- Email: [email protected]
The Challenge of Controlling the COPD Epidemic: Unmet Needs
Accepted Manuscript
The Challenge of Controlling the COPD Epidemic Chronic Obstructive Pulmonary Disease: Unmet Needs Francesca Polverino MD, PhD , Bartolome Celli MD PII: DOI: Reference:
S0002-9343(18)30414-5 10.1016/j.amjmed.2018.05.001 AJM 14665
To appear in:
The American Journal of Medicine
Received date: Accepted date:
6 March 2018 4 May 2018
Please cite this article as: Francesca Polverino MD, PhD , Bartolome Celli MD , The Challenge of Controlling the COPD Epidemic Chronic Obstructive Pulmonary Disease: Unmet Needs, The American Journal of Medicine (2018), doi: 10.1016/j.amjmed.2018.05.001
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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Highlights
Chronic obstructive pulmonary disease (COPD) is often under- or misdiagnosed and consequently under- or mistreated. It is important that clinicians, particularly those in primary care, are educated to
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be able to recognize and correctly diagnose COPD and treat patients in line with the guidance provided by treatment recommendations.
This review aims to address this and fill other important knowledge gaps.
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The Challenge of Controlling the COPD Epidemic Chronic Obstructive Pulmonary Disease: Unmet Needs
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Francesca Polverino, MD, PhD, Bartolome Celli, MD Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA
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Funding: This work was supported by Boehringer Ingelheim Pharmaceuticals Inc. Conflict of Interest: FP has nothing to disclose. BC reports personal fees from
GlaxoSmithKline, Boehringer Ingelheim, and Novartis, and grants and personal fees from
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AstraZeneca, all outside of the submitted work.
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Authorship: Both authors contributed equally to all aspects of the manuscript. Requests for reprints should be addressed to Francesca Polverino, MD, Pulmonary and
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Critical Care Medicine, Brigham and Women’s Hospital, Harvard Institute of Medicine,
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77 Avenue Louis Pasteur, Boston, MA 02115.
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E-mail address: [email protected]
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ABSTRACT Many unmet needs still remain in the assessment and treatment of patients with chronic obstructive pulmonary disease (COPD), particularly in relation to its under- and
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misdiagnosis, which lead to under- and mistreatment. This paucity of knowledge about the importance and presence of COPD, as well as its treatment, is seen with patients and carers as well as healthcare providers. This review considers the areas of key educational need, including the clinical characteristics of COPD, factors contributing to the disease,
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effective diagnosis, and clinical management of patients, and the implementation of
treatment guidelines. As COPD remains the third most frequent cause of death in the world, we must continue to expand the scope and reach of our efforts to improve
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outcomes in this debilitating disease.
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KEYWORDS: Burden; COPD
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INTRODUCTION Over recent decades, the progressive control of communicable diseases as the most important causes of morbidity and death in the world has resulted in three important changes: firstly, an
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increase in the world’s population; secondly, a simultaneous improvement in longevity; and thirdly, an increase in the prevalence of non-communicable diseases (NCDs).1 An NCD is a medical condition or disease that is, by definition, non-infectious and non-transmissible between humans. The four most important NCDs are cardiovascular diseases, cancers,
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respiratory diseases, and diabetes, leading to 17.7 million, 8.8 million, 3.9 million, and
1.6 million deaths annually, respectively, according to the World Health Organization.2 Besides having an important genetic determinant, the World Health Organization’s World Health Report identified tobacco smoke, alcohol consumption, being overweight, physical
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inactivity, high blood pressure, and high cholesterol as important risk factors for NCDs.2
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One important group of NCDs is the chronic lung diseases, with asthma and chronic obstructive pulmonary disease (COPD) representing the great majority. This review
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summarizes our current knowledge regarding COPD and attempts to identify the unmet
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needs surrounding its unfortunate emergence as a large contributor to poor health around the world.
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DEFINITION AND CLINICAL CHARACTERISTICS COPD is a lung disease that causes limitation to airflow in and out of the lungs. It results from an abnormal airway and parenchymal response to inflammation caused by the inhalation of toxic particles contained primarily in cigarette smoke, the combustion of biomass for cooking and heating purposes, and from environmental pollution.3 Although an
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accelerated loss of lung function is seen in half of individuals who develop COPD, the other half most likely reach the disease state from alterations in the pre- or post-natal period of lung development.4,5 COPD symptoms include breathing difficulty, cough, sputum production, and wheezing, which may be present for years before the diagnosis is made.
