week 5- Asthma Flashcards
who is asthma most prevalent in
kids (males)
then in adults (less common, but female)
low income and urban minority (i.e. Puerto Rican)
definition of asthma according to GINA Global Strategy for Asthma Management and Prevention Report
A heterogenous disease characterized by chronic airway inflammation resulting in airflow limitation
definition of asthma according to National Asthma Education and Prevention Program’s Expert Panel Report:
“A chronic inflammatory disease of the airways in which many cells and cellular elements play a role, including mast cells, eosinophils, neutrophils, T lymphocytes, macrophages, and epithelial cells.” “In susceptible individuals, this inflammation causes recurrent episodes of wheezing, breathlessness, chest tightness, and cough, particularly at night and/or in the early morning. These episodes are usually associated with widespread but variable airflow limitation that is often reversible either spontaneously or with treatment.”
3 characteristics of airway in asthma
- Variable airway obstruction or airflow limitation
- Airway hyperresponsiveness
- Airway inflammation
timing of asthma
recurrent, intermittent, episodic
chronic
worse at night or early morning
flares and exacerbations
endogenous risk factors of asthma
- Atopy
- Airway hyperresponsiveness
- Ethnicity
- Gender
- Genetic predisposition
environmental risk factors for asthma
- Allergens – indoor (pet dander, mites, cockroaches); outdoor (fungi, pollens)
- Obesity
- Occupational sensitizers
- Parasitic infections
- Respiratory infections (early childhood, viral)
- Socioeconomic status
- Tobacco smoking (active and passive)
- Premature birth and low birth weight
- Vitamin D deficiency
- Low intake of omega-3 fatty acids
microbial influence in asthma (protective and risk factors)
protective: microbial diversity, farm animal exposure, vaginal birth, innate immune stimulation, gut mucosa (T reg cells from SCFA)
risk: caesarean birth, gut microbes (clostridium, bifida…), lung microbes (m. catarrhalis, influenza, penumoniae….), airway mucosal (bronchial, Th17 and Th2 infilirate), gut mucosa (IgA, iNKT)
most common trigger of asthma
respiratory infections (acute respiratory tract viral infections such as rhinovirus infections)
exacerbating factors of asthma
respiratory infections (most common)
* Allergens (house dust mites, animal dander, cockroach, indoor fungi/mold, perennial allergens, and seasonal pollens)
* Weather changes (cold air, thunderstorms)
* Drugs (ACE inhibitors, aspirin, beta-blockers, NSAIDs)
* Comorbidities: chronic rhinosinusitis, food allergy, GERD, obesity, pregnancy
* Psychological difficulties, socioeconomic issues
* Exercise and hyperventilation
* Extreme emotional expression (laughing, hard crying, stress)
* Irritants (household sprays, paint fumes, perfumes, organophosphates)
* Sulfur dioxide and pollutant gases
* Tobacco smoking
* Poor adherence to inhaler medications and/or incorrect inhaler technique
2 types of asthma based on atopy
- atopic (extrinsic) asthma
- nonatopic (intrinsic) asthma
what is more common; atopic (extrinsic asthma) or nonatopic (intrinsic) asthma?
atopic
non atopic= 10%
what is the suspected etiologic factor of atopic (extrinsic) asthma
allergens
atopic (extrinsic) asthma and the role of allergens
exagerate immune response: IgE activation and mast cell degradation
comorbid with other atopic diseases (i.e. seasonal allergic rhinitis, allergic conjunctivitis, atopic dermatitis)
common features of nonatopic (intrinsic) asthma
later onset (adult)
more severe + persistent sx
more sensitive to aspirin
nasal polyps common
4 phenotypes of asthma
- Early-onset mild allergic asthma
- Early-onset allergic moderate to severe remodeled asthma
- Late-onset nonallergic eosinophilic asthma
- Late-onset noneosinophilic nonallergic asthma
endotype definition
Endotypes are groups defined by divergent molecular and immunologic mechanisms
2 main end-types of asthma
- T2-high asthma end-types (type 2 asthma)
- T2- low asthma end-types (non-type 2 asthma)
T2-high asthma endotypes (aka type 2 asthma) has which levels of which cytokines
high levels of Th2 cytokines such as IL-4, IL-5, IL-13
T2-low asthma endotypes (aka non-type 2 asthma) has which levels of which cytokines
low levels of Th2 cytokines such as IL-4, IL-5, IL-13
has Th1, Th17, IL-6, IL-8, IL-1B, IFNy
type 2 vs non type 2 asthma cytokines
type 2= high levels
non type 2= low levels
