Download Chronic obstructive pulmonary disease in the elderly

Asian J Gerontol Geriatr 2013; 8: 90–7
Chronic obstructive pulmonary
disease in the elderly: evaluation
and management
REVIEW ARTICLE
P Tayde, MD, S Kumar, MD
ABSTRACT
Chronic obstructive pulmonary disease (COPD) is a leading cause of
mortality and morbidity in older adults worldwide. It can be exacerbated
by other chronic and acute health problems (myocardial infarction,
angina, osteoporosis, respiratory infection, depression, diabetes, and
lung cancer). Although the prevalence of COPD in the elderly is high, it is
often undiagnosed and thus undertreated. Diagnosis is primarily based
on physiological airflow limitation using spirometry. Controversies exist
as to the range of predicted normal values in the elderly, in whom its
clinical presentation may be complicated by other comorbidities. Many
non-pharmacological and pharmacological interventions are available
for managing COPD. However, polypharmacy may pose a challenge
to the management of COPD, as it can interfere with compliance to
optimal therapy. This article highlights the evaluation of COPD in the
elderly and its management.
Key words: Aged; Disease management; Medication therapy management;
Pulmonary disease, chronic obstructive
INTRODUCTION
Chronic obstructive pulmonary disease (COPD) is
characterised by the slowly progressive impairment of
airflow such that symptoms are usually not exhibited
until the age of 55 years, and mortality usually
occurs after the age of 65 years. Manifestations of
COPD include dyspnoea, poor exercise tolerance,
chronic cough with or without sputum production,
wheezing, respiratory failure, and cor pulmonale.
Exacerbations and concomitant chronic diseases may
increase symptom severity, especially in the elderly,
in whom COPD is a common chronic condition. It is
associated with significant morbidity and mortality
and is the fourth leading cause of death in the
world. By 2020, the disease is expected to be the
third leading cause of death worldwide.1 The Global
Initiative for Lung Disease (GOLD) guideline has
defined COPD as a preventable and treatable disease
with significant extra-pulmonary effects that may
90
Department of Medicine, Jawaharlal Nehru
Medical College, Datta Meghe Institute
of Medical Sciences, Sawangi, Dt Wardha,
Maharashtra, India
Correspondence to: Dr Parimal Tayde,
Department of medicine, Datta Meghe
Institute of Medical Sciences, Sawangi, Dt
Wardha, Maharashtra, 442001, India. Email:
[email protected]
contribute to its severity in individuals. Its pulmonary
component is characterised by irreversible airflow
limitation, which is progressive and associated with
an abnormal inflammatory response of the lungs to
noxious particles or gases. Despite the increasing
burden of COPD in older people, underdiagnosis
and undertreatment is common.
GLOBAL INITIATIVE FOR LUNG
DISEASE GUIDELINES
The degree of airflow obstruction is an important
prognostic factor in COPD and the basis for the
GOLD redundant classification (Table 1). A
multifactorial index—the BODE index (for body
mass index, obstruction, dyspnoea, and exercise
capacity)—is a better predictor of mortality than
pulmonary function alone. The BODE index
discriminates mortality better than FEV1 alone.2
Scores range from 0 to 10 (most impaired) and are
Asian Journal of Gerontology & Geriatrics Vol 8 No 2 December 2013
Chronic obstructive pulmonary disease in the elderly
Table 1
Global Initiative for Lung Disease stages for chronic obstructive pulmonary disease severity
Stage
Severity
Symptoms
Spirometry
I
Mild
With or without chronic cough or sputum production
FEV1/FVC of <0.7 and FEV1 of >80% predicted
II
Moderate
With or without chronic cough or sputum production
FEV1/FVC of <0.7 and FEV1 of 50-80% predicted
III
Severe
With or without chronic cough or sputum production
FEV1/FVC of <0.7 and FEV1 of 30-50% predicted
IV
Very severe
With or without chronic cough or sputum production
FEV1/FVC of <0.7 and FEV1 of <30% predicted or
FEV1 of <50% predicted with respiratory failure or signs
of right heart failure
stratified into 4 stages:
exacerbations in the previous year.
Stage I (mild COPD): it is characterised by mild
airflow limitation (FEV1/FVC, <0.70; FEV1, >80%
predicted) with or without symptoms.
