Pathophys of Asthma
- Activation of mast cells and epithelial cells in the airway
- Release of histamine, leukotrienes, tryptase and other inflammatory mediators
- Inflammatory response results in airway smooth muscle constriction, vasodilation, edema and mucus secretion
- Narrowing of airway, wheezing, cough, SOB, this is the early asthmatic response (usually occurs within minutes of exposure and lasts about 1 hour)
- In 50% of pts they have a second wave of inflammation 4-6 hours after initial response: worsening SOB, wheeze, cough
- Chronic disease develops with ongoing inflammation which results in: permanent remodeling of the airway, chronic, persistent airflow limitation
Etiology of asthma
- genetic predisposition to hypersensitivity reaction due to production of specific IgE antibody
- Most common allergens leading to sensitization are house dust mites, cat and dog fur, cockroaches, grass, pollen, rodents
- Intrinsic (non-atopic) asthmatics: negative skin tests to inhalant allergens, normal serum IgE, usually later onset of disease
- Viral infections may trigger exacerbations, role in etiology uncertain
- High degree of concordance for asthma in identical twins
- Air pollution
- Occupations exposure
Asthma Triggers
- Allergens activate mast cells with bound IgE, leads to release of bronchoconstrictor mediators, results in early response
- Viral infections: URI, mechanism not fully understood, increased airway inflammation, eosinophils, neutrophils
- Drugs: β-blockers
- use of NSAIDs
- Exercise: Hyperventilation triggers mast cell release, results in bronchoconstriction, Usually begins after exercise has ended and resolves within 30 minutes, Worse in cold, dry climates
- Food may trigger
- air pollution
- occupational factors
- Hormonal factors: worsening of asthma during premenstrual period,
- GERD: reflux common in asthmatics
Sx of Asthma
- Wheezing
- Dyspnea
- Coughing (non-productive)
- Increased mucus production
- Symptoms may worsen at night
- In severe acute attack will see use of accessory muscles, retractions, tachypnea, diminished breath sounds, cyanosis
- On auscultation inspiratory/expiratory wheeze/rhonchi
Tests for Asthma
- Pulmonary Function Tests Measure: Airflow rates, Lung volumes, Ability of the lung to transfer gas across the alveolar-capillary membrane
- Pulmonary Function Tests :Help assess type and extent of lung dysfunction, causes of dyspnea and cough, detection of early lung dysfunction and follow-up in response to therapy, effort-dependent
- Spirometry: measurement of how much air can be inhaled/exhaled, allows assessment of the presence and severity of obstructive and restrictive pulmonary dysfunction
- Obstructive dysfunction is marked by a reduction in airflow rates judged by fall in the ratio of FEV1/FVC ratio: FEV1=forced expiratory volume in the first second, FVC=forced vital capacity, the largest amount of air that can be forcefully exhaled after a deep breath
- Restrictive dysfunction is marked by a reduction in lung volumes with a normal to increased FEV1/FVC ratio
- Peak expiratory flow meters are handheld devices used by patients to monitor severity of exacerbation.
- Labwork: ABGs can be helpful in an acute attack, labs not usually helpful in the diagnosis in the absence of symptoms
- Imaging: CXR usually normal but can show hyperinflated lungs (also found in COPD), on CT may see bronchiectasis (widened, scarred airways), thickening of bronchial walls
Mild Intermittent Asthma
- Symptoms of cough, wheeze, chest tightness or difficulty breathing less than twice a week
- Flare-ups-brief, but intensity may vary
- Nighttime symptoms less than twice a month
- No symptoms between flare-ups
- Lung function test FEV1 equal to or above 80 percent of normal values
- Peak flow less than 20 percent variability AM-to-AM or AM-to-PM, day-to-day.
Mild Persistent Asthma
- Symptoms of cough, wheeze, chest tightness or difficulty breathing three to six times a week
- Flare-ups-may affect activity level
- Nighttime symptoms three to four times a month
- Lung function test FEV1 equal to or above 80 percent of normal values
- Peak flow less than 20 to 30 percent variability.
