Exacerbations of COPD

Abstract

COPD exacerbations are associated with significant morbidity, mortality, and increased health care expenditures. The recently published Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommendations have further refined the definition of an exacerbation. A better understanding of the risk factors associated with the development of an exacerbation exists, and improvements are being made in earlier detection approaches. Pharmacologic treatment strategies have been the cornerstone of effective therapy. In addition, both pharmacologic and non-pharmacologic strategies have been proven successful in the prevention of future exacerbations. Newer technologies, including the use of artificial intelligence and wearable monitoring devices, are now being used to help in the earlier detection of exacerbations. Such preventive and earlier detection strategies can help to develop a more personalized care model and improve outcomes for patients with COPD.

Introduction

COPD exacerbations are episodes in which a patient who has COPD has worsening of underlying symptoms. These events are associated with significant adverse consequences including accelerated lung function decline, impaired quality of life, increased morbidity, and increased mortality.¹ The impact of severe exacerbations has been noted since 2005 when patients with the greatest mortality risk were those with 3 or more acute COPD exacerbations.² Whereas most patients who have a COPD exacerbation will recover, many have ongoing impairment, and in some instances that impairment is life long. We have learned a great deal regarding the evaluation and management of a patient with a COPD exacerbation over the last half century, but further research including the use of newer technologies is needed to help more effectively manage and prevent these episodes. This paper will present a general overview of COPD exacerbations with emphasis on the current evidence-based treatment and prevention guidelines.

Definition

A COPD exacerbation has been described as an acute event in a patient with COPD that is characterized by worsening of a patient’s respiratory symptoms beyond the normal day-to-day variation that leads to a change in medication regimen. The worsening of symptoms includes a change in at least one of the following symptoms: increase in sputum volume, change in sputum character, increase in dyspnea, or change in cough.^3,4 Associated comorbid conditions are often present and may account for similar symptoms. For example, an exacerbation of underlying congestive heart failure can be associated with an increase in cough and shortness of breath and may mimic those symptoms associated with a COPD exacerbation. An updated definition of an exacerbation⁵ describes the event as one in which a patient with COPD has dyspnea and/or cough and sputum that worsen over < 14 d, which may be accompanied by tachypnea and/or tachycardia and often associated with local and systematic inflammation caused by airway infection, pollution, or other insult to the airways.

A COPD exacerbation is often triggered by either an infectious (viral or bacterial) or an environmental (indoor or outdoor air pollution, biomass fuels, smoking) cause. Respiratory infections (primarily due to viruses) are estimated to trigger over 70% of cases.⁶ Bacterial infections are the second most likely source for triggers caused by one of a variety of types of bacteria: Hemophilus influenzae, Streptococcus pneumoniae, and Pseudomonas aeruginosa. An important consideration during the initial assessment of a patient is to determine their risk for the presence of P. aeruginosa. Its presence should be considered for those patients with very severe COPD (an FEV₁ < 30% of predicted), bronchiectasis on chest imaging, chronic systemic glucocorticoid use, or use of broad-spectrum antibiotics within the last 3 months.⁷ Specific antibiotic therapy directed at this organism should be initiated if this organism is suspected. An exacerbation may also be triggered or confused with a worsening of an underlying comorbid condition such as congestive heart failure or venous thromboembolism. Accurate determination of the underlying cause for an exacerbation is essential to provide optimal therapy.

Risks for Development of an Exacerbation

The risk of developing a COPD exacerbation is associated with a variety of other factors including patients with a history of at least one prior exacerbation within the last 12 months, with more severe COPD (as measured by the FEV₁), with the presence of chronic bronchitis, or associated with other clinical conditions (eg, gastroesophageal reflux, pulmonary hypertension).⁸ Computed tomography (CT) imaging showing a pulmonary artery:aorta ratio > one has also been found to be independent risk factor for future COPD exacerbations⁹ (Table 1).

Table 1.