Stage II (moderate COPD): it is characterised by
worsening airflow limitation (FEV1/FVC, <0.70;
FEV1, 50-80% predicted) with dyspnoea on
exertion and cough and sputum production may
be present. Patients usually seek medical attention
because of symptoms or an exacerbation.
Stage III (severe COPD): there is further
worsening of airflow limitation (FEV1/FVC, <0.70;
FEV1, 30-50% predicted), increased shortness of
breath, reduced exercise capacity, and repeated
exacerbations.
Stage IV (very severe COPD): there is severe
airflow limitation (FEV1/FVC, <0.70; FEV1, <30%
predicted or <50% predicted with the presence of
chronic respiratory failure or signs of right heart
failure). Clinical signs of cor pulmonale are raised
jugular venous pressure and pedal oedema.
In the recent revision of the GOLD strategy,
the concept of spirometric stages is replaced by
spirometric grades because the level of FEV1 alone
incompletely predicts disease status. A composite
measure of the level of symptoms and frequency of
exacerbations is added to FEV1 to categorise patients
into 4 groups:
Group A (low risk, fewer symptoms) includes
patients with an FEV1 of >50% (grade 1 or
2) and low level of symptoms based on the
COPD Assessment Test (CAT) score of <10,
or the modified Medical Research Council
(mMRC) Dyspnea Scale score of <2, and 0 to 1
Group B (low risk, more symptoms) includes
patients with an FEV1 of >50% and 0 to
1 exacerbations in the previous year but
symptomatic with a CAT score of >10 or a mMRC
Dyspnea Scale score of >2.
Group C (high risk, fewer symptoms) includes
patients with an FEV1 of <50% and a CAT score
of <10 or a mMRC Dyspnea Scale score of <2, but
with ≥2 exacerbations in the previous year.
Group D (high risk, more symptoms) includes
patients with an FEV1 of <50%, a CAT score of
>10 or a mMRC Dyspnea Scale of >2, and ≥2
exacerbations in the previous year.
The CAT and the mMRC Dyspnea Scale are
validated tools that assess symptoms and correlate
with the Saint George’s Respiratory Questionnaire,
a widely used quality-of-life instrument in COPD
research. The CAT is an 8-item questionnaire with
scores ranging from 0 to 5 for each question (total
range, 0-40) with a score of >10 being abnormal.
This test is easier to administer and correlates more
strongly with outcome measures in COPD patients
than does FEV1. It is adopted in the new GOLD
strategy approach to assess severity and grade
patients with COPD.3
SPECIAL CONSIDERATIONS IN OLDER
PATIENTS
COPD at any age may have reversible airflow
obstruction that can be assessed and treated in a
similar manner in both young and elderly patients.4
This hidden reversible obstructive component must
first be suspected before appropriate evaluation and
treatment can be initiated. In studies of older patients
Asian Journal of Gerontology & Geriatrics Vol 8 No 2 December 2013 91
Tayde and Kumar
with COPD, only 6 to 12% received bronchodilator
therapy even though as many as 40% demonstrated
reversible disease.5,6 This suggests that the reversible
component of COPD is commonly overlooked in the
elderly. In elderly patients with COPD, dyspnoea may
be attributed to old age, being out of shape, smoking
too many cigarettes, and comorbid illnesses such as
ischaemic heart disease, osteoporosis, depression,
diabetes, and lung cancer. Thus, COPD patients may
be deprived of improvement in their functional status
and quality of life and lead to secondary ageing.6
Old age and comorbidity are partly responsible
for the misdiagnosis and under treatment of COPD
in older adults. There is a disparity between practice
guidelines and their implementation. This results
in fewer subjects having spirometry and blood
gas analysis annually and receiving respiratory
medications and ventilatory support.7 Older adults
with COPD generally have a poor health status
because of chronic comorbidities and limitations in
activities of daily living. Up to 25% of population
aged >65 years suffer from 2 comorbid conditions,
and up to 17% have 3, and >50% of deaths in COPD
patients are caused by non-respiratory diseases.8
Diagnostic difficulty in relation to age-related
decline in lung function
Ageing causes decline in lung function, which
may be due to structural changes to the thoracic
cage leading to reduced chest wall compliance,
an example being kyphosis. Another reason may
be calcification of rib cartilages which stiffen the
thoracic cage and impair chest wall expansion as
well as the action of the diaphragm.9 Diaphragmatic
strength is reduced by 25% in healthy older people
