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Osteopathic Physicians’ Guide
Editors’ Message.............................................................................3
Improving Outcomes in Patients With COPD
Brian H. Foresman, DO
Fredric Jaffe, DO
Diagnostic Considerations
in Chronic Obstructive Pulmonary Disease..................................5
Rupen Amin, MD
Interventions for Patients
With Chronic Obstructive Pulmonary Disease...........................11
Thomas F. Morley, DO
Amita Pravinkumar Vasoya, DO
Comorbidities and Systemic Effects
in Chronic Obstructive Pulmonary Disease.................................18
Kartik Shenoy, MD
Fredric Jaffe, DO
Osteopathic Principles and Practice
in Chronic Obstructive Pulmonary Disease................................23
Stephen J. Miller, DO, MPH
Cover Credits
Nancy Horvat, AOA creative director.
Acknowledgment
With gratitude to the Galter Health Sciences Library of the Northwestern
University Feinberg School of Medicine in Chicago, Illinois.
This guide is available online at http://www.osteopathic.org/copd-guide.
Statements and opinions expressed in this guide are those of the
authors and not necessarily those of the American Osteopathic
Association or the institutions with which the authors are affiliated,
unless otherwise stated.
©2011 by the American Osteopathic Association. No part of this
guide may be reprinted or reproduced in any form without written
permission of the publisher.
Printed in the USA.
Osteopathic Physicians’ Guide
TABLE OF
CONTENTS
Editors’ Message
Improving Outcomes in Patients
With COPD
Brian H. Foresman, DO | Fredric Jaffe, DO
Chronic obstructive pulmonary disease (COPD) is a primary cause of more than
120,000 deaths annually.1 It is now the fourth leading cause of death in the United
States.2 Clinicians cannot cure this disease but can alleviate the debilitating
effects of this disease with early diagnosis and stepwise intervention. A majority
of COPD cases can be attributed to firsthand or secondhand tobacco smoke
exposure. Remaining cases can be a result of genetic susceptibility followed by
recurrent lung damage. This damage can come from infections or toxic exposure
to lung-injuring particles. Smoking cessation and avoidance of secondhand smoke
can arrest the acceleration of loss of lung function. However, although most COPD
interventions can improve patients’ quality of life, such interventions do not
reverse the progression of disease.
The present guide provides physicians with a concise review of the latest
research on assessing risk factors for COPD, diagnosing the disease, determining
the best treatment plan, and recognizing and addressing comorbidities that are not
recognized in patients with COPD.
In the first article, “Diagnostic Considerations in Chronic Obstructive Pulmonary Disease,”3 Rupen P. Amin, MD, analyzes COPD risk factors and symptoms
and assesses diagnostic approaches and tools. Dr Amin emphasizes the importance
of using simple spirometry in diagnosing COPD. This simple screening tool can
help measure the severity of the disease and therefore determine the best course of
treatment.
The second article, written by Thomas F. Morley, DO, and Amita P. Vasoya, DO,
and titled “Interventions for Chronic Obstructive Pulmonary Disease,”4 outlines
an incremental approach to treating patients with COPD. Paramount to the
From the Roudebush VA Medical Center in Indianapolis, Indiana (Dr Foresman), and from the
Division of Pulmonary and Critical Care Medicine at Temple University School of Medicine in Philadelphia,
Pennsylvania (Dr Jaffe).
Financial Disclosures: None reported.
E-mail: [email protected]
3
Osteopathic Physicians’ Guide: COPD
management of COPD is smoking cessation in all who continue to smoke. As the
disease becomes more severe, physicians may progress to treating patients with
bronchodilators and inhaled corticosteroids. Long-term oxygen therapy, oral
steroids, and surgical treatments may be indicated for very severe disease. Citing
the recommendations of the Global Initiative for Chronic Obstructive Lung Disease
(known as GOLD), Dr Morley and Dr Vasoya explain how this stepwise approach
improves the efficacy of interventions, minimizes complications, and reduces costs.
The authors provide a review of the various pharmacologic and nonpharmacologic
treatment options for patients with COPD.
Many physicians assume that COPD is a disease of only the lungs, but evidence
suggests that the disease has more far-reaching effects. There are many systemic
manifestations, including an increase in comorbidities such as cardiovascular disease, osteoporosis, and diabetes mellitus. All these comorbid conditions can affect
quality of life and ultimately morbidity and mortality. In the third article, “Comorbidities and Systemic Effects in Chronic Obstructive Pulmonary Disease,”5 Kartik
Shenoy, MD, and Fredric Jaffe, DO, discuss the interrelationship of comorbid conditions and COPD and the management of patients with COPD who experience
these diseases.
In the final article, “Osteopathic Manipulative Medicine in Chronic Obstructive Pulmonary Disease,”6 Stephen J. Miller, DO, MPH, reports that osteopathic
manipulative treatment (OMT) has yet to be proven to be of much benefit in treating patients for COPD. Research indicates that OMT may improve patients’ quality
of life and work capacity, but studies show that OMT may paradoxically worsen
COPD patients’ lung function. Dr Miller emphasizes that more research is needed
to fully assess the impact of OMT on patients with COPD. He suggests that research
be conducted to investigate the effects of osteopathic medicine’s whole-patient philosophy on treating patients with COPD.
Chronic obstructive pulmonary disease is a disease that all too often is undiagnosed until clinical symptoms become apparent. It is important for every physician
to realize that early detection of the disease, along with systematic intervention as
well as the recognition of comorbidities, can improve the quality of life and ultimately the survival rate of your COPD patients. We hope this publication will
help guide your clinical decision-making and raise awareness of the ravages of the
disease. We remain optimistic about the ability to intervene and to help increase
quality of life in our COPD patients.
References
1. National Heart, Lung, and Blood Institute. Morbidity & Mortality: 2009 Chart Book on Cardiovascular,
Lung, and Blood Diseases. Bethesda, MD: National Institutes of Health; 2009:59-68. http://www.nhlbi.nih.
gov/resources/docs/2009_ChartBook.pdf. Accessed May 27, 2011.
2. Jemal A, Ward E, Hao Y, Thun M. Trends in the leading causes of death in the United States, 19702002. JAMA. 2005;294(10):1255-1259.
3. Amin R. Diagnostic considerations in chronic obstructive pulmonary disease. In: Foresman BH, Jaffe
F, eds. Osteopathic Physicians’ Guide: COPD. Chicago, IL: American Osteopathic Association; 2011:5-10.
4. Morley TF, Vasoya AP. Interventions for patients with chronic obstructive pulmonary disease. In:
Foresman BH, Jaffe F, eds. Osteopathic Physicians’ Guide: COPD. Chicago, IL: American Osteopathic
Association; 2011:11-17.
5. Shenoy K, Jaffe F. Comorbidities and systemic effects in chronic obstructive pulmonary disease. In:
Foresman BH, Jaffe F, eds. Osteopathic Physicians’ Guide: COPD. Chicago, IL: American Osteopathic
Association; 2011:18-22.
6. Miller SJ. Osteopathic principles and practice in chronic obstructive pulmonary disease. In: Foresman
BH, Jaffe F, eds. Osteopathic Physicians’ Guide: COPD. Chicago, IL: American Osteopathic Association;
2011:23-27.
4
Osteopathic Physicians’ Guide: COPD
DIAGNOSTIC CONSIDERATIONS
in Chronic Obstructive
Pulmonary Disease
Rupen Amin, MD
Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death
in the United States. Frequently, the diagnosis of COPD is not considered until
patients experience symptomatic disease, at which point the disorder is usually
more advanced. Furthermore, other disease entities that mimic COPD symptoms
are known to occur and have specific treatments that can confound disease
progress. In all circumstances, modifying the disease progression associated with
COPD remains most effective when the condition is identified early. The present
article reviews risk factors for development of COPD and key elements of medical
history and physical examination associated with COPD. The article also provides
an overview of testing used to obtain a diagnosis of COPD.
Even with recent advances in treatment, chronic obstructive pulmonary
disease (COPD) remains a severely debilitating condition. As the fourth leading cause of death in the United States,
COPD claims more than 120,000 lives
annually in this country.1 Frequent
office visits and hospitalizations and
lengthy treatment periods lead to high
financial costs for COPD, estimated at
nearly $29 billion per year.1 Less than
half of this cost can be attributed to
hospitalizations for COPD exacerbations, suggesting that earlier identification and improvements in outpatient
therapy could substantially reduce
the economic impact of this disorder.
Moreover, smoking cessation and prevention of exposure to inciting agents
remain paramount issues at all stages of
COPD—independent of specific etiologic factors.
Prevalence of “mild” cases of
COPD in individuals between the ages
of 25 and 75 years is estimated at 6.9%,
whereas prevalence of “moderate”
cases of COPD (indicating increased
severity of airflow obstruction) in this
age group is estimated at 6.6%.2 Unfortunately, the prevalence of COPD
is underestimated, because many cases
of the disease remain undiagnosed until symptoms become grossly apparent
and after irreversible pathophysiologic
changes are established. Although
COPD remains most prevalent in men
worldwide, recent data have revealed
alarming increases in COPD incidence,
mortality, and morbidity among women.3 Much of these changes are attributable to the increased rate in smoking among women, though additional,
poorly quantified factors appear to be
present.3
From the Division of Pulmonary, Allergy, Critical Care, and Occupational Medicine in the Department of
Medicine at Indiana University School of Medicine in Indianapolis.
Financial Disclosures: None reported.
Address correspondence to Rupen Amin, MD, 301 W Michigan St, Apt 133, Indianapolis, IN 46202-3223.
E-mail: [email protected]
Risk Factors
Smoking
Tobacco exposure, including both firsthand and second-hand exposure, is the
single most important risk factor for
the development of COPD.1 Indeed,
roughly 73% of mortality from COPD
can be attributed to smoking.4 Despite
this high mortality rate, COPD will not
develop in all smokers. Observations
among individuals in Sweden revealed
upwards of 25% of smokers having
clinically significant COPD.5 This finding would argue that while the great
majority of COPD cases are attributable to the use of tobacco products, the
remaining cases may have other contributing factors. Well-known genetic
predispositions result in the development of COPD, as do environmental
factors and recurrent pulmonary damage (eg, infection).4,6
The cumulative-dose exposure of
smoking has been shown to correlate
with the severity of disease. According
to data derived in 1984 from a National
Health and Nutrition Examination
5
Osteopathic Physicians’ Guide: COPD
o Aerosolized oils
o Grain dust
o Vanadium
o Coal
o Osmium
o Welding fumes
o Cotton dust
o Portland cement
o Wood dust
o Engine exhaust
o Silica
o Fire smoke
o Synthetic fibers
Figure 1. Occupational environmental substances known to serve as risk factors for the
development of chronic obstructive pulmonary disease (COPD), primarily by acting as irritants in
the airways and leading to chronic inflammation.21
Survey in which 14,000 individuals were
examined, 8.8% of the individuals were
nonsmokers or former light smokers
(ie, with a history of <5 packs/year) who
had a diagnosis of mild COPD.7 Among
the individuals who had a history of
continuous smoking, the severity of
COPD escalated in a dose-dependent
manner.7 Studies assessing COPD risk
based on different types of tobacco and
filtered vs unfiltered cigarettes report
only slight variations in COPD risk
based on these differences.8
There is some controversy regarding the impact of reductions in tar content on lung function as measured by
forced expiratory volume in 1 second
(FEV1), with some studies showing a
beneficial influence and other studies
demonstrating no impact.9-11 The differences in study findings may be the
result of environmental influences,
cigarette characteristics, or compensatory mechanisms affecting the degree
of smoke inhalation. Although “not
inhaling” has been a bit of a political
joke, smokers who inhale deeply have
substantially higher rates of pulmonary
function decline compared to smokers
who do not inhale deeply, when controlled for type of cigarette, nicotine
and tar content, and filtered vs unfiltered cigarette.9-11
Active cigarette smoking produces
adverse affects through the stimulation
of lung inflammation and white blood
cell activation. This stimulation creates
a milieu in which higher concentrations of enzymes are active in the lungs,
causing a breakdown of the lungs’ collagen structures. This breakdown accelerates the normal age-related decline in lung function as measured by
FEV1. The accelerated decline in FEV1
leads to airflow obstruction, symptom6
atic dyspnea, and limitations to physical activity—the symptoms that often
prompt a diagnosis of COPD.12
Smoking cessation, regardless of
the severity of COPD, normalizes the
rate of lung function decline. To clarify,
in individuals who successfully quit
smoking, their lung function does not
return to normal, but the physiologic
age-related decline in lung function
(which was accelerated by smoking) returns to a normal rate of decline.13
Childhood Influences
Reduced lung growth and premature
decline of lung function during childhood or adolescence increase the risk
for development of COPD in adulthood. Individuals who had recurrent
childhood respiratory infections or
premature birth often have obstructions in their small airways, with a
higher risk for COPD development in
adulthood.4,14,15
Genetic Makeup
First-degree relatives of individuals
who have been diagnosed as having
COPD have a nearly 3-fold increased
relative risk for the development of
COPD, suggesting a genetic predisposition for the condition.15,16 Studies
in monozygotic twins have confirmed
that a genetic susceptibility exists for
the development of airflow obstruction
with exposure to tobacco smoke.17
A genetic predisposition to COPD
development is further supported by
the high incidence of premature emphysema in individuals with a deficiency of α-1-antitrypsin (A1AT), as well as
by recent findings regarding the complex interplay of cysteine proteases.18
Through a different mechanism, patients with cystic fibrosis have a defec-
tive cystic fibrosis transmembrane conductance regulator (CFTR) transporter
gene that facilitates the development of
early airway obstruction—presumably
because of chronic inflammation and
alteration of chloride channel physiologic mechanisms.19 Smoking can accelerate the disease progression in individuals with these genetic conditions.
