Chronic obstructive pulmonary disease (COPD) is a debilitating disease of the elderly that causes significant morbidity and mortality. Despite being a treatable and preventable disease, the prevalence continues to rise because of the worldwide epidemic of smoking. COPD is associated with enormous healthcare costs. It has systemic effects, and common co-morbid conditions such as cardiovascular disease, muscle wasting and osteoporosis may all be linked through a common systemic inflammatory cascade. Depression, anxiety and malnutrition are also common in elderly COPD patients. These factors not only affect quality of life (QOL) but also compliance with therapy. Malnutrition is an independent predictor of mortality and poor outcome. Spirometry is essential for the diagnosis of COPD, but the criteria defining airflow limitation are not clear cut for elderly patients and could result in over-diagnosis. However, older patients perceive their symptoms differently, and COPD could also be under-diagnosed in this population. Acute exacerbations result in worsening symptoms that necessitate additional treatment, and may cause a more rapid decline in lung function and QOL. The management of elderly patients with COPD should encompass a multidisciplinary approach. An evaluation of patients’ nutritional status and mental health should be undertaken, in addition to assessing their lung function and functional impairment. Significant underlying co-morbidities should be evaluated and treated to derive the maximal benefit of therapy. Specific therapy for COPD should start with cessation of exposure to the most important risk factor, tobacco smoke. Smoking cessation rates in the elderly have not declined, and this may reflect an underlying reluctance by physicians to counsel and offer smoking cessation therapies to the elderly. Unlike oxygen therapy in hypoxaemic patients, bronchodilators and corticosteroids do not decrease mortality in COPD patients and they are primarily directed towards symptom relief. However, they do have a positive effect on QOL and exacerbation rates. The choice of delivery devices for inhaled medications is important in the elderly, and patients’ inhaler technique and manual dexterity should be frequently assessed. Pulmonary rehabilitation and nutritional supplementation are other important components of care. End-of-life issues should be adequately addressed in the elderly with COPD, and an approach integrating curative and palliative interventions is recommended.
Chronic obstructive pulmonary disease (COPD) is one of the most common diseases that affects the lungs and is a major public health problem. It has a significant inflammatory component, and affects both the airways and the parenchyma in the form of bronchitis and emphysema. Its systemic effects are being increasingly recognized, and COPD especially has a significant impact in the elderly with multiple co-morbidities. COPD is the only worldwide leading cause of death with an increasing prevalence. In the US, analysis of the age-standardized death rates from 1970 to 2002 showed that although the death rates for heart disease and stroke decreased by 52% and 63%, respectively, the death rates due to COPD increased by 103%. COPD-related deaths are rising faster in women than in men. It is estimated that the global burden of the disease will continue to increase over the next few decades, and COPD will become the third leading cause of death by 2020.
Because of the increasing median age of the population, treatment of COPD will account for a major portion of our healthcare expenditures. COPD is a leading cause of hospitalization in the US, and accounts for nearly one-fifth of total hospitalizations for patients aged ≥65 years. More than half of the annual per-patient costs of COPD are associated with these hospitalizations. COPD exacerbations account for the largest fraction of the total cost of COPD, with hospitalizations accounting for 58% of the total cost. In the US, the attributable per-patient cost of COPD in patients aged ≥65 years was estimated to be approximately $US6300 in 2004, and the total healthcare costs in this age group were significantly higher in patients with COPD than in those without a diagnosis of COPD. Co-morbid conditions are very strong predictors of future costs of COPD and need to be taken into consideration when analysing the economic burden of COPD therapy.
This review aims to provide a general update of the diagnosis and management of COPD, with specific emphasis on issues that are particularly important in the elderly population. The authors researched the PubMed database using the search terms ‘COPD’ and ‘elderly’ without limiting the search period, but limited the retrieved literature to the English language for the preparation of this manuscript. Articles that contained the best available evidence were included for citation.
1. Definition and Diagnosis
COPD encompasses a heterogeneous group of conditions that involve both the airways and the lung parenchyma, such as chronic bronchitis and emphysema. These are often characterized by partially reversible expiratory airflow limitation. In addition, some have suggested that other phenotypes with systemic inflammation and chronic mucus hypersecretion should also be included under the term COPD. The diagnosis of COPD requires spirometric evidence of airflow limitation, and most elderly patients can perform the test adequately. Although COPD may be present without significant symptoms, the classic symptoms include cough, dyspnoea and sputum production. However, both symptom assessment and spirometry interpretation have potential diagnostic pitfalls in the elderly.
One barrier to accurate diagnosis in elderly patients is that age appears to reduce the perception of bronchoconstriction.[13,14] As a result, older COPD patients are less likely to report milder symptoms and are more likely to be undiagnosed.
A second diagnostic issue in elderly patients involves the definition of an obstructive defect on spirometry. An obstructive defect on spirometry is most often defined as a reduced post-bronchodilator forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) ratio. For the sake of simplicity and widespread applicability, the Global initiative for chronic Obstructive Lung Disease (GOLD) guidelines have proposed using a specific cut point of an FEV1/FVC ratio of 0.7, below which a diagnosis of COPD should be considered. However, this cut point has not been clinically validated, and some authorities have recommended setting the lower limit at the fifth percentile of the normal distribution range of FEV1/FVC ratios.[16–18]
The criteria used to define airflow limitation, and therefore to diagnose COPD, are especially important in older patients. With normal aging, there is some loss of lung elasticity and increased airway collapsibility,[19,20] so that the FEV1/FVC ratio decreases with age.[21–23] When a fixed FEV1/FVC ratio of 0.7 is used as a cut-off, there is a risk of over-diagnosing COPD in older adults whose lung function may actually be normal; by some estimates, this method would misclassify up to 20% of current smokers beyond the sixth decade and up to 80% of people beyond the seventh decade as having COPD.[18,23] On the other hand, a fixed ratio may identify an at-risk population. The Cardiovascular Health Study found that elderly subjects whose FEV1/FVC ratio was ≤0.7 had an increased risk of dying or having a COPD-related hospitalization, even though the ratio was still within normal distribution cut-offs. A clear consensus definition of pathological airflow limitation using age-specific cut points is needed.
2. Classification of Severity
The recent GOLD guidelines define airflow obstruction as FEV1/FVC <0.7, and classify COPD into four stages based on the post-bronchodilator FEV1. These stages are: stage 1 or mild COPD with an FEV1 ≥80% predicted; stage 2 or moderate COPD with FEV1 between 50% and 80% predicted; stage 3 or severe COPD with FEV1 between 30% and 50% predicted; and stage 4 or very severe COPD with FEV1 either <30% predicted, or <50% predicted combined with hypoxaemia (partial pressure of oxygen in arterial blood [PaO2] <60 mmHg) with or without hypercarbia (partial pressure of carbon dioxide in arterial blood [PaCO2] >50 mmHg). These updated guidelines removed the previously categorized stage 0, which included patients who were at risk of developing COPD but did not have evidence of airflow obstruction.
3. Risk Factors
COPD results from the exposure of susceptible individuals to a variety of inhaled noxious gases and particles. Exposure to tobacco smoke is by far the most important risk factor for COPD, and the intensity and duration of exposure correlate with the severity of impairment. Indoor air pollution from biomass fuels and wood burning are also implicated in causing COPD, particularly in women in developing countries.[27,28] Outdoor air pollution has not been implicated as a risk factor for COPD, but it does increase the rate of emergency room visits for COPD exacerbations, particularly in the elderly. Other inhaled particles and gases could also be risk factors. The US National Health and Nutrition Surveys demonstrated significant airway obstruction in some never smokers; some occupational exposures, especially in construction workers and freight, stock and material handlers, are also thought to cause COPD.[30,31]
A variety of genetic factors may play a role in the host-environment interaction, but only the role of homozygous mutations of the α1-antitrypsin gene in causing COPD is well established.[32,33] Genetic influences might explain why not all smokers develop COPD. Women may also have a higher risk of developing severe, early-onset COPD despite having similar exposures to men.[35–37] The aetiology for this gender-based difference in susceptibility is not entirely clear. X-linked genetic factors and their interaction with the environment may play a role, but further studies are needed to clarify this. Lower socioeconomic status during childhood may increase the risk of developing COPD in adult life, but this may be due to the increased risk of exposure to particles and gases other than tobacco smoke under those conditions. The role of infections in the pathogenesis of COPD is not clear, despite the established role of bacterial and viral infection in causing acute exacerbations (AEs) of COPD.
The worldwide prevalence of COPD was explored by the BOLD (Burden of Obstructive Lung Disease) study. This was designed to overcome some of the limitations of earlier studies, such as differences in the rates of disease occurrence, disease definition, sampling methods, and whether or not spirometry was used to confirm diagnosis. In the BOLD study, the overall prevalence of COPD GOLD stage II or higher across 12 countries was 11.8% for men and 8.5% for women. The study confirmed previous reports that the disease prevalence increases with age, with estimates of <5% in persons aged 40–49 years increasing to 19–47% in men and 6–33% in women aged ≥70 years. Prevalence was higher in smokers than in non-smokers, and increased with the intensity and duration of smoking.
