Transcript Case Conference Optimizing Treatment in a Patient With

Case Conference
Optimizing Treatment in a Patient With
COPD and Comorbid Disease
Presentation: R3 黃志宇
A 50-year-old female smoker is referred for lung
function testing following a hospital stay during
which diagnoses of atypical pneumonia and
congestive heart failure (CHF)
forced expiratory volume per second (FEV1) is 45%
FEV1/forced vital capacity (FVC) ratio is 60%
diffusion capacity is 45%
pulse oxygen level is 95% at rest, but it drops to 85%
during exercise
A diagnosis of chronic obstructive
pulmonary disease (COPD) GOLD stage III
is made, and the patient seems to be having
frequent exacerbations (three in the past year)
Physical examination reveals a frail, thinlooking woman who stands 5’4” tall
(162.5cm) and weighs 105 lb (47.6kg)
Her blood pressure is 132/82 mm Hg, pulse
rate 87, and respirations 17
Her breath sounds are slightly decreased,
with a prolonged expiration and occasional
crackles and wheezing. Review of the
extremities reveals edema in both legs
She is employed full time in a factory and
works in a paint booth, where she is exposed
to fumes all day
She is also a smoker, averaging one pack per
day since she was about 18 years old
She claims that for the past 20 years, she
quit smoking every year on New Year’s Day
but always resumed smoking after about
three days
Question 1
Which one of the following interventions
is considered to be the top priority in a
patient with COPD?
Oxygen therapy
Exercise
Bronchodilation
Smoking cessation
Smoking has been recognized as the dominant and
most common risk factor for the development and
progression of COPD (Mannino, 2002)
Smoking cessation is the single most important
factor for improving health outcomes in patients
with COPD and is the only therapy proven to slow
the accelerated decline in lung function related to
COPD (Celli, 2006; Sin, 2003; Mannino, 2002)
In smokers, the rate of FEV1 decline is
approximately 60 mL per year. However, the rate
of decline decreases to ~30 mL per year among exsmokers (Sin, 2003; Anthonisen, 1994)
If smoking cessation is maintained for a sustained
period of time, it is possible for the age-related
decline in lung function to match the rate observed
in individuals who have never smoked
(Henningfield, 2005, Anthonisen, 1994)
Question 2
What is the reported relative excess risk of
COPD among smokers who are exposed to dust
or other occupational hazards?
Exposure to occupational hazards does not confer any
excess risk of COPD among smokers
The excess risk of COPD in these patients is additive:
the excess risk is the sum of the risk of smoking plus the
risk of occupational exposure
The excess risk of COPD in these patients is about twice
the sum of the risk of smoking plus the risk of
occupational exposures
The excess risk of COPD in these patients is about three
times the sum of the risk of smoking plus the risk of
occupational exposures
A recent survey evaluated the occupational
burden of COPD in a randomly selected
sample of 2,061 adults between the ages of
55 and 75 years (Trupin, 2003)
Question 3
What percentage of cases of COPD in
patients who have never smoked may be
attributed to occupational exposure to
dust, gases, and fumes?
7%
12%
15%
31%
Inhaled dust causes inflammation, airway
narrowing, and hyperactivity, resulting in
edema, excess mucus production, and poorly
functioning cilia (Hunter, 2001)
It has been well documented that miners
exposed to mineral dust develop respiratory
symptoms, airflow obstruction, and COPD
There is also a significantly increased risk of
respiratory symptoms and COPD associated
with occupational exposure to biological
dust (Matheson, 2005)
In smokers, it is estimated that 15% to 19%
of COPD cases may be attributed to
occupational exposure, with a higher figure
(31%) for those who do not smoke
(Matheson, 2005)
Question 4
Malnutrition in patients with COPD is
associated with:
Greater gas trapping
Lower diffusing capacity
Lower exercise capacity
Higher mortality
All of the above
Patients with COPD who are of low weight
have greater gas trapping, lower diffusing
capacity, and lower exercise capacity than
patients with the same degree of bronchial
obstruction but who are of normal weight
(Ferreira, 2005)
Low body weight and recent loss of weight,
particularly depleted lean body mass, have
been shown to be independent predictors of
the following (Mallampalli, 2004):
Mortality
Outcome following acute COPD exacerbation
Hospital admission rates
Need for mechanical ventilation
It is not clear whether malnutrition causes COPD
or if malnutrition is just a natural progression of
the disease (Ferreira, 2006).
