Drugs Aging (2013) 30:479–502
DOI 10.1007/s40266-013-0080-1
REVIEW ARTICLE
The Pharmacological Approach to the Elderly COPD Patient
Timothy E. Albertson • Michael Schivo •
Amir A. Zeki • Samuel Louie • Mark E. Sutter •
Mark Avdalovic • Andrew L. Chan
Published online: 12 April 2013
 Springer International Publishing Switzerland (outside the USA) 2013
Abstract The elderly patient (65 years and older) with
chronic obstructive pulmonary disease (COPD) can be a
challenge to the clinician. This begins with the correct and early
diagnosis, the assessment of disease severity, recognizing
complicating comorbidities, determining the burden of symp-
toms, and monitoring the frequency of acute exacerbations.
Comprehensive management of COPD in the elderly patient
should improve health-related quality of life, lung function,
reduce exacerbations, and promote patient compliance with
treatment plans. Only smoking cessation and oxygen therapy in
COPD patients with hypoxemia reduce mortality. Bronchodi-
lators, corticosteroids, methylxanthines, phosphodiesterase-4
inhibitors, macrolide antibiotics, mucolytics, and pulmonary
rehabilitation improve some outcome measures such as spi-
rometry measures and the frequency of COPD exacerbations
without improving mortality. International treatment guide-
lines to reduce symptoms and reduce the risk of acute exacer-
bations exist. Relief of dyspnea and control of anxiety are
important. The approach to each patient is best individualized.
Earlier use of palliative care should be considered when tra-
ditional pharmacotherapy fails to achieve outcome measures
and before consideration of end-of-life issues.
T. E. Albertson (&)
M. Schivo
A. A. Zeki
S. Louie