In aggregate, about 50% to 60% of all
smokers will eventually have some level
of COPD.20
Environmental Exposures
Environmental risk factors other than
tobacco smoke, particularly those related to occupational exposure to inhalants and fumes, may also play a role in
COPD onset and progression. However, because of the frequency of concurrent smoking, the risk of COPD from
environmental exposure is difficult to
clearly define. The clinical presentation
of many patients who have COPD from
occupational exposure does not differ
from that of patients who have had no
occupational exposure to inhalants or
fumes. Furthermore, quantifying actual environmental exposure in a patient
is often difficult because of the variety
of environmental and occupational
situations that exist.
Despite these clinical difficulties,
several environmental substances have
been shown to serve as risk factors for
the development of COPD, primarily
by acting as irritants in the airways,
leading to chronic inflammation. These
substances are listed in Figure 1.21
Diagnosis
Spirometry remains the gold standard
for diagnosis of COPD. To refer a patient for this test, the physician must
have a suspicion of COPD based on
the patient’s medical history and physical examination findings. A thorough
history should be obtained and a complete physical examination should be
performed for patients with suggestive
symptoms, family histories of COPD,
or risk factors for COPD. Such an approach will aid in obtaining an accurate
diagnosis and in developing a treatment plan for patients.
Osteopathic Physicians’ Guide: COPD
Medical History
The most common symptoms for patients with established COPD include
chronic cough, dyspnea at rest or with
exertion, and chronic sputum production. Any of these symptoms should
prompt the consideration of COPD
in the differential diagnosis. In many
cases, chronic productive cough (>3
tablespoons/d for >3 months) is 1 of
the earliest presenting symptoms of
COPD and is typically indicative of
chronic bronchitis. However, by the
time that patients with COPD present
with these symptoms, they already have
well-established disease. By contrast,
many patients with mild COPD are
asymptomatic or simply have a mild
but chronic cough.18
A detailed history of tobacco exposure and environmental and occupational exposures (Figure 1) should be
elicited from the patient. Cigarette or
cigar smoke exposure should be quantified and defined as to whether it is
first-hand or second-hand exposure.
For cigarette smoking, the most common method of obtaining the patient’s
history is to assess the pack-years of
exposure (ie, the number of packs per
day multiplied by the number of years).
An increasing cumulative dose (ie, exposure) to tobacco smoke increases the
likelihood of development of airway
obstruction.7
Recurrent pulmonary infections
can be indicative of a potential cause
of COPD, or they may occur as a result of established COPD. Thus, a thorough history of respiratory infections
dating to childhood should be elicited
from the patient. A pattern of early, severe infections could indicate that the
pulmonary damage initially occurred
when the patient was a child. Later
development of recurrent infections
should be correlated with a smoking or
environmental exposure history. Other
confounding disorders that can be associated with such a history include
uncontrolled asthma, cystic fibrosis, or
immunodeficiency syndromes (eg, immunoglobulin A deficiency).2
A family history is useful for disclosing early cigarette smoke exposure,
potential environmental exposures, COPD Severity
and patterns of COPD development 100%
that might occur with genetic disorders. Any nonspecific—possibly genetic—associations that exist among
first-degree relatives with COPD may
increase suspicion of COPD as a clinical diagnosis. Environmental asso- 70%
ciations, as noted in Figure 1, can be
identified by obtaining an occupational
60%
history of the patient’s parents.
Age at symptom onset offers clues
to the etiologic mechanisms and future progression of COPD. Respiratory
manifestations of cystic fibrosis typically present in the first 3 decades of life.
Premature emphysema resulting from
A1AT deficiency typically manifests
in the fourth, fifth, and sixth decades
of life. Emphysema and severe COPD
most commonly present in the sixth
and seventh decades of life, though
they may occur earlier in individuals
with heavier smoking burdens.22
Review of Systems
In asymptomatic patients, an increasingly sedentary lifestyle may point to
early stages of COPD, because exercise
tolerance decreases with the onset of
airway obstruction. At the other extreme, patients presenting with unexplained weight loss or anorexia may
have severe COPD, because the high
metabolic requirements of advanced
COPD may contribute to weight
loss. Unexplained disorders of the
liver or pancreas may suggest A1AT
deficiency.23
Physical Examination—Early in
the disease process, physical examination has relatively little sensitivity from
a diagnostic standpoint, except for
disorders with multisystem manifestations. As the disease process becomes
more advanced, physical examination
yields greater diagnostic value. One of
the major reasons for a thorough physical examination lies in detecting disorders that mimic or confound COPD.
Yellowing teeth and fingernails
are often an indication of substantial
cigarette smoke exposure. A cyanotic
hue to the lips or fingernails may suggest the presence of severe COPD as-
MILD
MODERATE
MODERATELY SEVERE
50%
SEVERE
35%
VERY SEVERE
FEV1, % Predicted*
Figure 2. Spirometric indices used to grade
the physiologic severity of chronic obstructive
pulmonary disease (COPD), according to the
American Thoracic Society.36 Lung function is
measured with the forced expiratory volume in 1
second (FEV1) test. *FEV1 % predicted is the test
result for the patient as a percent of the predicted
values for healthy individuals with similar
characteristics (eg, age, height, race, sex, weight).
sociated with hypoxia. Clubbing of the
fingernails—often as a result of chronic
oxygen deficiency—may be present in
individuals with advanced COPD, but
it may also indicate other disorders.
Pursed-lip breathing typically occurs
spontaneously in patients with expiratory flow obstruction as a way to ease
dyspnea.24,25
Evaluation of the thoracic cavity
may reveal an increased anteroposterior diameter, also known as “barrel
chest.” This appearance results from
air trapping, which in turn results in
chronic hyperinflation of the thoracic
cavity. Individuals with more severe
disease and those in acute respiratory
distress may have intercostal or subcostal retractions, leading them to make
routine use of accessory respiratory
muscles. The use of these muscles is
usually a sign of increased work during
breathing or respiratory muscle fatigue.
7
Osteopathic Physicians’ Guide: COPD
Palpation and percussion have little
diagnostic value in detection of COPD
in its early stages. However, in the later
stages of COPD, an examiner may note
the presence of decreased tactile fremitus and hyperresonance to percussion.
Both findings are the result of hyperinflation of the lungs caused by airway
obstruction.
Auscultation should be performed
for all lung fields in a systematic manner. Such a systematic progression allows for the differentiation of focal
findings from global findings. In addition, detection of normal breath sounds
in abnormal locations should lead to
closer inspection and may suggest the
need for additional testing. Classic respiratory signs of COPD include a prolonged expiratory phase, wheezing on
forced exhalation, and decreased breath
sounds.26 With the variety of physical
manifestations of COPD, many of the
aforementioned findings may or may
not be present. It should be noted, however, that the presence of diminished
breath sounds in combination with a
suggestive history is the most consistent physical finding in individuals with
moderate COPD.26
A somewhat simple test that can be
used in the office setting is to time how
long the patient can forcibly exhale.
Typically, a forced exhale time of greater than 5 seconds may indicate some
form of airway obstruction.27 Similarly,
the inability of a patient to blow out a
candle at a distance of 12 inches can be
a useful indication of severe airway obstruction in some bedside settings.
Cardiac examination may reveal
evidence of right ventricular strain or
failure, particularly in patients with advanced COPD. Sustained point of maximal impulse, if present, may suggest
right ventricular dilatation or hypertrophy. Cardiac auscultation will often
reveal distant heart sounds, secondary
to lung hyperinflation. A right ventricular gallop, increased intensity of P2
(ie, pulmonic second heart sound), and
murmurs of pulmonary or tricuspid insufficiency are suggestive of right heart
failure, possibly resulting from severe,
chronic COPD. With the onset of right
8
Celli BR, MacNee W; ATS/ERS Task Force. Standards for the diagnosis and treatment of patients with COPD:
a summary of the ATS/ERS position paper. Eur Respir J. 2004;23(6):932-946.
Guidelines: Executive summary: global strategy for diagnosis, management, and prevention of COPD. Global
Initiative for Chronic Obstructive Lung Disease Web site; December 2009.
US Preventive Services Task Force. Screening for chronic obstructive pulmonary disease using spirometry:
US Preventive Services Task Force recommendation statement [published online ahead of print March 3,
2008]. Ann Intern Med. 2008;148(7):529-534.
Ferguson GT, Enright PL, Buist AS, Higgins MW. Office spirometry for lung health assessment in adults: a
consensus statement from the National Lung Health Education Program. Chest. 2000;117(4):1146-1161.
Figure 3. Recommended reading list for chronic obstructive pulmonary disease.
heart failure, increased jugular venous
distention and lower-extremity edema
may also be observed—findings that
are indicative of pulmonary hypertension or cor pulmonale.25,26
Imaging—Like the physical examination, most chest imaging techniques have relatively poor sensitivity
for detecting mild to moderate COPD.
Plain chest radiographs have a sensitivity of approximately 50% for diagnosing moderate COPD.28 Radiograph
findings may include flattening of the
hemidiaphragms, bullae, increased anteroposterior diameter on lateral films,
and narrowing of the cardiac silhouette.
Localized or regional emphysema can
be identified via radiographs in certain
cases. A finding of basilar emphysema
may suggest A1AT deficiency, especially
in younger individuals. Such a finding
results from a relative increase in blood
flow, contrasting with the usual finding
of apical emphysema in smokers.29
Computerized tomography (CT)
scans are useful in identifying bullous
lung disease and regional emphysema.
Techniques to assess lung volumes using CT scans are available but are not
routinely used.
Spirometry—As previously noted,
spirometry is essential in making a diagnosis of COPD and in grading the
severity of the disease. Standard flowvolume loop assessments can often be
performed in the office with good reliability. The objective of these assessments is to determine a gross estimation of effective lung volume (ie, forced
vital capacity [FVC]), the effect on airflow (ie, the ratio of FEV1/FVC), and
whether there is any reversibility. Reversibility is defined as a significant improvement in the FVC, FEV1, or FEV1/
FVC after the administration of a bronchodilator (ie, >200 mL improvement
in FVC or FEV1 or 12% increase from
prebronchodilator measurements).30
Physiologic severity of COPD may
be graded by using the spirometric
indices shown in Figure 2.2 Symptomatic grading is often more useful from a
clinical standpoint.
Indications for performing spirometry include the following: chest tightness, coughing, dyspnea, occupational
exposure to dust or chemicals, smokers
older than 45 years, assessment of bronchodilator function, wheezing, and the
presence of other lung disorders.
A diagnosis of airflow obstruction
is typically based on a reduction in the
FEV1/FVC ratio. For practical purposes, a ratio value less than 0.7 confirms
the presence of airflow obstruction. A
lack of reversibility or an incomplete reversibility of the obstruction after bronchodilator use secures the diagnosis
of COPD. Furthermore, the degree to
which FEV1 is decreased correlates with
the severity of COPD (Figure 2).
It should be noted that spirometric
severity of disease does not necessarily
correlate with functional debilitation.
To assess functional limitations, exercise testing is typically necessary.
Office-based spirometry has been
validated for use in the diagnosis of
COPD.31 However, despite recommendations in national COPD guidelines,
recent data suggest that spirometry in
the office remains underutilized.31,32
Equipment maintenance and quality
control requirements, practitioner attitudes, and inability to interpret results
are the major speculative reasons for its
underutilization.33 Further information
Osteopathic Physicians’ Guide: COPD
on the use of office-based spirometry
is available through the National Lung
Health Education Program (noted in
the recommended reading in Figure 3).
Differential Diagnoses
Many other conditions can have similar
clinical presentations as COPD. These
conditions may at times be difficult to
differentiate from COPD.
Of special note, asthma and COPD
can be difficult to differentiate. Both
diseases have a primary presentation of
airway obstruction and are associated
with environmental exposures. However, the single most definitive means of
differentiation between these 2 entities
concerns the identification of reversibility of airway obstruction. Chronic
obstructive pulmonary disease has
classically been defined as airway obstruction that is not reversible or that
is only partially reversible with use of
bronchodilators. Asthma, by contrast,
is a disease in which nearly complete
airway reversibility can be achieved. As
such, airway obstruction that is fully
reversible with administration of bronchodilators is considered to be asthma — not COPD. Patients with airway
obstruction that is not fully reversible
with administration of bronchodilators
are considered to have COPD.34
These 2 conditions may coexist
in the sense that an individual with
asthma as a child may have COPD as
an adult. Unfortunately, the overlap of
asthma and COPD, which occurs occasionally, creates some difficulty for
practitioners in regard to diagnosis and
treatment.35 For practical purposes,
however, irreversibility in airway obstruction should lead to a diagnosis
of COPD. Differential diagnosis criteria for COPD, based on the American
Thoracic Society Task Force report,36
are shown in Figure 4.
Conclusion
Without question, every healthcare
practitioner will encounter patients
with COPD, either as a primary
CONDITION
DIAGNOSTIC CONSIDERATIONS
Asthma
Hypersensitivity symptoms may be present
Nocturnal symptoms may predominate
Significant reversibility of airway obstruction is possible
Bronchiectasis
Copious sputum production
Recurrent infections
Coarse crackles on auscultation
Chest computed tomography reveals bronchial dilation and
bronchial wall thickening
Bronchiolitis Obliterans
Patient may have rheumatoid arthritis or fume exposures
Ground glass opacities seen on chest computed tomography
Congestive Heart Failure
Fine basilar crackles
Radiograph reveals pulmonary edema, cardiomegaly
No obstruction on spirometry, though restriction may be seen
Diffuse Panbronchiolitis
Predominant in men, nonsmokers
Chronic sinusitis present
Imaging may reveal centrilobular nodular opacities and
hyperinflation
Tuberculosis
Historical cues and risk factors (eg, exposure to endemic region,
history of incarceration, unexplained weight loss, hemoptysis)
Positive results to purified protein derivative test, sputum for acid
fast stain, interferon-γ gold assay
condition or as a confounding illness
contributing to another medical condition. Earlier diagnosis of COPD can
be achieved by keeping the disorder
in mind when patients present with
known risk factors, dyspnea, chronic
cough, and/or chronic sputum production. Furthermore, additional cues derived from the patient’s family history,
tobacco history, age at onset of symptoms, and environmental exposures
provide insights that may lead the practitioner to suspect COPD as the culprit.
