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Department of Medicine, Pulmonary and Critical Care Medicine, University Medical Center Giessen and Marburg, Philipps University of Marburg, Member of the German Center for Lung Research (DZL), Marburg, Germany
Challenges of COPD management include disease heterogeneity and under-diagnosis.
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The best available tools should be used for COPD diagnosis and assessment.
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Optimal management of COPD includes recognizing both symptoms and exacerbations.
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Both pharmacologic and non-pharmacologic treatment strategies should be considered.
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Novel strategies (e.g. precision medicine, point-of-care testing) may be of value.
Abstract
Chronic obstructive pulmonary disease (COPD) is currently a leading cause of death worldwide, and its burden is expected to rise in the coming years. Common COPD symptoms include dyspnea, cough and/or sputum production. Some patients may experience acute worsening of symptoms (known as an exacerbation), and therefore require additional therapy. Exacerbations are mainly triggered by respiratory infections and environmental factors. Healthcare professionals face many challenges in COPD management, including the heterogeneity of the disease and under-reporting of symptoms. The authors review these challenges and provide recommendations for the best methods to assess COPD. The goals of COPD treatment include recognising the impact that both symptoms and exacerbations have on patients’ lives when considering optimal patient-focused management. The review discusses the need for COPD management strategies to include both pharmacologic and non-pharmacologic approaches and provides recommendations for monitoring treatment outcomes and adjusting management strategies accordingly. Novel treatment strategies including precision medicine and point-of-care testing are also discussed.
GBD Disease Injury Incidence Prevalence Collaborators, Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017.
], with the burden of COPD expected to increase further in the coming years due to an aging population and continued exposure to COPD risk factors, including tobacco smoke, occupational dusts and chemicals, biomass fuel and air pollution [
]. In addition to the daily symptom burden, COPD may be punctuated by periods of acute worsening of respiratory symptoms (often referred to as ‘exacerbations’), which account for the greatest proportion of total COPD burden on healthcare systems [
]. COPD can be progressive, as indicated by reductions in spirometry measures such as forced expiratory volume in 1 s (FEV1) over time, though patients may progress at different rates [
This review examines the current goals of COPD management and discusses the challenges that many healthcare professionals face in trying to meet these goals. In the context of the 2020 Global Initiative for Chronic Obstructive Lung Disease (GOLD) strategy report [
], we consider both pharmacologic and non-pharmacologic treatment strategies for the management of symptoms and prevention of exacerbations to improve long-term outcomes and quality of life. Recommendations for monitoring treatment outcomes and adjusting management strategies are also discussed.
2. Challenges in management of COPD
COPD is a heterogeneous, multifaceted disease that is influenced by genetic and environmental factors [
]. The concept of COPD endotypes refers to the definition of patient subgroups based on underlying biologic differences, for example bacterial colonization, and more controversially, eosinophilic inflammation [
]. Precision medicine refers to the use of both clinical (phenotype) and biologic (endotype) information on an individual basis in order to tailor treatment strategies accordingly [
]. Currently, our level of understanding of COPD subtypes is limited, and improvements are needed to better develop novel targeted therapeutic approaches, rather than adopting a ‘one-size-fits-all’ approach to COPD treatment [
]. Healthcare professionals need to work with their patients to find the best combination of pharmacologic and non-pharmacologic treatment strategies (including lifestyle changes) to manage the condition [
]. Despite these findings, these concepts are not currently routinely considered, and COPD is often perceived as a progressive disease that responds poorly to treatment.
Evidence suggests that COPD is underdiagnosed, with most cases identified during an exacerbation or after significant loss of lung function [
]. The US Preventive Services Task Force continues to recommend against screening for COPD with spirometry due to a lack of data to indicate that this impacts long-term outcomes [
], but unfortunately this has been interpreted by some as meaning that identifying and treating COPD is not beneficial. A good option for diagnosing COPD is to use systematic and targeted case-finding approaches. For example, a case-finding methodology was reported [
] which entailed a brief five-item questionnaire (COPD Assessment in Primary Care to Identify Undiagnosed Respiratory Disease & Exacerbation Risk; CAPTURE) as an initial screen. Peak expiratory flow was then performed on a subset of patients with positive questionnaire results, to increase the accuracy of case identification [
Diagnostic accuracy of pre-bronchodilator FEV1/FEV6 from microspirometry to detect airflow obstruction in primary care: a randomised cross-sectional study.
