New Strategies in the Management of Asthma
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Transcript New Strategies in the Management of Asthma
Management of Asthma and COPD
W.S. Krell M.D.
Wayne State University
NIH Statement (1992, ‘97)
Chronic inflammatory disorder
multiple cellular components, mediators
recurrent wheeze, shortness of breath,
chest tightness, cough (pm & early am)
reversible airflow obstruction
secondary: hyperresponsiveness
Sub-basement membrane fibrosis
Treating Asthma
Medications:
– long term or controller medications
– quick relief medications
Stepped therapy: start high, back
down
Asthma monitoring and action plans
Environmental controls
Overview of Medications
Controller medications
– control inflammation
– long duration bronchodilation
– multiple medications
Quick relief medications
– for intermittent or breakthrough
symptoms
Controller Agents
Inhaled corticosteroids
Systemic corticosteroids
Long acting 2 agonists
Cromolyn and derivatives
Methylxanthines
Leukotriene Modifiers
Inhaled Corticosteroids
Control airway inflammation locally
Ideal: control asthma (high local
potency); no side effects (low systemic
effects)
fluticasone, budesonide ****
beclomethasone *
(triamcinolone, flunisolide)
Systemic Corticosteroids
May be needed initially
Side effect profile well known
Step down therapy
Alternatives: high dose inhaled
corticosteroids; methotrexate; other
immunosuppressive drugs; Omalizumab
Omalizumab (Xolair)
Recomb. DNA derived IgG - selectively
binds human IgE
Indication: mod. to severe persistent
asthma not controlled w/inhaled CS
IgE > 30, RAST A or skin tests +
Given SQ/ mo. or biweekly
Dose based on wt. and IgE level
Long acting ß2 Agonists
Salmeterol
Formoterol
Prolonged duration
Potentiate steroid effects?
Should we be using them????????
Leukotriene Modifiers
Anti-inflammatory
Precursor step affected
Compliance may be better than MDIs
Few side effects
Other Controllers
Cromolyn derivatives
– Safe, effective
– Less predictable, frequent dosing
Methylxanthines
– Mechanism not fully understood
– Therapeutic/Toxic ratio high
– Multiple drug interactions
Quick Relief Medications
ß2 Agonists
Systemic corticosteroids
Exacerbation of Asthma
History: Sudden (exposure) vs
gradual worsening vs viral infection vs
non-compliance
Tachypnea, tachycardia
Accessory muscles
Wheezing, prolonged expiration, silent
Speaking ability compromised
ABGs - Asthma
Respiratory alkalosis
Normal PCO2 is worrisome
Rising PCO2 is near respiratory failure
Note: O2 doesn’t fall until late so pulse
oximetry is not very sensitive
Emergency Management
Nebulized albuterol x 3
Monitor exam, peak flows, ABGs
If no improvement, start IV
corticosteroids and admit
DOSE?? (30 to 180 mg/day)
Asthma: CXR not likely helpful
Further Mgt of Asthma
Continue bronchodilators
Q 6 hour steroids
Hydration
Mucomyst may exacerbate
If failing: consider anticholinergics,
theophylline, single isomer β2, Mg2+
Impending Respiratory Failure
Respiratory acidosis
Decreasing mental status
Asthma: PCO2 above 40 or rising
despite therapy
Outpatient Asthma
Management
Classify by severity
Step up and down number of
medications based on symptoms and
peak flows
Severity of Asthma
Mild Intermittant:
– symptoms < 2X/wk
– nights<2/month
Mild persistent:
– > 2X/wk but < 1/day
– Nights > 2/month
(cont.)
Moderate:
– Daily symptoms
– Nights > 1/week
SEVERE:
– Continual symptoms
– Frequent nighttime symptoms
Rules of 2
2/week
PM sx > 2 nights/month
> 2 rescue MDIs/year
Sx >
Stepped Therapy
Inhaled beta agonist
Inhaled corticosteroid
Long acting beta agonist
Leukotriene modifiers
(Cromolyn derivatives)
(Theophyllines)
Systemic corticosteroids
Patient Education
Avoid triggers
Home monitoring
Proper inhaler techniques
Spacers
“Asthma Action Plan”
Compliance?
Few patients continue to document
Always give them Action Plans
Simple in office questionnaire
– validated in testing
– Snap shot of asthma control
Asthma
Sensitizing agent
↓
Inflammation
CD4 T-lymphocytes
Eosinophils
↓
Completely
reversible
airflow limitation
vs.
COPD
Noxious agent
↓
Inflammation
CD8 T-lymphocytes
Macrophages, PMNs
↓
Irreversible airflow
limitation
Treating COPD
Step up
Long acting Anticholinergics
Long acting beta agonists
Short acting bronchodilators
(steroids: inhaled and oral)
Soon: Cilomalist?