Spirometry is considered the diagnostic tool of choice for determining
the presence or absence of obstructive
airway disease, as well as for grading
the severity of any obstruction. Furthermore, office-based spirometry
used by properly trained technicians
and practitioners appropriately trained
in its interpretation is a recognized
and effective means of evaluating and
tracking patients with COPD.
Take-Home Points
• COPD should be considered in any
patient presenting with chronic
cough, dyspnea, or chronic sputum
production.
• Information on family history, tobacco use, and potential occupational exposures should be elicited
to discern a patient’s risk for having
COPD.
• Spirometry remains the gold standard for COPD diagnosis, whether
performed in a full pulmonary-function laboratory or in an appropriately
staffed office-based practice.
• Consider α-1-antitrypsin deficiency
and cystic fibrosis in patients younger than 40 years who present with a
diagnosis of COPD.
Acknowledgments
I thank Brian Foresman, DO, for his
guidance and support in the preparation of this article.
continued…
Figure 4. Differential diagnosis criteria for chronic obstructive pulmonary disease (COPD), based
on a report by the American Thoracic Society Task Force.36
9
Osteopathic Physicians’ Guide: COPD
References
1. National Heart, Lung, and Blood Institute.
Morbidity & Mortality: 2009 Chart Book on Cardiovascular, Lung, and Blood Diseases. Bethesda,
MD: National Institutes of Health; 2009:5968.
http://www.nhlbi.nih.gov/resources/docs/
2009_ChartBook.pdf. Accessed May 27, 2011.
2. Celli BR, MacNee W; ATS/ERS Task Force.
Standards for the diagnosis and treatment of patients with COPD: a summary of the ATS/ERS
position paper. Eur Respir J. 2004;23(6):932-946.
3. Kirkpatrick P, Dransfield M. Racial and sex
differences in chronic obstructive pulmonary
disease susceptibility, diagnosis, and treatment.
Curr Opin Pulm Med. 2009;15(2):100-104.
4. Mannino DM, Buist AS. Global burden of
COPD: risk factors, prevalence, and future trends
[review]. Lancet. 2007;370(9589):765-773.
5. Lundback B, Lindberg A, Lindstrom M, et al;
Obstructive Lung Disease in Northern Sweden
Studies. Not 15 but 50% of smokers develop
COPD?—Report from the Obstructive Lung
Disease in Northern Sweden Studies. Respir Med.
2003;97(2):115-122.
6. Mannino DM. COPD: epidemiology, prevalence, morbidity and mortality, and disease heterogeneity. Chest. 2002;121(5 suppl):121S-126S.
7. US Department of Health and Human Services. The Health Consequences of Smoking: Chronic
Obstructive Lung Disease. A Report of the Surgeon General. Washington, DC: US Government
Printing Office; 1984:32-39. http://profiles.nlm.
nih.gov/ps/access/NNBCCS.pdf. Accessed May
27, 2011.
8. Lange P, Nyboe J, Appleyard M, Jensen G,
Schnohr P. Relationship of the type of tobacco
and inhalation pattern to pulmonary and total
mortality. Eur Respir J. 1992;5(9):1111-1117.
9. Beck GJ, Doyle CA, Schachter EN. Smoking and lung function. Am Rev Respir Dis.
1981;123(2):149-155.
10. Withey CH, Papacosta AO, Swan AV, et al.
Respiratory effects of lowering tar and nicotine levels of cigarettes smoked by young male
middle tar smokers. II. Results of a randomised
controlled trial. J Epidemiol Community Health.
1992;46(3):281-285.
11. Lange P, Groth S, Nyboe J, et al. Decline of
the lung function related to the type of tobacco
smoked and inhalation [published correction
appears in Thorax. 1990;45(3):240]. Thorax.
1990;45(1):22-26.
12. Burrows B, Knudson RJ, Cline MG, Lebowitz
MD. Quantitative relationships between cigarette
smoking and ventilatory function. Am Rev Respir
Dis. 1977;115(2):395-205.
13. Scanlon PD, Connett JE, Waller LA, Altose
MD, Bailey WC, Buist AS. Smoking cessation
and lung function in mild-to-moderate chronic
obstructive pulmonary disease. The Lung Health
Study. Am J Respir Crit Care Med. 2000;161(2 pt
1):381-390.
10
14. Chronic bronchitis diagnosis. Physicians’
Desk Reference Web site. http://www.pdrhealth.
com/diseases/chronic-bronchitis/diagnosis. Accessed June 20, 2011.
15. Viegi G, Pedreschi M, Pistelli F, et al. Prevalence of airways obstruction in a general population: European Respiratory Society vs American
Thoracic Society definition. Chest. 2000;117(5
suppl 2):339S-345S.
16. Silverman EK, Chapman HA, Drazen JM, et
al. Genetic epidemiology of severe, early-onset
chronic obstructive pulmonary disease. Risk
to relatives for airflow obstruction and chronic
bronchitis. Am J Respir Crit Care Med. 1998;157(6
pt 1):1770-1778.
17. Webster PM, Lorimer EG, Man SF, Woolf CR,
Zamel N. Pulmonary function in identical twins:
comparison of nonsmokers and smokers. Am Rev
Respir Dis. 1979;119(2):223-238.
18. Stockley RA. Proteases/antiproteases: pathogenesis and role in therapy. Clin Pulm Med.
1998;5:203-210.
19. Davis PB. Pathophysiology of the lung disease
in cystic fibrosis. In: Davis PB, ed. Cystic Fibrosis.
New York, NY: Marcel Dekker; 1993:193.
29. Tobin MJ, Hutchison DC. An overview of the
pulmonary features of alpha 1-antitrypsin deficiency. Arch Intern Med. 1982;142(7):1342-1348.
30. Pellegrino R, Viegi G, Brusasco V, et al. Interpretative strategies for lung function tests. Eur
Respir J. 2005;26(5):948-968.
31. Han MK, Kim MG, Mardon R, et al. Spirometry utilization for COPD: how do we measure up
[published online ahead of print June 5, 2007]?
Chest. 2007;132(2):403-409.
32. Lee TA, Bartle B, Weiss KB. Spirometry use
in clinical practice following diagnosis of COPD.
Chest. 2006;129(6):1509.
33. Lin K, Watkins B, Johnson T, Rodriguez JA,
Barton MB, US Preventive Services Task Force.
Screening for chronic obstructive pulmonary
disease using spirometry: summary of the evidence for the US Preventive Services Task Force.
Ann Intern Med. 2008;148(7):535.
34. Goedhart DM, Zanen P, Lammers JW. Relevant and redundant lung function parameters
in discriminating asthma from COPD. COPD.
2006;3(1):33-39.
20. Fletcher C, Peto R. The natural history
of chronic airflow obstruction. Br Med J.
1977;1(6077):1645-1648.
35. Yawn BP. Differential assessment and management of asthma vs chronic obstructive
pulmonary disease [published online ahead
of print January 21, 2009]. Medscape J Med.
2009;11(1):20.
21. Becklake MR. Occupational exposures: evidence for a causal association with chronic obstructive pulmonary disease. Am Rev Respir Dis.
1989;140(3 pt 2):S85-S91.
36. Standards for the diagnosis and care of patients with chronic obstructive pulmonary disease. American Thoracic Society. Am J Respir Crit
Care Med. 1995;152(5 pt 2):S77-S121.
22. A registry of patients with severe deficiency
of alpha 1-antitrypsin. Design and methods. The
Alpha 1-Antitrypsin Deficiency Registry Study
Group. Chest. 1994;106(4):1223-1232.
This guide is supported by Boehringer Ingelheim
Pharmaceuticals, Inc.
23. Hogarth DK, Rachelefsky G. Screening and
familial testing of patients for α1-antitrypsin deficiency. Chest. 2008;133(4):981-988.
24. Spahija J, de Marchie M, Grassino A. Effects
of imposed pursed-lips breathing on respiratory
mechanics and dyspnea at rest and during exercise in COPD. Chest. 2005;128(2):640-650.
25. Currie GP, Legge JS. ABC of chronic obstructive pulmonary disease [review]. Diagnosis. BMJ.
2006;332(7552):1261-1263.
26. Badgett RG, Tanaka DJ, Hunt DK, et al. Can
moderate chronic obstructive pulmonary disease
be diagnosed by historical and physical findings
alone? Am J Med. 1993;94(2):188-196.
27. Siafakas NM, Vermeire P, Pride NB, et al. Optimal assessment and management of chronic obstructive pulmonary disease (COPD). The European Respiratory Society Task Force. Eur Respir J.
1995;8(8):1398-1420.
28. Wallace GM, Winter JH, Winter JE, Taylor A,
Taylor TW, Cameron RC. Chest X-rays in COPD
screening: Are they worthwhile [published online ahead of print July 24, 2009]? Respir Med.
2009;103(12):1862-1865.
Osteopathic Physicians’ Guide: COPD
INTERVENTIONS
for Patients With Chronic Obstructive
Pulmonary Disease
Thomas F. Morley, DO | Amita Pravinkumar Vasoya, DO
As the prevalence of chronic obstructive pulmonary disease grows, it is important
for physicians—especially primary care physicians—to understand the prevention
and treatment options available to patients. From smoking cessation to pulmonary
rehabilitation and the various pharmacologic and nonpharmacologic options in
between, the authors review interventions for patients at any disease stage.
Chronic obstructive pulmonary
disease (COPD) is a preventable and
treatable disease with substantial
extrapulmonary effects that may contribute to disease severity in some
patients.1 The current emphasis from
researchers and physicians on prevention and management of COPD, even
with established disease, represents an
extension of our prior understanding
of this condition. Various interventions can modify the course of COPD
and survival, as found in a 2008 review
by Celli.2 These interventions include
smoking cessation,3 long-term oxygen therapy in hypoxemic patients,4,5
noninvasive ventilation in selected patients,6-8 and lung volume reduction
surgery (LVRS) in patients with upper
lobe predominant emphysema and
poor exercise capacity.9
The cornerstone of interventions
at all stages of COPD remains focused
on prevention and smoking cessation.3 The Lung Health Study12 clearly
demonstrated that smoking cessation
decreased the rate of decline in lung
function and reduced the rate of death
for all-cause mortality.3,12 Similarly, the
use of vaccines has proven effective for
avoiding and reducing the severity of
several infectious diseases. Vaccination
is especially valuable in patients with
more severe stages of COPD in which
acute illnesses can lead to muscle loss
and permanent declines in lung performance.
In 1998, the Global Initiative for
Chronic Obstructive Lung Disease
(GOLD) was formed by experts from
the World Health Organization and the
US National Heart, Lung, and Blood
Institute. The major goals of the group
were to promote greater awareness of
COPD, publish evidence-based recommendations regarding the prevention
and management of COPD, and promote clinical research. The evidencebased guidelines from these initiatives
were made available on the Internet
and have been recently updated in the
report The Global Initiative for Chronic
Lung Disease: Global Strategy for the
Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary
Disease.1 Similar recommendations for
Dr Morley is a professor of medicine and Dr Vasoya is an assistant professor of medicine in the Division of
Pulmonary, Critical Care, and Sleep Medicine at the University of Medicine and Dentistry of New JerseySchool of Osteopathic Medicine in Stratford.
Financial Disclosures: None reported.
Address correspondence to Thomas F. Morley, DO, 42 E Laurel Rd, Suite 3100,
Stratford, NJ 08084-1501. E-mail: [email protected]
patients with COPD have also been
published by the American Thoracic
Society and European Thoracic Society10 and the American College of Physicians.11
Overall, the current approach to
COPD interventions is based on the
severity of disease as determined by
spirometry readings and clinical symptoms defined by GOLD (Figure 1).
Based on a patient’s disease severity,
the physician adds interventions in an
incremental or step-wise manner, starting with smoking avoidance and cessation. This approach improves the overall efficacy of interventions, reduces
cost by avoiding unnecessary interventions, and minimizes complications.
While relatively simple, the GOLD
panel treatment recommendations
are applicable to patients with stable
COPD and those with acute exacerbations. The recommendations also provide a good foundation for physicians
who treat patients with COPD.
Medical interventions for patients
with COPD can be divided into 2
interventions: (1) those that are directed at symptomatic relief but typically
have little or no survival benefit and
(2) those that have limited short-term
symptomatic benefit but may impart
survival benefit or disease avoidance.
11
Osteopathic Physicians’ Guide: COPD
IV: Very Severe
III: Severe
II: Moderate
I: Mild
FEV1/FVC < 0.70
FEV1 > 80% predicted
FEV1/FVC < 0.70
50%< FEV1 < 80%
predicted
FEV1/FVC < 0.70
30% < FEV1 < 50%
predicted
FEV1/FVC < 0.70
FEV1 < 30%
predicted or
FEV1 < 50% predicted
plus chronic respiratory
failure
Active reduction of risk factor(s): influenza vaccination
Add short-acting bronchodilator (when needed)
Add regular treatment with one or more long-acting bronchodilators
(when needed)
Add rehabilitation
Add inhaled glucocorticosteroids if repeated
exacerbations
Add long-term oxygen
if chronic respiratory
failure
Consider surgical
treatments
Figure 1. Therapy at each stage of chronic obstructive pulmonary disease (COPD). Postbronchodilator
FEV1 is recommended for the diagnosis and assessment of severity of COPD. Chronic respiratory
failure defined as arterial partial pressure of oxygen (PaO2) less than 8 kPa (60 mm Hg) with or without
arterial partial pressure of carbon dioxide (PaCO2) greater than 6.7 kPa (50 mm Hg) while breathing
air at sea level. Reprinted with permission from U.S. Health Network.1 Abbreviations: FEV1, forced
expiratory volume in 1 second; FVC, forced vital capacity.