5. Systemic Inflammation, Systemic Effects and the Role of Co-Morbidities
Recent definitions associate COPD with an abnormal inflammatory response to noxious inhalants. Both active and passive smokers have an inflammatory response in the airways that persists even after smoking cessation. The inflammation is significantly greater in subjects who have COPD and is more pronounced during AEs.[41–43]
Increasingly, COPD is being recognized as having systemic effects.[1,15] Some authors propose calling COPD the “chronic systemic inflammatory syndrome”. Systemic inflammatory markers such as C-reactive protein, fibrinogen and tumour necrosis factor-α are elevated in patients with COPD, and may have a role in the pathogenesis of other smoking-related conditions, such as muscle wasting, cardiovascular disease and osteoporosis.[45,46] Systemic inflammation may play a key role in skeletal muscle wasting, which is independently associated with a poor prognosis.[47,48] It also probably accounts for the higher risk for cardiovascular disease in smokers with COPD than in smokers who do not have COPD. COPD is also a risk factor for osteoporosis even in the absence of exposure to corticosteroids. Furthermore, patients with COPD are more likely to have features of the metabolic syndrome, a complex disorder associated with a pro-inflammatory state, than age and sex-matched controls. An inflammatory mechanism may be responsible for the increased all-cause morbidity and mortality that is independently associated with a low FEV1.
Systemic inflammation has an important effect on the interaction of COPD with co-morbid conditions, the prevalence of which increases with age. Co-morbid conditions affect health outcomes in patients with COPD; patients with COPD die more often because of cardiovascular disease and cancer than because of respiratory failure. In the Lung Health Study, only 7.8% of deaths among patients with mild to moderate COPD were caused by respiratory failure; lung cancer, cardiovascular events and other cancers caused 33%, 22% and 21% of the deaths, respectively. However, the low percentage of deaths due to respiratory failure may be due to under-reporting on death certificates. In an analysis of the causes of death of all patients with moderate to severe COPD enrolled in a large clinical trial, respiratory failure was the most frequent cause of death (35%), followed by COPD (26% of all deaths), cardiovascular disease (25%) and all cancers (21%). The presence of co-morbidities also affects the overall mortality due to COPD. Among patients hospitalized with a COPD exacerbation, even after adjustment for a wide range of confounders, such as age and sex, individuals with more co-morbidities are >5-fold more likely to die in hospital than patients without co-morbidities.
The origin of the systemic inflammation in patients with COPD is currently not clear. However, as we obtain a better understanding of the effects of the systemic inflammation and its interaction with associated co-morbidities, we may be able to devise management strategies that are directed towards a common central cascade of pathophysiological events.
6. Depression and Anxiety in Chronic Obstructive Pulmonary Disease (COPD)
Two other common co-morbidities in patients with COPD are depression and anxiety. The prevalence rate for depression in COPD patients is as high as 40%, which is higher than the rate in patients with other chronic conditions such as stroke, cancer, diabetes mellitus and coronary artery disease.[57,58] The rates are higher in the elderly with COPD and in patients who have more frequent exacerbations. Depressed COPD patients may experience increased morbidity and mortality. New-onset depression appears to be a risk factor for cognitive decline in the elderly with COPD. Depressed patients have poorer quality of Life (QOL), worse social isolation and lower compliance with treatment.[60,62] QOL measures correlate better with depression than with lung function or exercise tolerance. Whether this relationship is one of cause or effect is unclear. Depression is an independent predictor of mortality in COPD patients who are hospitalized for an exacerbation.
Up to 37% of the elderly with COPD may have anxiety, which is also associated with poor QOL. COPD patients are more prone to panic attacks, which increase patients’ perception of dyspnoea.[66,67] Anxiety is a strong independent predictor of hospitalization following an exacerbation.
Depression and anxiety in patients with COPD respond to cognitive behavioural therapy and COPD education. Pharmacotherapy is also effective in improving QOL, symptoms and exercise tolerance.[69,70] However, elderly patients may not be receptive to pharmacotherapy and may refuse antidepressants. Compliance with treatment of both depression and COPD may be improved by adding patient education.
7. Acute Exacerbations
An exacerbation of COPD is defined as an acute event that results in a change in the patient’s usual level of dyspnoea, cough or sputum production and that warrants a change in regular medication. Exacerbations have significant effects on patients’ health and healthcare costs.
Bacterial and viral infections are now thought to be the most common causes of AEs. Genotypic and phenotypic analyses show that acquisition of new strains of bacteria is associated with AEs,[73,74] while a change in the bacterial loads of pre-existing organisms is less likely to be a cause. A variety of viruses, such as rhinoviruses, influenza viruses and respiratory syncytial viruses, have been implicated in AEs. Other causes include air pollution due to diesel particulates, sulphur dioxide, nitrogen dioxide and ozone. Additional risk factors are older age, reduced FEV1 and higher frequency of prior exacerbations.[76,77] A cause cannot be identified in approximately one-third of cases.
Most AEs are accompanied by decreases in lung function. This decrease is usually transient but may not fully recover in a significant percentage of patients. AEs, especially if they occur frequently, may accelerate the rate of decline in lung function. Measures of QOL are dramatically lower following an AE, and the frequency of the AEs and the severity of the symptoms have the most significant effect on QOL.[80,81] QOL largely improves following treatment, except in those who have a relapse. Although the in-hospital mortality following the first AE is low (11%), 2-year mortality following the first admission approaches 50%.
Appropriate COPD management goals should include controlling exposure to risk factors, relieving symptoms, improving effort tolerance and QOL, recognizing and treating AEs, complications and co-morbid conditions, and improving survival. These aims require a comprehensive, multidisciplinary approach that includes assessment of respiratory, functional and psychosocial impairment, the level of patients’ coping skills and education, smoking cessation and nutritional strategies, and discussions about end-of-life decisions and the role of palliative care. Although spirometry is useful in the management and in the classification of the severity of COPD, other measures of physiological function such as the 6-minute walk test can also be used to monitor progress or response to therapy. In addition, disease-specific measures of physical disability and QOL, such as the Manchester Respiratory Activities of Daily Living scale and the St George’s Respiratory Questionnaire, can also be considered for assessing disability and response to treatment in older subjects. Screening questionnaires for depression and anxiety may also be invaluable in providing comprehensive care to these elderly patients. Although clinical guidelines are effective in improving the quality of care for the disease in general, the lack of age-specific recommendations ignores the influence of co-morbid conditions on a chronic disease such as COPD in the elderly.
8.1 Smoking Cessation
Since smoking cessation is the only intervention that conclusively alters the natural course of COPD, it is undoubtedly the most important intervention and is effective even in older individuals. Smoking cessation slows the smoking-induced accelerated rate of decline in lung function, improves health and reduces mortality, regardless of the severity of the pulmonary impairment.[88,89] Patients aged >65 years may still gain up to 4 years of added life expectancy when they quit smoking.
Recent data from the Centers for Disease Control and Prevention showed that the overall prevalence of smoking in the US across all age groups was significantly lower in 2007 (19.8%) than in 2006 (20.8%). The prevalence was also significantly lower in those aged ≥65 years in 2007 (8.3%) than in 2006 (10.2%), but was close to the prevalence rate in 2004 (8.8%) in the same age group, suggesting that the long-term trend in the elderly may not have changed much over recent years.[91,92]
Useful interventions for smoking cessation include physician counselling, behavioural therapy and pharmacotherapy. Intensive counselling by physicians adds a small but significant percentage to the quit rates. Patients with COPD may benefit from counselling paired with a yearly spirometric demonstration of lung function impairment and may achieve higher quit rates. Nicotine, bupropion and varenicline[97,98] are effective pharmacological agents that have been well tolerated in subgroups of subjects aged 65–75 years. Nicotine replacement therapy is available in several formulations, such as gum, inhalers, nasal spray and a transdermal patch. Varenicline currently is associated with the highest sustained abstinence rate and requires no dosage adjustment in the elderly. However, patients with mental illnesses were largely excluded from the clinical trials of varenicline. Recent reports of varenicline exacerbating underlying psychiatric illnesses, inducing suicidality, and causing alterations in the level of consciousness have prompted the US FDA to issue warnings to exercise caution when using this agent in susceptible patients.[99–101]
Approximately 7% of adults are successful in quitting smoking on their own, but smoking cessation rates can be increased to 15–30% by smoking cessation programmes that combine pharmacotherapy and intensive counselling. In the US, the rates of smoking cessation attempts are lowest in those aged ≥65 years. An important reason for this could be the reluctance of physicians to advise smoking cessation to older adults. Elderly participants in smoking cessation programmes achieve sustained abstinence rates of 20%, which is comparable to the long-term quit rates of the general population.[53,95]
8.2 Pharmacological Management of COPD
Pharmacotherapy for COPD includes bronchodilators, corticosteroids, antibacterials and combinations of these agents. The role of these agents is largely to improve symptoms and exercise tolerance.
8.2.1 Inhalational Delivery Devices
Inhaled medications can be delivered by way of metered-dose inhalers (MDIs), dry powder inhalers (DPIs) or compressor nebulizers. Multiple factors, such as user technique, particle size and type of delivery device, affect the efficacy of inhaled medications. In older patients, inhalational technique is particularly affected by cognitive impairment and physical limitations.[104,105] Studies show that only 36% of the elderly use an MDI correctly. A large volume spacer (LVS) attached to an MDI decreases the need for coordinating device actuation and inhalation. Although most older patients are able to use an MDI correctly when connected to an LVS, a significant majority of elderly patients do not use the spacer even when it is prescribed.
When used correctly with a spacer, MDIs are just as effective as nebulized medications, even during AEs. However, nebulized medications are a good option for sicker, less capable elderly patients with cognitive difficulties. Breath-activated DPIs require less coordination than MDIs but do require the patient to generate a certain minimum negative peak inspiratory flow (PIF). Some older patients may not be able to generate the necessary PIF rates because PIF declines with age. Proper patient education and assessment of inhalation technique should be an integral part of every visit of the COPD patient to the physician.
