This supplement aims to provide an introduction to 4 key topics in COPD management in primary care.
Barbara Yawn, MD, MSc, FAAFP
Department of Family and Community Health, University of Minnesota, Blaine, MN
Victor Kim, MD
Department of Thoracic Medicine and Surgery, Temple University School of Medicine, Philadelphia, PA
Dr. Yawn reports receipt of personal payments for COPD- related advisory boards for AstraZeneca; Boehringer Ingelheim Pharmaceuticals, Inc.; and GlaxoSmithKline; and COPD-related research grant funding from Boehringer Ingelheim Pharmaceuticals, Inc. She has served as a content developer and peer reviewer for Medscape and UpToDate, and has grant support from the National Heart, Lung, and Blood Institute and the Patient-Centered Outcomes Research Institute for COPD-related research.
Dr. Kim has attended advisory board meetings for AstraZeneca; Concert Pharmaceuticals Inc.; CSA Medical Inc.; and Gala Therapeutics Inc. He has been a peer reviewer for Medscape, and has received grant support from the National Heart, Lung, and Blood Institute.
Funding for this article was provided by AstraZeneca LP (Wilmington, DE, USA). Medical writing support was provided by Hannah Burke, BSc, of Core (London, UK) and editorial support was provided by Maryam Vahdat, PGDip, of Core (London, UK), which were funded by AstraZeneca LP (Wilmington, DE, USA), in accordance with Good Publication Practice guidelines (Battisti WP et al. Ann Intern Med. 2015;163:461–464. doi: 10.7326/M15-0288).
This article is being co-published in The Journal of Family Practice and Cleveland Clinic Journal of Medicine.
Chronic obstructive pulmonary disease (COPD) is common, often seen in primary care daily practice, and places a substantial burden on patients, their families, and society. 1-4 Although dyspnea, cough, wheezing, chest tightness, and/or sputum production are typical symptoms of COPD, some patients present with less obvious issues, such as a highly sedentary lifestyle, adjusted to match their limitations and fatigue. 5-7
Both pharmacologic and nonpharmacologic treatment options can reduce symptoms, treat comorbidities, prevent exacerbation, and improve quality of life, exercise tolerance, and health status in patients with COPD. 3 Patients require initial therapy based on symptoms, history, and their own treatment goals, with regular monitoring to determine when to enhance or discontinue unnecessary therapy, and when to refer to a pulmonologist.
Primary care physicians manage the care of approximately 80% of patients with COPD. 8 This provides the opportunity to engage patients in management goal-setting that facilitates more tailored treatments, and can improve adherence to therapy, which is historically poor in patients with COPD, thereby improving outcomes. 9-11
Both the Global Initiative for Obstructive Lung Disease (GOLD) and COPD Foundation guidelines recommend individualized care for patients with COPD. 3,12 This individualized care is based on comprehensive assessment of symptoms (including assessment of whether symptoms are persistent or worsening) and/or continuation of exacerbations to escalate therapy. COPD phenotypes, such as individuals with frequent exacerbations, chronic bronchitis, and asthma–COPD overlap syndrome (ACO) can also guide treatment. 13-15
Postbronchodilator spirometry confirms the diagnosis of COPD by a forced expiratory volume in 1 second/forced vital capacity (FEV 1/FVC) ratio of less than 0.7, and denotes levels of airflow limitation severity based on the postbronchodilator FEV 1 percentage predicted ( Figure 1 ). Repeated spirometry assessment can identify individuals with rapidly declining lung function who are appropriate for referral to a pulmonologist.
