Pulm exam 1 Flashcards
GINA definition of asthma
chronic airway inflammation; history of respiratory sx (wheeze, sob, chest tightness, cough) that vary over time and in intensity, together with variable expiratory airflow
What term defines wheezing, breathlessness, chest tightness, and coughing
obstruction (typically occurs at night or in the early morning)
All asthma patients are at risk for acute severe disease, you want to treat underlying airway inflammation with what two steps
control asthma
reduce asthma-associated risk
What is the most common chronic disease among children
asthma
What are the 3 predictors for persistent adult asthma
atopy (hypersensitivity to environmental allergens, type 1 allergic rxn with IgG antibody and asthma)
onset during school age
presence of bronchial hyperresponsiveness (BHR)
The severity of asthma in childhood is the predictor of severity in adulthood
true
How does genetic factors affect asthma
strong risk factor for offspring
risk increased with FH of atopy
How does enviornmental factors affect asthma
secondhand smoke exposure increase risk
outdoor pollutants
exposure to specific allergens in the workplace (late in life)
How does obesity affect asthma
child: risk factor for asthma especially girls
adult: risk factor for asthma
How does adult-onset asthma affect people
atopy
nasal polyps
aspirin sensitivity
occupational exposure
recurrence of childhood asthma
Pathophysiology of asthma
inhaled allergens are taken up by antigen presenting cells (t cells) activate Th2 response, b cell production of IgE and pro-inflammatory cytokines and chemokines, activation of eosinophils, neutrophils, alveolar macrophages
What is the early phase response to asthma
activation and degtanulation of mast cells and basophils
acute bronchoconstriction that lasts over 1 hour after exposure
What is the late phase response to asthma
activated airway cells release inflammatory cytokines and chemokines causing more inflammation
increased airwat inflammation and hyperresponsivness that occure 4-6 hours after initial allergen challenge
What is airway inflammation (chronic; although symptoms are intermittent)
T-lympohcytes release cytokines which cause eosinophilic infiltration, IgE production by B-lymphocytes
mast cells infiltrate airway smooth muscle and broncial epithelium causing mucous gland hyperplasia and mast cell degranulation (develop pro-inflammatory mediator, AHR and airway remodeling)
What is airway hyper responsiveness (AHR)
exaggerated ability of airways to narrow in response to stimuli
related to airway inflammation and structural airway changes
How does airway smooth muscle construction cause airway obstruction
-tone maintained by sym, parasym, and non-adrenergic
-constriction results form mediators like histamine and prostaglandins
How does airway edema cause airway obstruction
-inflammatory mediators (histamine, leukotriene, bradykinin) will increase microvascular permeability causing edema
-rigid airway limit air flow
How does mucus hyper secretion cause airway obstruction
increase number and volume of mucous glands
How does airway remodeling cause airway obstruction
some pt will have fixed obstruction
characterized by epithelial damage, subepithelial fibrosis, airway smooth muscle hypertrophy, increase mucous production/vascularity of airways
Range of clinical presentation and diagnosis
normal pulmonary function with symptoms only during acute exacerbation to significantly decreased pulmonary function with continuous symptoms
History of clinical presentation and diagnosis
FH, SH, precipitating factors, exacerbations, development of symptoms, treatment
Symptoms of asthma
defining: wheezing, sob, chest tightness, coughing (worse at night)
-anxious/agitated
-mental status change lead to respiratory failure
-presence of precipitating factors
Signs of asthma
tachypnea
tachycardia
use of accessory muscles
auscultation (end expiratory wheezes/through inspiration/expiration)
bradycardia and absence of wheezing (respiratory failure)
What are the 5 defining features of lab tests (variable expiratory flow limitation)
spirometry
increase in PEF >20% after bronchodilator
increase IgE
(+) redioallergosorbent test (RAST)
fractional exhaled nitric oxide (FeNO) use when clinical course and spirometry is unclear
What is the spirometry lab test
FEV1/FVC <80% and at least one after bronchodilator
-increase in FEV1 if 12% or 200ml
-increase in 10% in predicted FEV1 (may be normal if pt is not symptomatic)
What is the ppb for adults and children for FeNO
> 50 ppb adults
35 ppb for 5-12 yo
What is acute asthma
rapid (1-2 hr) more commonly deterioration over days to weeks
severity does not correspond with severity of chronic disease
