NIH Publication. 2008
• National Heart, Lung, and Blood Institute. Measures of asthma assessment and monitoring. Expert panel report 3: guidelines for the diagnosis and management of asthma. National Asthma Education and Prevention Program (NAEPP). Aug 2007
• National Heart, Lung, and Blood Institute. NAEPP Working Group Report: Considerations for Diagnosing and Managing Asthma in the Elderly. NIH Publication No. 96-3662. National Institutes of Health; 1996
• National Heart, Lung, and Blood Institute. Executive Summary: Management of Asthma During Pregnancy. NIH Publication No. 92-3279a. National Institutes of Health; 1992
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• Sly RM. Changing asthma mortality. Ann Allergy. Sep 1994;73(3):259-68
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• Suissa S, Ernst P, Boivin JF, et al. A cohort analysis of excess mortality in asthma and the use of inhaled beta-agonists. Am J Respir Crit Care Med. Mar 1994;149(3 Pt 1):604-10.
• Woolcock A, Lundback B, Ringdal N, Jacques LA. Comparison of addition of salmeterol to inhaled steroids with doubling of the dose of inhaled steroids. Am J Respir Crit Care Med. May 1996;153(5):1481-8
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