Smoking cessation and pulmonary rehabilitation are central to effective COPD disease management. 3 Smoking cessation has the greatest capacity to influence the natural history of COPD. 3 Nicotine replacement products, as well as varenicline and bupropion, have been shown to increase long-term smoking cessation rates. 16
Pulmonary rehabilitation (which includes exercise training, education, and self-management interventions aimed at behavior change) should be considered a fundamental part of COPD care. 3 Pulmonary rehabilitation is recommended for any COPD patient of GOLD grades B–D (postbronchodilator FEV 1/FVC ratio <0.70 and FEV 1 <80% of predicted). 3 The 2015 Cochrane Review of pulmonary rehabilitation for COPD assessed 65 randomized controlled trials involving 3822 participants, and concluded that pulmonary rehabilitation relieved dyspnea and fatigue, resulting in statistically improved functional exercise, maximal exercise capacity, and quality of life. 17 Inclusion of pulmonary rehabilitation in treatment regimens may provide greater benefit than other more commonly used therapies alone. 17
Long-term oxygen therapy has been shown to improve survival in COPD patients with severe resting hypoxemia (defined as a partial pressure of arterial oxygen [PaO 2] of ≤55 mm Hg, or an oxyhemoglobin saturation level [SpO 2] of ≤88% 18), and is recommended in the current GOLD guidelines for selected patients. 3 However, there is no clinical evidence demonstrating a mortality benefit with oxygen therapy in patients with stable COPD who have only moderate arterial oxygen desaturation (PaO 2 of 56–59 mm Hg or SpO 2 between 88%–90% 18) at rest or with exercise. 3 The Long-Term Oxygen Treatment Trial (LOTT) investigated the impact of the prescription of long-term supplemental oxygen in 738 patients with COPD and moderate resting (SpO 2 between 89%–93%) or exercise-induced (SpO 2 ≥80% for ≥5 min and <90% for ≥10 seconds during exercise) desaturation. Long-term oxygen supplementation did not result in either a longer time to death or first hospitalization. 19 In a Cochrane Review published in 2016, Ekström et al conclude with moderate confidence that oxygen can relieve breathlessness when given during exercise to mildly hypoxemic and nonhypoxemic individuals with COPD, but does not improve health-related quality of life. 20 Consultation with a pulmonologist is appropriate if when and how to prescribe oxygen therapy is not clear.
Recent updates of the GOLD recommendations acknowledge the discordance between lung function and symptoms in patients with COPD. The 2017 recommendations use symptoms and exacerbation risk to define the ABCD categories that guide therapy selection. However, the GOLD authors still acknowledge the importance of spirometry in diagnosis, prognostic evaluation, and treatment with nonpharmacologic interventions in patients with COPD. 3
GOLD grades provide a valuable guide for initiating therapy and continuing assessment and care. Initial therapy may provide sufficient disease control in some patients, but disease progression and persistent symptoms despite therapy often require treatment escalation. Assessing and escalating therapy should be based on changes in functional status and symptom burden, which can be identified by asking appropriate questions, or performing tests to evaluate functional capacity, such as the 6-minute walk test. 3 The modified Medical Research Council (mMRC) dyspnea scale is also a good example of a quick tool for baseline assessment of the patient’s functional status. This assessment must be coupled with appropriate follow-up. During follow-up visits, it is important to ask patients about their typical daily activities, and assess how these compare to what has been reported previously. Follow-up visits can also be an opportunity to check that a patient is using their inhaler device correctly.
Regular assessment of patients’ health status is important for optimal disease management. 22 The COPD Assessment Test (CAT) is a short, simple, COPD patient-completed questionnaire, designed to inform the clinician about the severity and impact of a patient’s disease. Changes in patients’ functional abilities and symptoms over time can be monitored with regular use of the CAT at COPD visits. 23 Although the CAT test facilitates prediction of COPD exacerbations, 24 it is not intended to identify comorbidities; for example, the mental health comorbidities of COPD (including anxiety, sleep disturbances, and depression) are often unreported by patients and so can be difficult for clinicians to detect. 25 Awareness of possible comorbid conditions, and appropriate screening for conditions such as depression (PHQ-2), anxiety (GAD-7), or osteoporosis (BMD) is recommended. 26 Further details of PHQ-2 and GAD-7 are provided in the second article ( Anxiety and Depression in Chronic Obstructive Pulmonary Disease: Recognition and Management ) of this supplement.
