EJINME-02614; No of Pages 9 European Journal of Internal Medicine xxx (2013) xxx–xxx

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European Journal of Internal Medicine journal homepage: www.elsevier.com/locate/ejim

Review article

Chronic Obstructive Pulmonary Disease in the elderly☆ Raffaele Antonelli Incalzi a,b,⁎, Simone Scarlata a, Giorgio Pennazza c, Marco Santonico c, Claudio Pedone a a b c

Geriatrics, Unit of Respiratory Pathophysiology, Campus Bio-Medico University and Teaching Hospital, Rome, Italy San Raffaele — Cittadella della Carità Foundation, Taranto, Italy Center for Integrated Research — CIR, Unit of Electronics for Sensor Systems, Campus Bio-Medico University, Rome, Italy

a r t i c l e

i n f o

Article history: Received 7 January 2013 Received in revised form 21 June 2013 Accepted 4 October 2013 Available online xxxx Keywords: Elderly COPD Spirometry Multidimensional assessment

a b s t r a c t The prevalence of Chronic Obstructive Pulmonary Disease (COPD) dramatically increases with age, and COPD complicated by chronic respiratory failure may be considered a geriatric condition. Unfortunately, most cases remain undiagnosed because of atypical clinical presentation and difficulty with current respiratory function diagnostic standards. Accordingly, the disease is under-recognized and undertreated. This is expected to impact noticeably the health status of unrecognized COPD patients because a timely therapy could mitigate the distinctive and important effects of COPD on the health status. Comorbidity also plays a pivotal role in conditioning both the health status and the therapy of COPD besides having major prognostic implication. Several problems affect the overall quality of the therapy for the elderly with COPD, and current guidelines as well as results from pharmacological trials only to some extent apply to this patient. Finally, physicians of different specialties care for the elderly COPD patient: physician's specialty largely determines the kind of approach. In conclusion, COPD, in itself a complex disease, becomes difficult to identify and to manage in the elderly. Interdisciplinary efforts are desirable to provide the practicing physician with a multidisciplinary guide to the identification and treatment of COPD. © 2013 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

1. Clinical vignette An 81-year-old male with a clinical presumptive diagnosis of Chronic Obstructive Pulmonary Disease (COPD) and several comorbidities (hypertension, chronic stable angina, peripheral artery disease, chronic renal failure, severe osteoporosis and diabetes mellitus (DM), Parkinson's disease) presented to the Emergency Department (ED) with progressively worsening confusion and hypersomnolence. Despite the high risk of COPD, due to the presence of chronic productive cough, wheezing and exertional dyspnea, as well as the smoking history (22 packs/year), he had never been definitively diagnosed as affected by COPD because he could not perform an acceptable flow-volume curve maneuver. At admission, he complained of mild chest pain and orthopnea in the last three days. Prior to this acute event, the patient was partially autonomous in basic and instrumental activities of daily living, was able to walk without aids and showed no overt cognitive impairment (Mini-Mental State Examination, MMSE score obtained 6 months earlier: 24/30). However, according to his caregivers, he was poorly compliant to inhalers due to coordination limitation related to his extra-pyramid rigidity. In the past 4 months, he had been hospitalized twice for worsening dyspnea and/or expectoration, and he

☆ Grant support: none. ⁎ Corresponding author at: Geriatrics and Unit of Respiratory Pathophysiology, Campus Bio-Medico University and Teaching Hospital, Via A. Del Portillo 200, 00128 Rome, Italy. Tel.: +39 0622541653; fax: +39 0622541456. E-mail address: [email protected] (R.A. Incalzi).

had experienced a weight loss of about 6 kg. He received annual fluvaccine and Streptococcus pneumoniae vaccination. His therapy included: inhaled triple therapy (long acting B2-agonists, anticholinergics and corticosteroids), cardio-selective B-blockers, ACE-inhibitors, acetylsalicylic acid, metformin, glibenclamide, diphosphonates and D-vitamin integration. Vital signs on arrival to the ED were: blood pressure 110/ 65 mm Hg, heart rate 120 bpm and respiratory rate 28 bpm, oxygen saturation 87% on room air and temperature 36.8 °C. The patient was dehydrated and delirious. Chest auscultation disclosed diminished lung rumors and diffuse mild wheezing. Chest X-ray (CXR) on admission showed diffuse hyper-inflated and hyper-lucent lungs with loss of vascular markings and flat hemidiaphragms; no areas of consolidation were evident. Laboratory analyses demonstrated normal white blood cell (WBC) count, blood glucose of 250 mg/dL, serum lactate of 11 mmol/L, serum creatinine 1.4 mg/dL and urea nitrogen (BUN) 68 mg/dL. Arterial blood gas showed an acute over chronic hypoxemic– hypercapnic respiratory failure with respiratory acidosis (pH 7.33, PaCO2 46 mm Hg, PaO2 41 mm Hg, HCO3 29 mmol/L on room air). The patient was subsequently admitted to the acute respiratory care ward and was started on non-invasive ventilation and ceftriaxone. Hypoxemia, hypercarbia, and the acid–base balance quickly recovered to normal values and delirium disappeared. Supportive therapy consisted of supplemental oxygen, intravenous fluid replacement, diabetes control optimization, prophylactic unfractionated heparin and a personalized diet. Respiratory, hemodynamic, and renal indexes were closely monitored. After 48 h the patient was mentally integer, left the NIV and started the respiratory rehabilitation. The pulmonary function

