Resp Flashcards
What is asthma?
asthma is a disease of airflow obstruction due to airway inflammation that varies over time
asthma is characterized by pathophysiology of bronchoconstriction, mucus plugging, airway inflammation and edema hyper-responsiveness to various stimuli
Samter’s triad
asthma + nasal polyps + sensitivity / intolerance to NSAID / aspirin
Asthma pathophysiology
eosinophilic inflammation causing narrowing of airway as an immune response to allergen
1) allergen taken up by antigen presenting cell (dendritic cell or macrophage)
2) antigen presenting cell activate CD4 Th2 T cell, which secrete IL-4 and activate B cell to produce IgE antibodies
3) IgE antibodies attach to Fc receptors on mast cells, arming mast cells
4) on subsequent exposure, allergen bind to IgE on mast cells, causing mast cell degranulation
5) mast cell degranulation release inflammatory cytokines causing inflammation resulting in early phase asthmatic response (early asthma attack) inflammatory cytokines include histamine, IL-4, IL-5, leukotriene, serotonin, prostaglandin, eotaxin inflammatory cytokines increase vascular permeability, vascular inflammation, bronchospasm, airway hyperresponsiveness
6) inflammatory cytokines recruit leukocytes (including eosinophils) into airway tissue, resulting in inflammation resulting in late phase asthmatic response (late asthma attack) leukocytes cause increased vascular permeability leading to edema, smooth muscle contraction leading to bronchoconstriction, activation of goblet cells leading to increased mucus secretion
7) chronic inflammation cause remodelling of airway resulting in chronic asthma post asthmatic attacks eosinophils and lymphocytes release factors inducing permanent remodelling of airway, resulting in permanent narrowing of airway, such that airway function cannot return to normal level completely in chronic asthma even when treated with bronchodilator
What is status asthmaticus
severe asthma attacks that are poorly responsive to bronchodilators
What is the asthma control criteria
Good asthma control if all conditions are met
Poor if one isn’t met
Daytime symptoms - <4 days per week
Need for a fast acting beta 2 agonist - <4 doses per week
Nighttime symptoms - <1 night per week
Physical activity - normal
Exacerbations - mild, infrequent
Absence from work or school due to asthma - never
FEV1 or PEF - 90% + of personal best
PEF diurnal variation - <10-15%
Sputum eosinophils - <2-3%
PFT results seen in asthma
scooped flow volume curve low FEV1 (<80% predicted)
significant improvement in FEV1 with bronchodilator (improvement in FEV >12% provided improvement >200mL)
low FEV1/FVC ratio (<0.7 in adults, <0.8 in children)
disproportionately low FEF25-75 and FEF75
decreased peak flow
DLCO normal
increased airway resistance
What is the methacholine challenge
in asthma, with airway challenge with methacholine, usually significant (>20%) drop in FEV1 with small amount of methacholine (<8mg/mL)
PC20 = concentration of methacoline at which FEV decrease by 20%
PC20 <8mg/mL suggest asthma
What is airway challenge with exercise diagnosis
in asthma, with airway challenge with exercise, usually significant (>10%) drop in FEV1 by 80% maximum heart rate
Diagnosis of asthma
asthma diagnosed based on all of the following
- clinical history of asthma symptoms and asthma attacks
- PFT showing reversible obstructive lung disease:
scooped flow volume curve
low FEV1 (<80% predicted)
significant improvement in FEV1 with bronchodilator (improvement in FEV >12% provided improvement >200mL)
low FEV1/FVC ratio (<0.7 in adults, <0.8 in children)
What is a parameter that can be used to monitor asthma at home
peak flow
Asthma pharmacological management
all patients start with fast acting bronchodilator (SABA) PRN and add ICS if require maintenance therapy with ICS
if asthma is not controlled (see asthma control criteria), add in the following order:
increase ICS dosage
add long acting beta-adrenoreceptor agonist (LABA) note that long term use of LABA increase risk of severe asthma attacks
ICS LABA combinations include budesonide/formeterol, fluticasone/salmeterol, mometasone/formoterol
ICS LABA combinations can also replace SABA as emergency puffer but is 2nd line to them
leukotriene receptor antagonist (LTRA) (Montelukast sold as Singulair)
Theophylline
oral prednisone
if patient ever had an asthma attack, automatically add ICS and LABA upon discharge