examples of type 2 vs non type 2 asthma
type 2:
* Allergic asthma
* Late-onset T2-high asthma
* Aspirin/NSAID-induced respiratory disease
* Exercise-induced asthma
non-type 2:
* Very late-onset asthma
* Neutrophilic asthma
* Paucigranulocytic asthma
* Obesity-associated asthma
type 2 asthma
-cytokines
-timeline
-other sx
Th2, eosinophils, mast cells, IL-4, IL-5, IL-13
-childhood with other allergic diseases
-with aeroallergen sensitization (immediate asthmatic response to allergy and late asthmatic response)
-sequelae of repeated viral infections
non-type 2 asthma
-cytokines and cells
-timeline
-severity
No type 2 inflammation
-Th1, Th17, IL-6, IL-8, IL-1B, IFN-y
-adults
more severe than type 2
exercise induced asthma is type 2 or non type 2
type 2
trigger of exercise-induced asthma
hyperventilation –> drying of airway mucosa –> mast cell release and bronchospasm
aspirin-exacerbated respiratory disease
-% of cases
-type 2 or non type 2
-caused by
-sx
-5-10%
type 2
- Severe asthma exacerbations after ingesting inhibitors of cyclooxygenase-1 (aspirin and NSAIDs) but can generally tolerate inhibitors of cyclooxygenase-2 and acetaminophen
sx: eosinophilia, sinusitis, nasal polyps
obesity related asthma
-type 2 or non type 2
-sx
-timeline
-mechanism
non type 2
childhood
little airway inflammation present
-decreased tidal volume from obesity
-genetics
-fetal development
-comorbid ie. GERD
-air pollution
-diet and microbiome
-proinflammatory cytokines made by adipocytes
2 types of occupational asthma
- sensitizer-induced asthma (i.e. gums, latex, seafood, wood dust, cereals, anhydrides, formalydehyde)
- irritant-induced asthma (acids, bleach, ammonia, cleaning agent, mustard, paints, endotoxin)
Ddx for occupational asthma
work-exacerbated asthma – worsening of asthma that is already pre-existing or concurrent, trigger by nonspecific irritants in the workplace
general sx of asthma (4)
wheezing, dyspnea, chest tightness, cough
features that decrease likelihood of asthma
isolated cough with no other symptoms, chronic sputum production, chest pain, shortness of breath with paresthesias
highest LR+ for asthma sx
wheezing and dyspnea at rest (29.54)
wheezing and nocturnal dyspnea (26.79)
wheezing and nocturnal chest tightness (16.44)
physical exam findings on asthma
prolonged expiration and wheezing (airflow obstruction)
but if mild may be normal between exacerbations
severe: too limited airflow for wheezing and might be globally reduced breath sounds with prolonged expiration
asthma and wheezing
Asthma is a common cause of wheezing BUT
the absence of wheezing does not exclude the
diagnosis of asthma!
other possible findings in asthma
- Tachypnea and tachycardia
- Use of accessory muscles of respiration
- Hunched shoulders and/or forward-leaning tripod position
- Chest signs of hyperinflation
possible signs in allergic asthma
- Nasal mucosal swelling, increased nasal secretions, pale/blue nasal turbinates
- Eczema, atopic dermatitis or other allergic skin disorders
sx in severe airway obstruction (asthma)
- Pulsus paradoxus – decrease of > 10 mmHg in systolic blood pressure during inspiration
- Stridor and intercostal retractions in infants/children
pulmonary function testing for asthma
- Spirometry
- Bronchoprovocation challenge
- Body plethysmography
- Peak expiratory flow
blood test for asthma
- Blood eosinophil count
- Total serum immunoglobulin E (IgE)
- Blood tests of specific IgE to inhaled allergies, radioallergosorbent testing (RAST), ImmunoCAP
- Arterial blood gas (ABG) measurements
other tests for asthma
- Skin prick testing
- Chest radiography
spirometry (pulmonary function test) for
determining the severity of airflow obstruction
- Findings supporting a diagnosis of asthma:
- Decreased forced expiratory volume in 1 second (FEV1)
- Decreased FEV1/forced vital capacity (FVC) ratio (generally below 0.7)
- Reversibility (defined as at least a 200 mL increase in FEV1 and >12% improvement with bronchodilators)
spirometry to determine severity of exacerbation of asthma
- Mild exacerbation: symptoms only with activity and FEV1 ≥70% of predicted
- Moderate exacerbation: symptoms with usual activities and FEV1 40- 69% of predicted
- Severe exacerbation: dyspnea at rest and dyspnea that interferes with conversation and FEV1 <40% of predicted
bronchoprovcation testing for asthma
assess bronchial hyper responsiveness
Provocation agents:
* Direct stimuli: histamine, methacholine
