Chronic Obstructive Pulmonary Disease
From a satellite symposium sponsored by the Academy for Healthcare Education, Inc., held in conjunction with the 2006
Scientific Assembly of the American Academy of Family Physicians
| Prevention and Diagnosis —Louis Kuritzky, MD, Clinical Assistant Professor of Community Health and Family
Medicine, University of Florida College of Medicine, Gainesville
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| Introduction: although small percentage of cases due to ⓫ antitrypsin deficiency, most cases of chronic obstructive
pulmonary disease (COPD) associated with tobacco smoking; COPD highly preventable; smoking cessation key to prevention;
smoking prevention education must begin in early grades (mean age at which people begin smoking 13.6 yr);
airflow limitation due to COPD not fully reversible, but patients usually can be helped “to improve their capacity to interact
in daily life” through therapy; initial therapy involves bronchodilators, usually anticholinergic drugs or long-acting
β-agonists; spirometry most helpful tool for making diagnosis
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| Natural history: COPD usually progressive; inflammatory response different from that seen with asthma (eosinophilia
predominates in asthma, but in COPD neutrophilia predominates); number of patients diagnosed with COPD
much smaller than those not diagnosed (“suffer in silence”; limit activities); unlike mortality from cardiovascular disease,
COPD mortality not declining and continues to rise; “physician prejudice” possible factor why COPD mortality
continues to rise (some patients fearful of discussing problem with physician for fear of being chastised for smoking);
deaths from COPD in women now surpass those in men
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| Pathophysiologic aspects: elastin primary structural element of lung; like bone, elastin constantly being produced
and broken down; over time, people lose elastin, but most people have enough elastin reserve to last through old age;
smokers lack elastin reserve; effects of cigarette smoke—activates macrophages that induce production of free radicals
that activate neutrophils, which induce production of elastase that degrades elastin; function of ⓫-antitrypsin to shut off
elastase, facilitating buildup of elastin; those with ⓫-anti-trypsin deficiency cannot shut off elastase, leading to diminution
of elastin and lung disease; cigarette smoking interferes with function of ⓫-antitrypsin (happens in ≈20% of smokers)
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| Concept of hyperinflation: normally, people have both expiratory and inspiratory reserves, but those with COPD
suffer from hyperinflation, characterized by increased residual and tidal volumes; people with severe COPD can develop
dyspnea even at rest; exercise—when those without COPD exercise and need more air, they capture part of
inspiratory and expiratory reserves and do not reach dyspnea threshold; when people with COPD exercise, because
end-expiratory lung volume elevated and inspiratory capacity decreased, tidal volume and end-expiratory reserve
increase, and end-expiratory volume goes up (instead of down as in healthy person); resulting increased work of
breathing makes it more difficult to exercise; good news—bronchodilator therapy can improve inspiratory capacity;
link between inspiratory capacity, ability to exercise, and experience of dyspnea
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 | Consequences of lack of exercise in COPD patients: increased incidence of osteoporosis; increase greater than that
due to lack of exercise alone; corticosteroid use and other unknown factors also contribute to this problem
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| Case of Judith: middle-aged woman who complains of cough and shortness of breath; has sputum production and exertional
dyspnea; 30-yr smoking history, still smokes, and not ready to quit; initially diagnosed with stage 1 COPD
and given inhaler
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| Recommended initial approach: assess risk factors (particularly smoking); inform patient that taking vitamins and
supplements will not protect lungs from effects of smoking; perform spirometry to assess COPD severity
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| Spirometry: best way to diagnose COPD (gold standard); obstructive airway disease defined as abnormality in relationship
between forced expiratory volume in 1 sec (FEV1) and forced vital capacity (FVC); if FEV1 to FVC ratio
<70%, patient has obstructive airway disease (asthma or COPD); 20% of patients with COPD have asthmatic component;
spirometry better than peak flow measurement for assessing mild and severe COPD (peak flow rate helpful in intermediate
severity), and helps to predict those who will decline further; ≈7% of people in physician’s waiting room
have abnormal spirometry; who should have spirometry?—smokers and former smokers; people with dyspnea,
cough, or wheezing; lung age—helpful diagnostic tool, eg, FEV1 of 3 L appropriate for 80-yr-old person; man 45 yr
of age with FEV1 of 3 L has lung age of 80 yr; use of bronchodilators can lower his lung age into mid 60s; if patient
still smoking, advise that it is never too late to quit
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| Cigar smoking: 1 cigar has tar, carbon monoxide, and nicotine of >20 cigarettes; alkalinity of cigar smoke promotes
more absorption of toxins through buccal mucosa than cigarettes; some people do not inhale cigar smoke, but those
with history of cigarette smoking do inhale
