ICL 2.1: Variable Obstructive Lung disease: Asthma Flashcards
how prevalent is asthma?
8% but increasing in developing countries
more common in african americans, obese, and in urban areas
boys > girls
what is the definition of asthma?
variable airway obstruction and hyperresponsiveness
how do you diagnose asthma?
- spirometry pre and post bronchodilator administration –> 12% increase in FEV1 means it’s asthma
- methacholine challenge –> administer methacholine and if a hyper-responsive bronchoconstriction response results in 20% reduction in FEV1 that’s asthma
what are the characteristics of asthma?
- episodic –> wheezing, breathlessness, chest tightness, cough
- worse at night and early morning
- triggers like allergens
- PFTs are normal between episodes!!
- completely reversible
most asthma deaths occur in the night and it’s highly correlated with extensive mucous plugging
how can asthma vary?
- triggers
- type and degree of inflammation (TH1 adult non-allergic vs. TH2 response atopic in children
- severity of symptoms
- response to treatment
what are some triggers of asthma?
- cold air
- allergens = pollens, grass, cockroaches, animal dander, dust mites, mold
- cigarette smoke
- air pollution, car exhaust
what is non-atopic asthma?
aka nonallergic, intrinsic asthma due to TH1 lymphocyte-drive inflammation
- adult onset
- associated with obesity
- tends to be difficult to control with more severe relapses
- skin prick tests are negative and no circulating IgE
- no familial pattern
- higher female prevalence
what is atopic asthma?
aka allergic or extrinsic asthma due to TH2 lymphocyte driven inflammation
- early onset, first two decades of life
- allergenic triggering
- positive skin prick test
- specific IgE
- familial pattern
less than 1/2 of asthma cases are this type despite contrary belief!
what are the genetic risk factors that contribute to the risk of asthma?
- ADAM 33
- HLA alleles
- IL4 polymorphisms
what are the environmental risk factors that contribute to the risk of asthma?
- allergen sesitization
- having few siblings
- excessive hygiene
- receipt of antibiotics in the first 2 years of life
- vaccination and prevention of disease
which cell types are involved in asthma inflammation?
- TH1 CD4 T-lymphocytes (intrinsic)
2. TH2 CD4+ T-lymphocytes (extrinsic)
how are TH1 CD4 T-lymphocytes involved in asthma?
they secrete:
1. TNF-alpha
- IL2
- INF-gamma
- lymphotoxin –alpha
these stimulate neutrophils
how are TH2 CD4 T-lymphocytes involved in asthma?
- they secrete IL4 which stimulates B-cell IgE production
IgE/allergen then stimulate mast cells and basophils that secrete histamine, leukotrienes, prostaglandins and proteases
- secrete IL5 which stimulates eosinophils
eosinophils secrete major basic protein, eosinophilic cationic protein, eosinophilic peroxidases and leukotrienes
what is major basic protein?
secreted by eosinophils which stimulated by IL5
they’re cytotoxic to epithelial cells
what is the role of leukotrienes in asthma?
they’re synthesized by eosinophils, mast cells, macrophages, and basophilic –> they are formed via the lipoxygenase pathway from arachidonic acid
LTC4 and LTD4 bind to cysteine leukotriene receptors and induce:
1. smooth muscle cells which leads to bronchial restriction and hyperactivity
- bronchial epithelial cells which leads to mucosal edema
- mucus hypersecretion from goblet cells
LTB4 binds to BLT1 receptors and induces neutrophil chemoattraction
what are the long-term consequences of asthma airway inflammation?
- airway smooth muscle hypertrophy
- epithelial cell shedding
- basement membrane thickening
- no alveolar disruption
- dendritic cells
- TH2 lymphocytes = eosinophils and mast cells
- goblet cell hypertrophy
- mucus plugs
which of the following concerning bornchoprovocation testing is most accurate?
A. exercise testing is more accurate than methacholine challenge testing for diagnosing asthma
B. a positive methacholine challenge test accurately separates asthma from COPD
C. negative methacholine challenge test has excellent negative predictive value in ruling out asthma
D. inhaled corticosteroid usage does not affect the sensitivity of the test
C. negative methacholine challenge test has excellent negative predictive value in ruling out asthma
it’s not specific but it’s really sensitive
so if it’s positive then that doesn’t necessarily mean you have asthma but if it’s negative, it means you definitely don’t
what are the initial steps of asthma management?