]. Following a postal questionnaire, patients reporting respiratory symptoms can be invited for spirometric assessment to confirm the diagnosis of COPD [
]. When full spirometry is not available or practical, for instance during a primary care consultation, then hand-held microspirometers have been shown to reliably and quickly measure pre-bronchodilator FEV1/FEV6, and to therefore identify patients for further spirometric assessment [
Diagnostic accuracy of pre-bronchodilator FEV1/FEV6 from microspirometry to detect airflow obstruction in primary care: a randomised cross-sectional study.
]. Both of these approaches may have a future role in reducing the underdiagnosis of COPD whilst also increasing the efficiency of full diagnostic spirometry use in primary care.
Currently, management of COPD focuses on the alleviation of symptoms and prevention of the future risk of exacerbations [
]. The negative impact of COPD symptoms on physical activity promotes muscle deconditioning, which can lead to further dyspnea, thereby promoting a cycle of decline that results in deterioration of health status [
]. Symptoms such as dyspnea affect family life and the patient's ability to perform everyday activities, for instance household chores and walking up stairs [
]. In addition to pulmonary symptoms, COPD can be associated with systemic features such as fatigue, weight loss and sleep disturbance, as well as psychiatric symptoms including depression and anxiety, significantly impacting quality of life [
3.1 Challenges of symptom recognition and management
Despite the significant impact of COPD symptoms on patients’ lives, there is evidence that the most common respiratory symptoms, such as dyspnea, cough and sputum production, are under-reported [
]. Some patients with COPD may adapt their lifestyle to compensate for symptoms, and often only present to physicians when their condition has deteriorated significantly [
]. A report describing the burden and impact of COPD in North America and Europe highlighted that even patients with severe dyspnea and significant compromise of daily physical activities requiring exertion tended to underestimate their disease burden, ranking it as mild or moderate [
]. In addition, the Medical Investigation of Respiratory COPD Perception (MIRROR) survey recently confirmed that there were differences between the perceptions that patients with COPD have of their disease and those of their physicians [
]. For instance, patients with severe or very severe COPD perceived their disease to have a greater impact than that perceived by their pulmonologists, particularly in terms of the impact on their quality of life (e.g. daily activities and work) [
FEV1 is a very important parameter at the population level, for predicting clinical outcomes such as mortality and hospitalizations, or prompting consideration for non-pharmacologic procedures such as lung volume reduction or lung transplantation [
]. However, it is important to note that, at the individual patient level, FEV1 loses precision and thus cannot be used to determine the most appropriate therapeutic option, as it does not necessarily correlate with all symptoms experienced by patients and their impact on quality of life or exacerbation frequency [
]; therefore, healthcare professionals must consider both spirometry and symptoms when assessing patients, to avoid disease progression and the development of acute respiratory events [
]. Evidence regarding the impact of COPD symptoms on younger patients (e.g. data on absenteeism, presenteeism and socio-economic status) is sparse; however, it has been reported that COPD likely represents a significant burden for patients of working age [
]. Lastly, although the benefits of COPD treatments are well established in terms of pulmonary symptoms, their impact on psychologic symptoms such as confidence, social interaction and sleep quality is less clear [
]. However, it has recently been shown that behavioral modifications that motivate patients to increase their daily physical activity can also improve anxiety, cognitive function and depression in patients with COPD [
Given the under-reporting and under-recognition of symptoms, there is a need for appropriate tools in clinical practice to identify symptoms and adjust treatment accordingly. The most efficient and accurate way for physicians to assess symptom severity, activity limitation and health-related quality of life is to use a standardized measure, such as a short patient-centered questionnaire [
]. A number of questionnaires are available for assessing symptoms, yet uptake is often limited in clinical practice, most likely due to a combination of lack of awareness, difficulty in incorporating questionnaires into practice flow, or lack of electronic medical record support for questionnaires.