compared to young adults.10 The ageing process
involves the degeneration of the elastic fibres around
the alveolar ducts resulting in air trapping and senile
hyperinflation.11 Age is inversely related to respiratory
muscle strength and pulmonary function.12 There is
no correlation between age and total lung capacity,
but functional residual capacity and residual
volume increase with age. Small airway calibre may
decline progressively with age. Thus, COPD is more
prevalent in very elderly populations.13
Diagnostic difficulty in older patients related to
spirometry testing
Spirometry is an important part of the diagnostic
workup of patients with COPD. It can be performed
92
adequately in most elderly people. However, a
proportion of such patients, particularly those aged
>75 years do not perform full spirometry reliably
owing to impairment of cognitive, ideo-motor,
and executive function, all of which affect inhaler
technique.14,15 For testing cognitive function, the
Mini-Mental State Examination (MMSE) and its
intersecting pentagon-copying component (IP)
has high specificity but with moderate sensitivity.16
The clock drawing tests (CLOX1 and 2) have an
embedded executive and ideo-motor component
and are validated for use in elderly patients. The
CLOX1 asks the subject to draw a clock face on a
paper and hence tests for executive dyscontrol in
a novel and ambiguous situation, whereas CLOX2
requires the subject to copy a clock face and hence
tests his ability to understand and plan a welldefined action and then carry it out accurately and
completely. Patients with a MMSE score of <24/30
or inability to copy overlapping pentagons are rarely
able to perform adequate spirometry. The MMSE and
copying overlapping pentagons are more useful than
CLOX for predicting inability to perform spirometry
in old age. Performing spirometry reliably appears
to be more dependent on intact global cognitive
function and ideo-motor praxis than on executive
control function.17
MANAGEMENT
The management of elderly patients with COPD
should encompass a multidisciplinary approach.
In addition to the assessment of lung ventilatory
performance and functional impairment, nutritional
status, and mental health should be evaluated.
Underlying comorbidities should also be evaluated
and treated. Therapy for COPD should start with
cessation of tobacco smoking. Smoking cessation
rates in the elderly have not declined. This may
reflect an underlying reluctance by physicians to
counsel and offer smoking cessation therapies to
the elderly. In contrast to prolonged oxygen therapy,
bronchodilators and corticosteroids do not decrease
mortality and are primarily used for symptom
relief. In old age, oxygen therapy has a beneficial
effect on quality of life and exacerbation rates. The
choice of delivery devices for inhaled medications
is important; patients should be properly trained to
use an inhaler and their dexterity should be assessed
frequently. Pulmonary rehabilitation and nutritional
supplementation are other important components of
Asian Journal of Gerontology & Geriatrics Vol 8 No 2 December 2013
Chronic obstructive pulmonary disease in the elderly
comprehensive care.
Elderly patients with COPD require special
attention
Because of the high susceptibility of older people
to disease, medication use is extensive and the
number taken daily increases progressively with age.
Prescribing for older subjects is a complex issue as
their behaviour towards medications and their effects
vary according to the health of the patient, the route of
drug metabolism/elimination, and its intrinsic safety.
Five key steps have been identified in prescribing:
determine evidence of efficacy in older subjects;
assess the likelihood of adverse drug events; discuss
the harm/benefit analysis with the patient; decide on
the dose, formulation, and delivery of the medication,
and monitor the patient very carefully.18 The process
of ageing can influence pharmacodynamic responses
as well as pharmacokinetics (absorption, distribution,
metabolism, and excretion of drugs).
Bronchodilators and anti-inflammatory drugs
These constitute the mainstay of the pharmacological
treatment for COPD. Bronchodilators currently used
as regular treatment and recommended in the GOLD
guidelines include a long-acting anticholinergic
(i.e. tiotropium) and long-acting beta agonists (i.e.
salmeterol and formoterol). Anti-inflammatory drugs
like inhaled corticosteroids are available, including
fluticasone propionate, budesonide, beclomethasone
dipropionate, flunisolide, triamcinolone, and
mometasone.