M. Avdalovic
A. L. Chan
Division of Pulmonary, Critical Care, and Sleep Medicine,
Department of Internal Medicine, University of California,
4150 V Street, Suite 3400, Davis, CA, USA
e-mail: tealbertson@ucdavis.edu
T. E. Albertson
M. Avdalovic
A. L. Chan
Veteran’s Administration Northern California Health Care
System, Mather, CA, USA
T. E. Albertson
M. E. Sutter
Department of Emergency Medicine, University of California,
Davis, CA, USA
1 Introduction
The burden of chronic obstructive pulmonary disease (COPD)
is a global public health problem with causative links to the
worldwide epidemic of cigarette smoking and the continued
exposure to the burning of wood and biomass fuels. COPD is
both a preventable and treatable disease. COPD has become
the third leading cause of death in the USA and ranks as a
major cause of morbidity [1]. As much as 5 % of the adult
population in the USA has COPD. Annual spending is nearly
US$50 billion for COPD when totaling direct and indirect
expenses [1]. The prevalence and mortality rates of COPD in
countries vary and are projected to increase in the coming
decades. Adjusted COPD prevalence varied significantly
(P B 0.0001) between five cities in Latin and South America
with the lowest found in Mexico City [11.9 % (95 % CI
11.3–12.5)] and highest reported in Montevideo [19.4 %
(95 % CI 17.8–22.8)] [2]. The BOLD study examined inter-
national variation in the prevalence of COPD in 12 cities. The
overall prevalence of Global Initiative for Obstructive Lung
Disease (GOLD) stage II or higher COPD was 10.1 %,
11.8 % for men and 8.5 % for women [3]. The city with the
highest prevalence of stage II or higher COPD was Cape
Town, South Africa (22.4 % men and 16.7 % women) and the
lowest city was Reykjavik, Iceland for men (8.5 %) and
Hannover, Germany for women (3.7 %).
A progressive decline in expiratory airflow with conse-
quent static lung hyperinflation and a fall in lung diffusion
capacity are the key pathophysiologic features of COPD.
This limitation is the result of small airway inflammation
(obstructive bronchiolitis), lung parenchymal destruction
(emphysema), and airway smooth muscle contraction
(bronchospasm). Pulmonary emphysema reduces lung
elastic recoil and diminishes both alveoli and pulmonary
vascular bed. The former adds to the obstructive
480
bronchiolitis and bronchospasm to limit the airway’s abil-
ity to remain open during expiration thus generating air-
flow limitation [4]. Even patients with GOLD stage I
COPD have significantly reduced ([20 %) peak oxygen
consumption and power output with higher dyspnea ratings
for a given work and ventilation compared to controls. This
is thought to be secondary to extensive small airway dys-
function, increased ventilation requirements, and increased
ventilation/perfusion abnormalities [5].
Patients diagnosed with COPD commonly suffer from
comorbid conditions associated with their COPD diagnoses.
The most common comorbidities include gastroesopha-
geal reflux, coronary artery disease, congestive heart fail-
ure, osteoporosis, obstructive sleep apnea, dementia, and
depression. Additional comorbidities seen in COPD patients
include skeletal muscle dysfunction, metabolic syndrome,
and lung cancer [6, 7]. Older COPD patients commonly have
depression, particularly the patients with the greatest degree
of disability [8]. Clusters of comorbidities have been
reported in older COPD patients. These included cardio-
vascular, cachectic, metabolic, psychological, and ‘‘less
comorbidity’’ [9]. Many of these comorbidities may have a
link to the chronic inflammation associated with COPD
including atherosclerotic disease, depression, chronic kid-
ney disease, cognitive impairment, obstructive sleep apnea,
lung cancer, osteoporosis, diabetes, arrhythmias, heart fail-
ure, and pulmonary embolisms [10]. The overall disability of
the older COPD patient is mainly a function of the severity of
comorbidities and significantly impacts treatment options
[11]. Between 10 and 59 % of COPD patient have at least one
of these comorbid conditions [12–14]. These conditions are
also more common in the elderly in general and must be
considered when choosing therapy for COPD [11].
This paper will review the approach to the diagnosis and
pharmacologic treatment of COPD in the elderly patient
(65 years and older). Special issues that relate to elderly
COPD patients include comorbidities, smoking cessation,
potential difficulties of various medication delivery devi-
ces, medication issues including multiple adverse drug
effects, and palliative care/end-of-life issues.
2 Diagnosis and Disease Severity
2.1 Pulmonary Lung Function Testing
and the Classification of Severity
COPD is often under-recognized in the elderly patient [15].
The increased prevalence of comorbid conditions in the
elderly COPD patient can contribute to the difficulty of the
diagnosis [16]. Symptoms of COPD and congestive heart
failure (CHF) can significantly overlap. Age is as an
independent variable predicting reduced sensation of
T. E. Albertson et al.
dyspnea for a given degree of bronchoconstriction. The
reduction in the perception of dyspnea appears to be a
specific feature of aging and delays diagnosing COPD in
this population [17]. A high index of suspicion for COPD is
needed on the part of the clinician. Clues will become
evident when a detailed history of smoking and occupa-
tional/environmental exposures are revealed.
Spirometry is required to confirm the clinical diagnosis
of COPD in the elderly patient. A post-bronchodilator
forced expiratory volume in 1 s (FEV1) divided by forced
vital capacity (FVC) or (FEV1/FVC) of less than 0.70
identifies airway obstruction typical of COPD [18]. Con-
founding the use of this measure is ‘‘senile emphysema’’
where 35 % of healthy elderly who have never smoked
aged over 70 years and 50 % of patients over 80 years
have a FEV1/FVC ratio less than 0.7 [18].
The elderly are at some increased risk of being inad-
vertently classified as having airway obstruction because of
the fixed 0.70 FEV1/FVC ratio criteria [15]. In the absence
of symptoms or risk factors, reliance solely on the FEV1/
FVC ratio in the elderly patient to diagnose COPD is not
recommended [15]. Physical examination findings such as
distant breath sounds, wheezes, a prolonged expiratory
phase, clubbing, a displaced point of maximal impulse of
the heart, increased thoracic cage dimensions, and evidence
of right heart failure can suggest advanced COPD. Chest
X-rays and chest computer tomography (CT) can have
findings suggesting COPD, though these may be normal in
patients with airflow obstruction. Complete pulmonary
functions tests (PFT) including spirometry, flow-volume
loops, lung volumes, and diffusion capacity of carbon
monoxide are frequently needed in elderly patients to
confirm the diagnosis of COPD, eliminate other lung dis-
eases, and further evaluate the severity of COPD. Osteo-
porosis and CHF can also alter the degree of airflow
limitation by lowering the FVC and thereby making the
FEV1/FVC ratio appear less alarming.
The GOLD guidelines provide a COPD severity classi-
fication system based on the FEV1/FVC ratio coupled with
the FEV1 expressed as a percent (%) of predicted values.
The post-bronchodilator spirometric GOLD classification
of COPD now starts with mild, grade 1, COPD with a
FEV1/FVC less than 0.70 (or \70 %) and a FEV1 at least
80 % of predicted. Moderate, grade 2, COPD also has a
FEV1/FVC ratio less than 0.70, but a FEV1 at least 50 and
less than 80 % of predicated values. Severe, grade 3,
COPD criteria include a FEV1/FVC ratio less than 0.70 and
a FEV1 greater than or equal to 30 %, but less than 50 % of
predicted values. The very severe, grade 4, group has a
FEV1/FVC ratio less than 0.70, a FEV1 less than 30 % of
predicted or a FEV1 less than 50 % of predicted coupled
with chronic respiratory failure. Chronic respiratory failure
is defined as arterial partial pressure of oxygen (PaO2) of
Treatment of the Elderly COPD Patient
less than 60 mmHg with or without arterial partial pressure
of carbon dioxide (PaCO2) greater than 50 mmHg at sea
level [4]. Increasing COPD severity is associated with
worsening mortality, morbidity, and health-related quality
of life scores. Three-year mortality for GOLD moderate or
grade 2 is 11.4 %, and mortality increases to 24.3 % for
very severe or grade 4 COPD [19]. Grade 2 COPD patients
tend not to die from COPD but rather from heart disease
and stroke. Grade 3 and grade 4 COPD patients more likely
die from COPD. Use of age-specific FEV1 and FEV1/FVC
ratios have also been advocated to reduce the overdiagnosis
of COPD in the elderly [20]. Adjustments to the GOLD
spirometry criteria have been suggested to avoid this error.
These include reducing the FEV1/FVC ratio to 65 % for
diagnosing COPD in patients aged 70 years or older [21].
The most recent revision of the GOLD document continues
to require the use of spirometry to diagnose COPD using
the FEV1/FVC ratio of less than 70 % criterion but now
also highlights the importance of assessing symptoms,
history of exacerbations, and comorbidities along with
spirometry [7]. The Modified British Medical Research
Council (mMRC) questionnaire on breathlessness or the
COPD Assessment Test (CAT) and a separate accounting
of exacerbation risk provides a more clinically relevant
COPD assessment than FEV1 alone [7]. Integrating all
these metrics has resulted in several COPD patient
assessment groups: group A—low risk, less symptoms—
GOLD 1–2, and 0–1 exacerbation per year and mMRC
grade 0–1 or CAT score less than 10; group B—low risk,
more symptoms—GOLD 1–2, and 0–1 exacerbation per
year and mMRC grade at least 2 or CAT score at least 10;
group C—high risk, less symptoms—GOLD 3–4 and/or at
least 2 exacerbations per year and/or at least 1 exacerbation
resulting in a hospitalization per year, and mMRC grade
0–1 or CAT score less than 10; and group D—high risk,
more symptoms—GOLD 3–4, and/or at least 2 exacerba-
tions per year and/or at least 1 exacerbation resulting in a
hospitalization per year, and mMRC grade at least 2 or
CAT score at least 10. When this approach is combined
with an analysis of the comorbidities, the complexity of the
COPD patient is better assessed than using the uni-
dimensional analysis of FEV1 alone [7]. This new GOLD
stratification system yielded surprising observations, e.g.,
group B, which is characterized by more severe dyspnea,
had significantly poorer survival than group C despite
having higher FEV1 measures and fewer exacerbations
[22].
Several metrics other than FEV1 alone can predict
mortality. One of the first developed was the BODE (Body
mass index, airflow Obstruction, Dyspnea, Exercise per-
formance) index. This simple multidimensional grading
system is better than FEV1 alone in predicting death in
COPD patients [23]. In a study from Spain, the lung
481
hyperinflation measure of inspiratory capacity-to-total lung
capacity ratio (IC/TLC \25 %) is an independent predictor
of all-cause and respiratory mortality. FEV1, lower body
mass index, poor 6-min walk performance, patients with
more dyspnea, and those with higher BODE index also
predict mortality [24]. Age also is a risk factor. In a pro-
spective study, patients at least 75 years of age with higher
levels of dyspnea and FEV1 at most 50 % of predicted
were found to have the highest 5-year mortality (0.74) and
patients less than 55 years of age with FEV1 greater than
35 % of predicted and one or no recent COPD exacerbation
requiring hospitalization were found to have the lowest
5-year mortality (0.04) [25].
2.2 The 6-Min Walk Test
Because COPD is associated with increased airflow limi-
tation due to dynamic air trapping with exertion, a self-
paced walking test can be used to evaluate dyspnea in the
elderly. This is particularly helpful when dyspnea is out of
proportion to the degree of airflow obstruction and
comorbid illnesses (e.g., CHF) are present. The 6-min walk
is a simple, inexpensive, and safe test often conducted in a
corridor that has minimal traffic. The test has minimal
requirements including a technician with a stopwatch, an
oximeter, and known hallway distance. The 6-min walk
test assesses disease severity, disease progression, and
therapeutic effectiveness of medications and pulmonary
rehabilitation programs in elderly patients with COPD [26].
When repeated over time, the distance walked provides
increasingly useful information as to the progression and
increased severity of COPD [27]. Additionally, the distance
walked in 6 min is an important component of the BODE
index in COPD [23]. A recent report using the Evaluation
of COPD Longitudinally to Identify Predictive Surrogate
Endpoints (ECLIPSE) cohort determined that the minimum
clinically important difference (MCID) in the 6-min walk
over a year was a reduction in walk distance of more than
30 m. This conferred a hazard ratio of 1.93 (95 % CI
1.29–2.90, P = 0.001) [28].
3 Treatment of COPD
3.1 Smoking Cessation
Although there has been a decrease in the prevalence of
cigarette smoking from 2005 to 2010, it still is at 19.3 % in
the USA and higher in many other countries [29]. In the
recent Global Adult Tobacco Survey (GATS), 62.2 % of
men in Russia and 52.9 % in China were found to smoke
tobacco products, whereas the highest proportion of adult
females was in Poland (24.4 %) and in Russia (21.7 %) [30].
482
In men over 65 years, 40.7 % of Russians, 40.2 % of Chi-
nese, and 12.6 % of Americans smoked. Lower rates are
seen in women in this age group ranging from 1.4 % in
Egypt, 7.4 % in the USA to 21.0 % in the Philippines [30].
A comprehensive smoking cessation approach requires
aspects of education, counseling, reinforcement, and phar-
macotherapy [31]. In one study of elderly Korean smokers
(C65 years), alcohol use (social drinking), alcohol use dis-
order, and depression were characteristics rendering subjects
less likely to quit smoking [32]. It is likely that addressing
these comorbidities may improve smoking cessation rates in
this age group. In a recent review, the importance of a brief
intervention by physicians to prompt smokers to quit was
underscored [33]. Physicians actively linking patients to
behavioral support or counseling, nicotine replacement
therapy (lozenge, gum, inhaler, or nasal spray), and bupro-
pion or varenicline when patients are trying to quit smoking
doubles their odds of success. Addressing smoking as a
chronic disease by giving it a high priority in health care
systems like diabetes mellitus, coronary heart disease, and
hypertension allows the use of a chronic disease manage-
ment model in supporting the elderly patient’s efforts [33]. A
recent evidence-based analysis concluded that moderate
quality evidence supports significantly higher smoking
abstinence rates in COPD patients receiving intensive
counseling or a combination of intensive counseling plus
nicotine replacement therapy compared to the usual care.
Limited moderate-quality data supports nicotine replace-
ment compared to placebo, and moderate quality evidence
exists for the antidepressant bupropion compared to placebo
in increasing smoking abstinence in COPD patients [34].
There is an increased risk of seizures with bupropion over-
doses. Neuropsychiatric symptoms including behavior
changes, hostility, agitation, depression, and increased risk
of suicide have been reported with both the use of bupropion
or varenicline in smoking cessation. The increased risk of
suicide declines in patients treated with bupropion who are
older than 65 years. The continued risk of smoking must be
weighed against the risks of the drug therapy but even elderly
COPD patients are likely to benefit from reduced airway
inflammation and further airway function decline.
3.2 Inhalation Delivery Devices
The preferred route to deliver drug therapy in COPD patients
is by inhalation. Hand-held drug delivery options include
pressurized metered-dose inhalers (MDIs), dry powder
inhalers (DPIs), spring-powered mist inhalers (SMIs), and
nebulizers. The main classes of medication delivered with
these devices include bronchodilators and corticosteroids
(Table 1).
In a systematic review evaluating the clinical effective-
ness of different inhaler devices delivering corticosteroids
T. E. Albertson et al.
(CS) or b2-bronchodilators (b2Bs) in patients with COPD or
asthma, no difference in clinical effectiveness between
nebulizers, alternative inhaler devices, and MDIs with or
without spacer devices were found [35]. Similarly, a sys-
tematic review and evidence-based guidelines by the
American College of Physicians and the American College
of Asthma, Allergy, and Immunology on the inhalation
delivery of CS, b2Bs, and antimuscarinic agents concluded
that none of the delivery devices were superior and all
provide similar outcomes in patients correctly using the
devices [36]. They recommend that the specific selection of
the device should be based on device/drug availability,
clinical setting, patient age, ability to use the device, inter-
actions with other medications or devices being used, con-
venience, cost/reimbursement, and drug administration time.
Unfortunately, none of the studies or reviews focus
exclusively on elderly patients. An example of the trials
used in reviews includes one by Turner et al. [37], where
patients with asthma or COPD exacerbations presenting to
the emergency department were randomized to an MDI
with a spacer or a nebulizer. A total of 75 patients were
included with age ranges from 18 to 73 years and no
advantages were seen with either delivery device. Most
clinical trials that focus on devices exclude subjects
deemed incapable of using the device properly, making it
hard to conclude on their relative merits [38]. Looking at
elderly patients, Chapman et al. [39] showed that subjects
more successfully used breath-actuated inhalers than reg-
ular MDIs in a group with a mean age of 70.8 years. In a
cross-sectional study of subjects 70 years and older, MDIs
were the most common devices used and when used with a
spacer, they were used correctly by most subjects [40],
suggesting that slight modifications to routinely used
devices may improve compliance in elderly COPD
patients. A study of technique using two DPIs to deliver the
anti-influenza drug zanamivir in the elderly found that most
could not use the Relenza Diskhaler compared to the
Turbuhaler device [41]. The major difference between the
inhalers was in the difficulty of loading and priming them.
A subjective component on the part of the individual
patient and or clinician exists that may influence decisions on
specific devices and their usage. Because of the 1987 Mon-
treal protocol, chlorofluorocarbon (CFC)-based propellants
are almost completely phased out and replaced by hydro-
fluoroalkane (HFA)-based propellants for MDIs [36]. A new
SMI device is also shown in Fig. 1. This device is currently
used in the USA to deliver albuterol and ipratropium bro-
mide combination therapy and is replacing the CFC-based
MDI that delivered this combination of medications. The
same SMI device is available in Europe to deliver tiotropium.
Figure 2 gives an example of an MDI with and without a
spacer device. Both the MDI and the spacer require train-
ing and retraining in many elderly patients to ensure proper
Treatment of the Elderly COPD Patient 483