The COPD Assessment Test (CAT) is a useful and practical questionnaire for clinical practice [
]. Items covered include physical symptoms such as cough, phlegm, chest tightness, breathlessness when going up hills and stairs, activity limitation at home, and energy, as well as related factors that affect patients’ quality of life, including confidence leaving home and sleep quality [
Other questionnaires include the modified Medical Research Council (mMRC) dyspnea scale, Clinical COPD Questionnaire (CCQ) and St. George's Respiratory Questionnaire (SGRQ) [
American thoracic society, European respiratory society Task Force on outcomes of COPD, outcomes for COPD pharmacological trials: from lung function to biomarkers.
]. Simple to administer, the mMRC dyspnea scale (0–4) is easily used to indicate the extent to which dyspnea impacts on daily activities alone; however, drawbacks include its insensitivity to change (e.g. in response to treatment), and it does not take into account the fact that patients often modify their behavior and the amount of effort exerted due to dyspnea [
]. The CCQ enables a more complete understanding of the impact of COPD on patients, including a more comprehensive assessment of activity limitation and emotional dysfunction, and is a useful tool in the everyday clinical setting to assess COPD [
]. Areas of assessment include symptoms (e.g. dyspnea, cough and phlegm), functional state and mental state. CCQ has also been shown to be sensitive to clinical improvement after smoking cessation, and during and after exacerbations [
], and is mainly triggered by respiratory infections (mostly viral, such as rhinovirus, as well as bacterial infections), and environmental factors such as air pollution. Exacerbations associated with viral infections tend to be more severe, last longer, and require more hospitalizations (e.g. during winter) [
]. Current treatment goals for exacerbations are to minimize the negative impact of the current exacerbation and reduce the risk of any future exacerbations [
]. The majority of patients that experience exacerbations can be managed on an outpatient basis with pharmacologic therapies; however, some patients may require hospitalization for a number of reasons, including severity of symptoms, failure to respond to initial treatment, poor or limited home-based care, and presence of comorbidities [
]. As the clinical presentation of exacerbations is heterogeneous, the GOLD report recommends that the determination of severity in hospitalized patients should be based on clinical signs [
The long-term prognosis following hospitalization for exacerbations is poor, especially in patients with additional risk factors such as older age, comorbidities, lower body mass index and poorer quality of life [
]. Some patients with COPD are particularly susceptible to frequent exacerbations, and these patients have been shown to have worse health status, morbidity and mortality than those with less frequent exacerbations [
]. Patient education on when to seek medical attention for exacerbations is of vital importance. A recent Cochrane review reported that COPD self-management interventions, which include written negotiated action plans for worsening symptoms, lead to a lower probability of respiratory-related hospitalization and all-cause hospitalizations [
]. Self-management programs are not intended to replace other components of patient care; however, the authors suggest that inappropriate use of self-managed therapies by patients may delay acute healthcare, with the potential of ultimately increasing the use of in-hospital healthcare.
