Transcript Millard_COPD

ACHIEVING OPTIMAL
MANAGEMENT OF COPD
MARK MILLARD MD
BAYLOR MARTHA FOSTER LUNG CARE
CENTER
Take home points:
• Improved office-based care of COPD means…
– Spirometry for diagnosis and staging
– Identification of active smokers for
intervention
– Identification of hypoxemic patients
– Stage-driven inhaler therapy
– Early treatment of exacerbations
Take home points:
• Improved survival in COPD happens with…
– Smoking cessation
– Continuous oxygen if saturation <88%
– High dose ICS with LABA in patients with
FEV1 <50% and frequent exacerbations
– LVRS with specific anatomy (upper lobe
disease) and poor exercise tolerance
Case #1
JW is a 55 y/o male with a history of mildly elevated cholesterol, on
medication, who comes in for a yearly check-up. As part of his preappointment questionnaire, he notes that he has smoked 1 pack of
cigarettes per day for 35 years. In direct questioning, he notes a
morning cough and slightly brown tinged sputum that he attributes to
“allergies”, and denies shortness of breath with exertion, although he
acknowledges that going up a flight of stairs causes temporary dyspnea,
quickly relieved with rest. He denies any exertional chest pain or
pressure. He has had no significant lower respiratory tract infections in
the last several years, and denies any antibiotic use for as long as he
can remember. He doesn’t wheeze. No significant family history other
than a brother who uses an inhaler when he gets short of breath for
possible asthma is obtained. Colonoscopy performed last year was
normal. Review of systems is otherwise negative.
His only medication is a low-dose statin.
Case #1
On physical exam, he is overweight but looks healthy.
BP is 140/90, pulse 65, oxygen saturation 95%, and he is
afebrile.
Weight 200 lbs., 5’10”
HEENT- mildly red posterior oro-pharynx and uvula with
slight edema
Chest- clear breath sounds
Heart- RRR, S1, S2, without gallops or murmurs
Abdomen- benign without hepato-splenomegaly
Neuro- non-focal
No cyanosis, clubbing or edema
Skin- no rashes
Case #1
Audience Response Question
What diagnosis cannot be assumed?
1)
2)
3)
4)
5)
6)
Hypertension
Dyslipidemia
Obesity
Tobacco abuse
COPD
Chronic bronchitis
Case #1
Audience Response Question
What is this patient’s greatest
health risk?
1)
2)
3)
4)
Hypertension
Dyslipidemia
Tobacco abuse
Obesity
Assessing Tobacco Use in the
Office Practice Setting
Case #1
Audience Response Question
Would this patient justify an ECG
(rest)?
1) Yes
2) No
Case #1
Audience Response Question
Would this patient justify a lipid
panel and liver function tests?
1) Yes
2) No
Case #1
Audience Response Question
Would this patient justify a chest xray?
1) Yes
2) No
Case #1
Audience Response Question
Would this patient justify a
spirometry?
1) Yes
2) No
Case #1
Audience Response Question
Can you perform spirometry in
your office?
1) Yes
2) No
Case #1 Data
Lipid profile- normal
Liver function testing- normal
ECG- NSR, NAD, NAC
Chest x-ray- normal inspiratory effort without
cardiomegaly. Clear lung fields.
SpirometryFVC 90% predicted,
FEV1 65% predicted,
FEV1/FVC 0.55. No response to inhaled
bronchodilator on re-testing.
WHY SPIROMETRY IN YOUR
OFFICE ?
• More objective and
accurate than clinical
assessment
• Results direct work-up
• Results direct therapy
• You get paid for better
quality care!
http://www.nlhep.org/resources.html
WHY IS SPIROMETRY A
PROBLEM IN YOUR OFFICE ?
• Requires pre-planning
• Requires trained office
staff
• Unclear coding?
– 94010 ($34.17)
– 94060 ($58.83)
– ICDM: 786.05,
496,493.90
WHO TO TEST WITH
SPIROMETRY?
• Every asthmatic
• Every smoker with >10 pack year history
• Patients with chief complaint of dyspnea,
especially with exertion
• Patients with chronic cough, phlegm, or
wheeze
NHLEP, GOLD, JRD Supplement 2000
OBJECTIVE MEASUREMENTS OF
AIRFLOW
The FEV1 is the
volume exhaled in
the first second.
The forced vital
capacity is the
total exhaled
volume in one
breath.