Tiotropium
Tiotropium is a long-acting antagonist of muscarinic
receptors. It undergoes minimal metabolism, as
74% of an intravenous dose is excreted unchanged
by the kidneys. After inhalation, 14% of the dose is
excreted unchanged in the urine, where it undergoes
active tubular secretion; the remainder (presumably
non-absorbed drug) is eliminated in the faeces. The
renal clearance and urinary excretion of tiotropium
is reduced in patients with renal impairment and
those of advanced age. Increasing age is associated
with reduced renal function. There is no study on the
effect of age and severe renal or hepatic impairment
on tiotropium pharmacokinetics.19
Beta agonists
Salmeterol and formoterol are commonly used by
inhalation. In older patients with COPD or hepatic
disorder, the pharmacokinetics of both drugs are
not well known. It is interesting to evaluate whether
the pulmonary distribution and absorption of
the inhaled drugs change in older patients with
COPD because of the impaired airway function.20
The beta adrenergic response to beta 2–agonists
decreases with increasing age. There are changes in
the beta adrenergic system in older people. Ageing
is associated with the down-regulation of beta
adrenergic receptors, elevated plasma noradrenaline
levels, and a reduced cAMP production in response
to beta adrenergic stimulation.21 A down-regulation
of beta 2–adrenergic receptors may also explain why
higher concentrations of these drug are needed to
produce a desired effect with increasing age. The
response to salbutamol also declines significantly
with age.22
Inhaled corticosteroids
Inhaled corticosteroids are widely used in COPD,
as they enable the delivery of steroids to the lung,
with minimal systemic side-effects. Most of the
inhaled dose is deposited in the oropharynx and is
then swallowed. Subsequently, the drug is absorbed
from the gastrointestinal tract and is subject to
first-pass metabolism in the liver. A much smaller
fraction of the delivered dose reaches the airways
and the systemic circulation if not removed by
mucociliary clearance. The pharmacodynamic effects
of inhaled corticosteroids are influenced by the
local concentration within the airways. Fluticasone
propionate has the greatest degree of topical
potency, followed by budesonide, beclomethasone
dipropionate, triamcinolone, and flunisolide.23-25
There is no study evaluating the effects of inhaled
steroids in very elderly persons.
Polypharmacy in elderly
Older people are the major consumers of drugs,
owing to increasing number of chronic diseases
with advancing age. On average, the elderly take
2 to 9 prescription medications daily.26-30 Factors
predisposing to such polypharmacy are poorer health,
multiple chronic diseases, multiple prescribing
physicians, therapeutic advances, expectations of
the patient, education, increasing demands for
health care, supplemental insurance, and reluctance
to discontinue old medications. Polypharmacy
increases the risk of inappropriate medications, nonadherence to treatments, morbidity, mortality, and
adverse drug reactions.31-33 Inappropriate prescription
Asian Journal of Gerontology & Geriatrics Vol 8 No 2 December 2013 93
Tayde and Kumar
in the elderly is an emerging health issue. It entails
inappropriate dose, formulation, duration, and drug
delivery. It also includes the use of unnecessary drugs,
the omission of necessary medicines, and possible
drug interactions and adverse effects. A populationbased cohort study found that 20% of ambulatory
older adults were prescribed at least 1 inappropriate
drug per year.34 Inappropriate medications are
detected according to various screening tools for the
assessment of the quality and safety of prescriptions,
for example the screening tool of older persons’
potentially inappropriate prescription (STOPP)
and the screening tool to alert doctors to the right
treatment (START) [Table 2].35
Smoking cessation
Smoking cessation is the most important means
of preventing and treating COPD. It slows the
progression of COPD and the rate of FEV1 decline.The
main interventions to stop smoking are behavioural
modification programmes and pharmacologic
agents (nicotine replacement products, atypical
antidepressants, bupropion). They reduce the severity
of nicotine cravings and withdrawal symptoms. A
combination of pharmacologic and behavioural
approaches and frequent maintenance visits are
helpful and enable better smoking cessation rates.36
Nicotine replacement is available as chewing gums,
inhalants, lozenges, patches, and sprays. Treatment
regimens include the use of transdermal patches,
usually starting at a dose of 21 mg/day for 4 to 6
weeks for at least 8 weeks, with a gradual taper;
supplementation with other short-acting nicotine
replacement products can be used as needed to
alleviate cravings.37 Sustained release bupropion is
also effective, although the likelihood of sustained
abstinence among patients with COPD is lower
with bupropion than with nicotine replacement.
Bupropion can lower the seizure threshold and
is contraindicated in elderly patients with seizure
disorders, those with liver or renal impairment
and when co-prescribed with drugs that cause
lowering the seizure threshold (antidepressants,
antipsychotics, systemic corticosteroids, theophylline,
and tramadol).37
Pulmonary rehabilitation
Pulmonary rehabilitation has an important role in
improving exercise capacity, dyspnoea, and quality of
life. It reduces hospitalisations and health care cost.