Table 1 Current and emerging drug treatments for COPD

Smoking cessation aids
Nicotine replacement treatments (NRT)
Zyban = bupropion
Chantix = varenicline
Nicotine vaccines—experimental
Bronchodilators
Short-acting
SABA or short-acting b2-agonists (e.g., racemic albuterol, Xopenex = levalbuterol)
SAMA or short-acting muscarinic antagonists (e.g., Atrovent = ipratropium)
Combination SABA ? SAMA (e.g., Combivent = combination albuterol ? ipratropium)
Long-acting
LABA or long-acting b2-agonists (e.g., Serevent = salmeterol, Foradil = formoterol, Brovana = arformoterol inhalation solution,
Performist = formoterol inhalation solution, Arcapta = indacaterol, and experimental or not yet available in USA—vilanterol,
carmoterol, milveterol, BI-1744-CL, PF-00610355, LAS-1000977)
LAMA or long-acting muscarinic antagonists (e.g., Spiriva = tiotropium, Tudoraza or Eklira = aclidinium, and experimental or not
yet available in the USA—glycopyrronium, darotropium, dexpirronium, umeclidinium, QAT-370, TD-4208)
Emerging treatment (MABA) dual pharmacophore with long-acting muscarinic antagonist and b2-agonist pharmacology
GSK-961081 (GSK) formerly TD-5959
THRX-200495 (Theravance)
Inhaled corticosteroids (in order of increasing potency; equal efficacy when dose-adjusted)
Azmacort = triamcinolone
Qvar = beclometasone
Pulmicort = budesonide
Zetonna = ciclesonide
Asmanex = mometasone
Flovent = fluticasone propionate
Double therapy (CS ? LABA) in single delivery device
Seretide or Advair = fluticasone proprionate ? salmeterola
Relovair = fluticasone furoate ? vilanterol—not yet available in the USA
Symbicort = budesonide ? formoterola
Dulera = mometasone ? formoterolb
Mometasone ? indacaterol—not yet available in the USA
Double therapy (LABA ? LAMA) in single delivery device—not yet available
Carmoterol ? tiotropium
Formoterol ? aclidinium
Formoterol ? glycopyrronium
Indacaterol ? glycopyrronium
Vilanterol ? umeclidinium
Milveterol ? darotropium
Vilanterol ? darotropium
Triple therapy (CS ? LABA ?LAMA) in single delivery device—not yet available
Mometasone ? indacaterol ? glycopyrronium
Fluticasone furoate ? milveterol or vilanterol ? darotropium or umeclidinium
Ciclesonide ? formoterol ? tiotropium
Phosphodiesterase-4 inhibitor
Daliresp or Daxas = roflumilast
Methylxanthine
Theophylline
Vaccines
NTHi oral immunotherapeutic (HI-1640V) against Haemophilus influenzae
Pneumococcal vaccine (23 and 13 valencies)
484 T. E. Albertson et al.

Table 1 continued
Influenza vaccine (configured yearly)
Tetanus, diphtheria, and pertussis (TDaP)
Antibiotics
Azithromycin—available, but not approved for COPD in USA
Mucoregulators
L-Carbocisteine—available, but not approved for COPD in USA
CS corticosteroid, SABA short-acting b2-agonist, SAMA short-acting muscarinic antagonist, LABA long-acting b2-agonist, LAMA long-acting
muscarinic antagonist, MABA combined effect muscarinic antagonist/b2-agonist
a
Only fluticasone 250 lg/salmeterol 40 lg fixed combination dry powder inhaler and budesonide 160 lg/formoterol 4.5 lg fixed combination
metered-dose inhaler are Food and Drug Administration (FDA)-approved for COPD in the USA
b
Approved in the USA only for asthma

use. Of interest, most of the HFA MDIs have little clinical
data supporting spacer use. The actuation of the MDI in
synchrony with breath initiation is a common problem for
all ages and usually improves with a spacer. Currently at
least one MDI is actuated by inspiratory effort making it
unsuitable for spacer use. The currently available SMI also
requires training and can be accidentally triggered which
may prove difficult for some elderly patients.
Nebulizer devices have small air compressors connected
by tubing to the Acorn reservoir that holds the medication/
saline. Airflow through the tubing moving air generates a mist
that is then inhaled through a mouthpiece. These have become
smaller, cheaper, and more mobile (rechargeable batteries)
over the years. Particular challenges to elderly patients
regarding nebulizers include the risk of contamination, limited
available types of medications, setup requirements, device
cleaning, and opening and loading the sterile unit dose med-
ications (Fig. 2). The lack of requiring actuation and breath
coordination with a nebulizer is a real advantage in some
elderly COPD patients and has been recently advocated [42].
DPIs are breath-actuated, but they do require a relatively
fast speed of inhalation (around 35 L/min inspiratory flow) to
drive the delivery of the medication into the lungs. They may
seem more complicated to some elderly patients, and the DPI
devices that require the elderly patient to open foil packages,
take out small capsules, and insert those capsules in the device
(Fig. 1) can be difficult for many elderly patients.
Combination medications seem to improve compliance
and are increasingly being used in the treatment of COPD
patients (Table 1). Elderly COPD patients may not benefit
from being prescribed multiple types of delivery devices
that require consistent proficiency to deliver different
bronchodilator and corticosteroids drugs. In the absence of
outcome data, drug device availability, cost, and patient
acceptance will often determine the optimal treatment
options for each elderly COPD patient.

Fig. 1 Top row: left a spring-powered mist-generating inhaler called

Respimat; middle metered dose inhaler; right a dry powder inhaler
that requires each dose to be loaded with foil-covered capsules.
Bottom row: left dry powder inhaler with built in doses; middle
another dry powder inhaler with built in doses; right a dry powder
inhaler that requires each dose to be loaded with a capsule from a foil-
covered packet
Fig. 2 Top a metered dose inhaler attached to a spacer device; bottom
left a sterile unit dose that is put into the Acorn to the right.
Compressed air is inserted in bottom of Acorn and the mist of drug
and saline is inhaled from mouthpiece
Treatment of the Elderly COPD Patient 485