The increased work associated with breathing that
characterizes the disease also seems to contribute
to weight loss in patients with COPD
Other factors that can increase metabolic rate are
systemic inflammation, tissue hypoxia, and/or
drugs that are commonly used in the treatment of
COPD, such as beta agonists (Agusti, 2005)
Question 5
Nutritional supplementation for patients
with COPD has been shown to:
Limit weight loss
Improve pulmonary function
Improve exercise capacity
All of the above
Providing COPD patients with a nutritional
formula that is high in calories has been shown to
increase the amount of carbon dioxide that patients
produce, thus increasing their ventilatory load
(Mallampalli, 2004)
Some trials of nutritional supplementation in
underweight patients have proven to be
disappointing, perhaps because these patients were
losing weight due to an exaggerated systemic
inflammatory response and responded poorly to
nutritional support (Steiner, 2003)
Most studies show that nutritional
supplementation can help limit weight loss
and negative energy balance, but the effect
of nutritional supplementation alone on
clinically significant outcomes such as
pulmonary function and exercise capacity is
minimal (Mallampalli, 2004)
Question 6
Candidates for pulmonary rehabilitation
in COPD should be chosen because of
their:
Prescription drug usage
FEV1 value
Symptoms
Partial pressure of oxygen (PAO2)
Comorbidities
Pulmonary rehabilitation may be indicated for
those patients whose symptoms are not relieved
with pharmacological therapy. The GOLD (Global
Initiative for Chronic Obstructive Lung Disease),
NICE (National Institute for Health and Clinical
Excellence), and ATS-ERS (American Thoracic
Society/European Respiratory Society) guidelines
all strongly endorse pulmonary rehabilitation as an
important component in the management of COPD
Both the ATS-ERS and NICE guidelines
emphasize that candidates for rehabilitation
should be chosen because of symptoms
(Pierson, 2006)
The objectives for pulmonary rehabilitation
are to control, alleviate, and reverse the
symptoms (Rabe, 2006)
Exercise training is the most important component
of such a program, and improvements may be seen
in oxygen uptake, exercise endurance, and a
decrease in the perception of dyspnea
Research studies have shown that pulmonary
rehabilitation is the best treatment option for
patients with symptomatic lung disease who have
moderate to moderately severe disease (Celli, 2006;
Plankeel, 2005)
Rehabilitation increases the anaerobic
threshold by enhancing the aerobic
metabolism of the skeletal muscles
There is a lower rate of production of lactic
acid, enabling increased tolerance of
exercise, because the ventilation rate is less
for a given amount of work (Higenbottam,
2005)
Question 7
The most common cause of exacerbations
of COPD is:
Cold weather
Warm weather
Infection
Air pollution
Vigorous exercise
Exacerbations of COPD may manifest as a
worsening cough, dyspnea, and/or sputum
production sufficient to warrant a change in
management
Exacerbation should be ruled out if heart
failure, myocardial infarction, arrhythmias,
or pulmonary embolism are occurring (Celli,
2006; Cote, 2005)
Viral and bacterial infections are the most
frequently identified causes of COPD
exacerbations (Burge, 2006; Hunter, 2001)
For severe exacerbations, the appropriate
antibiotic should be prescribed for the
prevalent pathogen (Celli, 2006)
Seasonal exacerbations occur in the winter months,
when incidences of respiratory and cardiovascular
disease tend to be more acute (Burge, 2006)
Exacerbations should be prevented, if possible, and
treated aggressively because their effects may be
felt long afterward
They reduce health-related quality of life and can
contribute to accelerated loss of lung function
(Hunter, 2001; Celli, 2006)
Question 8
Which one of the following is the primary
diagnostic tool for testing for COPD?