Exacerbation of COPD
Viral or secondary bacterial infection
Non-compliance
Cor pulmonale
Tachypnea, tachycardia
Rhonchi, wheezes, prolonged expiration
Signs of right heart failure, pulmonary
hypertension
Causes
Infections (bacterial)
Environmental (↑ pollution)
Unknown in 1/3
Management
Increase bronchodilators
Systemic steroids (PO if possible) (A)
– Shortens recovery time
– Quicker return to baseline function
– ↓ risk of early exacerbation
– 10 day to 2 week course
Antibiotics (B)
Additional Management:
COPD
Nebulized anticholinergics, β agonists
Antibiotics
Steroids
Manage other complications:
pneumonia, pneumothorax, right heart
failure
Oxygen to keep saturation near 90%
ABGs - COPD
Pay more attention to pH, bicarb
PCO2 elevations more significant when
acute
Expect increased (A-a)DO2
Hypoxia must be treated, despite fears
of hypercarbia
Impending Respiratory Failure
Non Invasive Ventilation
– Bi-level Positive Pressure
– Increase inspiratory P to ↓ pCO2
– Start expiratory P at 5-6 cm H2O and ↑ if
needed for oxygenation
– Evidence A for success
Management of COPD
Smoking cessation
Spirometry
Yearly influenza vaccine
Pneumovax
Antibiotics for exacerbations
Monitor rest and exercise oxygenation
Spirometry is KEY
FEV1
FEV1/FVC Ratio
Screen based on exposure and
symptoms
Follow at least yearly
Patients should KNOW THEIR NUMBERS
Spirograms
Classification
STAGE FEV1/FVC
FEV1
0
>70%
> 80% + Symptoms
I
< 70%
≥ 80% ± Symptoms
II
< 70%
≥ 50% but < 80% ± Sx
III
< 70%
≥ 30% but < 50% ± Sx
< 70%
< 30% or < 50% +
chronic respiratory failure
IV
Management: All Stages
Avoidance of noxious exposures
– SMOKING CESSATION (Evidence: A)
– Avoid occupational/environmental
exposures (Evidence: B)
Vaccination
– Influenza
– Pneumovax
Smoking Cessation Strategies
Repeated counseling
Nicotine replacement agents
Buproprion, anxiolytics
This is the ONLY measure available
proven to halt the decline in lung
function
Evidence: A
COPD Outpatient
SHORT ACTING BETA AGONISTS
ANTICHOLINERGICS ****
– Ipatropium
– Tiotropium
LONG ACTING BETA AGONISTS
Theophyllines
Inhaled corticosteroids
Management: Stage I
Short acting bronchodilator used PRN
Albuterol: beta 2 agonist
Ipatropium: M3 anticholinergic blocker
Both are effective
Albuterol has faster onset of action
Combination is additive for
bronchodilation
Evidence: A
Management: Stage II
Long acting bronchodilators
– Long acting beta agonists
– Long acting anticholinergic
Short acting bronchodilators PRN
Education
Inhaled corticosteroids if frequent
exacerbations
Evidence: A
Long Acting Beta Agonists
Formoterol
– Onset comparable to short acting agents
– Duration: 12 hours
Salmeterol
– Slower onset
– Duration: 12 hours
– Cautions re: use without inhaled steroids
applies to asthmatics not COPD patients
Tiotropium
Duration: 24 hours
Blocks M1 and M3 receptors
Stop ipatropium (M3 only)
Few side effects (some caution with
BPH)
Sustained improvement in FEV1
What about Theophylline?
Old drug, proven useful
If chosen, careful monitoring required
– High toxic to therapeutic ratio
– Multiple drug and food interactions
Aim for levels 8 – 12 mcg/mL
Cilomalist
Orally active PDE4 inhibitor cAMP
(inflam, bronchial reactivity)
Positives
– Improved FEV1, reduced sx (SGRQ)
Negatives
– Significant GI toxicity
– Study done prior to release of tiotropium
Rennard, CHEST 2006
Inhaled Corticosteroids
If indicated, choose long acting agents
Fluticasone
– Combination drug with salmeterol
Budesonide
– Also available for use in nebulizer
More is better???
Combinations can produce benefits
Long acting agents are ALL expensive
Optimal combinations not known
Management: Stage III
One or More Long acting
Bronchodilators
Short acting bronchodilators PRN
Inhaled corticosteroids if frequent
exacerbations
Pulmonary Rehabilitation
Evidence: A
Management: Stage IV
Long acting bronchodilators
Short acting bronchodilators PRN
Inhaled corticosteroids
Education
Evaluate need for oxygen therapy
Nighttime non-invasive ventilation?
Consider surgical options
Surgical Options
Lung transplantation
– Upper age limit: 60 years
– Consider for younger patients without
serious co-morbidities
– Few last long enough to get transplanted
Lung volume reduction surgery
– Consider if no serious co-morbidities
– Improves diaphragmatic function
Resources
NIH Asthma Guidelines:
www.nhlbi.gov/guidelines/asthma/
Global Initiative for chronic obstructive
lung disease:
www.goldcopd.com
Resource for asthma action plans, info:
www.cine-med.com/asthma/