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Asthma
Urooj Najm, MBBS
Najm Hasan Siddiqui, MD
image BASICS
DESCRIPTION
  • Chronic, reversible inflammatory airway disease characterized by recurrent attacks of breathlessness and wheezing
  • Four major classifications of asthma severity used primarily to initiate therapy (1,2):
    • Intermittent: symptoms ≤2 days/week, nighttime awakenings ≤2 times per month, short-acting β-agonist use ≤2 days/week, no interference with normal activity, and normal forced expiratory volume in 1 second (FEV1) between exacerbations with FEV1 (predicted) >80% and FEV1/forced vital capacity (FVC) >80%
    • Mild persistent: symptoms >2 days/week but not daily, nighttime awakenings 3 to 4 times per month, short-acting β-agonist use >2 days/week but not daily, minor limitations in normal activity, and FEV1 (predicted) >80% and FEV1/FVC >80%
    • Moderate persistent: daily symptoms, nighttime awakenings ≥ 1 times per week but not nightly, daily use of short-acting β-agonist, some limitation in normal activity, and FEV1 (predicted) 60-80% and FEV1/FVC 75-80%
    • Severe persistent: symptoms throughout the day, nighttime awakenings often 7 times per week, short-acting β-agonist use several times a day, extremely limited normal activity, and FEV1 (predicted) <60% and FEV1/FVC <75%
EPIDEMIOLOGY
Prevalence
  • Affects 5-10% of population
  • One of the most common chronic diseases of childhood, affecting 7 million children
  • In children, more common in boys than girls
  • In adults, more common in women than men, African Americans than Caucasians
Pregnancy Considerations
In the United States, maternal asthma complicates approximately 4-8% of all pregnancies.
Geriatric Considerations
Prevalence of asthma in seniors (age ≥65 years) is 5.3%.
ETIOLOGY AND PATHOPHYSIOLOGY
  • Airway inflammation begins with inflammatory cell infiltration, sub-basement fibrosis, mucus hypersecretion, epithelial injury, smooth muscle hypertrophy, angiogenesis that then leads to intermittent airflow obstruction, and bronchial hyperresponsiveness.
  • Remodeling of airways may occur (1).
Genetics
  • Inheritable component with complex genetics and environment interaction
  • A gene-by-environment interaction occurs in which the susceptible host is exposed to environmental factors that are capable of generating immunoglobulin (Ig) E and sensitization occurs.
RISK FACTORS
  • Host factors: genetic predisposition, gender, race, BMI
  • Environmental: viral infections, animal and airborne allergens, tobacco smoke, and so on
  • Exercise, obesity, and emotional stress
  • Aspirin or NSAIDs hypersensitivity or β-blockers
  • Food allergies and asthma → increased risk for fatal anaphylaxis from those foods
GENERAL PREVENTION
  • Eliminate or modify exposure to asthma triggers (e.g., allergens, smoking, aspirin, NSAIDs).
  • Consider allergen immunotherapy.
  • Treat comorbidities such as allergic rhinitis.
  • Annual influenza vaccine (inactivated influenza vaccine) for age <6 months
  • Patients at risk for anaphylaxis should carry an EpiPen.
COMMONLY ASSOCIATED CONDITIONS
  • Atopy: eczema, allergic conjunctivitis, allergic rhinitis
  • Obesity (associated with higher asthma rates)
  • Sinusitis
  • Gastroesophageal reflux disease (GERD)
  • Obstructive sleep apnea (OSA)
  • Allergic bronchopulmonary aspergillosis (rare)
  • Stress/depression
image DIAGNOSIS
It is important to classify asthma severity.
PHYSICAL EXAM
  • May be normal
  • Focus on
    • General appearance: signs of respiratory distress such as use of accessory muscles
    • Upper respiratory tract: rhinitis, nasal polyps, swollen nasal turbinates
    • Lower respiratory tract: wheezing, prolonged expiratory phase
    • Skin: eczema
DIFFERENTIAL DIAGNOSIS
  • In children
    • Upper airway diseases (allergic rhinitis or sinusitis)
    • Large airway obstruction (foreign body aspiration, vocal cord dysfunction, vascular ring or laryngeal web, laryngotracheomalacia, lymph nodes, or tumor)
    • Small airway obstruction (viral bronchiolitis, cystic fibrosis, bronchopulmonary dysplasia, heart disease)
    • Other causes (recurrent cough not due to asthma, aspiration/GERD)
  • In adults
    • Chronic obstructive pulmonary disease, congestive heart failure, pulmonary embolism, benign or malignant tumor, pulmonary infiltration with eosinophilia, Churg-Strauss syndrome, drugs such as an ACE inhibitor, vocal cord dysfunction
DIAGNOSTIC TESTS & INTERPRETATION
Initial Tests (lab, imaging)
  • Blood tests are not required but may find eosinophilia or elevated serum IgE levels.