sx - may be unable to communicate in full sentences
signs - pulsus paradoxus, diaphoresis, cyanosis
tx
asthma exacerbation severity: mild/moderate
PEF >50% predicted or personal best
dyspnea limiting activity
talks in phrases or sentences
prefers sitting to lying
possible accessory muscle use
SpO2 >90% on room air
HR <120
asthma exacerbation severity: severe
PEF <50% predicted or personal best
dyspnea at rest
sits hunched forward
talks in words
agitated, diaphoretic
accessory muscle use
SpO2 may be <90% on room air
RR >30
HE >120
asthma exacerbation severity: life-threatening
PEF <25% predicted or personal best
too dyspneic to speak
depressed mental status
cyanosis
inability to maintain respiratory effort
absent breath sounds
minimal or no relief from frequent inhaled SABA
bradycardia or hypotension
FEV1 (forced expiratory volume in 1 second)
normal 80-120% predicted
volume exhaled during first second of a forced expiratory maneuver started form the level of total lung capacity
-its reduced in both obstructive and restrictive lung disease
FVC (forced vital capacity)
normal 80-120%
total volume of air expired after a full inspiration
pts with obstructive lung disease usually have a normal or only slightly decreased vital capacity, pts with restrictive lung disease have a decreased vital capacity
FEV1/FVC
normal >0.7 of predicted
% of vital capacity which is expired the first second of maximum expiration
-healthy pt the FEV1/FVC usually around 70%
-obstructive lung disease it decreased and can be as low as 20-30% in severe obstructive airway disease
-restrictive disorders have a near normal level
Do bronchodilators do anything to inflammation
relax constricted smooth muscle in the airway
-improve airflow into the lungs -> relief
no effect on inflammation
PEF (Peak expiratory flow)
normal 80-100%
max airflow during forced expiration beginning with the lungs fully inflated; max speed of ecpiration
What are the SABAs
albuterol
levalbuterol
What are the LABAs
formoterol (can be used as an rescue inhaler)
salmeterol (cause headache)
arformoterol
What are the ultra LABAs
indancaterol (cause cough, headache)
olodaterol (cause nasopharyngitis)
vilanterol (only in combo inhalers)
beta 2 adrenergic agonists work on bronchial smooth muscle and ______ rates of metabolism and ______ duration of binding to the receptor prolonging their effects
decrease
increase
bronchodilator MOA
activate B2R decreasing Ca2+ levels and phosphorylation of proteins involved in smooth muscle relaxation
-inhibit PLC pathway
-decrease myosin actin interactions -> inhibit MLCK and activate MLC phosphatase decreasing phosphorylation of myosin
SABA side effects
common: muscle tremor
serious: tachycardia, hypokalemia
LABA and ultra LABA side effects
severe asthma exacerbation and asthma-related death when used as monotherapy
SABA DDI
nonselective beta blockers
diuretics (increase hypokalemia)
LABA and ultra LABA DDI
nonselective beta blockers
cannabinoids
haloperidol
MAOI and RCA
loop and thiazide diuretic
Muscarinic receptor antagonists are synthetic quaternary _________ compounds, chemically related to atropine
ammonium
What are the SAMAs
ipratropium (cause paradoxical beonchospasm)
What are the LAMAs
tiotropium
aclidinium bromide
umeclidinium bromide
glycopyrrolate
Muscarinic receptor MOA
block Ach binding to M3R
drugs bind to M1R, M2R, and M3R
rapid dissociation from presynaptic M2R, except ipratropium decrease its effectiveness at M3R
Side effects of muscarinic receptors
dry mouth or xerostomia
blurred vision
urinary retention
headache
V/D
nasopharyngitis, cough, rhinitis, sinusitis, tachycardia
What LAMA mat worsen symptoms of narrow-angle glaucoma
tiotropium
What are corticosteroids main effects
metabolic -> carbs and proteins
anti-inflammatory/immunosuppressive
What specific activity does prednisone, prednisolone, and methylprednisolone have
mineralocorticoid activity this can increase blood pressure from Na+ and water retention
corticosteroids MOA
bound in plasma to corticosteroid binding globulin (CBG)
enters the cell and interacts with intracellular glucocorticoid receptor
receptor changes conformation and translocated to nucleus
receptor binds to glucocorticoid response element which stimulate/inhibit gene transcription
What 3 corticosteroids have a higher GR affinity
budesonide
ciclesonide
fluticasone
Anti-inflammatory effects of corticosteroids
increase anti-inflam genes and decrease inflam genes
decrease pro-inflam factors secreted by cells
inhibits effect on inflammatory cells in airway epithelium and submucsoa
Side effects of ICS
headache
pharyngitis
oral candidiasis
cough
dysphonia
side effects of systemic corticosteroids
GI upset, hyperglycemia, psych disturbances