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| Diagnostic points: spirometry should be done routinely in people with dyspnea and evidence of COPD; most people
with asthma develop it during their youth, whereas COPD develops during adulthood; most people with asthma have
history of atopy and often positive family history; genetic component usually absent for COPD patients, except for
strong family history of smoking; asthmatics “nearly normal” between attacks (not so for those with COPD); differentiating
COPD from asthma—methacholine challenge; histamine inhalation challenge
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| Smoking issue: when seeing children with otitis, recurrent respiratory infections, or worsening of asthma, ask whether
anyone in household smokes; if smoker present, measure cotinine level in plasma, saliva, or urine of child; cotinine
levels—≈4 ng/mL normal for child in nonsmoking household; 30 ng/dL average for child whose parents smoke in
house, and 21 ng/dL average for child whose parents smoke outdoors; tell parents—even if unwilling to quit for own
health, smoking poses serious risk to child’s respiratory health
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| Study involving preschoolers: 50% of 500 children 5 and 6 yr of age thought smoking “cool”; best predictor for child
to later take up smoking was if mother smoked (6 times greater relative risk); comment—nicotine transmitted in
breast milk; some clinicians believe mothers who smoke and breast-feed sensitize their children to nicotine; these
children at greater risk for becoming smokers
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| More about Judith: FEV1/FVC ratio <70%, indicating obstructive airway disease; FEV1 56%, suggesting she was on
verge of going from moderate to severe COPD; according to Global Obstructive Lung Disease (GOLD) initiative staging
guidelines, she has late stage 2 to early stage 3 criteria for COPD
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| Pharmacologic Management —Fernando J. Martinez, MD, Professor of Internal Medicine and Director, Pulmonary
Outpatient Services, University of Michigan Medical Center, Ann Arbor
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| GOLD guidelines: one major approach; recommend incremental steps in therapeutic intervention, use of spirometry
for making diagnosis, and stress importance of reducing risk factors (eg, smoking cessation; influenza and pneumococcal
vaccines)
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| Patient-centered approach: more practical; intermittent therapy indicated if patient develops dyspnea only when
climbing stairs; add long-acting bronchodilator if patient has persistent symptoms; add another agent (from another
class of drugs) if patient still not doing well; comment—this approach based primarily on patient’s clinical symptoms
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| Smoking cessation: most important part of management; preserves lung function; within first 2 wk after cessation,
cough gets worse then starts to improve; after ≈3 mo, lung function actually improves (shown by Lung Health Study);
total elimination of cigarette smoking required to improve lung function (smoking 2 to 3 cigarettes/day still associated
with loss of lung function); at 1 yr after quitting, cardiovascular risk decreases by ≈50%, and by ≈15 yr after cessation,
risk drops to level seen in nonsmokers; lung cancer risk drops by ≈50% 10 yr after cessation, but it never drops to level
seen in lifelong nonsmokers
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| Interventions for smoking cessation: nicotine replacement products—first approved by Food and Drug Administration
(FDA) in mid 1980s; nasal spray associated with most rapid rise in blood nicotine level; nicotine patch associated
with slowest rise; none of these products comes close to providing individual with as much blood nicotine as
cigarettes do; bupropion—approved in 1997 as smoking-cessation product; comment—nicotine replacement products
and bupropion work best when combined with counseling; varen--icline—new; nicotine receptor partial agonist
and partial antagonist; agonist component helps patient feel better during nicotine withdrawal phase; trial suggests
varenicline more effective than bupropion; start with low dose (one-half pill for 3 days, then one-half pill bid for 3
days, followed by full dose next 2.5 mo); associated with quit rates of ≈40% at 3 mo and 25% to 30% at 1 yr
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| Pharmacologic treatment: goals espoused by GOLD include fewer symptoms, improved health status, improved
exercise capacity, and prevention of exacerbations
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| Bronchodilators: provide symptomatic relief; GOLD guidelines recommend short-acting agents for “as needed” therapy;
many agents available, but anticholinergic agents and β-agonists most widely used; other agents include theophyllines;
GOLD guidelines—consider using long-acting agent in anyone with FEV1 <80% of predicted value
(preferred over short-acting agents); points—ipratropium short-acting anticholinergic agent; 2 studies concluded that
long-acting agents improve both lung function and health status
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| Long-acting beta-agonists: include salmeterol and formoterol; both dosed twice daily, and lead to lung function improvement,
symptomatic relief, and overall improved health status
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| Anticholinergic agents: relieve bronchoconstriction (in COPD, bronchoconstriction closely tied to cholinergic
tone); act on muscarinic receptors (M1, M2, and M3) in lungs; M1 and M3 facilitate acetylcholine release and resulting
