36/37/38 - Asthma Flashcards
Asthma
Classification & Presentation
Chronic R_eactive + Obstructive_ airway disease
Characterized by:
airway INFLAMMATION** & **HYPERresponsiveness
Presentation:
Wheezing / SOB / chest Tightness
Cough
+/- Increased mucus Production
Asthma
DIAGNOSIS
Requires a combination of:
Medical History**+**Spirometry
Reduced FEV1/FVC ratio = airway obstruction
- *INCREASE in FEV1 > 12%**
- *AFTER BRONCHODIALATOR = Reversibility**
- or bronchoconstriction / HYPERresponsiveness on challenge test*
Phenotype Asthma
Clinical Characteristics
based upon:
Genetic makeup / Bio Mechanisms / Environmental Exposures
Endotype Asthma
Specific Biologic/Immunologic MECHANISM
that drives the
pathophysiologic cause of Asthma presentation
Eosinophilic Endotypes
HIGH /low TH2
NON-eosinophilic Endotypes
HIGH & low TH1
Which Endotype of Asthma?
Dominant Cytokines:
IL-1 / IL-8 / IL-17 / TNF-a / TRL4
Source Cell Types:
TH17 cells - Macrophages - NK/NKT Cells - CD8 TCells
End Result:
↑Neutrophil release of pro-inflammatory chemokines
- *low TH1**
- *NON-eosinophylic Endotypes**
Which Endotype of Asthma?
Dominant Cytokines:
IL-12 / INF-y / 15-Lipooxygenase
Source Cell Types:
TH1 - Goblet Cells
End Result:
↑Neutrophil release of Pro-inflammatory chemokines
- *HIGH TH1**
- *NON-eosinophilic Endotype**
Which Endotype of Asthma?
Dominant Cytokines:
IL-25 / IL-33 / IL-5 / IL-13 / TSLP
Source Cell Types:
TH2 - Mast Cells
End Result:
↑Eosinophil Differentiation & Maturation
↑NO production / ↑Periostin
↑ Mast Cell Degranulation
LOW TH2
Eosinophilic Endotype
just different Cytokines and No B-cell Involvement
Which Endotype of Asthma?
Dominant Cytokines:
IL-4 / IL-5 / IL-13 / TSLP
Source Cell Types:
TH2 - B Lymphocytes - Mast Cells
End Result:
↑Eosinophil Differentiation & Maturation
↑NO production / ↑Periostin
↑ Mast Cell Degranulation
HIGH TH2
EOSINOPHILIC Endytype
Goals of Asthma Therapy
Reduce Impairment
- *<** 2 Daytime Symptoms / WEEK & ↓Reliever meds
- *<** Nightime awakenings / MONTH from asthma
Reduce RISK of future exacerbations / airflow limitation / ADR
Prevent exacerbations
↓ED Visits or Hospitilzations
↓Loss of lung functions / lung growth
↓Drug ADR
What questions do we ask to
ASSESS ASTHMA SEVERITY & CONTROL?
OVER THE PAST 2-4 WEEKS
How much is Asthma Impairing Patient’s Life?
Daytime Asthma Symptoms?
Nighttime Awekenings?
Rescue Medication use?
Lung Function?
PERCEPTION of Limitation
Validated Questionaires
ACT / ATAQ / ACQ
Monitoring & Follow-Up
When to RE-EVALUATE?
Recommend to RE-Evaluate:
Within 1 WEEK after an EXACERBATION
- *1-3 Months after STARTING treatment**
- full benefit may take ~3 MONTHS+*
Every 3-12 Months once stable
WHO SHOULD USE CONTROLLER MEDICATION?
RULE OF 2
- *Daytime Symptoms** or Reliever use
- *>** 2 days per WEEK
- *Nightime Awakening from Asthma**
- *>** 2 days per MONTH
When would consider
STEPPING DOWN?
STABLE FOR 3+ MONTHS
Aims of stepping down:
Minimum effective treatment Dose
Continue encouraging controller dose
ASTHMA ACTION PLAN
Includes WHAT?
Daily Medications
List of TRIGGERS** + **ACTIONS to control
How to RECOGNIZE worsening asthma
based on SYMPTOMS or PEF (peak-flow)
How to RESPOND to worsening asthma
Bronchodilator use & when to INCREASE intnsity of treatment
What Medications
can WORSEN or TRIGGER Asthma?
ASPIRIN
NSAIDs
- *BETA-BLOCKERS**
- OLOLs
What can WORSEN or TRIGGER Asthma?
