Asthma

Asthma

BASICS
DESCRIPTION:
A disorder of the tracheobronchial tree characterized by mild to severe obstruction to airflow. Symptoms vary, generally episodic or paroxysmal, may be persistent. The clinical hallmark is wheezing, but cough may be the predominant symptom. Commonly misdiagnosed as recurrent pneumonia or chronic bronchitis.
  •Acute symptoms are characterized by narrowing of large and small airways due to spasm of bronchial smooth muscle, edema and inflammation of the bronchial mucosa, and production of mucus
  •Occurs in a setting in which asthma is likely and other, rarer conditions have been excluded
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System(s) affected: Pulmonary
Genetics: Search for an asthma gene underway; there is a familial association of reactive airway disease (RAD), ectopic dermatitis, and allergic rhinitis
Incidence/Prevalence in USA:
  •10 million new cases each year, however, there is confusion due to lack of a uniform definition
  •7-19% of children
  •A leading cause of missed school days - 7.5 million/year
Predominant age:
  •50% of cases are children under 10
  •Young adult (16-40 years); but may occur at any age
Predominant sex:
  •Children under 10: Male > Female
  •Puberty: Male = Female
  •Adult onset: Female > Male


SIGNS AND SYMPTOMS:
Variation in pattern of symptoms, paroxysmal, constant, abnormal pulmonary function tests without symptoms
  •Wheezing
  •Cough
  •Periodicity of symptoms
  •Exercise-induced wheezing or cough
  •Prolonged expiration
  •Hyperresonance
  •Decreased breath sounds
  •Nocturnal attacks
  •Pulsus paradoxus
  •Cyanosis
  •Tachycardia
  •Accessory respiratory muscle use
  •Flattened diaphragms
  •Nasal polyp; seen in cystic fibrosis and aspirin sensitivity
  •Clubbing is not seen in asthma
  •Growth is usually normal

CAUSES:
  •Allergic factors
      •Airborne pollens
      •Molds
      •House dust (mites)
      •Animal dander
      •Feather pillows
  •Other factors
      •Smoke and other pollutants
      •Infections, especially viral
      •Aspirin
      •Exercise
      •Sinusitis
      •Gastroesophageal reflux
      •Sleep (peak expiratory flow rate [PEFR] lowest at 4 am)
  •Current research focuses on inflammatory response (including abnormal release of chemical mediators, eosinophil chemotactic factor, neutrophil chemotactic factor, and leukotrienes, etc.)

RISK FACTORS:
  •Positive family history of asthma or atopy
  •Viral lower respiratory infection during infancy
  •Environmental tobacco smoke

DIAGNOSIS
DIFFERENTIAL DIAGNOSIS:
Foreign body aspiration - always consider; cystic fibrosis; viral respiratory infections (croup, bronchiolitis); epiglottitis; bronchopulmonary aspergillosis; tuberculosis; hyperventilation syndrome; mitral value prolapse; habit cough; recurrent pulmonary emboli; congestive heart failure; chronic obstructive pulmonary disease; hypersensitivity pneumonitis; vascular anomalies; mediastinal mass; tracheo-bronchomalacia; vocal cord dysfunction

LABORATORY:
  •CBC normal
  •Nasal eosinophils
  •Immunoglobulins
      •Screen for immunodeficiency
      •IgE elevated in allergic bronchopulmonary aspergillosis (ABPA)
  •Sweat test in chronic childhood asthmatics
  •Arterial blood gases in status asthmaticus

Drugs that may alter lab results: Antihistamines may alter allergy skin testing
Disorders that may alter lab results: N/A

PATHOLOGICAL FINDINGS:
Smooth muscle hyperplasia; mucosal edema; thickened basement membrane; inflammatory response; hyperinflated lungs; mucus plugging; bronchiectasis is not seen except in association with ABPA; increased airway resistance; decreased airflow rates; ventilation-perfusion mismatching

SPECIAL TESTS:
  •Home monitoring of peak flow rates - report if drops below 70% of baseline
  •Pulmonary function tests - reversible airway obstruction
  •Allergy testing
  •PPD
  •Exercise tolerance testing
  •Methacholine challenge
  •Cold air provocation