mucus formation and constriction of smooth muscle; M2 inhibitory, decreases acetylcholine release; ideal agent
does not exist; tiotropium best agent
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| Tiotropium: binds to all receptors and blocks M3 for up to 35 hr; dissociates quickly from M2; provides 24-hr
broncho-dilation for at least 1 yr; improves exercise capacity, dynamic hyperinflation, and breathlessness; increases
inspiratory capacity; end-expiratory lung volume still increases, but to lesser extent
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| Tiotropium vs ipratropium: both drugs effective early on; however, only tiotropium maintains benefit ≥1 yr; both
drugs improve health status of COPD patients and improve exacerbation rates
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| Inhaled corticosteroids: excellent for treating asthma; role still not clear for COPD; combination agents involving
steroids available, but fluticasone/salmeterol only combination agent available in United States; steroids currently
thought not to modify loss of lung function seen in COPD, but do help make patients feel better and thought to reduce
number of exacerbations by ≈30%; with fluticasone/salmeterol one sees improvement in pulmonary function
and reduced exacerbation rate; comments—long-acting β-agents (LABA) improve exacerbation rates “a little bit”;
exacerbation rates improve much more when inhaled steroids added; United Kingdom trial suggested that addition
of steroids could improve survival
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| Toward a Revolution in COPD Health (TORCH) study: done to determine whether high-dose fluticasone (500 mg)
plus salmeterol could improve mortality over 3 yr; concluded relative reduction ≈17%
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| Current status of inhaled steroids: potential disadvan--tages—osteoporosis; cataracts; indications—lung function
<50% of predicted value; frequent exacerbations; bottom line—inhaled steroids have role in COPD, but not in every
patient
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| Combination therapy: combination of long-acting anticholinergic agent and long-acting β-agonist has synergistic
effect; recent study showed this for tiotropium plus formoterol
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| Exercise therapy: tailor to individual patient; pulmonary rehabilitation (multidisciplinary care involving medications,
exercise training, education, and energy conservation) shown to improve symptoms and quality of life; multidisciplinary
approach decreases dynamic hyperinflation, improves patient’s exercise endurance, and has synergistic
effect; major advantages and very few drawbacks
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| Conclusions: treatment improves patient’s functional status; COPD preventable if tobacco issue addressed early; broncho-dilators
(short- and long-acting) improve pulmonary function, symptoms, patient’s overall health status, and reduce exacerbations;
smoking cessation definitely improves mortality
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| Questions and Answers —Drs. Kuritzky and Martinez
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| Frequency of spirometry: use at baseline; repeat after medication changes to convince patients drug working
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| Compensation for doing spirometry: granted for making diagnosis or assessing patient following acute exacerbations;
otherwise, compensation once yearly
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| Recently issued FDA “black box” warning for LABA: applies for increased mortality risk in asthmatics
(particularly blacks), but not COPD; β-agonists, however, clearly have role in treating severe asthma; in treating
asthmatics, give steroids first, then LABA if required; remark—black box warning on bupropion (Zyban) for
treating smoking cessation
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| Leukotriene inhibitors: effective only in treating asthma; consider use in COPD patient with atopic component
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| Concomitant use of ipratropium and tiotropium: official party line is they should not be used together; when
switching patients on Combivent (ipratropium and albuterol) to tiotropium, first switch them to albuterol alone and
then add tiotropium; Dr. Martinez likes to use tiotropium as long-acting agent and albuterol as rescue agent, and also
suspects there is “no big deal” in using ipratropium and tiotropium concomitantly
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| Prevalence of COPD in smokers: only 20% to 25% in United States, according to latest statistics; however, in
Sweden, closer to 50% to 80%
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| Efficacy of starting LABA earlier: Understanding the Potential Long-Term Impacts on Function with Tiotropium
(UPLIFT) study ongoing to determine this; hypothesis of this study that long-term anticholinergic (tiotropium qd vs
bid) preserves pulmonary function and has long-term benefits in improving lung function; Lung Health Study did not
show benefit of pharmacotherapy using short-acting agents in achieving these goals
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Educational Objectives
| The goal of this program is to improve the prevention, diagnosis, and treatment of chronic obstructive pulmonary disease
(COPD). After hearing and assimilating this program, the clinician will be better able to:
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| 1. Describe how smoking affects lung function in the development of COPD.
