Impact of Asthma in the U.S. per Year. Asthma Epidemiology and Pathophysiology. Risk Factors for Asthma. Childhood Asthma Costs of Asthma

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1 American Association for Respiratory Care Asthma Educator Certification Prep Course Asthma Epidemiology and Pathophysiology Robert C. Cohn, MD, FAARC MetroHealth Medical Center Cleveland, OH Impact of Asthma in the U.S. per Year 22 million asthmatics (6-7 million children) > 445,000 hospitalizations 1.2 million emergency room visits 10 million missed school days 30.5 million prescriptions > 5,000 deaths Childhood Asthma Between 3% - 7% of U.S. children The most common chronic illness of childhood 13 million physician visits / year 200,000 hospitalizations / year 3x the number of school absenteeism compared to children without asthma Risk Factors for Asthma Atopy Genetics Allergen / Irritant Exposure Gender Poverty $5.9 billion 1990 Costs of Asthma $5.2 billion - direct costs (ex. hospital, physician, meds) $0.7 billion - indirect costs (missed work, school, decreased work) 1990 Breakdown of Direct Costs $2.8 billion - hospitalizations (appx. 50% of total) $1.2 billion - ambulatory care $0.8 billion - medications / prescriptions $0.35 billion - ER visits

2 Costs of Asthma Today $13 billion Most in hospital care and prescriptions Distribution of Asthma-Related Physician Visits The majority of asthma care is delivered by primary care physicians (78% children vs. 58% adults) Specialist (20% children vs. 36% adults) Asthma Prevalence (2000) in U.S. 9% women 5% men 7.8% African American 7.4% Caucasian 8.5% other Childhood Asthma Prevalence 6-7 million children Asthma prevalence in children < 5 years of age has increased 160% from % of asthma has onset by 5 years of age 100,000 new cases diagnosed yearly in Childhood Asthma 10 million lost school days / year 36% of parents of asthmatics missed work in the last year 78% of parents report a negative impact in the family $1 billion in parental lost productivity Pediatric Asthma Mortality Deaths more than doubled for 0-14 year olds Most patients who died - not seen as high risk Some had mild disease

3 Asthma Pathophysiology Chronic Inflammation within the Airways Asthma: A Lung Disease Characterized by... Airway obstruction (at least partially reversible) Hyperreactivity (increased bronchial responsiveness to a variety of stimuli) Inflammation - mast cells, eosinophils, lymphocytes and neutrophils (alveolar macrophages are normal) The Airway in Asthma Increased mucus Disruption of the bronchial epithelium Edema Increased vascular permeability Increased thickness of the basement membrane Smooth muscle constriction/airway hyperresponsiveness Airway remodeling Histopathology of Asthma Disruption and denudation of bronchial epithelium (in some asthmatics, epithelial cells are found in sputum) Collagen deposition beneath basement membrane (increased fibroblasts) Edema (increased vascular permeability) Increased numbers of activated mast cells I fl t ll i filt ti

4 Inflammatory Cell Infiltration Most common infiltrating cells are eosinophils and lymphocytes Neutrophils are abundant in suddenonset, fatal asthma exacerbations TRIGGERS: Cell Mediator Release Symptoms Changes (Airway Hyperresponsiveness Physiological Airway Obstruction) Triggers Viral respiratory infections Exercise Irritants-tobacco smoke; strong odors; chemicals Allergens (ex. animal dander; dust; dust mites) Drugs ex. aspirin (NSAID): propranolol (beta blockers) Weather change / cold air Triggers - Cont d. Emotional expressions ex. Laughing; anger Food additives ex. Sulfites Gastroesophageal reflux disease Environmental Rhinitis / sinusitis Understanding Asthma Pathophysiology FEV Time (hrs.)

5 Asthma Early Phase 2 Distinct phases Early or immediate phase Late Occurs within 30 minutes of trigger exposure BRONCHOCONSTRICTION and BRONCHOSPASM Within 5 Minutes Late Phase - Chronic Inflammation Trigger (ex. allergen) Mast Cell Begins 4 hours after the initial trigger but can occur up to 8 hours later potent chemotactic factors for eosinophils and lymphocytes Degranulation - Histamine - Prostaglandins -Cytokines- (IL 1-5; TNF alpha ; IFN gamma ; CSF) - Platelet Activating Factor (PAF) Eosinophil is key to chronic inflammation (not the mast cell) Cytokines PAF Eosinophil Leukotrienes Bronchoconstriction (LTC 4 ) permeability Tissue Damage Major basic protein Eosinophil cationic protein Eosinophil derived neurotoxin Eosinophil peroxidase & other enzymes vascular Lymphocytes ( T lymphocytes) Antigen - presenting cells initiate the differentiation of T lymphocytes CD4+ cells (Th0) develop into Th1 - type cells (T helper 1) or Th2 - type cells Th1 produce interleukin 2 and interferon gamma both important in cell mediated immunity and cell defense mechanisms

6 Th2 cells produce interleukin (IL-4, IL- 5, IL-6, IL-9, IL-13) Participate in IgE - mediated reactions (allergic inflammation) B Lymphocytes Immunoglobulins D, E) (IgG, A, M, Imbalance or hygiene hypothesis IgE: relationship to asthma severity The ability to synthesize IgE antibodies to environmental allergens (atopy) remains a major risk factor in asthma pathogenesis Mast cells and basophils have high affinity IgE receptors Allergen Mast Cell IgE Degranulation and release of preformed and newly generated mediators Arachidonic Acid Pathway Leukotrienes and Prostaglandins are derived from the Arachidonic Acid Pathway Cyclooxygenase protein Prostaglandins Membrane phospholipids Phospholipase A2 Arachidonic Acid 5-lipoxygenase activating protein & 5-lipoxygenase Leukotrienes Thromboxanes LTC 4 LTD 4 LTE 4 LTB 4 (PGD 2 PGF 2 ) (cysteinyl LT s) Bronchoconstriction

7 Synthesis CELL LTC 4 LTD 4 LTE 4 Mast cell +++ Eosinophil +++ Alveolar macrophage + Neutrophil -- Leukotrienes interact with receptors on multiple cell types Effects of Cysteinyl Leukotrienes Bronchoconstriction (100x x more potent than histamine) Increased mucus secretion Decreased mucus clearance Eosinophil infiltration Eosinophil activation Protection Against Drug Early Asthmatic Late Asthmatic Response Response Inhaled corticosteroid Oral steroids Cromolyn (sodium cromoglycate) Beta agonist bronchodilator Ipratropium - - Theophylline - + Extrinsic vs. Intrinsic