Updates in

Treatment Options for

Asthma and C.O.P.D.
Patients
Jim Holliman, M.D., F.A.C.E.P.
Program Manager, Afghanistan Healthcare Sector
Reconstruction Project
Center for Disaster and Humanitarian Assistance
Medicine, Uniformed Services University
Bethesda, Maryland, U.S.A.

Asthma and C.O.P.D.

Lecture Objectives
Know presenting signs & symptoms
Be able to assess case severity
Know medication and other treatment
options
Be able to formulate appropriate plans
of care
Know indications for admission

Asthma : Definition &

General Demographics
Is a chronic inflammatory disorder of the airways, with
airflow obstruction & airway inflammation, & recurring
wheezing, dyspnea, & cough
Prevalence, morbidity, & mortality has increased since
1980's
Age - adjusted death rate for ages 5 to 34 increased 40
% from 1982 to 1992
About 5000 deaths per year in U.S.
However Rowe and Camargos editorial in 2006 notes
improved control and decreasing mortality in some
countries
About 2 million E.D. visits in U.S. per year

This prevalence trend is still true

Morbidity and mortality aspects of asthma

Triggers of asthma

Additional triggers of asthma

Markers of a Potentially Fatal

Asthma Attack
Historical factors :
Hyperacute
exacerbation
Lack of steroid use
Non-compliance
Psychiatric illness
> 3 hospital
admissions
Prior intubation or
barotrauma

Physical findings :
Altered mental status
Diaphoresis
Inability to speak
PEFR < 100 L / min.

Diagnostic Assessments to
Consider for Asthma

Peak Expiratory Flow Rate (PEFR)

Pulse oximetry
Arterial blood gas (ABG)
Hematology & chemistry studies
Chest X-ray (CXR)

PEFR Considerations for

Asthma
Probably the single most useful assessment test
Can stratify patients into severity groups :
< 25 % : Severe (impending resp. failure)
25 to 50 % : moderate to severe
50 to 70 % : mild to moderate
> 70 % : mild (can be discharged if at this value)

Initial value not highly correlated with admission

rate but higher risk if < 100 or improves < 60 with
Rx
Should usually not discharge if < 250 L / min.

Pulse Oximetry Considerations for

Asthma
Trend toward lower initial values correlating
with higher chance of admission, but not very
sensitive
Especially helpful in patients unable to
perform PEFR and in kids
Can be at normal levels in some with severe
bronchospasm

ABG Considerations for

Asthma
Initial ABG is poor predictor of outcome
and rarely influences therapy
NOT recommended routinely
Indications :
Suspected respiratory failure
Altered mental status (need to know pCO2)
Pulse oximeter unable to track, & hypoxia is
suspected
Worsening despite therapy

Hematology and Chemistry

Studies for Asthma
Generally are NOT needed for most cases
WBC count NOT reflective of severity or
associated infection
Most patients are not dehydrated, and do
not have electrolyte abnormalities (except
pseudohypokalemia from beta agonists)
Only useful test might be theophylline level
if the patient is taking a methylxanthine

CXR Considerations for

Asthma
NOT routinely needed for "typical"
exacerbations
May be needed for :
New onset asthma (especially in kids)
Unclear Dx (e.g., R / O CHF, foreign body, etc.)
Asthma refractory to treatment
Respiratory failure
ETT placement
Strong clinical suspicion for infection
Chest pain (R / O pneumo - thorax or - mediastinum)

26 year old male with asthma and chest pain

Same patient with arrows denoting pneumomediastinum

General E.D. Management

Scheme for Asthma
Triage
Primary treatments :
Beta agonists
Corticosteroids

Secondary (or "refractory") treatments :

Anticholinergics
Magnesium, leukotriene inhibitors, Heliox,
antibiotics, ketamine, mucolytics

Disposition

Triage Considerations for

Asthma
All patients with acute asthma should be
quickly taken to a monitored treatment area
Initial nursing interventions :
Pulse oximetry
Oxygen by nasal prongs (or blow-by mask for kids)
Cardiac monitor (if moderate to severe)
PEFR
IV line if severe
Notify physician

Main Therapy for Acute Asthma

Exacerbations :
Inhaled Beta Agonists
MDI-spacer delivery may be equivalent to
traditional nebulizer
The patient may think MDI Rx in E.D. will be
ineffective since has already tried it at home