  • Spirometry: Normal test does not rule out asthma. It measures the FVC and the FEV1. A reduced predicted ratio of FEV1/FVC with reversibility (increase of 200 mL or 12% of FEV1/FVC) after using a short-acting bronchodilator establishes the diagnosis.
  • Bronchoprovocation (methacholine, histamine, cold air, or exercise) is used to simulate bronchoconstriction, which is very useful in atypical presentation/normal baseline spirometry. Abnormal test is not entirely specific for asthma, but normal test excludes asthma.
  • Peak expiratory flow rates are inappropriate for diagnosis. Typically used for monitoring of symptoms in diagnosed asthma patients.
  • Chest x-ray is used to exclude alternative diagnoses and to evaluate patients for complicating cardiopulmonary processes.
Follow-Up Tests & Special Considerations
Asthma action plan: Patients monitor their own symptoms and/or peak flow measurements.
Diagnostic Procedures/Other
  • Allergy skin testing is not useful for diagnosis of asthma but may be considered to evaluate atopic triggers.
  • Sweat testing in diagnosis of cystic fibrosis.
  • Arterial blood gases are indicated for patients with respiratory distress and hypoxia.
Test Interpretation
Inflammatory cell infiltration, edema, goblet cell hyperplasia, smooth muscle hyperplasia, thickened basement membrane
image TREATMENT
GENERAL MEASURES
  • Identify triggers and control exposures.
  • Identify patients at risk for reactions to aspirin and NSAIDs and avoid exposure.
  • All patients requiring inhaled agents should be prescribed with spacer (holding chamber) device.
MEDICATION
First Line
  • Short-acting β-agonist (SABA) for quick relief of acute symptoms and to prevent exercise-induced bronchospasm (1)[A]
    • SABA include albuterol and levalbuterol (Xopenex) (3).
  • Anticholinergic agent
    • Ipratropium bromide: used in combination with SABA for acute treatment, mainly in the ED (1)[A]
  • Systemic corticosteroids can be used
    • In all patients with acute asthma exacerbations (4)[A]
    • In moderate to severe asthma as adjunct
    • Prednisolone 1 to 2 mg/kg/day or equivalent for up to 7 days in adults and for 3 days in children with no need for tapering (4)[A]
P.87

Second Line
For long-term control
  • Inhaled corticosteroids (ICS)
    • Most potent and effective long-term controller therapy for children and adults with persistent asthma and persistent asthma during pregnancy (1)[A]
    • Advice patients to rinse their mouth after inhalation to reduce adverse effects (1)[B].
    • Long-acting β2-agonists (LABA)
      • Salmeterol or formoterol
      • Should not be used as monotherapy (1)[A]; doing so leads to an increased risk of severe outcomes, including death
    • Combination products, including LABA and ICS, are available and are indicated if ICS alone do not provide control; preferred in moderate and severe persistent disease (1,3)[A]. This is not recommended to treat acute symptoms or exacerbation (1)[D].
    • Leukotriene receptor agonists: alternative, not preferable for mild and moderate persistent asthma (1)[A]
  • Montelukast or zafirlukast (patients ≥5 years)
    • Lipoxygenase pathway inhibitor: alternative, not preferred for adjunctive treatment in adults (1)[D]: zileuton (patients ≥12 years)
    • Theophylline: not preferred as adjunctive therapy with inhaled corticosteroids (1)[A]. Monitoring of serum theophylline level is essential.
    • Cromolyn sodium and nedocromil are also alternatives; not preferred options for mild persistent asthma (1)[A]; can also be used before exercise and exposure to allergens for prevention of asthma
    • Immunomodulators
      • Omalizumab: adjunctive; not preferred therapy for patients ≥ 12 years with allergies and severe persistent asthma (1)[B]
ISSUES FOR REFERRAL
Referral to an asthma specialist (either a pulmonologist or an allergist) should be considered when
  • Diagnosis unclear
  • Additional asthma education needed
  • Comorbidities: rhinitis, GERD, sinusitis, OSA
  • Specialized testing (e.g., bronchoprovocation, skin testing)
  • Specialized treatments (e.g., immunotherapy, anti-IgE therapy)
  • Poorly controlled, moderate to severe persistent asthma in adults
  • Moderate to persistent asthma in children
  • Poorly controlled asthma: multiple emergency room visits for asthma
Pregnancy Considerations
  • Poorly controlled asthma results in low birth weight, increased prematurity, and perinatal mortality.