- *VIRAL** illnesses
- *Exercise / Sport / Exertion**
ALLERGIES
mold / dust / animals / pollen / sulfides / cockroaches
- *Exposure to Irritants**
- *smoke** / air pollutants / perfumes
Stress / Emotions
Endocrine / Hormonal Changes
pregnancy / thyroid disorders / menses
Environmental Factors
vacuuming / open windows / weather / humidity
Medications
ASPIRIN / NSAIDS / BETA LOCKERS
What COMORBID CONDITIONS
may WORSEN ASTHMA?
Atopic Triad
Rhinitis / Sinusitis / Nasal Polypts
GERD
ALLERGIES
food or domestic / allergic bronchopulmonary Aspergillosis
Obesity / Anxiety / Stress
OSA
Obstructive sleep apnea
Role in Therapy:
Reliever / Rescue - Asthma Medications
Inhaled/Oral SABA = Albuterol / Levalbuterol
Inhaled SAMA = Ipratroprium Bromide
ALL PATIENTS NEED QUICK RELIEF MEDICATION
As NEEDED for:
Intermittent / Persistant Asthma - Step 1 +
PREVENTATIVE for:
Exercise Induced Bronchospasm = EIB
Albuterol / Levalbuterol
Drug Class / Onset of Action / ADR
- *SAMA =** Quick Onset:
- *MDI > DPI > Neb > oral**
- oral is NOT preferred*
ADR:
- *Tachycardia / Tremor / Excitement / Nervousness**
rare: Pharyngitis / Rhinitis / Bronchospasm
Precautions:
CV Disease / Arrythmia
HyperThyroidism / Diabetes / Seizures
Ipratropium Bromide
MDI / Neb
Drug Class / Indication / ADR
SAMA
NOT appropriate rescue medication ALONE in ASTHMA
used in COMBO + SABA (albuterol) in patients not responding in ER/hospital
less effective bronchodialator than SABA, NOT anti-inflammatory
ADR:
Well tolerated –> HA / Cough / Eye irritation (neb)
Precautions:
AntiCholinergic Precautions: Glaucoma / BPH
What is the:
PREFERRED INITIAL & BACKBONE CONTROLLER MED
for
PERSISTANT ASTHMA
Step 2+
- *INHALED CORTICOSTEROIDS**
- *-SONE / -NIDE**
Most Effective MONOTHERAPY
only therapy shown to reduce risk of DEATH from ASTHMA
What is the PREFERRED
INHALED CORTICOSTEROID (ICS)
in PREGNANCY?
BUDESONIDE
Pulmicort Flexhaler DPI
Pulmicort Respules Nebulizer (only Neb ICS available)
- *Ok to add LABA**
- if not well controlled*
- *Inhaled Corticosteroids**
- *-SONE / -NIDE**
BENEFITS / USES
- only therapy shown to* REDUCE RISK OF DEATH from ASTHMA
- *MOST effective MONOTHERAPY - Controller**
- *Symptom Improvement**
- *starts @1-2 Days** –> MAX in 4-8 Weeks
- *BHR/Inflammation Improvement**
- *starts @1-2 days** –> progressive up to 1 year
LUNG FUNCTION IMPROVEMENT
begins in 3-6 weeks
- does NOT reduce AIRWAY REMODELING
- -> discontinuation can cause HIGH RISK for EXACERBATION*
- *Inhaled Corticosteroids
- SONE / -NIDE**
ADR / DI
Local: Thrush / Dysphonia / Cough / reflex bronchospasm
Rare: systemic effects / stunted growth / bruising / cataracts
CYP3A4 INHIBITORS
–> increase SYSTEMIC exposure
DI Risk:
Fluticasone-Budesonide >
Ciclesonide,Flunisolide,Mometasone > Beclomethasone
- Reduce risk of LOCAL side effects*
- *RINSE MOUTH / SPACER**
- Reduce ALL ADRs*
- *Step down therapy / lowest effective dose**
Which ICS Drugs have the
HIGHEST DRUG INTERACTION RISK?
