ICL 2.1: Variable Obstructive Lung disease: Asthma

Question 1

how prevalent is asthma?

Answer 1

8% but increasing in developing countries

more common in african americans, obese, and in urban areas

boys > girls

Question 2

what is the definition of asthma?

Answer 2

variable airway obstruction and hyperresponsiveness

Question 3

how do you diagnose asthma?

Answer 3

1. spirometry pre and post bronchodilator administration –> 12% increase in FEV1 means it’s asthma
2. methacholine challenge –> administer methacholine and if a hyper-responsive bronchoconstriction response results in 20% reduction in FEV1 that’s asthma

Question 4

what are the characteristics of asthma?

Answer 4

1. episodic –> wheezing, breathlessness, chest tightness, cough
2. worse at night and early morning
3. triggers like allergens
4. PFTs are normal between episodes!!
5. completely reversible

most asthma deaths occur in the night and it’s highly correlated with extensive mucous plugging

Question 5

how can asthma vary?

Answer 5

1. triggers
2. type and degree of inflammation (TH1 adult non-allergic vs. TH2 response atopic in children
3. severity of symptoms
4. response to treatment

Question 6

what are some triggers of asthma?

Answer 6

1. cold air
2. allergens = pollens, grass, cockroaches, animal dander, dust mites, mold
3. cigarette smoke
4. air pollution, car exhaust

Question 7

what is non-atopic asthma?

Answer 7

aka nonallergic, intrinsic asthma due to TH1 lymphocyte-drive inflammation

1. adult onset
2. associated with obesity
3. tends to be difficult to control with more severe relapses
4. skin prick tests are negative and no circulating IgE
5. no familial pattern
6. higher female prevalence

Question 8

what is atopic asthma?

Answer 8

aka allergic or extrinsic asthma due to TH2 lymphocyte driven inflammation

1. early onset, first two decades of life
2. allergenic triggering
3. positive skin prick test
4. specific IgE
5. familial pattern

less than 1/2 of asthma cases are this type despite contrary belief!

Question 9

what are the genetic risk factors that contribute to the risk of asthma?

Answer 9

1. ADAM 33
2. HLA alleles
3. IL4 polymorphisms

Question 10

what are the environmental risk factors that contribute to the risk of asthma?

Answer 10

1. allergen sesitization
2. having few siblings
3. excessive hygiene
4. receipt of antibiotics in the first 2 years of life
5. vaccination and prevention of disease

Question 11

which cell types are involved in asthma inflammation?

Answer 11

1. TH1 CD4 T-lymphocytes (intrinsic)

2. TH2 CD4+ T-lymphocytes (extrinsic)

Question 12

how are TH1 CD4 T-lymphocytes involved in asthma?

Answer 12

they secrete:
1. TNF-alpha

2. IL2
3. INF-gamma
4. lymphotoxin –alpha

these stimulate neutrophils

Question 13

how are TH2 CD4 T-lymphocytes involved in asthma?

Answer 13

1. they secrete IL4 which stimulates B-cell IgE production

IgE/allergen then stimulate mast cells and basophils that secrete histamine, leukotrienes, prostaglandins and proteases

2. secrete IL5 which stimulates eosinophils

eosinophils secrete major basic protein, eosinophilic cationic protein, eosinophilic peroxidases and leukotrienes

Question 14

what is major basic protein?

Answer 14

secreted by eosinophils which stimulated by IL5

they’re cytotoxic to epithelial cells

Question 15

what is the role of leukotrienes in asthma?

Answer 15

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

2. bronchial epithelial cells which leads to mucosal edema
3. mucus hypersecretion from goblet cells

LTB4 binds to BLT1 receptors and induces neutrophil chemoattraction

Question 16

what are the long-term consequences of asthma airway inflammation?

Answer 16

1. airway smooth muscle hypertrophy
2. epithelial cell shedding
3. basement membrane thickening
4. no alveolar disruption
5. dendritic cells
6. TH2 lymphocytes = eosinophils and mast cells
7. goblet cell hypertrophy
8. mucus plugs

Question 17

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

Answer 17

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

Question 18

what are the initial steps of asthma management?

Answer 18

1. diagnose
2. asses severity
3. initiate medication and demonstrate use
4. develop written asthma action plan
5. schedule follow up

Question 19

how do you provisionally diagnose asthma?

Answer 19

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

Question 20

how do you differentiate asthma from vocal cord dysfunction?

Answer 20

wheezing loudness over the chest vs. neck

louder wheeze over the neck combined with predominant inspiratory wheeze is vocal cord dysfunction = GERD

Question 21

how do you definitively diagnose asthma?

Answer 21

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

2. 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

Question 22

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

Answer 22

A. significant bronchodilator response confirms the diagnosis of asthma

Question 23

what is hyperresponsiveness in relation to asthma?

Answer 23

the autonomic nervous system is influenced by inflammation in the airways

it regulates airway tone, permeability and secretion

dysfunction leads to/complicates asthma!