Although bronchodilators are the cornerstone of symptom management in COPD, they have not been shown to decrease mortality. The preferred route of delivery is by inhalation. The three main categories of bronchodilators are the β-adrenergic receptor agonists, anticholinergics and the phosphodiesterase inhibitors, such as the methylxanthines. Although the severity of physiological impairment may help in the choice of initial therapy, therapy is usually guided by individual response, adverse effects, the ability of patients to use the formulation and the availability of the medication. Short-acting agents are useful in patients with mild, intermittent symptoms. Long-acting agents are preferred in patients with persistent symptoms, and are more effective in reducing dynamic hyperinflation, which is thought to play an important role in dyspnoea. In clinical practice, response is determined primarily by whether treatment improves effort tolerance and QOL. Research trials have also shifted the focus to more clinically relevant endpoints rather than FEV1 alone.
β-Adrenergic Receptor Agonists
β-Adrenergic receptor agonists (β-agonists) are effective bronchodilators. They induce bronchodilation by stimulating the β2-adrenoceptors in airway smooth muscle. Salbutamol (albuterol), levosalbutamol (levalbuterol), pirbuterol, orciprenaline (metaproterenol), terbutaline and fenoterol are examples of short-acting β-agonists (SABAs), while salmeterol, formoterol and arformoterol are examples of long-acting β-agonists (LABAs) that provide at least 12 hours of bronchodilation. Indacaterol is a new ultra-long-acting β-agonist with a 24-hour duration of action that is currently being tested in clinical trials. Some SABAs are available as oral formulations. However, the inhaled formulations are much preferred because adverse effects such as muscle tremor, tachycardia, restlessness and hypokalaemia occur much less often.
LABAs improve symptoms, lung function and health status, and decrease the frequency of AEs when compared with placebo.[114–116] In contrast to some reports in patients with asthma, use of LABAs as monotherapy in COPD has not been associated with increased mortality. Formoterol has a quicker onset of action than salmeterol, and arformoterol, the R,R isomer of formoterol, is twice as potent as the racemic formoterol and is an effective nebulized LABA for maintenance therapy.[116,118] Compared with placebo, salmeterol was found to significantly decrease the rate of decline in FEV1 when used alone or in combination with an inhaled corticosteroid (ICS).
SABAs are helpful during AEs of COPD, but LABAs have not been systematically studied for use in AEs and are generally not recommended because of their longer time to action.
Inhaled anticholinergic medications block the muscarinic receptors in the airways, thereby inhibiting vagally mediated bronchomotor tone. They may also be effective in decreasing airway mucus secretion. Inhaled anticholinergics have minimal systemic adverse effects. When sprayed directly into the eye, they may precipitate acute glaucoma, and a few other adverse effects such as dry mouth and urinary retention have been reported. Although some studies reported a non-significant trend towards increased cardiovascular mortality with use of inhaled anticholinergics, a large recent trial showed no increased mortality.
Currently available agents include the short-acting ipratropium bromide and the long-acting tiotropium bromide, which has a 24-hour duration of action. Tiotropium bromide is superior to ipratropium bromide at standard doses and helps improve lung function, symptoms, QOL, frequency of exacerbations, hospitalizations and respiratory failure rates but has no impact on mortality or on the rate of decline in lung function in patients with COPD.[122,123]
Short-acting ipratropium bromide has an onset of action of 10–15 minutes and is useful in AEs. Tiotropium bromide, which induces peak bronchodilation after 1–2 hours, is not recommended for the treatment of AEs.
Theophylline is the most widely used methylxanthine and causes bronchodilation primarily through inhibition of phosphodiesterases. Theophylline has de novo anti-inflammatory effects and also reverses corticosteroid resistance, but the clinical significance of these effects is not clear.[125,126] Theophylline has a very narrow therapeutic window. Its plasma concentrations must be closely monitored to reduce the likelihood of adverse effects, including nausea, vomiting, cardiac arrhythmias and seizures. The unfavourable benefit-risk ratio limits its usefulness, especially in the elderly. Newer, more selective phosphodiesterase receptor 4 inhibitors are being developed, but results from clinical trials have shown no improvements in QOL or in the frequency of exacerbations.
8.2.3 Inhaled Corticosteroids
Because COPD has an inflammatory component, many studies have looked for potential benefits in patients with COPD. ICSs are available as DPIs, MDIs or as formulations that can be nebulized. Several studies show that ICSs improve lung function and symptoms, and decrease airway reactivity and frequency of exacerbations.[128–130] A recent post hoc analysis of a larger study showed that the rate of decline in FEV1 in patients who received fluticasone propionate was significantly lower at 42 mL/year than the 55 mL/year in patients who received placebo. However, a similar effect was also seen in patients who received salmeterol only in the same study, and methodological issues may have affected the results. ICSs have not been shown to decrease mortality in patients with COPD.
The beneficial effects of ICSs need to be balanced against the risks of their long-term use in elderly patients. Local adverse effects such as oral thrush can be effectively controlled with adequate mouth rinsing, or with short courses of topical or systemic antifungal medications. However, ICSs also increase cataract formation, precipitate glaucoma, decrease bone mineral density and increase fracture rates.[134,135] One of the most important questions is whether ICSs increase the risk of pneumonia[114,136] and, if so, whether that would outweigh other benefits; this issue requires further study.
8.2.4 Combination Therapy
Combining bronchodilators from different classes, with or without ICSs, is an attractive option and is very common clinical practice in the treatment of patients with COPD. This approach often results in better bronchodilation and symptom relief, and avoids the adverse effects associated with using higher doses of a single agent. A combination of a SABA and a short-acting anticholinergic agent produces greater improvement in spirometry than either agent alone.
Combinations of LABAs and ICSs are very popular because of the availability of combination formulations and delivery devices. Such combinations have been shown to improve symptoms, lung function and QOL, decrease AEs and even decrease the rate of decline in FEV1, but have no effect on mortality.[114,119,138] Combining tiotropium bromide with a LABA may produce greater improvements in FEV1 and reduce the need for rescue inhalers more than either agent alone, but studies are not consistent across the available LABAs.[139,140]
Lung function appears to improve when ICSs are added to the combination of a LABA and tiotropium bromide (‘triple therapy’),[140,141] but the choice of the LABA used seems to affect the results. Triple therapy may decrease overall hospital admissions.
Summarizing the currently available ICSs and long-acting bronchodilators, LABA or tiotropium bromide monotherapy, and several combinations of therapy — LABA + ICS, LABA + tiotropium bromide, and triple therapy — have shown some benefits with varying risk profiles. Because studies have not yet addressed all of the same outcomes across all of the available treatment strategies, many uncertainties remain about optimal treatment combinations. Additional well conducted, long-term studies are needed to answer some of these questions.
8.2.5 Systemic Corticosteroids
Long-term systemic corticosteroids are associated with significant adverse effects, such as myopathy, osteoporosis, vertebral and hip fractures, glucose intolerance and cataract formation. Such therapy is not recommended for the long-term management of COPD. However, systemic corticosteroids do have a positive role to play in the treatment of AEs. In one study, outpatient treatment of AEs with 10 days of oral prednisone resulted in fewer relapses and greater improvements in FEV1 and dyspnoea scores than placebo. Systemic corticosteroids are also effective in the hospital management of AEs; such treatment improves lung function, shortens hospital stay and reduces relapse rates.[144,145] Although the optimal dose is not known, dosages as low as prednisone 30 mg/day may be effective, and courses longer than 2 weeks do not improve outcomes.[144,145]
Many previous studies have demonstrated the lack of benefit of routine use of antibacterials in chronic stable COPD, and the GOLD guidelines do not recommend their use. Macrolides have anti-inflammatory actions in addition to their antibacterial actions, and are effective in decreasing exacerbations and improving lung function in diseases such as cystic fibrosis and diffuse panbronchiolitis.[147,148] A small trial in COPD patients showed that erythromycin administered at 250 mg twice daily for 12 months reduced the frequency and duration of exacerbations but had no effect on lung function or inflammatory markers in the sputum or serum. However, this approach needs to be confirmed by much larger trials to weigh the benefits against the risk of inducing widespread macrolide resistance, and is currently not recommended.
Antibacterials are more useful in the treatment of AEs, especially in patients who present with increased sputum purulence. In sicker patients with moderate to severe exacerbations, antibacterials decrease mortality, duration of mechanical ventilation and the length of hospital stay.[150–152] Shorter courses of antibacterials (≤5 days) are as effective as longer courses.
8.3 Oxygen Therapy
Long-term oxygen therapy (LTOT) for at least 15 hours per day is recommended in the following situations: (i) PaO2 ≤55 mmHg on room air; (ii) oxygen saturation in arterial blood (SaO2) <88% with or without hypercapnia; and (iii) PaO2 between 55 and 60 mmHg with evidence of pulmonary hypertension, peripheral oedema or polycythaemia with a haematocrit of >55%. The strongest evidence is in patients with PaO2 ≤55 mmHg, in whom LTOT has been shown to improve survival, exercise tolerance, sleep and cognitive function.[154,155] Comparable benefits have not been demonstrated for LTOT in patients with moderate daytime hypoxaemia (PaO2 56–65 mmHg) or for nocturnal oxygen therapy in patients with nocturnal hypoxaemia (defined as spending ≥30% of time in bed with SaO2 <90%) in the presence of mild to moderate daytime hypoxaemia (PaO2 56–69 mmHg). However, normoxic patients (PaO2 >60 mmHg) on LTOT in the NETT (National Emphysema Treatment Trial) had higher mortality, worse symptoms and QOL, and more severe exercise desaturations than normoxic patients who were not receiving LTOT. The reasons for the increased mortality are not entirely clear and use of oxygen may merely identify patients at risk. The National Heart, Lung and Blood Institute has identified several unanswered questions about LTOT for future research.