It is beneficial as adjunct treatment in patients whose
symptoms are not responding to drug therapy. It is
most effective when delivered as a comprehensive
education programme about disease, physical
training, psychosocial counselling, and nutritional
support.38
Mode of therapy
Inhaled bronchodilator therapy is the mainstay of
treatment in the management of COPD. Although
available in various formulations (metered
dose inhaler [pMDI]/dry powder inhaler [DPI]
or nebulised), the MDI is the most commonly
prescribed.39 Therapeutic benefit depends on
adequate airway drug deposition. Inhaler technique
is crucial but sub-optimal in many patient groups,
particularly the elderly.40 Arthritis, weakness, poor
manual dexterity, and visual limitations are potential
problems affecting inhaler use in the elderly.41
More patient-friendly devices such as breathactuated DPIs have been developed. In general,
DPIs require a higher peak inspiratory flow (PIF)
than MDIs for effective drug delivery, as a minimum
Table 2
Inappropriate prescription for patients with chronic obstructive pulmonary disease (COPD): criteria for the screening tool to
alert doctors to the right treatment (START) and the screening tool of older persons’ prescriptions (STOPP)
STOPP
START
Drug prescriptions potentially inappropriate in persons
aged ≥65 years:
Medications for people aged ≥65 years with the following conditions when
no contraindication to prescription exists:
• Theophylline as monotherapy for COPD
• Systemic corticosteroids instead of inhaled
corticosteroids for maintenance therapy in moderate-tosevere COPD
• Nebulised ipratropium with glaucoma
• Regular inhaled beta 2–agonist or anticholinergic agent for mild-tomoderate asthma or COPD
• Regular inhaled corticosteroid for moderate-to-severe asthma or COPD
when FEV1 is <50% predicted
• Continuous oxygen at home with documented chronic type 1 (pO2 <8.0
kPa and pCO2 <6.5 kPa) or type 2 (pO2 <8.0 kPa and pCO2 >6.5 kPa)
respiratory failure
94
Asian Journal of Gerontology & Geriatrics Vol 8 No 2 December 2013
Chronic obstructive pulmonary disease in the elderly
inspiratory flow is required to disaggregate and
disperse the drug powder in the inhaled air-stream.
Data are limited regarding the percentage of patients
with COPD who can achieve the minimum PIF to
use these devices satisfactorily. In elderly patients
with COPD, only 25% generated the minimum
recommended PIF for the highest resistance device.
Even when in a stable clinical condition, elderly
patients with COPD may be unable to gain optimum
benefit from their inhaler.42
Nebulisers are frequently used to deliver
bronchodilators in elderly patient. Elderly patients
are more able to inhale the medications from these
devices than from MDIs or DPIs. Drug delivery via
an MDI linked to a spacer or nebuliser improves
FEV1, FVC, and dyspnoea, equally without effects on
heart rate and diastolic blood pressure.43
Supplemental oxygen therapy
Supplemental oxygen for ≥15 hours per day reduces
the mortality.44 Medicare guidelines recommend
that oxygen therapy should be initiated in stable
patients if the resting arterial partial pressure of
oxygen is <55 mm Hg or if the oxygen saturation
is <88%. Long-term oxygen therapy (>15 hours
per day) increases survival in COPD patients with
respiratory failure and severe resting hypoxaemia.