Factors Associated With an Increased Risk of a COPD Exacerbation

Sex-based risk factors for developing an exacerbation exist. Whereas historically COPD was felt to affect older males who were smokers, females are more likely to experience an exacerbation than are males. In a recent study of over 22,000 patients followed for 3 years, the risk of the first moderate or severe exacerbation was 17% greater in females than in males, with a median time to the first exacerbation being 504 d for females and 637 d for males. These differences were more prominent in the younger age group (ages 40–65 y) and for those in GOLD groups B, C, and D.¹⁰

Newer methods to help predict the risk of developing an exacerbation have undergone investigation. The use of a disease-specific respiratory questionnaire (St George Respiratory Questionnaire [SGRQ]) for patients with chronic bronchitis, a known risk factor for development of a COPD exacerbation, has been able to identify 50% more patients with an exacerbation and was felt to be comparable, if not better, to the classic definition in the prediction of future total exacerbations.¹¹

The COPD Assessment Test (CAT), a questionnaire used extensively in the evaluation and management of patients with COPD, was used in a trial comparing the effectiveness of combination bronchodilator and inhaled corticosteroids (ICSs) therapy.¹² An elevated CAT score at baseline was associated with an increased rate of moderate to severe exacerbations. The use of triple inhaled therapy (eg, ICS, long-acting β agonist [LABA], long-acting muscarinic antagonist [LAMA]) showed a consistent reduction in the rate of moderate to severe exacerbations compared to dual therapy for patients with all levels of CAT scores. A current trial (CAPTURE) using a 5-item questionnaire and peak expiratory flows is being conducted to assess the specificity and sensitivity of an assessment by a primary care practitioner in the determination of exacerbation risk.¹³

Diagnosis and Determination of Severity of a COPD Exacerbation

The diagnostic approach to an exacerbation includes both clinical and laboratory evaluations. A complete and thorough clinical assessment of the patient for evidence of COPD and potential respiratory and non-respiratory concomitant diseases should be undertaken. This assessment should include symptoms (severity of dyspnea as measured by a visual analog scale and documentation of the presence of cough) and signs (tachypnea, tachycardia, sputum color and volume, accessory muscle use, bronchospasm). Determination of the severity of an exacerbation should include other appropriate investigations including pulse oximetry, complete blood count, brain natriuretic peptide (BNP), and C-reactive protein (CRP) and/or arterial blood gas (ABG) analysis. A general guide to the assessment of the severity of a COPD exacerbation has been proposed⁵ (Table 2). Further classification of the type of exacerbation (mild, moderate, severe) can be determined after the event has occurred and is helpful from both clinical and research perspectives.⁴

Table 2.

Severity Determination of a Patient With a COPD Exacerbation

Biomarkers

A biomarker is defined as a marker that is objectively measured and evaluated as an indicator of normal biologic processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention. Biomarkers have been helpful with the diagnosis and management of other disease process (eg, troponin use for cardiac disease, hemoglobin A1C for diabetes), yet their use in the evaluation and management of a patient with an exacerbation has yet to be shown to be helpful. In the ECLIPSE trial, biomarkers such as CRP, fibrinogen, surfactant, cytokines, and white blood cell differentiation were not significantly related to an improvement in risk prediction for a COPD exacerbation.¹⁴

Sputum and serum eosinophil and serum procalcitonin levels are other promising biomarkers that have been studied in relation to exacerbations. Up to 40% of patients with stable COPD have been found to have eosinophilic airway inflammation that may increase during an exacerbation. A higher blood eosinophil count has been associated with an increased risk of future exacerbations as well as being predictive of the treatment response to ICSs.¹⁵ Other biomarkers obtained from supernatant of sputum including sialic acid, hypoxanthine, xanthine, adenosine, and glutathione have been shown to be altered in COPD and may be predictive of a pulmonary exacerbation, but further studies are needed.¹⁶