* Indirect stimuli: adenosine monophosphate (AMP), mannitol, exercise, hypertonic saline, isocapnic hyperventilation
positive and negative bronchoprovocation test results
- A positive bronchoprovocation test is defined as a decrease of FEV1 of ≥20% at exposure to the provocative agent at a concentration of ≤ 8 mg/mL
- A negative bronchoprovocation test (defined as a decrease of FEV1 of <20%) has a 95% negative predictive value – excludes the diagnosis of asthma with a high degree of accuracy
body plethysmography for asthma
- Patient seated in an airtight chamber and breathing normally in and out of a mouthpiece similar to spirometry testing
- Changes in pressure inside the chamber determine patient’s residual volume and airway resistance
findings in asthma for a body plethysmography test
increase in residual volume and airway resistance
peak expiratory flow test for asthma
portable handheld device to measure how fast you can blow out air using maximum effect
findings from peak expiratory flow that suggest asthma
- Serial PEF readings that vary more than 20% spontaneously or in response to treatment
- Exaggerated diurnal variation in morning and evening PEF measurements
blood tests for asthma
increased blood eosinophil count (in atopic conditions)
IgE might be increased
specific allergy: specific IgE to inhaled allergies, radioallergosorbent testing (RAST), ImmunoCAP
arterial blood gas (ABG) measurement (measures O2 and CO2 in blood)
arterial blood gas (ABG) measurement findings in asthma
- Mild asthma exacerbation: normal or respiratory alkalosis (decreased arterial PaCO2) due to hyperventilation
- Severe asthma exacerbation: hypoxemia and increased arterial PaCO2 due to muscle fatigue and inability to maintain required alveolar ventilation
skin prick test in asthma
specific allergies (atopy)
common aeroallergens such as house dust mite, grass and tree pollens, Aspergillus mold, cat and dog fur, rodents, cockroaches
chest radiography for asthma
to exclude other diseases like infection (pneumonia) or complication (pneumothorax)
asthma shows; normal or hyperinflation AND bronchial wall thickening, prominent hilar vessels, diminished peripheral lung vascular markings
asthma clinical course
reversible possibly
mild asthma: can be sx free for long periods,
severe: dont respond well to treatment, lose lung functioning, morbid + mortality
asthma complications
- Exhaustion
- Dehydration
- Airway infection
- Tussive syncope
- Pneumothorax (rare)
- Acute hypercapnic and hypoxemic respiratory failure (in severe disease)
risk factors for asthma related deaths
- Previous severe exacerbations
- Multiple, recent emergency department visits or hospitalizations
- Use of more than 2 canisters of beta-agonists in the past month
- Current use or recent discontinuation of systemic corticosteroids
- Difficulty perceiving airflow obstruction
- Low socioeconomic status
- Illicit drug use
- Comorbid medical or psychiatric disease
5 step approach to manage asthma according to 2020 GINA Global Strategy for Asthma Management and Prevention
- assess asthma control and severity
- distinguish between severe and uncontrolled asthma
- personalize pharmacologic therapy
- treat modifiable risk factors and control environmental factors
- guide self management education and skills trianing
components of asthma control and classification
- Daytime asthma symptoms > 2x/week
- Nighttime awakenings due to asthma
- Interference with normal activity due to asthma
- Reliever medication needed for asthma symptoms > 2x/week
classification
* Well controlled = None of these components within past 4 weeks
* Partly controlled = 1-2 of these components within past 4 weeks
* Not controlled = 3-4 of these components within past 4 weeks
classification of asthma control
- Well controlled = None of these components within past 4 weeks
- Partly controlled = 1-2 of these components within past 4 weeks
- Not controlled = 3-4 of these components within past 4 weeks
risk of future exacerbations of asthma from
- Poor symptom control
- More than one exacerbation in the previous year
- Poor asthma medication adherence
- Incorrect inhaler technique
- Chronic sinusitis
- Smoking
asthma severity classification
- Mild asthma – responds to step 1 or 2 treatments
- Moderate asthma – responds to step 3 treatments
- Severe asthma – responds to step 4 or 5 treatments
SLIDE 55 chart for personalized asthma plan
controller and reliever etccccc
alternate classification of asthma severity
