ASTHMA PATHOPHYSIOLOGY ASTHMA OVERVIEW Presented by Martha Mullane
ASTHMA PATHOPHYSIOLOGY ASTHMA OVERVIEW Presented by: Martha Mullane CPNP MSN AE-C
This session will cover • Definition asthma • Outline key pathophysiologic features of asthmaearly and late phase inflammation and bronchoconstriction • Review signs and symptoms of asthma • Reference to NAEPP – EPR-3: asthma severity classification system-including impairment and risk domains • Diagnosing asthma
Evolution of the Definition of Asthma 1962 American Thoracic Society, 1962. • Episodic disease characterized by: – Reversible airway constriction – Increased airway responsiveness 2007 NAEPP, EPR 3, 2007. • Chronic disease characterized by: – Chronic airway inflammation – At least partially reversible airway obstruction – Increased airway responsiveness
3 M Resource Cards Doctors Designers 11 -96
3 M Resource Cards Doctors Designers 11/96
3 M Resource Cards Doctors Designers 11 -96
FACTORS LIMITING AIRFLOW IN ACUTE AND PERSISTENT ASTHMA NAEPP, EPR-3, pg. 15.
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
Pathologic airway changes induced in asthma Mucous gland hypertrophy Edema Mucus Thickening of basement membrane Adapted from National Asthma Education and Prevention Program. Expert Panel Report: Guidelines for the diagnosis and management of asthma. NHLBI, NIH. 1991. Epithelial damage Airway smooth muscle Inflammatory cell infiltration Vascular dilatation
Multiple Mechanisms Contribute to Asthma: Inflammatory Mediators • • • Mast Cells Macrophages Eosinophils T-Lymphocytes Epithelial Cells Platelets Neutrophils Myofibroblasts Basophils Bronchoconstriction Mediator Soup 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. 3 rd ed. Academic Press; 1998: 487 -506. Microvascular Leakage Mucus Hypersecretion Airway Hyperresponsiveness
Asthma is a Chronic Inflammatory Disease: Pathophysiologic Changes Normal Architecture Disrupted Architecture Bronchial Mucosa From a Subject Without Asthma Bronchial Mucosa From a Subject With Mild Asthma Hematoxylin and eosin stain. Photographs courtesy of Nizar N. Jarjour, MD, University of Wisconsin.
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
Epithelial Damage in Asthma Normal Asthmatic
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.
Consequences of Persistent Asthma: Smooth Muscle Hyperplasia Normal Airway Reprinted with permission from Solway J et al. CG. N Engl J Med. 2007; 356: 1367 -1369. Asthmatic Airway
Inflammation in Asthma Allergen/Trigger Mast cell T-cell Macrophage Histamine Cytokines Eosinophil Airway Inflammation Ig. E = 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. B-cell Ig. E
Consequences of Persistent Asthma: Progressive Decline in FEV 1 % Predicted 120 100 80 60 40 n = 89 r = -0. 47 P<. 001 20 0 10 20 30 Duration of Asthma (years) FEV 1 = forced expiratory volume in 1 second. Adapted with permission from Brown PJ et al. Thorax. 1984; 39: 131 -136. 40 50
Asthma is. . . 1. Chronic inflammatory disorder of the airways – Mast cells, eosinophils and lymphocytes infiltrate into airway lining – Airway hyperresponsiveness develops 2. Excessive reaction to “minor” irritants results in a host of deleterious airway changes – Bronchial wall edema – Smooth muscle contraction – Excess mucus production 3. Patchy, mostly reversible regions of airway narrowing cause asthma symptoms
Why Do People Get Asthma? • We Don’t Know, Really • Most likely a complex interaction between – Host Factors/Predisposition – Environmental Challenges
Risk Factors for Developing Asthma • • • Genetic predisposition Atopy Airway hyperresponsiveness Gender Race/Ethnicity
Asthma & Airway Inflammation Genetic Risk Factors Environmental (for development of asthma) INFLAMMATION Bronchial Hyperresponsiveness Airflow Obstruction Symptoms Risk Factors (for exacerbations)
Multiple Triggers Can Stimulate Acute 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