In COPD, the FEV1/FVC ratio is <0.7, and does
not normalize with bronchodilators.
SPIROMETRY IN COPD
• Identifies smokers in need of intervention
• FEV1 used by GOLD and ATS/ERS in assigning stage
severity, and “gold standard” of FDA
• Often mildly (+) to inhaled bronchodilators, but…
• Bronchodilator response may affect lung volumes more
than FEV1.
• Changes in inspiratory capacity predict exercise
improvements more than FEV1
Case #1
Audience Response Question
Does this patient have COPD?
1) Yes
2) No
Case #1
Audience Response Question
If he has COPD, what Stage severity?
1)
2)
3)
4)
5)
Stage 1 (mild)
Stage 2 (moderate)
Stage 3 (severe)
Stage 4 (life-threatening)
He doesn’t have COPD.
Case #1
Audience Response Question
Do his symptoms of cough and
sputum, in addition to dyspnea with
exertion reflect COPD alone or
other processes?
1) Primarily COPD
2) Obesity, and deconditioning primarily
3) Probably both
Case #1
Audience Response Question
Would his symptoms of chronic
bronchitis and shortness of breath
justify treatment?
1) Yes
2) No
Case #1
Audience Response Question
What would be the optimal treatment regimen?
1) Albuterol MDI 2 puffs, as needed for shortness of
breath
2) Tiotropium, one capsule inhaled daily with as needed
albuterol
3) Fluticasone/salmeterol 250/50, one puff inhaled
B.I.D. with back up albuterol
4) Albuterol/ipratropium combination MDI, 2 puffs, QID
5) Guaifenesin expectorant for chronic bronchitis
Case #1
Diagnoses
Impression:
1) COPD with chronic bronchitis, Class II,
based on abnormal FEV1/FVC (<70), and an
FEV1 between 50 and 80% predicted.
2) Mild hypertension
3) Mild hypercholesterolemia, on medication
4) Tobacco abuse
5) Obesity
DEFINITION OF COPD: GOLD
2001
Chronic Obstructive Pulmonary Disease (COPD)
is a disease state characterized by airflow
limitation that is not fully reversible. The
airflow limitation is usually both progressive
and associated with an abnormal inflammatory
response of the lungs to noxious particles or
gases.
COPD VS. ASTHMA:
A COMPARISON IN THE UNITED
STATES
Condition
COPD
Asthma
Annual
mortality (N)
Estimated
annual cost
100,000
5000-6000
$25 billion
$12 billion
Martin RJ. American Academy of Allergy, Asthma, and Immunology 56th Annual Meeting; March 4,
2000; San Diego, Calif.
WHY ARE PATIENTS WITH
COPD SO SHORT OF BREATH?
• Static and dynamic
hyperinflation increases
diaphragmatic work
• Reduced FEV1 reduces
maximal ventilation
(FEV1 X 36)
• Exercise-related
hypoxemia
• Deconditioning and
intrinsic muscle
weakness
Vital
Capacity
(VC)
Vital Capacity
Functional
Residual
Capacity
(FRC)
Residual
Volume
(RV)
Functional
Residual
Capacity
Residual Volume
Obstructive Pattern
Normal Pattern
HYPERINFLATION IN COPD
• STATIC
– Structural
changes are
irreversible
– Loss of
elastic recoil
– Reduced
tethering of
small airways
• DYNAMIC
– Increased
airway
resistance
– Increased
cholinergic
tone
– Adrenergic
responsive
GOLD STAGES OF COPD
Old
0: At Risk
I: Mild
New
0: At Risk
I. Mild
Characteristics
•
Chronic symptoms
•Exposures to risk
factors
•Normal spirometry
FEV1/FVC<70%
•FEV1>80%
•With or without
symptoms
•
IIA
II: Moderate
II. Moderate
FEV1/FVC<70%
•50%>FEV1<80
%
•With or without
symptoms
•
IIB
III. Severe
FEV1/FVC<70%
•30%>FEV1<50%
•With or without
symptoms
•
III: Severe
IV. Very severe
FEV1/FVC<70%
•FEV1<30% or
presence of
chronic
respiratory
failure or right
heart failure
•
Avoidance of risk factor(s); influenza vaccination
Add short-acting bronchodilator when needed
Add regular treatment with one or more long-acting
bronchodilators
Add rehabilitation
Add inhaled glucocorticosteroids if
repeated exacerbations
NHLBI/WHO Global Initiative for Chronic Obstructive Lung Disease. April 2001 (Updated
2003).