COPD exacerbations are usually identified based on an increase in a variety of symptoms, including increased breathlessness and/or increased sputum production [
]. It may also be difficult to distinguish true increased symptoms versus the patient's perception of symptoms. It has been reported that the sensation of dyspnea is enhanced in patients with COPD who experience frequent acute exacerbations and is blunted in those who suffer from exacerbations infrequently [
Identifying exacerbation triggers in COPD patients is often difficult in practice. Pulmonary inflammation varies greatly between individuals, and this has proven challenging in terms of biomarker evaluation or inflammation-targeted therapeutic intervention [
], other acute presentations of chronic diseases (e.g. myocardial infarction) have specific and sensitive diagnostic toolkits, such as biomarkers and imaging techniques, that are used in routine management of patients [
Exacerbations can also be difficult to recognize, and many patients presenting with a COPD exacerbation have comorbid conditions, which complicates evaluation and management. Indeed, it may be that events recorded as exacerbations are actually a presentation of a comorbidity [
]. Some studies suggest that clinicians are less likely to diagnose comorbidities (e.g. heart failure and myocardial infarction) if there is an existing diagnosis of COPD [
Many novel treatments have failed to prevent exacerbations. This may be due to the use of inappropriate or ineffective molecules, or because the concept of a single medicine treating a heterogeneous disease such as COPD is unrealistic [
]. Blood eosinophil counts can help healthcare professionals to predict the probability of clinical benefit with the addition of inhaled corticosteroids (ICS) to maintenance bronchodilators [
]. Treatment with macrolides may also have a role in COPD therapy. Low-dose erythromycin therapy for 12 months reduced the frequency and severity of exacerbations in patients with moderate-to-severe COPD, with an acceptable tolerability [
]. Daily azithromycin therapy has also been shown to reduce COPD exacerbations, and has been recommended for use in patients who are at risk of recurrent exacerbations [
]. However, besides the potential to generate resistant microbes, azithromycin has been associated with a small increased risk of hearing decrements, as well as cardiovascular events relating to QT-interval prolongation in some patients with concurrent risk factors [
]. Furthermore, data on macrolide treatment for longer than 12 months, and the use of other antibiotics for the treatment of COPD, are currently lacking.
5. Recommendations for COPD treatment
5.1 Control of risk factors and non-pharmacologic management
It is important to identify and reduce COPD risk factors in the prevention and treatment of COPD [
]. For instance, smoking cessation is a key intervention, and healthcare professionals are therefore encouraged to deliver smoking cessation messages and interventions to patients, such as using counseling, financial incentive programs and patient education [
]. Therapies for tobacco dependence, including varenicline, sustained-release bupropion, nortriptyline, nicotine gum, nicotine inhaler, nicotine nasal spray, and nicotine patches, can be effective as quitting aids and are recommended in the absence of contraindications [
]. In addition, reducing exposure to indoor and outdoor pollution, including biomass fuel and occupational inhalants, may require public policy changes, as well as protective steps taken by individuals [
] in combination with pharmacologic therapies. A Cochrane meta-analysis of 65 randomized controlled trials involving 3822 patients has reported that pulmonary rehabilitation can relieve dyspnea and fatigue, improve emotional function and enhance the sense of control that patients have over their condition [
]. The effect with pulmonary rehabilitation was larger for quality of life domains (Chronic Respiratory Questionnaire) than the minimal clinically important difference of 0.5 units [
]. In addition, statistically significant improvements were noted in all domains of the SGRQ, and both functional and maximal exercise showed statistically significant improvements [
]. Similarly, another Cochrane review including 1477 patients suggested that pulmonary rehabilitation after an exacerbation can improve health-related quality of life and exercise capacity [
It has been reported that patients who undertake regular physical activity have a lower risk of exacerbations, COPD hospital admissions and all-cause mortality [
]. Health education can also help patients cope with their illness, and it may be effective in influencing behavioral changes (e.g. smoking cessation) and attainment of certain treatment goals [
Pharmacologic therapy for COPD is used to treat symptoms, reduce the frequency and severity of exacerbations, and improve exercise tolerance and health status [
]. The classes of medications commonly used to treat COPD include long-acting β2-agonists (LABAs), long-acting muscarinic antagonists (LAMAs) and ICS [
Once the clinical and spirometric diagnosis of COPD is confirmed, clinical guidance from the GOLD strategy report can be applied for initial pharmacologic treatment using the best available evidence, emphasizing the importance of selecting the correct treatment from the start [
]. Rescue medication with short-acting bronchodilators should be prescribed for immediate symptom relief, but use of these is not generally recommended on a regular basis [
]. A long-acting bronchodilator is then usually offered. In some patients, a combination treatment such as LAMA/LABA (e.g. for patients with severe breathlessness) or LABA/ICS (for patients with a high risk of exacerbations and higher blood eosinophil counts) may be offered as initial treatment [
]. If response to initial treatment is not appropriate, it is important to consider whether symptoms or exacerbations are the predominant characteristic, and follow the most appropriate pharmacologic path, as per Fig. 3 [
]. The addition of a long-acting bronchodilator is used for dyspnea; for exacerbations, either a long-acting bronchodilator or an ICS is added. Factors that favor adding an ICS include more frequent exacerbations, higher eosinophil counts, or the coexistence of bronchial asthma [
Consider if eos ≥300 or ≥100 AND ≥2 moderate exacerbations or 1 hospitalization; ** Consider de-escalation of ICS or switch if pneumonia, inappropriate original indication or lack of response to ICS.
