case conference optimizing treatment in a patient with copd and comorbid disease presentation: r3...

Case Conference Case Conference

Optimizing Treatment in a Patient With Optimizing Treatment in a Patient With COPD and Comorbid DiseaseCOPD 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, thin-looking 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 1Question 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 ex-smokers (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)


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)


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)


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)


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)


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)


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)


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


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 lungsThere are an increased number of proinflammatory cells in patients with COPD that may link COPD to extrapulmonary disorders such as vascular diseaseMore patients with COPD die of ischemic heart disease or stroke (50%) than lung cancer or respiratory failure (20%) (Man, 2005)


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 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 first-line 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 withdrawalAdverse 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)


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 short-acting bronchodilators (beta-agonists and anticholinergics) and three pharmacologic classes of long-acting bronchodilators (beta-agonists, anticholinergics, and methylxanthines)

Inhaled corticosteroids are used as anti-inflammatory 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)


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)


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 anti-inflammatory effects for patients with COPDRecent evidence has shown that theophylline at low therapeutic concentrations is an activator of histone deacetylases, which enhance the anti-inflammatory 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)


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 COPDSupplemental 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)


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)


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 long-acting 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, double-blind, parallel-group, placebo-controlled study of approximately 6,200 patients with moderate-to-severe 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)

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