Add LTOT
Consider surgical
Rx
BRONCHODILATORS: SITE
OF ACTION
Anticholinergic
M1
M2
M3
Contraction
-agonist
Relaxation
cAMP
AMP
Theophylline
Smooth Muscle Cell
Spector SL. In: Anticholinergic Agents in the Upper and Lower Airways. New York, NY: Marcel Dekker; 1999.
INHALED BETA2 AGONISTS
SHORT-ACTING
• Albuterol MDI @ 90
mcg/puff vs. 2500 mcg
/ nebulizer tx.
• Improve PFTs and
exercise tolerance.
• Use may reflect patient
activity.
LONG-ACTING
• Salmeterol or
formoterol-different
onset of activity
• DPI: multi-dose vs. unit
dose
• Improved PFTs, ?QOL
ANTI-CHOLINERGICS
IPRATROPIUM
• Equal, but slower
bronchodilatation
• QID dosing
• Improves PFTs and
exercise tolerance.
• MDI or nebulized
with/without albuterol
TIOTROPIUM
• Equal bronchodilatation
• QD dosing
• Improved PFTs, QOL,
and exercise tolerance
• DPI
DURATION OF ACTION
1.00
Salbutamol
Ipratropium
Placebo
0.95
Mean
FEV1
(L)
0.90
0.85
0.80
0
1
2
3
4
5
6
Time (hours)
Matera MG et al. Pulmonary Pharmacol. 1995;8:267-271.
8
10
12
DOES ADDING INHALERS
IMPROVE LUNG FUNCTION?
100
Albuterol
Ipratropium + Albuterol
Ipratropium
% Responding
90
80
70
60
50
40
0
15
30
45
60
75
90
105
Minutes post-drug administration
Dorinsky PM, et al. Chest. 1999;115:966–971.
120
DURATION OF ACTION
1.00
Salmeterol
Salbutamol
Ipratropium
Placebo
0.95
Mean
FEV1
(L)
0.90
0.85
0.80
0
1
2
3
4
5
6
Time (hours)
Matera MG et al. Pulmonary Pharmacol. 1995;8:267-271.
8
10
12
IMPACT OF LONG-ACTING
ANTICHOLINERGIC ON PREDOSE
FEV1
1.35
1.30
1.25
Day 1
Day 92
Tiotropium
FEV1 (L)
1.20
1.15
1.10
1.05
Placebo
1.00
0.95
0.90
0.85
-1.0 -0.5 0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5
Hours after drug administration
Casaburi R, et al. Chest. 2000;118:1294-1302.
FEV1 RESPONSE: TIOTROPIUM,
SALMETEROL AND PLACEBO
• Mean FEV1 with
tiotropium was
statistically better
than salmeterol.
• The difference was
~50 ml.
ADDING LONG ACTING
BRONCHODILATORS: TIOTROPIUM &
FORMOTEROL
FEV1 IMPROVEMENT POST DOSE:
FSC 250/50 VS. FP250, SALMETEROL,
AND PLACEBO
 FEV1 (ml)
Placebo
Salmeterol
FP250
FSC 250/50
350
350
300
300
250
250
200
200
150
150
100
100
50
50
0
0
-50
-50
20
0
2
4
*P0.003 vs FP
6
8
12
Time (weeks)
Adapted from Hanania etal Chest 124: 834-843, 2003
16
*
(27%)
(19%)
(14%)
(6%)
24
Endpoint
TIOTROPIUM & LUNG
FUNCTION IN COPD
FSC 250/50 REDUCES
HYPERINFLATION
(Adjusted Mean Change From Baseline at Week 8*)
FSC 250/50
Placebo
Salmeterol
(n=62)
(n=64)
(n=59)
Primary Endpoint
Postdose FRC, mL
–392 + 95*
–40 + 92
–303 + 96*
Postdose RV, mL
–410 + 101*
–57 + 98
–359 + 103*
213 + 43*
18 + 44
165 + 46*
181 + 28‡
15 + 27
91 + 28*
Postdose Exercise IC,† mL
Predose FEV1, mL
Data are adjusted mean + SEM.
*P≤0.03 vs placebo.
†At isotime (defined as last common timepoint across exercise challenges).
‡P≤0.012 vs salmeterol; except mean change from Baseline at Endpoint.