Continuous nebulization may be more

effective in severe cases, but no difference
for moderate cases (although takes less
E.D. personnel time)
Albuterol doses are 10 to 30 mg / hr for adults, 5
to 7.5 mg / hr for kids

Choices for Short Acting

Beta Agonists (SABAs)
Albuterol (Ventolin, Proventil)
PO 0.1 to 0.2 mg/kg/dose up to 12 mg/day
MDI one to two puffs q 20 minutes X 3 or :
2.5 mg of 0.5 % solution via nebulizer q 20 minutes X 3
Levalbuterol (Xopenex)
R isomer of albuterol
MDI 1 to 2 puffs q 4 h
Not shown superior to racemic albuterol (but is more
expensive)
Metaproterenol (Alupent)
Same doses for MDI and nebulizer as albuterol
No big comparative studies versus albuterol

Considerations for Parenteral

Use of Beta Agonists
Subcutaneous may be useful for rare
patient not able to receive aerosol
Terbutaline probably safest (0.01 mg/kg, max.
0.3 mg)
Epinephrine (same dose; causes more HBP)

For "crashing" patient, give IV

0.1 mg diluted and via SLOW IV push
then 0.4 mcg/kg/min IV drip
Prior to discharge, can give Susphrine (epi tannate in oil)
SQ at 0.005 mg/kg (more useful for allergic reactions)
although availability of this med has decreased

Long Acting Beta Agonists

(LABAs)
Salmeterol (Serevent) MDI 50 mcg bid
Onset in 10 to 20 minutes & duration 12 hours
Twice as expensive as albuterol
Useful for nocturnal asthma
May be useful prior to E.D. discharge to help
prevent early relapse
Formoterol (Oxis, Foradil) MDI 12 to 25 mcg bid
Note FDA black box warning for these

Clinical Use Guidelines for the LABAs

NOT to be used as monotherapy for long term

control of asthma
Recommended in combination with Inhaled
Corticosteroids (ICS) for long term control in
moderate and severe persistent asthma
NOT to be used frequently or chronically before
exercise because this may mask poorly
controlled asthma

Other Medications for Acute Asthma

"Primary" Meds
Corticosteroids
Anticholinergics
Magnesium

"Secondary" Meds
Methylxanthines
Ketamine
Heliox
Halothane
Leukotriene inhibitors

Use of Systemic Steroids in

Asthma
Clearly shown to decrease admission & relapse
rates
Oral route is fine for most
40 to 60 mg prednisone / day for adults
2 mg / kg per day for kids
5 day duration best (typical length of attack)
taper usually not needed

IV only for severe dyspnea, emesis, altered

mental status, or intubated (IV versus PO shows
same acute effects)
Methylprednisolone, hydrocortisone, dexamethasone

Use of Inhaled Steroids for

Asthma
Regular use decreases need for beta
agonists & relapse rates
Use during an acute attack may just
increase cough
Use of spacer and post-Rx mouth
rinse decrease side effects
(dysphonia, oral Candidiasis)

Choices of Inhaled Steroids for

Asthma (via MDIs)
Fluticasone (Flovent) 250 to 500 mcg bid
Budesonide (Pulmicort, Rhinocort) 200 to 800
mcg bid
Triamcinolone (Azmacort) 2 to 4 puffs bid to qid
Beclomethasone (Vanceril, Beclovent) 84 to 840
mcg per day
Virtually all patients should be on one of these
after discharge

Use of Anticholinergics for Acute

Asthma
Inhaled (via MDI or nebulizer) these decrease
bronchospasm by reducing vagal tone
Atropine (0.2 to 0.5 mg)
Glycopyrrolate (Robinul) 0.2 to 0.4 mg
Ipratropium (Atrovent) 250 to 500 mcg

Several studies show mild added benefit when

added to first three beta agonist nebulizations
in E.D. (not helpful after this)
Ipratropium has low rate of side effects
May help undefined subsets of patients

Use of Magnesium for Acute

Asthma
Acts as smooth muscle relaxer &
suppresses neutrophil burst response
Conflicting results of efficacy in different
studies ( ? inadequate dosing in some)
Clearly safe & few side effects
2.0 to 5.0 gm IV dose reasonable to try for :
Severe symptoms
Respiratory failure
Non-response to standard Rx