With 1 possible exception,13 neither
inhaled corticosteroids nor long-acting β2-adrenergic agonists have been
shown to reduce the rate of decline in
lung function in COPD patients. In
the TORCH study,13 an inhaled steroid
alone or in combination with a longacting β2-adrenergic agonist decreased
the rate of lung function decline, but
this finding did not translate into significant survival benefit. Ultimately,
the goal of medical therapy for COPD
is to reduce symptoms, avoid adverse
effects and complications, and reduce
exacerbations. In the present article,
we review the currently used treatment
options (Figure 2) for patients with
COPD.
Pharmacologic Options
Delivery Mechanisms
Commonly used formulations of medications for patients with COPD are presented in the Table. When medications
are administered by inhalation, careful
attention must be given to the choice of
agent. For most patients, metered dose
12
inhalers are as effective as other inhaled
preparations and are substantially less
costly. For metered dose inhalers, patients must be instructed on the proper
technique for inhalation. Proper use remains a challenge for many patients attempting to coordinate the inhaler with
the actuator. Under most circumstances, the use of a chamber or spacer for
the delivery of inhaled medications will
improve delivery and efficacy. Powder
formulations of medications are typically designed to avoid the need for a
chamber and may be technically easier
for some patients. Patients with severe
COPD (ie, forced expiratory volume
in 1 second [FEV1], <500 cc) may require an aerosol device for optimal
delivery. The choice of inhalation device will depend on the medication,
cost, and availability, as well as the technical skills of the individual patient.
Bronchodilator Therapy
The cornerstone of pharmacologic
treatment for COPD patients is bronchodilator therapy. Medications with
bronchodilator effects include β2-
adrenergic agonists, anticholinergic
medications, and methylxanthine
agents. The β2-adrenergic agonists
and anticholinergic medications are
most commonly given by inhalation
to reduce systemic adverse effects.
Short- and longer-acting preparations
are available for each of these medications. Long-acting β2-adrenergic agonists and long-acting anticholinergic
agents can be used as monotherapy
in more stable patients and are associated with improved performance
status, better lung function, and
reduced exacerbations.24-27 Although
all of these bronchodilators have been
shown to improve exercise capacity,
this benefit does not always correlate
with improvements in FEV1.14-24
β2-Adrenergic Agonists
β2-Adrenergic agonists work directly
on the β2-receptor to cause bronchodilation. Short-acting β2-adrenergic
agents (eg, albuterol) are used for
patients with infrequent symptoms or as
a rescue medication in a more intensive
regimen. Long-acting β2-adrenergic
agonists (eg, formoterol, salmeterol)
provide bronchodilation for at least
12 hours and are used to control more
frequent or persistent symptoms. Patients on long-acting β2-adrenergic
agonists must be instructed to use the
medications as directed and not to use
them for acute symptoms (ie, rescue
medication). Most of these patients will
need to be given a second, short-acting
agent for acute symptoms. In general,
the use of long-acting β2-adrenergic
agonists is associated with decreased
exacerbations, whereas chronic use of
short-acting β2-adrenergic agonists is
not. If acute symptoms do not abate
after rescue medications are taken, if
medications are needed more than every 4 hours, or if symptoms are worsening despite the therapy, then immediate
evaluation with a physician is needed.
Adverse effects associated with β2adrenergic agonists are generally mild
and include headache, tremors, throat
irritation, dizziness, and hypersensitivity reactions.
Anticholinergics—Anticholinergic medications, available only via in-
Osteopathic Physicians’ Guide: COPD
o BRONCHODILATORS
• β2-adrenergic agonists
• Anticholinergic medications
>C
ombined short-acting β2-agonist
with short-acting anticholinergic
>C
ombined long-acting β2-agonist
with long-acting anticholinergic
• Methylxanthine agents
o ANTI-INFLAMMATORY AGENTS
• Corticosteroids
>C
ombined long-acting β2-agonists
with inhaled corticosteroids
o ANTIBIOTICS
o MUCOLYTIC AGENTS
o VACCINES
o ANTITUSSIVES
o NONPHARMACOLOGIC OPTIONS
• Oxygen
• Pulmonary rehabilitation
• Noninvasive ventilation
o SURGICAL TREATMENTS
• Lung volume reduction surgery
• Lung transplantation
• Bullectomy
Figure 2. Treatment options for patients with
chronic obstructive pulmonary disease.
halation, became more widely available
in the early 1990s. Working through
a cholinergic blockade mechanism,
these agents provided a bronchodilator effect through a different pathway
than β2-adrenergic agonists. In COPD,
as compared to asthma, the relative
bronchodilatory effect of anticholinergics was often greater than that of the
β2-adrenergic agonists. Adverse effects
were common until the first of the new
generation agents, ipratropium bromide, was released. The duration of
action was about 6 hours. Newer and
longer-acting agents are now available
and have improved the management
of COPD symptoms. For example,
the long-acting anticholinergic agent,
tiotropium, is efficacious for at least
24 hours. Adverse effects associated
with the newer anticholinergic medications are usually mild but may include
dry mouth, urinary retention, narrow
angle glaucoma, and hypersensitivity
reactions.
The combination of short-acting anticholinergic and short-acting
β2-adrenergic agonists has been ex-
amined in patients with moderately
severe, stable COPD. A 12-week prospective, double-blind trial compared
the combination of albuterol and ipratropium with each agent alone to
determine the degree of spirometric
improvement during the first 4 hours
after administration.28 The agents were
administered by metered-dose inhaler.
Results from the study28 indicated that
combination therapy was more effective than either agent alone in terms of
spirometric improvement. Symptom
scores did not change over time and
did not differ among treatment groups.
Similar findings have been noted when
a nebulized combination product containing both albuterol and ipratropium
was compared to single agent therapy.29
Methylxanthine Agents—Methylxanthine agents are older and less used
today because of their greater adverse
effects, lesser efficacy, and need for serum monitoring. However, these medications offer some selected patients
benefit through improved diaphragmatic function and effects on mucociliary function. Theophylline, the primary agent in this class, is a less potent
bronchodilator than β2-adrenergic or
anticholinergic agents. Theophylline
is given either intravenously or orally.
Serum levels should be monitored and
plasma levels should generally not exceed 12 μg/mL because higher levels
are associated with greater toxicity in
older patients.27 Dosing may also be affected by food, drug interactions, and
slowed metabolism in some patient
populations (eg, elderly patients, cirrhotic patients). Theophylline is most
beneficial for patients with severe
COPD in whom other therapies failed
and particularly patients with carbon
dioxide retention.
Corticosteroids
Corticosteroids, which are not approved for use as monotherapy, are
available in inhalation, oral, and intravenous forms. Regular treatment
with inhaled corticosteroids has been
shown to reduce the frequency of acute
exacerbations, improve health status,
improve lung function, and reduce use
of rescue medication.30-36 Most stud-
ies37-39 of inhaled corticosteroids have
not demonstrated any improvement
in the rate of decline in lung function.
However, the TORCH study group13
was able to demonstrate a slower rate
of decline of lung function in patients
treated with either fluticasone propionate alone or the combination of
fluticasone propionate and salmeterol.
This trial13 was a large, randomized,
double-blind, placebo-controlled study
that followed patients with moderate to
severe COPD for 3 years. When compared to placebo, the differences in the
primary end point of all-cause mortality was not statistically significant for
any treatment group.26
The adverse effects of inhaled corticosteroids are usually minor, including
upper airway thrush and dysphonia.
However, an increased potential for
pneumonia has been reported with the
use of inhaled corticosteroids,26,40 and
withdrawal of inhaled corticosteroids
may also be associated with acute exacerbations in certain patients.36
The use of oral maintenance corticosteroids is not recommended for
patients with stable COPD because the
systemic adverse effects of corticosteroids outweigh their potential benefits.
However, oral corticosteroids are indicated as outpatient therapy for patients
with acute COPD exacerbations.41
Intravenous corticosteroids may be
used for inpatient acute exacerbations,
although oral steroids are probably
equally efficacious.
Combined Bronchodilators
and Corticosteroids
Multiple studies 26,31,33,34,42-44 have demonstrated that an inhaled corticosteroid combined with a long-acting
β2-adrenergic agonist is more effective
than either component alone in improving lung function and health status
and reducing exacerbations. However,
such combined therapy may increase
the risk of pneumonia.26 Survival benefit of these combined agents remains
uncertain. As noted previously, a large
prospective trial was unable to demonstrate a survival benefit from combined
therapy.26 To our knowledge, only 1
13
Osteopathic Physicians’ Guide: COPD
DRUG
INHALER, μg
SOLUTION for
NEBULIZER,
mg/mL
ORAL
VIALS for
INJECTION,
mg
DURATION of
ACTION, hr
β2-agonists
Short-acting
Fenoterol
100-200 (MDI)
1
Levabuterol
45-90 (MDI)
0.21, 0.42
Salbutamol
(albuterol)
100, 200 (MDI,
DPI)
5
Terbutaline
400, 500 (DPI)
0.05% (syrup)
4-6
6-8
5 mg (pill),
0.024% (syrup)
0.1, 0.5
4-6
2.5, 5 (pill)
0.2, 0.25
4-6
Long-acting
Formoterol
4.5-12 (MDI, DPI)
Arformoterol
Salmeterol
0.01*
12+
0.0075
12+
25-50 (MDI, DPI)
12+
Anticholinergics
Short-acting
Ipratropium
bromide
20, 40 (MDI)
0.25-0.5
6-8
Oxitropium bromide
100 (MDI)
1.5
7-9
Long-acting
Tiotropium
18(DPI), 5 (SMI)
24+
Combination short-acting β2-agonists plus anticholinergic in 1 inhaler
Fenoterol/
Ipratropium
200/80 (MDI)
1.25/0.5
6-8
Salbutamol/
Ipratropium
75-15 (MDI)
0.75/4.5
6-8
Methylxanthines
Aminophylline
200-600 mg
(pill)
Theophylline (SR)
100-600 mg
(pill)
240
Variable, up
to 24
Variable, up
to 24
Inhaled glucocorticosteroids
Beclomethasone
50-400
(MDI, DPI)
0.2-0.4
Budesonide
100, 200, 400
(DPI)
0.20, 0.25, 0.5
Fluticasone
50-500 (MDI, DPI)
Triamcinolone
100 (MDI)
40
40
Combination long-acting β2-agonists plus glucocorticosteroids in 1 inhaler
Formoterol/
budesonide
4.5/160, 9/320
(DPI)
Salmeterol/
fluticasone
50/100, 250, 500
(DPI)
25/50, 125, 250
(MDI)
Systemic glucocorticosteroids
Prednisone
5-60 mg (pill)
Methylprednisolone
4, 8, 16 mg (pill)
* Formoterol nebulized solution is based on the unit dose vial containing 20 μg in a volume of 2.0 mL.
Abbreviations: DPI, dry powder inhaler; MDI, metered dose inhaler; SMI, soft mist inhaler.
Source: Reprinted with permission from U.S. Health Network.
Table. Commonly Used Formulations of Drugs Used in Chronic Obstructive Pulmonary Disease
14
study13 to date has shown that inhaled
salmeterol, fluticasone, or both salmeterol and fluticasone reduced the rate
of FEV1 decline in COPD patients with
moderate or severe disease. A 6-week,
multicenter, randomized, double-blind
trial of patients with moderate COPD
demonstrated superiority in lung function of the combination of inhaled
tiotropium plus formoterol compared
with the combination of salmeterol and
fluticasone.45 These data suggest that
some disease modification might occur
with combination bronchodilators and
corticosteroids; however, confirmation
of this effect awaits the completion of
long-term studies.
Nonpharmacologic
Therapy
Oxygen
Oxygen therapy has a positive impact
on hemodynamics, hematologic features, exercise capacity, lung mechanics, and mental state.46 Long-term oxygen given for longer than 12 hours per
day by nasal cannula has been shown to
improve survival in chronically hypoxemic COPD patients.4,5 Further benefit
is derived when used 24 hours per day.
Patients should be evaluated for the
need of oxygen therapy using arterial
blood gas or an assessment of oxygen
saturation when they are clinically
stable breathing room air. In most instances, an exercise evaluation may also
be helpful. If the arterial oxygen saturation is less than or equal to 88%, or
the arterial oxygen tension is less than
or equal to 55 mm Hg, then the patient
qualifies for supplemental oxygen. In
circumstances where the arterial oxygen tension is 56 to 59 mm Hg or the
saturation is 89%, the patient qualifies
for supplemental oxygen if they have
dependent edema suggesting congestive heart failure, pulmonary hypertension, cor pulmonale, or a hematocrit
greater than 56%.