- diagnose
- asses severity
- initiate medication and demonstrate use
- develop written asthma action plan
- schedule follow up
how do you provisionally diagnose asthma?
asthma is episodic so the patient might not have anything wrong with them during your PE so the provisional diagnosis is based on history and physical
ask them about triggers, seasonal, nocturnal, exercise, age of onset, eczema, wheezing, increased expiratory time, use of accessory muscles
how do you differentiate asthma from vocal cord dysfunction?
wheezing loudness over the chest vs. neck
louder wheeze over the neck combined with predominant inspiratory wheeze is vocal cord dysfunction = GERD
how do you definitively diagnose asthma?
documentation of variable airway obstruction OR hypersensitivity
variable airway obstruction is evaluated by :
1. peak expiratory flow (PEF) using hand-held personal peak-flow meter 2x daily for 2 weeks
- FEV1 before and after bronchodilator (12% increase)
if bronchodilator response is negative, evaluate the airway responsiveness through provocation test which is either the exercise challenge or the methacholine challenge
in differentiating asthma from COPD, which statement is true about spirometry?
A. significant bronchodilator response confirms the diagnosis of asthma
B. bronchodilator response does not differentiate asthma from COPD
C. the absence of significant bronchodilator response confirms the diagnosis of COPD
D. a pst-bronchodilator FEV1/FVC less than 70% confirms the diagnosis of asthma
A. significant bronchodilator response confirms the diagnosis of asthma
what is hyperresponsiveness in relation to asthma?
the autonomic nervous system is influenced by inflammation in the airways
it regulates airway tone, permeability and secretion
dysfunction leads to/complicates asthma!
how do you measure airway hyperresponsiveness with asthma?
methacholine challenge!
you give methacholine and look at how much FEV1 decreases
the smaller the dose to reach a decrease of 20% in FEV1, the more severe the hyper-responsiveness
the methacholine challenge test is highly sensitive but not that specific so if it’s negative you CAN be confident that they don’t have asthma but if it’s positive it doesn’t necessarily mean they have asthma
what factors classify the severity of asthma in patients who haven’t been on meds yet?
- symptom frequency
- nightime awakenings
- frequency of short acting B-agonist (SABA) use
- interference with normal activity
- lung function measured by spirometry
severity will range from mild, moderate to severe – there’s a big graph
what are the classes of asthma medication?
QUICK RELIEF
1. bronchodilators –> SABAs, anticholinergics
- anti-inflammatories –> systemic corticosteroids (prednisone)
LONG TERM
1. bronchodilators –> long acting B2 agonists (LABAs), phosphodiesterase inhibitors
- anti-inflammatories –> inhaled corticosteroids*, leukotriene antagonists, mast cell stabilizers, immunomodulators
what are corticosteroids used for in asthma treatment?
they’re highly effective anti-inflammatory substances and inhaled corticosteroids are the mainstay of asthma control!
systemic corticosteroids are used for temporary management of severe exacerbations because their systemic use is associated with significant side effects – so you want to minimize their use and get them on LABA and inhaled corticosteroids
what are the 2 main LABA drugs for asthma?
- salmeterol
2. formoterol
what are the advantages and disadvantages of LABA?
ADVANTAGES
1. reduce asthma exacerbations
- improve pulmonary function
- reduces airway responsiveness
- attenuate EIB
- provide brochodilation
- prevent nocturnal asthma
DISADVANTAGES
1. potential for reduced effect with long term treatment
- not recommended as monotherapy
should be combining with inhaled corticosteroids!
what is the MOA of leukotriene inhibitors?
- inhibit lipoxygenase directly to reduce production of LTC4, LTD4, and LTE4
- antagonize CysLT receptor to reduce mucus secretion, bronchoconstriction, edema and eosinophilia
which drug directly inhibit lipoxygenase?
zileuton
which drugs are CysLT receptor antagonists?
- zafirlukast
- pranlukast
- montelukast
which drugs are the biologics used for asthma management?
these drugs are used for when asthma/eczema is otherwise uncontrolled and the patient has become steroid dependent
- omalizumab = anti-IgE used when there’s high IgE levels
- dupilimab = blocks IL4 and IL13 actions by antagonizing IL4 receptor and is used when there’s eosinophilia
- mepolizumab is an anti-IL5 and is used when there’s eosinophilia
what are the symptoms of a severe asthma attack?