0953-6205/$ – see front matter © 2013 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.ejim.2013.10.001

Please cite this article as: Incalzi RA, et al, Chronic Obstructive Pulmonary Disease in the elderly, Eur J Intern Med (2013), http://dx.doi.org/ 10.1016/j.ejim.2013.10.001


R.A. Incalzi et al. / European Journal of Internal Medicine xxx (2013) xxx–xxx

tests after a quick pharmacologic washout were successfully performed by a trained technician and revealed a severe fixed obstruction (FEV1/ FVC ratio of 43% and FEV1 34% of predicted value after inhaled bronchodilator trial) associated with an increased air trapping (RV 138% of predicted). A geriatric multidimensional assessment was performed and a comprehensive home care program delivered. After discharge he was regularly assessed at home with regard to long term oxygen prescription and re-trained on how to correctly use inhalers and recognize early symptoms and signs of acute exacerbation. In the following six months the patient regained weight, had less dyspnea and improved physical limitation. He did not suffer any new acute exacerbation of COPD in the following six months. This case report includes some of the most common features of COPD in the elderly. These features are the object of this review.

2. Is Chronic Obstructive Pulmonary Disease (COPD) an age-related chronic condition? COPD is a typical disease of aging as its prevalence dramatically increases with age, ranging in the USA population from about 6.6% in the 45–54 year age group to about 12% in N64 age group [1]. Data pertaining to European countries refer to the adult or overall, but not to the geriatric population (Table 1) [2,3]. COPD accounts for most of the people on long-term oxygen therapy, that is on average a population aged over 70years [4]. This finding likely reflects the effect of cumulative exposure to smoke and pollutants. Furthermore, telomere shortening, a distinctive sign of the aging process, characterizes COPD patients, and age and COPD additively promote it [5]. Interestingly, telomerase dysfunction and the accelerated telomere shortening are also common in endothelial cells involved in the atherosclerotic process, a prototypal age-related condition, as well as in immunologic diseases, such as rheumatoid arthritis, which are strictly related to age [6,7]. Thus, a clear-cut biological basis seems to underlie the epidemiological evidence, although the link between COPD and defective telomerase should be depurated of the effects of previous infections such as Cytomegalovirus infection [8]. Several other similarities between aging lung and COPD lung are worth noting: vital capacity declines by 10–20 mL yearly in normal aging [9], about 30 mL in COPD patients [10], whereas residual volume increases in both normally aging and COPD lung [11]. Furthermore elastic recoil, mucociliary clearance, mucosal immunity and vascular reserve decrease in the elderly and, more, in COPD [12].

Despite the strong link to age, COPD prevalence in the elderly is incompletely known. Indeed, both age-related changes in the clinical presentation of COPD and the confounding effect of comorbidity as well as several problems with the execution of spirometry contribute to hamper the diagnosis of COPD in the elderly population. 3. Why COPD is often so difficult to diagnose in the elderly population? COPD is rarely presenting alone in elderly patients. Comorbidity and disability of various origins contribute to make the recognition of COPD problematic. Furthermore, cognitive impairment, mainly of verbal memory and constructive ability, and depression may dominate the clinical scene in subjects with hypoxemia and hypercapnia [13,14]. Even severe exacerbations of COPD can be recognized late due to atypical presentation. Indeed, at variance with the classical triad of dyspnea, cough and fever [15], muscle weakness, vertigo, confusion and leg edema, all reflecting severe hypoxemia, are the hallmark of atypical presentations [16], and occasionally delirium may be the main presenting feature. Agerelated increase in the threshold of dyspnea and physical disability, frequently multifactorial in origin, variously contribute to make dyspnea a secondary feature of exacerbation in selected patients. Finally, chest pain may reflect right ventricular overload secondary to pulmonary hypertension or worsening myocardial ischemia by hypoxemia [16]. Disability of non-respiratory origin, e.g. orthopedic or neurologic, can restrain physical activity at a level well below the threshold for dyspnea, hampering the recognition of stable COPD in the elderly. As a consequence, experience and skill are required to suspect and, then, diagnose COPD in the elderly. Spirometry plays a pivotal role in the diagnostic workup [17], but frail and disabled people may be unable to satisfactorily perform this test. Table 2 summarizes conditions more frequently accounting for a poor quality pulmonary function test [18]. These factors contribute to the “epidemic” underdiagnosis of COPD: about half of patients with COPD escape recognition [18]. Furthermore, the need of complying with spirometry criteria results in a biased selection of patients recognized as affected by COPD by automatically excluding the most frail. Indeed, subjects have to meet acceptability criteria of spirometry in at least three curves and, then, with repeatability criteria [19]. Table 3 displays the currently requested acceptability and reproducibility criteria, together with the corresponding technical

