Asthma Flashcards
Describe the epidemiology of asthma.
- Affects 5% of population
- Onset usually from 5 to 25 years
- Allergy is key risk factor
- Has increased prevalence over past 3-4 decades, mainly in industrialized countries
- More than 4,000 deaths/year despite availability of effective therapy
List the components of asthma
Airway obstruction
Airway hyper-responsiveness
Airway inflammation
Airway remodeling
Airway obstruction in asthma
o Reduced expiratory flows (low FEV1/FVC, PEFR, FFE25-75)
o Increased airway resistance
o Typically reversible obstruction:
• 12% increase in FEV1 in response to inhaled bronchodilator
• Reversibility may not always result in normal lung function
o Airway obstruction may be absent between attacks
Airway hyper-responsiveness in asthma
o Bronchoconstricting agents → increased airway obstruction o In almost all asthma patients o Also seen in other conditions (hay fever, smoking, bronchitis, influenza) but most severe in asthma Can be induced: • Cold air • Exercise • Histamine • Meathacholine
Airway inflammation in asthma
o Almost universal in asthma o Leukocyte infiltration o Cell activation (eosinophils, T lymphocytes, mast cells) o Damage to airway epithelium o Exposed or denuded basement membrane o Increased mucous secretions o May lead to airway remodeling
Airway remodeling in asthma
o Structural airway changes in asthma
Includes: • Subepithelial fibrosis • Increased smooth muscle mass • New vessel formation • Mucous gland hyperplasia Can cause airway obstruction, lack of reversibility, disease progression and morbidity
Causes of airway narrowing • Contraction of smooth muscle • Cellular debris and mucous in lumen • Edema of airway wall • Remodeling: • Hypertrophy/hyperplasia of smooth muscle • Subepithelial fibrosis
Describe the factors that provoke an asthmatic attack
Allergic reactions
o Cause acute airway obstruction; followed by late phase response
o Late response associated with increased airway inflammation
o Allergies provoking asthma: animal dander, house dust mites, molds, pollens
Infection
o Primarily from viruses: rhinovirus, influenza, respiratory syncytial virus
Mechanisms:
• Stimulate IgE production
• Damage airway epithelium
• Enhance allergic reaction
• Alter ANS function to promote inflammation or bronchospasm
o Heightened airway responsiveness follows viral infection and can persist for several weeks
Exercise
o Triggers bronchospasms
o Spontaneously resolves within 15-30 minutes
Medications
Occupational
o Asthma caused by workplace exposure
o Symptoms typically start after a period of exposure (sensitization)
o Patients may feel better during work absences
o Worse on return to work (Mondays)
o Can be allergic in nature or irritants
o Symptoms similar to asthma
o Spirometry can be normal
• BUT: often have positive methacholine test
o Treat:
• Asthma medications
• Identifying offending agent
• Avoid further exposure
Nocturnal (sleep-related)
o Asthma often worsens during sleep
o Usually have increased symptoms around 4 am
Illustrate how to make a diagnosis of asthma.
History
o Episodic symptoms of cough, wheezing, dyspnea
o Often with known triggers
o Family history of asthma, allergy, eczema
o Associated conditions: hay fever, atopic dermatitis, sinusitis
Exam
Typically normal between attacks
During severe attacks:
• Wheezing
• Tachypnea
• Use of accessory muscles
• Silent chest sounds with severe hyperinflation
Pulsus paradoxus
• An exaggerated (> 10 mmHg) variation in systolic BP during respiratory cycle
• Seen in several conditions (ex: cardiac tamponade, shock, acute severe asthma)
• Normally: BP declines during inspiration; increases during expiration
• In asthma = caused by more negative intrathoracic pressure during inspiration → increased lung volume and pulmonary vascular resistance = increases RV afterload
• Increased RV preload by boosting blood return to RV → over distends RV → shifts intra ventricular septum to left
• Result: exaggerated decreased in LV stroke volume during inspiration → lower BP
Confirm diagnosis Pulmonary functions • Airflow limitation (low FEV1/FVC) • Increased airway resistance • Reversible with inhaled beta agonists • Hyperresponsiveness (methacholine) • Low PPV (because other conditions can cause positive test) • High NPV
Laboratory
• Increased eosinophils (sputum, blood)
• IgE sensitivity
• Positive skin test or increased blood levels of total IgE
Additional tests may be necessary to rule out other conditions
Discuss the principles of management of asthma
Goals:
o Prevent attacks
o Control attacks
o Normalize pulmonary function
Bronchodilators Beta-agonists • Drug of choice for treating acute asthma and preventing airway obstruction • Short-acting = albuterol, pirbuterol • Long-acting = salmeterol, formeterol Anti-cholinergics • Short-acting = ipratropium • Long-acting = tiotropium Theophylline
Anti-inflammatory
Should be used for long term asthma control Corticosteroids
• Most effective anti-inflammatory agents for asthma therapy
Cromolyn sodium
• Modest effects
Anti-Leukotrienes
o Receptor blockers = zafirlukast, montelukast
o Synthesis inhibitors = zileoton
o Have both anti-inflammatory and bronchodilator effects
Anti-IgE monoclonal Ab (Omalizumab)
o Binds to circulating IgE = prevents mast cell attachment
o Reduces response to allergies and frequency of asthma attacks
Environmental controls
o Allergen avoidance
o Not easy to implement
Treat associated conditions
Patient education
o Lifelong disease
Identify the basic gross and microscopic pathologic changes seen in asthma
Gross findings:
• Mucus plugs
• Over inflation of bronchioles
Histologic findings
• Mucous plugs in bronchi and bronchioles
• Mucous infiltrated with eosinophils and Charcot-Leyden crystals
• Desquamation of bronchial epithelium
• Goblet cell metaplasia
• May have squamous metaplasia
• Thickened airway due to edema
• Increased number of smooth muscle cells
• Increased size of submucosal mucous glands
• Thickened epithelial basement membrane
• Airways infiltrated with eosinophils
Describe the spirometric pattern of asthma
Airway obstruction
• Reduced expiratory flows (low FEV1/FVC, PEFR, FFE25-75)
• Increased airway resistance
Typically reversible obstruction
• 12% increase in FEV1 in response to inhaled bronchodilator
• Reversibility may not always result in normal lung function
• Airway obstruction my be absent between attacks
Explain the abnormalities in FRC, RV, and TLC that characterize asthma
Lung volumes:
Typically no change in mild asthma
• Increased RV in more severe or acute disease
• From premature airway closure
Usually normal FRC and TLC
• More severe asthma = loss of lung elastic recoil may occur –> increased TLC
Describe the causes of hypoxia in asthma
o Airway obstruction → decreased ventilation relative to perfusion (low V/Q) → low PaO2
o During asthma attacks = patients hyperventilate due to anxiety and hypoxemia → low PaCO2
Describe the evolution of arterial blood gases during an attack of asthma as it progresses from mild to moderate to severe airways obstruction.
With increasing attack severity:
- -Decreasing PaO2
- -PaCO2 low (due to hyperventilation) until severe/very severe attack (lost ability to compensate via hyperventilation)
- -HCO3- normal until very severe attack (due to lactic acid generated)
- -pH increased until very severe attack = decreased
Define cor pulmonale
o Increased pulmonary vascular resistance → pulmonary HT
o Result: RV hypertrophy or failure
Occurs in COPD and CF