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Patients with COPD are at increased risk of developing several co-morbid diseases compared to age- and sex-matched patients without COPD [ref. to Criner suppl, Am J Med 2017].6 Although most patients with COPD die from cardiovascular disease or cancer, a substantial proportion die from respiratory failure as, once present, COPD tends to progress, causing a
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decrease in functional capacity, disability, the need for mechanical ventilation, and, eventually, death.3,7
Until recently, the degree of airflow limitation, measured using a spirometer, was the only
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tool used to determine the severity of COPD, assess the response to medications, and follow
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disease progression. Irreversible or partially reversible airflow limitation, measured by spirometry before and after administration of an inhaled bronchodilator (e.g., albuterol
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400 µg), is the characteristic physiologic feature of COPD. Spirometry is a simple test – reliable, affordable, and well tolerated – and its use should be encouraged at all levels of
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care.8 It not only improves the accuracy of diagnosis of COPD, but also results in significant
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improvements in management, without input from secondary care.9 Spirometry can lead to substantial over-diagnosis of COPD in never-smokers >70 years of age, but produces fewer false-positive results in younger adults.10,11 Early intervention strategy aimed at increasing smoking-cessation rates12-14 and smoking abstinence is likely to be more effective than an early detection strategy of performing spirometry on patients who do not recognize or report respiratory symptoms.
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On a personal clinical note, we would like to point out that spirometry not only helps in detecting the fixed obstruction of COPD, but, importantly, the reversibility that characterizes asthma, and it may suggest the presence of restrictive pulmonary diseases, an increasingly
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important clinical problem in everyday practice. EPIDEMIOLOGY
Globally, COPD accounted for 5% of all deaths in 2015, with >90% of COPD deaths
occurring in low- and middle-income countries.15 The prevalence of COPD hovers around
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10% across the world but varies in different regions, as has been determined in 2 population studies: PLATINO in Latin America16 and BOLD17 across the rest of the globe. In the United States, COPD has a prevalence of ~6.4% and is the third leading cause of death.18 The age-adjusted mortality rates can vary by state, from a low in Hawaii (27.1 per 100,000)
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to a high in Oklahoma (93.6 per 100,000).19 The disease affects men and women almost
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equally, due in part to increased tobacco use among women in high-income countries. Unfortunately, >50% of people with spirometric evidence of COPD have never been
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diagnosed.20 This proportion is likely to be higher in patients with mild COPD, who would benefit most from therapy.21 Following the introduction of smoke-free legislation in the
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United States, the number of COPD-related hospital admissions has declined.22 However,
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with close to 15% smoking rates in the country, COPD as a health problem is here to stay.23 AGE, SEX, ETHNICITY, EDUCATION, AND INCOME AS FACTORS CONTRIBUTING TO COPD COPD primarily affects individuals >40 years of age and its prevalence increases with age, with an approximate 5-fold increased risk for those aged >65 years compared to patients
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aged <40 years.24 The prevalence of COPD increases with smoking status, yet neversmokers comprise ~23% of individuals with COPD, suggesting the existence of other risk factors such as passive smoking or factors of occupational exposure.25 In the United States, the age-adjusted prevalence is usually higher among non-Hispanic white patients compared
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to African-American or Hispanic patients,26 and is higher among women than men.27
An association between educational level and COPD is present in both never-smokers and smokers.28,29 Possible mechanisms explaining the adverse effects of low socioeconomic
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status on COPD among never-smokers might be poor dietary habits (low in antioxidants and fresh fruit),30,31 poor housing conditions,32 more occupational dust exposure, and indoor air pollution from biomass combustion.3
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COST OF COPD TO SOCIETY
The growing burden of COPD exacts an economic cost, as people are less productive, less
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able to work, and die prematurely.33 The medical costs related to COPD were estimated to
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be $32.1 billion in 2010 and are projected to rise to $49 billion by 2020.34 Direct healthcare costs account for nearly two-thirds of total COPD costs, including physician office visits,
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hospitalizations, home care, and medications.35 Furthermore, there is a direct relationship between severity of COPD and the overall cost of care.35 Hospitalization was identified as
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the most important cost variable across all severity stages of COPD.36,37 In a survey of the burden of COPD in the United States, it was shown that 6% of patients took time off work due to COPD, whereas work loss among caregivers of patients with COPD was reported by 7% of respondents.38
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There is a strong association between COPD exacerbations and hospitalization. The number of admissions to hospital has remained stable since 1999 despite a decrease in the length of stay for a COPD-related hospitalization in the past 10 years.35 This trend is likely to continue as exacerbations requiring hospitalization only become more frequent and severe
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with increasing age and disease progression.35,39,40 Overall, the cost of caring for patients with COPD is alarming, so much so that the Centers for Medicare and Medicaid Services have singled out 30-day re-admission rates as 1 target to evaluate burden of care and quality
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of health delivery for hospitals across the country.41 EFFECTS ON THE INDIVIDUAL PATIENT
Although the economic cost is important, the physical and psychological effects of COPD on
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the individual are even more important. The cardinal symptom of dyspnea leads to considerable modifications in lifestyle, such as limitation or total elimination of outings and
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holidays to avoid crowds, hills, and stairs. The loss of work and subsequent social isolation
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related to limitations in leisure activities have a profound effect on individuals with COPD. A feeling of ―shame‖ is usually felt by patients with COPD and is mainly related to the
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notion that their disease is self-inflicted.42 COPD is stigmatized not only by patients but also by members of society because it has resulted primarily from what is now considered an
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abnormal behavior (smoking). In addition, the most severely affected patients require oxygen equipment that singles them out in crowds and effects bodily changes, thereby disrupting their social interactions.43 Patients with COPD who feel stigmatized may hesitate to seek care for fear of judgment or negative repercussions associated with having the condition.43 Not least is the effect of COPD on caregivers, who describe a constant sense of
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helplessness and preoccupation with their relative and a debilitating hypervigilance.44 Thus, COPD ceases to be a disease affecting a single person, but rather a disease affecting the surrounding family conglomerate.