Peak flow
Spirometry
Clinical examination
Echocardiography
The diagnosis of COPD is more accurately
confirmed by spirometry than by any other
method
According to the GOLD guidelines, a
diagnosis of COPD should be considered for
patients with cough, sputum production,
dyspnea, and/or a history of exposure to risk
factors for COPD (Pauwels, 2005)
Spirometric evaluation can be used to define
disease severity and occurrence (Wouters,
2006)
In the NHANES III survey, less than 50% of
individuals with any severity of COPD
(based on airflow limitation) had been
identified by a physician as having COPD
(Mannino, 2000)
Both asthma and COPD share airflow
limitation as a common functional
abnormality. They have different ranges of
reversibility, and there is considerable
overlap between the two conditions (Beeh,
2006)
Several easily obtained clinical parameters and a
few additional diagnostic investigations were
found to be all that was required to improve the
detection of heart failure (Rutten, 2005)
N-terminal pro-brain natriuretic peptide (NT-proBNP)
test
Electrocardiography
chest radiography
C-reactive protein (CRP)
history and physical examination
Question 9
Comorbidities among patients with COPD are
extremely common for which of the following
reasons?
These patients are usually of middle age or elderly
These patients are more likely to currently smoke or
have a history of smoking
These patients have increased levels of proinflammatory
cells
All of the above
None of the above
Middle-aged and elderly patients are most
often afflicted with COPD, and
comorbidities become more common as age
increases
Although smoking is linked to COPD, it is
also a major risk factor for numerous other
illnesses, including cardiovascular disease
(Man, 2005)
Chronic obstructive pulmonary disease is
recognized as a systemic disorder that involves
other organs in addition to the lungs
There are an increased number of proinflammatory
cells in patients with COPD that may link COPD
to extrapulmonary disorders such as vascular
disease
More patients with COPD die of ischemic heart
disease or stroke (50%) than lung cancer or
respiratory failure (20%) (Man, 2005)
Question 10
Which of the following is a comorbidity of
COPD?
Coronary artery disease
Atherosclerosis
Osteoporosis
A and B
All of the above
Coronary artery disease is a comorbidity of COPD,
as is pneumonia, atherosclerosis, coronary heart
disease, lung cancer, diabetes, peptic ulcers,
osteoporosis, depression, and anxiety (Man, 2005;
Sevenoaks, 2006)
These conditions cannot be explained solely as
being the result of abnormal blood gases
Oxidative stress and systemic inflammation are
mechanically linked to the extrapulmonary
manifestations of COPD (Man, 2005)
Pulmonary hypertension is often associated
with severe COPD (Higenbottam, 2005)
In patients with advanced COPD, 5% to
10% with pulmonary arterial hypertension
will also have right heart failure when
pulmonary artery pressures are higher than
35 to 40 mm Hg
Type II diabetes is more likely to develop in
patients with COPD than in the normal
population, most likely because of the
indicators of inflammation that are present
(Sevenoaks, 2006)
Atherosclerosis is linked to high levels of
CRP and IL-6 (Man, 2005)
Osteoporosis commonly occurs with steroid
use, but patients with COPD have an
increased risk of developing osteoporosis
and osteopenia, even in the absence of
steroid use (Sevenoaks, 2006)
Patients with COPD test seropositive to
Helicobacter pylori up to 77.8%, compared with
54% in control subjects
It is hypothesized that H. pylori induces chronic
activation of inflammatory mediators such as IL-1
and TNF-alpha, which could amplify the
development of COPD by enhancing the
endothelial adhesion and migration of
inflammatory cells into the lungs (Sevenoaks, 2006)
Question 11
Smoking cessation is an important
component of the management of COPD.
Which of the following have an FDA
indication for smoking cessation?