CRP levels have been used extensively in evaluation of the presence of an exacerbation. Patients who are healthy or who have stable COPD have serum CRP values < 10 mg/L. This value increases in both viral and bacterial exacerbations but is usually higher with the latter type of infection. Whereas there is lack of specificity of using the CRP level as a marker of airway/lung inflammation, a CRP level of ≥ 10 mg/L can help to separate mild versus moderate exacerbations.⁵ Procalcitonin levels have been associated with a higher likelihood that a bacterial process is associated with a COPD exacerbation and have been shown to help guide the initial and duration of antibiotic therapy. Its use in predicting the risk for an exacerbation has yet to be shown.¹⁷

Molecular-based biomarkers (eg, polymerase chain reaction testing) obtained from the sputum offer an intriguing way to help determine the causative agent for an exacerbation. This technology has arisen from the need to rapidly identify infectious-induced causes for a patient’s illness in the wake of the SARS-CoV-2 pandemic. This testing has been studied in the intensive care population and has helped to identify bacterial and viral causes for hospital- and ventilator-associated pneumonias. Whereas yet to be studied in the non-ICU setting, the earlier identification of a causative organism for the exacerbation should help to develop more targeted therapy.¹⁸ The use of such biomarkers included with phenotyping can ultimately lead to targeted treatment and prevention of COPD exacerbations.¹⁹

Exacerbation Treatment Strategies

The goals of treatment for a COPD exacerbation are to minimize the impact of the current illness and to prevent future events. Recommendations (eg, guidelines and best practices) have been proposed recently including pharmacologic and non-pharmacologic therapies^20-24 (Table 3).

Table 3.

Treatment of a COPD Exacerbation. Evidence-Based Guideline and Best Practices Recommendations

Pharmacologic Therapies

Short-acting bronchodilator therapy, including short-acting β₂ agonist and short-acting muscarinic antagonists, is the center of current treatments for an exacerbation. These short-acting therapies are administered either by a handheld metered-dose inhaler or by a nebulizer. Whereas the optimal mode of delivery has yet to be elucidated, the type of device used is dependent upon the severity of the underlying exacerbation and the patient’s ability to use the chosen delivery device. For those patients who are unable to effectively utilize a handheld device (eg, metered-dose inhaler), a delivery device using nebulization should be considered.^25,26

Glucocorticoid therapy should also be included in the initial treatment regimen. Initially, oral glucocorticoids (eg, prednisone) should be administered at a dose of 40 mg daily for a dose duration between 5–14 d.²⁷ Depending upon the severity of the exacerbation, higher doses may be necessary; however, prolonged treatment courses > 14 d have not been shown to be more effective than shorter courses of therapy.^28,29 For those patients who are hospitalized and may be unable to take an oral medication, intravenous corticosteroids (eg, methylprednisolone) beginning at doses of 40 mg once daily should be initiated. The use of ICSs during the acute phases of an exacerbation has yet to be studied.

Antimicrobial therapy has been shown to be effective in the treatment of an exacerbation since the late 1980s.⁴ Antibiotic therapy should be used for those patients who have or likely have a bacterial infection and are significantly ill. Initial studies showed that for those patients who have one or more of the following symptoms (increase cough, increased sputum volume, or increase sputum discoloration) antibiotic therapy was associated with an improvement in overall condition.^30,31 Historically, the initial antibiotic therapy included either amoxicillin-clavulanate, a macrolide, or a tetracycline. For those patients in which infection with Pseudomonas is possible, a fluoroquinolone should be considered. It has been proposed that for uncomplicated patients preference should be given to a macrolide, a cephalosporin, or trimethoprim/sulfamethoxazole. Recent studies have shown limited efficacy related to doxycycline use. For complicated patients, amoxicillin-clavulanate or a fluoroquinolone should be considered.³² In all cases, if clinical improvement does not occur within 72 h, a careful clinical assessment should be done and should include obtaining a sputum Gram stain and culture. There has been insufficient or no evidence supporting the use of other pharmacologic treatments (ie, magnesium sulfate, anti-inflammatory agents, or mucolytic therapy) in the initial treatment regimen. The GOLD panel recommends antibiotic use if 3 cardinal signs are present: sputum volume increase, sputum purulence, and dyspnea. In addition, it is recommended if 2 of these 3 signs are present (as long a one is sputum purulence) or mechanical ventilation is needed.²⁴