Use of Methylxanthines for

Asthma
Problems with aminophylline :
weak bronchodilator
high rate adverse side effects
narrow toxic / therapeutic window
requires monitoring of serum levels (goal 5 to 15 mcg/ml)
many medication interactions
Clearly shown to add no benefit to acute Rx with beta agonists
& steroids
However, slow release forms (Slo-Bid, Theo-Dur, Uniphyl)
may be useful in some patients for chronic maintenance
5 to 8 mg/kg/day

Use of Ketamine for Acute

Asthma
Dissociative anesthetic
Relaxes bronchial smooth muscle
Excellent agent for RSI for critically ill asthmatic
2 mg / kg IV or 4 mg / kg IM
Continued infusion 1 to 2.5 mg / kg / hr

May cause :
Laryngospasm
Hypertension
Hallucinations

Use of Heliox for Acute

Asthma
Is premixed air 20 % and helium 80 %
Gas density is lower than air so flow
resistance is less
Somewhat limited usefulness for asthma
because as more O2 is blended in, the
gas density re-increases (max. O2 is 40
%)
Expensive if used for extended period
No major extended benefits in controlled
studies

Use of Leukotriene Receptor

Antagonists (LTRAs) for Asthma
Leukotrienes are released from mast cells,
eosinophils, and basophils and mediate :
bronchoconstriction
mucus secretion
airway mucosal edema

The LTRAs are useful for :

Treatment of stable, mild, persistent asthma, and
prophylaxis of exercise induced asthma
decrease airway response to cold & allergens
Role in acute asthma not yet clear (IV montelukast
is in phase 3 research trials)

Choices of LTRAs for Asthma

Montelukast (Singulair)
10 mg PO hs or two hours before exercise
Systemic eosinophilia and vasculitis
consistent with Churg-Strauss Syndrome
rarely reported
Zafirlukast (Accolate)
20 mg PO bid
Rarely has caused liver failure

Another Category of Meds : 5Lipoxygenase Inhibitors

Zileuton (Zyflo, Zyflo CR)
Inhibits leukotriene formation
Dose 600 mg pc and hs for Zyflo
Dose 1200 mg bid for Zyflo CR
Can cause liver failure
Not studied for acute use

Still Another Category of Meds :

Mast Cell Degranulation Inhibitor
Cromolyn (Intal)
Inhibits degranulation of sensitized mast
cells
Attenuates bronchospasm caused by
exercise, cold air, aspirin, and
environmental pollutants
MDI dose 2 puffs qid or two puffs 15 to
60 minutes prior to exercise
Rarely has caused liver impairment

And the Final Category of Asthma

Medication : Omalizumab (Xolair)

Recombinant DNA-derived immunoglobulin G

monoclonal antibody which binds selectively
to human immunoglobulin E on the surface of
mast cells and basophils and then reduces
mediator release
Used when Sx are not controlled by inhaled
steroids
Dose 150 to 375 mg SQ q 2 to 4 weeks
Annual cost $12,000 to $15,000
Can cause anaphylaxis

Combination Medications Available

for Asthma
Ipratropium and albuterol (Combivent)
Nebulizer 3 ml q 20 min X 3 doses
MDI 4 to 8 puffs q 20 min X 3
Salmeterol and Fluticasone (Advair Diskus)
3 dosage forms ;
100, 250, or 500 mcg fluticasone with 50
mcg salmeterol
One inhalation bid

Expert Panel 3 (2007) List of

Ineffective Treatments for Asthma

Methotrexate
Cyclosporin
Colchicine
Acupuncture
Chiropractic
Homeopathy
Breathing techniques
Yoga

Airway Management in
Asthma
Endotracheal intubation should be required in <
5% of admitted pts.
Indications for ETT :
Altered mental status due to hypercarbia or hypoxia
Progressive resp. failure or resp. acidosis despite
maximal Rx
Base decision on clinical situation (not a particular
value of pCO2 or pO2 or pH)

Always preoxygenate & ETT attempt should be

made by most experienced operator

Considerations About Nasotracheal

Intubation of the Asthmatic Patient
Advantages :
Can leave pt. sitting up ( resp. distress may worsen if
forced supine)
Pt.'s resp. effort often makes the procedure easy
Tube may be more comfortable for pt.
Tube less likely to be dislodged