Bupropion
Nortriptyline
Clonidine
Varenicline
A and D
Many of the existing pharmacotherapies for
nicotine addiction rely on the strategy of
mimicking or replacing the effects of nicotine
(Foulds, 2006)
Bupropion increases quit rates in patients with
COPD by up to 20%
Bupropion’s principal mode of action is reduction
of withdrawal symptoms following smoking
cessation due to its ability to increase dopamine
and noradrenaline concentration via an inhibition
of reuptake
It has been approved by the US Food and
Drug Administration (FDA) for tobacco
dependence, and has been endorsed by the
US Clinical Practice Guidelines as a firstline therapy for smoking cessation (Buhl,
2005; Foulds, 2006; Henningfield, 2005)
Dry mouth and insomnia are the two most
common adverse effects
Nortriptyline is effective for use in smoking
cessation and is recommended as a second-line
therapy by the Agency for Health Research Quality
The most common adverse effects associated with
nortriptyline are fast heart rate, blurred vision,
urinary retention, dry mouth, constipation, weight
gain or loss, and low blood pressure upon standing
(Foulds, 2006; Henningfield, 2005)
Clonidine is an alpha-2-noradrenergic
agonist that suppresses sympathetic activity
and has been used for the treatment of
hypertension, as well as to reduce symptoms
associated with alcohol or opiate withdrawal
Adverse effects include sedation,
constipation, dizziness, dry mouth, and
postural hypotension (Foulds, 2006;
Henningfield, 2005)
Varenicline is a new drug with an FDA indication
as an aid for smoking cessation
It is a specific alpha-4-beta-2 nicotinic receptor
partial agonist that stimulates dopamine release
and simultaneously blocks nicotine receptors
Partial agonists reduce nicotine-induced dopamine
release but provide a low-to-moderate level of
dopamine release to reduce craving and withdrawal
symptoms (Foulds, 2006)
The phase III placebo-controlled trials
included randomization to bupropion
In these trials, varenicline produced
significantly higher one-year abstinence
rates than bupropion, and was also
significantly better than placebo (Foulds,
2006)
Question 12
Which of the following combinations of
pharmacologic therapies are NOT
recommended for patients with COPD?
A short-acting beta-agonist plus an inhaled
corticosteroid
A short-acting beta-agonist plus a long-acting
anticholinergic
A short-acting beta-agonist plus a short-acting
anticholinergic
A long-acting beta-agonist plus an inhaled
corticosteroid
All of the above are appropriate combinations of
pharmacotherapy
Bronchodilators and anti-inflammatory
medications are used to treat COPD
There are two pharmacologic classes of shortacting bronchodilators (beta-agonists and
anticholinergics) and three pharmacologic classes
of long-acting bronchodilators (beta-agonists,
anticholinergics, and methylxanthines)
Inhaled corticosteroids are used as antiinflammatory medications
Beta-agonists are recommended as initial
therapy for intermittent symptom
management for both asthma and COPD
The results of a recent meta-analysis suggest
that patients with COPD who use inhaled
beta-agonists have more than twice the risk
of respiratory death than those who use
anticholinergic agents (Salpeter, 2006)
Inhaled corticosteroids do not alter the rate of lung
function decline, but they have been shown to
reduce bronchial hyperreactivity, decrease the
frequency of exacerbations, and slow the patient’s
health decline
When beta-agonists are combined with
corticosteroids, the rate of glucocorticoid receptor
translocation may be accelerated, thus further
reducing local inflammation in the lung (Sin, 2006)
Improvement was seen in a small trial
utilizing fluticasone, salmeterol, and
tiotropium for one week, with higher FEV1
values observed when the triple combination
was used than with fluticasone and either
tiotropium or salmeterol (Donohue, 2005)
The combination may reduce airway
inflammation by blocking bronchial T-cell
infiltration (Reinberg, 2006)
Question 13
Which of the following statements regarding
patients with COPD and comorbid
cardiovascular disease are true?
Beta-blockers are contraindicated in patients with
COPD because they worsen airflow limitation
The use of beta-blockers has been associated with a
decrease in mortality from any cause in patients with
COPD
Beta-agonists, which are used to treat patients with
COPD, have been associated with an increased mortality
rate in patients with CHF
A and C
B and C
Beta-blockers are less likely to be prescribed for
patients with COPD because of concerns over
worsening airflow limitation, but they are effective
at reducing mortality and other important
cardiovascular disease outcomes among patients
with ischemic heart disease
Beta-blockers may have beneficial effects in
patients with COPD and are not contraindicated in
these patients (Au, 2004; Bryson, 2004)
Beta-adrenoceptor agonists should be used
with care in patients with CHF, as numerous
studies show increased risk of mortality
associated with their use
In a more recent study by Au and associates,
the use of beta-agonists was associated with
an increased risk of hospitalization for CHF
(Au, 2004)
Question 14
Which of the following drugs was
considered first-line therapy for COPD
patients but is currently considered a
third-line therapy?