chronic use: AEIOU(H)
inhaled corticosteroids DDI
azole/macrolides
CYP3A4 inducers
CYP3A4 inhibitors
systemic corticosteroids DDI
antacids
fluoroquinolone
CYP3A4 inducers/inhibitors
Phenytoin
Warfarin
avoid live vaccines
IgE binding immunomodulators
omalizumab (IgG monoclonal antibody against IgE)
IgE binding immunomodulators MOA
binds to free IgE generated during first exposure inhibiting IgE binding to IgE receptor on mast cells and basophils
decrease release of mediators from cells decreasing allergic inflammation
IL-4 and IL-13 receptor antagonists MOA
dupilumab (dupixent) recombinant human IgG4 monoclonal antibody that binds to IL4-R
blocks alpha subunit of IL-4 receptor
release of proinflammatory cytokines, chemokines, IgE
What does eosinophils do in IL-5
eosinophils migrate to inflamed tissues
IL-5 plays a fundamental role in esoinophil differentiation. maturation, activation, and inhibition of apoptosis
IL-5 and IL-5 receptor antagonists drugs
IgG monoclonal antibodies
benralizumab
mepolizumab (preferred in step 5 for 6-11yo)
reslizumab
IL-5 and IL-5 receptor antagonists MOA
mepolizumab and reslizumab bind to IL-5
benralizumab binds to IL-5 receptor
inhibit IL-5 signal reducing production, recruitment, activation, and survival of eosinophils
Tezepelumab: Inhibitor of TSLP action
its a cytokine released from the airwat epithelium in response to insults
it binds to its receptor and activated the production of inflammatory cytokines
tezepelumab binds to TSLP and prevents its interaction with the TSLP receptor complex which inhibits inflammatory pathways
it reduces the activity of IL-4, IL-5, and IL-13
monoclonal antibodies side effects
headache, injection site reaction, antibody development
BBW: anaphylaxis with omalizumab and reslizumab
dermatologic reactions and ocular effects with dupilumab
increase serum creatinine kinase with omalizumab
monoclonal antibodies DDIs
avoid live vaccines
Leukotriene modifiers drugs
montelukast
zafirlukast
Leukotriene modifiers side effects
headaches
montelukast: dizziness, stomach pain*, dyspepsia, diarrhea, serious neuropsychiatric events
Leukotriene modifiers MOA
block action of leukotrienes by binding to LT1 receptors in smooth muscle cells
reduce bronchoconstriction, bronchial reactivity, mucosal edema, mucus hypersecretion, resulting in less inflammation
montelukast DDI
CYP2C9, 2C8, 3A4/5 inducers/inhibitors
zafirlukast DDI
phenytoin
CYP2C9 substrates
food decreased bioavailability
What is chronic asthma
prevent chronic and troublesome symptoms
maintain normal or near normal pulm function
meet pt expectations of satisfaction with asthma care
prevent progressive loss of lung function
require infrequent use of SABA
maintain normal activity levels
prevent exacerbations of asthma and the need for ED visits/hospitalizations
provide optimal pharmacotherapy with min/no ADE
What is acute asthma
correct significant hypoxemia
reverse airflow obstruction rapidly
reduce likelihood of exacerbation relapse or recurrence of severe airflow obstruction in the future
Modifiable risk factors for asthma
avoid exposure to tobacco smoke
avoid known food allergies
weight (5-10% decrease if obese)
Strategies and interventions for asthma
smoking cessation (at every visit, advise caregivers to avoid smoking near children)
physical activity
occupational asthma (remove trigger)
severe asthma (refer to specialist)
Common asthma triggers
indoor/outdoor mold
tobacco smoke
medications
occupational substances
animal dander
strong odor/spray
cockroaches
pollen
cooking sources
dust mites
Digital health tools for asthma
small sensor clipped to inhaler will transmit data to an app on pt phone
send dose reminders
informs pt of air quality in area and potential triggers
transmits data regarding inhaler usage to EHR
MyAsthma App
provide info/training on asthma and inhaler techniques
include platform for asthma action plan, asthma monitoring checklist, and symptom tracker
send daily forecast to inform pt of triggers
Aspirin-exacerbated respiratory disease (AERD)
nasal congestion and anosmia that progresses to rhino sinusitis with nasal polyps
hypersensitivity to aspirin
asthma attack
can occur w/in min to 2 hours
What does non-selective beta blockers have to do with asthma
worsen asthma control
avoid use
beta 1 selective agents are best (metoprolol, atenolol)
(NO labetalol, carvedilol, pindolol, timolol, propranolol)
Vaccinations for asthma
PCV-20 (adults 19+ with chronic lung disease)
annual flu shot
covid-19
RSV vaccine (once over age 60)
Counseling for asthma
smoking cessation
meds
-difference btw maintenance/as needed inhalers
-assess technique and clean regularly
asthma action plan
-symptom based
PEF based (adults only)