Supplemental oxygen significantly improves exercise
tolerance even in patients in whom desaturation
does not occur during exercise.45
Indications for long-term oxygen therapy are:
resting PaO2 of <55 mm Hg, resting PaO2 of 56 to 59
mm Hg with either right heart failure (e.g. dependent
oedema or P pulmonale on electrocardiography) or
polycythaemia (haematocrit of 56%). Supplemental
oxygen should be adjusted to maintain an oxygen
saturation of at least 90%.46
Nutrition support
According to the European Society for Parenteral
and Enteral Nutrition guidelines,47 enteral nutrition
in combination with exercise and anabolic
pharmacotherapy may improve nutritional status and
function in COPD patients. Frequent small amounts
of oral nutritional supplements are preferred in order
to avoid postprandial dyspnoea and satiety and
improve compliance. Nutritional supplementation
may have a role in the management of COPD when
provided as part of integrated rehabilitation that
incorporates a structured exercise component as
an anabolic stimulus.48 Ghrelin is a novel growth
hormone–releasing peptide that also induces a
positive energy balance by decreasing fat utility
and stimulating feeding through growth hormone–
independent mechanisms. Plasma ghrelin levels
decrease in COPD patients, in contrast to other
weight-loss diseases.49 Repeated administration of
ghrelin improves body composition and functional
capacity, reduces muscle wasting, and enhances
sympathetic augmentation in cachectic patients with
COPD.50
Palliative and end-of-life care
Palliative care aims to prevent and relieve suffering
by controlling symptoms and to provide support
to patients and families in order to maintain and
improve their quality of living. Smoking cessation
and long-term oxygen therapy improve survival as
well as quality of life in COPD patients. Long-term
oxygen therapy (>18 hours per day) increases survival
in hypoxaemic COPD patients.51 Non-invasive
positive pressure ventilation delivered through nasal
or face mask avoids the risks associated with invasive
ventilation. It is an alternative to invasive ventilation
for symptom relief in end-stage COPD.51 A European
survey of respiratory intermediate care reported its
frequency of use and its role in almost a third of the
patients with poor life expectancy.52 The Society of
Critical Care Medicine developed an approach for
considering its use for patients who choose to forego
endotracheal intubation. As a palliative measure,
non-invasive positive pressure ventilation may be
appropriate when patients and families have chosen
to forego all life support and receive only comfort
measures. However, palliative care comes up against
important difficulties such as an indefinite beginning
of the palliative stage in COPD; insufficient palliative
care resources; insufficient communication and
insufficient utilisation of palliative care resources. All
these can be overcome by long-term oxygen therapy
and non-invasive positive pressure ventilation to
some extent.
CONCLUSION
COPD is a major public health problem that affects
a large proportion of the elderly. Its diagnosis is
complicated by the fact that many such patients
ignore or tolerate their symptoms and do not seek
medical attention. Management of COPD should
Asian Journal of Gerontology & Geriatrics Vol 8 No 2 December 2013 95
Tayde and Kumar
focus on smoking cessation and implementing
both non-pharmacological and pharmacological
interventions. Owing to the cumulative risks
related to COPD and ageing, several diagnostic and
management issues specific to the elderly need to be
considered, including pharmacological side-effects,
decreased physical and social autonomy, nutritional
impairment, and comorbidities. Given the lack of
specific data in elderly populations, pharmacological
indications are generally the same as in younger
populations, but additional precautionary measures
are necessary. Elderly COPD patients may have
problems with physical coordination and/or may
be cognitively impaired and unable to use a MDI
or DPI. It is essential to ensure that inhalation
device technique is correct, especially when disease
worsening is detected, and to undertake efforts to
correct the technique or change to a more appropriate
device as part of symptom management. Palliative
care can be difficult to apply, but can be managed by
long-term oxygen therapy and non-invasive positive
pressure ventilation. Global COPD management in
the elderly requires coordination, best reached in
health care network organisations involving medical
and/or social professionals. In addition, the course
of COPD in elderly patients is often complicated by
multiple comorbidities that need to be addressed to
optimise treatment outcomes.
REFERENCES
1. Global Initiative for Chronic Obstructive Lung Disease. Available at:
http://www.goldcopd.org. Updated 2011.
2. Reilly JJ, Silverman EK, Shaprio SD. Chronic obstructive
pulmoanary disease. In: Fauci A, Braunwald E, Kasper D, editors.
Harrison’s principles of internal medicine, 17th ed. New York:
McGraw-Hill; 2008:1640.
3. Jones PW, Harding G, Berry P, et al. Development and first
validation of the COPD Assessment Test. Eur Respir J 2009;34:64854.
4. Dow I, Holgate ST. Assessment and treatment of obstructive
airways disease in the elderly. Br Med Bull 1990;46:230-45.
5. Webster JR, Kadah H. Unique aspects of respiratory disease in
the aged. Geriatrics 1991;46:31-43.
6. Banerjee DK, Lee GS, Malik SK, Daly S. Underdiagnosis of
asthma in the elderly. Br J Dis Chest 1987;81:23-9.
7. Craig BM, Kraus CK, Chewning BA, Davis JE. Quality of care
for older adults with chronic obstructive pulmonary disease
and asthma based on comparisons to practice guidelines and
smoking status. BMC Health Serv Res 2008;8:144.
