Snapshot A five-year-old with severe asthma is being treated in the ER with a IV aminophylline drip. The child is slowly becoming sleepy and less responsive. Physical exam reveals less wheezing than on admission. Representative lung histology is shown. Introduction Definition episodic and reversible bronchoconstriction with bronchioles being the most susceptible respiratory segment result of inflammation bronchial smooth muscle hypertrophy and hyperactivity mucus plugging Classification Types extrinsic typically seen in children with a genetic predisposition type I hypersensitivty to an inhaled (external) allergen such as pollen proceeds by specific stages sensitization CD4 TH2 cells produce cytokines (IL-4 and IL-5) when initially stimulated by an allergen IL-4 induces antibody isotype switch to IgE IL-5 induces eosinophil activation early activation mast cells are activated by cross-linking of IgE and release immune activating substances (histamine, leukotrienes, and acetylcholine) when allergen is presented again histamine results in bronchoconstriction, chemotaxis for immune cells, and mucus production acetylcholine results in bronchoconstriction (parasympathetic mediated) leukotrienes C4, D4, and E4 induce bronchoconstriction late activation eosinophils are activated recruited by eotaxin produce major basic protein, which causes further constriction/damage in the airways intrinsic non-allergen mediated induced by infection viral URI (RSV, rhinovirus, and parainfluenza virus) behavioral exertion and stress chemical drug sensitivity (NSAIDs and aspirin) ozone produced free-radicals status asthmaticus life-threatening asthma attack that does not respond to standard treatments Presentation Symptoms wheezing cough mucus production note: a child who is becoming sleepy and less responsive is most likely failing, retaining CO2 (case intro) and needs intubation Physical exam tachycardia tachypnea with use of accessory muscles pulsus paradoxus result of reduced I/E ratio result of increased lung volume and vascular resistance auscultation prolonged expiratory wheezes (sometimes inspiratory) high pitched sibilant rhonchi dyspnea persistent cough with hyperinflation of the lungs Imaging Chest radiograph normal or hyperinflation Studies Labs ABG may initially show respiratory alkalosis if CO2 is normal, respiratory failure may be imminent elevated CO2 (respiratory acidosis) are ominous signs and patient likely requires intubation Pulmonary function tests peak flows are diminished obstructive pattern may be seen when symptomatic (↓ FEV1/FVC) improvement with bronchodilator administration high airway resistance Methacholine challenge provacative measure of hyperactivity in a well patient functions as a muscarinic cholinergic agonist reduction of FEV1 by > 20% is diagnostic of asthma Skin testing may result in hypersensitivity response to allergen when presented into skin (really diagnoses atopy, not asthma) Histological changes terminal bronchioles mucus plugs Curschmann's spirals presence of trapped epithelial cells killed by eosinophil produced major basic protein Charcot-Leyden crystals aggregated eosinophils increased mucus-producing cells bronchi thickened basement membrane unique to asthma hypertrophy of submucosal glands and smooth muscle also seen in other lung disorders including chronic bronchitis increased immune cell presence Treatment Acute exacerbation oxygen inhaled beta-2 agonists short acting preferred (e.g albuterol) appropriate for exercise induced asthma administer before exertion in known asthmatics systemic corticosteroids (PO or IV) Status asthmaticus oxygen, bronchodilators, and steroids sympathomimetic bronchodilators(e.g. epinephrine) intubation and mechanical ventilation Maintenance treatment inhaled corticosteroids (mainstay) long-acting bronchodilators (beta-2 agonists) in combintation with inhaled corticosteroids (increased risk of death if used without inhaled corticosteroid) montelukast cromolyn rarely used; supplemental treatment for exercise-induced asthma theophylline phosphodiesterase inhibitor; rarely used ipratropium bromide an anticholinergic that inhibits the contraction of smooth muscle used in the elderly with an asthmatic component to their COPD tiotropium more recently shown to be efficacious and safe