Drug delivery devices for asthma
particles need to be 1-5 to reach the lower airways
they are deposited by inertial impaction or gravitational sedimentation
appropriate device technique is essential to achieve optimal drug delivery and therapeutic effect
pt instruction + demonstration = improved inhaler technique
Corticosteroid use in asthma
best anti-inflammatory effect
improve beta 2 agonist response
ICS for asthma
preferred for all age groups
decrease systemic effects
max high dose 3-6 months to min risk of AE
give twice daily
2 weeks to see significant result
Dose for children 6-11: Beclometasone dipropionate (HFA), Budesonide (DPI), Fluticasone propionate (DPI), Fluticasone propionate (HFA)
Beclometasone dipropionate: L (50-100) M (100-200)
Budesonide: L (100-200) M (200-400)
Fluticasone propionate: L (100-200) M (200-400)
Fluticasone propionate: L (100-200) M (200-500)
Dose for >12 yo: Beclometasone dipropionate (HFA), Budesonide (DPI), Fluticasone furoate (DPI), Fluticasone propionate (HFA/DPI)
Beclometasone dipropionate: L (100-200) M (200-400)
Budesonide: L (200-400) M (400-800)
Fluticasone furoate: L (100) M (n/a)
Fluticasone propionate: L (100-250) M (250-500)
What is the main thing to counsel patients on for ICS
rinse mouth with water and spit
How does ICS variability response occur
GLCCI1 (pharmacogenomics help assist with individual asthma treatment plans)
Systemic corticosteroids for use in asthma
tx for acute asthma after starting SABA (4-12 h onset)
ORAL is better
cont until PEF >70% of personal best AND asthma symptoms are resoved
avoid as long-term controller meds (try to decrease always)
Beta 2 adrenergic agonists for asthma
better bronchodilator in acute asthma than anticoags and are better drug of choice
SABA for asthma
most effective agent for reversing acute airway obstruction
MDI + spacer is just as good as regular use
not for daily dosing
Albuterol/Levalbuterol
Dosing for asthma based on exacerbation
doses doubled and changed from PRN to scheduled
LABA for asthma
good for nocturnal symptoms
Step 1/2: formoterol only used in low ICS combo
Step 3/4/5: Laba indicated with low, medium, high dose ICS
NOOOOOO LABA MONOTHERAPY
can come in combo product
Anticholinergics (muscarinic antagonists) for asthma
bronchodilating effects are not as effective as beta agonists
When to use Ipratropium
add to SABA during mod-severe exacerbation
ONLY used in ED***
When to use Tioropium
if uncontrolled on ICS + LABA, then add
not for <12 yo, can be add-on for pt w/ h/o exaverbations
Leukotriene modifiers for asthma
improve FEV1 and decrease asthma symptoms, SABA use, and asthma exacerbations
less effective than low ICS (not effective if combo them)
Leukotriene modifiers BBW
neuropsychiatric events
Leukotriene modifiers are beneficial in pt with what
allergic rhinitis, aspirin sensitivity
IgE binding inhibitor (omalizumab) for asthma
Step 5 asthma tx when asthma is not controlled by ICS and if (+) skin test or aeroallergens
decrease ICS use/number of exacerbations, improve sx and QOL, reduce OCD dose
ADE and monitoring of IgE binding inhibitor (omalizumab)
inj site rxn
anaphylaxis (occur any time, provide prescription and education on use of SQ epi)
monitoring pt:
first 3 injections for 2 hours after administration
thereafter 30 minutes after admin
IL-5 antagonist / IL-5 receptor antagonist for asthma
severe eosinophilic asthma thats uncontrolled on Step 4/5 tx
reduce severe exacerbations, improve qol, lung function, symptom control
decrease med OCS dose
IL-4 receptor antagonist for asthma
add-on maintenance tx for step 5 eosinophilic phenotype or those requiring maintenance OCS
reduce severe exacerbations, improve qol, lung fx, sx control
IL-4 receptor antagonist ADE
inj site rxn
transient blood eosinophilia
rate cases of eosinophilic granulomatosis with polyangiitis (EGPA)
Thymic stromal lymphopoietin (TSLP) antagonist for asthma
add-on maintenance tx for severe asthma in >12 yo
reduce severe exacerbations, improve qol, lung fx, sx control
greater clinical benefit w/ higher blood eosinophils and/or higher FeNO
insufficient evidence in pt taking maintenance OCS
tezepelumab
Allergen-specific immunotherapy for asthma
adjunct tx to standard tx pharmacotherapy
need to identify and use correctly with allergen
assocaited w/ reduction in sx scores, med requirements, and improved airway hyperresponsiveness
SQ immunotherapy (SCIT) for >5 yo
guidelines against SLIT (sublingual)
What is the preferred initial tx and alternative initial tx: infrequent asthma symptoms (1-2 d/wk or less)
PRN low dose ICS + Formoterol
alt: low dose ICS taken when SABA taken
tezepelumab (TSLP) ADE
arthralgia, back pain, pharyngitis