]. A recommendation in the GOLD report is that the choice of inhaler device needs to be individually tailored based on access, as well as the patient's ability and preference [
Gruppo Educazionale Associazione Italiana Pneumologi Ospedalieri, Inhaler mishandling remains common in real life and is associated with reduced disease control.
Gruppo Educazionale Associazione Italiana Pneumologi Ospedalieri, Inhaler mishandling remains common in real life and is associated with reduced disease control.
Gruppo Educazionale Associazione Italiana Pneumologi Ospedalieri, Inhaler mishandling remains common in real life and is associated with reduced disease control.
]. Thus, inhaler technique and adherence should be assessed before concluding that the current therapy requires modification.
6. Summary and conclusions
Although COPD imposes a significant burden in terms of mortality and morbidity, it is both preventable (by reduction of exposure to risk factors) and treatable (by reducing COPD symptoms and exacerbations). The goals of COPD treatment include recognizing the significance of both symptoms and exacerbations when considering optimal management. The authors recommend using the best tools available to diagnose and assess COPD (including comorbidities), and combining both pharmacologic and non-pharmacologic measures for effective COPD management.
Funding
This work was supported by Boehringer Ingelheim.
Declaration of competing interest
CFV reports grants and personal fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Grifols, Mundipharma and Novartis, personal fees from Berlin Chemie/Menarini, CSL Behring, Nuvaira and Teva, and grants from the German Federal Ministry of Education and Research (BMBF) Competence Network Asthma and COPD (ASCONET), outside the submitted work. MR-R reports personal fees from AstraZeneca, Boehringer Ingelheim, Chiesi, Menarini, Mundipharma, Novartis, Pfizer, Teva and Bial, and grants and personal fees from GlaxoSmithKline, outside the submitted work. DS reports personal fees from Apellis, Cipla, Genentech, Peptinnovate and Skyepharma, and grants and personal fees from AstraZeneca, Boehringer Ingelheim, Chiesi, Glenmark, Merck, Mundipharma, Novartis, Pfizer, Pulmatrix, Teva, Theravance and Verona, outside the submitted work. MKH reports personal fees from Boehringer Ingelheim, GlaxoSmithKline, AstraZeneca, Boehringer Ingelheim and Mylan, and other from Novartis and Sunovion, outside the submitted work. RR-R has nothing to disclose. GTF reports grants, personal fees and non-financial support from Boehringer Ingelheim, during the conduct of the study; grants, personal fees and non-financial support from Boehringer Ingelheim, Novartis, AstraZeneca, Pearl Therapeutics and Sunovion; personal fees from Verona, Mylan, Innoviva, GlaxoSmithKline and Circassia; and grants and personal fees from Theravance, outside the submitted work.
Acknowledgments
Dave Singh is supported by the National Institute for Health Research (NIHR) Manchester Biomedical Research Centre (BRC). Editorial support was provided by MediTech Media, London, UK and was funded by Boehringer Ingelheim.
References
Global Initiative for Chronic Obstructive Lung Disease
Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease (2020 report).
GBD Disease Injury Incidence Prevalence Collaborators, Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017.
Diagnostic accuracy of pre-bronchodilator FEV1/FEV6 from microspirometry to detect airflow obstruction in primary care: a randomised cross-sectional study.
American thoracic society, European respiratory society Task Force on outcomes of COPD, outcomes for COPD pharmacological trials: from lung function to biomarkers.
Gruppo Educazionale Associazione Italiana Pneumologi Ospedalieri, Inhaler mishandling remains common in real life and is associated with reduced disease control.
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