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PREFACE
Asthma in older people is common and is an increasingly serious health issue. It is estimated
that the number of older people with asthma will rise in the next 20 years because of the
worldwide population trend to enhanced longevity and the disproportionate increase in
individuals aged older than 64 years.

The prevalence of asthma in the elderly in high-income countries is between 6% and 10%.
Interestingly, women predominate in the age group of 64–75 years, but asthma prevalence
is similar between the sexes after 75 years. Two-thirds of deaths attributed to asthma occur
in people aged 65 years or older.

Paradoxically, even though the asthma mortality worldwide has decreased considerably, it
remains high in the elderly due to the challenges in the diagnosis and treatment of asthma
in this population.

Now, the obvious question that remains to be answered is this — why is it a challenge to
diagnose and treat asthma in elderly? The following are some of the reasons:
 Diagnosis of asthma is complex as there is a prevalence of a number of co-morbidities.
 In the elderly, asthma and chronic obstructive pulmonary disease overlap and converge
and the management of this overlap “syndrome” is yet to be fully elucidated.
 There are additional concerns specifically for the elderly, such as sub-optimal compliance,
poor understanding of the medication regimes in case of co-morbidities and physical
and neurological impairments.

With the increase in the number of individuals surviving beyond the age of 60 years, it is
imperative that asthma in elderly receives its due attention.

This booklet focuses on providing practical insights in managing asthma in this special
population and is intended as a quick reference guide to all physicians who want to know more
about managing asthma in such everyday scenarios.
January 2012
CONTENTS
 Ageing and Asthma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1

 Presentation of Asthma in the Elderly . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1

 Diagnosis of Asthma in the Elderly . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2

 Management of Asthma in the Elderly . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7

 Managing Co-Morbidities in Asthma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11

 Managing Acute Asthma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12

 Patient Education and Self-Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13

 Reflections on the Management of Asthma in the Elderly . . . . . . . . . . . . . . . . . . 14

 References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
AGEING AND ASTHMA
Ageing does play an essential role in asthma pathogenesis and also has an implication
on its diagnosis and management in the elderly. The following figure explains the effects
of ageing on the respiratory system, immune system as well its manifestation on the
pathophysiology of asthma in the elderly:

Effects of Ageing
Respiratory System Immune System Asthma Pathogenesis
Fall in lung function and capacity Altered baseline airway Progressive decline in pulmonary
inflammation function
Decreased elastic recoil and chest Altered immune response to Poorer prognosis and higher death
wall compliance antigen or irritants rates
Decreased sensitivity of lung Altered pathogen clearance Specific IgE antibodies to indoor
receptors allergens
Decreased sensitivity of respiratory Predominant neutrophilic Airway remodelling
centres to dyspnoea and hypoxia inflammation

PRESENTATION OF ASTHMA IN THE ELDERLY

Despite increased morbidity and mortality in older patients with asthma, the pathogenesis
in this age group is not well-characterized. Asthma in the elderly may result from the
persistence of childhood asthma, the return in later life of childhood asthma that was
quiescent in adulthood, or asthma that developed in later life (late-onset asthma).
(Table 1).
As in childhood onset asthma, a family history of asthma is also a risk factor for late-onset
asthma in the elderly, in addition to allergen sensitization. However, respiratory infections
such as the respiratory syncytial virus (RSV) and Chlamydia pneumoniae may play a more
important role than atopy in the development of such late-onset asthma (Table 1). Having
a history of smoking is also an influential factor although it has been implicated more in the
pathogenesis of chronic obstructive pulmonary disease (COPD).

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Table 1: Potential mechanisms for asthma phenotypes in the elderly
Long-standing asthma Late-onset asthma
Age of onset Child or young adult (<40) Adult (>40)
(Years)
Genetic role Likely gene by environment Likely apigenetic, including oxidative stress and
shortened telomeres
Infection Viral-rhinovirus and RSV Viral-RSV, Influenza and bacterial (e.g. Chlamydia
pneumoniae). microbial superantigens
Allergy Likely Unlikely
Inflammation Th2 driven, eosinophilic Th1-or Th2-driven.
neutrophilic and /or
eosinophilic, innale immunity
Th17, Proteases
Environment Allergens, daycare school and workplace Workplace, dwelling type (house, apartment and
institutional)

Asthma in children and adults is primarily a clinical diagnosis. However, symptoms that
suggest asthma, such as wheeze and a sensation of bronchospasm, may be absent in older
asthmatic patients. Furthermore, even when present, typical respiratory symptoms of
wheeze, breathlessness, chest tightness and cough have poor predictive value in old age.