Physicians need to make decisions about whether (and how) treatment should be escalated using parameters in addition to frequency of exacerbations, such as a lack of improvement or worsening of symptoms or functional status. 3 For example, the addition of a second bronchodilator is recommended for a GOLD B patient with continued breathlessness on a single bronchodilator, and escalating from 1 to 2 long-acting bronchodilators is recommended for GOLD C patients with persistent exacerbations despite monotherapy with a LABA or LAMA. LAMA/LABA combinations that are currently approved for the treatment of COPD by the US Food and Drug Administration are umeclidinium/vilanterol, tiotropium/olodaterol, glycopyrrolate/formoterol, and glycopyrrolate/indacaterol. 27-30
For patients with high symptom burden (mMRC ≥2, CAT ≥10) experiencing frequent exacerbations, defined as 2 or more exacerbations per year, or 1 or more exacerbations per year that lead to a hospitalization (ie, GOLD D patients), LAMA/LABA is recommended as first-choice treatment. A recent study showed LAMA/LABA to be superior to ICS/LABA for preventing exacerbations; while it should be noted that the majority of exacerbations in this study were mild, LAMA/LABA was also found to be significantly more effective at reducing exacerbations classed as moderate or severe than ICS/LABA. 31 However, these findings may not be broadly generalizable, owing to limitations associated with the study’s exclusion criteria and the high discontinuation rate reported during the study’s run-in phase, which may have introduced a selection bias. 31
ICS/LABA may be considered for treating persistent exacerbations in some GOLD C patients, and may be first choice in GOLD D patients with asthma-like features, or possibly high blood eosinophil counts. 3 Patients who remain symptomatic on LAMA/LABA may also be considered for triple therapy (ICS/LAMA/LABA), as per the GOLD recommendations. 3 Care must be taken to use ICS appropriately, as ICS treatment may increase a patient’s risk of developing pneumonia, although risk profiles for pneumonia vary depending on the ICS treatment selected. 32 Increased risk of other adverse effects associated with ICS treatment should also be considered, including oral candidiasis (odds ratio [OR], 2.65; 95% confidence interval [CI], 2.03–3.46 [note, oral candidiasis can be avoided by mouth-rinsing 33]), hoarse voice (OR, 1.95; 95% CI, 1.41–2.70), and skin bruising (OR, 1.63; 95% CI, 1.31–2.03) compared with placebo in patients with COPD. 21 Nonetheless, use of ICS is not associated with a mortality risk, 34 and a 2017 study by Crim et al reported that the risk of pneumonia was not increased with ICS compared with placebo in patients with moderate airflow limitation who had/were at high risk of cardiovascular disease. 35 Physicians should therefore consider both the potential risks and benefits of ICS before prescribing them to patients with COPD.
While careful consideration of ICS is warranted, ICS/LABA combinations are often prescribed inappropriately in many patients with COPD in clinical practice, including those at low exacerbation risk. 15 Treatment de-escalation by stopping ICS may be appropriate in patients receiving ICS/LAMA/LABA who suffer from fewer than 2 exacerbations per year (ie, receiving ICS inappropriately), 36 or in those who continue to experience persistent exacerbations despite ICS. 3 The use of systemic steroids in stable COPD is not recommended. 37
At any stage of disease, patients may benefit from a referral by primary care to a pulmonologist for further evaluation. 38 Reasons include uncertain diagnosis, severe COPD, assessment for oxygen therapy, trouble finding or referring to pulmonary rehabilitation, and COPD in patients younger than 40 years of age (who may be suffering from α 1-antitrypsin deficiency). 38 Referring patients with significant emphysema or other co-existing lung diseases also allows evaluation for surgical interventions such as lung transplantation, lung volume reduction surgery (LVRS), or other therapies.
Patients with COPD may gain particular benefit from comanagement by primary care physicians and pulmonologists. 39 For example, primary care physicians may require guidance from pulmonologists regarding the management of patients with severe disease whose therapy requirements are becoming more complex. Similarly, pulmonologists may not be comfortable managing the comorbidities often encountered in COPD (eg, anxiety and depression), so would require support from the primary care physician to provide the patients with effective, holistic management.