8. Holguin F, Folch E, Redd SC, Mannino DM. Comorbidity and
mortality in COPD-related hospitalizations in the United States,
1979 to 2001. Chest 2005;128:2005-11.
9. Valente S, Pasciuto G, Bernabei R, Corbo GM. Do we need
different treatments for very elderly COPD patients? Respiration
2010;80:357-68.
10. Enright PL, Kronmal RA, Manolio TA, Schenker MB, Hyatt
96
RE. Respiratory muscle strength in the elderly. Correlates and
reference values. Cardiovascular Health Study Research Group.
Am J Respir Crit Care Med 1994;149:430-8.
11. Sharma G, Goodwin J. Effect of aging on respiratory system
physiology and immunology. Clin Interv Aging 2006;1:253-60.
12. Buchman AS, Boyle PA, Wilson RS, Gu L, Bienias JL, Bennett DA.
Pulmonary function, muscle strength and mortality in old age.
Mech Ageing Dev 2008;129:625-31.
13. Mannino DM. COPD: epidemiology, prevalence, morbidity
and mortality, and disease heterogeneity. Chest 2002;121(5
Suppl):121S-126S.
14. Allen SC, Yeung P. Inability to draw intersecting pentagons as
a predictor of unsatisfactory spirometry technique in elderly
hospital inpatients. Age Ageing 2006;35:304-6.
15. Pezzoli L, Giardini G, Consonni S, et al. Quality of spirometric
performance in older people. Age Ageing 2003;32:43-6.
16. Allen SC, Jain M, Ragab S, Malik N. Acquisition and short-term
retention of inhaler techniques require intact executive function
in elderly subjects. Age Ageing 2003;32:299-302.
17. Allen SC, Baxter M. A comparison of four tests of cognition
as predictors of inability to perform spirometry in old age. Age
Ageing 2009;38:537-41.
18. Hilmer SN, McLachlan AJ, Le Couteur DG. Clinical pharmacology
in the geriatric patient. Fundam Clin Pharmacol 2007;21:217-30.
19. Barnes PJ. The pharmacological properties of tiotropium. Chest
2000;117(2 Suppl):63S-6S.
20. Cazzola M, Testi R, Matera MG. Clinical pharmacokinetics of
salmeterol. Clin Pharmacokinet 2002;41:19-30.
21. Turnheim K. Drug dosage in the elderly. Is it rational? Drugs
Aging 1998;13:357-79.
22. Ullah MI, Newman GB, Saunders KB. Influence of age on
response to ipratropium and salbutamol in asthma. Thorax
1981;36:523-9.
23. Johansson SA, Andersson KE, Brattsand R, Gruvstad E, Hedner
P. Topical and systemic glucocorticoid potencies of budesonide
and beclomethasone dipropionate in man. Eur J Clin Pharmacol
1982;22:523-9.
24. Phillipps GH. Structure-activity relationships of topically active
steroids: the selection of fluticasone propionate. Respir Med
1990;84(Suppl A):19-23.
25. Andersson N, Klint S, Randwall G, Wiren JE. Equipotency of
budesonide and fluticasone propionate in the vasoconstriction
assay. Am J Respir Crit Care Med 1994;149:A467.
26. Cole A. Over 60s’ use of prescription drugs has doubled in past
decade in England. BMJ 2008;337:a1132.
27. Roth MT, Ivey JL. Self-reported medication use in communityresiding older adults: A pilot study. Am J Geriatr Pharmacother
2005;3:196-204.
28. Pizzuti R, Caffari B, Binkin N; Gruppo ARGENTO. Prescription
drugs and the elderly: results of the Argento study [in Italian]. Ig
Sanita Pubbl 2006;62:11-26.
29. Kennerfalk A, Ruigomez A, Wallander MA, Wilhelmsen L,
Johansson S. Geriatric drug therapy and healthcare utilization in
the United Kingdom. Ann Pharmacother 2002;36:797-803.
30. Frada G, Bennati E, Cardillo E, Ferlito L, Motta M; IMUSCE.
Pharmacotherapy in the extreme longevity. Arch Gerontol Geriatr
2009;49:60-3.
31. Fialova D, Topinkova E, Gambassi G, et al. Potentially
inappropriate medication use among elderly home care patients
in Europe. JAMA 2005;293:1348-58.
32. Steinman MA, Landefeld CS, Rosenthal GE, Berthenthal D,
Sen S, Kaboli PJ. Polypharmacy and prescribing quality in older
people. J Am Geriatr Soc 2006;54:1516-23.