3.3 Classification of Bronchodilators Used in Treating Table 2 Bronchodilator classifications

COPD A. Beta2 (b2) adrenergic agonist (sympathomimetics)
1. Short-acting b2
Outside of the pharmacological therapies directed at
a. Albuterol/salbutamol
smoking cessation, drugs used in treating COPD are clas-
b. Levalbuterol
sified into two major groups. These include bronchodila-
c. Fenoterol
tors, which relax airways, opening airways, and reduce air
d. Terbutaline
trapping; and anti-inflammatory agents, which modify and
e. Bitolterol mesylate
modulate the inflammation associated with COPD.
f. Pirbuterol
Bronchodilators are further classified by route (either
g. Metaproterenol
oral or inhaled), by length of duration (either short- or
h. Isoetharine
long-acting), and by mechanism of action. Long-acting
2. Long-acting b2-agonists (LABA)
bronchodilators are given no more than twice a day, and
a. Salmeterol
short-acting agents require more frequent dosing. Table 2
offers a classification system that merges the three b. Formoterol
parameters. Similarly, the corticosteroid anti-inflammatory c. Arformoterol
agents can be classified into systemic (oral or parenteral), d. Indacaterol
and inhaled or topical. In an attempt to improve medication e. Clenbuterol
usage and compliance, many inhalers have combined B. Muscarinic antagonists (anticholinergics)
therapies that include a bronchodilator with a steroid or two 1. Short-acting muscarinic antagonists (SAMA)
types of bronchodilators. Combined therapy with two types a. Ipratropium
of bronchodilators and an inhaled corticosteroid (i.e., 2. Long-acting muscarinic antagonists (LAMA)
‘‘triple therapy’’) is being evaluated (Table 1). a. Tiotropium
b. Aclidinium
3.3.1 b2-Adrenergic Agonists c. Oxitropium
d. Glycopyrrolate bromide
The periodic use of an inhaled short-acting b2-adrenergic C. Oral agents
agonist (SABA) is recommended for treatment on an ‘‘as 1. Oral SABA
needed’’ basis in all stages of COPD (http://www.goldcopd.org a. Albuterol/salbutamol
). Acute testing with an inhaled SABA during spirometry does 2. Methylxanthine
not always predict a clinical response to these agents, and a. Theophylline
exercise symptom improvement is frequently seen in COPD b. Oxtriphylline
patients that failed to show acute spirometric improvement 3. Phosphodiesterase-4 inhibitor
following a SABA dose [43]. In addition to the use of SABAs a. Roflumilast
as rescue or ‘‘as needed’’ medication, inhaled long-acting b2-
adrenergic agonists (LABAs) are used in the treatment of
COPD as maintenance therapy. A LABA provides at least 12 h when it compared twice daily salmeterol 50 lg combined
of bronchodilation coverage (salmeterol, formoterol, and ar- with high dose fluticasone (500 lg) to either twice daily
formoterol) and newer ones such as indacaterol can provide a salmeterol, placebo, or fluticasone alone over a 3-year
24-h duration of action (Tables 1, 2). period. The hazard ratio for death in the combination
Most efficacy data for the use of SABAs and LABAs treated group compared to placebo was 0.825 (95 % CI
have focused on improvement in spirometry (FEV1), 0.681–1.002, P = 0.052) [47]. Even though this very high
improvement in health-related quality of life, and fre- standard of efficacy has not been reached for a broncho-
quency of adverse drug-associated events [44, 45]. Other dilator, an anti-inflammatory agent, or a combination
trials have assessed the speed of FEV1 change after LABA preparation, improvement in other outcomes are now rou-
use, in spite of the fact that LABAs should be used only for tinely reported. Table 3 reviews several large trials with
maintenance therapy [46]. Some SABAs are formulated as various treatment options and their effect on reducing the
an oral preparation, but these offer less bronchodilation and frequency of COPD exacerbations. In the TORCH trial, the
more frequent b2-adrenergic agonist side effects including combination of salmeterol plus fluticasone significantly
hypokalemia, hyperglycemia, muscle tremor, tachycardia, improved health status, spirometric values, and reduced
and restlessness compared to inhaled formulations. the annual rate of exacerbations compared to placebo
No bronchodilator has shown an improvement in the (P \ 0.001 for all comparisons). A similar magnitude
mortality of COPD patients. The TORCH trial came close reduction in exacerbations was seen with salmeterol alone
486
or fluticasone alone compared to placebo (P \ 0.001 for
both comparisons) [47].
A recent systematic review of five randomized con-
trolled trials explored the efficacy and safety of the once-a-
day LABA indacaterol evaluated in COPD patients with an
average age of 63–64 years [48]. A total of 5,920 patients
were included and showed statistically significant
improvement and clinical reductions in the use of rescue
medication and dyspnea index compared to the use of
tiotropium. The once-a-day LABA indacaterol has been
shown to improve FEV1 and health-related quality of life
compared to placebo and to be as effective as salmeterol,
formoterol, and tiotropium [49–51]. Similarly, indacaterol
showed a statistically significant improvement in dyspnea
index, health status, and trough FEV1 compared to twice-a-
day LABAs [48].
In a small randomized crossover study of 44 previously
untreated elderly Japanese COPD patients, the 6-min walk
test and the health-related quality of life scores were both
statistically better with the experimental transdermal
LABA tulobuterol than inhaled twice-a-day salmeterol.
The adherence rate was also statistically improved (90.3 %
with the LABA patch versus a 75.5 % with the inhaled
LABA) [52].
Although long-acting antimuscarinic antagonists
(LAMAs) have been advocated as first-line therapy for
maintenance bronchodilators in COPD, recent guideline
updates and current data support the early use of LABAs
[4]. Specific trials focused on elderly patients and LABA
therapy in COPD are lacking. Table 3 reviews the average
age of COPD patients in the trials that focus on the out-
comes of COPD exacerbation frequency. Most therapy
trials use patients tested for their ability to use the device
being evaluated and studied patients who averaged
between 62 and 68 years and were predominately male.
Additional concerns about using beta-blockers in
patients who have CHF or history of coronary disease in
addition to COPD have been alleviated with multiple
studies. Initial recommendation for COPD patients was for
cardio-selective beta-blocker but more recently the safe use
of non-selective beta-blockers has been confirmed [53–55].
A recent Swedish study examined the use of cardiovascular
drugs in 2,249 patients with COPD [56]. Using a time-
dependent model and controlling for important sources
of bias, non-statistically significant reduced mortality
was seen for the use of angiotensin-converting enzyme
inhibitors/angiotensin receptor blockers and for statins
(HR = 0.88, 95 % CI 0.76–1.02 and HR = 0.86, 95 % CI
0.71–1.03, respectively) but not for the use of beta-blockers
(HR = 1.14, 95 % CI 0.99–1.30). Further study including
randomized prospective trials is needed on the long-term
use of cardiovascular drugs in elderly COPD patients.
T. E. Albertson et al.
3.3.2 Muscarinic Antagonists (Anticholinergics)
Large airways have muscarinic receptors, which result in
increased airway tone and decrease airway diameter and
flow when stimulated. These receptors are innervated by
the vagus nerve. Three subtype muscarinic airway recep-
tors M1, M2, and M3 have been recognized [57, 58]. Use of
muscarinic antagonists in COPD was pioneered with
inhaled atropine and Datura stramonium that was smoked,
both of which are tertiary amines which cross biological
membranes to enter the brain, bladder, pupils, and other
organs. The quaternary amine ipratropium bromide is
classified as a short-acting muscarinic antagonist (SAMA)
and does not easily cross biological membranes. It has been
shown to be as effective as the SABA metaproterenol in a
randomized, double-blind, 90-day study in COPD patients
[59]. Side effects with the SABA metaproterenol included
tremors that were not seen with the SAMA ipratropium.
A randomized, double-blind, placebo-controlled, multi-
center trial of 144 COPD patients with an average age of
64 ± 7 years examined the LABA salmeterol twice a day,
salmeterol plus the SAMA ipratropium four times a day, or
placebo alone for 12 weeks [60]. Symptom scores and
morning FEV1 determinations were statistically improved
and greater with both the salmeterol and the salmeterol
with ipratropium group compared to placebo. Compared to
the group receiving salmeterol alone, the combined treat-
ment group had more improvement in FEV1 and airway
conductance. The combined treatment of salmeterol and
ipratropium was associated with statistically less COPD
exacerbations than the placebo group (13 vs. 36 %,
P \ 0.01) [60]. In a study that evaluated the SABA albu-
terol, the SAMA ipratropium, and a combination of albu-
terol and ipratropium all given as MDIs in a 12-week,
double-blind, prospective study of COPD patients, both the
FEV1 and FVC were statistically improved with the com-
bination SABA/SAMA compared to each alone on all days
tested [61].
The SAMA ipratropium binds non-selectively to M1,
M2, and M3 receptors, whereas the quaternary amine
LAMA tiotropium binds selectively to M1 and M3 recep-
tors over M2 [58]. Tiotropium has a long half-life and is
administered once a day. The newer LAMA agent aclidi-
nium and the older agents oxitropium and glycopyrrolate
bromide are all quaternary amines and are dosed twice a
day [62, 63]. Tiotropium is available as a DPI and in
Europe in an SMI [64]. A 28-day safety and tolerability
study using the investigational LAMA umeclidinium in
combination with the experimental LABA vilanterol in a
once-a-day combination inhaler found marked improve-
ment in FEV1 on day 29 and no significantly different
adverse effects [65].
Table 3 Important studies evaluating the prevention of acute exacerbations of COPD
Drug or treatment Trial Demography Results Comments

Budesonide/formoterol 320/9 lg vs. N = 1,219 180 research centers in USA, 34.6 and 25.9 % reduction in exacerbations for high Pneumonia rates 6.4, 4.7, and 2.7 % for
budesonide/formoterol 160/9 lg vs. RDBMC— South Africa, and South and low dose budesonide/formoterol compared to high dose, low dose, and formoterol
formoterol 9 lg metered dose inhaler twice 1 year America formoterol alone alone
daily [197] Mean age = 63.0 ± 9.3
62 % male
Fluticasone 500 lg ? salmeterol vs. TORCH 444 research centers in 42 25 % reduction in exacerbations vs. placebo 14 % reduction in exacerbations with
fluticasone alone vs. salmeterol alone vs. study countries salmeterol alone; 18 % reduction
placebo N = 6,184 Mean age = 65.0 ± 8.3 with fluticasone alone vs. placebo
Treatment of the Elderly COPD Patient

RDBMC— 75.5 % male

3 years
[47]
Fluticasone 500 lg or placebo twice daily ISOLDE 18 hospitals in UK 25 % reduction in exacerbations Delayed the onset of clinically
metered dose added to standard treatment study Mean age = 63.7 ± 7.1 important reduction in health status
N = 751 74.6 % male
RDBMC—
3 years
[198]
Fluticasone/salmeterol 250/50 lg powder vs. N = 782 94 research sites in Canada 30.5 % reduction in moderate/severe exacerbations 40 % reduction in exacerbations
salmeterol 50 lg powder plus as needed RDBMC— and USA requiring oral corticosteroids
albuterol 52 weeks Mean age = 64.9 ± 9.0
[199] 55 % male
Fluticasone/salmeterol 250/50 lg or N = 797 98 research sites in USA and 30.4 % reduction in moderate/severe exacerbations Improvement in prn albuterol use,
salmeterol 50 lg as powder, twice daily RDBMC— Canada dyspnea scores, and nighttime
52 weeks Mean age = 65.4 ± 9.0 waking. Increased pneumonia (7 vs.
[200] 2 %)
54 % male
Mometasone furoate/formoterol 400/10 lg, N = 2,251 131 ? 164 research centers 21.4 % reduction in exacerbations with high dose High dose mometasone/formoterol had
mometasone/formoterol 200/10 lg, RDBMC— in Europe, USA, Central mometasone/formoterol group, compared to placebo 2 % pneumonia vs. 0.7 % placebo
mometasone 400 lg, formoterol 10 lg or 52 weeks and South America, Asia, group
placebo [97] and Africa
Mean age = 59.7 ± 8.8
76 % male
Azithromycin 250 mg orally vs. placebo N = 1,142 17 sites associated with 12 19.1 % reduction in exacerbations 125 % increase in hearing decrement
daily RPCMC— academic health centers (P = 0.04)
1 year USA
[133] Mean age = 65.5 ± 9
59 % male
487
Table 3 continued
488