Lung Volume Reduction Surgery
During LVRS, severely emphysematous tissue is removed from both upper lung lobes. This operation allows
the remaining lung to expand and the
Osteopathic Physicians’ Guide: COPD
sitization to dyspnea.57 Improvements
in depression and social interactions
may also contribute to the benefits of
pulmonary rehabilitation.57
diaphragm to assume a more normal
position. A randomized trial of LVRS
vs medical therapy for patients with
severe COPD did not demonstrate a
reduction in mortality for the LVRS
patients.9,47 However, improvement in
lung function, exercise capacity, and respiratory quality of life was statistically
significant. In a subgroup of patients
with mostly upper lobe emphysema
and low baseline exercise capacity, reduction of mortality was statistically
significant. However, for patients with
non-upper lobe predominant emphysema and higher baseline exercise
capacity mortality was higher in the
LVRS group than the medical therapy
group. Patients with a FEV1 of no more
than 20% predicted and either homogeneous emphysema or a carbon monoxide diffusing capacity of no more
than 20% had a higher mortality.47
Lung Transplantation
In patients with severe pulmonary emphysema, lung transplantation can normalize pulmonary function, improve
exercise capacity, and restore quality
of life.48-51 The effect of lung transplantation on survival is unclear.2 Median
survival for lung transplantation is
about 5 years and is significantly lower
than for other solid organs.27 When
selecting candidates for lung transplantation functional status, projected
survival without transplant, comorbidities, and patient preferences should be
considered. Generally, patients should
be younger than 65 years and without
medical or psychiatric conditions that
could worsen predicted survival.2 A
high BODE index, a multidimensional index for COPD survival, can help
select patients for lung transplantation.52 Criteria that may help primary
care physicians identify potential lung
transplantation candidates include a
FEV1 of less than 35% predicted, PaO2
less than 55 to 60 mm Hg, PaCO2 greater than 50 mm Hg, and secondary pulmonary hypertension.53,54
Pulmonary Rehabilitation
Pulmonary rehabilitation is a multidisciplinary program designed to
maximize lung function, improve gas
exchange, optimize conditioning, and
address nutritional issues. Typically,
pulmonary rehabilitation programs are
outpatient based. Patients in pulmonary rehabilitation are usually GOLD
stage 2 or 3 (Figure 1) in terms of disease severity, but patients with more
or less severe disease may also benefit.
Patients who cannot ambulate, have
unstable cardiac disease, or have neurologic problems or cognitive dysfunction may not be appropriate candidates
for rehabilitation.
Pulmonary rehabilitation does not
directly improve lung mechanics or
gas exchange.55 Rather, it optimizes
the function of other body systems to
reduce the impact of lung dysfunction.56 These effects are derived from
improved muscle function, reduction
in dynamic hyperinflation, and desen-
The major element of a pulmonary
rehabilitation program is exercise.
Generally, exercise of the legs is emphasized with walking (eg, on a treadmill)
or cycling. High-intensity (target, 60%
of maximal endurance) or lower-intensity regimens are determined based
on patient tolerance. Upper extremity
training can improve patients’ ability to
perform their activities of daily living.
Respiratory muscle training is no longer commonly used because it does not
lead to increased functional capacity.58
Ancillary treatments, including optimal bronchodilation during rehabilitation session and use of supplemental
oxygen, are also helpful.57
Cachexia in patients with COPD
causes a depletion of lean body mass
and is associated with a poor prognosis. Nutritional evaluation identified the patients with cachexia so that
nutritional support can be provided;
therefore, nutritional evaluations are a
routine part of pulmonary rehabilitation. Unfortunately, nutritional interventions have not been uniformly effective in clinical trials for a variety of
reasons.59 Patients with COPD who are
overweight have a greater degree of exercise limitation because of the effects
of obesity on lung function. Weight loss
is uniformly prescribed for these patients, but data on efficacy are lacking.
Studies60-62 have shown a positive
effect for pulmonary rehabilitation regarding reductions in hospitalizations
and other measures of healthcare utilization, as well as improvements in
cost-effectiveness. Although pulmonary rehabilitation has not been shown
to improve survival in COPD patients,
the randomized trials that have investigated survival were inadequately powered to detect this effect.58
Conclusion
Treatment of patients with COPD warrants an aggressive approach beginning
with smoking cessation at the earliest
15
Osteopathic Physicians’ Guide: COPD
possible stage. A variety of pharmacologic and nonpharmacologic therapies
are available for COPD patients, who
can improve their function and quality of life. Recent evidence suggests that
acute exacerbations of COPD play an
important part in disease progression
and, therefore, a focus on prevention
should be a part of any therapeutic consideration.63 Myriad medications have
been found to reduce the frequency
of exacerbations, and some medications or combinations of medications
may slow disease progression in these
patients. Together with smoking cessation, all of these therapies offer hope for
a population of patients becoming ever
more prevalent worldwide.
References
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16
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of tiotropium on lung hyperinflation, dyspnea,
and exercise tolerance in COPD. Euro Respir J.
2004;23(6):832-840.
22. Vincken W, van Noord JA, Greefhorst APM,
et al; Dutch/Belgian Tiotropium Study Group.
Improved health outcomes in patients with
COPD during 1 yr’s treatment with tiotropium.
Eur Respir J. 2002;19(2):209-216.
23. Mahler DA, Donohue JF, Barbee RA, et al. Efficacy of salmeterol xinafoate in the treatment of
COPD. Chest. 1999;115(4):957-965.
24. Tashkin DP, Celli B, Senn S, et al; UPLIFT
Study Investigators. A 4-year trial of tiotropium
in chronic obstructive pulmonary disease [published online ahead of print October 5, 2008]. N
Engl J Med. 2008;359(15):1543-1554.
25. Sin DD, McAlister FA, Man SFP, Anthonisen
NR. Contemporary management of chronic obstructive pulmonary disease: scientific review.
JAMA. 2003;290(17):2301-2312.
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26. Calverley PMA, Anderson JA, Celli B, et al;
TORCH Investigators. Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease. N Engl J Med.
2007;356(8):775-789.
27. Niewoehner DE. Outpatient management of
severe COPD [clinical practice]. N Engl J Med.
2010;362(15):1407-1416.
28. COMBIVENT Inhalation Aerosol Study
Group. In chronic obstructive pulmonary disease, a combination of ipratropium and albuterol
is more effective than either agent alone: an 85day multicenter trial. Chest. 1994;105(5):14111419.
29. Gross N, Tashkin D, Miller R, Oren J, Coleman W, Linberg S; Dey Combination Solution
Study Group. Inhalation by nebulization of albuterol-ipratropium combination (Dey combination) is superior to either agent alone in the treatment of chronic obstructive pulmonary disease.
Respiration. 1998;65(5):354-362.
30. Lung Health Study Research Group. Effect of
inhaled triamcinolone on the decline in pulmonary function in chronic obstructive pulmonary
disease. N Engl J Med. 2000;343(26):1902-1909.
31. Mahler DA, Wire P, Horstman D, et al. Effectiveness of fluticasone propionate and salmeterol combination delivered via the Diskus
device in the treatment of chronic obstructive
pulmonary disease. Am J Respir Crit Care Med.
2002;166(8):1084-1091.
32. Jones PW, Willits LR, Burge PS, Calverley PM;
Inhaled Steroids in Obstructive Lung Disease in
Europe study investigators. Disease severity and
the effect of fluticasone propionate on chronic
obstructive pulmonary disease exacerbations.
Eur Respir J. 2003;21(1):68-73.
33. Calverley P, Pauwels R, Vestbo J, et al; for
the TRISTAN (TRial of Inhaled STeroids ANd
long-acting β2 agonists) study group. Combined
salmeterol and fluticasone in the treatment of
chronic obstructive pulmonary disease: a randomised controlled trial [published correction
appears in Lancet. 2003;361(9369):1660]. Lancet.
2003;361(9356):449-456.
34. Szafranski W, Cukier A, Ramirez A, et al. Efficacy and safety of budesonide/formoterol in the
management of chronic obstructive pulmonary
disease. Eur Respir J. 2003;21(1):74-81.
35. Spencer S, Calverley PMA, Burge PS, Jones
PW. Impact of preventing exacerbations on deterioration of health status in COPD. Eur Respir J.
2004;23(5):698-702.
36. van der Valk P, Monninkhof E, van der Palen
J, Zielhuis G, van Herwaarden C. Effect of discontinuation of inhaled corticosteroids in patients with chronic obstructive pulmonary disease: the COPE Study [published online ahead
of print September 5, 2002]. Am J Respir Crit
Care Med. 2002;166(10):1358-1363. doi:10.1164/
rccm.200206-512OC.
37. Pauwels RA, Löfdahl CG, Laitinen LA, et al.
Long-term treatment with inhaled budesonide
in persons with mild chronic obstructive pulmonary disease who continue smoking. N Engl J
Med. 1999;340(25):1948-1953.
38. Vestbo J, Sørensen T, Lange P, Brix A,
Torre P, Viskum K. Long-term effect of inhaled
budesonide in mild and moderate chronic obstructive pulmonary disease: a randomised controlled trial. Lancet. 1999;353(9167):1819-1823.
39. Burge PS, Calverley PM, Jones PW, Spencer
S, Anderson JA, Maslen TK. Randomised, double
blind, placebo controlled study of fluticasone
propionate in patients with moderate to severe
chronic obstructive pulmonary disease: the
ISOLDE trial. BMJ. 2000;320(7245):1297-1303.
40. Drummond MB, Dasenbrook EC, Pitz MW,
Murphy DJ, Fan E. Inhaled corticosteroids in
patients with stable chronic obstructive pulmonary disease: a systematic review and metaanalysis [published correction appears in JAMA.
2009;301(10):1024]. JAMA. 2008;300(20):24072416.
41. Aaron SD, Vandemheen KL, Herbert P, Dales
R, Stiell IG, Ahuja J, et al. Outpatient oral prednisone after emergency treatment of chronic
obstructive pulmonary disease. N Engl J Med.
2003;348(26):2618-2625.
42. Hanania NA, Darken P, Horstman D, et al.
The efficacy and safety of fluticasone propionate
(250 µg)/salmeterol (50 µg) combined in th Diskus inhaler for the treatment of COPD. Chest.
2003;124(3):434-443.
43. Calverley PM, Boonsawat W, Cseke Z, Zhong
N, Peterson S, Olsson H. Maintenance therapy
with budesonide and formoterol in chronic obstructive pulmonary disease [published correction appears in Euro Respir J. 2004;24(6):1075].
Euro Respir J. 2003;22(6):912-919.
44. Kardos P, Wencker M, Glaab T, Vogelmeier
C. Impact of salmeterol/fluticasone propionate
versus salmeterol on exacerbations in severe
chronic obstructive pulmonary disease [published online ahead of print October 19, 2006].
Am J Respir Crit Care Med. 2007;175(2):144-149.
doi:10.1164/rccm.200602-244OC.
45. Rabe KF, Timmer W, Sagkriotis A, Viel K.
Comparison of a combination of tiotropium, plus
formoterol to salmeterol plus fluticasone in moderate COPD [published online ahead of print
April 10, 2008]. Chest. 2008;134(2):255-262. doi:
10.1378/chest.07-2138
46. Tarpy SP, Celli BR. Long-term oxygen therapy. N Engl J Med. 1995;333(11):710-714.
47. National Emphysema Treatment Trial Research Group. Patients at high risk of death after
lung-volume-reduction surgery. N Engl J Med.
2001;345(15):1075-1083.
48. Patterson GA, Maurer JR, Williams TJ, Cardoso PG, Scavuzzo M, Todd TR; The Toronto
Lung Transplant Group. Comparison of outcomes after double and single lung transplantation for obstructive lung disease. J Thorac Cardiovasc Surg. 1999;110(4):623-632.
51. Hosenpud JD, Bennett LE, Keck BM, Boucek
MM, Novick RJ. The Registry of the International
Society for Heart and Lung Transplantation:
eighteenth official report—2001. J Heart Lung
Transplant. 2001;20(8):805-815.
52. Orens JB, Estenne M, Arcasoy S, et al; Pulmonary Scientific Council of the International
Society for Heart and Lung Transplantation. International guidelines for the selection of lung
transplant candidates: 2006 update—a consensus
report from the Pulmonary Scientific Council of the International Society for Heart and
Lung Transplantation. J Heart Lung Transplant.
2006;25(7):745-755.
53. Hosenpud JD, Bennett LE, Keck BM, Edwards EB, Novick RJ. Effect of diagnosis on survival benefit of lung transplantation for end-stage
lung disease. Lancet. 1998;351(9095):24-27.
54. Maurer JR, Frost AE, Estenne M, Higenbottam T, Glanville AR; The International Society
for Heart and Lung Transplantation, the American Thoracic Society, the American Society of
Transplant Physicians, the European Respiratory
Society. International guidelines for the selection
of lung transplant candidates. Transplantation.
1998;66(7):951-956.
55. Cassaburi R, Petty TL, eds. Principles and
Practice of Pulmonary Rehabilitation. Philadelphia, PA: W.B. Saunders Company; 1993.
56. Nici L, Donner C, Wouters E, et al; ATS/
ERS Pulmonary Rehabilitation Writing Committee. American Thoracic Society/European
Respiratory Society statement on pulmonary
rehabilitation. Am J Respir Crit Care Med.
2006;173(12):1390-1413.
57. Cassaburi R, ZuWallack R. Pulmonary rehabilitation for management of chronic obstructive pulmonary disease. N Engl J Med.
2009;360(13):329-335.
58. Ries AL, Bauldoff GS, Carlin BW, et al. Pulmonary rehabilitation: Joint ACCP/AACVPR
Evidence-Based Clinical Practice Guidelines.
Chest. 2007;131(5 suppl):4S-42S.
59. Ferreira IM, Brooks D, Lacasse Y, Goldstein
RS, White J. Nutritional supplementation for
stable chronic obstructive pulmonary disease.
Cochrane Database Syst Rev. 2005;2:CD000998.
60. Griffiths TL, Burr ML, Campbell I, et al. Results at 1 year of outpatient multidisciplinary
pulmonary rehabilitation: a randomised controlled trial [published correction appears
in Lancet. 2000;355(9211):1280]. Lancet.
2000;355(9201):362-368.
61. California Pulmonary Rehabilitation Collaborative Group. Effects of pulmonary rehabilitation on dyspnea, quality of life, and healthcare costs in California. J Cardiopulm Rehabil.
2004;24(1):52-62.
49. Bando K, Paradis I, Keenan R, et al. Comparison of outcomes after single and bilateral lung
transplantation for obstructive lung disease. J
Heart Lung Transplant. 1995;14(4):692-698.
62. Griffiths TL, Phillips CJ, Davies S, Burr ML,
Campbell IA. Cost effectiveness of an oupatient
multidisciplinary pulmonary rehabilitation programme. Thorax. 2001;56(10):779-784.