Surgical and bronchoscopic interventions have the potential to significantly benefit carefully selected patient groups with emphysema. 3 LVRS resects parts of the lungs to reduce hyperinflation, and improves lung function and reduces exacerbations in patients with advanced emphysema. 3 It can prolong mortality in selected patients, 40 but can increase the risk of death in those with low FEV 1 and either homogenous emphysema or very low carbon monoxide diffusing capacity. 41
Nonsurgical bronchoscopic interventions continue to improve; they have been designed to achieve similar results to LVRS (but with less morbidity), and provide a possible intervention for patients with heterogenous or homogenous emphysema, and significant hyperinflation refractory to optimized medical care. 3 Use of endobronchial one-way valves and lung volume reduction coils has resulted in significant improvements in patients’ quality of life, exercise capacity, and pulmonary function for select patients with severe emphysema. 42,43 Other therapies, such as adhesives (where a biologic sealant collapses targeted areas of the lung to induce the formation of scar tissue, thus reducing lung tissue volume), and vapor therapy (where heated water vapor is used to deliver thermal energy to the lungs, inducing an inflammatory response that causes contraction fibrosis and atelectasis, and subsequently lung volume reduction) are also in development. 44 Consideration of surgical or nonsurgical interventions require referral to a pulmonologist.
Lung transplantation may be an option for patients with very severe COPD without significant comorbidities. Lung transplantation improves quality of life, but does not prolong survival. 3,45,46 The procedure is limited by donor availability, high cost, and potential complications. 3
The COPD Foundation guidelines note that some spirometry results are normal, but do not rule out the presence of chronic bronchitis, emphysema, or other lung disease; or are neither normal nor consistent with COPD or other lung disease. The guidelines therefore define 2 additional spirometric grades, referred to as SG 0 (representing patients with normal spirometry) and SG U (representing patients who have a FEV 1/FVC ratio >0.7 but FEV 1 <80% predicted). At present, neither SG 0 nor SG U are associated with therapeutic options distinct from other spirometric grades, but this may change as we learn more from clinical studies. 47,48
Comorbidities are common among patients with COPD, and COPD itself may increase the risk of developing other diseases. 3,49-52 It can be difficult to recognize the many comorbidities in patients with COPD, due to the diverse nature of these comorbidities, a lack of understanding of their underlying causes, patients’ failure to recognize or share symptoms, or misdiagnosing them as adverse effects associated with COPD medication. 53 Failure to recognize and treat comorbidities can increase risk of hospitalizations or exacerbations, worsen prognosis, increase morbidity, lower the chances of treatment adherence, and place a greater burden on the patient, family, and health care resources. 51,52,54-56 Common comorbidities include cardiovascular disease, musculoskeletal dysfunction, metabolic syndrome, anxiety/depression, osteoporosis, lung cancer, and heart failure. 3,51,52
The value of effectively managing comorbidities in improving outcomes and adherence to therapy is well documented. For example, personalized management of patients with COPD and comorbid anxiety and/or depression has been shown to reduce both the mental health symptoms and COPD-related outcomes (eg, exercise tolerance, disability). 57-59
Comorbidity burden may impact adherence to COPD medication. Depression, for instance, is a known risk factor for nonadherence to treatment. Patients with multiple untreated or uncontrolled comorbid conditions may also be less likely to benefit from pulmonary rehabilitation. 60 It is therefore important that comorbidities are managed effectively to improve adherence to therapy, and enhance the benefits of pulmonary rehabilitation.
Routine follow-up of patients with COPD is essential as lung function may worsen over time, even with the best available care. 3 Worsening of symptoms, activity limitation, and disease progression should be monitored closely to determine when to modify management/pharmacotherapy, and to identify any complications and/or comorbidities that may develop. 3 When patients with COPD do not receive the appropriate level of treatment or monitoring, it can be due to: under-reporting of disease severity, symptoms, and exacerbations during consultation; lack of information on the impact of the disease on the patient’s quality of life; and failure to recognize comorbidities. 23,25,53 Continued use of the patient questionnaires described previously is recommended, and the GOLD strategy advises that symptoms are assessed at each visit. These follow-up visits also provide an opportunity to monitor patients with COPD for key comorbidities, including heart failure, ischemic heart disease, arrhythmias, osteoporosis, depression/anxiety, and lung cancer, as well as to determine a patient’s current smoking status, taking appropriate action as needed. 3
COPD remains underdiagnosed in the United States, with only 50% of individuals with impaired lung function reported to receive a formal diagnosis of COPD. 61,62 Opportunities for diagnosing COPD earlier in its course are being missed; 85% of patients consult primary care for lower respiratory symptoms in the 5 years before diagnosis of COPD, and might have been candidates for further evaluation of those symptoms, including spirometry testing. 63 Initiating treatment at early stages of COPD has the potential to improve patients’ health-related quality of life, and may provide opportunities to slow disease progression through interventions such as smoking cessation. 64 Practical approaches to improving early diagnosis in primary care involve the use of questionnaires and clinical suspicion to identify those appropriate for spirometry, the most reliable method for identifying patients with COPD. 3,9,65 Such methodology is currently under investigation, with early studies demonstrating the potential benefit of the COPD Assessment in Primary Care To Identify Undiagnosed Respiratory Disease and Exacerbation Risk (CAPTURE) questionnaire in conjunction with peak expiratory flow to gauge whether a patient requires further diagnostic evaluation. 66
In addition, the GOLD strategy and COPD Foundation guidelines emphasize that correct assessment of symptoms is of paramount importance in determining the most appropriate therapy (both pharmacologic and nonpharmacologic) for patients with COPD, but traditionally has not been used to inform management choices. Both guidelines therefore highlight the importance of symptom assessment ahead of therapeutic decision-making.
