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Asthma Pathophysiology Asthma Overview

Asthma Pathophysiology Asthma Overview. Presented by: Michelle Harkins, MD University of New Mexico. This session will cover. Review asthma statistics Define asthma Outline key pathophysiologic features Review signs and symptoms of asthma

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Asthma Pathophysiology Asthma Overview

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  1. Asthma PathophysiologyAsthma Overview • Presented by: • Michelle Harkins, MD • University of New Mexico

  2. This session will cover Review asthma statistics Define asthma Outline key pathophysiologic features Review signs and symptoms of asthma Reference to NAEPP – EPR-3: asthma severity classification system-including impairment and risk domains Diagnosing asthma

  3. Prevalence vs Incidence • Prevalence - the proportion or percentage of a population that has disease at a specific point or period of time • Incidence – the number of new cases of disease that develop in a population of individuals at risk during a specific point or period of time

  4. 1980-1996 prevalence of asthma in US increased • Since 1999, mortality and hospitalization due to asthma have decreased

  5. Trends in Asthma Morbidity and Mortality. American Lung Association, Epidemiology and Statistics Unit, Research and Program Services Division. September, 2012.

  6. Trends in Asthma Morbidity and Mortality. American Lung Association, Epidemiology and Statistics Unit, Research and Program Services Division. September, 2012.

  7. Trends in Asthma Morbidity and Mortality. American Lung Association, Epidemiology and Statistics Unit, Research and Program Services Division. September, 2012.

  8. New Mexico BRFSS Results for 2010: Current Prevalence: Percent of New Mexico Children who Currently Have Asthma by Various Demographic Characteristics Race/Ethnicity: White, Non-Hispanic 8.1% Hispanic 7.4% Native American 13.1% SOURCE: Centers for Disease Control and Prevention (CDC). Behavioral Risk Factor Surveillance System Survey Data. Atlanta, Georgia: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, 2009

  9. Trends in Asthma Morbidity and Mortality. American Lung Association, Epidemiology and Statistics Unit, Research and Program Services Division. September, 2012.

  10. Trends in Asthma Morbidity and Mortality. American Lung Association, Epidemiology and Statistics Unit, Research and Program Services Division. September, 2012.

  11. Asthma age-adjusted hospitalization rates per 10,000 standard population by county, New Mexico, 2007-2011 average

  12. Asthma hospitalization rates per 10,000 standard population among youth (0-14 years) by county, New Mexico, 2007-2011 average

  13. Trends in Asthma Morbidity and Mortality. American Lung Association, Epidemiology and Statistics Unit, Research and Program Services Division. September, 2012.

  14. Trends in Asthma Morbidity and Mortality. American Lung Association, Epidemiology and Statistics Unit, Research and Program Services Division. September, 2012.

  15. Asthma Age-Adjusted Death Rates Based on the 1940 and 2000 Standard populations, 1979-2005

  16. Asthma Impact – Economic Burden • Childhood asthma accounts for 14.4 million days missed from school annually • The number-one chronic condition causing children to be absent from school and the third highest ranked cause of pediatric hospitalizations in the United States • On average, a child with asthma will miss one full week of school each year due to the disease

  17. Asthma Impact – Economic Burden • Adult asthma accounts for 14.2 million missed workdays annually • 4th leading cause of missed work days

  18. National Burden of Asthma $19.7 billion annually • $14.7 billion in direct costs (prescription medications, hospital care, and physician services) • $5 billion in indirect costs (lost productivity due to missed work or school and premature mortality)

  19. Define Asthma Develop a collaborative working definition of asthma

  20. Evolution of the Definition of Asthma 19622007 • Episodic disease characterized by: • Reversible airway constriction • Increased airway responsiveness • Chronic disease characterized by: • Chronic airway inflammation • At least partially reversible airway obstruction • Increased airway responsiveness American Thoracic Society, 1962. NAEPP, EPR3, 2007.