The symptomatology in elderly asthmatics is relatively non-specific because of the presence

of co-morbidities. However the “hallmark” of asthma remains the same across all ages,
i.e., symptoms tend to be variable, intermittent, worse at night and provoked by triggers,
including exertion, and eliciting these features remains at the core of diagnosing asthma
in older people.

DIAGNOSIS OF ASTHMA IN THE ELDERLY

Under-diagnosis of asthma in the elderly remains a major issue and the reasons for this are
multifactorial and include reduced perception of symptoms, misattribution of symptoms to
other causes and underuse of objective testing such as spirometry. The diagnosis of asthma

2
is made by determining the symptoms by examining the medical history and obtaining an
objective assessment of the variable airflow obstruction.

History and Differential Diagnosis

The typical symptoms of asthma such as dyspnoea, chest tightness, cough and wheezing
are similar in both elderly and young patients. However, when considering the diagnosis of
asthma in an older patient, there are a number of diseases that should be included in the
differential diagnosis. But, it is important to rule out the conditions that mimic asthma. Hence,
the following list of conditions can be considered for the differential diagnosis of asthma in
older patients:

Table 2: Differential diagnosis of asthma in older patients

1. Congestive heart failure
2. COPD
3. Angina
4. Gastro-oesophageal reflux disease Asthma
5. Pulmonary embolus Mimics
6. Recurrent aspiration
7. Respiratory tract tumours
8. Vocal cord dysfunction
9. Anaemia
10. Cardiac arrhythmias
11. Pneumonia
12. Bronchial neoplasm
13. Tracheal stenosis
14. Post-nasal drip

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 It is vital to evaluate whether the elderly individual is a poor perceiver of symptoms by ask-
Practice point

ing about any physical activity modifications secondary to the symptoms consistent with
asthma.
A careful medication history is required to identify any therapeutic agents, such as angio-
tensin converting enzyme (ACE) inhibitors, which may produce a cough that mimics asth-
ma. Other examples include aspirin and beta-adrenergic blockers.
The medical history should include both a family and patient history of previous allergic dis-
eases, including eczema, allergic rhinitis, and drug and food allergies as a guide to allergic
asthma.
It is also important to consider the smoking history of the patient (not only pack/years of
cigarette smoking but also passive exposure to environmental tobacco smoke (ETS) as well
as biomass fuels and air pollution) since this might have induced co-existing COPD.

Distinguishing asthma from COPD

Table 3: Clinical pointers to distinguish asthma from COPD
Clinical Features Asthma COPD
Onset of symptoms Early adulthood likely Recent-onset symptoms Late (Usually when 50
(and normal FEV1) suggests late-onset asthma years of age or above)
Smoking history Possible Very often
History of atopy Often “intrinsic” but when present, atopy is a No
strong predictor of asthma in the elderly.
Symptoms Diurnal and/or day-to-day variability present Persistent/progressive
(may be lost in long-standing or early-onset
disease)
Noctumal Common Uncommon
Symptoms
Sputum production Can be present with co-existent COPD Common
Seasonal Winter exacerbations likely in “late-onset” Winter exacerbations
exacerbation asthma more likely
Spirometry “Reversibility” the hallmark of disease, but “fixed” airway
childhood onset asthma late in life may have obstruction and
only partial reversibility progressive deterioration

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 Clinical Features Asthma COPD
Chest radiograph In uncomplicated cases and without co-existing Signs or air trapping,
disease, chest radiograph is usually normal. relative lack of
Bronchial wall thickening due to inflammation vascular markings
and low flat diaphragm due to hyperinflation due to diminution of
may be seen pulmonary vessel calibre
and bullous changes
Gas transfer factor Usually well preserved, often increased Usually reduced
FEV1= Forced Expiratory Volume in 1 second.