IMAGING:
Chest x-ray (hyperinflation, atelectasis, air leak)

DIAGNOSTIC PROCEDURES:
  •Bronchoscopy: rarely indicated.
  •Spirometry: decreased FEV1
  •Chest x-ray: do at least one, but not necessary with each exacerbation

TREATMENT
APPROPRIATE HEALTH CARE:
  •Outpatient
  •Inpatient for bronchospasm not relieved by beta-agonists and steroids

GENERAL MEASURES:
  •Environmental control of irritants
  •Education is essential
  •Appropriate prophylactic management with anti-inflammatories such as inhaled steroids, cromolyn sodium. Role of leukotriene modifiers being defined.
  •Increase beta-agonists in response to symptoms
  •Consider hyposensitization
  •The following are NOT recommended: mist, large volumes of fluid, breathing exercises, IPPB

SURGICAL MEASURES:
N/A

ACTIVITY:
Early diagnosis and appropriate treatment facilitate unrestricted activity.

DIET:
No special diet

PATIENT EDUCATION:
  •American Lung Association, 1740 Broadway, New York, NY 10019, (212)315-8700
  •Asthma and Allergy Foundation of America, Suite 305, Washington, DC 20036, (800)7-ASTHMA, (800)727-8462

MEDICATIONS
DRUG(S) OF CHOICE:
  •Six major classes of drugs are used:
      •Cromoglycate and nedocromil
      •Steroids (budesonide, fluticasone, prednisone, etc)
      •Beta-agonists (albuterol, bitolterol, salmeterol, etc.)
      •Methylxanthines (theophylline)
      •Anticholinergics (atropine, ipratropium)
      •Leukotriene modifiers
  •With all MDI use, a spacer device is recommended
  •Mild intermittent asthma: brief wheezing once or twice a week:
      •Intermittent beta-agonist (MDI or nebulizer - albuterol, 2 puffs or 0.25-1.0 mL neb q2hr prn)
      •Long acting beta-agonists [e.g., salmeterol (Serevent) 2 puffs bid]
      •Oral beta-agonist or theophylline may be considered, but have more side effects
  •Mild persistent asthma: symptoms > 2 times a week, but < 1 time a day; affects activity. Once daily medication - choose from:
      •Cromolyn qid or nedocromil bid (2 puffs or 2 ml neb)
      •Inhaled steroids (low doses)
      •Consider zafirlukast or montelukast
      •Consider oral theophylline (10-20 mg/kg/day); not preferred
  •Moderate persistent asthma: weekly symptoms interfering with sleep or exercise, occasional ER visits, PEFR 60-80% of predicted, PEFR variability >30%
      •Regular maintenance schedule
      •Inhaled steroids (beclomethasone dipropionate) 400-800 µg/day.
      •Consider cromolyn qid or nedocromil bid (2 puffs or 2 mL neb)
      •If not controlled with moderate dose inhaled steroid (600 µg/day), consider addition of oral slow-release xanthines or inhaled ipratropium bromide
      •Consider zafirlukast or montelukast
  •Severe persistent asthma: frequent symptoms affecting activity, nocturnal symptoms, frequent hospitalizations, PEFR <60% predicted
      •High dose inhaled steroids; some patients may need alternate day oral steroids
      •Theophylline often useful, particularly for nighttime symptoms; therapeutic level 10-20 µg/mL (56-111 µmol/L)
      •Consider zafirlukast or montelukast
      •Consider cromolyn, ipratropium
  •Acute exacerbation - outpatient management
      •Inhaled beta-agonist (albuterol) to reverse airflow obstruction (1 mL albuterol neb)
      •Look for increased work of breathing, air leak syndromes, atelectasis, lowered PEFR
      •Short course of steroids, 2 mg/kg po qam for 5-7 days
      •IV aminophylline adds toxicity only
      •Observe at least one hour
  •Delivery systems
      •Children under 2 - nebulizer or MDI with valved spacer and mask
      •Children 2-4 years - MDI and valved spacer
      •Over 5 years - MDI with spacer or powder inhaler
  •Hospital management
      •Steroids IV: methylprednisolone (Solu-Medrol) 2 mg/kg once, then 1 mg/kg IV q6h
      •Frequent beta-agonist aerosols
      •Ipratropium neb and/or aminophylline IV drip if not responding well
      •Rarely: isoproterenol or terbutaline IV; mechanical ventilation