Disadvantages :
May cause epistaxis
Requires smaller tube diameter than oral (so more airflow
resistance)
May predispose pt. to sinusitis later

Considerations About Orotracheal

Intubation of the Asthmatic Patient
Advantages :
Method of choice if pt. apneic or markedly bradypneic
No predisposition to epistaxis or sinusitis
Larger diameter tube can be used (may permit later
bronchoscopy)
Disadvantages :
Generally requires "full" Rapid Sequence Intubation
(RSI) technique & supine position
May be less comfortable for pt. & more likely to
dislodge

Options for RSI Meds for the

Asthmatic Patient
For nasal ETT may only need etomidate or
benzodiazepine IV (after topical anesthesia in
nose)
Usual oral ETT sequence :
Preoxygenate
Lidocaine 1.0 to 1.5 mg/kg IV
Ketamine 1.0 to 2.0 mg/kg IV
+/- benzodiazepine 1 to 5 mg IV
Succinylcholine 1.0 to 1.5 mg/kg IV
Perform intubation

General Considerations for Mechanical

Ventilation of the Asthmatic Patient
Mortality of ventilated pts. prior to
1984 reported as 20 to 40 %
Current mortality < 10 % using
"permissive hypercapnia"
uses smaller tidal volumes
goal is to limit barotrauma
does not require normalization of pCO2 or
pH

Specific Guidelines for Mechanical

Ventilation of the Asthmatic Patient
1. Volume control (A/C or SIMV) preferred
over pressure control to avoid
overventilation
2. Tidal volume set at 5 to 8 ml/kg
3. Initial rate set at 6 to 10 breaths per min.
allows increased time for exhalation & avoids
dynamic hyperinflation ("breath stacking")

Specific Guidelines for Mechanical

Ventilation of the Asthmatic Patient (cont.)
4. Set FIO2 to keep arterial pO2 > 60 mm Hg
Should be < 50% to avoid O2 toxicity if ventilation
prolonged

5. Set PEEP adjusted to 75 to 80 % of measured

auto-PEEP level
Make sure endogenous (auto) PEEP does not exceed
the amount dialed on the ventilator

6. Set Peak Insp. Flow Rate 70 to 90 L/min

Produces rapid inspiration allowing time for exhalation
End-inspiratory plateau pressures should be < 35 mm Hg

Specific Guidelines for Mechanical

Ventilation of the Asthmatic Patient (cont.)
7. Sedation to prevent tachypnea & allow pt. to
rest
8. Aerosolized beta agonists should be given via
ventilation circuit (continuous Rx can be done)
9. As wheezing improves, may increase TV & rate
10. Monitor for barotrauma (risk greater if endinsp. plateau pressure > 35 mm Hg)
11. Monitor for clinical improvement allowing
extubation

Complications of Mechanical
Ventilation of the Asthmatic Patient
Barotrauma due to alveolar rupture
Pneumomediastinum, pneumothorax, or SQ emphysema
Should usually treat with chest tube
May need to reset ventilation parameters to decrease
end-inspiratory plateau pressure
Prolonged muscle weakness
Can be due to prolonged effect of paralytic agent used for
intubation (esp. if renal insufficiency)
May be partly due to steroid Rx
Can be a myopathic syndrome with increased muscle enzymes &
require ventilation for several weeks

Education of the Asthmatic Patient to

be Discharged from the E.D.
Consider pt. education regarding the following items
prior to D/C :
MDI / spacer use training
Review of medications
Self use of short course oral steroids
Home use of PEFR
Identify PEFR #'s for which pt. should come to E.D.
Arrange F/U with primary care doctor
Asthma diary
Identify avoidable triggers (shoot any cats in the
house)

Other Considerations for Education of

the Asthmatic Patient
Make sure family members are also
educated re meds & severity assessment
Emphasize planning & early response to
minimize time lost from school or work
Remember it is a chronic recurrent disease,
so limit diagnostic tests unless there are
atypical features or severity of an attack

Asthma
Lecture Summary

Assess severity at presentation

Start multiple simultaneous Rx if severe
Decide if diagnostic studies needed
Monitor for response to Rx
Consider second line Rx's & intubation &
ventilation for refractory cases
Provide careful education & post - E.D.
planning for discharged pts.

