Adult Asthma- Prager Flashcards
Definition of Asthma
• Chronic inflammatory disease of the airways
• Recurrent episodes of wheezing breathlessness,
chest tightness, and cough
• Reversible airflow obstruction (as opposed to COPD), either spontaneously
or with treatment
• Increased bronchial responsiveness to a variety of
stimuli (“twitchy lungs”
What is the inflammatory mechanism in asthma?
- High concentration of cells not normally in the lungs: eosinophils and lymphocyte infiltration
- Cells normally found in the lung (cytokine secreting mast cells and smooth muscle cells) dysfunction and hyperfunction, more and bigger. Pseudostratified epithelium become disarrayed.
- Noncellular components: basement membrane thickens from collagen deoposition, space between cells becomes edematous.
What is airway remodeling?
Irreversible structural changes in the epithelium, smooth muscle and vasculature causing narrowing. Factors:
- Mucus (pluging)
- Bronchospasm
- Edema
What cells from the bone marrow infiltrate during asthma?
– effector inflammatory cells (eosinophils with cytotoxic granules), which contribute to airway inflammation
– fibrocytes, which contribute to airway remodeling (thicken basement membrane)
Risk factors for developing asthma
Family history
Sensitization to common allergens
Maternal smoking
Obesity
Western lifestyle (antibiotic use, urban environment, diet, sensitization to dust mites and cockroach dust, lack of older siblings, lack of daycare, no TB, measles or Hep A infections)
IgE production in asthma
T-cell activates B-cell into an IgE plasma cell through IL-4 and IL-13. IgE is releast and attaches to mast cells and lymphocytes. Allergen attaches to IgE on mast cells causing mediator release of Histamine, Leukotrienes and Cytokines. Early response: bronchospasm, edema, flow obstruction, late response: airway inflammation, airflow obstruction and hyperresponsiveness.
Role of eosinophils in asthma
Antigens activate mast cells and Th2 cells via dendritic cells (in previously stated mechanism). Mast cells release histamine and leukotrienes and both Th2 cells and mast cells release LK-4, GM-CSF (prolongs eosinophil survival), IL-5. IL-F goes into bone marrow and stimulates eosinopoeisis. Eosinophils travel to capillaries in bronchiole submucosa, transmigrate and cause airway injury from cytokine activation and release of granules.
Asthma triggers
- Antigen exposure
- Respiratory infections
- Vigorous exercise
- Cold air
- Dust
- Roach antigens
- Air pollution
- Cigarette smoke
- Strong odors
- Drugs
- Pets—cats
- Laughing; crying
What is the effect of asthma on pulmonary function tests?
• Reduced FEV1 and FEV1/FVC ratio (obstructive defect)
• Reversible airflow limitation with a significant (>12% or
200ml) increase in FEV1 in response to inhaled
bronchodilator-except in cases of remodeling.
• Increased bronchial responsiveness (Methacholine airway challenge causes FEV1 drop)
– Reduction in expiratory flow due to airway narrowing
– Increase in lung volumes (RV, FRC, TLC) due to air trapping
because of airway narrowing/closure in expiration
pCO2 in asthma
Arterial pCO2<40 mmHg due to alveolar
hyperventilation; then normalization; then in severe cases pCO2 > 40
mmHg due to alveolar hypoventilation due to
respiratory muscle fatigue (indicative of respiratory distress)
Factors for diagnosis of asthma
-Wheezing
– Chronic/tight cough—often disturbing sleep
– Dyspnea/chest tightness
– What triggers symptoms?
– Recurrent respiratory infections
– Atopic—multiple allergies, sinus infections, allergic or
seasonal rhinitis (“hay” or “rose” fever), polyps (contain lymphocytes)
- prolonged expiration
- FEV1/FVC ratio decreased <80%
- improvement with bronchodilator
Signs of increased severity of asthma during office visits
• Nocturnal awakenings from asthma
symptoms
• Days per week with symptoms
• Need for rescue bronchodilators
• Activity limitation because of asthma
• Peak flow variability > 20%
• Frequency of exacerbations/inhaler use, urgent care
visits
National Asthma Education and Prevention Program (NAEPP) Severity classification
• Mild intermittent: symptoms < 2x/week,
nocturnal symptoms < 2x/month, normal FEV1
• Mild persistent: symptoms 3-6x/week, 3-4
awakenings/month, normal FEV1
• Moderate persistent: daily symptoms, >5
nocturnal awakenings, FEV1 60-80%
• Severe persistent: continual symptoms, FEV1 <
60%
Treatment of asthma: Short-Acting Beta-2 agonists
Rescue inhaler
– Immediate but short term relief of
bronchoconstriction
• Short acting: duration of action 3-6 hours
(albuterol)
– Most effective bronchodilators for acute
bronchoconstriction: “rescue medication”
Relaxation of smooth muscle; increase in cyclicAMP by activating adenylate cyclase
• Increased intracellular cyclic AMP increases the
activity of cAMP-dependent protein kinase A
• which inhibits the phosphorylation of myosin
and lowers intracellular calcium concentrations.
• A lowered intracellular calcium concentrations
leads to a smooth muscle relaxation
• Bind to B2
receptors on airway smooth muscle cells
• Side effects are due to overlap B1
activity in other
organs
– Cardiac: tachycardia
– Activation of non-airway B2
receptors in skeletal muscle
causing tremor
• No effect on inflammation
Asthma therapy: Long Acting Beta Agonist
Always combined with a steroid
• Inhaled salmeterol (component of Advair®)and formoterol
(Symbicort®); duration of action 12 hours
• Use of LABA may be associated with increased asthma risk.
• Preferred add-on therapy in patients not adequately controlled on
inhaled corticosteroids (STEROID SPARING).
• Not monotherapy