Drug or treatment Trial Demography Results Comments

Azithromycin 500 mg orally vs. placebo EMBRACE 3 New Zealand centers 64.4 % reduction in exacerbations in the azithromycin No difference in FEV1 or health-related
daily 9 3/week study Mean age = 60.0 ± 13.2 group compared to placebo quality of life scores
N = 141
RDBMC—
6 months
[134]
Tiotropium 18 lg vs. placebo powder daily MISTRAL 177 research centers in 35 % reduction in exacerbations 17 % reduction in number of patients
plus usual care, but no oral or inhaled study France experiencing more than one
LABA, any other inhaled anticholinergics N = 1,010 Mean age = 68.8 ± 9.3 exacerbation
or theophylline
RDBMC— 88 % male
1 year
Add
MISTAL
[201]
Tiotropium 18 lg or placebo added to UPLIFT 37 countries 14 % reduction in exacerbations with tiotropium; mean 62 % pts on ICS
regular treatment study 490 investigation centers FEV1 elevated (P \ 0.001) compared to placebo 60 % pts on LABA
LABA ± ICS ± theophylline N = 5,993 Mean age = 65 ± 8 28 % pts on theophylline
RDBMC— 74.6 % male
44 years
[202]
Tiotropium 18 lg once daily vs. salmeterol POET study 25 countries at 725 research 11.1 % reduction in moderate/severe exacerbations 30.8 % reduction in severe
50 lg twice daily plus usual medications N = 7,376 centers exacerbations Increased time to first
except LABA and anticholinergic Mean age = 62.9 ± 9.0 exacerbation 187 vs. 145 days
RDBMC–
medications
DD— 74.6 % male
1 year
[203]
Roflumilast 500 lg once daily vs. placebo M2–124/ 10 countries at 246 research 17 % reduction in moderate/severe exacerbations A 2.17-kg weight decrease with
plus usual treatment 125 study centers roflumilast compared to placebo
N = 3,091 Mean age = 64 ± 9
RDBMC— 75.5 % male
1 year
[124]
Roflumilast 500 lg one daily plus either M2–127/ M2–127 study—10 38.9 % reduction in moderate/severe exacerbations Roflumilast was used to replace ICS;
salmeterol or plus tiotropium no other 128 study countries in 135 centers with salmeterol/roflumilast vs. salmeterol/placebo significant increase in FEV1 with
LAMA/LABA, ICS or theophylline N = 1,676 and M2–128 study—7 (P = 0.0015); 31.2 % reduction in moderate/severe either salmeterol or tiotropium
permitted countries in 85 centers exacerbations with tiotropium ? roflumilast vs. compared to placebo
RDBMC—
Mean age = 64.6 ± 9 placebo/ ? tiotropium but N.S. (P = 0.0867)
24 weeks
[204] 68.4 % male
T. E. Albertson et al.
Treatment of the Elderly COPD Patient 489

double-blind, multicenter trial, RPCMC randomized, placebo-controlled, multicenter trial, FEV1 forced expiratory volume in 1 s, N number of patients (pts), RR relative risk, CI 95 %
N.S. no significant difference, prn as needed, DD double-dummy, LABA long-acting beta agonist, LAMA long-acting muscarinic antagonist, ICS inhaled corticosteroids, RDBMC randomized,
The use of LAMA inhalers is a first-line maintenance
therapy for moderate-to-severe COPD. Adding tiotropium
No difference in adverse events to COPD patients already treated with a LABA/cortico-
steroid (CS) resulted in significantly improved health-
related quality of life scores, FVC, FEV1, and inspiratory
capacity (IC) compared to treatment with LABA/CS alone
[66]. Combination inhaled therapy with tiotropium plus the
LABA formoterol with or without the CS budesonide also
Comments

resulted in improved lung function [67]. The addition of

the SABA fenoterol or the SAMA ipratropium to 60 COPD
patients on maintenance tiotropium therapy in a random-
ized, placebo-controlled study resulted in improved lung
function. Both drugs were effective in increasing FEV1
with the SABA improving the FEV1 statistically greater
24.5 % reduction in exacerbations (P = 0.004)

than the SAMA [68]. The addition of a SAMA onto

maintenance tiotropium in COPD patients has resulted in
small FEV1 improvement, but has not yet been shown to
significantly improve other clinically relevant parameters
[69]. A systematic review found a small improvement in
health-related quality of life with the addition of the
LAMA triotropium to an inhaled LABA compared to
tiotropium alone in COPD patients [70]. Looking at pre-
scription claims from the Ontario Drug Benefit Program
% = all listed reductions statistically significant at P B 0.05 except as noted. ± = ±1 standard deviation

over 12 months found that persistence with inhaled treat-

ment in COPD patients was low, but was highest with
Results

tiotropium [71]. Table 3 summarizes significant studies

that generally demonstrate reduced rates of COPD exac-
erbations with LAMA use, but no reductions in mortality
rates have been demonstrated to date. The LAMA tiotro-
Mean age = 65.2 ± 8.9

pium is well tolerated with anticholinergic side effects such

22 centers in China

as dry mouth, constipation, gastrointestinal obstruction,

and dysuria being the most common. Dilated pupils and
Demography

78.5 % male

worsening of intraocular pressure in those patients with

glaucoma have also been noted. Men with lower urinary
tract symptoms or benign prostate hyperplasia may develop
acute urinary retention with the use of an inhaled SAMA or
LAMA, but the frequency of this happening is not known
RDBMC—

despite widespread use of the agents [72]. Potential anti-

N = 709

1 year
PEACE

[138]
study

cholinergic-related adverse events were reported to be

Trial

seen in at most 2.5 % of patients in large trials with ac-

lidinium [73].
Carbocisteine 1,500 mg orally or placebo

In systematic reviews of the cardiovascular risk of

inhaled SAMA/LAMAs in COPD patients that include the
large 4-year UPLIFT trial, no significant difference was
found between tiotropium and placebo in the risk of a
stroke. The risks of serious cardiac adverse events includ-
ing myocardial infarction and CHF were significantly
lower with tiotropium [67, 74]. This contrasts with the
confidence interval
Table 3 continued
Drug or treatment