if SABA is used more frequent than Q4H, then send to emergency
SABA should be used sparingly, because frequent use of bronchodilator results in tolerance and increases frequency of asthma attacks
all medications are safe to use during pregnancy
Management of acute asthma exacerbation
- Assess for current state and complications
- SABA and short acting anti-cholinergic (SAAC) to relieve dyspnea
if symptoms still uncontrolled, can use IV SABA in ICU
setting systemic oral or IV corticosteroid to reduce inflammation, which aborts exacerbation, prevent relapse, speeds recovery and decrease need for hospitalization
proper hydration
if hypoxemia, then oxygen therapy
if respiratory failure, mechanical ventilation
- Treat underlying cause (ex. infection, beta blocker…), treat cormobidities
Why is ICS not used during asthma attack
ICS is slow acting and may not be breathed in during respiratory distress, so not used during asthma attack
Metered dose inhaler (MDI) procedure
1) shake inhaler
2) take off cap
3) sit up straight or stand with chin lifted up
4) exhale completely
5) seal with lips on the inhaler tightly and start inhaling slowly
6) depress top of inhaler once
7) hold breath for >10 seconds
8) wait 45-60 seconds between puffs
9) rinse mouth
Dry powder inhaler (DPI) procedure
1) hold disk level with one hand
2) push notch away from user as far as possible with other hand, such that the mouth piece appears
3) push lever away from user as far as possible with other hand until it clicks
4) lock lips onto the mouth piece
5) breath deeply with mouth
6) hold breath for >10 seconds
7) slide notch and lever back to original position, such that disk is ready for another dose
Common ICS
Budesonide (Pulmicort)
Fluticasone (Flovent)
What is the only asthma medication shown to decrease mortality
ICS
ICS MOA
late onset with greatest effect within 3 months
inhibit production of cytokine resulting in anti-inflammatory effects (reduce eosinophil infiltration, inhibit macrophage function and reduce production of leukotrienes)
ICS adverse effects
ICS is inhaled, so its effect is localized to lung and do not have any systemic adverse effects
thrush oral candidiasis, which can be reduced by using inhaler with spacer and followed by mouth rinse
dysphonia (impaired ability to produce voice)
osteoporosis (only for high dose steroid in high risk patient population who need to be monitored regularly with bone mineral density scan)
decreased growth velocity in short term for children, but no change in adult height
adrenal suppression
worsening of glaucoma (only in high risk patient with glaucoma who need to be monitored regularly in terms of intra-ocular pressure)
increased risk of cataract, which is rare and does not require routine surveillance
skin thinning
Long acting beta 2 agonist LABA examples
Salmeterol (Serevent), green diskus DPI
Formeterol (Oxeze), green turbuhaler MDI
LABA MOA
same mechanism as SABA, but with longer lasting effect
1) beta agonist binds beta adrenergic receptor, which activate intracellular adenyl cyclase to convert ATP to cAMP
2) increased cAMP relaxes bronchial smooth muscle, resulting in bronchilation
LABA adverse effects
similar to SABA
sympathetic effects: tachycardia, tremor, headache, agitation, irritability
metabolic: hypokalemia, hyperglycemia
prolonged QT, which can lead to arrythmia
Commonly used combined ICS/LABA
Fluticasone/Salmeterol (Advair), MDI or diskus DPI
Budesonide / Formoterol (Symbicort), turbuhaler MDI
Indication for LTRA use
used as controller (i.e. taken regularly no matter if symptoms appear) and 2nd or 3rd line therapy
usually added to ICS for uncontrolled symptoms
can substitute LABA with LTRA, but usually added to ICS and LABA
preferred treatment and more effective for asthmatic patient with more allergic profile of eczema, nasal polyps, rhinitis, aspirin allergy
Commonly used LTRA
Montelukast (Singulair), PO
LTRA MOA
LTRA has anti-inflammatory and bronchodilator properties
1) LTRA is a selective antagonist of cysterinyl leukotriene receptor
2) blocking cysterinyl leukotriene receptor decreases airway edema, relaxes smooth muscle (bronchodilator) and decrease mucus secretion
LTRA adverse effects
LTRA usually very well tolerated with rare adverse effects
Theophylline MOA
theophylline is a methylxanthine, which directly relaxes smooth muscle around bronchi and pulmonary blood vessels, causing bronchodilation