Antiviral therapy should be considered for those patients who test positive for either influenza A or B or the SARS COVID-19 virus. With the availability of rapid testing for these organisms, targeted treatments can be started. Consideration for the use of oseltamivir (for influenza) and monoclonal antibodies and/or ritonavir/nimtendavir (for SARS-CoV-2) should be considered in the appropriate patient.

Non-Pharmacologic Therapies

Non-pharmacologic therapies may also be useful during the acute treatment of an exacerbation. Airway clearance techniques and whole-body vibration were associated with improved functional outcomes in patients hospitalized for moderate to severe exacerbations. In addition, resistance training and range-of-motion exercises were associated with a better quality of life.³³ Many unmet needs are still present in the search for the most effective treatment regimen.³⁴

Place for Treatment

A COPD exacerbation is most often managed in the out-patient setting. Early detection and initiation of therapy are essential and should include the patient and the health care provider working as a team. Appropriate education and the use of an action plan can help the team determine whether an exacerbation is present and to decide on the appropriate therapy. Recent reviews have shown that a single short educational program reduces in-hospital health care utilization and increases treatment of COPD exacerbations with corticosteroids and antibiotics. Overall quality-of-life score on the SGRQ showed a small improvement with action plans compared to usual care over 12 months.³⁵

In some instances, hospitalization for an exacerbation is necessary and is based upon the patient’s clinical condition and/or failure of out-patient therapy. Elevation in heart rate or breathing frequency, oxygen desaturation, use of accessory respiratory muscles, and presence of severe bronchospasm are some of the signs that should be used in the clinical assessment guiding the need for hospitalization. Further testing should include measurement of ABGs, complete blood count, and BNP and CRP levels. Oxygen saturation measurements by pulse oximetry can be helpful; however, limitations to this measurement exist (eg, lack of determination of carbon dioxide levels, the accuracy of pulse oximetry in individuals with deeply pigmented skin) and must be considered in each individual.^36,37 Other initial studies should include chest roentgenography and electrocardiography. Additional studies (eg, CT pulmonary angiography, echocardiography) should be considered if appropriate. Therapy should be started with inhaled bronchodilators (often administered via a nebulizer), corticosteroids, and antibiotics.²⁴

For those patients with an exacerbation associated with hypoxemia, supplemental oxygen therapy should be administered based on current guidelines.³⁸ Some patients may require additional respiratory support in attempts to avoid intubation and mechanical ventilation. For those who have hypercapnic respiratory failure, the use of noninvasive ventilation has been shown to reduce the rate of deterioration and the need for intubation and mechanical ventilation. In general, noninvasive ventilation should be used as first-line therapy for appropriate patients.³⁹ The delivery of oxygen with heated, humidified, high-flow nasal cannula has been used as an alternative for those patients with acute hypoxemic respiratory failure.^40-42

Exacerbation Prevention Strategies

Significant progress has been made in the prevention of COPD exacerbations. Current evidence-based and best practice guidelines have been developed^24,43-45 (Table 4). In addition to the avoidance of those factors that may provoke an exacerbation (eg, primary smoking or secondhand smoking exposures, indoor or outdoor air pollution, biomass fuel exposures), various pharmacologic/non-pharmacologic therapies have been shown to be effective in the prevention of an exacerbation (Table 5). Interestingly since the beginning of the SARS-CoV-2 pandemic the incidence of COPD exacerbations has decreased.^46,47 Handwashing, social distancing, and mask wearing should be a cornerstone of therapy to help with the prevention of COPD exacerbations. The SARS-CoV-2 vaccine is currently recommended by the Centers for Disease Control and Prevention,⁴⁸ yet the overall effectiveness of this vaccine and its relationship to the prevention of COPD exacerbations is under investigation. Other vaccinations have been shown to be effective in the management of a patient with COPD (eg, pneumococcal, influenza, Tdap, Zoster)²⁴ (Table 6).

