Asthma Flashcards
What are obstructive lung diseases?
Lung disorders characterized by impaired airflow caused by an airway obstruction (partial or complete) at any level from the trachea to the bronchioles.
Includes:
1. asthma
2. COPD (emphysema and/or chronic bronchitis)
3. cystic fibrosis (also restrictive)
What are the 4 mechanisms of airway obstruction?
- increased thickness of airway walls.
- Airway occlusion
- Loss of elastic fibres
- bronchoconstriction
What are the effects of airway obstructive lung disease on ventilation?
During inhalation the airways are pulled open and air rushes past the obstruction.
During exhalation obstructed airways collapse before exhalation is complete (can’t get the air out).
- trapped air makes it difficult to take another breath
- increased work of breathing = accessory muscles are required
- air trapping causes lung hyperinflation
What is FVC (forced vital capacity)?
Part of a pulmonary function test that measures the volume forcibly exhaled after a full inhalation.
What is FEV1 (forced expiratory volume in 1 second)?
Part of a pulmonary function test that measures volume forcibly exhaled within 1 second.
How is spirometry measured?
Expressed as a ratio (FEV1/FVC) or FEV1 as a percentage of a predicted value.
What is asthma?
Chronic inflammatory disease of airways characterized by airway hyperresponsiveness (exaggerated tendancy to narrow in response to various triggers) resulting in airflow limitation.
Asthma mainly affects which part of the lungs?
Bronchioles and small bronchi. The more airway inflammation present the more hyperresponsive the airways.
What is the clinical presentation of asthma?
- variability of frequency, severity and triggers
- recurrent episodes of wheezing, chest tightness, cough an dyspnea
- airflow limitation is at least partially reversible (spontaneously or with treatment)
- treatment goals involve reducing the frequency of asthma episodes and severity of symptoms.
- poorly managed asthma results in airway remodeling (= permanent thickening of airway walls) and chronic obstruction
Describe the etiology of asthma.
Genetic and environmental factors are proposed to play a role in the underlying airway inflammation and hyperresponsiveness.
- genetic predispostion (> 100 genes identified in genome-wide studies associated with asthma)
What are some proposed environmental factors across the lifespan that cause asthma?
- prenatal/perinatal: exposure to maternal smoking, maternal vitD deficiency, prematurity, c-section delivery
- childhood: exposure to allergens, microbiome dysbiosis (early abx exposure), childhood respiratory infections (RSV), exposure to air pollution and tobacco smoke
- adolescence/adult: exposure to chlorinated pools, active smoking, occupational exposures.
What is the difference between allergic and non-allergic asthma?
- Allergic (atopic) = initiated by exposure to an allergen.
- non-allergic (non-atopic) = initiated by exposure to an airway irritant
Many asthmatics have a combination of both.
Which kind of asthma accounts for most cases of childhood onset asthma?
Allergic asthma.
Describe the genetic component to allergic asthma.
Individuals with allergic (atopic) asthma have a genetic predisposition to develop IgE in response to allergens (=atopy)
What other atopic disorders are often present with allergic asthma?
- eczema, food allergies, allergic rhinitis
- tend to present with eczema from birth, food allergies around 1-2 years, rhinitis around 3 years and asthma around 7 years
Describe the bodies initial immune response in allergic asthma.
With initial exposure to allergen:
- an abnormal immune response = large amounts of allergen specific-IgE in those genetically predisposed
- response involves an imbalance between Th1 and Th2 production (favouring Th2 cells and activation of B cells)
- IgE that isn’t exposed to the allergen, binds to airway mast cells = airway sensitization
Describe the bodies subsequent response to an allergen in allergic asthma.
- The allergen cross-links IgE molecules bound to mast cells of sensitized airways
- Mast cell activation & degranulation cause the early phase of an acute asthma attack.
What are triggers for non-allergic asthma?
Viral respiratory infections and exposure to bronchial irritants
What percentage of asthmatics does non-allergic asthma account for?
30%
When in the lifetime does non-allergic asthma typically evolve?
Adulthood
How do respiratory infections lead to non-allergic asthma?
- viral infections harm the epithelium, causing airway inflammation
- increases airway sensitivity, including to other triggers
What is exercise-induced bronchoconstriction?
