Asthma Review of Pathophysiology and Treatment

n definition of asthma –Asthma is a chronic inflammatory disorder of the airways in which many cells & cellular elements play a role (mast cells, eosinophils, T lymphocytes, macrophages, neutrophils, & epithelial cells).

Introduction n Chronic inflammatory disease of the airways n Most common childhood chronic disease n Affects ~4.8 million

Pathogenesis and Definition n Key points –Chronic inflammatory disorder of the airways –Immunohistopathologic features < denudation of airway epithelium < collagen deposition beneath basement membrane < edema < mast cell activation

–Immunohistopathologic features < inflammatory cell infiltration –Neutrophils (sudden, fatal asthma) –Eosinophils –Lymphocytes n Airway inflammation (AI) contributes to hyperresponsiveness, airflow limitation, symptoms & chronicity

n AI causes types of airflow limitation: –Bronchoconstriction, edema, mucus plug formation, airway wall remodeling n Atopy is strongest predisposing factor for developing asthma

–In susceptible individuals, inflammation causes recurrent episodes of wheezing, breathlessness, chest tightness, and coughing, particularly at night/early morning. These episodes are associated with variable airflow obstruction often reversible spontaneously/treatment

n Child-onset asthma –Associated with atopy –IgE directed against common environmental antigens (house-dust mites, animal proteins, fungi

n Adult-onset asthma –Many situations –Allergens important –Non-IgE asthma have nasal polyps, sinusitis, aspirin sensitivity

Airway Inflammation & Lung Function n Airway hyperresponsiveness –Post exposure wheezing & dyspnea –Degree correlates to asthma severity –Measured by methacholine/histamine inhalation challenge or non-drug stimuli (cold, dry air)

n Airway hyperresponsiveness –Correlation to airway inflammation clear but complex < airway inflammation markers

n Airflow limitation –Acute bronchoconstriction < IgE -dependent mediator release from mast cell (leukotrienes, histamine, tryptase, prostaglandins) < aspirin /NSAID < non-IgE response (cold air, exercise, irritants)

n Airflow limitation –Chronic mucus plug formation < persistent airflow limitation in severe asthma –Airway remodeling < irreversible component of airflow limitation secondary to structural airway matrix changes

n Airflow limitation –Airway remodeling < attributed to chronic, severe airway inflammation < early intervention with anti-inflammatory therapy suggests prevention of permanent airflow limitation

Measures of Assessment and Monitoring n Asthma diagnosis criteria –+ episodic symptoms of airflow obstruction –Airflow obstruction reversible

n Techniques to establish diagnosis –History –Physical exam (resp. tract, skin, chest) –Spirometry to demonstrate reversibility

–Severity classifications: < mild intermittent < mild persistent < moderate persistent < severe persistent

Severe Persistent Asthma n Symptoms –Limited physical activity –Frequent exacerbations –Frequent nighttime symptoms n Lung Function –FEV 1 < 60% of predicted

Moderate Persistent Asthma n Symptoms –Daily symptoms –Daily use of inhaled short-acting beta 2 agonist –Nighttime symptoms >1 time/wk n Lung Function –FEV 1 > 60% - < 80% predicted

Mild Persistent Asthma n Symptoms –Symptoms > 2 X/wk but <1 X/day –Exacerbations may affect activity –Nighttime symptoms > 2 X/mo n Lung Function –FEV 1 > 80% predicted

Mild Intermittent Asthma n Symptoms –Symptoms < 2 X/wk –Asymptomatic and normal FEV 1 between exacerbations –Exacerbations brief (few hrs - few days); intensity may vary –Nighttime symptoms < 2 X/mo n Lung Function –FEV 1 > 80% predicted

Asthma Management n Goals of therapy –Prevent symptoms –Maintain (near) “normal” FEV 1 –Maintain normal activity –Prevent exacerbations –Optimal drug, minimal problems –Patient/family satisfaction

Assessment Measures n Asthma treatment effectiveness –Monitor signs & symptoms - daytime, nocturnal, early morning symptoms response to short-acting Beta agonist –Pulmonary function (spirometry,) < patients with moderate-to-severe persistent asthma should learn how to monitor symptoms

n Asthma treatment effectiveness –Monitoring quality of life/functional status < missed work, school < activities < sleep –Monitoring asthma exacerbation history

n Asthma treatment effectiveness –Monitoring asthma exacerbation history < urgent or emergent care < frequency, severity & causes of exacerbations < hospitalization info

n Asthma treatment effectiveness –Monitoring Drug Therapy < patient compliance < inhaler technique < frequency of use the short-acting beta2 agonist < frequency of oral steroid “burst” therapy < dose changes of inhaled anti-inflammatory meds.

Pharmacologic Therapy n Long-term control medications –corticosteroids < inhaled form < systemic steroids used to gain prompt control of disease

n Long-term control medications –Long-acting beta2-agonists < Used with anti-inflammatory meds for long-term symptom control especially nocturnal symptoms < prevents exercise-induced bronchospasm –Methylxanthines < prevention of nocturnal symptoms

n Long-term control medications –Leukotriene modifiers < leukotriene receptor antagonist < alternative to low dose inhaled steroids

n Quick relief medications –Short acting beta2-agonists - relief of acute symptoms –Anticholinergics - may provide additive benefit to beta2 drugs in severe exacerbation. May be alternative to beta2-agonists –Systemic steroids - moderate-to-severe persistent asthma in acute exacerbations or to prevent recurrence of exacerbations

Treatment/Long Term Control n Corticosteroids –Most potent and effective –Reduction in symptoms, improvement in and spirometry, diminished airway hyperresponsiveness, prevention of exacerbations, –prevention of airway wall remodeling –Suppresses: airway eosinophilic recruitment, chemical mediators

n Long-acting beta- 2 agonists –Relax airway smooth muscle –Duration of action >12 hrs

n Methylxanthines –Provides mild-moderate bronchodilation –Low dose has mild anti-inflammatory action

n Leukotriene modifiers –Leukotrienes are potent biochemical mediators released from mast cells, eosinophils, and basophils that: < contract bronchial smooth muscle < increase vascular permeability < increase mucus secretions < attract & activate inflammatory cells in airways

Asthma Treatment/Quick Relief n Short-acting beta 2 agonists –Relax airway smooth muscle and increase in airflow in <30 minutes –Drug of choice for treating symptoms and exacerbations –Regularly scheduled use NOT recommended

n Systemic steroids –speed resolution of airflow obstruction –reduce rate of relapse

Hospitalization n Decision to hospitalize depends upon: < duration < severity (symptoms & airflow obstruction) < course & severity of previous exacerbations < medication use at time of exacerbation < home conditions

n Treatment: –Emergency dept. treatment < Permission hypercapnia is recommended ventilator strategy