8.4 Non-Invasive Ventilation
Non-invasive ventilation (NIV) is an effective modality for the management of AEs of COPD with impending respiratory failure. Early use of NIV in this setting decreases mortality, the need for intubation and mechanical ventilation, complications and length of hospital stay. NIV is well tolerated by the elderly and is as effective as in younger patients during AEs.[161,162] Use of NIV for chronic, stable, hypercapnic COPD is controversial. Although it may help improve dyspnoea, it has no positive effect on lung function and other clinically important endpoints, such as mortality and frequency of exacerbations, and its use is not routinely recommended.[163–165]
Immunization is an effective strategy to prevent complications in older patients with COPD. Immunization against influenza is very cost effective because it reduces mortality, hospitalizations and outpatient visits.[166,167] The role of pneumococcal vaccine in the elderly with COPD is less clear. Although it decreases bacteraemia, it does not decrease the risk of pneumonia or death in this population.[168–171] Nonetheless, it is recommended in all patients with COPD. A reduction in the rate of AEs was noted when pneumococcal and influenza vaccinations were administered at the same time but only during the first year after the combined vaccination. Large-scale studies are needed to clarify the role of pneumococcal vaccine in the elderly with lung disease.
8.6 Pulmonary Rehabilitation
Multiple studies in COPD support the benefits of pulmonary rehabilitation (PR). Through supervised exercise training, PR improves symptoms and effort intolerance by improving skeletal and respiratory muscle weakness, cardiac dysfunction and deconditioning. The programme can also address other components of care, such as nutrition, patient education, psychosocial well-being and QOL. Such a comprehensive approach has been shown to improve dyspnoea, exercise tolerance, QOL, anxiety and depression.[174,175] Home- and hospital-based outpatient programmes are equally effective, and home-based programmes effectively overcome the major limitations of travel time and lack of widespread availability of hospital-based programmes.[176,177] PR is cost effective and its positive gains are maintained over an extended period of time.
PR has a potential role in any symptomatic patient with COPD and benefits patients in all disease stages. Because PR is effective across all age groups, including the very old, physicians should not withhold PR on the basis of patient age.[179–181]
In the elderly, progressive weight loss and low body mass index (BMI) are common findings and important predictors of increased morbidity and mortality.[182,183] There is also an association between COPD and malnutrition, and the degree of malnutrition correlates with the severity of the underlying lung disease. Malnutrition and a low BMI of <20 kg/m2 may be found in up to 30% of patients with advanced COPD and represent an independent risk factor for increased mortality and hospitalization in patients with COPD.[185,186]
The systemic inflammation in COPD likely plays a key role in the pathogenesis of malnutrition and skeletal muscle dysfunction, although other factors such as increased energy expenditure from increased work of breathing have also been proposed.[1,48] A multidimensional scale that includes BMI (the BODE [Body mass index, airflow Obstruction, Dyspnoea and Exercise] index) appears to be a better predictor of mortality than FEV1 alone.
Nutritional intervention in the elderly is effective in stopping and even reversing progressive weight loss. Supplemental enteral nutrition in malnourished patients with COPD improves respiratory muscle strength and endurance but has no effect on lung function.[189–191] In one study, the weight gained with oral nutritional supplementation or with the use of an injected anabolic hormone, nandrolone decanoate, was associated with increased survival.
A low fat-free mass index is an independent predictor of mortality,[193,194] and this may partly explain the increased mortality in COPD patients despite having a normal BMI. Anabolic steroids tend to increase free fat mass more than nutritional supplementation alone.[192,196,197] However, because these agents may cause more adverse events in the elderly, their risks and benefits should be carefully considered. Larger studies evaluating the effectiveness of nutritional interventions on morbidity and mortality in patients with COPD are needed.
8.8 Palliative Care and End-of-Life Issues
Because most COPD therapies are aimed at symptom relief and are relatively non-toxic, ‘active’ and ‘palliative’ treatments are much the same during periods of relative stability or less severe acute illnesses. More distinctions and decisions are required to manage life-threatening illness. What is important is that treatments address the actual goals and needs of the patients. COPD patients may be just as unwilling to remain on mechanical ventilation as patients with lung cancer, yet are less likely to receive palliative care either in the hospital or at home.[199,200] Older patients with COPD have worse dyspnoea and QOL and, at times, more palliative care needs than patients with lung cancer.[201,202] Discussion and management of these issues should be undertaken well before the end of life. Ideally, palliative care should be available throughout the course of the disease. During critical illness, an individually tailored model integrating palliative care with curative care is likely to yield the best results for the patient. At different stages of the disease, dyspnoea can be palliated with PR, NIV, supplemental oxygen or even air by nasal cannula, opioids and anxiolytics. Recently released guidelines by the American Thoracic Society provide a detailed discussion of the various components of palliative care. Healthcare providers should use every available opportunity to discuss the benefits and burdens of aggressive curative/restorative interventions and palliative care, and should formulate a plan that meets the patient’s needs. Older and more severely ill patients should identify surrogate decision makers early on, and these surrogates should be involved in end-of-life discussions whenever possible. Caregivers also experience excess strain and may have psychological problems comparable to those of the patients themselves.[207,208] A comprehensive approach involving patients and their caregivers will be in the best interests of all parties.
COPD is a disease of the elderly, and guidelines with specific criteria for diagnosis in this population will be helpful. Recent advances in the overall care of the elderly patient with COPD are summarized in tables I and II. Systemic manifestations of the disease are increasingly being recognized, and a comprehensive multidisciplinary approach is needed to manage COPD in the elderly. The elderly are more susceptible to the adverse effects of drugs. Drug delivery devices that are appropriate for the degree of inspiratory effort and the patient’s cognitive and functional limitations should be prescribed. Smoking cessation needs to be more effectively targeted in the elderly, and attention should also be paid to nutritional and psychosocial needs. The palliative care needs of the elderly with COPD need to be recognized, and appropriate treatment plans should be formulated early on to effect a wholesome improvement in the care of this vulnerable population.
Agusti A. Systemic effects of chronic obstructive pulmonary disease: what we know and what we don’t know (but should). Proc Am Thorac Soc 2007 Oct 1; 4(7): 522–5
Sin DD, Anthonisen NR, Soriano JB, et al. Mortality in COPD: role of comorbidities. Eur Respir J 2006 Dec; 28(6): 1245–57
Hurd SS. International efforts directed at attacking the problem of COPD. Chest 2000 May; 117 (5 Suppl. 2): 336S–8S
Jemal A, Ward E, Hao Y, et al. Trends in the leading causes of death in the United States, 1970–2002. JAMA 2005 Sep 14; 294(10): 1255–9
CDC. Deaths from chronic obstructive pulmonary disease: United States, 2000–2005. MMWR Morb Mortal Wkly Rep 2008 Nov 14; 57(45): 1229–32
Lopez AD, Shibuya K, Rao C, et al. Chronic obstructive pulmonary disease: current burden and future projections. Eur Respir J 2006 Feb; 27(2): 397–412
Garrett N, Martini EM. The boomers are coming: a total cost of care model of the impact of population aging on the cost of chronic conditions in the United States. Dis Manag 2007 Apr; 10(2): 51–60
Mannino DM. COPD: epidemiology, prevalence, morbidity and mortality, and disease heterogeneity. Chest 2002 May; 121(5 Suppl.): 121S–6S
Miller JD, Foster T, Boulanger L, et al. Direct costs of COPD in the US: an analysis of Medical Expenditure Panel Survey (MEPS) data. COPD 2005 Sep; 2(3): 311–8
Miravitlles M, Murio C, Guerrero T, et al. Pharmacoeconomic evaluation of acute exacerbations of chronic bronchitis and COPD. Chest 2002 May; 121(5): 1449–55
