- Slides: 38
Asthma: Definition, Pathophysiology & Pathogenesis (1) Ø Asthma is a chronic inflammatory disorder of the airways. Ø The immunohistopathologic features of asthma include inflammatory cell infiltration. Ø Airway inflammation contributes to airway hyperresponsiveness, airflow limitation, respiratory symptoms, and disease chronicity. Ø In some patients, persistent changes in airway structure occur, including sub-basement fibrosis, mucus hyper-secretion, injury to epithelial cells, smooth muscle hypertrophy, and angiogenesis. (remodeling)
Asthma: Definition, Pathophysiology & Pathogenesis (2) Ø Gene-by-environment interactions are important to the expression of asthma. Ø Atopy, the genetic predisposition for the development of an immunoglobulin E (Ig. E)mediated response to common aeroallergens, is the strongest identifiable predisposing factor for developing asthma. Ø Viral respiratory infections are one of the most important causes of asthma exacerbation and may also contribute to the development of asthma.
Pathogenetic Mechanism of Asthma
Diagnosis of Asthma
Symptoms and Signs of Asthma • The cardinal symptoms of asthma : the combination of shortness of breath, wheezing; chest tightness; and cough. • Dyspnea : as an isolated symptom can be attributed to asthma in at least 15% of patients evaluated for this complaint. • asthma has a circadian rhythm – characteristic increase in symptoms (e. g. , cough, dyspnea, and wheezing) during sleep – frequency of nocturnal asthma : key indicator of asthma severity
Physical Examination • Examination of the chest in patients with mild intermittent asthma: typically normal when performed between exacerbations • In more severe disease and during attacks – tachypnea, tachycardia – exaggeration of normal inspiratory fall of systolic blood pressure (pulsus paradoxus) > 10 mm. Hg – hyperinflation of the chest with flattened diaphragmatic excursion, use of accessory muscles of respiration, – hyperresonance of percussion note, prolongation of expiration, – inspiratory and expiratory musical-sonorous rhonchi and wheezes heard on auscultation • Absence of wheezing on auscultation – does not always mean lack of airway obstruction – patients with very severe obstruction may have minimal airflow
Laboratory Diagnosis of Asthma (1) • Pulmonary Function Tests: establish the diagnosis of asthma, to quantify the severity of the disease, and to monitor the course of the disease and response to therapy. – Spirometry – Bronchoprovocation- Nonspecific Airway Hyperresponsiveness • Spirometry – Low FEV 1, Low FEV 1/FVC ( < 0. 75 -0. 8 ) – Bronchodilator response(+): inc FEV 1( >12% or 200 ml) • Bronchoprovocation • Methacholine: PC 20 FEV 1 < 16 mg/dl
Laboratory Diagnosis of Asthma (2) • Pulse oximetry and arterial blood gas (ABG) measurements. • Self-monitoring by serial measurements and recordings of PEFRs (peak expiratory flow rates) – performed by the patient using a peak flow meter – provide insights into perceptions of airways obstruction; course of disease, including severity, response to therapy, and prediction and detection of exacerbation; and the identification of environmental precipitants of asthma
Typical Spirometric (FEV 1) Tracings Volume FEV 1 Normal Subject Asthmatic (After Bronchodilator) Asthmatic (Before Bronchodilator) 1 2 3 Time (sec) Note: Each FEV 1 curve represents the highest of three repeat measurements 4 5
FV curve Pre-&post-BD
Bronchoprovocation: Methacholine challenge test Normal BHR (+)
Mini-Wright Peak Flow Meter
A Simple Index of PEF Variation Highest PEF (670) PEF (L/min) 800 700 600 500 Lowest PEF (600) Morning PEF Evening PEF 400 300 0 7 Days 14 PEFR variability: (Highest-Lowest PEFR)/ (Higest + Lowest) x ½ e. g. (670 -600) / (670+600) x ½ = 11%
Laboratory Diagnosis of Asthma • Tests for Ig. E Antibodies/ serum total Ig. E concentration • Peripheral blood eosinophil count • Microscopic examination of induced sputum or "wet preps" from patients with asthma – bronchial epithelial cells in clusters (Creola bodies) – eosinophils, Charcot-Leyden crystals – Curschmann's spirals of mucinous material of varying sizes from small airways • Chest radiographs – increased residual air manifested by overexpansion of the lungs with an increase of anteroposterior (AP) dimension, increase in retrosternal lucency, flattening of the diaphragm • Chest CT/High-resolution computed tomography (HRCT) : more sensitive for detecting subtle airways changes, such as early bronchiectasis, pulmonary fibrosis, and emphysema
Acute asthma: chest X-ray
Mucus Plug in Bronchial Asthma One of the response of the bronchiole in asthma is the metaplastic proliferation of goblet or mucus-producing cells. Often, this results in the over-production of mucus, which plugs otherwise severely broncho-constricted bronchioles. One sometimes sees eosinophils within the mucus, occasionally with crystallized eosinophilic granules (Charcot-Leyden crystals).