  21. 3M Resource Cards Doctors Designers 11-96

  22. 3M Resource Cards Doctors Designers 11/96

  23. 3M Resource Cards Doctors Designers 11-96

  24. Pathophysiology of Asthma

  25. Epithelial Damage in Asthma Normal Asthmatic

  26. Asthma: Pathophysiology Inflammatory cell infiltrate consists of mainly of eosinophils and lymphocytes “Sudden death” asthma associated with an infiltrate of neutrophils Denudation of airway epithelium Mucus gland hyperplasia and hypersecretion Smooth muscle cell hyperplasia Submucosal edema and vascular dilatation Fibrin deposition/airway remodeling

  27. Multiple Mechanisms Contribute to Asthma: Inflammatory Mediators Bronchoconstriction Mediator Soup Microvascular Leakage Mucus Hypersecretion AirwayHyperresponsiveness Histamine Lipid Mediators* Peptides† Cytokines‡ Growth Factors *For example, prostaglandins and leukotrienes.†For example, bradykinin and tachykinin.‡For example, tumor necrosis factor (TNF). Adapted with permission from Barnes PJ. In: Barnes PJ et al, eds. Asthma: Basic Mechanisms and Clinical Management. 3rd ed. Academic Press; 1998:487-506. Mast Cells Macrophages Eosinophils T-Lymphocytes Epithelial Cells Platelets Neutrophils Myofibroblasts Basophils

  28. FACTORS LIMITING AIRFLOW IN ACUTE AND PERSISTENT ASTHMA NAEPP, EPR-3, pg. 15.

  29. Inflammation in Asthma Allergen/Trigger Mast cell T-cell Macrophage Histamine Cytokines B-cell IgE Eosinophil Airway Inflammation IgE = immunoglobulin E. National Asthma Education and Prevention Program Guidelines, 1997. Busse WW et al. N Engl J Med. 2001;344:350-362. Bousquet J et al. Am J Resp Crit Care Med. 2000;161:1720-1745.

  30. Aftermath of Inflammation • Reversibility • Occurs in most asthma episodes • Airway returns to normal caliber • Flow of air through airways returns to normal “speed” • Remodeling • Airway lining builds up persistent fibrotic changes • Airway caliber remains abnormal • Air flow is decreased • Permanent changes appear to begin in childhood, but become recognizable in adults

  31. Asthma is a Chronic Inflammatory Disease: Pathophysiologic Changes Normal Architecture Disrupted Architecture Bronchial Mucosa From a Subject With Mild Asthma Bronchial Mucosa From a Subject Without Asthma Hematoxylin and eosin stain. Photographs courtesy of Nizar N. Jarjour, MD, University of Wisconsin.

  32. Consequences of Persistent Asthma:Subepithelial Collagen Deposition Lumen Epithelium Subepithelial Collagen Deposition Reprinted with permission from Holloway L et al. In: Busse WW, Holgate ST, eds. Asthma and Rhinitis. Blackwell Scientific Publications; 1995:109-118.

  33. Consequences of Persistent Asthma: Progressive Decline in FEV1 120 100 80 FEV1 % Predicted 60 40 n = 89 r = -0.47 20 P<.001 0 10 20 30 40 50 Duration of Asthma (years) FEV1 = forced expiratory volume in 1 second. Adapted with permission from Brown PJ et al. Thorax. 1984;39:131-136.

  34. Asthma is. . . • Chronic inflammatory disorder of the airways • Mast cells, eosinophils and lymphocytes infiltrate into airway lining • Airway hyperresponsiveness develops • Excessive reaction to “minor” irritants results in a host of deleterious airway changes • Bronchial wall edema • Smooth muscle contraction • Excess mucus production • Patchy, mostly reversible regions of airway narrowing cause asthma symptoms

  35. Acute Reaction to Triggers • Irritated airways become more inflamed after exposure to stimuli • Muscle layers around airway constrict • Airway lining swells • Excess mucus builds up in lumen • Result: symptoms of cough, wheeze, shortness of breath, chest tightness

  36. Risk Factors for Developing Asthma • Genetic predisposition • Atopy • Airway hyperresponsiveness • Gender • Race/Ethnicity

  37. Intrinsic factors Genetics Duration of asthma Severity of childhood asthma Gender Response to therapy Extrinsic factors Viral infections Allergen exposure Airway irritants Exercise Compliance Season Time of day Occupational—10-15% of adult asthma Western Lifestyle--obesity What Parameters Affect Disease ?