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UNDER-DIAGNOSIS AND MISMANAGEMENT AS A HEALTHCARE PROBLEM
Currently, COPD is suspected and diagnosed late in the clinical course of the disease. A study conducted by Damarla et al45 showed that whereas 78% of patients admitted to a
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tertiary referral hospital in Boston, USA with the diagnosis of congestive heart failure received an echocardiogram in the previous 8 years, only 31% of patients with a diagnosis of COPD received a confirmatory spirometry test over the same time span.
vital capacity maneuver.
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Among these patients, 19% had a restrictive and not an obstructive pattern on the forced
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There are several reasons for the failure to diagnose COPD in a timely fashion.
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Respiratory symptoms are often underestimated by patients, who consider their symptoms as logical effects of age or smoking. Consequently, patients do not consult
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their doctors until symptoms are aggravated, mainly due to exacerbations. Also, general practitioners can underestimate the situation, diagnosing the episode only as an
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independent acute event (acute bronchitis) rather than an epiphenomenon of an unrecognized chronic problem. The result is that >80% of individuals affected with airway obstruction have never had a diagnosis of COPD and, even among those with severe obstruction, fewer than half have already been diagnosed.46 A missed diagnosis influences the timing of therapeutic intervention, thus contributing to the evolution to
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more severe stages of the illness. These findings suggest that adults who attend a primary care practice with known risk factors for COPD are important targets for case detection and early intervention.47
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Given that the majority of reported COPD costs in the United States are associated with inpatient hospitalizations, one strategy to reduce the burden of COPD would be to
improve the long-term management of the disease in primary care by increasing the
availability and usage of interventions that can prevent exacerbations, reduce the risk of
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hospitalizations, improve symptom control, delay disease progression, and reduce the risk of co-morbidities.48
THE PARADOXICAL DILEMMA OF COPD DIAGNOSIS
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Compared to the diagnosis and follow-up of other NCDs, such as coronary artery disease (which requires electrocardiogram, echocardiogram, stress test, cardiac catheterization, or
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angiogram) or diabetes mellitus (which requires several blood tests such as a
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glycohemoglobin test, fasting plasma glucose test, or oral glucose tolerance test), the diagnosis of COPD (which relies on spirometry) is relatively simple. Spirometry is
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objective, non-invasive, sensitive to early change, and reproducible. With the availability of portable instruments, it can be performed almost anywhere and, with the right training,
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it can be performed by most healthcare practitioners.49 Despite the proven value of spirometry, healthcare systems have been slow to accept its routine use. While no physician would give insulin to a diabetic patient without measuring blood sugar, or an antihypertensive to a patient without measuring blood
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pressure, these same physicians often prescribe powerful beta-agonists, anticholinergics, and even corticosteroids without performing spirometry. PATIENTS WITH RESPIRATORY SYMPTOMS BUT NO SPIROMETRIC
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OBSTRUCTION Many smokers manifest respiratory symptoms (cough, sputum production, and even dyspnea) without meeting the spirometric definition required to confirm a COPD
diagnosis (forced expiratory volume in 1 second:forced vital capacity after bronchodilator
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use ≤0.70). The SPIROMICS study collected data on symptoms, pulmonary function, and biomarkers between 2010 and 2015 for 2,736 current and former smokers from
multiple centers in the United States.50 The study revealed that about half of the smokers
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had COPD-like symptoms and symptomatic smokers were more likely to have computed tomography scan-identified thickening of the airways (typical of chronic bronchitis). Use
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of respiratory medications and medical attention, including hospitalization, were higher among symptomatic versus asymptomatic current and former smokers, despite having
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normal spirometry readings.50 Other studies have found that smokers and non-smokers without COPD but with signs of emphysema on computed tomography scans had higher
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all-cause mortality rates than those without lung damage.51-53
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To date, the best way to treat symptomatic smokers without airflow limitation is still unknown. The great majority of clinical trials have only studied COPD as defined by spirometry. More studies aimed at studying the natural course and management of patients with COPD-like symptoms, but without spirometric evidence of obstruction, are recommended.
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MANAGEMENT OF COPD: THE HEALTHY LIFESTYLE PARADIGM The goals of effective COPD management are to: 1) prevent disease progression; 2) relieve symptoms; 3) improve exercise tolerance; 4) improve health status; 5) prevent
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and treat complications; 6) prevent and treat exacerbations; and 7) reduce mortality. To date, treatment with medication alone is not enough to completely control COPD
symptoms or drastically alter the progression of disease in the majority of patients. Introduction of additional bronchodilators or non-pharmacologic therapies such as
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pulmonary rehabilitation is often required to help control symptoms with disease
progression. Promotion of a healthy lifestyle and non-pharmacologic interventions in the treatment of COPD have received great attention in recent decades [ref. to Yawn /Make suppl, Am J Med 2017]. A general health campaign promoting a healthy lifestyle in
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patients with COPD should focus on physical activity, smoking cessation, limited alcohol
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intake, and a balanced calorie intake.54,55
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GUIDELINES AND THEIR IMPLEMENTATION Evidence-based clinical guidelines for the diagnosis and management of COPD are now
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widely available. However, several studies in COPD have demonstrated that actual clinical practice may deviate significantly from guideline recommendations.56 A low
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awareness of clinical guidelines that can translate into low adherence to recommendations is a continuing issue.56 The potential ways to increase adherence to guidelines include to facilitate its distribution, improve continuous medical education, use electronic health records to increase the provider’s knowledge of the guideline, and make the guidelines readily accessible.