Strong CYP3A4 Inhibitors
Fluticasone & Budesonide
>>>
Ciclesonide / FLunisolide / Mometasome
>>
Beclomethasone
least drug ineracton risk
(Ritonavir / Ketoconazole / Protease Inhibitors)
LABA = -TEROL
Uses in Asthma Therapy
- *Preferred ADJUNCT to ICS therapy = Step 3+**
- superior to LTRA / LAMA / cromolyn / theo when ADDED to ICS*
- NEVER use LABA ALONE in ASTHMA*
- *ALWAYS COMBINED WITH ICS**
- not an ALTERNATIVE to ALBUTEROL/ICS*
- *Formoterol = FASTEST onset of Action (Minutes)**
- *Vilanterol = slowest (hours)** –> but long duration (22hours)
What Asthma drug has a
BLACK BOX WARNING?
- *LABA_ _= -terol**
- *ON ITS OWN** –> INCREASE in ASTHMA RELATED DEATHS
LABA should ALWAYS be in COMBO with ICS
LAMA = -IUMs
Asthma Therapy / ADR
ADD-ON
to Med/High dose ICS + LABA = Step 4 or 5
Cause bronchodilation + reduce mucus secretion by:
- inhibiting* muscarinic cholinergic receptors
- *4-8 Week benefit**
ADR:
Dry Mouth / Metallic Taste / AUR
Caution:
NAG / Bladder Obstruction
Which Phenotypic Guided Asthma Therapy?
Can be administered AT HOME?
- *DUPILUMAB = Dupixent**
- *IL-4R / IL-13** Target
- *SUBQ every other week**
>12 y/o
Requires:
Blood EOS > 300 cells/uL
Which Phenotypic Guided Asthma Therapy?
Is indicated for
ALLERGIES** & **HIGH IgE Levels?
- *OMALIZUMAB** = Xolair
- *IgE target** // >6 y/o
IgE has to be 30-700 IU/mL & ALLERGIES
- *SUBQ every 2-4 weeks**
- *DOSED BY WEIGHT & BASELINE IgE**
Which Phenotypic Guided Asthma Therapy?
ONLY IV DRUG
- *RESLIZUMAB** = Cinqair
- *IL-5**
Also 18 y/o+
(others are >12yo)
Requires BLOOD EOS > 400 cells/uL
Which Phenotypic Guided Asthma Therapy?
Biomarker targets are
IL-5
& what are their INDICATIONS?
MEPOLIZUMAB = Nucala
12yo // Blood EOS >150 (90 days) // >300 (1year)
- *RESLIZUMAB** = Cinqair
- *> 18 y/o** // IV // >400 EOS
- *BENRALIZUMAB** = Fasenra
- *IL-5R** // 12yo // >300
Which Phenotypic Guided Asthma Therapy?
Anti-TSLP Antibody
good for BOTH
HIGH & LOW TH2
TEZEPULUMAB
not yet FDA approved
Phenotypic Guided Asthma Therapy
ADR / Requirements
ADR:
- *Nasopharyngitis / HA / Back Pain / Fatigue+Myalgias**
- *INJECTION SITE REACTIONS**
Anaphylaxis / Hypersensitivity
VV
ALL PATIENTS MUST HAVE EPINEPHRINE
- *All ADMIN in healthcare setting**:
- EXCEPT for DUPILUMAB*
Leukotriene Receptor Antagonist = LTRA
Asthma Uses / ADR / DI
Montelukast / Zariflukast / Zileuton
ORAL
- Less effective than ICS* & LABA + ICS
- Safer**, but *no more effective than adding Theophylline
Zileuton = Monitor LFTs
Oral Corticosteroids
Asthma Uses
- *Prednisolone** > Prednisone
- *FOR ORAL SOLUTION, TASTE**
- *Add-On therapy in STEP 6**
- low daily dose*
Asthma EXACERBATIONS
Short course = burst
Methylxanthines
Asthma Uses / ADR
Theophylline = IV/PO —- Aminophylline = IVonly
- *Only modest Asthma Effects**
- not for use in SEVERE asthma*
NARROW THERAPEUTIC WINDOW
life-threatening side effects
- *DRUG INERACTIONS**
- *CYP1A2** & CYP3A4
Mast Cell Stabilizer = Cromolyn Sodium
Asthma Use
Inhibits early/late
Asthma Response&EIB (exercise induced)
not very effective compared to other agents
- *20mg QID** –> 4 weeks
- *2-4 weeks for effectiveness**
NEEDS DAILY CLEANING
hard to use
NEBULIZER SOLUTION
Macrolide Antibiotics
ASTHMA USE?