Beclomethasone
Theophylline
Methylprednisolone
Albuterol
International guidelines currently specify
theophylline as a third-line therapy for
COPD (Barnes, 2005)
The British Thoracic Society guidelines on
management of COPD recommend the use
of xanthine derivatives as a last resort, and
only after all other treatments have failed to
show a response (Ram, 2005)
Theophylline directly relaxes the smooth
muscle in the human airway in vitro
Theophylline brings about an improvement
of the mechanical advantage of the
diaphragm and chest wall muscles
Theophylline will also stimulate the
medullary respiratory center (Ram, 2006)
At lower plasma concentrations,
theophylline has significant antiinflammatory effects for patients with
COPD
Recent evidence has shown that
theophylline at low therapeutic
concentrations is an activator of histone
deacetylases, which enhance the antiinflammatory effect of corticosteroids
Patients with COPD have a marked reduction in
histone deacetylase-2 in macrophages and
peripheral lung, which accounts for amplified
inflammation and resistance to steroids
Theophylline can restore steroid sensitivity in vitro
(Barnes, 2005)
Low-dose, slow-release oral theophylline was
found to be effective and well tolerated for the
long-term treatment of COPD (Zhou, 2006)
Theophylline continues to have an important,
albeit controversial, role in the management
of symptomatic, stable COPD (Ram, 2005;
Ram, 2006)
Question 15
At which level of nocturnal oxygen
saturation should long-term oxygen
therapy be given?
44% or less
55% or less
66% or less
77% or less
88% or less
The Nocturnal Oxygen Therapy Trial and
studies done by the Medical Research
Council have established that long-term
oxygen therapy extends survival in patients
with hypoxemic COPD
Supplemental oxygen and smoking
cessation are the only therapies that have
been shown to reduce mortality in patients
with COPD (Cote, 2005)
Long-term oxygen therapy is beneficial for those
patients with a measured partial pressure of oxygen
(PAO2) of 55 mm Hg or less while at rest or awake,
or an oxygen saturation of 88% or less while
sleeping (Sin, 2003; Cote, 2005)
The skeletal muscles are generally underused and
the respiratory muscles are overused. Oxygen
therapy helps to balance out these muscles (Agusti,
2005)
Question 16
For every __% decrease in FEV1,
cardiovascular mortality increases by
__%.
5%; 18%
10%; 28%
12%; 33%
17%; 39%
Poor lung function has been shown to be a
powerful predictor for cardiac mortality (Sin,
2005)
In the Baltimore Longitudinal Study of
Aging, for every 10% decrease in FEV1,
cardiovascular mortality increases by about
28%, and nonfatal coronary events increase
by about 20% in mild-to-moderate COPD
(Sin, 2005)
In a study of lung function decline in an
elderly population, 4,923 adults aged 65
years and older were analyzed using
spirometry to determine
More rapid decline in lung function was
found to be independently associated with a
modest risk of hospital admissions and
deaths from COPD (Mannino, 2006)
Question 17
Inhaled corticosteroids and long-acting
bronchodilators, alone or in combination, have
demonstrated benefit in reducing symptoms
and exacerbations. The goals of the TORCH
(Towards a Revolution in COPD Health) study
are expected to provide further insight into the
effects of inhaled corticosteroids and longacting bronchodilators on COPD with regard to:
Quality of life in patients with COPD
Mortality in patients with COPD
Rate of exacerbations
All of the above
The TORCH (Towards a Revolution in COPD
Health) trial is a multicenter, randomized, doubleblind, parallel-group, placebo-controlled study of
approximately 6,200 patients with moderate-tosevere COPD who were randomly assigned to
twice-daily treatment with either
salmeterol/fluticasone propionate (50/500 mg),
fluticasone propionate (500 mg), salmeterol (50
mg), or placebo for three years
The primary endpoint is all-cause mortality
Secondary endpoints are COPD morbidity
relating to rate of exacerbations and health
status (The TORCH Study Group, 2004)
Thanks for your attention