However, the diagnosis of these two distinct diseases is not always straightforward since
many elderly individuals may present with an “overlap syndrome”.
Table 4: Features of an overlap of asthma and COPD
Onset May have a history of asthma occurring early in life
Risk factors Smoking, ageing
Symptoms Slowly progressive
Family history May be present
FEV1/FVC ratio <70%
FEV1 percent predicted <80%
Bronchodilator response Absent
FVC=Forced Vital Capacity

Objective Measurements
It is important to evaluate the clinical symptoms of asthma by office spirometry, which
measures the FEV1 and the FVC. If the spirometry results are consistent with airway
obstruction, it is essential to perform the bronchodilator reversibility test; a 12% or 200 ml
increase in the FEV1 values is suggestive of reversible obstructive airway disease.
Spirometry in the elderly
There is a misperception that reliable spirometry measurements cannot be obtained from
elderly individuals. Several studies have demonstrated that between 82% and 93% of
elderly patients are able to perform good spirometry.

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Ageing is associated with a decline in the FVC and FEV1 by 15–30 ml/year, and the decline
in the FEV1 often exceeds the reduction in the FVC, resulting in a decline in the predicted
values and lower limit of normal. Using a fixed cutoff value (<70%), as is recommended
by Global initiative for chronic Obstructive Lung Disease(GOLD), potentially results in
overestimation and misclassification of obstructive lung disease in older adults.

Good quality testing from an elderly patient may require 20–30 minutes more than the
time required for younger subjects. The minimum number of FVC manoeuvres needed to
achieve consistent results is higher in older adults (up to 5–8 manoeuvres required). Older
patients have difficulty in achieving end-of-test thresholds and using slow vital capacity
manoeuvres or the measurement of FEV1/FEV6 (forced expiratory volume in 6 seconds) to
detect airflow obstruction.

In patients who are unable to perform spirometry, the patient should be asked to undergo
Practice point

body plethysmography; this allows the patients to breathe more “normally”.

 To distinguish between asthma and COPD, formal spirometry, lung volumes and diffusion
capacity should be performed; in patients with COPD, the diffusion capacity is reduced
whereas in asthma it remains normal or is elevated.
 It is important to note when performing bronchodilator reversibility that in the elderly,
there may be decreased reversibility due to age-related decline in the sympathetic and
parasympathetic nervous system functions as well as permanent airway changes due to
fibrosis, tracheal instability or bronchiectasis.
 A ratio of FEV1/FVC <0.7 or FEV1 <80% predicted suggests obstructive lung disease but does
not distinguish between asthma and COPD.
 Measuring the peak expiratory flow rate (PEFR) variability, especially the diurnal variability
of ≥20% (ideally at least 60 l/minute), for 3 days in 2 weeks, over a period of time, may be a
useful option in the absence of office spirometry.
 It is important to note that age-related decrease in the diurnal variability does not exclude
the diagnosis of asthma.
Alternative methods for examining significant airflow reversibility to the PEFR or FEV1:
 Inhalation of a short-acting beta2-agonist (SABA), e.g. with metered dose inhaler (MDI) sal-
butamol 400 mcg with spacer or nebulizer 2.5 mg; and,
 Corticosteroid trial with prednisolone 30 mg/day for 14 days.

6
Other Investigations
Investigations in suspected asthma at first presentation in older people are important
to differentiate asthma from the various diseases that may present with wheeze or
breathlessness. Investigations are also important in asthma in following the course of the
disease, response to treatment and in the management of acute severe attacks.

Table 5: List of other investigations in asthma

1. Blood tests
2. Chest radiograph
3. Electrocardiogram (ECG)
4. Pulmonary function tests (PFT)
5. Arterial blood gas (ABG) analysis (usually for acute severe asthma)
6. Radioallergosorbent test (RAST) or allergy skin tests
7. Fractional expiratory nitric oxide (FeNO)
8. Bronchoalveolar lavage, sputum eosinophilia
9. High-resolution CT
10. Bronchial biopsy

MANAGEMENT OF ASTHMA IN THE ELDERLY

Generally speaking, the principles of asthma management in the elderly remain the same as
in the younger population, with special considerations for education and medication use.
The goals of management revolve around the same components of asthma management
as in the younger population, namely, assessment and monitoring, education, control of
triggers and pharmacotherapy.