Environmental Risk Factors for Development of Asthma • • • Indoor allergens Outdoor allergens Occupational sensitizers Tobacco smoke Air Pollution Respiratory Infections • Parasitic infections • Socioeconomic factors • Family size • Diet and drugs • Obesity • Hygiene hypothesis
Acute Reaction to Triggers 1. Irritated airways become more inflamed after exposure to stimuli 2. Muscle layers around airway constrict 3. Airway lining swells 4. Excess mucus builds up in lumen 5. Result: symptoms of cough, wheeze, shortness of breath, chest tightness
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
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 shortacting beta 2 –agonist
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
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
Measures of Assessment & Monitoring • Spirometry should be performed: – at initial assessment – after treatment is initiated and symptoms and PEFs have stabilized – at least every 1 -2 years to assess maintenance of airway function if well controlled – More often if poor asthma control
Measures of Assessment & Monitoring • Peak Flows may be performed: – In all moderate and severe persistent asthmatics • establish a personal best • useful in exacerbations and maintenance/ changes of therapy, • Can be helpful with ‘poor perceivers’
< 2 Years Old: When Is It Asthma? TWO GROUPS OF INFANTS WHEEZE ASTHMA NOT ASTHMA
< 2 Years Old: When Is It Asthma? Risk Factors for Developing Asthma • Family history of asthma • Atopy, eczema • Perinatal exposure to aeroallergens and irritants (e. g. , passive smoke) • Wheezing triggered by factors other than upper respiratory infections
• Present with symptoms of cough ± noisy or rapid breathing, usually before 5 years of age Adults Children Asthma: Children vs. Adults • Present with symptoms of cough, shortness of breath, chest pain, wheezing, often intermittent or nocturnal
Asthma Misdiagnosis Commonly Misdiagnosed in Children as: Commonly Misdiagnosed in Adults as: CHRONIC/WHEEZY BRONCHITIS RECURRENT CROUP RECURRENT UPPER RESPIRATORY INFECTION RECURRENT PNEUMONIA RECURRENT BRONCHITIS
Asthma Severity Assessments • < 6 year old often cannot perform reliable Pulmonary Function Test’s (PFT’s) or peak flow measurements • Older children with even severe symptoms often have fairly normal PFT’s between episodes • Severity assessment often focuses on symptoms more than lung function measurements • PFTs play more important role in assessment • PFT’s performed at diagnosis and routinely at least every 1 -2 years CHILDREN ADULTS
Long-Term Management of Asthma in Children: Initiation of Control Therapy • Symptoms > 2 x week • Severe exacerbations < 6 weeks apart • 2 or more burst of prednisone in 6 months for ages 0 -4 • 2 or more burst of prednisone in 1 year for ages 5 -11 • Positive Asthma Predictive Index
Asthma Predictive Index In an infant or young child with > 3 episodes of wheezing in the past year 1 of 2 major criteria or 2 minor criteria • MAJOR CRITERIA – Atopic dermatitis – Parental Asthma • MINOR CRITERIA – Wheezing apart from colds – Allergic rhinitis – Blood eosinophilia > ¾ of children with a positive index had some active asthma symptoms between 6 and 13 years of age
Acknowledgements • Rhonda Vosmus, RRT-NPS, AE-C Asthma Education Specialist AH! Program Maine Medical Center • NIH. NAEPP Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma, October 2007.
We will breathe easier when the air in every American community is clean and healthy. We will breathe easier when people are free from the addictive grip of cigarettes and the debilitating effects of lung disease. We will breathe easier when the air in our public spaces and workplaces is clear of secondhand smoke. We will breathe easier when children no longer battle airborne poisons or fear an asthma attack. Until then, we are fighting for air.
- Slides: 39