50. Orens JB, Becker FS, Lynch JP III, Christensen PJ, Deeb GM, Martinez FJ. Cardiopulmonary exercise testing following allogenic lung
transplantation for different underlying disease
states. Chest. 1995;107(1):144-149.
63. Anzueto A. Impact of exacerbations on
COPD. Eur Respir Rev. 2010;19(116):113-118
This guide is supported by Boehringer Ingelheim
Pharmaceuticals, Inc.
17
Osteopathic Physicians’ Guide: COPD
COMORBIDITIES and
Systemic Effects in COPD
Kartik Shenoy, MD | Fredric Jaffe, DO
Chronic obstructive pulmonary disease (COPD) is primarily thought to be a
disease confined to the lungs. However, recent evidence suggests that COPD
is a systemic disease with associated comorbidities that can affect quality
of life, morbidity, and mortality. Conditions such as cardiovascular disease,
musculoskeletal dysfunction, osteoporosis, and diabetes mellitus are all part
of the systemic manifestations of COPD. The present article reviews the causal
link between COPD and these comorbid conditions and touches on management
of these diseases in patients with COPD.
Chronic obstructive pulmonary
disease (COPD) has been viewed as a
disease that is confined to the lungs.
However, recent evidence suggests
that a variety of comorbidities are associated with COPD and can affect the
course of disease in a patient.1 Many of
these comorbidities, which have smoking as a common risk factor, include—
but are not limited to—cardiac disease,
diabetes mellitus, and skeletal muscle
dysfunction. Large epidemiologic studies have established an independent
detrimental effect of these conditions
on patients with COPD.2 Therefore,
treatment strategies for patients with
COPD should include management of
these nonpulmonary sequelae that contribute to the burden of COPD.
Mortality and
Cardiovascular Disease
Currently, COPD is the fourth leading
cause of death in the United States, and
compared with other diseases, such as
heart disease or stroke, death rates are
on the rise.3 In patients with COPD, it
is unclear whether patients are more
likely to die from other comorbidities
or whether COPD is the main cause
of death. Cardiovascular disease, one
of the leading causes of death in the
United States, is the most common comorbidity in patients with COPD. In a
cohort of nearly 400,000 patients from
Veterans Administration (VA) clinics,
researchers found that the prevalence
of coronary artery disease was significantly higher in those with COPD
than those without COPD (33.6% compared with 27.1%).4 In another study of
45,000 patients, Sidney et al5 found that
those patients with COPD had a higher
risk of hospitalization and mortality
from cardiovascular disease.5 Similarly,
Holguin et al6 studied comorbidity and
mortality in COPD-related hospitalizations. They found that there was an
increased prevalence and higher
in-hospital mortality in patients with
From the Division of Pulmonary and Critical Care Medicine at Temple University School of Medicine in
Philadelphia, Pennsylvania.
Financial Disclosures: None reported.
E-mail: [email protected] or [email protected]
18
COPD who had ischemic heart disease
and congestive heart failure than in
those without COPD.6 It can be argued that the common
risk factor of smoking has increased
the incidence of cardiovascular disease in patients with COPD. However,
there is evidence that patients with
COPD have a risk that is above and beyond that related to smoking alone. In
one study,7 patients with symptoms of
chronic bronchitis had a 50% increase
in cardiovascular mortality when controlled for age, sex, and amount of
smoking.
There is also a link between lower
forced expiratory volume in 1 second
(FEV1), a surrogate measure of smoking, and cardiovascular disease. Hole et
al8 found that subjects with lower FEV1
(<73% of predicted) had an increased
risk of ischemic heart disease (hazard
ratio: 1.56 in men, 1.88 in women). Interestingly, there was also an increased
risk of heart disease among those with
FEV1 between 73% and 83% than in
those with FEV1 measurements that
were higher.8 Although specific questions about cumulative cigarette consumption (eg, pack-years) were not
Osteopathic Physicians’ Guide: COPD
asked, risk of cardiovascular mortality
was present whether the patients were
current smokers, previous smokers, or
never smokers.
Still, questions remain as to why
there is an elevated risk of cardiovascular disease in patients with COPD;
this has not been fully elucidated. One
reason may be related to systemic inflammation, as there have been strong
links between systemic inflammation and cardiovascular disease. Serum markers of inflammation such as
C-reactive protein (CRP) have been
linked to increased risk of cardiac disease and have also been shown to be
increased in patients with stable COPD
as well as in those with exacerbations.
An inflammatory link between cardiovascular disease and COPD can thus
be speculated. Once again, smoking
tobacco may play a role in that smoking can increase inflammatory markers.9 Some have postulated that in addition to smoking cessation, the use of
statin medications may be of benefit in
those with COPD by exerting an antiinflammatory effect. Although there
have been no prospective studies, some
retrospective studies have shown the
use of statins along with angiotensinconverting enzyme inhibitors or angiotensin receptor blockers may reduce
cardiovascular mortality in patients
with COPD.10
The accurate assessment of coronary artery disease in a COPD patient
can be problematic because of ventilatory limitations during exercise and
inability to attain a target heart rate
needed for accurate assessment of cardiac ischemia. In addition, pharmacologic tests can be problematic due to
the use of adenosine or dipyridamole,
which may cause bronchospasm in
patients with COPD. If needed, dipyridamole testing may be used in select
patients with COPD, where disease
is less severe. Assessment of cardiac
function with dobutamine echocardiography testing may be safe in the
general population, but hyperinflation
related to COPD can limit the accuracy
of this testing. Lung tissue of patients
with COPD can obscure the echocar-
diogram probe resulting in imaging
that is difficult to interpret. Coronary
computed tomography is an alternative to the above testing, but it has not
been specifically validated in those
with COPD. Careful consideration of
respiratory reserve should be made before ordering assessment for coronary
artery disease in patients with COPD.
β-Blockers are a cornerstone drug
in the medical management of coronary
artery disease. Some clinicians fear precipitating bronchospasm in those with
COPD with β-blockers. Data suggest
that cardioselective β-blockers can be
used safely in COPD patients for the
management of known coronary disease.11 Nonetheless, caution should be
exercised when treating patients with
reversible airflow obstruction such as
asthma. The large amount of data that
support the use of these medications
in patients with heart disease suggests
that every effort should be taken to
administer these medications. Coexistent cardiovascular disease should be
carefully considered in a patient with
COPD. Efforts to diagnose and treat
cardiovascular disease likely will improve patient outcomes.
Skeletal Muscle
Dysfunction and
Nutritional Status
Musculoskeletal dysfunction can cause
significant morbidity in patients with
COPD and affects survival in these patients. Patients with a low body mass
index (BMI) and decreased fat-free
mass have been linked to increased
mortality compared to patients with a
normal BMI.12 The cause of musculoskeletal dysfunction in COPD is multifactoral. A combination of malnutrition, decreased activity, and use of
glucocorticoids all play a role in musculoskeletal dysfunction. Recent data
point to oxidative stress and systemic
inflammation contributing to muscle
dysfunction. Clinicians may assume
that musculoskeletal dysfunction only
occurs in those with more severe disease; however, new evidence suggests
otherwise. For instance, Coronell et
al13 assessed quadriceps endurance in
patients with mild to moderate COPD.
Even during normal physical activity,
these patients had decreased strength
and endurance.13 Therapies that exist to ameliorate muscle dysfunction
in patients with COPD consist of pulmonary rehabilitation, modified nutritional supplementation, and use of
pharmacologic agents to increase fatfree mass.
The GOLD II guidelines14 recommend pulmonary rehabilitation in all
patients with moderate COPD, but
it is likely that even those with mild
disease can derive benefit. Upper and
lower extremity strength training with
light aerobic exercise increases endurance, improves symptoms of dyspnea,
and enhances quality of life.14 Cote
et al15 found, in patients with severe
COPD (mean FEV1 32%), that rehabilitation provided a survival advantage and decreased hospital utilization.15 Unfortunately, improvements
conferred by pulmonary rehabilitation
diminish if exercise is discontinued,
and patients should be urged to continue exercises at home. Fewer data are
available on the optimal time to begin
rehabilitation and whether repeating
rehabilitation program has benefit.
Overall, patients who start to develop even subtle functional limitations
should be referred to a rehabilitation
program.
Having a low BMI is a risk factor
for all-cause mortality, but the optimal
timing of referral to nutritional support
has not been established in patients
with COPD. Most studies of nutritional
support involve patients whose COPD
is well controlled without multiple exacerbations. More evidence suggests
that weight loss follows a stepwise
progression and worsening nutritional
status may be related to acute exacerbations of COPD.16 Schols and Wouters17 proposed a
simple screening process that involves
measurement of BMI and weight course
(Figure 1). First, patients are characterized as underweight (BMI <21), normal weight (BMI ≥21-<25), and overweight (BMI ≥25-<30). Second, weight
loss is determined, defined by greater
19
Osteopathic Physicians’ Guide: COPD
than 10% loss in the past 6 months or
greater than 5% in 1 month. Nutritional supplementation would then be indicated in specific subgroups. Nutritional
interventions may only involve diet
modification; however, some patients
require energy-dense supplements.
These products should be spaced out
throughout the day to avoid appetite
loss and adverse ventilatory effects due
to higher caloric encumbrance.
Other options to help combat musculoskeletal dysfunction involve the
use of anabolic steroids and growth
hormone replacement therapy. Unfortunately, most studies with these agents
have yielded less than ideal results with
respect to increases in weight, muscle
mass, and exercise tolerance, but others have shown modest yet consistent
increases in muscle function. In one
study, addition of growth hormone in
patients with COPD increased muscle
mass but did not increase exercise tolerance.18 The use of testosterone in
healthy subjects increases muscle mass
and power, which are compounded
by strength training; however, as with
growth hormone, use of testosterone in
patients with COPD has yielded mixed
results.
There are many factors related to
COPD that may cause musculoskeletal dysfunction, including inactivity,
steroid use, malnutrition, and oxidative stress. Goals of increased physical
activity, improved nutritional intake,
limitation of systemic steroids, and
possible pharmacologic interventions
may improve quality of life and possibly mortality in patients with COPD by
improving skeletal muscle function.
Osteoporosis
Patients with COPD are at risk for osteoporosis for several reasons, such as
smoking tobacco, inactivity, malnutrition, and a low BMI. These risk factors,
combined with increased age and corticosteroid use, all play a role in putting
these patients at high risk for the development of osteoporosis. For patients
with COPD, the approach to minimize
osteoporosis risk should involve screening, risk reduction, and treatment.
20
SCREENING
Underweight
Weight
Loss
Normal Weight
Weight
Loss
Stable
Low FFM
Normal
Overweight
Weight
Loss
Stable
Low FFM
Stable
Normal
Control
TREATMENT
Nutrition Intervention
Responder
Nonresponder
Maintenance
Therapy
Compliance
Improvement
Oral/Enteral
Suppletion
Oral/Enteral
Suppletion
Anabolic
Stimulation
Anabolic
Stimulation
CONTROL
Figure 1. Nutritional screening and treatment algorithm for patients with chronic obstructive
pulmonary disease. Abbreviation: FFM, fat-free mass. Reprinted with permission from Clinics in
Chest Medicine.17
Traditionally, screening was offered to postmenopausal women or
patients with COPD taking oral glucocorticoids. However, screening a
larger cohort of patients with COPD
may be prudent. Evidence from Praet
et al,19 who studied bone mineral density (BMD) in men with chronic bronchitis, suggests more patients may be at
risk. They found that patients who were
on bronchodilators alone had substantially worse BMD than an age-matched
control population.19 Pino-Montes et
al20 also studied COPD patients who
had no prior use of glucocorticoids and
found that they had lower BMD compared to age-matched controls.
The risk of osteoporosis in patients
on inhaled corticosteroids is debatable.
Studies specifically looking at patients
with COPD who use inhaled corticosteroids lack conclusive evidence.21 Some
have found worsening BMD, while others have found no significant difference
compared with placebo arms.21 Overall
it seems short-term use of ICS at low
doses does not pose a statistically significant risk. However, those who are
on inhaled corticosteroids at higher
doses may be at a risk above and beyond the already increased risk of being a patient with COPD.
Osteoporosis or osteopenia is often
asymptomatic and may cause little
morbidity. However, the fractures related to them can be detrimental, especially in patients who are respiratory
limited. Thoracic and vertebral fractures can substantially alter lung function. Hip fractures can cause pain and
immobility. Worsening lung function
coupled with immobility worsens the
quality of life for patients with COPD.
Further studies are needed to specifically address morbidity and mortality
effects of fractures in COPD.
With the high potential for morbidity and mortality in patients with
osteoporosis and COPD, physicians
should screen and treat these patients
aggressively. Establishing which patients should be screened can be difficult. It can be argued that screening
every COPD patient for osteoporosis
is important because of the fact that
Osteopathic Physicians’ Guide: COPD
patients with COPD have worsened
BMD compared to age-matched populations, as previously discussed. However, Biskobing22 suggested a more
narrow population of screening postmenopausal women, premenopausal
women, men with hypogonadism, and
men and women with low BMI or history of fracture related to osteoporosis
(Figure 2). Screening is also recommended for patients who are about to
start long-term, high-dose inhaled corticosteroids or an oral corticosteroid
program (>7.5 mg/d). These patients
should be followed with repeat BMD
testing every 2 years.22 Those taking
long-term oral glucocorticoids should
be evaluated more frequently, generally
every 6 to 12 months.22
Treatment strategies involve calcium and vitamin D supplementation,
physical therapy, hormonal replacement, and use of bisphosphonates.
Those at risk for osteoporotic fractures
should be started on calcium and vitamin D supplementation. Hormone
replacement can be offered to those
who have hypogonadism unless contraindicated. All patients who are at
risk will benefit from physical therapy.