Some patients had emphysema without chronic bronchitis
Data on File, GlaxoSmithKline (SCO40030).
Case #1
Treatment
This patient was begun on Tiotropium, one capsule
inhaled daily, as well as being given a prescription of
albuterol MDI, 2 puffs as needed for shortness of breath
not relieved within 3-5 minutes of rest. He was asked to
return in one month for a follow-up spirometry and
clinical assessment. If he was still symptomatic, then
substitution of FSC 250/50, one puff twice daily would be
recommended with another follow-up visit in one month
to assess for improvement.
STAGE
2006 OPTIONS FOR
TREATMENT IN COPD
Albuterol p.r.n.
I
+
II
+
Tiotropium q.d.
FSC 250/50 b.i.d.
(+ LABA)
III
IV
Tiotropium q.d. +
Fluticasone 440 b.i.d.
FSC 500/50 b.i.d.
Tiotropium q.d. +
FSC 500/50 b.i.d.
Tiotropium q.d. +
FSC 500/50 b.i.d.
?theophylline
Case #1
Audience Response Question
What is the most pressing additional
issue to be addressed in health
status of this patient?
1)
2)
3)
4)
Hypertension
Obesity
Tobacco abuse
Dyslipidemia
Case #1
Audience Response Question
What would likely happen to his spirometry
if this patient quits smoking?
1)It will normalize
2)It will continue to decline as previously from
normal because he has COPD which is
“progressive”
3)It may slightly improve, but will decline now at
the rate of a non-smoker
4)I don’t know
FEV1 (% of value at age 25 y)
Quit before its too late!
Never smoked or not susceptible to smoke
Stopped at 45 y
Stopped at 65 y
Smoked regularly and susceptible to its
effects
100
75
Dyspnea on exertion
50
Disability
25
Death
0
25
50
Age (y)
Adapted with permission from Fletcher C, Peto R. BMJ. 1977;1:1645-1648.
75
Options for Smoking Cessation
• U.S. Public Health Service Guidelines for quit
attempts:
– Offer effective pharmacotherapy
– At least 3 minutes of behavioral counseling
•
•
•
•
Behavioral approaches/Patient education
Nicotine replacement therapy (NRT)
Buproprion SR
Varenicline
NICOTINE REPLACEMENT
From: Urso, in The 2003 Sourcebook for Advanced Practice Nurses.
pp 11-21; Lippincott Williams & Wilkins
Abstinence Rates for Weeks 9-52:
Varenicline vs. Bupropion or Placebo
Any questions?
Case #2
SA is a 70 year old female who presents with shortness of breath and
cough. She has recently moved from another city to be near to her
children and comes in somewhat upset about her diagnosis. She had
been hospitalized in the past for congestive heart failure and told by her
doctor elsewhere that she had a weak heart predisposing her to recurrent
episodes of pneumonia that required hospitalization. She receives
antibiotics and “cortisone” for treatment several times per year. However,
a cardiologist recently told her that her heart was just “fine”.
She smoked 2 packs per day for 30 years, stopping when she turned 50,
at which time she had no symptoms except for chronic bronchitis.
Currently, she is short of breath walking one block, and has to stop and
rest after vacuuming one room in her daughter’s house where she now
lives. She has a night-time tickle in her throat and in the morning
produces about 2 tbs. of yellowish sputum.
Case #2
Other significant history is high cholesterol, hypertension (both treated), and
degenerative arthritis in her hip. She has had bilateral cataract extractions in the
past.
Medications include: statin, ACE-inhibitor, diuretic, and cox-2 inhibitor.
Physical exam: a mildly anxious senior female, accompanied by her daughter. BP
135/85 P70, oxygen saturation 88% at rest while sitting.
HEENT: small pupils, white nasal discharge, dentures
Chest: increased AP diameter, mild kyphosis, diminished breath sounds with a few
high pitched expiratory wheezes
Heart: PMI indistinct, S1, S2, without gallops, murmurs
Abdomen: benign
No cyanosis, clubbing, trace edema
Neuro: non focal
Skin: no rash
Case # 2
Audience Response Question
Which tests would be reasonable to
order before initiating treatment?
1)
2)
3)
4)
5)
Chest x-ray
Spirometry
ECG
None of the above
All of the above
Case #2
Chest xray: large lung volumes, with increased markings
bilaterally. Pulmonary arteries appear enlarged centrally.
Flattening of diaphragm.