Table 4.

Prevention of an Exacerbation of COPD. Evidence-Based Guidelines and Best Practice

Table 5.

Preventive Interventions for an Exacerbation of COPD

Table 6.

Vaccination for Stable COPD

Inhaled bronchodilators and ICSs have also been shown to prevent exacerbations. In the FLAME trial, the use of a combination of a long-acting β₂ agonist and a long-acting muscarinic antagonist compared to the combination of a long-acting β agonist and ICS significantly reduced the rate of moderate or severe exacerbations.⁴⁹ In the SUMMIT trial, the use of an ICS led to a reduced frequency of exacerbations.⁵⁰ These and several other trials have shown that long-acting bronchodilator therapy is effective in preventing exacerbations.^51,52 ICSs may be more effective to reduce exacerbations for those patients who have an eosinophilic-associated exacerbation.^24,53 The use of triple therapy with a long-acting β₂ agonist, a muscarinic antagonist, and an ICS has also been associated with a decrease in the COPD exacerbation rate.⁵⁴ Consideration must be made when using an ICS given the potential for the development of pneumonia associated with their use.⁵⁴

Several other oral pharmacologic therapies have been shown to help prevent a COPD exacerbation. Smoking cessation is of prime importance, and therapy to address this should be instituted for every patient who continues to smoke.²⁴ Roflumilast (a phosphodieserase-4 inhibitor) has been shown to effectively reduce exacerbations for patients with chronic bronchitis who have severe or very severe COPD.⁵⁵ Long-term macrolide therapy (ie, azithromycin) administered several times weekly has also been shown to reduce the incidence of COPD exacerbations⁵⁶ as has the use of mucolytics.⁵⁷

Non-pharmacologic therapy is also useful to help reduce exacerbations. Comprehensive pulmonary rehabilitation (PR), including exercise training, symptom management, patient education, smoking cessation intervention, nutritional counseling, respiratory therapy techniques, and lung volume reduction surgery, has been shown to reduce exacerbation rates. Guidelines for the performance of PR are well established, and it is recommended patients with symptomatic chronic lung disease be referred for PR.⁵⁸ PR is not recommended for those patients who are hospitalized with an exacerbation during their hospital stay⁵⁹ but is recommended to be started within 3 weeks of hospital discharge.⁶⁰ Mortality has been shown to be reduced for those patients starting rehabilitation following a hospitalization for an exacerbation.⁶¹

Unfortunately, less than 5% of those patients who could potentially benefit from PR receive this therapy.⁶² Access to PR is limited for many reasons including lack of program availability, inability to attend a program, lack of awareness by the health care team of the potential benefits, and lack of adequate insurance reimbursement. Home-based programs are being developed and should offer an exciting opportunity to provide PR to many more patients who might not otherwise have access to a program.⁶³ The use of PR following those exacerbations not requiring hospitalization requires further study.

Process Improvement

Many patients with COPD do not report worsening symptoms to their health care provider and thus delay seeking care.⁶⁴ Several primary treatment themes for patients’ perceptions of their breathing symptoms and identification of factors that led to seeking or delaying care for a COPD exacerbation have been shown. Access to health care providers and attitudinal barriers are the primary reasons for this delay in seeking care. It is important to encourage earlier care and develop the appropriate educational strategies regarding self-care management approaches. For those patients who presented for follow-up care in the 4 weeks following primary care provider evaluation, it was shown that those patients with COPD who had diabetes, obesity, or who had been prescribed oral antibiotics in the prior 12 months had significantly worse outcome scores. Knowledge of the patient’s comorbid conditions is an important aspect of providing full care to a patient, and particular emphasis to these conditions and their impact on exacerbations should be recognized by the health care team.⁶⁵ Recognition of a patient’s adherence to therapy and the development of strategies to improve adherence must be included as part of every patient evaluation.^66,67