Poor adherence to prescribed therapies and inadequate patient monitoring also need addressing. Two studies analyzing refill adherence data in patients with COPD and asthma in Sweden reported that only 28%–29% of prescribed treatments were dispensed with refill adherence that covered more than 80% of prescribed treatment time 67,68; a study in 5504 patients in the United States with a prescription of fluticasone propionate/salmeterol combination therapy found that more than half of patients only refilled their prescription once over the course of the 1-year study. 69 With studies showing incorrect use of inhalers in more than 50% of patients with COPD, incorrect inhaler technique is a significant contributor to poor treatment adherence. 70,71 Inhaler technique should be reviewed regularly with direct observation of patients’ technique. Assessment of the patients’ ability to use their current prescribed inhaler(s) is recommended before considering a change in treatment. 70 Errors in inhaler use are also associated with an increased rate of severe COPD exacerbations, increased risk of hospitalization, and poor disease control. 71,72 Important factors affecting inhaler use include age, education, product design, costs (copays and deductibles) for medications, and instruction and inhaler technique education from the health care providers. 70,72,73 Recent data support improvements in product design, training by the health care provider, and “self-training” by the patient (assisted by instructional video or other digital media) to increase adherence and reduce the frequency of handling errors. 10,70,74 Electronic monitoring devices, messaging systems, and cell phone applications are also being considered as ways to increase adherence. 75
Maintenance medication is an essential component of COPD management. However, patients with COPD often report that their preference is for medication that they can “feel” working, which may be implicated in their motivation to adhere to therapy. 76 Conversely, while maintenance medication may reduce exacerbations, and lessen a patient’s decline in lung function, 77 it may not have a significant impact on how they “feel.” As a result, patients may not take it as prescribed, contributing to poor adherence. It is therefore important for primary care physicians to acknowledge that the impact of taking the maintenance medication may not be felt immediately, and articulate the importance of maintenance therapy to their patients, as failure to adhere to treatment can have significant implications for longer-term outcomes such as symptom burden, quality of life, and exacerbation risk. 11
Regular patient follow-up is necessary to reinforce such information: patients with milder or stable COPD may be followed at 6-month intervals, while patients with severe or frequent exacerbations, or patients who have recently been hospitalized, require follow-up at 2- to 4-week intervals. 78
Defining personal treatment goals for patients with COPD can enhance patient and physician communication and encourage continued collaboration to improve adherence and outcomes. Regularly monitoring symptoms, exacerbations, and comorbidities via patient-focused questionnaires, and closely examining patient adherence and technique, form a fundamental part of care for patients with COPD. Recent updates to the GOLD and the COPD Foundation guidelines have emphasized the importance of symptom assessment in initiating COPD therapy, and continued assessment to appropriately escalate treatment. Nonpharmacologic therapies such as smoking cessation and pulmonary rehabilitation are recommended at all stages of COPD alongside pharmacologic treatment.
This supplement aims to provide an introduction to 4 key topics in COPD management in primary care.
Patients with COPD may enter a downward spiral of dyspnea-induced inactivity, resulting in deconditioning.
Anxiety and depression are common in patients with COPD and result in worse outcomes.
Pressurized metered-dose inhalers, dry powder inhalers, soft-mist inhalers, and nebulizers each have advantages and limitations.