  • Albuterol is the preferred SABA, and budesonide is the preferred ICS due to excellent safety profile (1).
  • Other ICS agents are pregnancy Category C, but no data indicate their unsafety in pregnancy (1). Montelukast and zafirlukast are Category B but are not studied extensively in pregnancy.
ADDITIONAL THERAPIES
  • Allergen immunotherapy when clear relationship between symptoms and exposure to an unavoidable allergen
  • Omalizumab (Xolair): anti-IgE therapy, approved for patients > 12 years with moderate to severe asthma
INPATIENT CONSIDERATIONS
Admission Criteria/Initial Stabilization
No single measure is predictive.
  • Dyspnea/hypoxia
  • Poor or no response to SABA
  • Peak expiratory flow (PEF) or FEV1 <40%
  • Decision for admission should be based on duration and severity of symptoms, severity of airflow obstruction, response to ED treatment, course and severity of prior exacerbations, access to medical care and medication, and adequacy of home condition (1).
  • Supplemental oxygen to correct hypoxemia
  • Repeated doses or continuous administration of SABA (1)[A]
  • Ipratropium bromide may be used in the ED but is not for inpatient treatment (1)[B].
  • Systemic corticosteroids for acute exacerbations (1)[A].
  • Adjunctive therapy with MgSO4 or helium-oxygen mixture (heliox) may be considered in severe cases (1)[B].
IV Fluids
  • Avoid aggressive hydration in older children and adults.
  • Monitor electrolytes.
Nursing
  • Careful respiratory monitoring including vital signs, pulse oximetry, response and duration of response to SABA, and when possible, an objective measure of lung function such as PEF or FEV1
  • Asthma education
Discharge Criteria
  • Minimal or absent asthma symptoms
  • Hypoxia has resolved.
  • FEV1 or PEF ≥ 70% predicted or personal best
  • Bronchodilator response sustained ≥60 minutes
image ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
Smoking cessation counseling or elimination of secondhand smoke, if applicable
Patient Monitoring
  • Quality-of-life measures: impact on activities, sleep, ED visits/hospitalizations, and so forth
  • Pharmacotherapy: efficacy, compliance, side effects, technique
  • Peak flow to evaluate if cough is due to exacerbation in those with known asthma.
DIET
Food allergies and sulfites (in food and wine) can precipitate symptoms for some patients.
PATIENT EDUCATION
  • Patients' care plan and inhaled medication technique at every visit.
  • American Academy of Allergy, Asthma & Immunology: 800-822-2762 or http://www.aaaai.org/
  • American Lung Association: www.lungusa.org
  • Asthma and Allergy Foundation of America: 800-727-8462 or http://www.aafa.org/
  • Mattress and pillow covers DO NOT improve outcomes and should not be recommended.
PROGNOSIS
  • Prognosis is good for male patients, nonsmokers, and children with mild disease.
  • Asthma worsens in 1/3 of women during pregnancy and improves in another 1/3.
REFERENCES
1. National Heart, Lung, and Blood Institute. National Asthma Education and Prevention Program Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma. Washington, DC: National Institutes of Health; 2007. NIH publication 08-5846.
2. Reddel HK, Taylor DR, Bateman ED, et al. An official American Thoracic Society/European Respiratory Society statement: asthma control and exacerbations: standardizing endpoints for clinical asthma trials and clinical practice. Am J Respir Crit Care Med. 2009;180(1):59-99.
3. Fanta CH. Asthma. N Engl J Med. 2009;360(10): 1002-1014.
4. Doherty S. Prescribe systemic corticosteroids in acute asthma. BMJ. 2009;338:b1234.
5. Stupka E, deShazo R. Asthma in seniors: part 1. Evidence for underdiagnosis, undertreatment, and increasing morbidity and mortality. Am J Med. 2009;122(1):6-11.
Additional Reading
Dombrowski MP, Schatz M. ACOG practice bulletin: clinical management guidelines for obstetriciangynecologists number 90, February 2008: asthma in pregnancy. Obstet Gynecol. 2008;111(2, Pt 1): 457-464.
See Also
Algorithm: Asthma Exacerbation, Pediatric Acute
Codes
ICD10
  • J45.909 Unspecified asthma, uncomplicated
  • J45.901 Unspecified asthma with (acute) exacerbation
  • J45.20 Mild intermittent asthma, uncomplicated
Clinical Pearls
  • SABA is the most effective rescue therapy for acute asthma symptoms.
  • Holding chambers should be used by all
  • ICSs are the preferred long-term control therapy for patients of all ages.
  • Peak flow is an inexpensive and easily available monitoring device once the diagnosis of asthma has been established.