Menzin J, Boulanger L, Marton J, et al. The economic burden of chronic obstructive pulmonary disease (COPD) in a US Medicare population. Respir Med 2008 Sep; 102(9): 1248–56
Mannino DM, Watt G, Hole D, et al. The natural history of chronic obstructive pulmonary disease. Eur Respir J 2006 Mar; 27(3): 627–43
Rutgers SR, ten Hacken NH, Koeter GH, et al. Borg scores before and after challenge with adenosine 5′-monophosphate and methacholine in subjects with COPD and asthma. Eur Respir J 2000 Sep; 16(3): 486–90
Ottanelli R, Rosi E, Ronchi MC, et al. Perception of bronchoconstriction in smokers with airflow limitation. Clin Sci (Lond) 2001 Nov; 101(5): 515–22
Rabe KF, Hurd S, Anzueto A, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med 2007 Sep 15; 176(6): 532–55
Pellegrino R, Viegi G, Brusasco V, et al. Interpretative strategies for lung function tests. Eur Respir J 2005 Nov; 26(5): 948–68
Hankinson JL, Odencrantz JR, Fedan KB. Spirometric reference values from a sample of the general US population. Am J Respir Crit Care Med 1999 Jan; 159(1): 179–87
Hansen JE, Sun XG, Wasserman K. Spirometric criteria for airway obstruction: use percentage of FEV1/FVC ratio below the fifth percentile, not <70%. Chest 2007 Feb; 131(2): 349–55
Gelb AF, Zamel N. Effect of aging on lung mechanics in healthy nonsmokers. Chest 1975 Oct; 68(4): 538–41
Burrows B, Lebowitz MD, Camilli AE, et al. Longitudinal changes in forced expiratory volume in one second in adults: methodologic considerations and findings in healthy nonsmokers. Am Rev Respir Dis 1986 Jun; 133(6): 974–80
Medbo A, Melbye H. Lung function testing in the elderly: can we still use FEV1/FVC <70% as a criterion of COPD? Respir Med 2007 Jun; 101(6): 1097–105
Celli BR, Halbert RJ, Isonaka S, et al. Population impact of different definitions of airway obstruction. Eur Respir J 2003 Aug; 22(2): 268–73
Hardie JA, Buist AS, Vollmer WM, et al. Risk of over-diagnosis of COPD in asymptomatic elderly never-smokers. Eur Respir J 2002 Nov; 20(5): 1117–22
Mannino DM, Buist AS, Vollmer WM. Chronic obstructive pulmonary disease in the older adult: what defines abnormal lung function? Thorax 2007 Mar; 62(3): 237–41
Pauwels RA, Buist AS, Calverley PM, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. NHLBI/WHO Global Initiative for Chronic Obstructive Lung Disease (GOLD) workshop summary. Am J Respir Crit Care Med 2001 Apr; 163(5): 1256–76
Burrows B, Knudson RJ, Cline MG, et al. Quantitative relationships between cigarette smoking and ventilatory function. Am Rev Respir Dis 1977 Feb; 115(2): 195–205
Orozco-Levi M, Garcia-Aymerich J, Villar J, et al. Wood smoke exposure and risk of chronic obstructive pulmonary disease. Eur Respir J 2006 Mar; 27(3): 542–6
Perez-Padilla R, Regalado J, Vedal S, et al. Exposure to biomass smoke and chronic airway disease in Mexican women: a case-control study. Am J Respir Crit Care Med 1996 Sep; 154 (3 Pt 1): 701–6
Halonen JI, Lanki T, Yli-Tuomi T, et al. Urban air pollution, and asthma and COPD hospital emergency room visits. Thorax 2008 Jul; 63(7): 635–41
Celli BR, Halbert RJ, Nordyke RJ, et al. Airway obstruction in never smokers: results from the Third National Health and Nutrition Examination Survey. Am J Med 2005 Dec; 118(12): 1364–72
Hnizdo E, Sullivan PA, Bang KM, et al. Association between chronic obstructive pulmonary disease and employment by industry and occupation in the US population: a study of data from the Third National Health and Nutrition Examination Survey. Am J Epidemiol 2002 Oct 15; 156(8): 738–46
Zeskind JE, Lenburg ME, Spira A. Translating the COPD transcriptome: insights into pathogenesis and tools for clinical management. Proc Am Thorac Soc 2008 Dec; 5(8): 834–41
Tobin MJ, Cook PJ, Hutchison DC. Alpha 1 antitrypsin deficiency: the clinical and physiological features of pulmonary emphysema in subjects homozygous for Pi type Z: a survey by the British Thoracic Association. Br J Dis Chest 1983 Jan; 77(1): 14–27
Smith CA, Harrison DJ. Association between polymorphism in gene for microsomal epoxide hydrolase and susceptibility to emphysema. Lancet 1997 Aug 30; 350(9078): 630–3
Silverman EK, Weiss ST, Drazen JM, et al. Gender-related differences in severe, early-onset chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2000 Dec; 162(6): 2152–8
Chen Y, Horne SL, Dosman JA. Increased susceptibility to lung dysfunction in female smokers. Am Rev Respir Dis 1991 Jun; 143(6): 1224–30
Prescott E, Bjerg AM, Andersen PK, et al. Gender difference in smoking effects on lung function and risk of hospitalization for COPD: results from a Danish longitudinal population study. Eur Respir J 1997 Apr; 10(4): 822–7
Prescott E, Lange P, Vestbo J. Socioeconomic status, lung function and admission to hospital for COPD: results from the Copenhagen City Heart Study. Eur Respir J 1999 May; 13(5): 1109–14
Sethi S, Murphy TF. Infection in the pathogenesis and course of chronic obstructive pulmonary disease. N Engl J Med 2008 Nov 27; 359(22): 2355–65
Buist AS, McBurnie MA, Vollmer WM, et al. International variation in the prevalence of COPD (the BOLD study): a population-based prevalence study. Lancet 2007 Sep 1; 370(9589): 741–50
Hogg JC, Chu F, Utokaparch S, et al. The nature of small-airway obstruction in chronic obstructive pulmonary disease. N Engl J Med 2004 Jun 24; 350(26): 2645–53
Vernooy JH, Kucukaycan M, Jacobs JA, et al. Local and systemic inflammation in patients with chronic obstructive pulmonary disease: soluble tumor necrosis factor receptors are increased in sputum. Am J Respir Crit Care Med 2002 Nov 1; 166(9): 1218–24
Hurst JR, Perera WR, Wilkinson TM, et al. Systemic and upper and lower airway inflammation at exacerbation of chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2006 Jan 1; 173(1): 71–8
Fabbri LM, Rabe KF. From COPD to chronic systemic inflammatory syndrome? Lancet 2007 Sep 1; 370(9589): 797–9
Gan WQ, Man SF, Senthilselvan A, et al. Association between chronic obstructive pulmonary disease and systemic inflammation: a systematic review and a metaanalysis. Thorax 2004 Jul; 59(7): 574–80
Gerhardsson de Verdier M. The big three concept: a way to tackle the health care crisis? Proc Am Thorac Soc 2008 Dec; 5(8): 800–5
Agusti A, Morla M, Sauleda J, et al. NF-kappaB activation and iNOS upregulation in skeletal muscle of patients with COPD and low body weight. Thorax 2004 Jun; 59(6): 483–7
Agusti AG, Sauleda J, Miralles C, et al. Skeletal muscle apoptosis and weight loss in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2002 Aug 15; 166(4): 485–9
Sin DD, Man SF. Why are patients with chronic obstructive pulmonary disease at increased risk of cardiovascular diseases? The potential role of systemic inflammation in chronic obstructive pulmonary disease. Circulation 2003 Mar 25; 107(11): 1514–9
McEvoy CE, Ensrud KE, Bender E, et al. Association between corticosteroid use and vertebral fractures in older men with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1998 Mar; 157 (3 Pt 1): 704–9
Marquis K, Maltais F, Duguay V, et al. The metabolic syndrome in patients with chronic obstructive pulmonary disease. J Cardiopulm Rehabil 2005 Jul–Aug; 25(4): 226–32; discussion 33-4
Young RP, Hopkins R, Eaton TE. Forced expiratory volume in one second: not just a lung function test but a marker of premature death from all causes. Eur Respir J 2007 Oct; 30(4): 616–22
Anthonisen NR, Skeans MA, Wise RA, et al. The effects of a smoking cessation intervention on 14.5-year mortality: a randomized clinical trial. Intern Med 2005 Feb 15; 142(4): 233–9
Jensen HH, Godtfredsen NS, Lange P, et al. Potential misclassification of causes of death from COPD. Eur Respir J 2006 Oct; 28(4): 781–5
McGarvey LP, John M, Anderson JA, et al. Ascertainment of cause-specific mortality in COPD: operations of the TORCH Clinical Endpoint Committee. Thorax 2007 May; 62(5): 411–5
Patil SP, Krishnan JA, Lechtzin N, et al. In-hospital mortality following acute exacerbations of chronic obstructive pulmonary disease. Arch Intern Med 2003 May 26; 163(10): 1180–6
Schane RE, Woodruff PG, Dinno A, et al. Prevalence and risk factors for depressive symptoms in persons with chronic obstructive pulmonary disease. J Gen Intern Med 2008 Nov; 23(11): 1757–62
Light RW, Merrill EJ, Despars JA, et al. Prevalence of depression and anxiety in patients with COPD: relationship to functional capacity. Chest 1985 Jan; 87(1): 35–8
Yohannes AM, Baldwin RC, Connolly MJ. Depression and anxiety in elderly outpatients with chronic obstructive pulmonary disease: prevalence, and validation of the BASDEC screening questionnaire. Int J Geriatr Psychiatry 2000 Dec; 15(12): 1090–6
Quint JK, Baghai-Ravary R, Donaldson GC, et al. Relationship between depression and exacerbations in COPD. Eur Respir J 2008 Jul; 32(1): 53–60
Incalzi RA, Chiappini F, Fuso L, et al. Predicting cognitive decline in patients with hypoxaemic COPD. Respir Med 1998 Mar; 92(3): 527–33
Bosley CM, Corden ZM, Rees PJ, et al. Psychological factors associated with use of home nebulized therapy for COPD. Eur Respir J 1996 Nov; 9(11): 2346–50