Spirometry:
FVC 70% predicted,
FEV1 40% predicted,
FEV1/FVC 0.45.
Bronchodilator response of 220 ml (13%) was noted.
ECG: sinus rhythm with PACs. NAD, NSSTW changes noted
Audience Response Question
What is the most likely pulmonary
diagnosis?
1. Stage III COPD with recurrent
exacerbations
2. Adult onset asthma
3. Congestive heart failure
4. You can’t tell; further testing is necessary
FEV1 (% of value at age 25 y)
Why quit when you’re 50?
Never smoked or not susceptible to smoke
Stopped at 45 y
Stopped at 65 y
Smoked regularly and susceptible to its
effects
100
75
Dyspnea on exertion
50
Disability
25
Death
0
25
50
Age (y)
Adapted with permission from Fletcher C, Peto R. BMJ. 1977;1:1645-1648.
75
Audience Response Question
What would be the appropriate inhaler
therapy, based on evidence-based medicine?
1. Albuterol MDI, 2 puffs as needed for shortness
of breath only
2. Tiotropium, one capsule inhaled daily
3. Fluticasone-Salmeterol 250/50, inhaled twice
daily
4. Fluticasone-Salmeterol 500/50, inhaled twice
daily
WHY WORRY ABOUT
EXACERBATIONS IN COPD?
• Raise “misery index” of COPD
• Increase health care utilization and cost
– Drugs
– PCP VISIT/ED/HOS
• Prolonged time to recover in some; permanent
worsening of lung function in others: <50%
FEV1 at risk population
Chest. 121(3):688-696, March 2002
COPD EXACERBATIONS: TIOTROPIUM,
SALMETEROL AND PLACEBO
• The proportion of
each patient group
with exacerbations
was no different
within treatment
groups, ~1/3.
• The number of
patients requiring
steroids was no
different.
FSC 500/50 REDUCES
EXACERBATION RATE
DO ICS/LABA IMPACT
MORTALITY IN COPD?
•
•
•
Observational study: COPD, >65
y/o, post-discharge
ICS Rx reduced rate of rehospitalization & mortality
Sin & Tu. AJRCCM 164:580-584,
2001
• TORCH 2006
• Randomized to detect
mortality difference with FSC
500/50
• 17% improved mortality at 3
yrs.
• P=.052
• March 2006, GSK
Treating COPD Exacerbations
• Exacerbations defined:
– Increased cough and dyspnea and
– Change in color or quantity of sputum
• Early antibiotics reduce complications
– Tm-Smx; macrolide; amox/clav
– Quinolone if at high risk
• Prednisone improves symptoms and function
– 40-60mg per day for 10-14 day course
Audience Response Question
Should she be prescribed oxygen?
1.
2.
3.
4.
Yes, continuously for 16-18 hours per day
Yes, but only as she feels like she needs it
Yes, but only with exertion
No
Oxygen Therapy Trial
100
90
80
COT
70
Cumulative
Survival
(%)
60
50
MRC
O2
NOT
40
30
MRC
controls
20
10
0
0
10
20
30
40
50
60
70
COT = continuous oxygen therapy; NOT = nocturnal oxygen therapy; MRC controls = no
oxygen therapy; MRC = domiciliary oxygen therapy.
Flenley DC. Chest. 1985;87:99-103.
Case #2
Treatment
The patient was begun on fluticasone/salmeterol combination
500/50, to reduce recurrent episodes of bronchitis, an off-label
use, although well documented in the peer-reviewed literature.
Additional bronchodilatation with a long-acting anticholinergic
(tiotropium) may be tried after the initial use of FSC, if symptom
relief is not optimal, as the combination of both anti-cholinergic
and beta agonists has been shown to improve FEV1 more than
with either agent alone. Tiotropium has also been associated
with a reduction in number of bronchitic exacerbations. She
should also be prescribed supplemental oxygen for use at least
16-18 hours per day and referred to a pulmonary rehabilitation
program.
Questions?
Take home points:
• Improved office-based care of COPD
– Spirometry for diagnosis and staging
– Identification of active smokers for
intervention
– Identification of hypoxemic patients
– Stage-driven inhaler therapy
– Early treatment of exacerbations
Take home points:
• Improved survival in COPD
– Smoking cessation
– Continuous oxygen if saturation <88%
– High dose ICS with LABA in patients with
FEV1 <50% and frequent exacerbations
– LVRS with specific anatomy (upper lobe
disease) and poor exercise tolerance