Asthma Flashcards
Asthma
Definition
Chronic inflammatory disorder of the airways.
- Many cells and cellular elements involved
- Airway hyper-responsiveness
- Caused by reversible generalized narrowing of the airways
- Periodic ↑ contraction of airway smooth muscle and hypersecretion of bronchial mucus in response to internal or external stimuli
Asthma
Epidemiology
- 24 million people in USA
-
Most common chronic childhood disease ⇒ ~ 5 million kids
- Boys > Girls
- Women > men (over age 40)
- Prevalence rate ↑ 1%/yr
- Mortality rates ↑ in late-half of 20th century
- Highest risk population ⇒ urban minorities living in poverty areas
Asthma
Risk Factors
- Genetics
-
Atopy ⇒ genetic tendency to develop allergic diseases
- Typically associated with heightened immune responses to common allergens, especially inhaled and food allergens
-
Atopy ⇒ genetic tendency to develop allergic diseases
- Environmental cigarette smoke exposure
- House dust mite exposure
- Cockroach allergen
- RSV infection
Asthma
Bronchial Changes
Bronchial Wall
Comparison
Asthma
Histological Changes
- Thickened basement membrane
- Edema
- Inflammatory infiltrates
- Prominence of eosinophils in bronchial wall and sputum
- Hypertrophy of bronchial wall smooth muscle
- Mucus gland proliferation
Asthmatic Sputum
Sputum can include:
- Curshmann spirals ⇒ dried out mucus
- Charcot Leyden crystals ⇒ eosiniphil breakdown product
- Bronchial casts
Mucus Histology
Airway Inflammation
Causes obstructive lung disease by four mechanisms:
- Acute bronchoconstriction
- Swelling and edema of the airway walls
- Airway remodeling
- Mucus plug formation
Asthma Phenotyping
- Asthma is not one disease
- Several pathologic phenotypes lead to same sx manifestations
- Characterizing phenotype ⇒ more customized asthma threatment
- Increasing importance w/ new biologic treatments
Airway
Hyper-responsiveness
Exposure to specific and nonspecific irritants cause airways to become narrow and obstructed.
Level of airway responsiveness correlates with severity of disease.
Airway
Inflammation
-
Asthmatics usually have increased leukocytes
- Activated eosinophils
- Mast Cells
- MΦ
- T-cells
- Cells may be present when pt clinically asymptomatic
- E/O asthma phenotypes with similar disease manifestations
- Many inflammatory mediators involved
Allergic Asthma
Asthma exacerbation precipitated by exposure to allergens in many patients.
Atopic mechanism.
Binding of Ag to cell-bound IgE stimulates mediator release from mast cells, MΦ, and basophils.
Preformed vs non-preformed mediators.
Preformed Mediators
-
Histamine and serotonin
- Bronchoconstriction, swelling, edema
-
Proteolytic enzymes and histamine
- Disrupt or destroy pulmonary lining
- Allows fluid to leak in
- Leads to swelling, edema, obstruction
- Removes barrier to inhaled irritants
- Easier to trigger another attack
- Allows fluid to leak in
- Disrupt or destroy pulmonary lining
Non-preformed Mediators
Formed at time of activation from arachidonic acid.
-
Lipoxygenase products
-
Leukotriene B4
- Chemoattractant for inflammatory cells
-
Leukotriene C4
- Bronchoconstriction
-
Leukotriene D4
- Bronchoconstriction
-
Leukotriene B4
-
Cycooxygenase products
-
Prostaglandin D2
- Potent bronchoconstrictor
-
Prostaglandin D2
Non-allergic Asthma
Airway epithelial cells can respond to injury or irritants by releasing cytokines.
GM-CSF ⇒ stimulate eosinophils and mast cells
Neutrophilic Asthma
Some asthmatics have a predominantly Th1 type inflammation ⇒ neutrophils
- High levels of PMNs can be found in pts with severe asthma or during acute exacerbations
- Correlated with lower FEV1
-
Do not respond as well to therapy
- Corticosteroids do not reduce PMNs
- Most therapy targeted at eosinophils
- Linked to fatal asthma
Bronchoconstriction
Caused by contraction of circular smooth muscle within bronchial walls.