Table 1 COPD prevalence in selected European countries. Country

COPD prevalence

Reference population

Data source


Austria Belgium

4.6% 5.3%

Adult population sample Middle-aged population

2007 2004

Czech Republic


Adult population


Total population


Over 5% have diagnosed COPD; a further 5% estimated to have concealed COPD 6% to 8%

Statistik Austria Ministry of Health. Health for all database Institute of Health — Information and Statistics The National Finnish COPD Programme

Germany Ireland Italy Netherlands

13.2% 7.3% 4.5% 2%

Adult population Adult population Total population Estimated



Adult population

Serbia United Kingdom

6.0% 1.5% correctly diagnosed; 3.7 million (6%) estimated to be affected

Adult population Population over 40 years old

Adult population

Ministère de la Santè et des Solidaritès Geldmacher et al. (BOLD study) [2] The Irish Thoracic Society ISTAT National Institute for Public Health and the Environment National Observatory of respiratory disease Institute of Public Health of Belgrade Stang et al. [3]

2007 2007

2005 2008 2008 2007 2006 2008 2007 2000

Please cite this article as: Incalzi RA, et al, Chronic Obstructive Pulmonary Disease in the elderly, Eur J Intern Med (2013), http://dx.doi.org/ 10.1016/j.ejim.2013.10.001

R.A. Incalzi et al. / European Journal of Internal Medicine xxx (2013) xxx–xxx Table 2 Main conditions potentially affecting the quality of spirometry and, consequently, the achievement of a state of art COPD diagnosis in the elderly. Patient related conditions • Motor and sensory deficits, e.g. pyramidal or e tra-pyramidal disorders – Lack of de terity and poor control of ventilation during spirometry; – Difficulty in coordination and properly sequencing the flow volume maneuver and the breath holding. • Dementia or cognitive impairment: deteriorated constructive functions, verbal attainment and, mainly, secondary verbal memory – Difficulty in learning and recall instruction to perform spirometry – Poor ability to interact with the technician or physician • Mood depression and psychological factors – Poor motivation, early discouragement for unsuccessful trials. • Educational level – Ability to understand technical instructions • Malnutrition/undernutrition, deconditioning: respiratory muscles weakness – Difficulty in providing acceptable and reproducible tests Environment and technician related conditions • Poor geriatric eXpertise of the physician or technician – She/he is unable to teach the patient through a variety of non-verbal tools, like visual eXamples or touch-guided respiratory maneuver. – She/he does not motivate the proband by stressing any, even minimal, improvement, and does not tailor the teaching process to the individual learning potential. • Unpleasant or stressful environment – The diagnostic test does not fit the age-related slowing of learning process and, then, the need for gently repeated or even fractioned maneuvers.

index to determine quality control and the factors most commonly affecting the achievement of a good spirometric curve. Indeed, in the context of a study dedicated to spirometry for the elderly, the SaRA (Salute Respiratoria nell'Anziano = Respiratory Health in the Elderly) study, 4 out of 5 subjects over 64 with or without COPD could comply with acceptability criteria; cognitive impairment, poor physical performance and lower educational status characterized non-performers, while older age, male gender and severe bronchial obstruction were associated with unacceptable reproducibility [18]. Interestingly, the volume of spirometries performed correlated positively with combined acceptability and reproducibility, stating that the experience of individual laboratory of respiratory pathophysiology contributes to the overall quality of the spirometry [20]. In an attempt at expanding the number of elderly people having a diagnostic spirometry, FEV6, i.e. the maximum volume of air expired at any time before the 6° s of the forced expiratory maneuver has been introduced and repeatedly tested. If the patient is unable to reach an