- persistent SOB
- inability to speak full sentences
- breathless even lying down
- acrocyanosis
- agitation, confusion, inability to concentrate
- hunches shoulders and strained abdominal and neck muscles = use of accessory muscles
- need to sit or stand up to breath more easily
what is status asthmatics?
acute severe asthma attack and that doesn’t respond to usually use of inhaled bronchodilators
associated with symptoms of potential respiratory failure
life threatening
what is the stepwise approach for long term asthma control?
- SABA
- low dose inhaled corticosteroid
can add mast cell stabilizer or leukotriene inhibitor
- add LABA or medium doseICS
- high dose ICA + LABA and consider omalizumab for patients who have allergies
- high does ICS + LABA + oral corticosteroids and consider omalizumab for patients who have allergies
what is the use of peak flow meter?
- establish baseline
- quantify increase in airway restriction at time of symptoms
- act according to asthma action plan based on results
how do obesity and GERD effect asthma?
they increase the risk for asthma and severe asthma
association between obesity and asthma is stronger for non-atopic/intrinsic asthma
comorbid with obesity and asthma are GERD, OSA and DM which all increase the risk for aspiration! especially when lying down
patient prone to severe asthma phenotype often have which of the following characteristics?
A. GERD as comorbid condition
B. gastroparesis from long-standing DM as a comorbid condition
C. OSA as a comorbid condition
D. all of the above
D. all of the above
what is the aspirin-exacerbated respiratory disease triad?
- asthma
- recurrent nasal polyps
- sinusitis
this is caused by a sensitivity to aspirin and other NSAIDs that inhibit COX –> increased expression of LTC4 synthetase and production of cysteine-leukotrienes possibly associated with polymorphism of the cysteinyl-leukotriene synthase gene
AERD commonly develops suddenly in adulthood between 20-50 years old
how do you treat aspirin-exacerbated respiratory disease?
AERD patients not desensitized shoulda avoid all NSAIDs to prevent reactions
to desensitize a patient, administer aspirin gradually increasing the dose –> the goal is long term daily aspirin therapy to decrease the regrowth of nasal polyps and reduce the need for corticosteroid medications
in the mean time give inhaled corticosteroids
give zileuton to inhibit production of leukotrienes or give montelukas/zafirlukast to block the function of the leukotrienes at the CysLT1 receptor
surgically remove nasal polyps but they reoccur often
what is exercise induced bronchospasm?
bronchospasm occurring 5-10 minutes AFTER completion of exercise caused by mast cell degranulation
cough may be the only symptoms but they could also have chest pain, tightness, wheezing, SOB
it resolves spontaneously 30-45 minutes after finishing exercise
cold or dry climates or running are the worst triggers
how do you diagnose exercise induced bronchospasm?
make them exercise then if there’s a 15% decrease in FEV1 that suggests EIB
how do you treat exercise induced bronchospasm?
- pre-exercise short acting B agonist inhaler = albuterol
- mast cells stabilizers = cromolyn
- anti-leukotrienes = zileutin or montelukast
- encourage warm up period or mask or scarf over the mouth for cold-induced EIB
how do you prevent exercise induced bronchospasm?
- SABAs
- LTRAs, cromolyn or LABAs are also protective
frequent or chronic use of LABA to prevent EIB is discouraged because it may be disguising poorly controlled persistent asthma
EIB is often a marker of inadequate asthma control and responds well to regular anti-inflammatory therapy
32 year old woman present with symptoms of exercise induced SOB and chest tightness. she admits to nocturnal chest tightness and difficulty breathing. PE is normal. spirometry shows a normal FVC and no airflow obstruction. FEV1 is 80% predicted. you suspect asthma. if she does in fact have asthma, which of the following tests is most likely to confirm your suspicion of asthma?
A. post bronchodilator increase in FEB1 by 8%
B. methacholine inhalation challenge test 20% reduction in FEV1
C. a treadmill exercise challenge causing FEV1 to decrease 10%
D. post-bronchodilator increase in FEV1 by 100 mL
B. methacholine inhalation challenge test 20% reduction in FEV1
what is the most common cause of occupational asthma?
isocyanate exposure (found in paint!)
which conditions can mimic asthma?
- vocal cord dysfunction
- GERD
- strong emotions and stress
- irritants like tobacco
- exercise
- hyperventilation syndrome
- allergic bronchopulmonary aspergillosis
- Churg-Strauss syndrome