What is the preferred initial tx and alternative initial tx: asthma symptoms less than 3-5 d/wk, with normal or mild reduced lung function
PRN low dose ICS + Formoterol
alt: low-dose ICS + PRN SABA
What is the preferred initial tx and alternative initial tx: asthma sx most days (4-5 d/wk or more) or waking due to asthma once a week or more, or low lung function
Low-dose ICS-formoterol maintenance and reliever therapy (MART)
alt: low dose ICS-LABA + PRN SABA
(or + PRN ICS-SABA)
(or + med-dose ICS + as needed SABA)
(or + PRN ICS-SABA)
What is the preferred initial tx and alternative initial tx: daily asthma sx, waking at night w/ asthma once a week or more with low lung function
Med-dise ICS-formoterol maintenance and reliever therapy (MART)
alt: med-high dose ICS-LABA
(+PRN SABA)
(+PRN ICS-SABA)
What is the preferred initial tx and alternative initial tx: initial asthma presentation is during an acute phase
treat as exacerbation including short course OCS id severe; commence medium dose MART
alt: tx as exacerbation including short course of OCS if severe; commenece med/high dose ICS-LABA + PRN SABA
Before starting initial controller tx for asthma what should you do
record evidence for the diagnosis of asthma
record the pt level of sx control and risk factors, including lung function
schedule follow-up
After starting initial controller tx for asthma what should you do
check adherence and pt response after 2-3 months
step down tx once good control has been maintained for 3 months
Mild asthma
well controlled with Step 1/2 tx (low intensity tx)
Moderate asthma
well controlled with Step 3/4 tx (low/med dose ICS-LABA0
Severe asthma
uncontrolled despite optimized tx with high-dose ICS-LABA or requires high-dose ICS-LABA to prevent it from becoming uncontrolled
must distinguish from asthma that is difficult to treat to inadequate or inappropriate tx, or persistent problems w/ adherence or comorbidities
Asthma severity cannot be assess unless what 2 things happen
good asthma control and tx stepped down to find pt min effective dose
OR
unless asthma remains uncontrolled despite at least several months of optimized max therapy
What is the 4 questions for asthma symptoms control (initial tx) and what constitutes as well controlled, partly controlled, and uncontrolled
daytime asthma symptoms more than 2x/wk
night waking due to asthma
SABA reliever for sx more than 2x/wk
any activity limitation due to asthma
0: well controlled
1-2: partly
3-4: uncontrolled
Risk factors for poor asthma outcomes
assess risk factors at diagnosis and periodically
measure FEV1 at start of tx, after 3-6 months of ICS tx to record pt personal best lung function, then periodically
Track 1 (personalized asthma)
Step 1/2: PRN low dose ICS-formoterol
Step 3: low dose maintenance ICS-formoterol
Step 4: med dose maintenance ICS-formoterol
Step 5: +LAMA. consider high dose maintenance ICS-formoterol, +/- anti-IgE, anti-IL5/5R, anti-IL4Ram anti-TSLP
Track 2 (personalized asthma) with all these therapies a reliever as needed ICS-SABA or PRN SABA is used
Step 1: take ICS when SABA taken
Step 2: low dose maintenance ICS
Step 3: low dose maintenance ICS-LABA
Step 4: med/high dose maintenance ICS-LABA
Step 5: +LAMA. consider high dose maintenance ICS-LAMA, +/- anti-IgE, anti-IL5/5R, anti-IL4Ram anti-TSLP
What can also be used as a last line add-on therapy for asthma
azithromycin (TIW)
-for persistent symptomatic asthma despite high dose ICS LABA
-sputum for atypical mycobacteria
-check ECG at baseline; ensure QTc <450
When to review pt response after starting controller tx
2-3 months or earlier
before increasing therapy:
evaluate pt inhaler technique and adherence to therapy
When to review pt response after pt have controlled asthma
1-6 months
once controlled for 3 months a step down can occur
use LABA for the shortest time possible
Tx for acute asthma (exacerbation)
early and appropriate intensification of therapy is important to resolve the exacerbation and prevent relapse and future severe airflow obstruction
early and aggressive tx for quick resolution
optimal tx depends on severity
pt condition deteriorated over time
Initial at home treatment
inhaled SABA: up to two treatments 20 min apart of 2-6 puffs by metered dose inhaler or nebulizer
Good response to initial at home treatment
no wheezing or dyspnea
PEF >80% predicted or personal best
-contact clinician for followup instructions and further management
-may cont inhaled SABA q3-4h for 24-48 h
-consider short course of oral systemic corticosteroids
Incomplete response to initial at home treatment
persistent wheezing and dyspnea
PEF 50-79% predicted or personal best
-add oral systemic corticosteroid
-cont inhaled SABA
-contact clinician urgently (this day) for further instruction