Yohannes AM, Roomi J, Baldwin RC, et al. Depression in elderly outpatients with disabling chronic obstructive pulmonary disease. Age Ageing 1998 Mar; 27(2): 155–60
Almagro P, Calbo E, Ochoa de Echaguen A, et al. Mortality after hospitalization for COPD. Chest 2002 May; 121(5): 1441–8
Cully JA, Graham DP, Stanley MA, et al. Quality of life in patients with chronic obstructive pulmonary disease and comorbid anxiety or depression. Psychosomatics 2006 Jul-Aug; 47(4): 312–9
Livermore N, Butler JE, Sharpe L, et al. Panic attacks and perception of inspiratory resistive loads in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2008 Jul 1; 178(1): 7–12
Smoller JW, Pollack MH, Otto MW, et al. Panic anxiety, dyspnea, and respiratory disease: theoretical and clinical considerations. J Respir Crit Care Med 1996 Jul; 154(1): 6–17
Kunik ME, Veazey C, Cully JA, et al. COPD education and cognitive behavioral therapy group treatment for clinically significant symptoms of depression and anxiety in COPD patients: a randomized controlled trial. Psychol Med 2008 Mar; 38(3): 385–96
Eiser N, Harte R, Spiros K, et al. Effect of treating depression on quality-of-life and exercise tolerance in severe COPD. COPD 2005 Jun; 2(2): 233–41
Argyropoulou P, Patakas D, Koukou A, et al. Buspirone effect on breathlessness and exercise performance in patients with chronic obstructive pulmonary disease. Respiration 1993; 60(4): 216–20
Yohannes AM, Connolly MJ, Baldwin RC. A feasibility study of antidepressant drug therapy in depressed elderly patients with chronic obstructive pulmonary disease. Int J Geriatr Psychiatry 2001 May; 16(5): 451–4
Sirey JA, Raue PJ, Alexopoulos GS. An intervention to improve depression care in older adults with COPD. Int J Geriatr Psychiatry 2007 Feb; 22(2): 154–9
Murphy TF, Brauer AL, Eschberger K, et al. Pseudomonas aeruginosa in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2008 Apr 15; 177(8): 853–60
Sethi S, Evans N, Grant BJ, et al. New strains of bacteria and exacerbations of chronic obstructive pulmonary disease. N Engl J Med 2002 Aug 15; 347(7): 465–71
Sethi S, Sethi R, Eschberger K, et al. Airway bacterial concentrations and exacerbations of chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2007 Aug 15; 176(4): 356–61
Anzueto A, Sethi S, Martinez FJ. Exacerbations of chronic obstructive pulmonary disease. Proc Am Thorac Soc 2007 Oct 1; 4(7): 554–64
Miravitlles M, Guerrero T, Mayordomo C, et al. Factors associated with increased risk of exacerbation and hospital admission in a cohort of ambulatory COPD patients: a multiple logistic regression analysis. The EOLO Study Group. Respiration 2000; 67(5): 495–501
White AJ, Gompertz S, Stockley RA. Chronic obstructive pulmonary disease: 6. The aetiology of exacerbations of chronic obstructive pulmonary disease. Thorax 2003 Jan; 58(1): 73–80
Donaldson GC, Seemungal TA, Bhowmik A, et al. Relationship between exacerbation frequency and lung function decline in chronic obstructive pulmonary disease. Thorax 2002 Oct; 57(10): 847–52
Miravitlles M, Ferrer M, Pont A, et al. Effect of exacerbations on quality of life in patients with chronic obstructive pulmonary disease: a 2 year follow up study. Thorax 2004 May; 59(5): 387–95
Seemungal TA, Donaldson GC, Paul EA, et al. Effect of exacerbation on quality of life in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1998 May; 157 (5 Pt 1): 1418–22
Aaron SD, Vandemheen KL, Clinch JJ, et al. Measurement of short-term changes in dyspnea and disease-specific quality of life following an acute COPD exacerbation. Chest 2002 Mar; 121(3): 688–96
Connors Jr AF, Dawson NV, Thomas C, et al. Outcomes following acute exacerbation of severe chronic obstructive lung disease. The SUPPORT Investigators (Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments). Am J Respir Crit Care Med 1996 Oct; 154 (4 Pt 1): 959–67
Kuzma AM, Meli Y, Meldrum C, et al. Multidisciplinary care of the patient with chronic obstructive pulmonary disease. Proc Am Thorac Soc 2008 May 1; 5(4): 567–71
Yohannes AM, Roomi J, Winn S, et al. The Manchester Respiratory Activities of Daily Living questionnaire: development, reliability, validity, and responsiveness to pulmonary rehabilitation. J Am Geriatr Soc 2000 Nov; 48(11): 1496–500
Jones PW, Quirk FH, Baveystock CM. The St George’s Respiratory Questionnaire. Respir Med 1991 Sep; 85Suppl. B: 25–31; discussion 3-7
Boyd CM, Darer J, Boult C, et al. Clinical practice guidelines and quality of care for older patients with multiple comorbid diseases: implications for pay for performance. JAMA 2005 Aug 10; 294(6): 716–24
Higgins MW, Enright PL, Kronmal RA, et al. Smoking and lung function in elderly men and women: the Cardiovascular Health Study. JAMA 1993 Jun 2; 269(21): 2741–8
Pelkonen M, Tukiainen H, Tervahauta M, et al. Pulmonary function, smoking cessation and 30 year mortality in middle aged Finnish men. Thorax 2000 Sep; 55(9): 746–50
Taylor Jr DH, Hasselblad V, Henley SJ, et al. Benefits of smoking cessation for longevity. Am J Public Health 2002 Jun; 92(6): 990–6
Centers for Disease Control and Prevention. Cigarette smoking among adults: United States, 2007. MMWR Morb Mortal Wkly Rep 2008 Nov 14; 57(45): 1221–6
Centers for Disease Control and Prevention. Cigarette smoking among adults: United States, 2004. MMWR Morb Mortal Wkly Rep 2005 Nov 11; 54(44): 1121–4
Stead LF, Bergson G, Lancaster T. Physician advice for smoking cessation. Cochrane Database Syst Rev 2008; (2): CD000165
Stratelis G, Molstad S, Jakobsson P, et al. The impact of repeated spirometry and smoking cessation advice on smokers with mild COPD. Scand J Prim Health Care 2006 Sep; 24(3): 133–9
Tait RJ, Hulse GK, Waterreus A, et al. Effectiveness of a smoking cessation intervention in older adults. Addiction 2007 Jan; 102(1): 148–55
Hurt RD, Sachs DP, Glover ED, et al. A comparison of sustained-release bupropion and placebo for smoking cessation. N Engl J Med 1997 Oct 23; 337(17): 1195–202
Gonzales D, Rennard SI, Nides M, et al. Varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs sustained-release bupropion and placebo for smoking cessation: a randomized controlled trial. JAMA 2006 Jul 5; 296(1): 47–55
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 Jul 5; 296(1): 56–63
Popkin MK. Exacerbation of recurrent depression as a result of treatment with varenicline. Am J Psychiatry 2008 Jun; 165(6): 774
Lasser KE, Boyd JW. Varenicline and smokers with mental illnesses. Lancet 2008 Oct 4; 372(9645): 1218–9
Hays JT, Ebbert JO. Varenicline for tobacco dependence. N Engl J Med 2008 Nov 6; 359(19): 2018–24
A clinical practice guideline for treating tobacco use and dependence: a US Public Health Service report. The Tobacco Use and Dependence Clinical Practice Guideline Panel, Staff, and Consortium Representatives. JAMA 2000 Jun 28; 283(24): 3244–54
Maguire CP, Ryan J, Kelly A, et al. Do patient age and medical condition influence medical advice to stop smoking? Age Ageing 2000 May; 29(3): 264–6
Allen SC, Ragab S. Ability to learn inhaler technique in relation to cognitive scores and tests of praxis in old age. Postgrad Med J 2002 Jan; 78(915): 37–9
Diggory P, Fernandez C, Humphrey A, et al. Comparison of elderly people’s technique in using two dry powder inhalers to deliver zanamivir: randomised controlled trial. BMJ 2001 Mar 10; 322(7286): 577–9
Chapman KR, Love L, Brubaker H. A comparison of breath-actuated and conventional metered-dose inhaler inhalation techniques in elderly subjects. Chest 1993 Nov; 104(5): 1332–7
Ho SF, O’Mahony MS, Steward JA, et al. Inhaler technique in older people in the community. Age Ageing 2004 Mar; 33(2): 185–8
Jarvis S, Ind PW, Shiner RJ. Inhaled therapy in elderly COPD patients; time for re-evaluation? Age Ageing 2007 Mar; 36(2): 213–8
Berry RB, Shinto RA, Wong FH, et al. Nebulizer vs spacer for bronchodilator delivery in patients hospitalized for acute exacerbations of COPD. Chest 1989 Dec; 96(6): 1241–6
Janssens W, VandenBrande P, Hardeman E, et al. Inspiratory flow rates at different levels of resistance in elderly COPD patients. Eur Respir J 2008 Jan; 31(1): 78–83
Dolovich MB, Ahrens RC, Hess DR, et al. Device selection and outcomes of aerosol therapy: evidence-based guidelines: American College of Chest Physicians/American College of Asthma, Allergy, and Immunology. Chest 2005 Jan; 127(1): 335–71
Ofir D, Laveneziana P, Webb KA, et al. Mechanisms of dyspnea during cycle exercise in symptomatic patients with GOLD stage I chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2008 Mar 15; 177(6): 622–9
Rennard S, Bantje T, Centanni S, et al. A dose-ranging study of indacaterol in obstructive airways disease, with a tiotropium comparison. Respir Med 2008 Jul; 102(7): 1033–44
Calverley PM, Anderson JA, Celli B, et al. Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease. N Engl J Med 2007 Feb 22; 356(8): 775–89