end expiratory plateau ≥ 1 s, forced vital capacity (FVC) is not measurable, while FEV6 is. In Fig. 1 these differences are graphically represented. Accordingly, FEV1/FEV6 can substitute for FEV1/FVC. FEV6 has been proved to have good diagnostic properties for both obstructive and restrictive respiratory diseases [21]. It also identifies smokers at risk of faster respiratory decline [22]. The availability of reference standards, even for the elderly population, makes FEV6 of practical use [23,24]. Unfortunately, FEV6 is not a panacea: 440 out of the 1971 enrolled in the SaRA study could not perform spirometry (n = 101) or achieve a retrograde extrapolated volume b150 mL, i.e. did not achieve the requested explosive expiration [25]. Thus, neither FVC nor FEV6 could be measured in 440/1971 probands. Furthermore, achievement and repeatability of FVC and FEV6 were defective in 262 and 186 people out of the 1531 who successfully performed spirometry respectively. Older age, a restrictive pattern, cognitive impairment and lower education were the main correlates of inability to achieve an acceptable and repeatable FEV6 (Fig. 1) [26]. An additional diagnostic problem even for subjects able to perform spirometry is represented by the diagnostic criteria used. All the current guidelines use a reduction of the FEV1/FVC (or VC =slow vital capacity) as the hallmark for the diagnosis of bronchial obstruction. Reduction of FEV1/VC can be defined against a “fixed” cut-off (usually 0.7) or a lower limit of normal that corresponds to the 5th percentile of the theoretical distribution of the parameter in a healthy population of the same age, gender and body size. The former definition is recommended by the Global initiative against chronic Obstructive Lung Disease (GOLD), the latter by the ATS/ERS guidelines [17]. Both definitions have their drawbacks. On the one hand, the fixed cut-off does not take into account that FEV1 and VC do not decrease at the same rate with aging [26]. As a consequence, a fixed cut-off tends to over-diagnose bronchial obstruction in elderly people. On the other hand, the lower limit of normal is calculated using predictive equations based on the assumption that the variability is proportional to the predicted values across ages; its validity also depends on the availability of standards developed in a reference normal population as similar as possible to the population under study. Both these assumptions are often unrealistic, especially in elderly people. The use of a lower cut-off in elderly people (0.65 and 0.67 in men and women, respectively) has been proposed and may overcome the shortcomings of the fixed cut-off and of the lower limit of normal [27]. Despite these limitations, spirometry remains the mainstay for the diagnosis of COPD and, broadly speaking, respiratory diseases at any age. Furthermore, it can provide important information on dynamic

Table 3 Factors limiting the achievement of acceptability and repeatability criteria in performing spirometry among elderly [18]. Acceptability criteria [12]

Quality control

Limiting factors in elderly

Good start (no hesitation to begin the maneuver)

• E trapolated volume is b5% of FVC or 0.15 L, whichever is greater or • Time to PEF is b120 ms (optional until further information is available) • 6 s of e halation and/or a plateau in the volume–time curve or • Reasonable duration or a 1-second plateau in the volume–time curve or • The subject cannot or should not continue to e hale • Cough or glottis closure during the first second of e halation • Early termination or cutoff • Variable effort • Leak • Obstructed mouthpiece • Two largest FVCs within 0.2 L of each other • Two largest FEV1s within 0.2 L of each other

• Motor and sensory deficit • Respiratory muscle weakness • Deconditioning

Satisfactory and complete e halation

Absence of artifacts

At least three acceptable spirograms satisfying repeatability quality control criteria

• Severe air trapping or airway obstruction • Restrictive lung disease • Poor motivation • E piratory dyspnea • Difficulty on learning and recall instruction to perform spirometry • Poor ability to interact with the technician

• Respiratory muscles weakness or poor endurance • Physical unfitness and deconditioning • Poor motivation

Please cite this article as: Incalzi RA, et al, Chronic Obstructive Pulmonary Disease in the elderly, Eur J Intern Med (2013), http://dx.doi.org/ 10.1016/j.ejim.2013.10.001


R.A. Incalzi et al. / European Journal of Internal Medicine xxx (2013) xxx–xxx

Fig. 1. Spirometric representation, in a volume/time curve, of a maximal expiratory maneuver. Acceptability criteria for FVC and FEV6 are illustrated. Panel A: The proband achieved a good start and a complete exhalation. Thus, both FVC and FEV6 were measurable; panel B: Good start, but incomplete exhalation. FEV6, but not FVC could be measured; panel C: the maneuver lacked a good start and a complete exhalation. Neither FVC nor FEV6 could be measured.