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While the individual interventions recommended by clinical practice guidelines are evidence-based, there are relatively few studies assessing patient outcomes following the implementation of COPD guidelines per se.57 In addition, although 55% of physicians are aware of major COPD guidelines (Global initiative for chronic Obstructive Lung
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Disease or American Thoracic Society/European Respiratory Society guidelines), only 25% use them to guide decision-making.58 Clinicians may be less likely to prescribe
chronic COPD pharmacotherapy to older patients receiving multiple medications who may have cognitive impairment or difficulty using inhalers. In an analysis of a large
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population of patients with COPD to determine frequency of medication use and patterns of pharmacotherapy, 71% of older Medicare patients and 69% of high-complexity Medicare patients did not receive even 1 long-term COPD maintenance
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pharmacotherapy.59
Guidelines also tend to be comprehensive and very extensive, and perhaps simplification
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may be advisable, as 1 recent attempt appears to suggest. Marin et al60 from the BODE
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group summarized current evidence in 10 simple steps that provide the backbone for all
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of the steps that could improve the care of patients suffering from COPD (Figure 1).60 CONCLUSIONS
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Although great advances have been achieved in our understanding of COPD and its treatment, there are still many unmet needs (Table 1). The most significant of these is perhaps the lack of knowledge about its importance and presence, among both sufferers and healthcare providers. There are still many misconceptions, with a huge problem of under- and misdiagnosis, which in turn lead to under- and mistreatment. It is our duty as
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caregivers to convey a message of hope and optimism. Deaths from COPD appear to be decreasing, perhaps not only as a result of a decrease in the overall prevalence of smoking worldwide, but also from improvement in therapies. However, as it remains the third most frequent cause of death in the world, we must continue to expand the scope
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and reach of our efforts to improve outcomes in COPD and thereby improve human health overall.
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ACKNOWLEDGMENTS
The authors meet criteria for authorship as recommended by the International Committee of Medical Journal Editors. They take full responsibility for the scope, direction, content
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of, and editorial decisions relating to, the manuscript, were involved at all stages of development, and have approved the submitted manuscript. The authors received no
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compensation related to the development of the manuscript. This work was supported by
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Boehringer Ingelheim Pharmaceuticals Inc. Medical writing assistance was provided by Rob Kite, BSc, of Complete HealthVizion, which was contracted and compensated by
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Boehringer Ingelheim Pharmaceuticals Inc.
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AUTHOR DISCLOSURES FP has nothing to disclose. BC reports personal fees from GlaxoSmithKline, Boehringer Ingelheim, and Novartis, and grants and personal fees from AstraZeneca, all outside of the submitted work.
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51. Oelsner EC, Hoffman EA, Folsom AR, et al. Association between emphysema-like lung on cardiac computed tomography and mortality in persons without airflow obstruction: a cohort study. Ann Intern Med. 2014;161:863-873.
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52. Oelsner EC, Carr JJ, Enright PL, et al. Per cent emphysema is associated with respiratory and lung cancer mortality in the general population: a cohort study. Thorax. 2016;71:624-632.
53. Zulueta JJ, Wisnivesky JP, Henschke CI, et al. Emphysema scores predict death
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from COPD and lung cancer. Chest. 2012;141:1216-1223.
54. Hansen H, Johnsen NF, Molsted S. Time trends in leisure time physical activity, smoking, alcohol consumption and body mass index in Danish adults with and
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without COPD. BMC Pulm Med. 2016;16:110.
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55. Lee IM, Shiroma EJ, Lobelo F, et al. Effect of physical inactivity on major noncommunicable diseases worldwide: an analysis of burden of disease and life
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expectancy. Lancet. 2012;380:219-229.
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56. Overington JD, Huang YC, Abramson MJ, et al. Implementing clinical guidelines for chronic obstructive pulmonary disease: barriers and solutions. J Thorac Dis.
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2014;6:1586-1596.
57. Heffner JE, Ellis R. The guideline approach to chronic obstructive pulmonary disease: how effective? Respir Care. 2003;48:1257-1266.
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58. Foster JA, Yawn BP, Maziar A, et al. Enhancing COPD management in primary care settings. MedGenMed. 2007;9:24. 59. Make B, Dutro MP, Paulose-Ram R, et al. Undertreatment of COPD: a
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retrospective analysis of US managed care and Medicare patients. Int J Chron Obstruct Pulmon Dis. 2012;7:1-9.