recent UK general practitioner electronic medical record

database analysis of new users of tiotropium compared to
new users of LABA in patients with COPD. A small
increase in rates of stroke, angina, and myocardial infarc-
tion were seen with the new use of the LAMA compared to
490
the LABA [75]. Small increased risk of arrhythmias in
COPD patients treated particularly with the SAMA iprat-
ropium and the use of LABAs/SABAs has been suggested
in the Saskatchewan cohort study and in a reassessment of
the larger Quebec cohort study [76]. Using Ontario Canada
databases, Gershon et al. [77] evaluated mortality at
6 months in elderly (C65 years) COPD patients treated
with a LABA or the LAMA tiotropium. They found a 20 %
reduction in mortality with the use of the LAMA compared
to the LABA (HR = 0.80, 95 % CI 0.70–0.93). However,
when these same investigators looked at the use of LABA
versus LAMA in elderly (C65 years) COPD patients using
the same databases for up to 5.5 years, mortality was
higher in patients prescribed a LAMA compared to a
LABA (adjusted HR = 1.14, 95 % CI 1.09–1.19) [78].
Further trials are needed to evaluate this in other elderly
patients, younger patients, and in more randomized con-
trolled studies that focus on elderly COPD patients.
3.3.3 Combination Inhaler Therapy
One of the first combination inhalers for COPD was the
MDI that combined the SABA albuterol with the SAMA
ipratropium bromide. Although the use of the combination
of a SAMA/SABA in one inhaler has been shown to be
more efficacious than each alone, no study has shown that a
combined inhaler is better than using the two drugs in
separate inhalers. One analysis of a large claims database
reported that the use of a single inhaler has better adher-
ence rates than those with multiple inhalers in COPD
patients [79]. In another analysis of the same database, the
use of multiple inhalers was associated with a higher risk of
exacerbations, higher health care resource utilization, and
higher costs compared to single inhaler users in patients
with COPD [80]. The use of the combination therapy of
albuterol/ipratropium was approved for use in COPD
almost 20 years ago, but has been supplanted in most
COPD treatment guidelines by longer-acting inhalers
containing a LAMA or LABA and newer combination
inhalers of CS/LABA in the treatment of COPD [81]. New
inhalers with once-a-day combinations of LAMA/LABA
are under investigation and the first triple inhaler contain-
ing the CS ciclesonide, the LABA formoterol, and the
LAMA tiotropium has already been released in India [82].
Combination inhalers appear to improve medication use
compliance and may be particularly useful in elderly
COPD patients.
3.4 Inhaled and Systemic Corticosteroids
COPD involves significant airway inflammation in its path-
ophysiology. Elevated levels of circulating interleukin-8,
tumor necrosis factor alpha, and C-reactive protein (CRP)
T. E. Albertson et al.
seem to correlate with increased disease severity, exacer-
bation rates, and decline in lung function in COPD patients
[83]. Increases in CRP in COPD patients are also associ-
ated with poor health status and comorbidities such as
cardiovascular disease, cancer, and poor skeletal muscle
function. The importance of inflammation in the patho-
genesis of COPD and associated comorbidities has resulted
in the use of topical and systemic CS in the treatment of
COPD.
Although the acute treatment of COPD exacerbations is
outside the focus of this review, randomized controlled,
double-blind, and cohort trials have demonstrated that
systemic CS contributes to moderate improvement in
clinical outcomes among patients experiencing COPD
exacerbations [84–86]. This includes shorter duration of
symptoms, faster improvement of FEV1, and less chance of
relapse exacerbations. A number of reviews have also
concluded that short courses of oral or parenteral CS in
acute COPD exacerbations improve clinical outcomes [87,
88]. At least one study has shown that oral CS is not
inferior to parenteral CS in hospitalized patients with acute
COPD exacerbations [89]. Short courses of less than
2 weeks and maybe as short as 3 days of oral or parenteral
followed by oral CS appear to be well-established treat-
ment approaches during COPD exacerbations [90].
The use of oral or inhaled/topical CS in stable moderate-
severity COPD patients significantly reduced a number of
selected systemic cytokines measured in a randomized trial
[91]. It is recognized that the majority of COPD patients do
not benefit from long-term systemic CS [92].
Those COPD patients with more atopic/asthmatic or
bronchospastic symptoms appear to benefit the most from
CS, and patients with irreversible airway obstructive
disease benefit the least from inhaled CS [92]. A recent
Cochrane review supports the use of inhaled LABA over
inhaled CS with inhaled CS suggested as adjunct therapy
in COPD patients [93]. A randomized, double-blind,
placebo-controlled, crossover study compared fluticasone
propionate to placebo in COPD patients with an average
age of 67.2 ± 6.9 years. The study underscores the
importance of topical CS when it found that the addition
of the inhaled CS to patients already on a stable LABA
improved FEV1, static lung volumes, dynamic lung vol-
umes, and exercise endurance in moderate to severe
COPD [94]. The experimental LABA vilanterol when
combined with fluticasone furoate has been studied in a
once-a-day combination inhaler in a randomized, placebo-
controlled, three-way, crossover study in COPD patients.
The once-a-day CS/LABA resulted in significantly
improved pulmonary function compared to placebo over
the 28 days of this preliminary trial [95]. The addition of
inhaled CS has been shown to improve FEV1 and quality
of life, and reduce COPD exacerbations in a meta-
Treatment of the Elderly COPD Patient
analysis, but with significantly increased risk of pneu-
monia [96].
Many fixed combinations of inhaled CS/LABA have
been studied in COPD patients. A 52-week study in 2,251
patients reported a lower incidence of COPD exacerba-
tions, improved FEV1, and improved quality of life with
inhaled mometasone furoate/formoterol combination ver-
sus mometasone, formoterol, or placebo alone [97].
Table 3 offers a summary of several clinical trials in COPD
patients evaluating inhaled CS/LABA combination inhalers
in reducing the frequency of COPD exacerbations. The use
of a combined inhaler of CS/LABA compared to a LABA
alone in COPD patients has been systematically reviewed,
though the review could not endorse the use of a combined
CS/LABA over the LABA because of concerns regarding
the analysis and data availability from the studies [98].
Similarly, systematic reviews of combined CS/LABA
use in COPD patients comparing inhaled CS/LABA to
inhaled tiotropium have failed to conclude superiority of
either therapy because of data quality concerns. The
reviewers noted that more high-quality data as seen in two
large trials (TORCH and UPLIFT) is needed to appropri-
ately perform the systematic review [99]. Three trials
evaluated adding combined inhaled CS/LABA to tiotropi-
um (LAMA) compared to tiotropium or combination CS/
LABA alone and found no statistically significant differ-
ence in mortality, rate of hospitalizations, episodes of
pneumonia, or other adverse events between the groups.
Because of the heterogeneous nature of the exacerbation
data, the authors were unable to determine exacerbation
frequencies. However, benefit was seen in health-related
quality of life and lung function when the inhaled LAMA
was added to the inhaled CS/LABA compared to the
LAMA or CS/LABA alone [100]. In contrast, a retro-
spective cost-effective ‘‘real-world’’ study of COPD
patients suggests that the combination CS/LABA inhaler is
associated with significantly better clinical and economic
outcomes compared to the use of inhaled SAMA or LAMA
therapy alone [101]. A single-center, double-blind ran-
domized controlled trial evaluated the removal of the
inhaled CS fluticasone propionate after 4 months in 244
COPD patients (average age 64 years) on the rate of COPD
exacerbations [102]. The placebo-treated group was found
to have an increased risk of a first exacerbation compared
to the inhaled CS group (HR = 1.5, 95 % CI 1.05–2.1).
The mean time to the first exacerbation was 42.7 days for
the placebo group and 75.2 days for the inhaled CS group
[102]. Further randomized controlled trials are needed to
better understand when inhaled CS can be withdrawn in
elderly COPD patients.
In addition to the increased risk of pneumonia with inhaled
CS in COPD patients, thrush, vertebral fractures, osteoporo-
sis, and the risk of diabetes onset and progression have been
491
suggested [96, 103, 104]. In elderly COPD patients, the cli-
nician must balance the limited data on benefits against the
long-term risks of inhaled and systemic CS.
3.5 Methylxanthines, Phosphodiesterase-4 Inhibitors,
Antibiotics, and Mucolytics
Maintenance theophylline and the more water-soluble
agent aminophylline (theophylline in an ethylenediamine
complex) have been controversial drugs used in COPD
management for more than 25 years [105]. Theophylline
causes bronchodilation, enhances diaphragmatic contrac-
tility and endurance, increases myocardial contractility,
and increases central respiratory drive [105–108]. The
clinical significance of these effects is debated, however,
especially in light of theophylline’s notoriously narrow
therapeutic window and toxicity profile. In low concen-
trations, theophylline appears to have anti-inflammatory
effects, but again the clinical significance has not been
clearly shown [109, 110].
A double-blind crossover study of 40 ambulatory COPD
patients compared theophylline to placebo and demon-
strated a small, but statistically significant, increase in
FEV1. Of the 40 patients, six were identified as theophyl-
line ‘‘responders’’, but theophylline was not beneficial to
most of the COPD patients [111]. Similarly, a significant
improvement in lung function was seen when theophylline
and an inhaled SABA were combined compared to each
separately, though no improvement in symptoms was
reported [112]. When low dose theophylline (plasma levels
of 8.8–12.4 mg/L) was added to inhaled CS, statistical
improvement in FEV1 was seen compared to the use of
inhaled CS by itself [113]. Using the results of randomized
controlled clinical trials totaling 2,087 patients, a meta-
analysis concluded that compared to placebo, theophylline
can improve lung function, arterial blood gas exchange,
and walking distance at the cost of higher drug-related
adverse events [114]. A newer methylxanthine derivative,
doxofylline, appears to have less drug-induced side effects
and still demonstrates a bronchodilator effect [115].
Higher blood levels of theophylline are associated with
greater bronchodilation but increased risk of toxicity. Sig-
nificant variations in theophylline pharmacokinetics asso-
ciated with age, active smoking, disease states, and drug
interactions exist [116–119]. The large variations in serum
half-life and pharmacokinetics make theophylline a very
challenging treatment in elderly COPD patients with little
convincing evidence of clinically meaningful improvement
in outcomes.
The drug-associated side effects with theophylline
include diarrhea, tremor, nervousness, confusion, cardiac
arrhythmias, myocardial infarctions, and seizures [120,
121]. COPD patients receiving treatment regimens that
492
include theophylline have slightly increased mortality,
COPD exacerbations, and COPD hospitalization risk
compared to patients without theophylline [122]. In fact,
some experts have called for an end to theophylline use in
COPD management [123].
The oral phosphodiesterase-4 inhibitor roflumilast rep-
resents a new class of medication approved for use in
COPD. Although roflumilast has been shown to improve
FEV1 by 40–60 mL compared to placebo, it has not been
classified as a bronchodilator [124]. Perhaps its greater
benefit has been its ability to reduce COPD exacerbations
(Table 3). A post hoc pooled analysis of two studies with
2,686 randomized patients evaluated roflumilast 500 lg or