The discharge process for a patient hospitalized with an exacerbation is particularly problematic in most health care environments. Despite many national and local policy efforts to improve the discharge planning processes for patients hospitalized with an exacerbation, little evidence exists regarding their effectiveness in improving overall outcomes or quality of care. In a best practices study done in England with patients hospitalized with a COPD exacerbation, a specialist reviewed the overall discharge care bundle and communicated the findings to the primary care team following discharge. Using this discharge planning approach, a reduction in patient morbidity occurred. Unfortunately, a reduction in the 30-d mortality or 30-d readmission rate did not occur.⁶⁸

In a Department of Veterans Affairs study, an interdisciplinary team reviewed the health records for patients recently discharged following an exacerbation. Treatment recommendations were then delivered to both urban and rural primary care providers by electronic means. Minimization of the increased workload and autonomy for the primary care providers was assured. On average, the multidisciplinary team made 5 recommendations per patient, with order activation of these recommendations by the primary care provider approaching 80%. This virtual review improved condition-specific quality of life but did not significantly reduce the COPD admission rate or death rate over the 6 months following discharge. The population health management techniques used in this program including surveillance, hovering, and proactive fee consultation may be able to be expanded to other health care systems and help to improve the overall outcomes for patients with an exacerbation.⁶⁹

In most instances, follow-up with the health care provider within one month and again at 3 months is recommended. During those visits, a review of the symptoms, associated comorbid conditions and medication regimens, assessment of the response to therapy and use of inhaled devices, and appropriate adjustments to therapy should be made. In addition, performance of spirometry and possibly chest CT scanning (particularly for those patients with recurrent exacerbations to evaluate for the presence of bronchiectasis) should be done.²⁴

The Use of Telemedicine and Artificial Intelligence

Earlier prediction and detection of an acute exacerbation of COPD should result in more effective treatment and preventive strategies. Telemonitoring generated by wearable technology (eg, fitness trackers, smart watches) may well help to develop effective models for such prediction and detection. These technologies have been shown to have good user acceptance and have been able to measure vital signs effectively in patients with COPD.⁷⁰

By combining telemonitoring with artificial intelligence, those factors responsible for the development of an exacerbation (ie, a previous history of exacerbations, the COPD phenotype, presence of gastroesophageal reflux disease) may be more identified much earlier in an individual patient. In a model using automatically explaining machine learning, a strategy starting with an initial 229 separate clinical features and subsequently reduced to 80 clinical features was used to evaluate their relationship with health care use. Over 12 months, this strategy was shown to correctly identify exacerbation risk and to significantly reduce hospital readmission rates and overall hospital use.⁷¹ Other digital tools have been used to assist with the diagnosis and the prevention of exacerbations, yet most of these studied have only been done in the short term.^72,73 Digital solutions strategies for those who are at high risk for the development of a COPD exacerbation should be jointly developed via health care providers, policymakers, and third-party payers.

A combination of wearable technology and artificial intelligence has been used successfully in other industries worldwide. One example is a wearable wristband (ie, MagicBand+) by the Disney corporation that is being used throughout many of its properties.⁷⁴ This wristband provides the user hotel room access, park access, and payment for services provided throughout their facilities (with a link to a credit card). In addition, the technology allows the company to monitor activity, movement, and resource use throughout the parks on a timely basis. Benefits to both the user and company are numerable, including potential safety benefits (eg, location of a lost child, access to emergency medical services). This type of technology and its associated processes could potentially be transitioned to the health care environment and may possibly improve patient-centered outcomes.

