adult asthma Flashcards
A heterogenous disease usually characterized by chronic airway inflammation
Asthma
Defined by history symptoms (wheezing, shortness of breath, chest tightness, and cough) that vary over time and in intensity together with variable expiratory airflow limitation
Asthma
Peak of age for asthma
3 years old
Airway narrows easily and too much in response to stimuli
Bronchial hyperresponsiveness
Major risk factor of asthma
Atopy
Factors that influence Asthma Development and Expression
Endogenous Factors
Environmental Factors
Hygiene hypothesis
Lack of early childhood exposure to infectious agents, symbiotic microbes and parasites increases susceptibility to allergic diseases
Preservation of TH2
Top 3 inddor allergens
House dust mite, cockroaches, animal allergens
Most common trigger of acute severe exacerbations
Upper respiratory tract viral infections
RSV rhinovirus, coronavirus
Drugs known to trigger asthma attacks
aspirin, beta blockers, coloring agents
Asthma pathogenesis
Sensitizers -> chronic inflammation (eosinophilic bronchitis) ->cough, dyspnea, wheezing
Th2 cytokines
IL-4, IL-5, IL-13: mediate allergic airway inflammation
Proinflammatory response in more severe asthma
TNF-a , IL-1B
Eosinophils are attracted by chemokine called_____ and is secreted by epithelial cells
Eotaxin
Cells that induces bronchospam
Mast cells
APC present allergens to T lymphocytes
dendritic cells
Airflow limitation in Asthma
Acute bronchospam
Swelling of the airway wall
Chronic Mucus plug formation
Airway remodeling
Gross pathology in asthma
Very red mucous
Distinct histological features of an asthmatic airway
Denuded mucosa/epithelial denudation Thickened BM/subepithelial fibrosis Wall/mucosa edema Hypertrophied and hyperplastic cells Inflammatory cells
Lung parenchyma become hyperinflated due to air trapping
Fatal hyperinflation
Main effect of fatal hyperinflation
Increase in carbon dioxide
Hyperinflation leads to:
Hypoventilation Respiratory acidosis Pneumothorax Hypotension Respiratory Failure
Airway Remodeling Components
Chronic epithelial injury Subepithelial fibrosis Smooth muscle hyperplasia Goblet cell hyperplasia Angiogenesis mucus gland hypertrophy
Airway smooth muscle mass is related to disease severity
Smooth muscle mass is higher in severe than in moderate or mild
Increased probability that symptoms are due to asthma if:
> 1 type of symptoms (Wheeze, shortness of breath, cough, chest tightness)
Often worse at night or in the early morning
Vary over time and in intensity
Often with identifiable triggers
Decreased probability that symptoms are due to asthma
Isolated cough with no other RS Chronic production of sputum Shortness of breath associated with diziness, lightedheadedness or peripheral tingling Chest pain Exercise-induced dyspnea
Wheezing may be absent during severe asthma
Silent Chest
Variable Airflow Limitation in asthma
Low FEV1 and low FEV1/FVC
Positive bronchodilator reversibility test
Normal FEV1/FVC ratio
> 75-80% in healthy adults
>90% in children
Positive bronchodilator reversibility test
Adults: increase in FEV1 >12% and >200mL from baseline, 10-15 mins after 200-400 mcg of albuterol or equivalent
Children: increase >12% predicted
Confirm variation in lung function
Excessive diurnal PED variability over 2 weeks of monitoring:
>10% in adults
>13% in children
Significant increase in FEV1 (>12% +>200ml) or PEF (>20%) after 4 weeks of controller treatment
Positive exercise challenge test
Positive bronchoprovocation test
Important biomarkers of TH2-driven aiway inflammation and potential predictors of airway eosinophilia and steroid response
Serum Periostin and FeNO
Endotypes of Asthma
Endotype 1: Allergen driven Endotype 2: severe eosinophilic non-allergic Endotype 3 Endotype 4 Endotypes not yet iddentified or rare
Endotype specific medications
anti-IL5, anti-IL13, CRTH2 antagonist, new anti-IGE
Known asthma phenotypes
Allergic/Exogenous/Extrinsic Asthma Non allergic asthma/Endogenous/ Intrinsic Asthma Late-onset asthma Asthma with fixed airflow limitation Asthma with Obesity
Allergic asthma
Most easily recognized
Often begins n childhood
Have eosinophilic airway inflammation, respond well to ICS therapy
Non allergic Asthma
Cellular profile variable
Late onset asthma
Tend to be non-allergic, relatively refractory to ICS treatment
ASthma with fixed airflow limitation
long standing often severe asthma; airway remodeling
Asthma with obesity
Often very symptomatic, little eosinophilic airway inflammation
ASthma-COPD overlap syndrome
persistent airflow limitation with several features usually associated with both asthma and COPD
ASthma control: 2 domains
Assess symptom control over the last 4 weeks
Assess risk factors for poor outcomes, including low lung function
GINA assessment of asthma control
In the past 4 weeks:
- Daytime sx >2/week
- Night waking
- reliever >2x/week
- Activity limitation
Well controlled : none
PArtly controlled: 1-2
Uncontrolled: 3-4 of these
Categories of asthma severity and their treatment
Mild: Steps 1 or 2
Moderate: Step 3
Severe: Step4/5
first line controllers
ICS only
ICS/LABA
First line Reliever
SABA
Anti-IGE
Omalizumab
Anti IL5
Mepolizumab, reslizumab
Reduce airway inflammation and BHR
Controllers
ICS treatment response assessment and dose assessment
sputum/blood eosinophilia and/or INH FeNO
Provide long term protection againts bronchoconstrictor stimuli and for EIA. Preferred add-on therapy for asthmatics who remain symptomatic despite the use of ICS
LABA
Fixed dose combinations of LABA
Budesonide/fluticasone/Beclomethasone-formeterol
FLuticasone-salmeterol
Drug of choice for aspirin induced asthma
Oral anti-leukotrienes
Zileuton
5-lipoxygenase inhibitor
Activates histone deacetylase-2 to swtich off activated inflammatory genes, reducing steroid insensitivity
Oral theophylline
Drug of choice for treatment of acute asthma exacerbations and episodes
SABA
Reliever of choice for beta-blocker induced asthma
SAMA
Add on therapies for severe asthma
Tiotropium
Phenotype-guided add-on treatment
Low dose oral steroid
Bronchial thermoplasty
Inhibits M1, M2 and M3 receptors but dissociates more quickly from pre-junctional M2 receptors
Tiotropium
For patients >12 y/o with a hx of exacerbations despite Step 4 Tx
Tiotropium
Delivers radiofrequency energy to the airways via FOB.
Bronchial thermoplasty
Add on for patients >6y/ with moderate to severe allergic asthma (high serum IgE) that is uncontrolled on GINA step 4 treatment
Omalizumab
Add on therapy for patients aged >12 years with severe eosinophilic asthma that is uncontrolled on GINA Step 4 treatment
SQ Mepolizumab or IV Reslizumab
Long term goals of asthma management
Symptom control
Risk reduction
Add on in adult HDM-sensitive patients with allergic rhinitis who have exacerbations despite ICS treatment, provided FEV1 is 70% predicted
SILT (Sublingual immunotherapy)
COnsider stepping down if symptom is____
controlled for 3 months + low risk of exacerbations