Loss of heat and water from airways causes irritation and inflammation (worse in cool, dry weather)
Attacks often occur when exercise stops and airways are less dilated (within 3 mins)
Tend to resolve within 60 mins
How do aspirin, NSAIDs cause to non-allergic asthma?
- block the COX enzyme and PG synthesis and a relative increase in leukotrines = bronchoconstriction
- attacks occur within minutes to hours (up to 12 hours) of ingestion
How do inhaled irritants cause non-allergic asthma?
- cigarette smoke, air pollutants, strong odours = stimulate irritant receptors in airway walls causing reflex bronchoconstriction
What happens in the acute asthmatic response phase?
- allergens activate mast cells and Th2 cells within airway walls
- mast cell activation = release of preformed inflammatory mediators such as histamine and chemotactic factors
- Th2 cells produce cytokines that contribute to B cell activation and IgE synthesis
Airway changes:
- bronchoconstriction
- airway swelling (edema)
- mucous production
How does a bronchodilater work?
relaxes bronchial smooth muscle and typically increases airflow within 5 mins
What happens in the late asthmatic response?
- the effects of slower acting cytokines, prostaglandins, and leukotrines
- epithelial injury by recruited eosinophils
- the activation of parasympathetic reflexes
What the slower acting prostaglandins and leukotrines do in asthma?
Contribute to inflammation, bronchoconstriction, and mucus production.
What role to eosinophils play in asthma?
Eosinophils are recruited by chemotactic factors released by Th2 cells (IL-5) and mast cells.
They release damaging proteins (e.g. major basic protein)
- normally toxic to parasites
- cause airway epithelial damage (along with tryptase from mast cells) and inflammation
What are creola bodies?
Shed epithelial cells found in the sputum of symptomatic asthmatics.
Describe the activation of parasympathetic reflexes in late asthmatic response?
Epithelial damage exposes subendothelial sensory nerve endings.
- activates the parasympathetic (vagal) reflexes causing further bronchoconstriction and mucus secretion
What are the effects of partial obstruction on lung function?
- air trapping and hyperinflation
- increased work of breathing
What are the effects of total obstruction of airways?
- obstructive atelectasis = collapse of alveoli
What is airway remodelling?
Occurs with frequent asthma attacks and persistent inflammation and is irreversible.
- epithelial cell damage stimulates collagen deposition and subepithelial fibrosis
- airway smooth muscle layer thickens
Why do attacks occur at night or upon waking?
- muscle relax during sleep and tend to narrow
- reclining position causes secretions to accumulate
- low epinephrine (especially at 4am) which normally causes bronchodilation
Describe 6 steps in diagnosing asthma.
- patient history
- physical exam
- spirometry (pre and post bronchodilator), peak flow monitoring (PFM), methacholine challenge
- lab tests (CBC (elevated eosinophils, serum IgE)
- chest x-ray (r/o other causes, may show lung hyperinflation during an attack)
- allergy testing
What do FEV1 and FVC stand for in spirometry?
FEV1 = forced expiratory volume in 1 second, or the amount of air you can exhale in the first second after a deep breath.
FVC = Forced vital capacity, or the total amount of air you can exhale forcefully in one breath
Describe 4 steps to manage asthma.
- Prevention:
- removal of triggers (#1 preventative measure)
- vaccinations - Develop an asthma action plan/ regular follow up care
- educate patient on how to self-manage worsening symptoms and when to seek medical help - Quick relief of acute attacks e.g. short-acting beta-2 agonist (SABAs) or budesonide/formeterol (symbicort)
- goal is to minimize use (>2 uses/week is a sign of poorly controlled asthma) - Long-term management (controller meds)
- used on a regular basis
- treat underlying inflammation, maintain asthma control, and prevent attacks
- e.g. inhaled corticosteroids, long-acting beta-2 agonists (LABAs), leukotrine receptor antagonists.
What is ‘good control’ of asthma defined as?
- daytime asthma symptoms < or equal to 2 days/week and no nighttime symptoms
- little to no need for reliever meds (< or equal to 2 days/week)
- no limitations to physical activity or absence from school/work
- normal or near normal lung function