Treatment for postmenopausal women
has been established by the American
College of Physicians.23 Any postmenopausal woman with a T score on BMD
testing of less than -2 or less than -1.5
with risk factors should begin treatment.23 When it comes to men who are
not on oral corticosteroids the data are
less clear. Orwoll24 suggested that men
with T scores less than -2.0 may be candidates for treatment.
Every patient on long-term oral
corticosteroids should receive calcium
and vitamin D supplementation.22 The
use of bisphosphonates in this group
should be guided by BMD testing and
risk factors. High-risk postmenopausal
women with normal BMD can be offered hormone replacement therapy
or bisphosphonates if contraindicated.
Others should have bisphosphonates
added if T score on BMD testing is less
than -1. Women on oral corticosteroids
with normal T scores and no other risk
factors should be followed up every 6
o Measure bone mineral density in the following high-risk patients at baseline:
• Those on chronic oral glucocorticoids or high-dose inhaled glucocorticoids
• Postmenopausal women
• Premenopausal women with amenorrhea
• Hypogonadal men
• History of fracture
• Body mass index <22
o Follow bone mineral density every 6-12 months in those receiving oral glucocorticoids or every
12-24 months in those not taking oral glucocorticoids.
o Give supplements to ensure daily intake of 1000-1500 mg calcium and 400-800 IU vitamin D.
o Encourage an exercise program to improve strength and balance.
o Offer gonadal hormone replacement to all postmenopausal women, premenopausal women with
amenorrhea, and hypogonadal men (unless contraindicated).
o Consider bisphosphonates or calcitonin in patients with osteoporosis or in high-risk patients in
whom HRT is not effective or indicated.
Figure 2. Screening and treatment algorithm for patients with osteoporosis. Abbreviation: HRT,
hormone replacement therapy. Reprinted with permission from Chest.22
to 12 months to determine if bisphosphonates need to be added. Treatment
options for those on inhaled corticosteroids involve the use of calcium and
vitamin D and close follow-up with repeat BMD testing thereafter (generally
every 12-18 months).
Patients with COPD should be followed closely for bone mineral loss.
Those who continue to lose BMD despite calcium and vitamin D therapy
should have bisphosphonates or hormone replacement added. Current
studies recognize the increased risk for
osteoporosis in patients with COPD.
Further studies are needed to establish
specific recommendations in osteoporosis management in COPD.
Diabetes and Dyslipidemia
Patients with COPD have an increased
prevalence of diabetes mellitus. Several
risk factors are common between diabetes mellitus and COPD. One major
risk factor is smoking. In addition, the
use of glucocorticoids may affect blood
glucose levels; however, there is likely
an independent link between diabetes
mellitus and COPD.
Initial evidence of the link between
COPD and diabetes mellitus was seen
in studies that showed increased risk
of development of diabetes mellitus
with reduced lung function. One such
study, by Walter et al,25 showed a strong
association between diabetes mellitus
and reduced lung function. Subjects
in the worst quartile of fasting glucose
(102-305 mg/dL) had lower FEV1 compared to predicted FEV1 whether they
were never smokers (-82 mL), current
smokers (-104 mL), or former smokers
(-98 mL). The reason for this connection may lie in systemic inflammation,
which, as previously stated, has been
linked to musculoskeletal dysfunction and cardiovascular disease. Studies have shown that there is increased
insulin resistance in COPD related
to elevations in inflammatory mediators such as IL-6 and tumor necrosis
factor α.26 Clinically, diabetes mellitus affects COPD morbidity and mortality
in patients with COPD. Specifically, in
patients hospitalized with acute exacerbations of COPD, those with hyperglycemia have increased mortality. Baker
et al27 showed that patients admitted
for acute exacerbations of COPD with
hyperglycemia had an increased relative risk of death or longer hospitalization.27 This risk increased independent
of age, sex, or COPD severity. Diabetes
mellitus is also a risk factor for mortality after hospital discharge for AECOPD. Though long-term mortality
increases in COPD patients with comorbidities, more studies are needed to
address morbidity and mortality with
COPD and diabetes mellitus. More
data are also needed to determine optimal glucose control in those admitted
21
Osteopathic Physicians’ Guide: COPD
for acute exacerbations of COPD and
in long-term diabetes mellitus management as it relates to COPD.
Dyslipidemia, like diabetes mellitus,
has strong links to smoking and cardiovascular disease.28 Smoking is known to
cause an increase in low-density lipoprotein (LDL), triglycerides, and verylow-density lipoproteins. However,
studies on lipid profiles and COPD are
lacking. It is currently unknown if dyslipidemia is another disease process independently associated with COPD. A
systematic review29 revealed that there
have been small retrospective trials to
show the benefit of statin use in COPD.
Though most of these trials investigated
exacerbation rates, intubations, and
lung function, a small subset has shown
decreased mortality rates.29 It is unclear
whether this mortality benefit lies in
correcting dyslipidemia, reducing systemic inflammation, or halting decline
of lung function. Further studies need
to elucidate the relationship between
lipid profile and COPD.
Conclusion
Chronic obstructive pulmonary disease
has long been thought of as a disease
limited to the lungs. However, emerging evidence elucidates the impact of
comorbidities in this patient population. Strong links to cardiovascular disease, musculoskeletal dysfunction, and
osteoporosis have been made. Weaker
links have been made to dyslipidemia
and diabetes mellitus. The concept of
systemic inflammation is an emerging subject that may link COPD and
these comorbidities. For primary care
physicians, aggressive management of
these comorbidities is paramount to
the treatment of patients with COPD.
Further data are needed in the optimal
management of comorbidities in relation to COPD. Aggressive treatment
of these conditions likely will improve
quality of life and may alter outcomes
in patients with COPD.
References
1. Chatila WM, Thomashow BM, Minai OA,
Criner GJ, Make BJ. Comorbidities in chronic
obstructive pulmonary disease [review]. Proc Am
Thorac Soc. 2008;5(4):549-555.
22
2. van Mannen JG, Bindels PJ, Ijzemans CJ, van
der Zee JS, Bottema BJ, Schadé E. Prevalence of
comorbidity in patients with a chronic airway obstruction and controls over the age of 40. J Clin
Epidemiol. 2001;54(3):287-293.
3. Jemal A, Ward E, Hao Y, Thun M. Trends in the
leading causes of death in the United States, 19702002. JAMA. 2005;294(10):1255-1259.
4. Maple DW, Dedrick D, Davis K. Trends and
cardiovascular comorbidities of COPD patients
in the Veterans Administration Medical System,
1991-1999. COPD. 2005;2(1):35-41.
5. Sidney S, Sorel M, Quesenberry CP Jr, Deluise C, Lanes S, Eisner MD. COPD and incident
cardiovascular disease hospitalizations and mortality: Kaiser Permanente Medical Care Program.
Chest. 2005;128(4);2068-2075.
6. Holguin F, Folch E, Redd SC, Mannino DM.
Comorbidity and mortality in COPD-related
hospitalization in the United States; 1979 to 2001.
Chest. 2005;128(4);2005-2011.
7. Jousilahti P, Vartiainen E, Tuomilehto J, Puska
P. Symptoms of chronic bronchitis and the risk
of coronary disease. Lancet. 1996;348(9027):567572.
8. Hole DJ, Watt GC, Davey-Smith G, Hart CL,
Gillis CR, Hawthorne VM. Impaired lung function and mortality risk in men and women: findings from the Renfrew and Paisley prospective
population study. BMJ. 1996:313(7059):711-715.
9. Wannamethee SG, Lowe GD, Sharper AG,
Rumley A, Lennon L, Whincup PH. Associations
between cigarette smoking, pipe/cigar smoking,
and smoking cessation and haemostatic and inflammatory markers for cardiovascular disease
[published online ahead of print April 7, 2005].
Eur Heart J. 2005;26(17):1765-1773.
10. Mancini GB, Etminan M, Zhang B, Levesque
LE, Fitzgerald JM, Brophy JM. Reduction of
morbidity and mortality by statins, angiotensin
converting enzyme inhibitors, and angiotensin
receptor blockers in patients with chronic obstructive pulmonary disease [published online
ahead of print May 2, 2006]. J Am Coll Cardiol.
2006:47(12);2554-2560.
11. Salpeter S, Ormiston T, Salpeter E. Cardioselective β-blockers for chronic obstructive
pulmonary disease. Cochrane Database Syst Rev.
2005;(4):CD003566. doi:10.1002/14651858.
12. Vestbo J, Prescott E, Almdal T, et al. Body
mass, fat-free body mass, and prognosis in patients with chronic obstructive pulmonary disease from a random population sample: findings
from the Copenhagen City Heart Study. Am J
Respir Crit Care Med. 2006:173(1);75-83.
13. Coronell C, Orozco-Levi M, Méndez R,
Ramírez-Sarmiento A, Gáldiz JB, Gea J. Relevance of assessing quadriceps endurance in patients with COPD. Eur Respir J. 2004;24(1):129136.
14. Rabe KF, Hurd S, Anzueto A, et al. Global
strategy for the diagnosis and management of
chronic obstructive pulmonary disease: GOLD
executive summary. Am J Respir Crit Care Med.
2007;176(6):532-555.
15. Cote CG, Celli BR. Pulmonary rehabilitation and the BODE index in COPD. Eur Respir J.
2005;26(4):630-636.
16. Vermeeren MA, Schols AM, Wouters EF. Effects of an acute exacerbation on nutritional and
metabolic profile of patients with COPD. Eur
Respir J. 1997;10(10):2264-2269.
17. Schols AM, Wouters EF. Nutritional abnormalities and supplementation in chronic obstructive pulmonary disease. Clin Chest Med.
2000;21(4):753-762.
18. Burdet L, de Muralt B, Schutz Y, Pichard C,
Fitting JW. Administration of growth hormone
to underweight patients with chronic obstructive
pulmonary disease. Am J Respir Crit Care Med.
1997:156(6);1800-1806.
19. Praet J, Peretz A, Rozenberg S, Famaey JP,
Bourdoux P. Risk of osteoporosis in men with
chronic bronchitis. Osteoporos Int. 1992:2(5);257261.
20. del Pino-Montes J, Fernandez J, Gomez F.
Bone mineral density is related to emphysema
and lung function in chronic obstructive pulmonary disease [abstract]. J Bone Miner Res.
1999;14(suppl):SU331.
21. Gartlehner G, Hansen RA, Carson SS, Lobr
KN. Efficacy and safety of inhaled corticosteroids
in patients with COPD: a systematic review and
meta-analysis of health outcomes. Ann Fam Med.
2006:4(3);253-262.
22. Biskobing DM. COPD and osteoporosis [review]. Chest. 2002:121(2);609-620.
23. Qaseem A, Snow V, Shekelle P, Hopkins R,
Forclea M, Owens D; Clinical Efficacy Assessment Subcommittee of the American College
of Physicians. Pharmacologic treatment of low
bone mineral density or osteoporosis to prevent
fractures: a clinical practice guideline from the
American College of Physicians. Ann Intern Med.
2008:149(6);404-415.
24. Orwoll ES. Treatment of osteoporosis in men
[review] [published online ahead of print July 29,
2004]. Calcif Tissue Int. 2004:75(2);114-119.
25. Walter RE, Beiser A, Givelber RJ, O’Connor
GT, Gottlieb DJ. Association between glycemic state and lung function: the Framingham Heart Study. Am J Respir Crit Care Med.
2003:167(6);911-916.
26. Bolton CE, Evans M, Ionescu AA, et al. Insulin
resistance and inflammation—a further systemic
complication of COPD. COPD. 2007:4(2);121126.
27. Baker EH, Janaway CH, Phillips BJ, et al. Hyperglycemia is associated with poor outcomes in
patients admitted to hospital with acute exacerbation of chronic obstructive pulmonary disease
[published online ahead of print January 31,
2006]. Thorax. 2006:61(4);284-289.
28. Craig WY, Palomaki GE, Haddow JE. Cigarette smoking and serum lipid and lipoprotein
concentrations: an analysis of published data.
BMJ. 1998:298(6676);784-788.
29. Janda S, Park K, FitzGerald JM, Etminan M,
Swiston J. Statins in COPD: a systematic review
[published online ahead of print April 17, 2009].
Chest. 2009:136(3);734-743.
Osteopathic Physicians’ Guide: COPD
OSTEOPATHIC PRINCIPLES
and Practice in Chronic Obstructive
Pulmonary Disease
Stephen J. Miller, DO, MPH
The author reviews the literature to identify investigations on the use of
osteopathic principles and practice in patients with or suspected of having chronic
obstructive pulmonary disease (COPD). The author primarily sought to determine
the impact of osteopathic structural diagnosis as a guide to treatment and the
role of manipulative interventions in the treatment of patients with COPD. Some
studies tested the use of osteopathic manipulation in a test population of patients
with COPD vs a control population; however, no studies tested a fully integrated
approach that combined osteopathic principles with osteopathic manipulative
treatment. Because successful management of COPD requires substantial lifestyle
changes, including smoking cessation, diet, exercise, occupational, family, and
other considerations, studies are needed that consider physicians’ practice of both
osteopathic principles and OMT appropriately targeted to patients with COPD.
Chronic obstructive pulmonary
disease (COPD) is caused by chronic
bronchial and parenchymal inflammation that progressively obstructs
expiratory airflow and is not fully reversible.1 The prevalence of COPD is
increasing worldwide. It was the sixth
leading cause of death worldwide in
1990, and it is projected to be the third
leading cause of death by 2020.2 Because of the condition’s prevalence,
thousands of published studies related
to the diagnosis and management of
chronic obstructive pulmonary disease
exist. However, there are relatively few
studies that approach treatment from
an osteopathic perspective—specifically, the use of osteopathic principles and
practice (OPP), of which osteopathic
manipulative treatment (OMT) is a
very important and useful modality.3,4
Osteopathic medicine’s philosophy
is based on the following 4 principles3,4:
1. The human being is a dynamic unit
of function.