Future Research Studies

Current diagnostic, management, and preventive strategies have significantly reduced the impact that exacerbations have on patients with COPD. Further research is needed and should be centered on the earlier detection of exacerbations including the development of protocols to more effectively determine the causative agents for an exacerbation. For example, this might include an increase in the performance of nasal swabbing for viral-induced illnesses. More personalized care models for treatment also need to be developed.⁷⁵ Finally, more research into the incorporation of telemonitoring and artificial intelligence should be conducted.

Clinical trials are complicated methodologically and practically, and many concerns of such trials have arisen. The European Respiratory Society has developed a core outcome set of measures for clinical trials evaluating the management of COPD exacerbations.⁷⁶ These practical and utilization-appropriate measures include death, treatment success, need for higher level of care, level of oxygen and carbon dioxide in the blood, patient-reported outcomes, future impact, safety, and treatment adherence. The use of these outcome measures will help with the development of future research trials.

Summary

COPD exacerbations are associated with significant morbidity and mortality. Over the last half century, effective evaluation and treatment strategies have been developed, but further research is needed. Refinements in the definition of an exacerbation and improved strategies for the detection of an exacerbation (including the use of biomarkers, telemonitoring, and artificial intelligence) should help to provide earlier and more effective treatments. Effective evidence-based guidelines and best practice recommendations exist for both treatment and prevention of COPD exacerbations and should be used by all members of the health care team for all patients with COPD. Newer treatment strategies (pharmacologic and non-pharmacological) combined with improved processes of care (from both the patient and caregiver perspectives) should then help to lessen the associated morbidity and mortality for patients with a COPD exacerbation.

Discussion

MacIntyre: Brian, I’ve always been interested in the role of an action plan. I tell my COPD patients when I see them in rehab that exacerbations always seem to come along on Friday night at 9:00 pm when their doctor is being covered by a dermatologist! Being able to start a steroid or an antibiotic right away rather than waiting 48 hours to finally get your pill makes a big difference. I was fascinated with the big VA studies.^1,2

Carlin: That’s a great question, Neil. Interestingly the one study showed an increase in mortality in those subjects who underwent education prior to their hospital discharge, and this created a lot of controversy about action plans. That was only one study. Most experts today feel that action plans are an important component in the management of patients with COPD. I liken this to using GPS to get you from one point to another. It is a general map that can get you most efficiently to your end point, but you can certainly use another route to get to your destination if necessary. One of my colleagues in Southern California (Brian Tiep MD) has used these action plans for many years for all of his patients and reports that they are an invaluable resource to help quell an exacerbation at its outset before further morbidity occurs.

Criner: Brian, very nice. I wanted to ask a question in terms of what do you think an exacerbation is because when I have looked in the literature there is no pathologic description of an exacerbation. The only autopsies that exist of exacerbation show that they don’t die of exacerbation.

Carlin: I think an exacerbation is a worsening of a patient’s underlying condition albeit including more shortness of breath, increased sputum, or other increase in symptoms above the day-to-day variation that patients already have. Interestingly, as you mentioned, most people don’t die from the exacerbation per se but from another cause such as pulmonary embolism or myocardial infarction.

Criner: So, is an exacerbation only a physiologic consequence of worsening respiratory distress that it doesn’t matter what the etiology is, it’s the response of the host?