Assessment and Monitoring

At the initial visit, the patient’s asthma should be classified either according to the severity
or the level of control as per the asthma guidelines, as is done in the younger adults.

7
 All patients with asthma should be seen every 1–6 months to assess the medical control of
Practice point

their disease.
 If a change in medication has been made, patients should be seen sooner, i.e., within 2–6
weeks.
 Spirometry and a PEFR meter are recommended for the assessment and monitoring of
asthma.
 When using PEF meters, a personal best should be established and this should be ideally
obtained in the middle to late part of the day.

Control of Triggers
When performing the initial assessment, it is critical to ask patients what triggers their
asthma as these exposures may be modified. Common triggers include aeroallergens,
infections (commonly viruses and sometimes bacteria), irritants and psychosocial
factors, including depression and social isolation, and allergen avoidance measures
should be applied. Since viral and pneumococcal infections are frequent risk factors for
asthma as well asthma exacerbations in the elderly, it may be beneficial to administer the
pneumococcal vaccination more frequently than every 5–10 years because, with ageing,
IgG opsonophagocytic activity and response to polysaccharide vaccination diminish.

Pharmacotherapy
The principles of pharmacologic treatment are similar for all ages. The medications used to
treat older patients with asthma are not significantly different from those used in younger
patients. However, there are several important considerations when prescribing these
medications in older patients, including dosage adjustments for metabolic rates, drug
interaction adverse effects, costs and delivery.

Since it is highly likely that asthma and COPD converge in the elderly individuals, the
pharmacological management should take this fact into account while treating this
population. Inhaled corticosteroids (ICS) have been a cornerstone of asthma treatment
and, in combination with long-acting beta2-agonists (LABAs), have proven their efficacy in
COPD. Additionally, patients with asthma and COPD should be advised to stop smoking.

8
ICS in the elderly
Corticosteroid therapy is the most effective form of anti-inflammatory medication for
asthma; however, whether they inhibit the development of long-term structural changes
in the airways is not known. To determine if ICS will have clinical benefit, patients may be
given a 2-week trial of oral corticosteroids at a dose of 0.3–0.5 mg/kg (a dose lower than
used in younger patients), after which the lung function test can be repeated to determine
if the airways hyper-responsiveness is reversible.

Patients should be prescribed an ICS with the lowest oral bioavailability and also be given
Practice point

the lowest dose of ICS to control their disease, i.e., <1,600 mcg/day of budesonide or 1,000
mcg/day of fluticasone.
 Patients on corticosteroids should be closely followed for osteoporosis and cataract, and to
lessen the effects of corticosteroids on bone resorption, patients should be encouraged to
exercise, avoid excess alcohol intake and take daily supplemental calcium with vitamin D.
 Theophylline use in the elderly should be limited; if unavoidable, then it is critical to use the
drug at a lowest possible dose and aim for a range of 8 to 12 mcg/ml while monitoring the
serum levels.
 Beta-agonists must be used cautiously in patients with heart disease and hypertension be-
cause an overdose may cause life-threatening arrhythmias and hypokalaemia.
 Combining non-potassium-sparing diuretics (e.g., thiazides) and beta2-agonists may cause
significant hypokalaemia and hypomagnesaemia, increasing the risk of cardiac arrhyth-
mias.
 An annual influenza and pneumococcal vaccine is recommended in all elderly patients 65
years of age or older, immunocompromised patients, and in patients with any chronic respi-
ratory condition, including asthma.

Inhalational device selection in the elderly

Drug delivery by the inhaled route offers the best efficacy–to–safety ratio for many asthma
therapies. However, an ineffective inhalation technique remains a substantial problem that
contributes to poor symptom control. The error rate increases with both age and the extent
of airflow obstruction. It has been reported that up to 82% of the elderly (older than 70
years) patients do not have an adequate pressurized MDI (pMDI) technique.
Older people with asthma can acquire and retain an appropriate technique after specific
instructions, but these instructions need to be repeated and reinforced to ensure continuous