Moderate Persistent Asthma
- Symptoms of cough, wheeze, chest tightness or difficulty breathing daily
- Flare-ups-may affect activity level
- Nighttime symptoms 5 or more times a month
- Lung function test FEV1 above 60 percent but below 80 percent of normal values
- Peak flow more than 30 percent variability.
Severe Persistent Asthma
- Symptoms of cough, wheeze, chest tightness or difficulty breathing continual
- Nighttime symptoms frequently
- Lung function test FEV1 less than or equal to 60 percent of normal values
- Peak flow more than 30 percent variability.
Short Acting Beta Agonist
- Levalbuterol (more sensitive), Albuterol
- Bronchodilate
- relax airway smooth muscle
- increase mucociliary clearance
- stabilize mast cell membranes
- drug of choice for quick relief of sxs and prevention of exercise-induced brochospasm
- duration 4-6 hrs, onset 5 min
- metered-dose inhaler
- 2 puffs every 4-6 hrs
- 2 puffs 5 min before exercise
- regular use not recommened
Anticholinergics
Ipratropium
-Bronchodilate
-inhibit the effects of acetylcholine on muscarinic receptors
-Not first line, add on therapy
-onset 30 min, duration 4-8
AE: blurred vision, dry mouth, urinary retention, constipation
-rarely used with Asthma usually COPD, not good for long term
-add to beta agonist to improve function
Systemic corticosteroids
-Prednisone, Mtheylprednisone, prednisolone
-decrease airway inflammation
-decrease hyperresponsiveness
-decrease mucus production and secretion
-improve response to beta agonist
-Long term control, once daily or every other day if all other therapies fail
-effective for worsening asthma that is not responding - acute sever asthma
-use minimal dose until controlled then reduce dose
-
inhaled corticosteroids
-Gold Standard
-decrease airway inflammation
-decrease hyperresponsiveness
-decrease mucus production and secretion
-improve response to beta agonist
-preferred therapy for persistent asthma
-onset w/in 12 hrs - taken daily, long term therapy
-takes two weeks to see effects
AE: oral candidiasis, cough, hoarseness, dyspnea, adrenal suppression, skin thinning, cataracts, delayed growth, easy bruising
inhaled long acting beta agonist
Salmeterol (onset 30 min), Formoterol
- not a quick relief or rescue inhaler
- add on therapy for asthma not controlled on low to medium dose of corticosteroids
- reduce amt of corticosteroid
- acts up to 12 hrs.
- cant be used as monotherapy only add on with corticosteroids - black box dont use alone!
- Combo: Advair, Symbicort
leukotriene modifiers
Zileuton, Montelukast, Zafirlukast
- improve FEV1 and decrease asthma sxs, decrease inhaler use and exacerbations
- less effective than inhaled corticosteroids
Methylxanthines
theophylline
-bronchodilator
-limited use
-inferior efficacy compared to ICS
-narrow therapeutic index
-life threatening toxicity
AE: HA, N & V, insomnia, GI upset, irritability occur at serum conc less than 20 mg
-AE: arrhythmias, seizures, encephalopathy at high conc
-Many drug interactions, must monitor serum levels which can be affected by many things
Anti-IgE antibody
Omalizumab
- inhibits binding of IgE to receptors on mast cells and basophils, results in inhibition of mediator release
- moderate to sever persistent asthma
- 12 yo or older
- high cost
- SQ injection, cant self admin, every 2-4 weeks
- decreases ICS use and reduces # and length of exacerbation
- AE: injection site rxn, anaphylactic rx,
Mast cell stabilizer
-Cromolyn
-Nebulizer solution
-Block both early and last phase response by inhibiting release of mediators from mast cells
-alt to inhaled corticosteroids in moderate asthma
-max benefit 4-6 weeks
well tolerated
-prophylaxis