mild intermittent
(lung: peak expiratory flow >80% predicted)
(sx < 2x/ week, asymptomatic between exacerbations, nighttime sx < 2x monthly)
mild persistent
(lung: peak expiratory flow >80% predicted)
(sx btw once a day and 2x/ week, asymptomatic between exacerbations, exacerbations may limit activity, nighttime sx > 2x/month)
moderate persistent
(lung: peak expiratory flow 60-80% predicted)
(daily sx, exacerbations limit activity, nighttime sx > weekly)
severe persistence
(lung: peak expiratory flow <60% predicted)
(continual sx, sx chronically limit physical activity, frequent nighttime sx)
differentiate between severe and uncontrolled asthma
control: inhaler technique, medication adherence, comorbidities (GERD, sleep apnea), ongoing allergen exposure
if resolve these issues then severe asthma and reverse to specialist
refractory asthma
asthma that does not respond well to standard treatment
causes of refractory asthma
- Problem with adherence to the prescribed regimen
- Unrecognized/untreated precipitants or comorbid conditions
- Incorrect diagnosis
- Presence of rare diseases that can cause or worsen asthma
goals of pharmacologic therapy in asthma
- Minimize chronic symptoms that interfere with normal activity including exercise
- Prevent recurrent exacerbations
- Reduce/eliminate need for ER visits or hospitalizations
- Maintain normal or near-normal pulmonary function
personalized asthma tx
- Personalized asthma management requires continuous assessment, treatment and review
- Select therapeutic agents with fewest adverse effects while controlling the patient’s symptoms
- Step up therapy if asthma remains uncontrolled despite adherence and good inhaler technique
- Step down therapy to find the minimum effective therapeutic dose
3 main categories of asthma medication
- long term controller medciations (use long term to reduce airway inflammation, sx and risk of future exacerbations)
- reliever medications (as needed with sx)
- add on therapies (if severe)
comorbid conditions with asthma
- Smoking, rhinosinusitis, GERD, obesity, obstructive sleep apnea, atopy, allergy
pregnancy outcomes and asthma
Poor asthma control during pregnancy is associated with poor fetal outcomes (e.g., preterm birth, low birth weight, congenital anomalies, pre-eclampsia, placenta previa)
avoid triggers (esp smoking)
asthma- COPD overlap (ACO)
symptoms due to coexistence of both asthma and chronic obstructive pulmonary disease (COPD)
- COPD and smoking can alter the response to asthma therapies
DDX for asthma
- Upper airway disorders – vocal cord paralysis, vocal cord dysfunction syndrome, narrowing of the supraglottic airway, laryngeal masses, laryngeal dysfunction, foreign body aspiration, postnasal drip, upper airway obstruction
- Lower airway/pulmonary disorders – foreign body aspiration, tracheal masses, tracheal narrowing, tracheobronchomalacia, airway edema (e.g., angioedema, inhalation injury), COPD (chronic bronchitis, emphysema), bronchiectasis, allergic bronchopulmonary aspergillosis, cystic fibrosis, eosinophilic pneumonia, hypersensitivity pneumonitis, sarcoidosis, bronchiolitis obliterans, interstitial lung disease, lung cancer, pneumothorax
- Systemic vasculitis with pulmonary involvement (e.g., eosinophilic granulomatosis with polyangiitis)
- Cardiac disorders – heart failure, pulmonary hypertension, angina, mitral valve disease
- Psychiatric causes – conversion disorders (“functional” asthma), emotional laryngeal wheezing, episodic laryngeal dyskinesis
- Gastroesophageal reflux
SLIDE 69
DDX for asthma and COPD
asthma
- <40 yrs old
-not casual smoking
-infrequent sputum production
-often allergies/atopy
-stable disease course with exacerbations
-spirometry often normalizes
-sx are intermittent and variable
COPD
->40 yrs old
-usually >10 pack cigarette for years
-often sputum production
-infrequent allergies/atopy
-progressive worsening of disease (with exacerbations)
-spirometry may improve but never normalizes
-persistent clinical sx
asthma is hetero or homogenous presentation
heterogeneous
how to diagnose asthma
diagnosis of asthma is clinical, based on findings in the history, physical exam and spirometry. There is no single test to diagnose asthma.
asthma and the absence of wheezing
- The absence of wheezing does not rule out asthma.
key points in asthma diagnosis
- Episodic symptoms of airflow obstruction,
- Reversibility of the airflow obstruction,
- Exclusion of other likely diseases.