60. Marin JM, Cote C, Casanova C, et al. Simplifying the guidelines: the 10 COPD
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commandments. Arch Bronconeumol. 2016;52:179-180.
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FIGURE LEGEND
Figure 1. ―The 10 COPD-mandments‖.60 Published with permission of SEPAR. Copyright © 2016. Grupo BODE.
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COPD = chronic obstructive pulmonary disease; BMI = body mass index.
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Table 1 Current Unmet Needs in the Field of COPD
Proposed actions
Patient involvement
Public education about the disease itself
Case finding
Perform spirometry in suspected cases
Correct diagnosis
Appropriate interpretation of the clinical and
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spirometric evaluation
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Needs
Use of inappropriate therapy
Simplify guidelines and facilitate implementation
Recognition of the importance
Education of patients and caregivers
toward COPD
Disseminate the current knowledge of effective available therapy
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Reverse the nihilistic attitude
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of exacerbations
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COPD = chronic obstructive pulmonary disease.
The Challenge of Controlling the COPD Epidemic Chronic Obstructive Pulmonary Disease: Unmet Needs Francesca Polverino MD, PhD , Bartolome Celli MD PII: DOI: Reference:
S0002-9343(18)30414-5 10.1016/j.amjmed.2018.05.001 AJM 14665
To appear in:
The American Journal of Medicine
Received date: Accepted date:
6 March 2018 4 May 2018
Please cite this article as: Francesca Polverino MD, PhD , Bartolome Celli MD , The Challenge of Controlling the COPD Epidemic Chronic Obstructive Pulmonary Disease: Unmet Needs, The American Journal of Medicine (2018), doi: 10.1016/j.amjmed.2018.05.001
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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Highlights
Chronic obstructive pulmonary disease (COPD) is often under- or misdiagnosed and consequently under- or mistreated. It is important that clinicians, particularly those in primary care, are educated to
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be able to recognize and correctly diagnose COPD and treat patients in line with the guidance provided by treatment recommendations.
This review aims to address this and fill other important knowledge gaps.
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The Challenge of Controlling the COPD Epidemic Chronic Obstructive Pulmonary Disease: Unmet Needs
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Francesca Polverino, MD, PhD, Bartolome Celli, MD Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA
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Funding: This work was supported by Boehringer Ingelheim Pharmaceuticals Inc. Conflict of Interest: FP has nothing to disclose. BC reports personal fees from
GlaxoSmithKline, Boehringer Ingelheim, and Novartis, and grants and personal fees from
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AstraZeneca, all outside of the submitted work.
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Authorship: Both authors contributed equally to all aspects of the manuscript. Requests for reprints should be addressed to Francesca Polverino, MD, Pulmonary and
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Critical Care Medicine, Brigham and Women’s Hospital, Harvard Institute of Medicine,
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77 Avenue Louis Pasteur, Boston, MA 02115.
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E-mail address: [email protected]
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ABSTRACT Many unmet needs still remain in the assessment and treatment of patients with chronic obstructive pulmonary disease (COPD), particularly in relation to its under- and
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misdiagnosis, which lead to under- and mistreatment. This paucity of knowledge about the importance and presence of COPD, as well as its treatment, is seen with patients and carers as well as healthcare providers. This review considers the areas of key educational need, including the clinical characteristics of COPD, factors contributing to the disease,
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effective diagnosis, and clinical management of patients, and the implementation of
treatment guidelines. As COPD remains the third most frequent cause of death in the world, we must continue to expand the scope and reach of our efforts to improve
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outcomes in this debilitating disease.
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KEYWORDS: Burden; COPD
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INTRODUCTION Over recent decades, the progressive control of communicable diseases as the most important causes of morbidity and death in the world has resulted in three important changes: firstly, an
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increase in the world’s population; secondly, a simultaneous improvement in longevity; and thirdly, an increase in the prevalence of non-communicable diseases (NCDs).1 An NCD is a medical condition or disease that is, by definition, non-infectious and non-transmissible between humans. The four most important NCDs are cardiovascular diseases, cancers,
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respiratory diseases, and diabetes, leading to 17.7 million, 8.8 million, 3.9 million, and
1.6 million deaths annually, respectively, according to the World Health Organization.2 Besides having an important genetic determinant, the World Health Organization’s World Health Report identified tobacco smoke, alcohol consumption, being overweight, physical
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inactivity, high blood pressure, and high cholesterol as important risk factors for NCDs.2
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One important group of NCDs is the chronic lung diseases, with asthma and chronic obstructive pulmonary disease (COPD) representing the great majority. This review
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summarizes our current knowledge regarding COPD and attempts to identify the unmet
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needs surrounding its unfortunate emergence as a large contributor to poor health around the world.
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DEFINITION AND CLINICAL CHARACTERISTICS COPD is a lung disease that causes limitation to airflow in and out of the lungs. It results from an abnormal airway and parenchymal response to inflammation caused by the inhalation of toxic particles contained primarily in cigarette smoke, the combustion of biomass for cooking and heating purposes, and from environmental pollution.3 Although an
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accelerated loss of lung function is seen in half of individuals who develop COPD, the other half most likely reach the disease state from alterations in the pre- or post-natal period of lung development.4,5 COPD symptoms include breathing difficulty, cough, sputum production, and wheezing, which may be present for years before the diagnosis is made.