-
Bronchoconstriction
- Inflammatory mediators
- PNS ⇒ irritant or cold air may trigger a parasympathetic vagal reflex ⇒ constriction
-
Bronchodilation
-
SNS
- NE/Epi ⇒ cAMP ⇒ relaxation
-
Non-adrenergic, non-cholineric inhibitor nerves
- Releases NO ⇒ potent bronchodilator
-
SNS
Mucus Plugs
- Produced by glands located below epithelial lining
-
Asthma ⇒ ↑ production
- Inflammatory mediators
- PNS stimulation
- Can plug up airways causing further narrowing
Airway Remodeling
- Inflammation & cytokines (TGF-β) ⇒ myofibroblast activation
- Myofibroblasts ⇒ collagen and fibronectin production
-
Results in airway remodeling ⇒ fixed obstruction
- Not reversed by bronchodilators
- Leads to residual obstructive lung disease despite max therapy
Asthma
Etiologies
- Environmental
- Viral infection
- Sinusitis
- Exercise induced
- GERD ⇒ vagal response
- ASA induced
- Sampter’s triad: a chronic condition defined by asthma, sinus inflammation with recurring nasal polyps, and aspirin sensitivity
- Obesity
- Occupational
- Farmers ⇒ dust, hay, chemicals
- Painters ⇒ isocyanite asthma
- Cleaners ⇒ household products
Aggrevating Factors
Asthma
Presentation
- Any age group
- 75% dx prior to age 7
- Some show remission during adolescence
- Recurrent episodes
- Wheezing
- Breathlessness
- Chest tightness/pain
- Coughing
- Sputum production
- Particularly at night or early morning
- Widespread and variable airflow obstruction
- Often reversible either spontaneously or with treatment
Asthma
Clinical Work-Up
- H&P
- PFTs
- FENO
- Bronchoprovocation testing
- Peak flow monitoring
- CBC and sputum for eosinophils
- CXR
Asthmatic History
- Recurrent episodes of cough, wheezing, or SOB
- Return of function between episodes
- Atopic history?
- Family history?
- Symptoms triggered by usual asthma triggers
- Exercise, allergens, airborne irritants, seasonal changes, after illness
Conditions That Mimic Asthma
Physical Findings
Varies with intensity of asthma.
May have no signs between attacks.
- Asthma exacerbations
- Tachycardia
- Tachypnea
- Fragmented speech
- Accessory muscle use
- Diaphoresis
- Mild asthmatics
- Persistent cough
- ± Wheezing
- Severe asthmatics
- Quiet chest ⇒ no wheezing and minmal breath sounds; implies minimal air flow
- ± Larger chest volume ⇒ hyperinflation d/t air trapping
Asthmatic
Pulmonary Function Tests
-
Spirometry
- Obstructive lung disease
- FEV-1% < 70% or lower limit of normal
- May be normal between attacks
- Improvement after trial of bronchodilator therapy
- Obstructive lung disease
-
Peak flow meters
- Measures initial flow rate with forced expiratory effort
- Absolute reduction in peak flow
- Variability in peak flow of more than 20%
Bronchodilator Response
Defined as:
12% improvement in FEV-1 & at least 200 cc improvement
or
12% improvement in FVC & at least 200 cc improvement
or
30% improvement in FEF 25-75%
Peak Flow Meters
- May be 1st sign of worsening asthma
- Have pt do 3 times and take their best number
- Pt should know their “personal best”
-
Clinical relavence
- Used with asthma action plan to improve health outcomes
- Triage severity of asthma exacerbation
- Used to determine triggers
FeNO
-
Marker of eosinophilic inflammation of the lungs
- Measures exhaled NO
- Levels decrease with inhaled corticosteroids (ICS)
- Can be used to assess compliance and predict exacerbations
- Clinically practical
Bronchial Provocation Testing
Inhaling an agent that provokes an asthmatic response to establish diagnosis.