placebo daily for 52 weeks and found that the use of rof-
lumilast significantly decreased exacerbations by 14.6 %
compared to placebo. Subjects most likely to benefit from
roflumilast included those with cough, sputum production,
and concomitant inhaled CS use, suggesting that roflumi-
last affects inflammatory cascades to reduce exacerbations
[125]. Significant adverse effects, including diarrhea,
nausea, and weight loss, limit the use of roflumilast [125,
126]. As a result, roflumilast is recommended as an adjunct
therapy in patients with severe or symptomatic COPD
associated with frequent exacerbations [127, 128].
The use of antibiotics in acute exacerbations of COPD,
particularly associated with acute exacerbation of chronic
bronchitis (AECB), has a long history. Antibiotics such as the
fluoroquinolone moxifloxacin is as effective as amoxicillin/
clavulanic acid in the treatment of acute exacerbations of
COPD associated with bacterial infections and AECB [129,
130]. The use of macrolide antibiotics to treat COPD exac-
erbations associated with AECB is also well documented
[131]. Long-term use of macrolide antibiotics for diffuse
panbronchiolitis began in the 1980s with at least six ran-
domized controlled trials demonstrating evidence of benefit in
cystic fibrosis [132]. A randomized controlled trial of daily
azithromycin compared to placebo in COPD patients given
over a year demonstrated a significant reduction in the rate of
COPD exacerbations (Table 3). Improved health-related
quality of life scores were noted, but hearing decrements were
also statistically more common in the azithromycin-treated
group [133]. A smaller randomized, double-blind trial of
COPD patients in three centers in New Zealand also tested
azithromycin versus placebo each three times a week for
6 months. A significant reduction in COPD exacerbations and
improvement in health-related quality of life were seen
without any improvement in FEV1 [134]. The mechanism of
action of the macrolide antibiotics in these lung diseases is
possibly due to their antibiotic effects, their ability to restore
corticosteroid receptor sensitivity, and their direct anti-
inflammatory actions [135]. Newer macrolides are being
developed that lack antibiotic effects and the ability to induce
microbial resistance. Nevertheless, these agents still have
T. E. Albertson et al.
anti-inflammatory properties that will potentially improve
efficacy while minimizing the risks of long-term use.
Mucolytics are used in patients with COPD and chronic
sputum production. A review of mucolytics in the man-
agement of COPD patients concluded that despite the poor
quality of published evidence, small reductions in exacer-
bation frequency were seen, but there were few additional
health benefits [136]. A systematic review of the use of
mucolytics in COPD and chronic bronchitis patients
included 28 trials and 7,042 patients. Oral mucolytics were
associated with a significant 21 % reduction in exacerba-
tions, but this was only seen in patients not taking inhaled
CS [137]. A large Chinese study found a significant 25 %
reduction in COPD exacerbations and improvement in
health-related quality of life with daily carbocisteine
compared to placebo for a year (Table 3). Carbocisteine is
a mucolytic and likely has antioxidant and anti-inflamma-
tory properties [138]. The use of chronic oral mucolytics in
elderly COPD patients will likely be limited to those
patients with chronic mucus production who are not on
inhaled corticosteroids.
3.6 Oxygen Therapy
The use of long-term oxygen therapy (LTOT) for specific
elderly patients with COPD is common and defined by
physiological criteria that vary little between the USA, UK,
Europe, and Australia [139]. Although slight variations in
criteria exist, a PaO2 less than 55 mmHg or an arterial pulse
oximetry (SaO2) of less than 88 % on room air at rest at sea
level will qualify most elderly COPD patients for LTOT.
Demonstrating these same parameters with exercise will
usually qualify a patient for LTOT during exercise. The
presence of pulmonary hypertension, cor pulmonale, elevated
hematocrit ([56 %), or a commitment to palliative care in a
patient with refractory dyspnea that does not otherwise meet
the LTOT criteria will often qualify. The goal of LTOT is
correction of the hypoxemia, and this correction needs to be
documented [139]. Overall, the need for LTOT in elderly
COPD patients is a prognostic factor for markedly reduced
survival and poor quality of life [140–142].
Two major studies (MRC and the NOTT trials) have
reported mortality improvement in COPD patients on
LTOT who met criteria compared to controls [6, 143]. A
systematic review of six studies on the effect of LTOT in
COPD patients concluded that LTOT improved survival in
a selected group of patients with severe hypoxemia [PaO2
\55 mmHg (8.0 kPa)] and did not improve survival with
mild to moderate hypoxemia or in those COPD patients
with only nocturnal desaturations [144]. A recent ‘‘mega-
analysis’’ has concluded, on the basis of a low quality of
evidence, that LTOT of at least 15 h/day decreases all-
cause mortality and improves health-related quality of life
Treatment of the Elderly COPD Patient
in COPD patients with severe hypoxemia, but does not
reduce hospital readmission rates [145]. A small reduction
of COPD-related pulmonary hypertension after the first
2 years of LTOT followed by a return to initial values
occurs [146–148]. In selected elderly COPD patients, it
appears that LTOT can improve physiological parameters,
health-related quality of life, and mortality.
Picking the best LTOT source and delivery device for the
elderly COPD patient is often a balance between insurance
and expense issues and logistical issues concerning the
oxygen-supplying device (i.e., weight, portability, com-
plexity, and comfort associated with using a device). Liquid
oxygen, oxygen concentrators, and tank oxygen devices are
changing rapidly in the market place, often with little out-
come data to support the changes [149, 150]. In evaluating
the compliance of the elderly COPD patient with their
LTOT, it is important to reinforce with the patient and their
care support team the unacceptable risks of combining
oxygen therapy with flames. The simultaneous use of LTOT
and smoking cigarettes results in several fatal fires a year in
the USA [151]. The use of LTOT in elderly COPD patients
meeting hypoxemic criteria reduces mortality, pulmonary
hypertension, dyspnea, and improves the health-related
quality of life, but it requires many practical considerations
to ensure safety and patient compliance.
3.7 Vaccinations
The single-stranded RNA influenza virus A and B cause
seasonal and pandemic disease in humans. Each year the
World Health Organization’s Global Influenza Surveillance
Network in conjunction with the USA’s Center for Disease
Control (CDC) develops a new injectable trivalent inactivated
viral vaccine. Seasonal influenza annually leads to more than
200,000 hospitalizations, 36,000 deaths, and billions of dol-
lars of direct and indirect health care costs in the USA [152].
Influenza infections are also associated with acute COPD
exacerbations, increased hospitalizations, increased episodes of
pneumonia, and respiratory failure in COPD patients. Data on
the effectiveness of influenza vaccination in COPD patients is
inconsistent with some studies reporting reductions in influ-
enza-related metrics, whereas other studies have reported no
improvement [152]. In general, elderly patients ([65 years)
have been shown to have a 70 % reduction in mortality after
influenza vaccinations [153]. A recent evidence-based review
concluded that influenza vaccination in COPD patients reduced
influenza-related acute respiratory tract infections and reduced
the rate of hospitalizations and episodes of mechanical venti-
lation. The patient’s age, sex, severity of COPD, smoking sta-
tus, and comorbid disease status did not modify its effectiveness
[154]. As a result, GOLD and other guidelines on the treatment
of COPD stress annual influenza vaccination in both elderly and
younger patients with COPD.
493
Pneumococcal pneumonia is a disease associated with
meningitis, pneumonia, and sepsis in adults. It has been
shown to colonize the airway of COPD patients at a higher
rate than healthy patients and to be associated with higher
rates of exacerbation in these patients [152]. Historically,
the 23-valent pneumococcal/polysaccharide vaccine has
been recommended and studied in COPD patients with
mixed efficacy reported [152]. A recent evidence-based
analysis of COPD patients concluded that the 23-valent
pneumococcal vaccination significantly reduces the risk of
acquiring pneumococcal pneumonia [154]. The risk of
acquiring pneumococcal pneumonia was significantly
reduced by 80 % in patients younger than 65 years
and also in those patients with severe airflow limitations
(FEV1 \40 % of predicted), but the risk was not reduced in
COPD patients 65 years of age or older [154]. The GOLD
guidelines stress the importance of pneumococcal vacci-
nations for all COPD patients. The CDC recommendations
suggest a second vaccination 5 years after the original
[152]. The CDC Advisory Committee on Immunization
Practices as of June 2012 is recommending the routine use
of the 13-valent pneumococcal conjugate vaccine in eli-
gible immunocompromised adults including COPD
patients on long-term systemic steroids. This vaccination is
in addition to the currently recommended 23-valent pneu-
mococcal polysaccharide vaccine [155]. The new 13-valent
pneumococcal conjugate vaccine succeeds the 7-valent
pneumococcal conjugate vaccine used in children between
the ages of 6 weeks and 71 months in the USA. It includes
the capsular polysaccharide antigens of serotypes 1, 3, 4, 5,
6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F all individ-
ually conjugated to a non-toxic diphtheria CRM 197 carrier
protein, which was used in the older 7-valent product
[156]. There is some evidence that in adults, the conjugated
7-valent or the 13-valent pneumococcal vaccine in com-
bination with the 23-valent pneumococcal polysaccharide
vaccine is more effective in immunocompromised patients
[155]. The use of this product combination has not been
widespread and no trials to date in immunocompromised
COPD patients have been reported. In pneumococcal
vaccine-naive immunocompromised patients, the recom-
mendation is that the 13-valent product should be given
first and then followed by the 23-valent vaccination at least
8 weeks later. If patients have previously been vaccinated
with the 23-valent product, the 13-valent vaccination
should be done a year or more later. Elderly COPD patients
who are not immunocompromised are still recommended
by the CDC only to be vaccinated with the 23-valent
pneumococcal vaccine [155]. Others have advocated
for only the use of the conjugated 13-valent vaccine in
older patients [157–159]. The Joint Committee on Vacci-
nation and Immunization of the UK (JCVI) has recom-
mended discontinuing the routine use of the 23-valent
494
pneumococcal vaccine in patients older than 65 years, but
did not substitute it with the conjugated 13-valent vaccine
[160].
Highly infectious pertussis-like illnesses caused by
Bordetella pertussis and similar organisms (i.e., Bordetella
holmesii/Bordetella parapertussis) are associated with a
persistent cough and may include the classic ‘‘whoop’’
sound lasting up to 3 months. In recent outbreaks in the
states of Washington and Ohio, the vast majority of the
cases were less than 20 years old [161, 162]. Pertussis
clusters and outbreaks have been reported in adults
including recent outbreaks of B. pertussis among oncology
nurse specialists in the UK [163]. A 71-year-old, unim-
munized social contact of one of the primary cases of
pertussis was infected. Although no specific trials of B.
pertussis vaccination have been reported in COPD patients,
there is evidence that pertussis can have a role in acute
asthma exacerbations [164]. On the basis of serologic
evidence, B. pertussis has also been associated with exac-