Poor response to initial at home treatment
marked wheezing and dyspnea
PEF <50%
-add oral systemic corticosteroid
-repeat inhaled SABA immediately
-if distress is severe and non-responsive to initial tx:
call doc and process to ED, may need 911
Discharged home for ED management
responding to therapy in the ED w/ sustained response to SABA
meds: SABA, 3-10d course of PO corticosteroid, ICS, other long-term controller med
Admitted to hospital for ED management
do not repsond to intensive therapy w/in 3-4 h
meds: oxygen, cont nebulization of SABA, and systemic corticosteroid
When to give oxygen in asthma
children, pregnant women, pt w/ coexisting heart disease, give to maintain 94-98%
all other pt five to maintain 93-95%
Written asthma action plan
-part of standard of care, does not decrease mortality
-give pt freedom to adjust therapy based on personal assessment of disease control using predetermined plan
What does a written asthma action plan include
instruction on daily management
how to recognize and handle worsening asthma
-evaluate sx/monitor PEF
-early signs of deterioration (increase nocturnal symptoms, increase use of SABA, not responding to increased use of SABA)
Pt may get script for oral corticosteroid to use on a PRN basis
Peak expiratory flow measurement is considered for pt with
mod to severe asthma
poor perception of worsening asthma or airflow obstruction
unexplained response to enviornmental or occupational exposures
measured daily upon wakening and when asthma symptoms worsen
For PEF based asthma action plans what should you do
pt personal best PEF establish over 2-3 wk period when pt is receiving optimal therapy
subsequent PEF measurements are evaluated in relation to their variability from the pt best PEF measurement
What is green zone
PEF 80-100% of personal best
current therapy is acceptable
What is yellow zone
PEF 50-79% of personal best
impending exacerbation, intensify therapy with SABA, possibly add oral corticosteroid, call physician
What is red zone
PEF <50% of personal best
medical alert, use SABA immediately, take oral corticosteroid, go to ED
Special Populations for asthma: Pregnancy
1/3 of women will experience worsening asthma
using meds to achieve good symptom control and prevent exacerbations is justified even when safety in pregnancy has not been unequivocally proven
manage aggressively
use Budesonide category B
albuterol DOC for tx of asthma sx and exacerbations
Special Populations for asthma: Young Children
tx 0-4 yo is extrapolated from studies completed in adults and older children
albuterol and ICS are DOC
montelukast is common due to formulation
nebulization is commonly used
MDI + VHS becoming more popular due to decreased time of admin compared to nebulization
bedesonide: only corticosteroid available as nebulization and is approved for this age group
What are the phosphodiesterase inhibitors
Methylxanthines (theophylline)
Phosphodiesterase 4 inhibitor (roflumilast)
Phosphodiesterase 3/4 inhibitors (ensifentrine)
What are the main effects of phosphodiesterase inhibitors
Bronchodilation and decrease inflammation
Difference between theophylline and caffeine
Theophylline has more selectivity for smooth muscle than caffeine
Does theophylline cross the placenta
Yes and it is also secreted in milk
Theophylline MOA
Inhibitor of phosphodiesterase (PDE) non selectively which acts on cAMP and cGMP
The inhibitory effects on number and activity of inflammatory cells in airway epithelium/submucosa
Prevent translocation of pro inflammatory transcription factors into the nucleus
Which drugs decrease theophylline clearance
Cimetidine
Microliters
Allopurinol
Propranolol
Quinolones
Which drugs increase theophylline clearance
Carbamazepine
Phenytoin
Moricizine
Theophylline side effects
Headache
N/V
Insomnia
Arrhythmias
Seizures
Death
The higher concentrations of theophylline cause adenosine effects which are
Increase HR and vasoconstriction
Decrease bronchi construction
Roflumilast MOA
Selective inhibitor of phosphodiesterase 4 (PDE4)
Inhibit PDE4 which decreases cAMP leading to decreased inflammatory effects, fibrosis and relaxes smooth muscle l
Side effects of roflumilast vaccine
N/V
Wt loss
Decreased appetite
(NO cardiac effects because it doesn’t antagonize the adenosine system)
Ensifentrine MOA
Dual inhibitor of PDE 3 and 4
Works on cAMP and cGMP which increases them
NOT 5 and 7
Causes bronchodilation, anti inflammatory effects, and mucocillary clearance
Definition of COPD by the GOLD standard
heterogeneous lung condition characterized by chronic respiratory symptoms (dyspnea, cough, sputum production, and/or exacerbations) due to abnormalities of the airways and/or alveoli that cause persistent airway obstruction