Azithromycin = AZISAST trial
Beneficial for:
NON-EOSINOPHILIC ASTHMA
Blood Eos < 200 cell/uL
Vitamin D
Asthma Use?
low VIT D –> INCREASED risk of Asthma Exacerbations
Vitamin D:
Inhibits production of IL-17
- good for:*
- *NON-EOSINOPHILIC ASTHMA**
Bronchial Themoplasty
Asthma Use?
Add-on Therapy
for select patients with unconctrolled ASTHMA
Thermal Energy (150*F)
- Reduces:*
- *Bronchial airway smooth muscle MASS** // Airway Narrowing
Which ICS is preferred in CHILDREN?
BUDESONIDE
because it is the
NLY ICS available via NEBULIZER
When to consider
REFERRAL to ASTHMA SPECIALIST?
2+ Exacerbations in 1 Year
that was TREATED with SHORT COURSE STEROIDS
ICU admission** or **Intubation
Unresponsive to Therapy
Uncontrolled on STEP 4+ or STEP 3+ for Children
Atypical Presentation / difficult diagnosis
Phenotypic Guided Therapy
Presence of SEVERAL Comorbidities
SINGLE INHALER THERAPY?
FORMOTEROL** + **ICS
Used as:
Maintenance AND RELIEVER
- reduces EXACERBATIONS*
- *cheaper / mixed results**
- limited evidence*
Which DOSAGE FORM?
Highly dependent on:
TIMING of ACTUATION & BREATH
Hand-Breath Coordination
- SLOW &* DEEP BREATH
- tilt head back to open up airways*
- *MDI**
- *Metered Dose Inhaler**
If coordination is bad:
Use DPI or Breath-Activated MDI or SPACER
MDI + Spacer
has EQUAL EFFICACY to NEBULIZER
Which DOSAGE FORM?
Has an Activation Step (differs for each one)
- *Breath Activated / Actuated**
- less dependent on hand-breath coordination*
DEEP / FORCEFUL BREATH
requires sufficient inspiratory force
- *DPI**
- *DRY POWDER INHALER**
can NOT use spacer or holding chamber
Requires:
clean with DRY cloth when dirty
Spacers & Holding Chambers
For use with WHICH INHALER?
Recommended for WHO?
ONLY (not breath actuated MDI nor DPI)
- *MDI** = METERED DOSE INHALER
- decreases the need for:*
- *Hand-Breath Coordination**
Recommended for:
- *Young Children <4y/o + MASK**
- poor MDI technique*
- *Poor Response to SABA MDI**
should be cleaned with:
soap + water
Asthma Exacerbations
How do we GRADE them?
Mild-Moderate
Talks in PHRASES / Prefers SITTING/LAYING
RESPIRATORY RATE < 30bpm
PULSE 100-120
O2 SAT
PEF >50%
SEVERE
LIFE THREATENING
RISK FACTORS
for
Asthma Exacerbations & Death
- Uncontrolled Asthma Symptoms*
- *OVER-USE of SABA** (>1 /month)
Inadequate ICS Use
Low FEV (<60% predicted
Psychiatric Disease // Trigger Exposure
Pregnancy // Uncontrolled Comorbidities
allergies / obesity / GERD
EOSINOPHILIA** or **Elevated IgE
blood / sputum
>1 Exacerbation in past YEAR
Outpatient Management of EXACERBATIONS
Early +/- Mild Symptoms
Reduction in PEF/FEV (60-80%)
INCREASE
FREQUENCY or # of ALBUTEROL PUFFS
or
NEBULIZER TREATMENT
or
ADD SPACER if MDI
Outpatient Managment of Exacerbations
Late / Severe Symptoms
Reduction in PEF/FEV <60%
- *SYSTEMIC STEROIDS**
- *Prednisone 40-60mg PO 3-7 Days**
Continue rescue / maintanence meds
What Dosage forms are considered
- *DPI’s**
- *Dry Powdered Inhalers**
- *Deep & Forceful Breath**
- less coordination*
DISKUS
- *TWIST / FLEX / TURBO / NEO** - HALERS
- EXCEPT for REDIHALER = BREATH ACTIVATED MDI*
Ellipta / Respiclick
Which drug is considered a
BREATH ACTIVATED MDI?
- REDIHALE*R
- *Beclamethasone = ICS**
easier to use than MDI
Which drug types can cause / should be cautioned with:
BPH / Bladder Neck Obstruction?
MUSCARINICS
SAMA / LAMA
Ipratropium / -iums
Which Drugs should we be cautioned with
GLAUCOMA ?
- *LAMA_ / _SAMA**
- iums
ICS / Oral Corticosteroids