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Patients with COPD are at increased risk of developing several co-morbid diseases compared to age- and sex-matched patients without COPD [ref. to Criner suppl, Am J Med 2017].6 Although most patients with COPD die from cardiovascular disease or cancer, a substantial proportion die from respiratory failure as, once present, COPD tends to progress, causing a
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decrease in functional capacity, disability, the need for mechanical ventilation, and, eventually, death.3,7
Until recently, the degree of airflow limitation, measured using a spirometer, was the only
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tool used to determine the severity of COPD, assess the response to medications, and follow
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disease progression. Irreversible or partially reversible airflow limitation, measured by spirometry before and after administration of an inhaled bronchodilator (e.g., albuterol
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400 µg), is the characteristic physiologic feature of COPD. Spirometry is a simple test – reliable, affordable, and well tolerated – and its use should be encouraged at all levels of
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care.8 It not only improves the accuracy of diagnosis of COPD, but also results in significant
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improvements in management, without input from secondary care.9 Spirometry can lead to substantial over-diagnosis of COPD in never-smokers >70 years of age, but produces fewer false-positive results in younger adults.10,11 Early intervention strategy aimed at increasing smoking-cessation rates12-14 and smoking abstinence is likely to be more effective than an early detection strategy of performing spirometry on patients who do not recognize or report respiratory symptoms.
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On a personal clinical note, we would like to point out that spirometry not only helps in detecting the fixed obstruction of COPD, but, importantly, the reversibility that characterizes asthma, and it may suggest the presence of restrictive pulmonary diseases, an increasingly
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important clinical problem in everyday practice. EPIDEMIOLOGY
Globally, COPD accounted for 5% of all deaths in 2015, with >90% of COPD deaths
occurring in low- and middle-income countries.15 The prevalence of COPD hovers around
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10% across the world but varies in different regions, as has been determined in 2 population studies: PLATINO in Latin America16 and BOLD17 across the rest of the globe. In the United States, COPD has a prevalence of ~6.4% and is the third leading cause of death.18 The age-adjusted mortality rates can vary by state, from a low in Hawaii (27.1 per 100,000)
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to a high in Oklahoma (93.6 per 100,000).19 The disease affects men and women almost
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equally, due in part to increased tobacco use among women in high-income countries. Unfortunately, >50% of people with spirometric evidence of COPD have never been
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diagnosed.20 This proportion is likely to be higher in patients with mild COPD, who would benefit most from therapy.21 Following the introduction of smoke-free legislation in the
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United States, the number of COPD-related hospital admissions has declined.22 However,
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with close to 15% smoking rates in the country, COPD as a health problem is here to stay.23 AGE, SEX, ETHNICITY, EDUCATION, AND INCOME AS FACTORS CONTRIBUTING TO COPD COPD primarily affects individuals >40 years of age and its prevalence increases with age, with an approximate 5-fold increased risk for those aged >65 years compared to patients
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aged <40 years.24 The prevalence of COPD increases with smoking status, yet neversmokers comprise ~23% of individuals with COPD, suggesting the existence of other risk factors such as passive smoking or factors of occupational exposure.25 In the United States, the age-adjusted prevalence is usually higher among non-Hispanic white patients compared
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to African-American or Hispanic patients,26 and is higher among women than men.27
An association between educational level and COPD is present in both never-smokers and smokers.28,29 Possible mechanisms explaining the adverse effects of low socioeconomic
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status on COPD among never-smokers might be poor dietary habits (low in antioxidants and fresh fruit),30,31 poor housing conditions,32 more occupational dust exposure, and indoor air pollution from biomass combustion.3
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COST OF COPD TO SOCIETY
The growing burden of COPD exacts an economic cost, as people are less productive, less
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able to work, and die prematurely.33 The medical costs related to COPD were estimated to
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be $32.1 billion in 2010 and are projected to rise to $49 billion by 2020.34 Direct healthcare costs account for nearly two-thirds of total COPD costs, including physician office visits,
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hospitalizations, home care, and medications.35 Furthermore, there is a direct relationship between severity of COPD and the overall cost of care.35 Hospitalization was identified as
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the most important cost variable across all severity stages of COPD.36,37 In a survey of the burden of COPD in the United States, it was shown that 6% of patients took time off work due to COPD, whereas work loss among caregivers of patients with COPD was reported by 7% of respondents.38
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There is a strong association between COPD exacerbations and hospitalization. The number of admissions to hospital has remained stable since 1999 despite a decrease in the length of stay for a COPD-related hospitalization in the past 10 years.35 This trend is likely to continue as exacerbations requiring hospitalization only become more frequent and severe
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with increasing age and disease progression.35,39,40 Overall, the cost of caring for patients with COPD is alarming, so much so that the Centers for Medicare and Medicaid Services have singled out 30-day re-admission rates as 1 target to evaluate burden of care and quality
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of health delivery for hospitals across the country.41 EFFECTS ON THE INDIVIDUAL PATIENT
Although the economic cost is important, the physical and psychological effects of COPD on
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the individual are even more important. The cardinal symptom of dyspnea leads to considerable modifications in lifestyle, such as limitation or total elimination of outings and
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holidays to avoid crowds, hills, and stairs. The loss of work and subsequent social isolation
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related to limitations in leisure activities have a profound effect on individuals with COPD. A feeling of ―shame‖ is usually felt by patients with COPD and is mainly related to the
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notion that their disease is self-inflicted.42 COPD is stigmatized not only by patients but also by members of society because it has resulted primarily from what is now considered an
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abnormal behavior (smoking). In addition, the most severely affected patients require oxygen equipment that singles them out in crowds and effects bodily changes, thereby disrupting their social interactions.43 Patients with COPD who feel stigmatized may hesitate to seek care for fear of judgment or negative repercussions associated with having the condition.43 Not least is the effect of COPD on caregivers, who describe a constant sense of
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helplessness and preoccupation with their relative and a debilitating hypervigilance.44 Thus, COPD ceases to be a disease affecting a single person, but rather a disease affecting the surrounding family conglomerate.