What are some characteristics of COPD
progressive
airflow limitation that is not reversible
persistent exposure to noxious particles/gases
lung airways and parenchyma are susceptible to inflammation
causes extra pulmonary effects
What are the 2 classifications of COPD
Chronic bronchitis
-mucus secretion with cough
Emphysema
-destruction of alveoli, no fibrosis
Causes of COPD
cig smoking or second hand smoke
occupational exposure
environmental air pollution
genetics
Host factors for COPD
alpha 1 antitrypsin (AAT) deficiency causes emphysema
AHR
recurrent infections
Pathophysiology of COPD
change in central airway, peripheral airway, lung parenchyma, and pulmonary vasculature from repeated exposures to noxious particles and gases and chronic inflammation
What is the mechanistic triad of COPD
Inflammation
Imbalance between proteases and antiproteases
Oxidative Stress
mechanistic triad of COPD: Inflammation
neutrophils, macrophages, and CD8 T cells
leukotriene B4, IL-8, TNF-alpha
elastase, cathepsin G, protease 3
mediators sustain inflammation causes damage to lung structure
eosinophils may be increased
mechanistic triad of COPD: Imbalance between proteases and antiproteases
proteases are part of the normal protective and repair
increase production of destructive proteases
decrease production or protective antiproteases
AAT (inhibit proteolytic enzymes, decreased protease activity causing destruction of alveolar walls and parenchyma)
mechanistic triad of COPD: Oxidative Stress
hydrogen peroxide and nitric oxide found in epithelial, breath, urine
promotes inflammation
protease imbalance
oxidants cause airway narrowing and damage to lung extracellular matrix
Central airways: inflammatory cells and mediators stimulate what
mucus secreting gland hyperplasia
mucus hyper-secretion
-cause cough and sputum production
Peripheral airways (major site of airflow obstruction)
airway blocked by inflammatory exudates + mucus hyper secretion
loss of elasticity and destruction of alveolar attachments
infiltration of inflammatory cells, increased smooth muscle tissue, and fibrosis
As airflow obstruction worsens what happens
rate of lung emptying is slowed (increased air left in lung after exhalation)
-pt breathes at higher vol
-decrease amount if air pt inhales (dyspnea)
Air trapping -> pulmonary hyperinflation
-flattening the diaphragm
Impaired gas exchange causes hypoxemia and hypercapnia what are those
hypoxemia: inequality in Va/Q, increase erythrocytes to get more oxygen
hypercapnia: elevated CO2 levels in blood
Extra-pulmonary effects of COPD
CVD comp, late COPD after hypoxemia, lead to cor pulmonale with PE
progressive loss of skeletal muscle
Symptoms of COPD
chronic cough (>3 months)
chronic sputum production
dyspnea on exertion
recurrent LRT infections
Signs of COPD
use of accessory muscles
pursed lip breathing
increased RR
shallow breathing
hyperinflation of chest
auscultation
cyanosis, tachycardia
cor pulmonale
Lab tests for COPD
polycythemia (elevated hematocrit by 55%)
FEV1 <35% check pulse ox
O2 <92% check ABG
AAT level if <45 yo and present with COPD
How can medical history contribute to COPD
risk factor exposure
past MH
FH of COPD
pattern of sx development
h/o exacerbations or hospitalizations
presence of comorbidities (heart disease, osteo, malignancy)
impact of disease on pt life
Diagnosis of COPD
post bronchodilator FEV1/FVC <0.7 confirms presence of persistent airflow limitation
spirometric assessment required to establish diagnosis
What is GOLD 1 (mild) in pt with FEV1/FVC <0.7
FEV1 >80% predicted
What is GOLD 2 (moderate) in pt with FEV1/FVC <0.7
50% < FEV1 <80% predicted
What is GOLD 3 (severe) in pt with FEV1/FVC <0.7
30% < FEV1 <50% predicted
What is GOLD 4 (very severe) in pt with FEV1/FVC <0.7
FEV1 <30% predicted
Assessment of symptoms in COPD diagnosis
measure breathlessness
CAT recommended
- measure of health status impairment, 0-40 score
Assessment of exacerbation risk in COPD diagnosis
largest COPD burden on healthcare system
increase decline in lung function and deterioration in health status
poor prognosis with increased risk of death
What category of COPD are you in if you have 2 or more moderate exacerbations or 1 or more leading to hospitalization
E
What category of COPD are you in if you have 0 or 1 moderate exacerbations (no hospital)
A: mMRC 0-1, CAT <10
B: mMRC >2, CAT >10
Green zone COPD
doing well
usual activity
take daily med
Yellow zone COPD
bad day or COPD flare
more breathless
more cough
cont daily meds and add reliever inhaler, oral corticosteroids, and/or macrolide
Red zone COPD
urgent medical care needed
severe SOB
cough blood
call 911
What are the brief aids in smoking cessation
5 R’s
5 A’s