33. Sorensen L, Stokes JA, Purdie DM, Woodward M, Roberts
MS. Medication management at home: medication-related
risk factors associated with poor health outcomes. Age Ageing
2005;34:626-32.
Asian Journal of Gerontology & Geriatrics Vol 8 No 2 December 2013
Chronic obstructive pulmonary disease in the elderly
34. van der Hooft CS, Jong GW, Dieleman JP, et al. Inappropriate drug
prescribing in older adults: the updated 2002 Beers criteria—a
population-based cohort study. Br J Clin Pharmacol 2005;60:13744.
35. Gallagher P, Ryan C, Byrne S, Kennedy J, O'Mahony D. STOPP
(Screening Tool of Older Person’s Prescriptions) and START
(Screening Tool to Alert doctors to Right Treatment). Consensus
validation. Int J Pharmacol Ther 2008;46:72-83.
36. Anthonisen NR, Connett JE, Kiley JP, et al. Effects of smoking
intervention and the use of an inhaled anticholinergic
bronchodilator on the rate of decline of FEV1. The Lung Health
Study. JAMA 1994;272:1497-505.
37. Jorenby DE, Hays JT, Rigotti NA, et al. Efficacy of varenicline, an
alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs
placebo or sustained-release bupropion for smoking cessation: a
randomized controlled trial. JAMA 2006;296:56-63.
38. British Thoracic Society Standards of Care Subcommittee on
Pulmonary Rehabilitation. Pulmonary rehabilitation. Thorax
2001;56:827-34.
39. Chrystyn H. Is inhalation rate important for a dry powder
inhaler? Using the In-Check Dial to identify these rates. Respir
Med 2003;97:181-7.
40. Diggory P, Fernandez C, Humphrey A, Jones V, Murphy M.
Comparison of elderly people’s technique in using two dry
powder inhalers to deliver zanamivir: randomised controlled
trial. BMJ 2001;322:577-9.
41. Armitage JM, Williams SJ. Inhaler technique in the elderly. Age
Ageing 1988;17:275-8.
42. Jarvis S, Ind PW, Shiner RJ. Inhaled therapy in elderly COPD
patients; time for re-evaluation? Age Ageing 2007;36:213-8.
43. Berry RB, Shinto RA, Wong FH, Despars JA, Light RW. Nebulizer
44.
45.
46.
47.
48.
49.
50.
51.
52.
vs spacer for bronchodilator delivery in patients hospitalized for
acute exacerbations of COPD. Chest 1989;96:1241-6.
Long term domiciliary oxygen therapy in chronic hypoxic cor
pulmonale complicating chronic bronchitis and emphysema.
Report of the Medical Research Council Working Party. Lancet
1981;1:681-6.
Emtner M, Porszasz J, Burns M, Somfay A, Casaburi R. Benefits
of supplemental oxygen in exercise training in nonhypoxemic
chronic obstructive pulmonary disease patients. Am J Respir Crit
Care Med 2003;168:1034-42.
Stoller JK, Panos RJ, Krachman S, Doherty DE, Make B; Longterm Oxygen Treatment Trial Research Group. Oxygen therapy
for patients with COPD: current evidence and the long-term
oxygen treatment trial. Chest 2010;138:179-87.
Anker SD, John M, Pedersen PU, et al. ESPEN Guidelines
on Enteral Nutrition: cardiology and pulmonology. Clin Nutr
2006;25:311-8.
Mallampalli A. Nutritional management of the patient
with chronic obstructive pulmonary disease. Nutr Clin Pract
2004;19:550-6.
Luo FM, Liu XJ, Li SQ, Wang ZL, Liu CT, Yuan YM. Circulating
ghrelin in patients with chronic obstructive pulmonary disease.
Nutrition 2005;21:793-8.
Nagaya N, Itoh T, Murakami S, et al. Treatment of cachexia with
ghrelin in patients with COPD. Chest 2005;128:1187-93.
Sinuff T, Cook DJ, Keenan SP, et al. Noninvasive ventilation
for acute respiratory failure near the end of life. Crit Care Med
2008;36:789-94.
Nava S, Sturani C, Hartl S, et al. End-of-life decision-making in
respiratory intermediate care units: a European survey. Eur Respir
J 2007;30:156-64.
Asian Journal of Gerontology & Geriatrics Vol 8 No 2 December 2013 97