Dahl R, Greefhorst LA, Nowak D, et al. Inhaled formoterol dry powder versus ipratropium bromide in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2001 Sep 1; 164(5): 778–84
Hanrahan JP, Hanania NA, Calhoun WJ, et al. Effect of nebulized arformoterol on airway function in COPD: results from two randomized trials. COPD 2008 Feb; 5(1): 25–34
Kottakis J, Cioppa GD, Creemers J, et al. Faster onset of bronchodilation with formoterol than with salmeterol in patients with stable, moderate to severe COPD: results of a randomized, double-blind clinical study. Can Respir J 2002 Mar-Apr; 9(2): 107–15
Handley DA, Senanayake CH, Dutczak W, et al. Biological actions of formoterol isomers. Pulm Pharmacol Ther 2002; 15(2): 135–45
Celli BR, Thomas NE, Anderson JA, et al. Effect of pharmacotherapy on rate of decline of lung function in chronic obstructive pulmonary disease: results from the TORCH study. Am J Respir Crit Care Med 2008 Aug 15; 178(4): 332–8
Gupta P, O’Mahony MS. Potential adverse effects of bronchodilators in the treatment of airways obstruction in older people: recommendations for prescribing. Drugs Aging 2008; 25(5): 415–43
Anthonisen NR, Connett JE, Enright PL, et al. Hospitalizations and mortality in the Lung Health Study. Am J Respir Crit Care Med 2002 Aug 1; 166(3): 333–9
Tashkin DP, Celli B, Senn S, et al. A 4-year trial of tiotropium in chronic obstructive pulmonary disease. N Engl J Med 2008 Oct 9; 359(15): 1543–54
Vincken W, van Noord JA, Greefhorst AP, et al. Improved health outcomes in patients with COPD during 1 yr’s treatment with tiotropium. Eur Respir J 2002 Feb; 19(2): 209–16
Rabe KF, Magnussen H, Dent G. Theophylline and selective PDE inhibitors as bronchodilators and smooth muscle relaxants. Eur Respir J 1995 Apr; 8(4): 637–42
Barnes PJ. Theophylline in chronic obstructive pulmonary disease: new horizons. Proc Am Thorac Soc 2005; 2(4): 334–9; discussion 40-1
Culpitt SV, de Matos C, Russell RE, et al. Effect of theophylline on induced sputum inflammatory indices and neutrophil chemotaxis in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2002 May 15; 165(10): 1371–6
Rabe KF, Bateman ED, O’Donnell D, et al. Roflumilast: an oral anti-inflammatory treatment for chronic obstructive pulmonary disease. A randomised controlled trial. Lancet 2005 Aug 13–19; 366(9485): 563–71
Burge PS, Calverley PM, Jones PW, et al. Randomised, double blind, placebo controlled study of fluticasone propionate in patients with moderate to severe chronic obstructive pulmonary disease: the ISOLDE trial. BMJ 2000 May 13; 320(7245): 1297–303
Lung Health Study Research Group. Effect of inhaled triamcinolone on the decline in pulmonary function in chronic obstructive pulmonary disease. N Engl J Med 2000 Dec 28; 343(26): 1902–9
Vestbo J, Sorensen T, Lange P, et al. Long-term effect of inhaled budesonide in mild and moderate chronic obstructive pulmonary disease: a randomised controlled trial. Lancet 1999 May 29; 353(9167): 1819–23
Suissa S. Medications to modify lung function decline in chronic obstructive pulmonary disease: some hopeful signs. Am J Respir Crit Care Med 2008 Aug 15; 178(4): 322–3
Ernst P, Baltzan M, Deschenes J, et al. Low-dose inhaled and nasal corticosteroid use and the risk of cataracts. Eur Respir J 2006 Jun; 27(6): 1168–74
Garbe E, LeLorier J, Boivin JF, et al. Risk of ocular hypertension or open-angle glaucoma in elderly patients on oral glucocorticoids. Lancet 1997 Oct 4; 350(9083): 979–82
Hubbard RB, Smith CJ, Smeeth L, et al. Inhaled corticosteroids and hip fracture: a population-based case-control study. Am J Respir Crit Care Med 2002 Dec 15; 166 (12 Pt 1): 1563–6
Suissa S, Baltzan M, Kremer R, et al. Inhaled and nasal corticosteroid use and the risk of fracture. Am J Respir Crit Care Med 2004 Jan 1; 169(1): 83–8
Ernst P, Gonzalez AV, Brassard P, et al. Inhaled corticosteroid use in chronic obstructive pulmonary disease and the risk of hospitalization for pneumonia. Am J Respir Crit Care Med 2007 Jul 15; 176(2): 162–6
The COMBIVENT Inhalation Solution Study Group. Routine nebulized ipratropium and albuterol together are better than either alone in COPD. Chest 1997 Dec; 112(6): 1514–21
Calverley PM, Boonsawat W, Cseke Z, et al. Maintenance therapy with budesonide and formoterol in chronic obstructive pulmonary disease. Eur Respir J 2003 Dec; 22(6): 912–9
van Noord JA, Aumann JL, Janssens E, et al. Comparison of tiotropium once daily, formoterol twice daily and both combined once daily in patients with COPD. Eur Respir J 2005 Aug; 26(2): 214–22
Aaron SD, Vandemheen KL, Fergusson D, et al. Tiotropium in combination with placebo, salmeterol, or fluticasone-salmeterol for treatment of chronic obstructive pulmonary disease: a randomized trial. Ann Intern Med 2007 Apr 17; 146(8): 545–55
Singh D, Brooks J, Hagan G, et al. Superiority of “triple” therapy with salmeterol/fluticasone propionate and tiotropium bromide versus individual components in moderate to severe COPD. Thorax 2008 Jul; 63(7): 592–8
Rabe KF, Timmer W, Sagkriotis A, et al. Comparison of a combination of tiotropium plus formoterol to salmeterol plus fluticasone in moderate COPD. Chest 2008 Aug; 134(2): 255–62
Aaron SD, Vandemheen KL, Hebert P, et al. Outpatient oral prednisone after emergency treatment of chronic obstructive pulmonary disease. N Engl J Med 2003 Jun 26; 348(26): 2618–25
Niewoehner DE, Erbland ML, Deupree RH, et al. Effect of systemic glucocorticoids on exacerbations of chronic obstructive pulmonary disease. Department of Veterans Affairs Cooperative Study Group. N Engl J Med 1999 Jun 24; 340(25): 1941–7
Davies L, Angus RM, Calverley PM. Oral corticosteroids in patients admitted to hospital with exacerbations of chronic obstructive pulmonary disease: a prospective randomised controlled trial. Lancet 1999 Aug 7; 354(9177): 456–60
Shinkai M, Henke MO, Rubin BK. Macrolide antibiotics as immunomodulatory medications: proposed mechanisms of action. Pharmacol Ther 2008 Mar; 117(3): 393–405
Clement A, Tamalet A, Leroux E, et al. Long term effects of azithromycin in patients with cystic fibrosis: a double blind, placebo controlled trial. Thorax 2006 Oct; 61(10): 895–902
Nagai H, Shishido H, Yoneda R, et al. Long-term low-dose administration of erythromycin to patients with diffuse panbronchiolitis. Respiration 1991; 58(3–4): 145–9
Seemungal TA, Wilkinson TM, Hurst JR, et al. Long-term erythromycin therapy is associated with decreased chronic obstructive pulmonary disease exacerbations. Am J Respir Crit Care Med 2008 Dec 1; 178(11): 1139–47
Anthonisen NR, Manfreda J, Warren CP, et al. Antibiotic therapy in exacerbations of chronic obstructive pulmonary disease. Ann Intern Med 1987 Feb; 106(2): 196–204
Ram FS, Rodriguez-Roisin R, Granados-Navarrete A, et al. Antibiotics for exacerbations of chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2006; (2): CD004403
Nouira S, Marghli S, Belghith M, et al. Once daily oral ofloxacin in chronic obstructive pulmonary disease exacerbation requiring mechanical ventilation: a randomised placebo-controlled trial. Lancet 2001 Dec 15; 358(9298): 2020–5
El Moussaoui R, Roede BM, Speelman P, et al. Short-course antibiotic treatment in acute exacerbations of chronic bronchitis and COPD: a meta-analysis of double-blind studies. Thorax 2008 May; 63(5): 415–22
Nocturnal Oxygen Therapy Trial Group. Continuous or nocturnal oxygen therapy in hypoxemic chronic obstructive lung disease: a clinical trial. Ann Intern Med 1980 Sep; 93(3): 391–8
Report of the Medical Research Council Working Party. Long term domiciliary oxygen therapy in chronic hypoxic cor pulmonale complicating chronic bronchitis and emphysema. Lancet 1981 Mar 28; 1(8222): 681–6
Gorecka D, Gorzelak K, Sliwinski P, et al. Effect of long-term oxygen therapy on survival in patients with chronic obstructive pulmonary disease with moderate hypoxaemia. Thorax 1997 Aug; 52(8): 674–9
Chaouat A, Weitzenblum E, Kessler R, et al. A randomized trial of nocturnal oxygen therapy in chronic obstructive pulmonary disease patients. Eur Respir J 1999 Nov; 14(5): 1002–8
Drummond MB, Blackford AL, Benditt JO, et al. Continuous oxygen use in nonhypoxemic emphysema patients identifies a high-risk subset of patients: retrospective analysis of the National Emphysema Treatment Trial. Chest 2008 Sep; 134(3): 497–506
Croxton TL, Bailey WC. Long-term oxygen treatment in chronic obstructive pulmonary disease: recommendations for future research: an NHLBI workshop report. Am J Respir Crit Care Med 2006 Aug 15; 174(4): 373–8
Ram FS, Picot J, Lightowler J, et al. Non-invasive positive pressure ventilation for treatment of respiratory failure due to exacerbations of chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2004; (3): CD004104
Balami JS, Packham SM, Gosney MA. Non-invasive ventilation for respiratory failure due to acute exacerbations of chronic obstructive pulmonary disease in older patients. Age Ageing 2006 Jan; 35(1): 75–9
Rozzini R, Sabatini T, Trabucchi M. Non-invasive ventilation for respiratory failure in elderly patients. Age Ageing 2006 Sep; 35(5): 546–7