also block phosphodiesterase, increasing cAMP causing bronchodilation
decrease eosinophil infiltration into bronchial mucosa
Theophylline adverse effects
theophylline is last line controller, because it has narrow therapeutic range, it has many drug interaction and there are individual differences in metabolic clearance
patients on theophylline require regular monitoring of serum theophylline due to potential toxicities if outside therapeutic range
adverse effects at therapeutic dosages include insomnia hyperactivity gastric upset difficulty urinating with prostatism
adverse effect due to high dose
sympathetic effects: tachycardia, tachyarrhythmia, headache
metabolic effects: hypokalemia, hyperglycemia
seizure
hematemesis
1st line controller medication for COPD
LAAC
Commonly used LAAC
Tiotropium (Spiriva)
LAAC MOA
long acting M3 muscarinic receptor antagonist, resulting in bronchodilation and decreased mucus secretion
LAAC adverse effects
anticholinergic effects
worsening of glaucoma and BPH
Indications for SAAC or systemic corticosteroid in asthma and COPD
SAAC, systemic corticosteroid usually only used for asthma or COPD exacerbations
SABA indication in asthma and COPD
SABA PRN given to all asthma or COPD patients for respiratory symptoms
Commonly used SABA
Salbutamol (Ventolin) MDI, blue puffer
Terbutaline (Bricanyl) DPI
SABA MOA
fast onset within 1-3 minutes and last ~45 minutes
1) beta agonist binds beta adrenergic receptor, which activate intracellular adenyl cyclase to convert ATP to cAMP
2) increased cAMP relaxes bronchial smooth muscle, resulting in bronchilation
SABA adverse effects
sympathetic effects: tachycardia, tremor, headache, agitation, irritability
metabolic: hypokalemia, hyperglycemia
Commonly used SAAC
Ipatropium, green puffer MDI
SAAC MOA
competitive inhibitor of muscarinic cholinergic receptor, decreasing parasympathetic activity and resulting in bronchodilation
SAAC is a less potent bronchodilator than SABA
SAAC adverse effects
anticholinergic
may increase wheezing
Commonly used systemic corticosteroids
Prednisone oral pills PO
Solumedrol IV
Systemic corticosteroids MOA
systemic anti-inflammatory effect, mainly reducing eosinophilic inflammation in asthma
Systemic corticosteroid adverse effects
unlike ICS, systemic corticosteroid associated with many adverse effects
- short term adverse effects include:
metabolic effects: weight gain, increased appetite, hyperglycaemia
psychiatric effects: mood alteration
immune effects: immunocompromise
peptic ulcer disease
fluid retention
- long term adverse effects include:
metabolic effects: diabetes, adrenal axis suppression, Cushing’s syndrome
cataract
hypertension
muscle weakness
peptic ulcer disease
osteopenia with increased risk for fracture
skin thinning
What is the CURB65 score
CURB65 score calculation
confusion = 1 point BUN >7mmol/L = 1 point respiratory rate >30 = 1 point blood pressure low (systolic <90mmHg or diastolic <60mmHg) = 1 point age >65 = 1 point
CURB score
0-1 = treat as outpatient
2-3 = hospitalize or monitor closely as outpatient
4-5 = hospitalization including consideration for ICU
Outpatient management of pneumonia
Azithromycin or clarithromycin or doxycycline
Acute cough
<3 weeks
Subacute cough
3-8 weeks
Chronic cough
> 2 months
Normal neck circumference
- 5 inches women
17. 5 inches men
CPAP requirements for driving
driving guidelines usually require patients with OSA to be compliant with CPAP treatment for >4 hours of use on >70% of nights they may drive
What is a hypopnea
decreased airflow (>50% reduction) with decreased oxygen saturation (>4% decrease) or EEG aoursal
AHI equation and meaning of results
AHI = (# apnea events + # hypopnea events) / time asleep in hours
in adults AHI <5 / hour is normal >5 / hour is OSA 6-15 / hour is mild OSA 16-30 / hour is moderate OSA >30 / hour is severe OSA
Diagnostic criteria of OSA
OSA is diagnosed in a patient who has (A or B) plus C
A - excessive daytime sleepiness that cannot be explained otherwise
B - 2+ of the following with no other explanation recurrent choking or gasping in sleep
recurrent awakening from sleep
daytime fatigue
C - AHI >5
Indications for OSA treatment
symptomatic (daytime sleepiness, daytime fatigue, recurrent awakening in sleep, choking / gasping in sleep etc)
AHI >15, which is associated with significant increased risk of cardiovascular disease