  38. Environmental Risk Factors for Development of Asthma Parasitic infections Socioeconomic factors Family size Diet and drugs Obesity Hygiene hypothesis Indoor allergens Outdoor allergens Occupational sensitizers Tobacco smoke Air Pollution Respiratory Infections

  39. Asthma & Airway Inflammation Risk Factors(for development of asthma) Genetic Environmental INFLAMMATION BronchialHyperresponsiveness Airflow Obstruction Symptoms Risk Factors(for exacerbations)

  40. Multiple Triggers Can StimulateAcute Reaction • Upper Respiratory Infections (URI’s) • Viral Respiratory infections are the #1 trigger behind asthma hospitalizations • Influenza vaccines are recommended for people with asthma • Allergens • Irritants • Sudden or extreme changes of weather • Exercise • Intense emotions

  41. Exercise Induced Bronchospasm • Bronchospasm caused by activity • Some activity more likely than others to trigger it • Cold environment: skiing, ice hockey • Heavy exertion: Soccer, long distance running • Exercising when you have a viral cold

  42. Exercise Induced Bronchospasm • Symptoms include • Coughing • Wheezing • Chest tightness • Symptoms may begin during activity and peak in severity 10-20 minutes after stopping • Can spontaneously resolve 20-30 minutes after its onset

  43. Epidemiology • Prevalence 7-20% of the general population • 80% of patients with asthma have some degree of EIB • Exercise is not a risk factor for asthma, rather a trigger • ?Exercise may help prevent onset of asthma in children • Decrease in physical activity may play a role in increased in asthma prevalence • JACI 2005 Lucas SR, Platts-Mills TA

  44. Prevention of EIB Use bronchodilator 10-15 minutes before onset of activity Do warm-up/cool down exercises Check ozone/allergy warnings Never encourage anyone to “tough it out”

  45. Management • Increasing fitness: decreases minute ventilation needs with exercise • Less severe if inspired air is warmer, more humid (Evidence Class C) • Scarf or mask if cold weather • Warm-up period before exercise • Good asthma control: EIB more frequent in patients with poorly controlled disease (Class A) • Check for asthma control • Treating appropriately will reduce frequency and severity of EIB

  46. Impairment and Risk Domains Impairment-frequency and intensity of symptoms and functional limitations the patient is experiencing or has experienced Risk-the likelihood of either asthma exacerbations, progressive decline in lung function or risk of adverse effects from medication NIH. NAEPP Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma, October 2007.

  47. Risk Factors for Death from Asthma • History of severe exacerbations • Prior intubation for asthma • Prior admission to Intensive Care Unit • 2 or more hospital admissions in the past year • 3 or more emergency room visits in the past year • Hospital or emergency room visit past month • Use of >2 canisters per month of inhaled short-acting beta2 –agonist

  48. Risk Factors for Death from Asthma • Chronic use of systemic corticosteroids • Poor perception of airflow obstruction or its severity • Co-morbid conditions (other diseases) • Serious psychiatric disease or psychosocial problems • Low socioeconomic status and urban residence • Illicit drug use • Sensitivity to alternaria-mold • Lack of written asthma action plan

  49. Diagnosing Asthma • Recurrent episodes of coughing or wheeze • Asthma may be present without a wheeze - cough may be the sole symptom • Shortness of breath or difficulty breathing • Chest Tightness • Wheezing does not always mean asthma • Absence of symptoms and physical findings at the time of the examination does not exclude asthma

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