air trapping. i.e. on exercise-related decrease in inspiratory vital capacity due to increased expiratory reserve volume. Dynamic hyperinflation is a major correlate of dyspnea [28], and interventions able to limit it effectively prevent dyspnea [29]. Thus, spirometry can guide the therapy besides allowing a correct diagnosis. Recently, efforts have been made at developing alternative diagnostic methods, but no solution has so far been made available. A very interesting and promising possibility is represented by the technology of the electronic nose that is an array of sensors that mimics the olfactory epithelium. It is based on six microbalance sensors covered with metalloporphyrins that upon interaction

with volatile organic compound undergo frequency shifts that can be displayed as a sort of graphical breath print (Fig. 2). Such a technique has proved to have important diagnostic properties versus lung cancer, asthma and COPD [30,31]. Preliminary results available for elderly COPD patients are very encouraging [32]. The method is very easy, inexpensive, highly repeatable and safe [33]. However, up to now the electronic nose should be considered a research tool. Large studies are needed to confirm its diagnostic and classificatory properties. Table 4 shows currently available evidence supporting the use of an electronic nose in lung diseases [31–39].

Fig. 2. Seven-sensor response pattern registered by a Quartz micro balance based e-nose [22] for four patients over 64 years (A: control; B: COPD Gold standard 1; C: COPD Gold standard 3; D: COPD Gold standard 4). The four fingerprints are reported in statistical terms (whiskers plot) because they average three measurements along a period of three weeks. Three patterntypes are evidently different in terms of profile and of dimensionality: A (ranging from 500 to 3500 Hz), B and C (ranging from 100 to 800 Hz), D (ranging from 300 to 1300 Hz).

Please cite this article as: Incalzi RA, et al, Chronic Obstructive Pulmonary Disease in the elderly, Eur J Intern Med (2013), http://dx.doi.org/ 10.1016/j.ejim.2013.10.001

R.A. Incalzi et al. / European Journal of Internal Medicine xxx (2013) xxx–xxx Table 4 Diagnostic accuracy of volatile organic compounds fingerprint in the diagnosis of respiratory diseases. Lung cancer

Results widely depend on the different sensor system used. Quartz microbalances currently show the best diagnostic accuracy around 90%. Sensitivity and specificity range from 70 to 90% [31]. Asthma The sensor system was able to separate mild asthmatics from controls, and moderate to severe asthmatics from controls, but not mild and moderate from severe asthmatic groups [35]. COPD Breath fingerprint was highly sensitive and specific in discriminating COPD patients from controls [32], hypo emic from non-hypo emic COPD [33] and COPD from asthma [30,34] Interstitial lung disease E haled ethane seems a valuable indicator of disease activity and prognosis for ILDs [36]. Tuberculosis and The system was 89% sensitive and 91% specific at identifying other lung infections M. tuberculosis [37]. It was also able to differentiate several in-vitro gram + and gram − bacteria [38]. E-nose fingerprints correctly classified 77% of the BAL samples, with and without microbiological growth, from ventilated patients not on antibiotics. Inclusion of patients on antibiotics resulted in 68% correct classification. Seventy percent of isolates were accurately discriminated into four clinically significant groups [39].

Finally, asthma is not uncommon in the elderly and should be distinguished from COPD. Two types of asthma have been described in the elderly: an early onset form, which dates back to young adulthood and is easily recognized, even if it recurs after several years, and a late onset form. This latter form is frequently misclassified as COPD, and older age and disability are the main correlates of misclassification [40]. Sputum eosinophilia and need of frequent steroid therapy may raise the suspect of asthma, but reversibility of the bronchial obstruction may be partial. Furthermore, based on a cluster analysis, a group of older obese women with late onset non-atopic asthma has been characterized as having moderate reductions in FEV1 and frequent exacerbations requiring oral corticosteroids [41]. A tentative diagnostic algorithm is proposed in Table 5.

4. How does COPD impact health status in old patients? COPD affects health status throughout all its natural history, but this effect becomes dramatic for FEV1 b 50% predicted [42]. Furthermore, even subjects who have not had their disease recognized suffer from noticeable health status impairment [43]. Loss of muscle mass, dyspnea, cognitive and affective disorders, osteoporosis and sleep troubles variously interact to impair personal independence and perceived health status [44]. A tentative synopsis of mechanisms affecting health

Table 5 A proposed diagnostic algorithm for asthma in the elderly. History

Respiratory function tests

Supportive elements

H1. Recurrent wheeze

R1. Positive methacholine test

H2. Nocturnal wheeze

R2. Completely reversible bronchial obstruction R3. Partially reversible bronchial obstruction

S1. Early onset (in adolescence or young adulthood) S2. History of atopy

H3. Dry cough (variant clinical presentation)

S3. Triggers identified S4. Sputum eosinophilia S5. Steroid dependence S6. Normal DLCO

Proposed diagnostic criteria: A. H1 and/or H2 plus R1 and/or R2 (supportive elements unnecessary); B. H3 plus R1 and/or R2 (supportive elements unnecessary); C. Any combination of H and R3: one or more supportive elements (S1 to S6).