Chronic Obstructive
Pulmonary Disease (COPD)
Refers to triad of disease processes :
Asthma (airway reactivity)
Bronchitis (airway inflammation)
Emphysema (airway collapse)
All 3 coexist to some degree in same pt.

Definitions :
Chronic bronchitis = chronic cough with sputum
production for at least 3 months / yr. for at least 2 yrs.
Emphysema = enlargement of distal air passages due to
alveolar septal destruction (& obliteration of pulm. capillary
bed)

COPD Epidemiology
4th leading cause of death in U.S.
Leading cause of death in smokers > age
55
12.5 million in U.S. have chronic bronchitis
14 million in U.S. have emphysema
2nd most common cause of permanent
disability
Huge economic impact

Risk Factors to Develop COPD

Major factor is cigarette smoking
Less common factors :
Inhalation of "second hand" smoke
Occupational exposure
Cystic fibrosis
Alpha 1 antitrypsin deficiency
Intravenous drug abuse

Pathophysiologic Features of
COPD
airflow
lung volumes, hyperinflation
V/Q mismatch
Arterial hypoxemia & hypercarbia
Often intrinsic airway inflammation
Note typical inflammatory cells in
COPD are usually neutrophils,
whereas they are usually
eosinophils in asthma

Sequence of Pathophysiologic
Events with COPD
Parenchymal destruction continues
Distal air spaces enlarge
Loss of elastic recoil
Increases lung volumes when resp. rate
Expiratory time then
Hyperinflation results

Pathophysiologic Results of
Dynamic Hyperinflation in COPD
Inspiratory muscle dysfunction
Acts at stiffer portion of its volume pressure relationship
Muscle fibers forced from vertical to
horizontal position
Increased reliance on accessory muscle
fibers

Causes increased work of breathing &

increased dyspnea

Goals of the E.D. Evaluation of

the COPD Patient

Rapidly stabilize the pt. in resp. failure

Identify precipitating causes
Treat complications
Rule out or treat concurrent
conditions

Clinical Presentation of Patients

with Exacerbations of COPD
Dyspnea ; most common ; may be severe
Other Sx may or may not be present
Chest pain ; may be :
Diffuse or vague
Pleuritic
Chest wall (from cough injury)
Cough
Fever
Altered mental status
Apprehension

Signs Associated with COPD

Exacerbations

Dyspnea
Tachypnea
Tachycardia
Ashen skin color or cyanosis
Diaphoresis
Accessory muscle use
Intercostal retractions
Rales / rhonchi / wheezes / decreased BS
Apprehension

Signs of Severe or Critical Airflow

Obstruction in a COPD Exacerbation
Altered mental status
Inability to speak
"Silent chest" (no or limited audible
BS)
Combativeness / seizures

Differential Dx of COPD
Exacerbation

CHF
Acute myocardial ischemia
Airway obstruction
Pneumonia
Pneumothorax
Pulmonary embolus
Pleural effusion
Acute aortic dissection
Allergic reaction

Caveats About Differential Dx

of COPD Exacerbation
COPD exacerbation may coexist or be
concurrent with any of Dx's on previous
slide
Particularly CHF may cause COPD
exacerbation & vice versa
PEFR > 150 L/min suggestive of Dx of CHF

Pulm. embolus particularly difficult to Dx

in COPD pt.

Spirometry Use for COPD

Exacerbation
Should be performed on all pts.
Determine initial severity
Determine response to Rx

Clinical eval. alone is unreliable at estimating

airflow obstruction
Many pts. with post-Rx FEV1 > 40% can be
safely discharged
Another discharge criterion is PEFR > 250
(assuming pt.'s baseline PEFR is > 300 ; need to know pt.'s
prior PFT's to determine this)

Use of ABG's in COPD

Exacerbation
Some recommend on all pts.
I favor using only in pts. who :
Appear critical at presentation
Do not respond well to Rx
Have altered mental status

ALL pts. should have continuous pulse

oximetry
Pt. can have hypoxemia even when pulm.
function approaches 50% of normal