2. The body possesses self-regulatory
mechanisms that are self-healing in nature.
3. Structure and function are interrelated at all levels.
4. Rational treatment is based on these
principles.
The Educational Council on Osteopathic Principles (ECOP) developed
a curriculum for osteopathic medical
Dr Miller discloses that he sees patients with COPD and uses OMT as part of his treatment plan, for which
LMU-DCOM bills and receives payment for in the course of usual healthcare delivery.
Address correspondence to Stephen J. Miller, DO, MPH, Lincoln Memorial University-DeBusk College of
Osteopathic Medicine, 6965 Cumberland Gap Parkway, Harrogate, TN 37752-8245.
E-mail: [email protected]
education based on these principles
designed to create physicians who are
health—rather than disease—oriented
by treating each patient as an equal
partner (adult-to-adult) in attaining
health. The ECOP developed “five basic integrative and coordinated body
functions … that were considered in a
context of healthful adaptation to life
and its circumstances” to nurture such
physician growth. These functions are
as follows3:
1. Posture and motion
2. Gross and cellular respiratory and
circulatory factors
3. Metabolic processes of all types
4. Neurologic integration
5. Psychosocial, cultural, behavioral,
and spiritual elements.
When practiced together, these
functions represent a holistic approach
to patient care.3,4 I conducted the
23
Osteopathic Physicians’ Guide: COPD
present review to uncover studies that
used or supported the use of OPP and
OMT with COPD patients.
Methods
Between July 2010 and September 2010,
I conducted a search on PubMed using
the following MeSH terms: pulmonary
disease, chronic obstructive; lung diseases, obstructive; primary health care;
physicians, family; manipulation, osteopathic; manipulation, orthopedic;
smoking cessation; and counseling. I
also conducted searches in UpToDate,
ClinicalTrials.gov, OSTMED.DR, and
http://www.osteopathic-research.com/
using the same terms. During this time,
articles were also found by examining
the bibliographies of helpful articles.
Review articles, trials with results, and
other articles were chosen based on
their containing relevant content. Articles with similar content, such as management techniques for smoking cessation, were sometimes excluded when
another article provided more relevant,
more extensive, or newer coverage of
the topic. Findings were grouped to
better understand the role of OPP in
COPD management.
Results
Two articles were found through the
PubMed search on the use of OPP and
OMT in patients with COPD. The bibliographies of the articles were used to
find additional articles. The PubMed
24
search was expanded to include MeSH
terms for lung diseases, primary care,
family physicians, and orthopedic manipulation as well as appropriate keywords. Of the more than 300 articles
found, recent articles were chosen
based on relevance and other criteria.
A PubMed MeSH search that incorporated terms for smoking cessation,
primary healthcare, family physicians,
and COPD yielded 34 articles, which
are referenced in the remainder of the
present article.
Recognizing the Presence of
Disease
Despite its common occurrence,
COPD remains difficult to diagnose in
its prodromal and early stages. Clinical
signs may be vague,1,5-7 and spirometry remains underutilized as a simple,
office-based diagnostic tool because of
reimbursement issues and other factors.8,9 Clinical guidelines such as the
Global Initiative for Chronic Obstructive Lung Disease (GOLD) have set
objective standards for diagnosis and
staging of COPD by pulmonary function.1 In addition, several researchers,
such as Stallberg et al,10 have developed
clinical questionnaires in an effort to
improve disease recognition and to encourage treatment.
Osteopathic physicians appear to
underutilize their palpatory skills to aid
in diagnosis or management of COPD.
In an Ohio study published in 2003, few
osteopathic physician specialists used
OMT in patients with COPD.11 This
behavior may represent an observed
downward trend by residents in osteopathic graduate medical education
programs to practice their skills while
in training.12 Likewise, a 2003 study by
Chamberlain and Yates13 found that
most osteopathic medical students
believed they would use palpatory diagnosis and osteopathic manipulative
treatment (OMT) for fewer than 25%
of their patients (and primarily for
structural complaints). These studies
suggest a downward trend in perceived
usefulness of manipulation as a current
medical best practice. The value of detecting and treating viscerosomatic re-
flexes14-17 appears to be on the decline
in daily osteopathic medical practice.
Recognizing and Addressing
Risk Factors
Patients at risk of developing COPD
frequently have clinical signs that include chronic cough (with or without
sputum production), wheeze, and exertional dyspnea.6 These signs should
alert physicians to the possibility of
COPD. The additional presence of
smoking tobacco in 80% to 90% of
patients with these chronic symptoms
should be an obvious signal of increased risk of COPD.5 Nonetheless,
physicians routinely fail to recognize
and act on these important clues to the
absence of health in their patients and
prevent progression to COPD.1
In a 2003 review, Mannino found
that nearly half of patients with chronic
cough suggesting COPD were undiagnosed, despite exhibiting symptoms
that might have led their physicians to
perform pulmonary function testing.6
van der Molen7 cited a study by van
Schayck,18 in which pulmonary function testing found that 1049 of 3016
smokers had COPD undiagnosed by
their physicians. Holistic emphasis is
an important part of osteopathic medical training. Dating back to Andrew
Taylor Still, MD, DO, we understand
that practicing healthy behaviors leads
to wellness, and we recognize the importance of detecting symptoms that
signal incipient disease. We are trained
to help the ill patient back to health,
rather than just treat disease.19 This
training is especially helpful as we craft
treatments with our patients.
Crafting Evidence-Based
Treatment Options With Your
Patients
Smoking Cessation—Smoking cessa​
tion remains the cornerstone for
treatment of patients with COPD and
are the major interventions known to
reduce disease morbidity and mortality.20 However, patients face a difficult
task in the decision to quit smoking.
They may be emotionally drained, frequently blaming themselves for their
Osteopathic Physicians’ Guide: COPD
illness, and they may despair that the
onset of symptoms heralds an irreversible decline that smoking cessation will
not stop.21 They may have a history of
several failed attempts to quit that further haunts them. The primary care
physician who elicits and addresses
these emotional cues in their patients
may empower them to successfully quit.
Education for accurate self-assessment of disease risk, co-morbid conditions, and family support are also
important factors that the primary
care physician must help their patients
address as part of their empowerment.
Self-help programs and cessation medication can be beneficial as well.22,23
Pulmonary rehabilitation programs
are another possible intervention. One
such activity led by Bourbeau et al24
in the late 1990s found statistically
significant improvements in patients’
health status through in-home weekly
visits by health professionals. Another
by Norrhall et al25 in 2009 enrolled
84 smokers with COPD in a lifestyle
modification course with healthcare
professionals. According to the study,
47% of the patients quit smoking tobacco and remained smoke-free up to
1 year after the intervention. A 2008
review of Canadian pulmonary rehabilitation programs using inspiratory
muscle training and exercise training
showed improved quality of life of the
programs’ participants and a nearly
50% reduced risk of hospitalization for
acute exacerbations.26
All of these examples highlight the
importance of knowing your patients’
needs in order to craft treatment with
the most likelihood for success. That
success comes most often when physician, patient, family, and available
healthcare and community supports
work together, yet another example of
osteopathic principles in practice.
Pharmacotherapy—The goal of
pharmaceuticals in treating patients
with COPD is to improve quality of
life—no medication has been shown
to reduce COPD-related mortality.2,21
β-Agonists, anticholinergics, combination therapy, and inhaled corticosteroids all are given to reduce patient
symptoms, ease exacerbations, enhance possible exercise, and improve
ability to perform activities of daily
living. Physicians who reduce patients’
symptoms and improve their abilities
to perform activities of daily living incur trust. Creating patient trust is an
important outcome.21 The physician
who practices the holistic approach will
emphasize these positive outcomes not
as chronic disease treatment, but rather
as paths to better health. A patient so
motivated and who has well-founded
trust in a physician is more likely to
consider attempting the most beneficial, but hardest to accomplish, treatment option—smoking cessation.
Osteopathic Manipulative Treatment—Several articles have chronicled
the use of OMT in diagnosis and management of chronic COPD. In 1973,
Howell et al27 reported results of OMT
in a patient with COPD diagnosed by
clinical symptoms. The authors progressively applied OMT in the areas
of greatest restriction in the thoracic
spine and chest cage for 16 months.
There was a reported reduction in the
patient’s clinical symptoms and improvement in his oxygen saturation,
but objective measures did not support
the clinical improvement.27 A followup study28 of 11 patients followed for
9 months with a similar protocol had
similar results.
In a small study of COPD patients,
Miller29 found that 92% of patients
treated with spinal manipulation and
thoracic lymph drainage had improvement in their physical work capacity.
Similar to other studies, there was a
worsening of patients’ residual volume
and total lung capacity.
More recently, in 2006, Noll et al30
conducted a study of 35 patients with
COPD based on GOLD criteria. Eighteen patients received a session of OMT
and 17 had a sham treatment. Again,
the OMT group had a worsening of
residual volume and total lung capacity following this single treatment session of 7 protocol techniques, which
included thoracic lymphatic pump
(TLP) with activation. Patients also
had a statistically significant decrease
in forced expiratory flow at 25% and
50% of vital capacity and at the midexpiratory phase. The authors postulated that the worsening residual volume and total lung capacity were due
to overmanipulation. In a follow-up
study in 2009, Noll et al31 tested this
hypothesis in 25 patients with TLP and
activation, TLP without activation, rib
raising, and myofascial release in sequential sessions of 4-week intervals.
Again, all OMT sessions worsened pulmonary function mildly, with the TLP
with activation group having the most
deleterious effect on residual volume.31
Despite the worsening objective data,
all patients reported an easing of symptoms.31 None of these studies identified
or determined long-term impact on the
subjects.
Monitoring Management Efforts
With Evidence-Based Modalities
The most successful monitoring may
be diaries that chronicle patients’ abilities to perform activities of daily living
and exercise and that showcase reduced
symptoms alongside smoke-free days.21
Conversely, efforts to link objective
data such as peak flow measurements
with smoking cessation have had mixed
results.32,33 The holistically practicing primary care physicians’ task then
is to help patients focus on daily life
successes such as symptom improvement, better work capacity, and fewer
exacerbations as a result of smoking
cessation. Crane34 suggests managing
tobacco addiction as a chronic illness
requiring expert care, adding counseling to patient-individualized plans and
psychosocial support that is overseen
by the patient’s primary care physician.
Pederson and Blumenthal35 stressed
the need for primary care physicians
to ask patients about tobacco use—the
primary intervention a clinician can do
to motivate a patient to quit. Pederson
and Blumenthal35 also highlighted the
US public health service “five R” clinical
guidelines (relevance, risks, rewards,
roadblocks, and repetition)36 for those
patients who are pre-contemplative or
contemplative as a useful method for
helping such patients reach the conclusion to plan for and attempt cessation.
25
Osteopathic Physicians’ Guide: COPD
Research published in 2009 by Secades-Villa et al37 showed success using
these strategies. Patients randomly assigned to a smoking cessation program
consisting of 20-minute sessions with
a psychologist weekly for 5 weeks and
overseen by their primary care physician maintained a cessation rate of
42.8% 12 months after the intervention. The intervention tasked patients
to compare their subjective view of
health to number of days abstaining
from smoking, social reinforcement of
abstinence to number of days abstaining, social reinforcements available and
used to continue abstinence, and physiologic feedback on cigarette abstinence
through reductions in carbon monoxide levels.37
A 2005 Cochrane review included
an analysis of 58 trials where treatment
conditions differed in format (self help,
individual counseling with person-toperson contact, proactive telephone
counseling, or group counseling) and
estimated an odds ratio of 1.7 (95%
confidence interval, 1.4-2.0) for successful cessation with individual counseling compared to no intervention.38
The 2008 update for managing tobacco
use and dependence by the US Agency
for Healthcare Research and Quality39
showed that adding tobacco use status to vital signs in typical patient encounters with primary care physicians
dramatically increased the incidence
of physician-driven interventions. This
intervention was shown to be effective
even when the only assessment to determine patients’ readiness to quit was
to simply ask if the patient is ready to
quit. It was successful when it involved
patient-physician discussion of at least
3 minutes duration delivered during 4
or more separate encounters. Therefore,
if possible, clinicians should address
tobacco use each visit and schedule 3
to 4 follow-up visits with any patient
expressing a willingness to consider
quitting.39 Lastly, Conroy et al40 found a
direct correlation between patient satisfaction with their primary care physician and their physician’s efforts to help
them quit smoking. We found no studies that combined such simple sequential intervention with OMT.
Comment
Many studies have demonstrated a
beneficial therapeutic effect of OMT
in acute pulmonary conditions such as
pneumonia.41-43 However, in the treatment of patients with chronic COPD,
there has been a clear trend that symptomatic improvement occurs with mild
worsening of objective pulmonary
measurements of lung function. Study
design may be a factor—multiple treatment protocols, small patient numbers,
and overmanipulation have been postulated as potential explanations for
these spirometric findings. Thus, there
appears to be a symptomatic benefit
from manipulative interventions that
may be useful in the clinical setting.
The only treatment modality that
has been shown to reduce morbidity and mortality in COPD is smoking
cessation. Osteopathic principles and
practice strongly support treating the
person as a whole, using techniques
specific to osteopathic physicians as
well as more standard interventions
(eg, smoking cessation). Unfortunately,
the established benefit of OMT interventions to date is relatively marginal
and primarily affects symptomatic improvement.
26
Conclusion
In the future, osteopathic manipulative
medicine protocols might be designed
to facilitate smoking cessation as part
of a holistic, patient-centered approach
to management and support. This may
be the best approach and strength of
osteopathic manipulative medicine for
patients with COPD.
Acknowledgments
I would like to thank Gregory Smith,
DO, for his support and guidance. I
would also like to thank the Lincoln
Memorial University-DeBusk College of
Osteopathic Medicine medical librarian,
Lisa Travis, MS, EdS, for her editorial
assistance and help with data collection
and processing.
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