Download 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/