How is addiction behavioral and physiological
behavioral: break habit
physiological: reduce and eliminate dependence
What does pulmonary rehabilitation do
improve dyspnea, health status, exercise tolerance
decrease hospital and death
all pt with high symptoms
6-8 wks
What are the 3 components of pulmonary rehabilitation
exercise training
breathing techniques
education
Timing for pulmonary rehabilitation
at diagnosis of COPD
hospital discharge
Bronchodilators for COPD
mainstay of tx for systematic COPD
inhaled preferred
long acting (more expensive, better for outcome)
beta 2-agonist (SABA, LABA)
LABA key points for COPD
decrease exacerbations and improve exercise tolerance , dyspnea, and QOL
pt should receive a SABA PRN
Tiotropium key points for COPD
significant decrease exacerbations
good in combo
also need SABA PRN
Methylxanthines indication in COPD
pt who cannot use inhaled meds or ate symptomatic despite appropriate use of inhaled bronchodilators
Methylxanthines concentrations for COPD
5-15: target
>15 ADE
<20: HA, n/v, insomnia
Conditions that affects theophylline concentrations
increase: HF, liver disease
decrease: high protein diet
Aminophylline to theophylline conversion
multiply by 0.8
When to use corticosteroids for COPD
group E with LABA + LAMA, is eosinophils >300
PDE4-I indication for COPD
severe or very severe COPD and a h/o exacerbations
for pt not controlled on long-acting bronchodilator or on fixed dose of LABA/ICS combo
onset is 4 wks
When to add IL-4 receptor antagonist for COPD
pt with COPD, chronic bronchitis, h/o >2 moderate exacerbations or >1 severe exacerbation in last year despite triple therapy and blood eosinophil >300
When to use long-term oxygen therapy in COPD
increase survival in pt with severe chronic hypoxemia
PaO2 <55 mmHg or SaO2 <88% with evidence of right sided HF, polycythemia, or pulmonary HTN
AAT augmentation therapy for COPD
AAT deficiency and mod airflow obstruction (35%-60% FEV1)
What to use in group E COPD
LABA + LAMA + SABA PRN
(add ICS if eos >300)
What to use in group A COPD
bronchodilator + SABA PRN
What to use in group B COPD
LABA + LAMA + SABA PRN
Strong favor of ICS use in COPD
h/o hospital exacerbations
>2 mod exacerbations
eos >300
h/o concomitant asthma
Against use of ICS use in COPD
repeated pneumonia events
eos <100
h/o mycobacterial infection
When patient had dyspnea and is on LABA or LAMA what do you do
LABA + LAMA
When to use azithromycin in COPD
preferentially in former smokers after LABA + LAMA + ICS
When to use rofluilast in COPD
FEV1 <50% and chronic bronchitis after LABA + LAMA + ICS used
When to use dupilumab in COPD
when eos >300 and have chronic bronchitis after LABA + LAMA + ICS
COPD exacerbations definition
an event characterized by increased dyspnea and/or cough and sputum that worsens <14 days which may be accompanied by tachypnea with increased local and systemic inflammation caused by infection, pollution, or other insult to airway
COPD exacerbations etiology
RTI (viral or bacterial)
-number of pt have bacteria colonizing their lower airways in the stable phase of disease
-bacterial burden increased during some exacerbations
Peaks in air pollution
Diagnosis for COPD exacerbations
relies exclusively on pt complaining of an acute change of symptoms: dyspnea, cough and/or sputum production
Tests for COPD
pulse ox
ABG
chest x-ray
EKG
CBC
presence of purulent sputum
biochem tests
First line therapy for COPD exacerbations
bronchodilators
SABA +/- short acting anticholinergics
cont LABDs +/- ICS or initiate as soon as possible
When to use oral corticosteroids
shorten recovery time and length of hospital stay
improve lung function and arterial hypoxemia
pred 40 mg po qd x5d
Antibiotics for COPD exacerbations
3 cardinal symptoms
dyspnea, sputum volume, sputum purulence
presence of 2 cardinal symptoms (one must be sputum purulence)
5-7 days
Antibiotics for uncomplicated exacerbations: <4 exac/year, no comorbid illness, FEV1 >50% of predicted
macrolide
sec/third gen cephalosporin
doxycycline
Antibiotics for complicated exacerbations: >65 yo and >4 exac/year, FEV1 <50% but >35%
augmentin
fluoroquinolone
Antibiotics for complicated exacerbations with risk of p. aeruginosa
fluoroquinolone
IV beta lactamase resistant penicillin with antipeudomonal activity
3/4 gen cephalosporin w/ antipseudomonal activity
Oxygen therapy for COPD patients
titrate to improve hypoxemia with target of 88-92%
NIV Assisted ventilation indications
respiratory acidosis (pH <7.35 and PaCO2 >45 mmHg)
severe dyspnea with clinical signs suggestive of respiratory muscle fatigue such as use of accessory muscles and paradoxical ad motion
Invasive assisted ventilation indications
for pt with more severe symptoms
pts failing NIV