status in COPD is provided in Fig. 3. It is also worth noting that the relationship between COPD course and health status may be to some extent reciprocal: for example, cognitive problems variously affect the adherence to the therapy (see Which are the main therapeutic problems in elderly COPD patients and which evidences are still lacking in this population? section), and sleep troubles may foster the improper use of respiratory depressant drugs [45]. Furthermore, depression is associated with persistent smoking and increased mortality [46]. These and other examples testify to the possibility that worsening health status further accelerates the progression of COPD. Thus, any effort should be made to interrupt this vicious circle. In the SaRA study, 31% of COPD patients had good health status, as reflected by physical and cognitive performance, affective status and quality of sleep, while 41% and 27% had moderately and severely deteriorated health status, respectively [42]. Variables exploring the physical domain, i.e. independence in activities assessed by the Barthel test and submaximal physical performance, were the main determinants of the health status pattern. Unexpectedly, the concordance between severity of airway obstruction and health status impairment was only moderate: 24.3% of patients with mild COPD had severely deranged health status, while 15.5% of those with severe COPD had fine health status. These findings caution against oversimplifying the relationship between bronchial obstruction and health status. Both phenotypic variability and comorbidity variously affect health status. For instance, dynamic hyperinflation, the phenomenon of exercise dependent air trapping, is associated with important dyspnea and, then, physical limitation [47]. Social factors also contribute to health status and, in a special way, to the use of health care resources. The latter item is also relevant to the evolution of health status: it has been demonstrated that health status measurably declines after a hospital stay for exacerbated COPD [48]. Indeed, the rate of hospitalization of elderly people for exacerbated COPD is inversely related to the income; the same relationship has been demonstrated for other chronic conditions such as diabetes mellitus and congestive heart failure or for stroke, an acute condition deeply rooted in chronic conditions, but not for hip fracture [49]. Thus, even the optimal therapy should be supported by social interventions to improve health status. Measuring basic and instrumental activities of daily living (ADL and IADL) and selected measures of physical performance and analyzing their combinations allow verification that COPD affects personal independence in a distinctive way with regard to other chronic conditions such as congestive heart failure and diabetes mellitus [50]. This difference extends also to needs of care: for instance, the combination of three physical limitations, e.g. in going around outside, climbing up or down the stairs and walking for at least 400 m, identifies patients with a longer stay for exacerbated COPD. 5. What's about the prognosis of COPD? The overall prognosis of COPD is poor. The 3-year mortality in a COPD population without respiratory failure or other serious disease has been reported to be 23% [51]. More recently, data from the TORCH (Towards a Revolution in COPD Health) trial on patients with average FEV1 of 44% showed a mortality of 15% in the placebo group [52]. Similar data came from the UPLIFT (Understanding Potential Long-term Impacts on Function with Tiotropium) trial [53] that enrolled patients with comparable severity. The stratification of COPD severity is classically based on the degree of FEV1 reduction, although the most recent GOLD guidelines [54] also include frequency of exacerbations in their grading systems. In the elderly, however, a risk stratification only based on respiratory characteristics may be inadequate. In a population of COPD patients with a mean age N 65 years, mortality was best predicted by a composite index (the BODE index) including FEV1 along with nutritional status, exercise capacity, and dyspnea [55]. The drawbacks of expressing FEV1 using predicted values (see above) also apply to risk stratification. Alternative ways of expressing

Please cite this article as: Incalzi RA, et al, Chronic Obstructive Pulmonary Disease in the elderly, Eur J Intern Med (2013), http://dx.doi.org/ 10.1016/j.ejim.2013.10.001


R.A. Incalzi et al. / European Journal of Internal Medicine xxx (2013) xxx–xxx

Fig. 3. Synopsis of factors and interactions conditioning health status in the elderly COPD patient.

FEV1, such as FEV1 divided by the height cubed, may be more appropriate in the elderly population [56]. A further major issue that needs to be taken into account with respect to prognosis is the heterogeneity of COPD itself. Beyond the classic distinction between the “bronchitic” and the “emphysematous” phenotype, different distinctive characteristics – such as responsiveness to bronchodilators, frequency of exacerbations, and presence of pulmonary hypertension – have been described that allow identifying different phenotypes with different prognoses. Phenotype heterogeneity likely underpins the highly variable rate of FEV1 decline observed in COPD patients [57]. Finally, comorbidity is a major prognostic factor in elderly COPD patients. A list of COPD-associated comorbidities is showed in Table 6. In a sample of 270 patients, mean (±SD) age 67 ± 9 years, followed up for 3.5 years, mortality was more strictly associated with chronic renal failure and coronary artery disease than with depressed FEV1 at baseline [58]. However, age per se was the main negative predictor followed by EKG signs of right heart dysfunction: 6 year survival was 7% in patients with both a P wave consistent with right atrial overload and S1S2S3 (an S wave in D1, D2 and D3 leads), 18% if one of these signs was present and 36% in the absence of both, stating that the EKG effects of pulmonary hypertension mark a condition with a very poor prognosis [59]. Neuropsychological dysfunction, as expressed by defective copying design, also contributes to worsen the prognosis [60], likely as a marker of damage of the deep brain, mainly the insula, secondary to hypoxemia and hypercapnia and ensuing autonomic dysregulation [61]. In-hospital mortality also is affected by non-respiratory factors such as atrial fibrillation and ventricular arrhythmias [62]. Unfortunately,