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UNDER-DIAGNOSIS AND MISMANAGEMENT AS A HEALTHCARE PROBLEM
Currently, COPD is suspected and diagnosed late in the clinical course of the disease. A study conducted by Damarla et al45 showed that whereas 78% of patients admitted to a
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tertiary referral hospital in Boston, USA with the diagnosis of congestive heart failure received an echocardiogram in the previous 8 years, only 31% of patients with a diagnosis of COPD received a confirmatory spirometry test over the same time span.
vital capacity maneuver.
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Among these patients, 19% had a restrictive and not an obstructive pattern on the forced
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There are several reasons for the failure to diagnose COPD in a timely fashion.
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Respiratory symptoms are often underestimated by patients, who consider their symptoms as logical effects of age or smoking. Consequently, patients do not consult
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their doctors until symptoms are aggravated, mainly due to exacerbations. Also, general practitioners can underestimate the situation, diagnosing the episode only as an
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independent acute event (acute bronchitis) rather than an epiphenomenon of an unrecognized chronic problem. The result is that >80% of individuals affected with airway obstruction have never had a diagnosis of COPD and, even among those with severe obstruction, fewer than half have already been diagnosed.46 A missed diagnosis influences the timing of therapeutic intervention, thus contributing to the evolution to
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more severe stages of the illness. These findings suggest that adults who attend a primary care practice with known risk factors for COPD are important targets for case detection and early intervention.47
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Given that the majority of reported COPD costs in the United States are associated with inpatient hospitalizations, one strategy to reduce the burden of COPD would be to
improve the long-term management of the disease in primary care by increasing the
availability and usage of interventions that can prevent exacerbations, reduce the risk of
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hospitalizations, improve symptom control, delay disease progression, and reduce the risk of co-morbidities.48
THE PARADOXICAL DILEMMA OF COPD DIAGNOSIS
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Compared to the diagnosis and follow-up of other NCDs, such as coronary artery disease (which requires electrocardiogram, echocardiogram, stress test, cardiac catheterization, or
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angiogram) or diabetes mellitus (which requires several blood tests such as a
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glycohemoglobin test, fasting plasma glucose test, or oral glucose tolerance test), the diagnosis of COPD (which relies on spirometry) is relatively simple. Spirometry is
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objective, non-invasive, sensitive to early change, and reproducible. With the availability of portable instruments, it can be performed almost anywhere and, with the right training,
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it can be performed by most healthcare practitioners.49 Despite the proven value of spirometry, healthcare systems have been slow to accept its routine use. While no physician would give insulin to a diabetic patient without measuring blood sugar, or an antihypertensive to a patient without measuring blood
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pressure, these same physicians often prescribe powerful beta-agonists, anticholinergics, and even corticosteroids without performing spirometry. PATIENTS WITH RESPIRATORY SYMPTOMS BUT NO SPIROMETRIC
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OBSTRUCTION Many smokers manifest respiratory symptoms (cough, sputum production, and even dyspnea) without meeting the spirometric definition required to confirm a COPD
diagnosis (forced expiratory volume in 1 second:forced vital capacity after bronchodilator
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use ≤0.70). The SPIROMICS study collected data on symptoms, pulmonary function, and biomarkers between 2010 and 2015 for 2,736 current and former smokers from
multiple centers in the United States.50 The study revealed that about half of the smokers
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had COPD-like symptoms and symptomatic smokers were more likely to have computed tomography scan-identified thickening of the airways (typical of chronic bronchitis). Use
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of respiratory medications and medical attention, including hospitalization, were higher among symptomatic versus asymptomatic current and former smokers, despite having
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normal spirometry readings.50 Other studies have found that smokers and non-smokers without COPD but with signs of emphysema on computed tomography scans had higher
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all-cause mortality rates than those without lung damage.51-53
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To date, the best way to treat symptomatic smokers without airflow limitation is still unknown. The great majority of clinical trials have only studied COPD as defined by spirometry. More studies aimed at studying the natural course and management of patients with COPD-like symptoms, but without spirometric evidence of obstruction, are recommended.