Contraindications:
  •Sedatives, mucolytics
  •Antibiotics are usually not necessary
  •Avoid beta-adrenergic blocking drugs
Precautions: Concern regarding deleterious effects of chronic use of beta agonists. Use only when symptomatic (chronic asthma may necessitate chronic use). If using beta-agonist more than twice a week, should also be on anti-inflammatory.
Significant possible interactions: Erythromycin and ciprofloxacin slow theophylline clearance and can increase levels 15-20%.

ALTERNATIVE DRUGS:
  •Ketotifen
  •H1-antagonists
  •Troleandomycin (TAO)
  •Methotrexate
  •IV immune globulin (IVIG)
  •Furosemide (Lasix)

FOLLOW UP
PATIENT MONITORING:
  •PEFR meter at home - record for trend; call if < 70% baseline, ER if < 50% baseline
  •pH and arterial blood gases
  •Oximetry with status asthmaticus
  •Electrolytes - frequent albuterol lowers K+
  •A written and periodically revised action plan is critical
  •MDI technique should be reviewed periodically

PREVENTION/AVOIDANCE:
  •Co-management is essential
      •Understand medication, inhalers, nebulizers, peak flow meters
      •Monitor symptoms, peak flows
      •Pre-arranged action plan for exacerbations
      •Written guidelines
  •Investigate and control triggering factors (pollutants, exercise, house-dust mite, molds, animal dander) if severe
  •Annual influenza immunization
  •Avoid aspirin
  •Avoid sulfites (food additives)

POSSIBLE COMPLICATIONS:
  •Respiratory failure; mechanical ventilation
  •Atelectasis in 25% of hospitalized patients
  •Flaccid paralysis after exacerbation (self-limited)
  •Death
  •Air leak syndromes (pneumothorax, etc.)
  •SIADH
  •Altered theophylline metabolism
  •Steroid myopathy

EXPECTED COURSE AND PROGNOSIS:
  •Excellent, with attention to general health and use of medications to control symptoms
  •Less than 50% of children with asthma "outgrow it"
  •Mortality risk increases with:
      •Greater than 3 emergency room visits/year
      •Nocturnal symptoms
      •History of ICU admission
      •Mechanical ventilation
      •Greater than 2 hospitalizations/year
      •Steroid dependence (systemic use)
      •History of syncope with asthma
      •History of noncompliance
  •Mortality rates are increasing
  •If responsive to treatment is poor, review diagnosis and compliance prior to adding more potent therapy

MISCELLANEOUS
ASSOCIATED CONDITIONS:
  •Reflux esophagitis
  •Sinusitis

AGE-RELATED FACTORS:

Pediatric: 50% of new cases of asthma occur in children below 10 years
Geriatric: Unusual for initial episode to occur
Others: N/A

PREGNANCY:
  •About 50% of asthma patients have no changes, 25% seem to improve and 25% have worse symptoms
  •Stress prevention
  •Avoid medications with contraindications

SYNONYMS:
  •Bronchial asthma
  •Reactive airway disease

SEE ALSO:
  • Cystic fibrosis
  • Bronchitis, acute
  • Immunodeficiency diseases
  • Bronchiolitis
  • Laryngotracheobronchitis
  • Epiglottitis
  • Congestive heart failure
  • Chronic obstructive pulmonary disease & emphysema
  • Hypersensitivity pneumonitis
  • Tuberculosis
OTHER NOTES:
Antihistamines are not contraindicated in asthma

ABBREVIATIONS:
ABPA = allergic bronchopulmonary aspergillosis
PFT = pulmonary function test
RAD = reactive airway disease
PEFR = peak expiratory flow
MDI = metered dose inhaler

REFERENCES

  •Barnes PJ: A new approach to the treatment of asthma. New Engl J Med 1989;321:1517
  •NHLBI Guidelines, 1997
  •Rachelefsky G, Warner J: International Consensus on the Management of Pediatric Asthma. Ped Pulmon 1993;15:125-127