comorbidity, a conditio sine qua non of COPD in the elderly, has not been systematically collected and taken into consideration as a prognostic determinant in most of the studies. 6. Which are the main therapeutic problems in elderly COPD patients and which evidences are still lacking in this population? Many problems affect the quality of therapy for COPD in elderly people: 1) The source of information from pharmacological trials is intrinsically biased by selection criteria: 12 exclusion criteria are reported in the TORCH trial [52], 19 in the UPLIFT [53] and 22 in the POET-COPD (Prevention of Exacerbations with Tiotropium in COPD) trial [63]. Comorbidity, cognitive impairment, depression and physical limitations, which are the hallmark of COPD in the elderly, are among the most recurrent exclusion criteria. For instance, the means of participants in these trials were 65 years (range 40–80; SD 8.2) for TORCH, 65 years (SD 8.0) for UPLIFT, and 63 (SD 9.0) for POET-COPD. As a consequence, trial-based information “may not” apply to the average elderly COPD patient, the one we daily care for in our wards and ambulatories. 2) Inhaler devices, seemingly simple to use, may be quite demanding for an elderly COPD patient. Indeed, coordination and respiratory muscle strength are variously required to correctly inhale the drug. It has been proved that cognitive impairment dramatically impacts the ability to correctly use the inhalers: scoring less than 24 on the Mini-Mental State Examination (MMSE) test, a simple screening instrument, is associated with a very high risk of failure [64]; even

Table 6 Comorbid conditions classified according to their relationship with COPD *. Con-causal: sharing risk factors, mainly smoke

Coe isting in the absence of shared risk factors, e cept for age

Complicating COPD

Atherosclerotic disease: coronary, cerebral, lower limbs Chronic renal failure Lung cancer Congestive heart failure Aortic aneurysm Bladder cancer Pulmonary fibrosis (respiratory bronchiolitis–interstitial lung disease)

Glaucoma Cognitive impairmenta Diabetes mellitus Benign prostatic hypertrophy Degenerative joint disease Hypertension Obstructive sleep apnea

An iety/depression Cognitive impairmenta Osteoporosis Sarcopenia Arrhytmias Dysphagia Pulmonary embolism

* The list of comorbidities is not exhaustive. It focuses on the conditions for which the available clinical and epidemiological evidence is more solid. a Cognitive impairment may either complicate COPD or coexist with COPD, being degenerative or atherosclerotic in origin. It rarely complicates COPD in the absence of chronic hypoxemia.

Please cite this article as: Incalzi RA, et al, Chronic Obstructive Pulmonary Disease in the elderly, Eur J Intern Med (2013), http://dx.doi.org/ 10.1016/j.ejim.2013.10.001

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an abnormal pentagon copying test, a component of the MMSE assessing constructive ability, identifies patients unable to use inhaler devices (Fig. 4). The adherence to both pharmacological and non-pharmacological therapy is frequently poor in the presence of cognitive impairment. Either a screening test, such as the MMSE, or a confirmatory neuropsychological assessment, like the Mental Deterioration Battery, or a test of secondary memory, e.g. the Rey's fifteen word test, successfully identifies COPD patients at risk of poor compliance [65–67]. Repeated rehabilitation can dramatically slow the decline of health status and decrease the need of health care as well as improve COPD-related mood disorders [68,69]. Based on these evidences, depressed and disabled patients should be considered for and not excluded from rehabilitation programs. These beneficial effects are also evident in older [70] and severely diseased patients [71], but rehabilitation remains under-prescribed [72]. Many problems characterize this patient and require dedicated care to minimize her/his sufferance (suffering) and to help relatives and caregivers [73]. Unfortunately, at variance from palliative care for the neoplastic patient, palliative care for the respiratory patient, is poorly available and less perceived as an important health need [74]. The few available experiences show that providing at home palliative care is quite demanding and poses important organization problems [75]. For a comprehensive overview of the subject, the reader is referred to the state of art review by Halpin and colleagues [76]. Elderly COPD patients are exposed to an important risk of adverse drug reactions due to overdosage of drugs with renal clearance. Indeed, sarcopenia, a common trait of severe COPD, blunts the creatinine rise due to depressed glomerular filtration rate. Thus, moderate (GFR = 60–30) and even severe renal failure may remain unrecognized [77]. This problem can emerge in the occasion of acute exacerbation requiring antibiotics or chronically for non-respiratory drugs and also for some topic bronchodilators which are fractionally adsorbed and cleared by the kidney. Polypathology and inherent polypharmacy is the rule in the elderly COPD patient [78]. It is frequently unclear to which extent guidelines for individual diseases apply to such a complex patient. For example, beta-blockers for coexisting CHF have historically been considered to worsen bronchial obstruction in COPD, whereas they are currently contraindicated in asthma, but not in COPD [79]. Furthermore, highly prevalent comorbidities can dramatically impact the respiratory function; for example, osteoporosis can account for vertebral fractures and, then, a restrictive component