9
good inhaler technique. Nebulized treatment can be replaced by the more efficient
pressurized inhaler devices or, if not, then home nebulization can be recommended for
daily use.
Specific factors leading to impaired inhaler technique in older people are learning difficulties
from impaired cognitive function, impaired vision and fine motor skills and decreased
generation of inspiratory flow. The following chart may be considered when selecting an
inhalation device for the elderly (Table 6).
Table 6: Device selection for elderly asthmatics
Device Recommended Use Possible Use Not Recommended
pMDI For patients with decreased In patients with im- In patients with de-
peak inspiratory flow paired cognition creased manual dexter-
ity and poor press-and-
breathe coordination
pMDI + For patients with decreased In patients with
Spacer peak inspiratory flow, poor impaired cogni-
press-and-breathe coordina- tion and decreased __
tion. actuation-inhalation
co-ordination.
DPI For patients with poor press- In patients with de- In patients with de-
and-breathe coordination creased manual dex- creased inspiratory flow
terity and impaired
cognition
BAI For patients with poor press-
and-breathe co-ordination,
decreased peak inspiratory __ __
flow, impaired cognition and
decreased manual dexterity
Nebuliser For patients with poor press-
and-breathe co-ordination,
decreased peak inspiratory __ __
flow, impaired cognition and
decreased manual dexterity.
pMDI= Pressurized Metered Dose Inhaler, DPI= Dry Powder Inhaler, BAI= breath-actuated inhaler

10
MANAGING CO-MORBIDITIES IN ELDERLY ASTHMATICS
The prevalence of co-morbidity from chronic disease increases with age. More than 50% of
older people, aged 65 years or more, have at least three co-morbidities and a substantial
portion have five or more, which are often unrecognized and untreated. Co-morbidity both
compounds and confounds the management of asthma in older adults. Drug interactions
and polypharmacy are important complications that accompany co-morbidity and ageing.
Some of the common co-morbid disorders that complicate asthma and ageing are shown
in the following table.

Table 7: Co-morbidities and that complicate asthma and ageing and their management
Co-morbidity Treatment
Obesity Weight loss in older adults must consider the specific nutritional
needs and include exercise and strength training to prevent
functional decline and the loss of muscle mass that occurs as older
people lose weight.
Gastro-oesophageal Proton-pump inhibitors; non-pharmacological treatment includes
reflux disease weight loss and diet modification; improvement in asthma once
gastro-oesophageal reflux disease is treated is variable.
Sleep disorders and Nasal continuous positive airway pressure is an effective treatment
obstructive sleep apnoea for obstructive sleep apnoea syndrome.
syndrome
Cataracts Reduce risk by keeping to minimum corticosteroid doses; surgical
treatment.
Osteoporosis The lowest possible dose of ICS must be prescribed to control
symptoms; physical activity should be encouraged; supplements
of calcium with vitamin D are needed in those at risk. Treatment of
established osteoporosis should be according to guidelines and
might include bisphosphonates.

Other than the above-mentioned co-morbidities, it is also essential to manage others such
as psychiatric co-morbidities (depression, panic attacks and general anxiety) as well as
cardiovascular co-morbidities, all of which complicate asthma management.

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 Non-asthma drugs that may affect asthma:
1. Beta-blockers
2. Non-steroidal anti-inflammatory drugs (NSAIDS)
3. Non-potassium-sparing diuretics
4. Cholinergic agents
5. Angiotensin-converting enzyme (ACE) inhibitors

MANAGEMENT OF ACUTE ASTHMA IN THE ELDERLY

The management of acute severe asthma is no different in the elderly than in the young,
but co-existing diseases and medications can make diagnosis and management very
challenging, and complications more likely. Objective measures of disease severity are
particularly important in the management of acute asthma in the elderly. Older asthmatics
patients often have an impaired perception of acute bronchoconstriction; doctors tend to
underestimate the severity of their symptoms and older patients take, on average, three
times as long to present to a hospital, compared with younger patients.

Healthcare professionals need to make sure elderly patients understand how to monitor
symptoms and identify signs (such as awakening at night due to asthma; an increased need
for inhaled beta2-agonists to relieve symptoms or diminished response to inhaled beta2-
agonists) or changes in the PEFR (if PEFR monitoring is used) that indicate their asthma is
worsening.

Each patient should be given a management plan (in the form of a printed handout) that
includes clear information on what to do and this action plan should also take into account
the co-morbidities that the patient may suffer from.