Casanova C, Celli BR, Tost L, et al. Long-term controlled trial of nocturnal nasal positive pressure ventilation in patients with severe COPD. Chest 2000 Dec; 118(6): 1582–90
Clini E, Sturani C, Rossi A, et al. The Italian multicentre study on noninvasive ventilation in chronic obstructive pulmonary disease patients. Eur Respir J 2002 Sep; 20(3): 529–38
Tsolaki V, Pastaka C, Karetsi E, et al. One-year noninvasive ventilation in chronic hypercapnic COPD: effect on quality of life. Respir Med 2008 Jun; 102(6): 904–11
Nichol KL, Baken L, Nelson A. Relation between influenza vaccination and outpatient visits, hospitalization, and mortality in elderly persons with chronic lung disease. Ann Intern Med 1999 Mar 2; 130(5): 397–403
Nichol KL, Margolis KL, Wuorenma J, et al. The efficacy and cost effectiveness of vaccination against influenza among elderly persons living in the community. N Engl J Med 1994 Sep 22; 331(12): 778–84
Alfageme I, Vazquez R, Reyes N, et al. Clinical efficacy of anti-pneumococcal vaccination in patients with COPD. Thorax 2006 Mar; 61(3): 189–95
Granger R, Walters J, Poole PJ, et al. Injectable vaccines for preventing pneumococcal infection in patients with chronic obstructive pulmonary disease. Cochrane Database Syst 2006; (4): CD001390
Moberley SA, Holden J, Tatham DP, et al. Vaccines for preventing pneumococcal infection in adults. Cochrane Database Syst 2008; (1): CD000422
Jackson LA, Neuzil KM, Yu O, et al. Effectiveness of pneumococcal polysaccharide vaccine in older adults. N Engl J Med 2003 May 1; 348(18): 1747–55
Furumoto A, Ohkusa Y, Chen M, et al. Additive effect of pneumococcal vaccine and influenza vaccine on acute exacerbation in patients with chronic lung disease. Vaccine 2008 Aug 5; 26(33): 4284–9
Nici L, Donner C, Wouters E, et al. American Thoracic Society/European Respiratory Society statement on pulmonary rehabilitation. Am J Respir Crit Care Med 2006 Jun 15; 173(12): 1390–413
Paz-Diaz H, Montes de Oca M, Lopez JM, et al. Pulmonary rehabilitation improves depression, anxiety, dyspnea and health status in patients with COPD. Am J Phys Med Rehabil 2007 Jan; 86(1): 30–6
Guell R, Casan P, Belda J, et al. Long-term effects of outpatient rehabilitation of COPD: a randomized trial. Chest 2000 Apr; 117(4): 976–83
Maltais F, Bourbeau J, Shapiro S, et al. Effects of home-based pulmonary rehabilitation in patients with chronic obstructive pulmonary disease: a randomized trial. Ann Intern Med 2008 Dec 16; 149(12): 869–78
Sabit R, Griffiths TL, Watkins AJ, et al. Predictors of poor attendance at an outpatient pulmonary rehabilitation programme. Respir Med 2008 Jun; 102(6): 819–24
Takigawa N, Tada A, Soda R, et al. Comprehensive pulmonary rehabilitation according to severity of COPD. Respir Med 2007 Feb; 101(2): 326–32
Baltzan MA, Kamel H, Alter A, et al. Pulmonary rehabilitation improves functional capacity in patients 80 years of age or older. Can Respir J 2004 Sep; 11(6): 407–13
Couser Jr JI, Guthmann R, Hamadeh MA, et al. Pulmonary rehabilitation improves exercise capacity in older elderly patients with COPD. Chest 1995 Mar; 107(3): 730–4
Di Meo F, Pedone C, Lubich S, et al. Age does not hamper the response to pulmonary rehabilitation of COPD patients. Age Ageing 2008 Sep; 37(5): 530–5
Constans T, Bacq Y, Brechot JF, et al. Protein-energy malnutrition in elderly medical patients. J Am Geriatr Soc 1992 Mar; 40(3): 263–8
Payette H, Coulombe C, Boutier V, et al. Weight loss and mortality among free-living frail elders: a prospective study. J Gerontol 1999 Sep; 54(9): M440–5
Openbrier DR, Irwin MM, Rogers RM, et al. Nutritional status and lung function in patients with emphysema and chronic bronchitis. Chest 1983 Jan; 83(1): 17–22
Chailleux E, Laaban JP, Veale D. Prognostic value of nutritional depletion in patients with COPD treated by long-term oxygen therapy: data from the ANTADIR observatory. Chest 2003 May; 123(5): 1460–6
Landbo C, Prescott E, Lange P, et al. Prognostic value of nutritional status in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1999 Dec; 160(6): 1856–61
Celli BR, Cote CG, Marin JM, et al. The body-mass index, airflow obstruction, dyspnea, and exercise capacity index in chronic obstructive pulmonary disease. N Engl J Med 2004 Mar 4; 350(10): 1005–12
Payette H, Boutier V, Coulombe C, et al. Benefits of nutritional supplementation in free-living, frail, undernourished elderly people: a prospective randomized community trial. J Am Diet Assoc 2002 Aug; 102(8): 1088–95
Efthimiou J, Fleming J, Gomes C, et al. The effect of supplementary oral nutrition in poorly nourished patients with chronic obstructive pulmonary disease. Am Rev Respir Dis 1988 May; 137(5): 1075–82
Rogers RM, Donahoe M, Costantino J. Physiologic effects of oral supplemental feeding in malnourished patients with chronic obstructive pulmonary disease: a randomized control study. Am Rev Respir Dis 1992 Dec; 146(6): 1511–7
Whittaker JS, Ryan CF, Buckley PA, et al. The effects of refeeding on peripheral and respiratory muscle function in malnourished chronic obstructive pulmonary disease patients. Am Rev Respir Dis 1990 Aug; 142(2): 283–8
Schols AM, Slangen J, Volovics L, et al. Weight loss is a reversible factor in the prognosis of chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1998 Jun; 157 (6 Pt 1): 1791–7
Schols AM, Broekhuizen R, Weling-Scheepers CA, et al. Body composition and mortality in chronic obstructive pulmonary disease. Am J Clin Nutr 2005 Jul; 82(1): 53–9
Vestbo J, Prescott E, Almdal T, et al. Body mass, fat-free body mass, and prognosis in patients with chronic obstructive pulmonary disease from a random population sample: findings from the Copenhagen City Heart Study. Am J Respir Crit Care Med 2006 Jan 1; 173(1): 79–83
Marti S, Munoz X, Rios J, et al. Body weight and comorbidity predict mortality in COPD patients treated with oxygen therapy. Eur Respir J 2006 Apr; 27(4): 689–96
Schols AM, Soeters PB, Mostert R, et al. Physiologic effects of nutritional support and anabolic steroids in patients with chronic obstructive pulmonary disease: a placebo-controlled randomized trial. Am J Respir Crit Care Med 1995 Oct; 152 (4 Pt 1): 1268–74
Creutzberg EC, Wouters EF, Mostert R, et al. A role for anabolic steroids in the rehabilitation of patients with COPD? A double-blind, placebo-controlled, randomized trial. Chest 2003 Nov; 124(5): 1733–42
Yeh SS, Lovitt S, Schuster MW. Pharmacological treatment of geriatric cachexia: evidence and safety in perspective. J Am Med Dir Assoc 2007 Jul; 8(6): 363–77
Goodridge D, Lawson J, Duggleby W, et al. Health care utilization of patients with chronic obstructive pulmonary disease and lung cancer in the last 12 months of life. Respir Med 2008 Jun; 102(6): 885–91
Claessens MT, Lynn J, Zhong Z, et al. Dying with lung cancer or chronic obstructive pulmonary disease: insights from SUPPORT. Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments. J Am Geriatr Soc 2000 May; 48(5 Suppl.): S146–53
Edmonds P, Karlsen S, Khan S, et al. A comparison of the palliative care needs of patients dying from chronic respiratory diseases and lung cancer. Palliat Med 2001 Jul; 15(4): 287–95
Gore JM, Brophy CJ, Greenstone MA. How well do we care for patients with end stage chronic obstructive pulmonary disease (COPD)? A comparison of palliative care and quality of life in COPD and lung cancer. Thorax 2000 Dec; 55(12): 1000–6
Lanken PN, Terry PB, Delisser HM, et al. An official American Thoracic Society clinical policy statement: palliative care for patients with respiratory diseases and critical illnesses. Am J Respir Crit Care Med 2008 Apr 15; 177(8): 912–27
Shee CD, Green M. Non-invasive ventilation and palliation: experience in a district general hospital and a review. Palliat Med 2003 Jan; 17(1): 21–6
Booth S, Kelly MJ, Cox NP, et al. Does oxygen help dyspnea in patients with cancer? Am J Respir Crit Care Med 1996 May; 153(5): 1515–8
Jennings AL, Davies AN, Higgins JP, et al. Opioids for the palliation of breathlessness in terminal illness. Cochrane Database Syst Rev 2001; (4): CD002066
Kara M, Mirici A. Loneliness, depression, and social support of Turkish patients with chronic obstructive pulmonary disease and their spouses. J Nurs Scholarsh 2004; 36(4): 331–6
Seamark DA, Blake SD, Seamark CJ, et al. Living with severe chronic obstructive pulmonary disease (COPD): perceptions of patients and their carers. An interpretative phenomenological analysis. Palliat Med 2004 Oct; 18(7): 619–25
No sources of funding were used to assist in the preparation of this review. The authors have no conflicts of interest that are directly relevant to the content of this review.
About this article
Cite this article
Nazir, S.A., Erbland, M.L. Chronic Obstructive Pulmonary Disease. Drugs Aging 26, 813–831 (2009). https://doi.org/10.2165/11316760-000000000-00000
- Chronic Obstructive Pulmonary Disease
- Smoking Cessation
- Palliative Care
- Chronic Obstructive Pulmonary Disease Patient