Carlin: I think it is. How do we define it? I’d love to come up with some type of number that says this is an exacerbation. I don’t think we’ll ever get there for something such as an exacerbation given the varied way that they present, unlike an acute myocardial infarction or diabetic ketoacidosis. I think we will get there eventually using a combination of clinical information as well as laboratory information to help define what a true exacerbation might be. There is a lot of discussion now from both a clinical and research perspective regarding the definition. On another note, as we are better able to integrate this clinical and laboratory information, likely through the use of artificial intelligence, we should be able to not only define the problem but develop more personalized treatment strategies. I think we will come to the point where a patient is able to wear, for example, a wristband/monitor that will help to not only detect vital signs, including oxygen saturation measurements, but also detect trends with the data that would recognize when a patient might not be doing as well as she/he once was. This type of technology is available in other areas right now. For example, Disney has what is called a MagicBand. This wristband can be used for your admission to the park, your hotel room key, and your credit card. Not only that, it is useful to help track your (and your children’s) location at the parks. Wouldn’t it be nice if we had such technology available for our patients with COPD? One that could not only measure their vitals but their activity levels and body status that could help detect an exacerbation as the earliest stages so that effective treatment can be started early in the course of the illness.

Orr: I enjoyed that, thank you. One of my experiences doing long-term monitoring in a variety of settings is that (1) some people are very resistant to being monitored. They can get freaked out by that for whatever reason. And (2) even when you can strap it on their wrist, they take it off to take a shower and forget to put it back on. When we do research studies of 2 weeks of actigraphy and we say, “what happened on day 7?” They say, “oh I forgot to put it on.” Do you see that as a challenge in this population? Do we need to really target times where we think people are most at risk and try to focus on those times, or is the goal to monitor everyone all the time?

Carlin: That can certainly be a challenge. The ideal type of monitoring should be very unobtrusive for the person. Interestingly, when thinking now back to the MagicBands, I see many people wearing them fully throughout their stay at the parks, even continuing to wear them on their travel home. Obviously, there needs to be some type of incentive to continue wearing them, and I don’t have a great idea what that might be at this point. The Disney example does have benefit as your access to parks, hotel rooms, and credit card information is contained all within that monitor. Maybe other ways to monitor, such as attaching something to your car keys or house keys might be another option in the future.

Orr: I think there’s an element of engagement. I like to wear this Apple Watch, for example, to see how many calories I burn on a daily basis. It feels empowering. I don’t know how much of a difference it makes to me, but I like that engagement. Maybe the time where it’s most successful is when there’s this partnership rather than we’re going to monitor you, just keep wearing it, and we’ll tell you when there’s a problem.

Carlin: You’re exactly correct. Engagement of the patient is of prime importance. Unlike Disney that has a vested interest in you wearing the band given the large amount of information that can be obtained regarding your behavior while on their property, such monitoring must be made to engender the patient’s engagement overall. And be provided at no, or a very low cost, to them. And boy, wouldn’t it be nice to have that technology available to address Gerry’s and Neil’s points so we can get to these people early and start the appropriate therapy right away? Overall, I think this can only improve the patient-centered outcomes.

Haynes: Right now we can monitor whether someone’s using their CPAP or not, and I wonder about the role of nonadherence with medications. There are data showing that many COPD patients aren’t taking their COPD medications.³ If you just talk to them, they’ll tell you. How many exacerbations could be prevented if there was a way to monitor whether they’re taking their medications or not? Or maybe too much, like why are you taking albuterol every 2 hours?

Carlin: Exactly. Particularly the inhaled medications. I’d love to be able to see that the patients are using their medications as prescribed. It’s very easy for me when I see people in the sleep out-patient office and I know, even prior their arrival that day, how much they are using their PAP equipment. This helps me to know where the patient stands with treatment and I think helps me to more effectively design a treatment plan for that patient who they can follow successfully.

Haynes: That’s the limitation of looking at the puff counter. In the Lung Health Study, there were puff counters. They affixed on the inhaler a little device that would count how many puffs the patient took. What the patients didn’t know was that this device also had a time-stamp function, and the time-stamp data indicated that 30% of the subjects had actuated their inhaler > 100 times over a few hours before their visit to deceptively indicate that they were adhering to their treatment plan.⁴

Carlin: We have a great opportunity here because we can develop the technology that can help to monitor this. It has been developed in many other medical and non-medical fields. We simply need to use the existing technology and refine it for our own patients. Ultimately this will result in better patient management and improved patient outcomes.