Use of CXR in COPD

Exacerbation
CXR should be obtained on all pts.
At least 15 % of CXR's show a directly
treatable finding :
Pneumonia
Pleural effusion
Pneumothorax
Atelectasis
Aortic dissection

Also allows R/O CHF

E.D. Management of COPD

Exacerbations
For ALL Pts. :
Oxygen
Beta agonist aerosol
Consider SQ terbutaline if unable to take aerosol
Anticholinergic aerosols

For some pts. :

Corticosteroids
Antibiotics
Diuretics
CPAP / BiPAP / Intubation / Ventilation

Considerations for O2 Therapy for

COPD Exacerbations
Risk of eliminating hypoxic drive (&
causing further resp. acidosis / failure) is
overstated
Only applies to < 5% of COPD
population
Venturi mask can be used to give precise
regulated O2 concentrations
Pts. that develop resp. acidosis with O2
Rx usually need to be intubated &
ventilated anyway

Anticholinergic Med Choices &

Doses for COPD Exacerbations
Medication
Ipratropium
Atropine
Glycopyrrolate

Dose
0.5 mg
1 to 2 mg (0.025 mg/kg)

0.2 to 1.0 mg

Ipratropium preferred because of less side

effects such as tachycardia

Considerations in Use of Corticosteroids for

Rx of COPD Exacerbation
Not of benefit to all pts. with COPD
Should be considered if :
Pt. on chronic steroid Rx
Wheezing component is prominent
Allergic trigger
Prior response to steroids
IV versus PO is equivalent

Considerations in Use of Antibiotics

for COPD Exacerbation
Not indicated for all pts.
Usually indicated for COPD exacerbation with :
Fever / chills
Increased sputum production
Change in color of sputum
Persistent increased cough
Atelectasis or infiltrate on CXR

Most common pathogens :

Strep pneumoniae (with increasing rates of PCN resistance)
Hemophilus influenzae
Moraxella (Branhamella) catarrhalis

Antibiotic Choices for COPD

Exacerbation
Best first line agents :
Azithromycin
Cefuroxime
Trimethoprim - sulfa
? levofloxacin

Problems with other choices :

Doxycycline, amoxicillin : resistance
Erythromycin : no H. flu coverage
Amoxil / clavulanate : cost, side effects
Clarithromycin : cost, drug interactions, taste

Ventilatory Assistance Considerations

for COPD Exacerbation
3% of COPD pts. require ETT & ventilation
for resp. failure
Indications & complications same as for
asthma
Need to be careful to avoid barotrauma
Intubated COPD pts. have higher mortality
& longer time on ventilator than asthma
pts.
CPAP or BiPAP can be tried prior to ETT

Disposition Considerations for

COPD Exacerbation
Indications for hospital admission :
Persistent hypoxemia (O2 sat. < 90%)
Persistent hypercarbia / resp. acidosis
Persistent dyspnea
Overt resp. failure
Altered mental status
Usually if associated pneumonia
Pneumothorax

"Borderline " admission candidate may

be considered for observation unit first

Suggested E.D. Management

of COPD Exacerbation

Immediate O2 & beta 2 aerosol

Rapid CXR to R/O CHF or pneumothorax
Evaluate for cardiac ischemia (EKG)
Consider other Dx tests
Early PEFR & repeat after each Rx
Continued Rx (aerosols, +/- steroids, +/antibiotics, etc.)
Monitor for response :
ETT / ventilation if worsening
Admission if not improving satisfactorily

Adjunctive Treatments to Consider for

COPD Exacerbations
Phosphodiesterase-4 Inhibitors
Reduce inflammation via macrophages and
lymphocytes
Cilomilast 15 mg PO bid
Mucolytic agents
N-acetycysteine
Efficacy debatable
Referral for surgical bullectomy, lung volume
reduction surgery, or lung transplantation

Web Sites with Useful Clinical

Guidelines for Asthma and COPD
Expert Panel Report 3 Summary Report 2007
440 pages ; summary is 74 pages
http://www.nhlbi.nih.gov/guidelines/asthma/asthgdl
n.htm
http://www.medscape.com/viewarticle/564670 , and
564654
emedicine.com has 4 nice articles under both
emergency medicine and pulmonology :
http://www.emedicine.com/med/topic177.htm , & 373
http://www.emedicine.com/emerg/topic43.htm , & 99