- Non-specific agents
- Methacholine
- Mannitol
- Histamine
- Cold air challenge
- Exercise challenge
- Inhaled antigens
- 20% drop in FEV-1 is significant
- Excellent negative predictive value
CXR
- Usually done during preliminary evaluation
- Typically normal
- Asthmatic CXR
- Hyperinflation ⇒ see more ribs
- Flattening of diaphragm
Asthma
Evaluation
- Assess severity ⇒ intermittent or persistent; mild, moderate, or severe
- Assess likelihood for exacerbation in the future
-
Assess for degree of asthma control using a standard metric
- E.g. Asthma Control Test
Asthma
Severity
Warrants daily therapy if experiencing sx:
> 2 days per week
> 2 nights per month
Asthma Control
Asthma Control Test
5 questions
Score ≤ 19 means poorly controlled
Asthma Therapy
Goals
Outlined by NAEPP and GINA:
- Achieve and maintain symptom control
- Prevent exacerbations
- Maintain pulmonary function as close to normal as possible
- Maintain normal activity levels, including exercise
- Avoid adverse effects of asthma medications
- Prevent development of irreversible airflow obstruction
- Prevent asthma mortality
Asthma Therapy
Components
Recommendations based on severity, control, and responsiveness.
Includes:
-
Patient education
-
Asthma Action Plan
- How to monitor asthma on a daily basis
- What to do if they have an exacerbation
-
Avoidance of asthma triggers
- Allergens, irritants, respiratory viruses
-
Asthma Action Plan
-
Pharmacotherapy
- Stepwise management ⇒ goal to limit sx or rescue inhaler use < 2 days/wk or 2 nights/month
- Immunotherapy when appropriate
Pharmacotherapy
Patient Education
Provide patients with the info needed to self-manage their own asthma in conjunction with physician guidance.
-
Knowledge of avoidance measures
- Active & passive smoking
- Beta-blockers
- In patients who are sensitive:
- ASA and NSAIDS
- Occupational agents
- Dust mites
- Other common allergens
- Foods and additives
-
Knowledge of treatment modalities
- Diagnosis
- Rescue inhalers vs controllers
- Inhaler use training
- Advice regarding prevention
- Signs that might suggest asthma is worsening and actions to take
- Training in monitoring asthma
- How and when to seek medical attention
- Written self-management plan
Asthma
Management
- Intermittent
- SABA only
- Persistent
- Inhaled corticosteroids
- Add LABA
- Consider LTRA
- Biologics for appropriate patients
- Consider LAMA
Acute Exacerbation
Management
-
Short-acting β-agonists
- Albuterol ⇒ intermittent neb, continuous neb, MDI
- MDI equivalent to nebulizers if proper technique used
- Albuterol ⇒ intermittent neb, continuous neb, MDI
-
Inhaled anticholinergic
- Ipratropium bromide (Atrovent)
- May be given with albuterol with additive effects (Duoneb)
-
Steroids
- Prednisone, methylprednisolone, or prednisolone
- PO or IV based on severity
- Dose: 40-80 mg/day until PEF reaches 70% of predicted or personal best
- Higher doses do not appear to offer added benefit
-
Adjunctive treatments
- Oxygen if hypoxic
- Goal: O2 sat ≥ 90% if not pregnant, ≥ 95% if pregnant
- Magnesium ⇒ 2g IV over 20 minutes
- Heliox: 70/30 mixture
- Low viscosity gas ↓ WOB
- May prevent intubation in severe asthmatics
- CPAP/BiPAP
- ↓ WOB and may prevent intubation
- Oxygen if hypoxic
Indications for Intubation
Clinical judgement based on:
- Rising or normal pCO2
- Progressive deterioration despite aggressive treatment
- Deteriorating mental status
- Refractory hypoxia
- Hemodynamic instability
Asthma
Summary
- Common disease
- Diagnosis based on history and findings suggestive of inflammation and airway contriction
- Treatment geared towards bronchodilation and decreasing inflammation