Question 24

how do you measure airway hyperresponsiveness with asthma?

Answer 24

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

Question 25

what factors classify the severity of asthma in patients who haven't been on meds yet?

Answer 25

1. symptom frequency 2. nightime awakenings 3. frequency of short acting B-agonist (SABA) use 4. interference with normal activity 5. lung function measured by spirometry severity will range from mild, moderate to severe -- there's a big graph

Question 26

what are the classes of asthma medication?

Answer 26

QUICK RELIEF 1. bronchodilators --> SABAs, anticholinergics 2. anti-inflammatories --> systemic corticosteroids (prednisone) LONG TERM 1. bronchodilators --> long acting B2 agonists (LABAs), phosphodiesterase inhibitors 2. anti-inflammatories --> inhaled corticosteroids*, leukotriene antagonists, mast cell stabilizers, immunomodulators

Question 27

what are corticosteroids used for in asthma treatment?

Answer 27

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

Question 28

what are the 2 main LABA drugs for asthma?

Answer 28

1. salmeterol | 2. formoterol

Question 29

what are the advantages and disadvantages of LABA?

Answer 29

ADVANTAGES 1. reduce asthma exacerbations 2. improve pulmonary function 3. reduces airway responsiveness 4. attenuate EIB 5. provide brochodilation 6. prevent nocturnal asthma DISADVANTAGES 1. potential for reduced effect with long term treatment 2. not recommended as monotherapy should be combining with inhaled corticosteroids!

Question 30

what is the MOA of leukotriene inhibitors?

Answer 30

1. inhibit lipoxygenase directly to reduce production of LTC4, LTD4, and LTE4 2. antagonize CysLT receptor to reduce mucus secretion, bronchoconstriction, edema and eosinophilia

Question 31

which drug directly inhibit lipoxygenase?

Answer 31

zileuton

Question 32

which drugs are CysLT receptor antagonists?

Answer 32

1. zafirlukast 2. pranlukast 3. montelukast

Question 33

which drugs are the biologics used for asthma management?

Answer 33

these drugs are used for when asthma/eczema is otherwise uncontrolled and the patient has become steroid dependent 1. omalizumab = anti-IgE used when there's high IgE levels 2. dupilimab = blocks IL4 and IL13 actions by antagonizing IL4 receptor and is used when there's eosinophilia 3. mepolizumab is an anti-IL5 and is used when there's eosinophilia

Question 34

what are the symptoms of a severe asthma attack?

Answer 34

1. persistent SOB 2. inability to speak full sentences 3. breathless even lying down 4. acrocyanosis 5. agitation, confusion, inability to concentrate 6. hunches shoulders and strained abdominal and neck muscles = use of accessory muscles 7. need to sit or stand up to breath more easily

Question 35

what is status asthmatics?

Answer 35

acute severe asthma attack and that doesn't respond to usually use of inhaled bronchodilators associated with symptoms of potential respiratory failure life threatening

Question 36

what is the stepwise approach for long term asthma control?

Answer 36

1. SABA 2. low dose inhaled corticosteroid can add mast cell stabilizer or leukotriene inhibitor 3. add LABA or medium doseICS 4. high dose ICA + LABA and consider omalizumab for patients who have allergies 5. high does ICS + LABA + oral corticosteroids and consider omalizumab for patients who have allergies

Question 37

what is the use of peak flow meter?

Answer 37

1. establish baseline 2. quantify increase in airway restriction at time of symptoms 3. act according to asthma action plan based on results

Question 38

how do obesity and GERD effect asthma?

Answer 38

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

Question 39

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

Answer 39

D. all of the above

Question 40

what is the aspirin-exacerbated respiratory disease triad?

Answer 40

1. asthma 2. recurrent nasal polyps 3. 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

Question 41

how do you treat aspirin-exacerbated respiratory disease?

Answer 41

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

Question 42

what is exercise induced bronchospasm?

Answer 42

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

Question 43

how do you diagnose exercise induced bronchospasm?

Answer 43

make them exercise then if there's a 15% decrease in FEV1 that suggests EIB

Question 44

how do you treat exercise induced bronchospasm?

Answer 44

1. pre-exercise short acting B agonist inhaler = albuterol 2. mast cells stabilizers = cromolyn 3. anti-leukotrienes = zileutin or montelukast 4. encourage warm up period or mask or scarf over the mouth for cold-induced EIB

Question 45

how do you prevent exercise induced bronchospasm?

Answer 45

1. SABAs 2. 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

Question 46

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

Answer 46

B. methacholine inhalation challenge test 20% reduction in FEV1

Question 47

what is the most common cause of occupational asthma?

Answer 47

isocyanate exposure (found in paint!)

Question 48

which conditions can mimic asthma?

Answer 48

1. vocal cord dysfunction 2. GERD 3. strong emotions and stress 4. irritants like tobacco 5. exercise 6. hyperventilation syndrome 7. allergic bronchopulmonary aspergillosis 8. Churg-Strauss syndrome