occupation in which safety is critical (e.g. pilot)
presence comorbid medical condition of which OSA may contribute to (hypertension, cardiovascular disease, pulmonary hypertension, heart failure)
Indication for BiPAP in OSA
Bi-level therapy Positive Airway Pressure (BiPAP) may be used instead of CPAP for large size adults requiring more positive pressure
Small bowel obstruction top 3 causes
- Adhesions
- Hernia
- Malignancy
Large bowel obstruction top 3 causes
- Malignancy
2. Volvulus
What is dyspepsia
1+ of the following symptoms
post-prandial fullness
early satiety
epigastric pain or burning
What tests can be performed to test for H. Pylori in order of sensitivity and specificity
sensitivity & specificity: serology < fecal antigen test / urea breath test < EGD biopsy
Cause of peptic ulcer from most to least common
1) H. pylori infection in 75% of cases
2) NSAID in 5-25% of cases
3) cancer (rare, but important to consider)
4) idiopathic and other stress ulcer in severely ill patients chemotherapy or radiation ulcer acid hyper secretion syndrome crack cocaine
H Pylori eradication therapy
Treatment only for patients with dyspepia, ulcer, malignancy -> most with H Pylori are asymptomatic
1st line = triple therapy of 2 antibiotics and 1 PPI for 10-14 days
- clarithromycin
- amoxicillin (or Metronidazole for patients allergic to penicillin)
- PPI
2nd line = quadruple therapy of PPI, bismuth and 2 antibiotics for 10-14 days
- Metronidazole
- Tetracycline (or Doxycycline)
- Bismuth
- PPI
H. pylori eradication is difficult with success rate of ~90%
4+ weeks after completion of therapy, eradication confirmed by urea breath test, fecal antigen test or EGD biopsy
confirmation of eradication recommended for all patients, but especially for patients with persistent symptoms after eradication therapy, peptic ulcer, gastric lymphoma or gastric cancer
Imaging modality of choice for gastric cancer
CT
Functional dyspepsia diagnosis
diagnosis based on Rome criteria fulfilled for >6 months
A) >1 of the following symptoms
post-prandial fullness
early satiety
epigastric pain or burning
B) no evidence of structural disease to explain symptoms
Functional dyspepsia management
- Test and treat PRN H pylori
- Anti-secretory therapy trial 4-8 weeks
1st line - PPI
2nd line - H2RA - Antidepressants trial of 4-6 weeks
3rd line = tricyclic antidepressants - Prokinetic agents trial of 4 weeks
dopamine antagonist: Metoclopramide, Domperidone
IBS clinical presentation
chronic abdominal pain or discomfort
chaotic defecation (period of normal bowel movement punctuated by episodes of constipation and / or diarrhea)
IBS diagnostic criteria
ROME III
patients have irritable bowel syndrome if they have all of the following 2 criteria for >3 months with onset >6 months prior to diagnosis
1) recurrent abdominal pain or discomfort
2) 2+ of:
improvement with defecation
onset associated with change in stool frequency
onset associated with change in appearance of stool
Definition of constipation
defecation <3 times a week of hard and lumpy stool with straining
Rome III criteria for functional constipation
1) 2+ of the following
straining for >1/4 of defecation
lumpy or hard stool for >1/4 defecation
sensation of incomplete evacuation for >1/4 defecation
sensation of anorectal blockage for >1/4 defecation
manual maneuver for >1/4 defecation
<3 bowel movements per week
2) loose stools rarely present without use of laxative
Diagnostic approach to constipation
1) always perform history, physical exam and standard work up (laboratory test, decal occult blood test, colonoscopy)
2) after ruling out causes by history, physical exam and standard work up, start trial of lifestyle modification, fiber and laxatives
3) if trial of lifestyle modification, fiber and laxatives were inadequate, consider further work up (anorectal manometry, balloon expulsion test, defecography, colonic transit test)
Constipation management
1) Treat underlying cause
2) Symptomatic management
lifestyle modification: increase fluid intake, physical exercise, going to washroom regularly
1st line = fiber supplementation including Psyllium (Metamucil)
2nd line = laxative, which are added in the following priority
a) Magnesium Hydroxide (Milk of Magnesia)
b) Bisacodyl (Duclolax)
c) Polyethylene Glycol (Golytely, Colyte)
last line = enema PRN after several days of constipation to prevent fecal impaction
