Download Chronic Obstructive Pulmonary Disease

A Concise Workup of COPD
E. James Britt, MD
Common diseases are common
3rd leading cause of mortality
COPD is overlooked
Women > men but
underdiagnosed
Core w/u is simple
We will quickly outline an office eval
We will review goals of therapy, and
how and what goals can be met today
Natural History of COPD
(Fletcher and Peto)
Never smoked
or not
susceptible to
smoke
100
Forced
Expiratory
Volume in
1 Second
(FEV1)
[% of Value
at Age 25]
75
50
Smoke regularly
and susceptible
to its effects
Stopped at age 45
Disability
25
Stopped at age 65
Death
*
*
0
25
50
75
Age (Years)
* Death due to irreversible chronic obstructive lung disease.
Reprinted with permission from Fletcher C, Peto R. The natural history of chronic airflow
obstruction. Br Med J. 1977;1(6077):1645-1648
COPD Mortality in the United States
Absolute No. Deaths
per 100,000
70
Not What You Would Suspect?
1980-2000
Men
60
Women
50
40
30
20
10
0
1980
1985
1990
1995
Year
Mannino et al. MMWR Morb Mortal Wkly Rep. 2002;51(SS-6):1-16.
2000
Questioning a patient thought to have COPD
Cough, SOB, Chest Pain
• Smoker?
• Childhood allergies, asthma?
• SOB:
– House/apartment, 1-3 floors?
– Up/down at will; once daily; ask others?
– Yard work, laundry, mail,daily errands, trapped?
– Arm work?
– Nocturnal attacks?
• Hospital or ER?
• Medication Review
Criteria for Diagnosis of COPD
• Clinical history
– Exposure: smoke, other
– Symptoms: cough, sputum, dyspnea
• Functional assessment
–
–
–
–
Spirometry (FEV1, forced vital capacity [FVC], and FEV1/FVC ratio)
Oxygenation
Lung volumes
Diffusion capacity
• Anatomic assessment
– Chest x-ray
– High resolution CT scan
Pauwels RA, et al, on behalf of the GOLD Scientific Committee. Am J Respir Crit Care Med.
2001;163:1256-1276.
Prognosis of Airways Obstruction in Tuscon >age 65
Pharmacologic RX of COPD
•
•
•
•
•
•
•
Short Acting Bronchodilators
Long Acting Maintanance Drugs
Supplemental Medications
Meds to Rx Exacerbations
Meds to Prevent Exacerbations
Medications to Preserve Lung Function
Medications to Reduce Mortality
Short Acting Bronchodilators
• Beta Agonist Family
– Pro Air; Proventil; Ventolin; Albuterol;
Xopinex $40-$45
• Anticholinergic Family
– Atrovent,
• Combination
– Combivent; Respimat $210
Long Acting Bronchodilators
• Anticholinergics
– Tiotropium; Aclidinium $250
• Beta Agonists
Salmeterol, Formoterol, Indacaterol
$250
• Steroid/Beta Agonist Combinations
– Advair 250/50; Salmeterol 160/4.5 $250
Supplemental Medications
• Theophylline
Theophylline1
• If response to initial anticholinergic/2-agonist
therapy suboptimal, consider adding theophylline
• Long-acting formulations generally preferred
– Modest bronchodilation, mild anti-inflammatory effects
• Useful for noncompliant patients and those who
have trouble with inhalation aerosols and those
preferring oral drugs
1. NCAP. J Respir Dis. 2000;21(suppl):S5-S21.
Medications to Prevent Exacerbations
• Rofumulast $300
• Azithromycin
PD4 Inhibitors-Roflumilast
• Six and Twelve month data document decreased
exacerbations in a COPD cohort with recurrent
exacerbations of chronic bronchitis and use of
inhalled glucorticoids
• Limited by headache, nausea, diarrhea and weight
loss
• **Never gone head-head against theophylline
• Many in pipeline…special interest in inhalled
Azithromycin and COPD
• COPD consortium: UMMD/Scharf (Albert)
• 250 mg AZ/d
570 patients
• Time to Exacerbation extended by 92 days
– Placebo=174d
– Risk Rate
• Placebo=1.83/yr
Az=266d
Az=1.48/yr
• Limited by ototoxicity, cardiac toxicity,
drug-drug toxicity
Recommendation for Azithromycin Use in
COPD
•
•
•
•
•
•
•
•
>= 2 exacerbation/yr
Compliant patient
Pulse <100
QT<450 msec.
SGOT/SGPT < 3X normal
No QT drugs
Hearing OK, Audiogram ?
Exclude high cardiac risk patient
Principal of Mix & Match
Combination therapy
• My role here is that of a shopping assistant
really recommending ways in which a
patient may mix and match medications to
achieve goals…challenging given the $$
involved
Escalating Menu of Choices
A moderate to severe patient
•
•
•
•
•
Long acting anticholinergic
Steroid/Long act beta agonist
Long acting beta agonist
Short acting rescue drug
Preventitave drug
$260
$250
$120
$ 50
$300
Prevention of Relapse
• Tiotropium and two Steroid/beta agonist
maintanance inhalers have secondary
endpoint claims from large long-term
studies.
• Additional preventative strategies were
reviewed
Preservation of Lung function
• No major studies document preservation of
lung function at this time. It remains the
elusive goal.
Statins
• Observations
– Diminished decline in PFT
– Decreased ER & H documented
• COPD Consortium: STATSCOPE
– 3 yr 1000 participants
– ? Direct effect on COPD
– ? Indirect benefit thru heart disease
Improve exercise performance
• Both long acting anticholinergics and long
acting beta agonists have data that show
increased esercise time and or endurance
oner two months of regular use likely thru
the lung volume reduction effect
Tiotropium Exercise Trial: Endurance Time
During Constant Work Exercise
Exercise duration (seconds)
Placebo (n=91)
Tiotropium (n=96)
700
**
*
600
+ 105.2 sec
+ 21.4 %
+ 66.8 sec
+ 13.6 %
500
491.7 sec
400
-5
0
* p<0.05
** p<0.01
Baseline
O’Donnell et all ERJ 2004 (in press).
5
10
15
20
Days
25
30
35
40
45
ACP Clinical Practice Guidelines
COPD
•
•
•
•
•
•
Spirometry to dx airflow obstruction, but not to screen
Stable FEV1 60-80% bronchodilators MAY be used
Stable FEV1 <60% monotherapy with long act bd
FEV1<60% Rx LAMA or LABA patient pref, cost,
adverse event profile
May adm combination rx for symptomatic pts
Rehab for <50% FEV1
O2 for resting hypoxemia, usual guidelines