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MANAGEMENT OF COPD: THE HEALTHY LIFESTYLE PARADIGM The goals of effective COPD management are to: 1) prevent disease progression; 2) relieve symptoms; 3) improve exercise tolerance; 4) improve health status; 5) prevent
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and treat complications; 6) prevent and treat exacerbations; and 7) reduce mortality. To date, treatment with medication alone is not enough to completely control COPD
symptoms or drastically alter the progression of disease in the majority of patients. Introduction of additional bronchodilators or non-pharmacologic therapies such as
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pulmonary rehabilitation is often required to help control symptoms with disease
progression. Promotion of a healthy lifestyle and non-pharmacologic interventions in the treatment of COPD have received great attention in recent decades [ref. to Yawn /Make suppl, Am J Med 2017]. A general health campaign promoting a healthy lifestyle in
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patients with COPD should focus on physical activity, smoking cessation, limited alcohol
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intake, and a balanced calorie intake.54,55
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GUIDELINES AND THEIR IMPLEMENTATION Evidence-based clinical guidelines for the diagnosis and management of COPD are now
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widely available. However, several studies in COPD have demonstrated that actual clinical practice may deviate significantly from guideline recommendations.56 A low
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awareness of clinical guidelines that can translate into low adherence to recommendations is a continuing issue.56 The potential ways to increase adherence to guidelines include to facilitate its distribution, improve continuous medical education, use electronic health records to increase the provider’s knowledge of the guideline, and make the guidelines readily accessible.
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While the individual interventions recommended by clinical practice guidelines are evidence-based, there are relatively few studies assessing patient outcomes following the implementation of COPD guidelines per se.57 In addition, although 55% of physicians are aware of major COPD guidelines (Global initiative for chronic Obstructive Lung
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Disease or American Thoracic Society/European Respiratory Society guidelines), only 25% use them to guide decision-making.58 Clinicians may be less likely to prescribe
chronic COPD pharmacotherapy to older patients receiving multiple medications who may have cognitive impairment or difficulty using inhalers. In an analysis of a large
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population of patients with COPD to determine frequency of medication use and patterns of pharmacotherapy, 71% of older Medicare patients and 69% of high-complexity Medicare patients did not receive even 1 long-term COPD maintenance
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pharmacotherapy.59
Guidelines also tend to be comprehensive and very extensive, and perhaps simplification
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may be advisable, as 1 recent attempt appears to suggest. Marin et al60 from the BODE
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group summarized current evidence in 10 simple steps that provide the backbone for all
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of the steps that could improve the care of patients suffering from COPD (Figure 1).60 CONCLUSIONS
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Although great advances have been achieved in our understanding of COPD and its treatment, there are still many unmet needs (Table 1). The most significant of these is perhaps the lack of knowledge about its importance and presence, among both sufferers and healthcare providers. There are still many misconceptions, with a huge problem of under- and misdiagnosis, which in turn lead to under- and mistreatment. It is our duty as
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caregivers to convey a message of hope and optimism. Deaths from COPD appear to be decreasing, perhaps not only as a result of a decrease in the overall prevalence of smoking worldwide, but also from improvement in therapies. However, as it remains the third most frequent cause of death in the world, we must continue to expand the scope
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and reach of our efforts to improve outcomes in COPD and thereby improve human health overall.
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ACKNOWLEDGMENTS
The authors meet criteria for authorship as recommended by the International Committee of Medical Journal Editors. They take full responsibility for the scope, direction, content
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of, and editorial decisions relating to, the manuscript, were involved at all stages of development, and have approved the submitted manuscript. The authors received no
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compensation related to the development of the manuscript. This work was supported by
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Boehringer Ingelheim Pharmaceuticals Inc. Medical writing assistance was provided by Rob Kite, BSc, of Complete HealthVizion, which was contracted and compensated by
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Boehringer Ingelheim Pharmaceuticals Inc.
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AUTHOR DISCLOSURES FP has nothing to disclose. BC reports personal fees from GlaxoSmithKline, Boehringer Ingelheim, and Novartis, and grants and personal fees from AstraZeneca, all outside of the submitted work.
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37. Toy EL, Gallagher KF, Stanley EL, et al. The economic impact of exacerbations of chronic obstructive pulmonary disease and exacerbation definition: a review. COPD. 2010;7:214-228.
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FIGURE LEGEND
Figure 1. ―The 10 COPD-mandments‖.60 Published with permission of SEPAR. Copyright © 2016. Grupo BODE.
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COPD = chronic obstructive pulmonary disease; BMI = body mass index.
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Table 1 Current Unmet Needs in the Field of COPD
Proposed actions
Patient involvement
Public education about the disease itself
Case finding
Perform spirometry in suspected cases
Correct diagnosis
Appropriate interpretation of the clinical and
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spirometric evaluation
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Needs
Use of inappropriate therapy
Simplify guidelines and facilitate implementation
Recognition of the importance
Education of patients and caregivers
toward COPD
Disseminate the current knowledge of effective available therapy
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Reverse the nihilistic attitude
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of exacerbations
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COPD = chronic obstructive pulmonary disease.