Fig. 4. Mini-Mental State Examination test: the two pentagons copy figure for the evaluation of constructive ability. A defective performance targets elderly patients at risk of misuse of inhalation devices.


of the respiratory dysfunction [80]. Analogously, obstructive sleep apnea syndrome, which is very common but has atypical presentations in the elderly [81], can directly affect the respiratory function. The screening, assessment and treatment of comorbidities in COPD patients are therefore a pivotal approach deserving systematic attention by clinicians. 7) Hypercatabolism and accelerated loss of muscle mass characterize severe exacerbations of COPD, but they also are a sort of phenotypic trait of an important fraction of COPD patients. Thus, attempts at treating promptly the exacerbation, so that the inflammatory response ceases, and providing nutritional support and rehabilitation are key issues in the treatment of exacerbated COPD. Nutritional interventions could improve both respiratory and peripheral muscle strength, but not respiratory function indexes [82]. As for very frail and disabled geriatric patients [83], a comprehensive intervention program, mainly based on exercise and nutritional support, seems worth testing. 7. How should the physicians approach the elderly COPD patient? Does the real world approach change as a function of specialty? While guidelines for the treatment of COPD, mainly GOLD, NICE, and ATS/ERS, have been produced and disseminated in the last ten years, the approach to COPD has been reported to vary as a function of the physician's specialty [84]. It has been reported that both geriatricians and pulmonologists conform to a specialty-specific approach to COPD, whereas internists are characterized by a great variety of approaches [84]. Interestingly, the comprehensive approach to the health status is the hallmark of the geriatrician's approach, while the attention to phenotypic heterogeneity of COPD is that of the pulmonologist's approach. Indeed, multidimensional assessment is common practice for the geriatrician, whereas pulmonologists pay attention to clinical implications of dynamic hyperinflation. Since both approaches are highly motivated for the elderly COPD patient, it seems desirable to combine elements of both in order to improve the quality of care. Unfortunately, the most widely used guidelines (GOLD, NICE, and ATS/ERS) neither refer to specific issues of interest for the elderly nor underline the distinctive features of COPD in this large subset of patients. Indeed, only in their last version recently GOLD guidelines have started to mention comorbidity [54] In addition, the ATS/ERS guideline on rehabilitation partly addressed these topics when considering depression and anxiety [85]. 8. Conclusions COPD is a “blanket” definition for a very heterogeneous disease. Older age adds to this heterogeneity mainly in terms of atypical presentation, confounding by comorbidity and poor knowledge of age-related changes in responsiveness to therapy proved useful in adult populations. Efforts should be made to provide respiratory function standards really valid for the elderly as well as to make the diagnostic procedures suitable for the vast majority of the elderly patients so that also frail and disable people be screened and diagnosed to have or not to have COPD. Clinical trials should be rethought to include frail people and, thus, generate real world results. The overall approach to these patients should ideally share expertise and skills from different specialties to provide a comprehensive approach to a multifaceted disease. However, preliminary and introductory to these actions is the spreading of awareness of COPD as a major health and social problem by the public opinion and political authorities. Indeed, chronic non-communicable diseases like ischemic heart disease or diabetes mellitus are correctly perceived as a dramatic burden for our societies, while the same is not true for COPD, despite the clear epidemiological evidence [86]. Knowledge precedes and motivates action: the well evident diagnostic and therapeutic difficulty with COPD in the elderly will probably wane only if COPD will be correctly

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Chronic Obstructive Pulmonary Disease in the elderly.

The prevalence of Chronic Obstructive Pulmonary Disease (COPD) dramatically increases with age, and COPD complicated by chronic respiratory failure ma...
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