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 Practice point

For emergency care, hospital management and intensive care:

 Accurate diagnosis is important.
 Repeated doses of aerosolized beta2-agonists every 20–30 minutes during the first hour,
with a close watch on possible adverse events, is safe in most elderly persons with asthma.
 Patients who demonstrate hypoxaemia (PaO2 of less than 60 torr) should receive supple-
mental oxygen.
 Immediate administration of systemic corticosteroids (intravenous or by mouth) should be
considered in patients with severe exacerbations who fail to improve after the initial dose
of beta2-agonists, in patients who develop an exacerbation while already taking oral corti-
costeroids, and in patients who have a history of frequent refractory episodes that require
corticosteroids for resolution.
 Ipratropium bromide is a therapy to consider in patients with coexistent COPD, and to be
continued for those who have been taking the drug on a regular basis.
 Theophylline should be avoided in the initial (e.g., first 4 hours) emergency treatment of
severe exacerbations in the elderly because of the uncertain benefits and the increased risk
of toxicity and cardiac arrhythmias.
 Antibiotics are not recommended as routine therapy for asthma exacerbations. However,
some elderly patients with asthma and co-existing COPD may benefit from a course of an-
tibiotic therapy, especially if the exacerbation is characterized by an increase in sputum
volume and viscosity.

PATIENT EDUCATION AND SELF-MANAGEMENT IN ELDERLY

ASTHMATICS
Good communication and rapport between healthcare professionals and the patient has
long been recognized as crucial to asthma management. This entails an individualized
approach, tailored to each patient’s age, level of education, wishes for autonomy and social
and psychological status, to educate patients and/or their caregivers to take charge of
their disease. Adherence can be a complex issue in older people with chronic respiratory
disease, which can also be improved by applying patient education and self-management
strategies.

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Components of patient education and self-management for elderly asthmatic
patients
1. Education of the patient’s family and/or caregiver
2. Individualized written action plan
3. Periodic review

Asthma education in elderly patients centres on several key issues such as the need for
assistance with medication administration, assessment of inhaler technique, cognitive and/
or physical impairment, etc.

 Placebo inhalers that do not contain active medication can be used to teach and observe
Practice point

the patient’s inhaler technique.

 The usual components of asthma education, such as what is asthma, how to recognize
worsening, what steps to take, etc., should be discussed at the initial visit and needs to be
reviewed at follow-up visits.
 Asthma action plans are helpful, especially when given in the form of a handout (in a large
font size).
 Building of a successful partnership by discussing the goals of asthma treatment with the
patient as well as the caregiver; also, issues regarding non-compliance or lack of under-
standing should be addressed.

REFLECTIONS ON THE MANAGEMENT OF ASTHMA IN THE

ELDERLY
It has been suggested that a multidimensional strategy for the management of asthma in
older people might be appropriate

This approach allows for personalized interventions that can be applied to manage the
biological, clinical, functional and behavioural characteristics of the elderly asthmatics. A
model of this approach places the patient in the centre of their own care and recognizes
the many and divergent management issues that affect the health status and morbidity in
older people with asthma.

14
Specific recommendations for the management of asthma in the elderly

Hence, although highly prevalent, asthma in the elderly can be managed successfully
with the help of correct diagnosis, addressing co-morbidities as well as following an
individualized and multidisciplinary approach to therapy.

REFERENCES
1. Lancet 2010; 376:803–13
2. Drugs Aging 2009; 26 (1):1–22
3. Respir Med 2009; 103:1614–1622
4. Drugs Aging 2005; 22 (12):1029–1059
5. J Allergy Clin Immunol 2010; 126:690–9
6. Current Opinion in Pulmonary Medicine 2010, 16:55–59
7. J Allergy Clin Immunol 2010; 126: 681–7
8. J Allergy Clin Immunol 2010; 126:702–9
9. NAEPP Working Group Report. Considerations for diagnosing and managing asthma in the elderly (NIH # 96–
3662). National Heart, Lung and Blood Institute, National Institutes of Health, 1996.
10. Eur Respir Mon 2009; 43:56–76
11. Age and Ageing 2004; 33:185–188

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Notes

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Notes

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