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| 2. Utilize spirometry in the diagnosis of COPD.
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| 3. Treat COPD patients with bronchodilators (eg, β-antagonists, anticholinergics).
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| 4. Know when to consider adding inhaled cortico-steroids to the treatment regimen.
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| 5. Assist patients to stop smoking.
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Suggested Reading
Adams SG et al: Systemic review of the chronic care model in chronic obstructive pulmonary disease prevention and
management. Arch Intern Med 167:551, 2007; Appleton S et al: Ipratropium bromide vs long-acting ⓶-agonists for
stable chronic obstructive pulmonary disease. Cochrane Database Syst Rev (3):CD006101, 2006; Barreiro TJ, Perillo
I: An approach to interpreting spirometry. Am Fam Physician 69:1107, 2004; Dewar M, Curry RW Jr: Chronic
obstructive pulmonary disease: diagnostic considerations. Am Fam Physician 73:669, 2006; Flaherty KR, Martinez
FJ: Cigarette smoking in interstitial lung disease: concepts for the internist. Med Clin North Am 88:1643, 2004; Halbert
RJ et al: Global burden of COPD: systematic review and meta-analysis. Eur Respir J 28:523, 2006; Hunter MH,
King DE: COPD: management of acute exacerbations and chronic stable disease. Am Fam Physician 64:603, 2001;
Hutton SF: Tiotropium (Spiriva) for COPD. Am Fam Physician 69:2901, 2004; Incalzi RA et al: From Global Initiative
for Chronic Obstructive Lung Disease (GOLD) guidelines to current clinical practice: an overview of the pharmacological
therapy of stable chronic obstructive pulmonary disorder. Drugs Aging 23:411, 2006; Karnani NG et al:
Evaluation of chronica dyspnea. Am Fam Physician 71:1529, 2005; Mallin R: Smoking cessation: integration of behavioral
and drug therapies. Am Fam Physician 65:1107, 2002; Martinez FJ et al: Is it asthma or COPD? The answer determines
proper therapy for chronic airway obstruction. Postgrad Med 117(3):19, 2005; Martinez FJ et al: Predictors
of mortality in patients with emphysema and severe airflow obstruction. Am J Respir Crit Care Med 173:1326, 2006;
Martinez FJ: Acute exacerbation of chronic bronchitis: expanding short- course therapy. Int J Antimicrob Agents
26(Suppl 3):S156, 2005; Poole PJ et al: Influenza vaccine for patients with chronic obstructive pulmonary disease. Cochrane
Database Syst Rev (1)CD002733, 2006; Somand H, Remington TL: Tiotropium: a bronchodilator for
chronic obstructive pulmonary disease. Ann Pharmacother 39:1467, 2005; Walters JA et al: Oral corticosteroids for
stable chronic obstructive pulmonary disease. Cochrane Database Syst Rev (3):CD005374, 2005.
Faculty Disclosure
In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty members to disclose relevant
financial relationships within the past 12 months that might create any personal conflicts of interest. Any identified
conflicts were resolved to ensure that this educational activity promotes quality in health care and not a proprietary business
or commercial interest. For this program, the following has been disclosed: Dr. Kuritzky is a member of the Speakers’
Bureaus for Boehringer Ingelheim Pharmaceuticals, GlaxoSmithKlein, and Pfizer. Dr. Martinez is a consultant and
a member of the Speakers’ Bureaus for Boehringer Ingelheim Pharmaceuticals and Pfizer.
Acknowledgements
Drs. Kuritzky and Martinez were recorded September 28, 2006, at a satellite symposium sponsored by the Academy for
Healthcare Education, Inc, held in conjunction with the annual Scientific Assembly of the American Academy of Family
Physicians in Washington, DC. The Audio-Digest Foundation thanks the speakers and the Academy for Healthcare Education,
Inc for making this program possible.
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