Curschmann's spiral in sputum from asthma patient • CURSCHMANN'S SPIRAL - Spiral shaped mucous plug. Seen in asthma patients and patients with COPD.
CHARCOT LEYDEN CRYSTALS, MICRO - Eosinophilic needleshaped crystalline structures. Represents breakdown products of eosinophils. Seen in asthma and eosinophilic pneumonia.
Differential Diagnosis of Asthma • • Chronic Obstructive Pulmonary Disease (COPD) Cardiac Asthma Pulmonary Embolism Eosinophilic Lung Disease Carcinoid Tumor, carcinoid syndrome Mastocytosis In children – Viral bronchiolitis – Anatomic anomalies: vascular ring, T-E fistula, Rt. side aortic arch – Laryngomalacia – Gastroesophageal reflux disease (GERD) – Pneumonia – Pulmonary edema – Foreign body aspiration – Vocal cord dysfunction (VCD)
Treatment of Asthma
Key Points – Asthma Control (Goals of Therapy) Reducing impairment – Prevent chronic & troublesome symptoms. – Prevent frequent use (< 2 days /wk) of inhaled SABA for symptoms. – Maintain (near) “normal” pulmonary function. – Maintain normal activity levels (including exercise & other physical activity & attendance at work or school). – Meet patients’ and families’ expectations of and satisfaction with asthma care. EPR- 3, p. 50
Key Points – Asthma Control (Goals of Therapy) Reducing Risk – Prevent recurrent exacerbations of asthma and minimize the need for ER visits and hospitalizations. – Prevent progressive loss of lung function - for children, prevent reduced lung growth. Ø Ø Ø – Provide optimal pharmacotherapy with minimal or no adverse effects. Periodic assessments at 1 -6 month intervals. Patient self-assessment (w/clinician). Spirometry testing. NAEPP 2007 guidelines, sec. 3, p. 53
Asthma Control = Asthma Goals Ø Ø Definition of asthma control is the same as asthma goals reducing impairment and risk. Monitoring quality of life, any: – work or school missed because of asthma? – reduction in usual activities? – disturbances in sleep due to asthma? – Change in caregivers activities due to a child's asthma?
Assessing Asthma Control In Youths 12 Years of Age & Adults
NOT Currently Taking Controllers
Classifying Severity AFTER Control is Achieved – All Ages Classification of Asthma Severity Lowest level of treatment required to maintain control Intermittent Step 1 Persistent Mild Moderate Severe Step 2 Step 3 or 4 Step 5 or 6 (already on controller)
Key Points - Medications Ø Controller medications: – Corticosteroids – Long Acting Beta Agonists (LABA’s) – Leukotriene modifiers (LTRA) – Cromolyn & Nedocromil Ø Methylxanthines: (Sustained-release theophylline) Ø Quick- relief medications – Short acting bronchodilators (SABA’s) – Systemic corticosteroids – Anticholinergics
Stepwise Approach for Managing Asthma in Youths >12 Years of Age & Adu Intermittent Asthma Persistent Asthma: Daily Medication Consult asthma specialist if step 4 care or higher is required. Consider consultation at step 3 Step 5 Step 4 Step 3 Preferred: Step 1 Low dose ICS Low-dose ICS + LABA OR – Medium dose ICS Preferred: SABA PRN Alternative: Cromolyn, LTRA, Nedocromil or Theophylline Alternative: Low -dose ICS + either LTRA, Theophylline, or Zileuton Step 2 Preferred: Preferred High Dose ICS + Preferred: Medium Dose ICS + LABA Alternative: Mediumdose ICS + either LTRA, Theophylline , or Zileuton LABA AND Consider Omalizumab for patients who have allergies Step 6 Step up if needed Preferred (first check adherence, environment al control & comorbid conditions) High dose ICS + LABA + oral corticosteroid AND Consider Omalizumab for patients who have allergies Assess control Step down if possible (and asthma is well controlled at least 3 months) Each Step: Patient Education and Environmental Control and management of comorbidities Steps 2 – 4: Consider subcutaneous allergen immunotherapy for patients who have allergic asthma • Quick-relief medication for ALL patients -SABA as needed for symptoms: up to 3 tx @ 20 minute intervals prn. Short course of o systemic corticosteroids may be needed. • Use of SABA >2 days a week for symptom relief (not prevention of EIB) generally indicates inadequate control & the need to step up treatment.