erbation of chronic bronchitis [165].
A one-time (tetanus, diphtheria, and acellular pertussis)
TDaP vaccination is estimated to reduce the incidence of
pertussis by 44 % over a 10-year period [152]. A review of
vaccinations in adult asthma and COPD patients endorsed
by the CDC recommends that adults between the ages of 19
and 64 years should have one dose of TDaP [152].
3.8 Pulmonary Rehabilitation
The use of pulmonary rehabilitation in older elderly
patients with COPD has been shown to improve their
exercise capacity [166, 167]. In a recent Cochrane meta-
analysis of nine trials including 432 COPD patients
undergoing pulmonary rehabilitation of variable durations
compared to usual care, there was a significant mortality
reduction over 107 weeks in those patients enrolled in
pulmonary rehabilitation (OR 0.28, 95 % CI 0.10–0.84;
number needed to treat 6, 95 % CI 5–30) [168]. There still
exists some controversy about the utility of pulmonary
rehabilitation in the elderly COPD patient, but its use
remains generally accepted in those elderly patients capa-
ble of participating in a program [169, 170]. An evidence-
based analysis of pulmonary rehabilitation in COPD
patients included 17 randomized controlled trials of mod-
erate quality of evidence and concluded that programs of at
least 4 weeks of exercise training lead to clinically and
statistically significant improvement in health-related
quality of life, functional exercise capacity, and hospital
readmission rates [171]. Pulmonary rehabilitation should
be considered for every COPD patient without regard to
age. Comorbidities including both physical and mental
limitations should be evaluated in the elderly COPD patient
before committing them to a program.
T. E. Albertson et al.
3.9 Non-Invasive Ventilation
Non-invasive mechanical ventilation (NIMV) is a useful
treatment in hypoxemic respiratory failure and reduces the
need for endotracheal tube placement and invasive mechani-
cal ventilation (IMV) [172]. In a series of elderly (mean age
81 ± 4.8 years) patients with hypercapnia in which the
majority (50/62) had COPD, treatment with NIMV resulted in
successful avoidance of IMV in the majority of patients with a
12.9 % failure rate (death or the need for IMV) [173]. A recent
randomized controlled study evaluated NIMV in 82 elderly
(mean age 81 ± 3.5 years) patients with chronic pulmonary
disease and hypercapnic respiratory failure against standard
medical therapy [174]. Both the mortality (OR = 0.40, 95 %
CI 0.19–0.83, P = 0.014) and the rate of patients meeting
endotracheal tube intubation criteria (7.3 vs. 63.4 %,
P \ 0.001) were significantly reduced in the NIMV treatment
group compared to the standard medical treatment group.
NIMV should be considered an alternative to early endotra-
cheal intubation and IMV in elderly COPD patients and in
selected ‘‘do not intubate’’ elderly COPD patients.
3.10 Treatment Guidelines
The diagnosis and treatment of the COPD patient are out-
lined in several national, regional, and global guidelines
[1, 4, 175, 176]. A review of new inhalational therapies
notes that prescribing aerosol treatment to the elderly
patient has many similar problems to prescribing to children
[177]. Cognitive and dexterity limitations should be taken
into account and more complex maneuvers that may be
challenging to the elderly should be avoided. The clinician
should only prescribe a delivery system that the elderly
patient can and will use effectively. A stepwise or pyramid
approach is common to all the treatment guidelines. As the
severity of the physiological alterations and symptoms in
COPD increase, the more the interventions and medications
are layered in for the patient [178]. Figure 3 offers a hybrid
pyramid of current recommendations for the treatment of
the COPD patient with increasing interventions as the dis-
ease severity increases.
4 Palliative Care and End-of-Life Issues
In a retrospective study of the last year of life of 209
Londoners who died from COPD, the average age was
76.8 years, 98 % were breathless all or some of the year,
96 % noted fatigue or weakness, 77 % had low mood, and
70 % reported pain [179]. These investigators concluded
that patients who died from COPD lacked surveillance,
care coordination, and received inadequate services in the
year before their death.
Treatment of the Elderly COPD Patient
Fig. 3 The COPD pyramid of treatment. Adapted from the Canadian
Thoracic Society and GOLD guidelines [4, 205]. LVRS lung volume
reduction surgery including endobronchial approaches, LTS lung trans-
plant surgery, LABA long-acting b2-agonist, CS inhaled corticosteroid,
LAMA long-acting muscarinic antagonist, SABA short-acting b2-agonist,
SAMA short-acting muscarinic antagonist, Vaccinations annual influ-
enza, pneumococcal, and pertussis vaccinations, OCS oral corticoste-
roids, Theo theophylline, Roflum roflumilast, Azith azithromycin
The need for coordinated and multidisciplinary palliative
care at the end-of-life of elderly COPD patients that addresses
breathlessness is clearly needed [180]. In a prospective com-
munity survey and interview study of 128 COPD patients
(mean age 72 years) in London, 57 % had severe breathless-
ness, 92 % said breathlessness was their most important prob-
lem, and 21 % felt they were on suboptimal treatment [181].
Elderly patients with COPD have been shown to have worse
dyspnea and poorer quality of life than many patients with
cancer [182, 183]. Early discussions with the elderly patient
about end-of-life issues and palliative approaches are needed
before the terminal phase of COPD [184]. Standard approaches
to dyspnea in the COPD patient include oxygen therapy, but
may include opioids and anxiolytics. The last two are more
generously and commonly used in conjunction with a palliative
medicine approach in treating severe COPD because of the risk
of increasing carbon dioxide retention. The American Thoracic
Society guidelines for treating end-stage respiratory disease and
critically ill patients stress the importance of palliative care in
COPD [185]. Integrating palliative care into the management of
the severe COPD patient is a realistic goal [186].
4.1 Opioids and Anxiolytics
As noted, breathlessness is a significant problem in elderly
patients with severe or end-stage cases of COPD. A sys-
tematic review of the use of opioids in 18 double-blind,
randomized, placebo-controlled trials of the treatment of
dyspnea in COPD patients were included in the analysis.
Nine of the trials used oral or parenteral opioids including
morphine subcutaneous, dihydrocodeine oral, diamorphine
oral, and slow-release morphine oral. The nine studies on
495
nebulized opioids used morphine. The meta-analysis
showed a statistical reduction (P = 0.0068) in breathless-
ness with the use of opioids. The meta-regression revealed
a greater effect (P = 0.02) with oral/parenteral opioids
than with nebulized opioids [187]. A specific subgroup
analysis also failed to show improvement in breathlessness
after nebulized opioid treatment in severe COPD patients.
A recent small study of 16 patients with COPD (average
age 70.5 ± 7.3 years) demonstrated that a single inhaled
dose of fentanyl citrate improved exercise endurance without
changing dyspnea or measured spirometric or plyethysmo-
graphic lung volumes [188]. Side effects of oral/parenteral
opioid treatment include constipation, drowsiness, nausea,
and anorexia. Bitter taste, cough, and a ‘‘pricking’’ sensation
in the throat have been reported with nebulized opioids.
Statistical increases in the partial pressure of arterial carbon
dioxide (pCO2) were found in one study that measured it
after oral opioids, but these were not clinically concerning
increases and none had elevated arterial pCO2 determina-
tions at the beginning. Nine of the 18 studies reported oxygen
saturations and none reported a significant change during the
study [187]. The use of opioids in severe COPD patients with
baseline pCO2 elevations comes with the risk of increasing
their narcotizing effect by encouraging further carbon
dioxide retention. Potentially off-setting the central nervous
system’s negative effects is the possible advantage of
slowing the respiratory rate in those patients reducing breath
stacking and allowing more time for exhalation. The overall
effect of reducing dynamic hyperinflation may be improved
ventilation and exercise tolerance, but this can be difficult to
predict in a patient with severe COPD. As a result, routine
use of opioids for breathlessness in COPD patients is
reserved for those in a palliative medicine program.
A Cochrane systematic review has evaluated the use
of benzodiazepines in breathlessness associated with
advanced stages of cancer, idiopathic fibrosis, chronic heart
failure, motor neuron disease, and COPD [189]. They only
found seven studies with about 200 patients that had either
advanced cancer or COPD. In these patients, no beneficial
effect was found in reducing breathlessness with benzodi-
azepines or in preventing breakthrough dyspnea. To date,
no evidence of routine relief of breathlessness exists in
patients with advanced cancer or COPD [189].
4.2 Systemic Anticholinergics/Antimuscarinic Agents
The use of tertiary amine antimuscarinic agents in the
treatment of COPD historically included nebulized or
smoked atropine and Datura stramonium, but their use was
limited by the systemic effects including dilated pupils,
urinary retention, and tachycardia. This resulted in the
development of antimuscarinic quaternary amine agents
such as ipratropium bromide that is less likely to cross
496
biological membranes and manifest systemic symptoms. In
the treatment of severely disabled and hospice patients, the
tertiary amine scopolamine (hyoscine), often as a patch,
has been used to decrease drooling and reduce noisy res-
pirations (‘‘death rattle’’) in hospice patients [190–192].
This noisy breathing is thought to be caused by inspiratory
and expiratory movement of respiratory secretions in the
upper and lower airway. The drying effects of antimu-
scarinic agents seem to improve this situation and in the
dying COPD patient, they actually also provide a second-
ary bronchodilation effect. The central nervous system
(CNS) complications of tertiary amine anticholinergic/
antimuscarinic agents have led to evaluating glycopyrro-
late, which is another quaternary amine antimuscarinic
agent that is associated with less CNS effects. No consis-
tent advantage was noted in its use in palliative care
patients [193–196]. Since the use of these agents is pri-
marily symptom control, the limited data in the palliative
care patients does not focus on their secondary broncho-
dilator effects nor does it justify their use in this patient
population as bronchodilators.
5 Conclusion
The elderly COPD patient represents an increasingly pre-
valent challenge, particularly in diagnosis and pharmaco-
therapy to help reduce symptoms and decrease the risk of
acute exacerbations from their disease and associated
comorbidities. New and improved drug delivery devices and
medications have increased therapeutic options for the elderly
patient. Smoking cessation remains a cornerstone therapy and
should be initiated as soon as possible. New oral medication
options now exist and adjunctive approaches such as LTOT
and pulmonary rehabilitation remain important. Infection
control with timely vaccinations can help reduce morbidity
and mortality from influenza and pneumococcal pneumonia.
Palliative approaches that focus on symptom improvement
should be considered early in the course of COPD manage-
ment in concert with appropriate pharmacotherapy and defi-
nitely for the end-stage elderly COPD patient.
Acknowledgments S. Louie has received payment for lectures and
is on the Speaker’s Bureaus for AstraZeneca, Boehringer-Ingelheim,
Forest, GlaxoSmithKline, and Pfizer. M. Avdalovic is a paid speaker
for Novartis. T. Albertson is a paid speaker for GlaxoSmithKline.
A. Chan is a paid speaker for Forest, Intermune, Gilead, and Boeh-
ringer-Ingelheim. The other authors have nothing to disclose.
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